Researcher in the lab

Photo by Darren Baker

Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.

The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.

Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.

“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.

“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”

ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.

“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.

“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”

Researcher in the lab

Photo by Darren Baker

Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.

The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.

Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.

“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.

“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”

ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.

“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.

“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”

Researcher in the lab

Photo by Darren Baker

Researchers say they have designed an online tool that can predict the role of proteins and genes involved in immunological diseases and processes.

The tool uses information compiled from 38,088 public experiments to predict new immune pathway interactions, mechanisms, and disease-associated genes.

Details on this publicly available tool, known as ImmuNet, were recently published in Immunity.

“This new tool unlocks the insight contained in big data, the world’s biomedical research output, to help understand immunological mechanisms and diseases,” said Stuart Sealfon, MD, of Mount Sinai Health System in New York, New York.

“The goal of ImmuNet is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component.”

ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration and machine learning algorithms to “interrogate” this compendium of public data.

“We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data,” said Olga Troyanskaya, PhD, of Princeton University in New Jersey.

“By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology.”

AML cells

Image by Lance Liotta

The investigational therapy SL-401 has received orphan designation to treat acute myeloid leukemia (AML) in the European Union (EU).

SL-401 targets the interleukin-3 receptor (IL-3R). It is comprised of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is under development to treat a range of hematologic malignancies, as IL-3R is overexpressed on cancer stem cells in multiple hematologic malignancies.

SL-401 has orphan designation from the US Food and Drug Administration (FDA) for the treatment of AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 research

At ASH 2012 (abstract 3625), researchers reported results with SL-401 in a study of patients with AML, BPDCN, and myelodysplastic syndromes (MDS).

At that time, the study had enrolled 80 patients, including 59 with relapsed or refractory AML, 11 with de novo AML unfit for chemotherapy, 7 with high-risk MDS, and 3 with relapsed/refractory BPDCN.

Patients received a single cycle of SL-401 as a 15-minute intravenous infusion in 1 of 2 dosing regimens to determine the maximum tolerated dose (MTD) and assess antitumor activity.

With regimen A, 45 patients received doses ranging from 4 to 12.5 μg/kg every other day for up to 6 doses. With regimen B, 35 patients received doses ranging from 7.1 to 22.1 μg/kg daily for up to 5 doses.

Of the 59 patients with relapsed/refractory AML, 2 achieved complete responses (CRs), 5 had partial responses (PRs), and 8 had minor responses (MRs). One CR lasted more than 8 months, and the other lasted more than 25 months.

Of the 11 patients with AML who were not candidates for chemotherapy, 2 had PRs and 1 had an MR.  Among the 7 patients with high-risk MDS, there was 1 PR and 1 MR.

And among the 3 patients with BPDCN, there were 2 CRs. One CR lasted more than 2 months, and the other lasted more than 4 months.

The MTD was not achieved with regimen A, but the MTD for regimen B was 16.6 μg/kg/day. The dose-limiting toxicities were a gastrointestinal bleed (n=1), transaminase and creatinine kinase elevations (n=1), and capillary leak syndrome (n=3). There was no evidence of treatment-related bone marrow suppression.

Last year, researchers reported additional results in BPDCN patients (Frankel et al, Blood 2014).

Eleven BPDCN patients received a single course of SL-401 (at 12.5 μg/kg intravenously over 15 minutes) daily for up to 5 doses. Three patients who had initial responses to SL-401 received a second course while in relapse.

Seven of 9 evaluable (78%) patients responded to a single course of SL-401. There were 5 CRs and 2 PRs. The median duration of responses was 5 months (range, 1-20+ months).

The most common adverse events were transient and included fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia.

Three multicenter clinical trials of SL-401 are currently open in the following indications:

1. BPDCN and relapsed/refractory AML
2. AML patients in first complete remission with minimal residual disease
3. Four types of advanced, high-risk myeloproliferative neoplasms, including systemic mastocytosis, advanced symptomatic hypereosinophilic disorder, myelofibrosis, and chronic myelomonocytic leukemia.

Additional SL-401 studies are planned for patients with myeloma, lymphomas, and other leukemias.

About orphan designation

In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.

Companies that obtain orphan designation for a drug in the EU benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is on the market. Fee reductions are also available, depending on the status of the sponsor and the type of service required.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

In the US, orphan designation provides the sponsor of a drug with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

AML cells

Image by Lance Liotta

The investigational therapy SL-401 has received orphan designation to treat acute myeloid leukemia (AML) in the European Union (EU).

SL-401 targets the interleukin-3 receptor (IL-3R). It is comprised of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is under development to treat a range of hematologic malignancies, as IL-3R is overexpressed on cancer stem cells in multiple hematologic malignancies.

SL-401 has orphan designation from the US Food and Drug Administration (FDA) for the treatment of AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 research

At ASH 2012 (abstract 3625), researchers reported results with SL-401 in a study of patients with AML, BPDCN, and myelodysplastic syndromes (MDS).

At that time, the study had enrolled 80 patients, including 59 with relapsed or refractory AML, 11 with de novo AML unfit for chemotherapy, 7 with high-risk MDS, and 3 with relapsed/refractory BPDCN.

Patients received a single cycle of SL-401 as a 15-minute intravenous infusion in 1 of 2 dosing regimens to determine the maximum tolerated dose (MTD) and assess antitumor activity.

With regimen A, 45 patients received doses ranging from 4 to 12.5 μg/kg every other day for up to 6 doses. With regimen B, 35 patients received doses ranging from 7.1 to 22.1 μg/kg daily for up to 5 doses.

Of the 59 patients with relapsed/refractory AML, 2 achieved complete responses (CRs), 5 had partial responses (PRs), and 8 had minor responses (MRs). One CR lasted more than 8 months, and the other lasted more than 25 months.

Of the 11 patients with AML who were not candidates for chemotherapy, 2 had PRs and 1 had an MR.  Among the 7 patients with high-risk MDS, there was 1 PR and 1 MR.

And among the 3 patients with BPDCN, there were 2 CRs. One CR lasted more than 2 months, and the other lasted more than 4 months.

The MTD was not achieved with regimen A, but the MTD for regimen B was 16.6 μg/kg/day. The dose-limiting toxicities were a gastrointestinal bleed (n=1), transaminase and creatinine kinase elevations (n=1), and capillary leak syndrome (n=3). There was no evidence of treatment-related bone marrow suppression.

Last year, researchers reported additional results in BPDCN patients (Frankel et al, Blood 2014).

Eleven BPDCN patients received a single course of SL-401 (at 12.5 μg/kg intravenously over 15 minutes) daily for up to 5 doses. Three patients who had initial responses to SL-401 received a second course while in relapse.

Seven of 9 evaluable (78%) patients responded to a single course of SL-401. There were 5 CRs and 2 PRs. The median duration of responses was 5 months (range, 1-20+ months).

The most common adverse events were transient and included fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia.

Three multicenter clinical trials of SL-401 are currently open in the following indications:

1. BPDCN and relapsed/refractory AML
2. AML patients in first complete remission with minimal residual disease
3. Four types of advanced, high-risk myeloproliferative neoplasms, including systemic mastocytosis, advanced symptomatic hypereosinophilic disorder, myelofibrosis, and chronic myelomonocytic leukemia.

Additional SL-401 studies are planned for patients with myeloma, lymphomas, and other leukemias.

About orphan designation

In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.

Companies that obtain orphan designation for a drug in the EU benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is on the market. Fee reductions are also available, depending on the status of the sponsor and the type of service required.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

In the US, orphan designation provides the sponsor of a drug with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

AML cells

Image by Lance Liotta

The investigational therapy SL-401 has received orphan designation to treat acute myeloid leukemia (AML) in the European Union (EU).

SL-401 targets the interleukin-3 receptor (IL-3R). It is comprised of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is under development to treat a range of hematologic malignancies, as IL-3R is overexpressed on cancer stem cells in multiple hematologic malignancies.

SL-401 has orphan designation from the US Food and Drug Administration (FDA) for the treatment of AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 research

At ASH 2012 (abstract 3625), researchers reported results with SL-401 in a study of patients with AML, BPDCN, and myelodysplastic syndromes (MDS).

At that time, the study had enrolled 80 patients, including 59 with relapsed or refractory AML, 11 with de novo AML unfit for chemotherapy, 7 with high-risk MDS, and 3 with relapsed/refractory BPDCN.

Patients received a single cycle of SL-401 as a 15-minute intravenous infusion in 1 of 2 dosing regimens to determine the maximum tolerated dose (MTD) and assess antitumor activity.

With regimen A, 45 patients received doses ranging from 4 to 12.5 μg/kg every other day for up to 6 doses. With regimen B, 35 patients received doses ranging from 7.1 to 22.1 μg/kg daily for up to 5 doses.

Of the 59 patients with relapsed/refractory AML, 2 achieved complete responses (CRs), 5 had partial responses (PRs), and 8 had minor responses (MRs). One CR lasted more than 8 months, and the other lasted more than 25 months.

Of the 11 patients with AML who were not candidates for chemotherapy, 2 had PRs and 1 had an MR.  Among the 7 patients with high-risk MDS, there was 1 PR and 1 MR.

And among the 3 patients with BPDCN, there were 2 CRs. One CR lasted more than 2 months, and the other lasted more than 4 months.

The MTD was not achieved with regimen A, but the MTD for regimen B was 16.6 μg/kg/day. The dose-limiting toxicities were a gastrointestinal bleed (n=1), transaminase and creatinine kinase elevations (n=1), and capillary leak syndrome (n=3). There was no evidence of treatment-related bone marrow suppression.

Last year, researchers reported additional results in BPDCN patients (Frankel et al, Blood 2014).

Eleven BPDCN patients received a single course of SL-401 (at 12.5 μg/kg intravenously over 15 minutes) daily for up to 5 doses. Three patients who had initial responses to SL-401 received a second course while in relapse.

Seven of 9 evaluable (78%) patients responded to a single course of SL-401. There were 5 CRs and 2 PRs. The median duration of responses was 5 months (range, 1-20+ months).

The most common adverse events were transient and included fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia.

Three multicenter clinical trials of SL-401 are currently open in the following indications:

1. BPDCN and relapsed/refractory AML
2. AML patients in first complete remission with minimal residual disease
3. Four types of advanced, high-risk myeloproliferative neoplasms, including systemic mastocytosis, advanced symptomatic hypereosinophilic disorder, myelofibrosis, and chronic myelomonocytic leukemia.

Additional SL-401 studies are planned for patients with myeloma, lymphomas, and other leukemias.

About orphan designation

In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.

Companies that obtain orphan designation for a drug in the EU benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is on the market. Fee reductions are also available, depending on the status of the sponsor and the type of service required.

The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

In the US, orphan designation provides the sponsor of a drug with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

Learning about death and dying in residency is perhaps one of the hardest things about being a doctor. ... This list might make it a tiny bit easier.

1. The Hippocratic oath challenges us to be teachers not only to students, but also to our patients – especially to our dying patients. Remember you are teachers.

2. Nurses spend the most time with your patients; utilize them and learn from them. Nurses will make you better teachers and physicians.

3. When a patient is dying, hold that person’s hand if family isn’t around. Touch your patient.

4. Accompany your residents, fellows, or attending physicians to deliver bad news.

5. Ask to debrief after a patient dies.

6. While discussing treatment or prognosis with families, pay attention to the emotional data in the room. Tears should prompt tissues or hand holding. A wrinkled forehead or fearful face warrants a pause in conversation for the family to absorb the content. Tears don’t mean to hurry.

7. Attempt to understand your patient’s expectations. In other words, learn what the family’s goals are for treatment.

8. When a patient dies, reflect upon it in moderation. Don’t just move on to the next task. It’s okay to feel and to grieve … you are human.

9. When families declare DNR [do not resuscitate], don’t ask them repeatedly if they are sure. Also, make certain that they know they can change their minds at any time. Respect a patient’s values and wishes.

10. Take the time to have the difficult conversations early in diagnosis so families know what to expect. This empowers decisions that are proactive as opposed to reactive. Be proactive in your role as a teacher.

11. When discussing options, talk about what you CAN do before you talk about what you CAN’T do.

12. Withdrawing treatment and forgoing treatment are the same thing ethically and legally, but not emotionally.

13. When your patient is actively dying, see it out. Stay with the family, even if it’s time to go home.

14. When the family prays, be present.

15. Palliative care is neither hospice nor social work.

16. Ask your dying patients if they are afraid of anything – if the moment presents itself. Answer questions about death or find someone who can answer their questions.

17. No patient should die in pain. The doctrine of double effect allows a caregiver to provide medication for pain even though it may hasten death.

18. For the dying child, ask the family where they want their child to die. Don’t assume the family wants the death of their child to be at home or in the hospital. Ask.

19. Transitioning from treatment-oriented management to comfort care does not ever mean “there is nothing we can do.”

20. Lastly, and most importantly, I leave you with a question that should be in the back of our minds regarding quality of life and treatment options: Just because we can, should we?

Dr. Morvant is a second-year pediatric resident at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn. E-mail her at pdnews@frontlinemedcom.com.

Learning about death and dying in residency is perhaps one of the hardest things about being a doctor. ... This list might make it a tiny bit easier.

1. The Hippocratic oath challenges us to be teachers not only to students, but also to our patients – especially to our dying patients. Remember you are teachers.

2. Nurses spend the most time with your patients; utilize them and learn from them. Nurses will make you better teachers and physicians.

3. When a patient is dying, hold that person’s hand if family isn’t around. Touch your patient.

4. Accompany your residents, fellows, or attending physicians to deliver bad news.

5. Ask to debrief after a patient dies.

6. While discussing treatment or prognosis with families, pay attention to the emotional data in the room. Tears should prompt tissues or hand holding. A wrinkled forehead or fearful face warrants a pause in conversation for the family to absorb the content. Tears don’t mean to hurry.

7. Attempt to understand your patient’s expectations. In other words, learn what the family’s goals are for treatment.

8. When a patient dies, reflect upon it in moderation. Don’t just move on to the next task. It’s okay to feel and to grieve … you are human.

9. When families declare DNR [do not resuscitate], don’t ask them repeatedly if they are sure. Also, make certain that they know they can change their minds at any time. Respect a patient’s values and wishes.

10. Take the time to have the difficult conversations early in diagnosis so families know what to expect. This empowers decisions that are proactive as opposed to reactive. Be proactive in your role as a teacher.

11. When discussing options, talk about what you CAN do before you talk about what you CAN’T do.

12. Withdrawing treatment and forgoing treatment are the same thing ethically and legally, but not emotionally.

13. When your patient is actively dying, see it out. Stay with the family, even if it’s time to go home.

14. When the family prays, be present.

15. Palliative care is neither hospice nor social work.

16. Ask your dying patients if they are afraid of anything – if the moment presents itself. Answer questions about death or find someone who can answer their questions.

17. No patient should die in pain. The doctrine of double effect allows a caregiver to provide medication for pain even though it may hasten death.

18. For the dying child, ask the family where they want their child to die. Don’t assume the family wants the death of their child to be at home or in the hospital. Ask.

19. Transitioning from treatment-oriented management to comfort care does not ever mean “there is nothing we can do.”

20. Lastly, and most importantly, I leave you with a question that should be in the back of our minds regarding quality of life and treatment options: Just because we can, should we?

Dr. Morvant is a second-year pediatric resident at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn. E-mail her at pdnews@frontlinemedcom.com.

Learning about death and dying in residency is perhaps one of the hardest things about being a doctor. ... This list might make it a tiny bit easier.

1. The Hippocratic oath challenges us to be teachers not only to students, but also to our patients – especially to our dying patients. Remember you are teachers.

2. Nurses spend the most time with your patients; utilize them and learn from them. Nurses will make you better teachers and physicians.

3. When a patient is dying, hold that person’s hand if family isn’t around. Touch your patient.

4. Accompany your residents, fellows, or attending physicians to deliver bad news.

5. Ask to debrief after a patient dies.

6. While discussing treatment or prognosis with families, pay attention to the emotional data in the room. Tears should prompt tissues or hand holding. A wrinkled forehead or fearful face warrants a pause in conversation for the family to absorb the content. Tears don’t mean to hurry.

7. Attempt to understand your patient’s expectations. In other words, learn what the family’s goals are for treatment.

8. When a patient dies, reflect upon it in moderation. Don’t just move on to the next task. It’s okay to feel and to grieve … you are human.

9. When families declare DNR [do not resuscitate], don’t ask them repeatedly if they are sure. Also, make certain that they know they can change their minds at any time. Respect a patient’s values and wishes.

10. Take the time to have the difficult conversations early in diagnosis so families know what to expect. This empowers decisions that are proactive as opposed to reactive. Be proactive in your role as a teacher.

11. When discussing options, talk about what you CAN do before you talk about what you CAN’T do.

12. Withdrawing treatment and forgoing treatment are the same thing ethically and legally, but not emotionally.

13. When your patient is actively dying, see it out. Stay with the family, even if it’s time to go home.

14. When the family prays, be present.

15. Palliative care is neither hospice nor social work.

16. Ask your dying patients if they are afraid of anything – if the moment presents itself. Answer questions about death or find someone who can answer their questions.

17. No patient should die in pain. The doctrine of double effect allows a caregiver to provide medication for pain even though it may hasten death.

18. For the dying child, ask the family where they want their child to die. Don’t assume the family wants the death of their child to be at home or in the hospital. Ask.

19. Transitioning from treatment-oriented management to comfort care does not ever mean “there is nothing we can do.”

20. Lastly, and most importantly, I leave you with a question that should be in the back of our minds regarding quality of life and treatment options: Just because we can, should we?

Dr. Morvant is a second-year pediatric resident at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn. E-mail her at pdnews@frontlinemedcom.com.

The Food and Drug Administration has issued a new warning and precaution for the type 2 diabetes drug canagliflozin, saying that risks of decreased bone density associated with the drug are more serious than previously stated.

Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, will now have a revised adverse reactions section on its drug label. Taking canagliflozin can significantly increase an individual’s chances of incurring bone fractures, due to the decreased bone mineral density caused by the drug. According to the FDA, these fractures can start to appear 12 weeks after starting a canagliflozin regimen, and can lead to bone mineral density loss in the hip and lower spine.

“FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empagliflozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed,” the FDA stated, adding that all health care providers and patients are urged to contact the FDA if they experience adverse effects while taking any of these drugs.

Canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013. The FDA is advising all health care professionals to carefully assess patients’ risk for developing bone fractures before prescribing the drug. Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

dchitnis@frontlinemedcom.com

The Food and Drug Administration has issued a new warning and precaution for the type 2 diabetes drug canagliflozin, saying that risks of decreased bone density associated with the drug are more serious than previously stated.

Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, will now have a revised adverse reactions section on its drug label. Taking canagliflozin can significantly increase an individual’s chances of incurring bone fractures, due to the decreased bone mineral density caused by the drug. According to the FDA, these fractures can start to appear 12 weeks after starting a canagliflozin regimen, and can lead to bone mineral density loss in the hip and lower spine.

“FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empagliflozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed,” the FDA stated, adding that all health care providers and patients are urged to contact the FDA if they experience adverse effects while taking any of these drugs.

Canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013. The FDA is advising all health care professionals to carefully assess patients’ risk for developing bone fractures before prescribing the drug. Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

dchitnis@frontlinemedcom.com

The Food and Drug Administration has issued a new warning and precaution for the type 2 diabetes drug canagliflozin, saying that risks of decreased bone density associated with the drug are more serious than previously stated.

Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, will now have a revised adverse reactions section on its drug label. Taking canagliflozin can significantly increase an individual’s chances of incurring bone fractures, due to the decreased bone mineral density caused by the drug. According to the FDA, these fractures can start to appear 12 weeks after starting a canagliflozin regimen, and can lead to bone mineral density loss in the hip and lower spine.

“FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empagliflozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed,” the FDA stated, adding that all health care providers and patients are urged to contact the FDA if they experience adverse effects while taking any of these drugs.

Canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013. The FDA is advising all health care professionals to carefully assess patients’ risk for developing bone fractures before prescribing the drug. Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

dchitnis@frontlinemedcom.com

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

The prevalence of diabetes increases as patients age and gain weight. More than one-third of nursing home residents have diabetes. The overall treatment goals for elderly patients with diabetes are similar to those for younger patients, but somehow the stakes feel higher. Polypharmacy, decreased activity, shifting dietary patterns, hyperglycemia, fears of hypoglycemia leading to falls, worsening comorbid conditions, and hospitalization pose great challenges to ideal management.

Because of these concerns, caution is raised about the use of insulin or oral agents that cause hypoglycemia in frail older adults in long-term care facilities. But these agents are used, and perhaps we understand little about their comparative risks.

Dr. Francisco J. Pasquel of Emory University, Atlanta, and his colleagues conducted a randomized clinical trial evaluating the comparative safety and effectiveness of basal insulin or an oral antidiabetic drug (OAD) for 26 weeks (BMJ Open Diab Res Care. 2015;3:e000104).

A total of 150 patients, average age 79 years, with a blood glucose level greater than 180 mg/dL or a hemoglobin A_1c greater than 7.5%, treated with diet or an oral agent, were randomized to either 0.1 U/kg per day of glargine or continuation of oral agents (metformin, insulin secretagogues, thiazolidinediones, or DPP-4 inhibitors). Glargine was adjusted based on blood sugar readings.

In the OAD group, 16% of patients were treated with metformin plus sulfonylurea, 27% with a sulfonylurea alone, and 8% with sulfonylurea and a DPP-4 inhibitor.

There were 62 hypoglycemic events in the OAD group and 43 in the basal insulin group (P = .4). Overall, daily blood glucose levels did not differ between the groups. Rates of cardiovascular events, renal failure, infection, falls, emergency department visits, hospital admissions, and mortality were similar between the two groups.

Although these data are somewhat reassuring, power may have been an issue, and a larger sample size may have resulted in detection of more hypoglycemic events in the OAD group. On the other hand, the data are balanced and resonate with previous data showing that in older adults with diabetes (about 74 years of age), intensive glycemic control is associated with an increased risk of falls in insulin users but not in those treated with OADs. The goal of the current study was not intensive glycemic control.

So, for patients in a long-term care facility, metformin and the DPP-4 inhibitors will be weight neutral without risk of hypoglycemia. Therefore, these may be the “go-to” drugs if the DPP-4 inhibitors are affordable and you do not have a long way to go for control (DPP-4 inhibitors tend to be relatively mild agents, lowering HbA_1c by 0.6%). If a sulfonylurea must be used, glipizide should be chosen, because it has a shorter half-life.

Balance all of this with appropriate HbA_1c goals for your patient adjusted for medical comorbidity, goals of care, and life expectancy.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of diabetes increases as patients age and gain weight. More than one-third of nursing home residents have diabetes. The overall treatment goals for elderly patients with diabetes are similar to those for younger patients, but somehow the stakes feel higher. Polypharmacy, decreased activity, shifting dietary patterns, hyperglycemia, fears of hypoglycemia leading to falls, worsening comorbid conditions, and hospitalization pose great challenges to ideal management.

Because of these concerns, caution is raised about the use of insulin or oral agents that cause hypoglycemia in frail older adults in long-term care facilities. But these agents are used, and perhaps we understand little about their comparative risks.

Dr. Francisco J. Pasquel of Emory University, Atlanta, and his colleagues conducted a randomized clinical trial evaluating the comparative safety and effectiveness of basal insulin or an oral antidiabetic drug (OAD) for 26 weeks (BMJ Open Diab Res Care. 2015;3:e000104).

A total of 150 patients, average age 79 years, with a blood glucose level greater than 180 mg/dL or a hemoglobin A_1c greater than 7.5%, treated with diet or an oral agent, were randomized to either 0.1 U/kg per day of glargine or continuation of oral agents (metformin, insulin secretagogues, thiazolidinediones, or DPP-4 inhibitors). Glargine was adjusted based on blood sugar readings.

In the OAD group, 16% of patients were treated with metformin plus sulfonylurea, 27% with a sulfonylurea alone, and 8% with sulfonylurea and a DPP-4 inhibitor.

There were 62 hypoglycemic events in the OAD group and 43 in the basal insulin group (P = .4). Overall, daily blood glucose levels did not differ between the groups. Rates of cardiovascular events, renal failure, infection, falls, emergency department visits, hospital admissions, and mortality were similar between the two groups.

Although these data are somewhat reassuring, power may have been an issue, and a larger sample size may have resulted in detection of more hypoglycemic events in the OAD group. On the other hand, the data are balanced and resonate with previous data showing that in older adults with diabetes (about 74 years of age), intensive glycemic control is associated with an increased risk of falls in insulin users but not in those treated with OADs. The goal of the current study was not intensive glycemic control.

So, for patients in a long-term care facility, metformin and the DPP-4 inhibitors will be weight neutral without risk of hypoglycemia. Therefore, these may be the “go-to” drugs if the DPP-4 inhibitors are affordable and you do not have a long way to go for control (DPP-4 inhibitors tend to be relatively mild agents, lowering HbA_1c by 0.6%). If a sulfonylurea must be used, glipizide should be chosen, because it has a shorter half-life.

Balance all of this with appropriate HbA_1c goals for your patient adjusted for medical comorbidity, goals of care, and life expectancy.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of diabetes increases as patients age and gain weight. More than one-third of nursing home residents have diabetes. The overall treatment goals for elderly patients with diabetes are similar to those for younger patients, but somehow the stakes feel higher. Polypharmacy, decreased activity, shifting dietary patterns, hyperglycemia, fears of hypoglycemia leading to falls, worsening comorbid conditions, and hospitalization pose great challenges to ideal management.

Because of these concerns, caution is raised about the use of insulin or oral agents that cause hypoglycemia in frail older adults in long-term care facilities. But these agents are used, and perhaps we understand little about their comparative risks.

Dr. Francisco J. Pasquel of Emory University, Atlanta, and his colleagues conducted a randomized clinical trial evaluating the comparative safety and effectiveness of basal insulin or an oral antidiabetic drug (OAD) for 26 weeks (BMJ Open Diab Res Care. 2015;3:e000104).

A total of 150 patients, average age 79 years, with a blood glucose level greater than 180 mg/dL or a hemoglobin A_1c greater than 7.5%, treated with diet or an oral agent, were randomized to either 0.1 U/kg per day of glargine or continuation of oral agents (metformin, insulin secretagogues, thiazolidinediones, or DPP-4 inhibitors). Glargine was adjusted based on blood sugar readings.

In the OAD group, 16% of patients were treated with metformin plus sulfonylurea, 27% with a sulfonylurea alone, and 8% with sulfonylurea and a DPP-4 inhibitor.

There were 62 hypoglycemic events in the OAD group and 43 in the basal insulin group (P = .4). Overall, daily blood glucose levels did not differ between the groups. Rates of cardiovascular events, renal failure, infection, falls, emergency department visits, hospital admissions, and mortality were similar between the two groups.

Although these data are somewhat reassuring, power may have been an issue, and a larger sample size may have resulted in detection of more hypoglycemic events in the OAD group. On the other hand, the data are balanced and resonate with previous data showing that in older adults with diabetes (about 74 years of age), intensive glycemic control is associated with an increased risk of falls in insulin users but not in those treated with OADs. The goal of the current study was not intensive glycemic control.

So, for patients in a long-term care facility, metformin and the DPP-4 inhibitors will be weight neutral without risk of hypoglycemia. Therefore, these may be the “go-to” drugs if the DPP-4 inhibitors are affordable and you do not have a long way to go for control (DPP-4 inhibitors tend to be relatively mild agents, lowering HbA_1c by 0.6%). If a sulfonylurea must be used, glipizide should be chosen, because it has a shorter half-life.

Balance all of this with appropriate HbA_1c goals for your patient adjusted for medical comorbidity, goals of care, and life expectancy.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

Psoriasis and acne appear to be susceptible to seasonal variations of clearing and worsening, with an analysis revealing both conditions maintained a significant trend of summer clearing and winter worsening, according to a research letter published in the Journal of the American Academy of Dermatology.

Using Physician’s Global Assessment scales for psoriasis and acne, Dr. Vanessa Lindsay Pascoe and Dr. Alexandra Boer Kimball, both of Massachusetts General Hospital, Boston, collected data from 5,468 psoriasis patients and 9,301 acne patients between June 2011 and May 2014 in the New England area. Among the psoriasis patient group, 16% were seen in the summer, 25% in the fall, 31% in the winter, and 28% in the spring. The trend was similar for acne patients, with 18% seen in the summer, 25% in the fall, 28% in the winter, and 29% in the spring. There were no significant seasonal differences in age or sex for either group.

©olavs/thinkstockphotos.com

The percentage of psoriasis patients with clear/almost clear disease was highest in the summer at 20.4%, while the percentage of patients with moderate/severe disease was highest in the winter at 40.5%. For acne, the percentage of patients with clear/almost clear disease was highest in the fall at 17.5%, and the percentage of patients with moderate/severe disease was highest in the winter at 45.9%. Fewer psoriasis and acne patients presented to the clinic in the summer, which the researchers suggested could be due to disease improvement.

“Although the climate of the Northeastern United States may not generalize to regions with less seasonal variation, providers may consider seasonal adjustment of acne plans as they have traditionally done for psoriasis,” the authors wrote. “For example, they may wait until after winter to taper a systemic antibiotic for acne, just as some providers may wait until spring to change systemic psoriasis treatments.”

Read the full article in the Journal of the American Academy of Dermatology.

mbock@frontlinemedcom.com

Psoriasis and acne appear to be susceptible to seasonal variations of clearing and worsening, with an analysis revealing both conditions maintained a significant trend of summer clearing and winter worsening, according to a research letter published in the Journal of the American Academy of Dermatology.

Using Physician’s Global Assessment scales for psoriasis and acne, Dr. Vanessa Lindsay Pascoe and Dr. Alexandra Boer Kimball, both of Massachusetts General Hospital, Boston, collected data from 5,468 psoriasis patients and 9,301 acne patients between June 2011 and May 2014 in the New England area. Among the psoriasis patient group, 16% were seen in the summer, 25% in the fall, 31% in the winter, and 28% in the spring. The trend was similar for acne patients, with 18% seen in the summer, 25% in the fall, 28% in the winter, and 29% in the spring. There were no significant seasonal differences in age or sex for either group.

©olavs/thinkstockphotos.com

The percentage of psoriasis patients with clear/almost clear disease was highest in the summer at 20.4%, while the percentage of patients with moderate/severe disease was highest in the winter at 40.5%. For acne, the percentage of patients with clear/almost clear disease was highest in the fall at 17.5%, and the percentage of patients with moderate/severe disease was highest in the winter at 45.9%. Fewer psoriasis and acne patients presented to the clinic in the summer, which the researchers suggested could be due to disease improvement.

“Although the climate of the Northeastern United States may not generalize to regions with less seasonal variation, providers may consider seasonal adjustment of acne plans as they have traditionally done for psoriasis,” the authors wrote. “For example, they may wait until after winter to taper a systemic antibiotic for acne, just as some providers may wait until spring to change systemic psoriasis treatments.”

Read the full article in the Journal of the American Academy of Dermatology.

mbock@frontlinemedcom.com

Psoriasis and acne appear to be susceptible to seasonal variations of clearing and worsening, with an analysis revealing both conditions maintained a significant trend of summer clearing and winter worsening, according to a research letter published in the Journal of the American Academy of Dermatology.

Using Physician’s Global Assessment scales for psoriasis and acne, Dr. Vanessa Lindsay Pascoe and Dr. Alexandra Boer Kimball, both of Massachusetts General Hospital, Boston, collected data from 5,468 psoriasis patients and 9,301 acne patients between June 2011 and May 2014 in the New England area. Among the psoriasis patient group, 16% were seen in the summer, 25% in the fall, 31% in the winter, and 28% in the spring. The trend was similar for acne patients, with 18% seen in the summer, 25% in the fall, 28% in the winter, and 29% in the spring. There were no significant seasonal differences in age or sex for either group.

©olavs/thinkstockphotos.com

The percentage of psoriasis patients with clear/almost clear disease was highest in the summer at 20.4%, while the percentage of patients with moderate/severe disease was highest in the winter at 40.5%. For acne, the percentage of patients with clear/almost clear disease was highest in the fall at 17.5%, and the percentage of patients with moderate/severe disease was highest in the winter at 45.9%. Fewer psoriasis and acne patients presented to the clinic in the summer, which the researchers suggested could be due to disease improvement.

“Although the climate of the Northeastern United States may not generalize to regions with less seasonal variation, providers may consider seasonal adjustment of acne plans as they have traditionally done for psoriasis,” the authors wrote. “For example, they may wait until after winter to taper a systemic antibiotic for acne, just as some providers may wait until spring to change systemic psoriasis treatments.”

Read the full article in the Journal of the American Academy of Dermatology.

mbock@frontlinemedcom.com

Cryptogenic stroke patients and their caregivers recently surveyed by the American Heart Association/American Stroke Association said that they experience several negative consequences of having an undetermined cause of their stroke, and only one-fifth received information about cryptogenic stroke at the time of diagnosis.

This lack of information prompted the organization to start the Cryptogenic Stroke Initiative. The initiative will inform cryptogenic stroke patients and help “them to work with their healthcare team to prevent a second stroke,” Dr. Mary Ann Bauman, chair of the American Stroke Association Advisory Committee, said in an announcement.

©American Stroke Association

This month, the American Heart Association/American Stroke Association, with support from Medtronic, published a free informational document. This Patient Guide to Cryptogenic Stroke is the first of several guides that the American Stroke Association plans to create for cryptogenic stroke patients. This edition of the guide includes “information on cryptogenic stroke diagnosis, what happens during a stroke, secondary prevention information, questions [for patients to ask their doctor, and] support resources,” the Association said.

In the organizations’ survey, which included 309 cryptogenic stroke patients and caregivers, more than 50% reported anxiety and frustration when the cause of stroke is undetermined. Of the 20% of patients and caregivers who received information about cryptogenic stroke at the time of diagnosis, the information was verbally communicated 75% of the time.

klennon@frontlinemedcom.com

Cryptogenic stroke patients and their caregivers recently surveyed by the American Heart Association/American Stroke Association said that they experience several negative consequences of having an undetermined cause of their stroke, and only one-fifth received information about cryptogenic stroke at the time of diagnosis.

This lack of information prompted the organization to start the Cryptogenic Stroke Initiative. The initiative will inform cryptogenic stroke patients and help “them to work with their healthcare team to prevent a second stroke,” Dr. Mary Ann Bauman, chair of the American Stroke Association Advisory Committee, said in an announcement.

©American Stroke Association

This month, the American Heart Association/American Stroke Association, with support from Medtronic, published a free informational document. This Patient Guide to Cryptogenic Stroke is the first of several guides that the American Stroke Association plans to create for cryptogenic stroke patients. This edition of the guide includes “information on cryptogenic stroke diagnosis, what happens during a stroke, secondary prevention information, questions [for patients to ask their doctor, and] support resources,” the Association said.

In the organizations’ survey, which included 309 cryptogenic stroke patients and caregivers, more than 50% reported anxiety and frustration when the cause of stroke is undetermined. Of the 20% of patients and caregivers who received information about cryptogenic stroke at the time of diagnosis, the information was verbally communicated 75% of the time.

klennon@frontlinemedcom.com

Cryptogenic stroke patients and their caregivers recently surveyed by the American Heart Association/American Stroke Association said that they experience several negative consequences of having an undetermined cause of their stroke, and only one-fifth received information about cryptogenic stroke at the time of diagnosis.

This lack of information prompted the organization to start the Cryptogenic Stroke Initiative. The initiative will inform cryptogenic stroke patients and help “them to work with their healthcare team to prevent a second stroke,” Dr. Mary Ann Bauman, chair of the American Stroke Association Advisory Committee, said in an announcement.

©American Stroke Association

This month, the American Heart Association/American Stroke Association, with support from Medtronic, published a free informational document. This Patient Guide to Cryptogenic Stroke is the first of several guides that the American Stroke Association plans to create for cryptogenic stroke patients. This edition of the guide includes “information on cryptogenic stroke diagnosis, what happens during a stroke, secondary prevention information, questions [for patients to ask their doctor, and] support resources,” the Association said.

In the organizations’ survey, which included 309 cryptogenic stroke patients and caregivers, more than 50% reported anxiety and frustration when the cause of stroke is undetermined. Of the 20% of patients and caregivers who received information about cryptogenic stroke at the time of diagnosis, the information was verbally communicated 75% of the time.

klennon@frontlinemedcom.com

There was a 2.4-fold increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), for Air Force veterans exposed to Agent Orange, according to a study reported in JAMA Oncology. Already, veterans who develop MM and were exposed to Agent Orange during military service are eligible to receive benefits, but the study further highlights the relationship.

Related: Management of Myeloma and Its Precursor Syndromes

The Agent Orange used during aerial spray missions of herbicides in the Vietnam War contained 2, 4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as human carcinogen 2,3,7,8-tetrachlorodibenzo-p-doxin in variable amounts. After obtaining the laboratory data from 958 serum samples from Air Force personnel, the Air Force Health Studies questionnaire, and results from the physical exam from all participants, researchers were able to compare their findings with control group veterans.

Related: Nephrotic Syndrome Is a Marker for Occult Cancer

The researchers created 2 test groups from Air Force veterans. The first were 777 participants of Operation Ranch Hand, who conducted aerial herbicidal missions from 1962 to 1971, and the second group was made up of 1,174 participants, who had similar duties but did not participate in the missions.

The risk of MGUS was more pronounced in veterans aged > 70 years (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.27-4.44; P = .007). Among veterans aged > 70 years, there was not a significant increase in risk (OR, 1.4%; 95% CI, 0.55-3.63; P = .63). The crude prevalence of overall MGUS was 7.1% (34 of 479) in the exposed veterans, compared with 3.1% (15 of 479) in the comparison group.

Source
Landgren O, Shim YK, Michalek J, et al. JAMA Oncol. [Published online ahead of print September 3, 2015.]
doi: 10.1001/jamaoncol.2015.2938.

There was a 2.4-fold increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), for Air Force veterans exposed to Agent Orange, according to a study reported in JAMA Oncology. Already, veterans who develop MM and were exposed to Agent Orange during military service are eligible to receive benefits, but the study further highlights the relationship.

Related: Management of Myeloma and Its Precursor Syndromes

The Agent Orange used during aerial spray missions of herbicides in the Vietnam War contained 2, 4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as human carcinogen 2,3,7,8-tetrachlorodibenzo-p-doxin in variable amounts. After obtaining the laboratory data from 958 serum samples from Air Force personnel, the Air Force Health Studies questionnaire, and results from the physical exam from all participants, researchers were able to compare their findings with control group veterans.

Related: Nephrotic Syndrome Is a Marker for Occult Cancer

The researchers created 2 test groups from Air Force veterans. The first were 777 participants of Operation Ranch Hand, who conducted aerial herbicidal missions from 1962 to 1971, and the second group was made up of 1,174 participants, who had similar duties but did not participate in the missions.

The risk of MGUS was more pronounced in veterans aged > 70 years (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.27-4.44; P = .007). Among veterans aged > 70 years, there was not a significant increase in risk (OR, 1.4%; 95% CI, 0.55-3.63; P = .63). The crude prevalence of overall MGUS was 7.1% (34 of 479) in the exposed veterans, compared with 3.1% (15 of 479) in the comparison group.

Source
Landgren O, Shim YK, Michalek J, et al. JAMA Oncol. [Published online ahead of print September 3, 2015.]
doi: 10.1001/jamaoncol.2015.2938.

There was a 2.4-fold increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), for Air Force veterans exposed to Agent Orange, according to a study reported in JAMA Oncology. Already, veterans who develop MM and were exposed to Agent Orange during military service are eligible to receive benefits, but the study further highlights the relationship.

Related: Management of Myeloma and Its Precursor Syndromes

The Agent Orange used during aerial spray missions of herbicides in the Vietnam War contained 2, 4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as human carcinogen 2,3,7,8-tetrachlorodibenzo-p-doxin in variable amounts. After obtaining the laboratory data from 958 serum samples from Air Force personnel, the Air Force Health Studies questionnaire, and results from the physical exam from all participants, researchers were able to compare their findings with control group veterans.

Related: Nephrotic Syndrome Is a Marker for Occult Cancer

The researchers created 2 test groups from Air Force veterans. The first were 777 participants of Operation Ranch Hand, who conducted aerial herbicidal missions from 1962 to 1971, and the second group was made up of 1,174 participants, who had similar duties but did not participate in the missions.

The risk of MGUS was more pronounced in veterans aged > 70 years (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.27-4.44; P = .007). Among veterans aged > 70 years, there was not a significant increase in risk (OR, 1.4%; 95% CI, 0.55-3.63; P = .63). The crude prevalence of overall MGUS was 7.1% (34 of 479) in the exposed veterans, compared with 3.1% (15 of 479) in the comparison group.

Source
Landgren O, Shim YK, Michalek J, et al. JAMA Oncol. [Published online ahead of print September 3, 2015.]
doi: 10.1001/jamaoncol.2015.2938.

Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders¹.

Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities².In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function³. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)^4.

After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment³. It is thought to have some antiacne properties as well¹. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance¹.

In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity⁵.

In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans¹.

Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-3².

Antimicrobial and mosquito repellent activity

In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency⁶.

Photoaging

Forest & Kim Starr/Wikimedia Commons/CC BY 3.0

Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents⁷.

In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity⁸. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol⁹. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response¹⁰.

The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use⁴.

Transdermal delivery

A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin¹¹. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.¹².

Conclusion

Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.

References

1. J Ethnopharmacol. 2014;154(2):408-18.

2. Eur J Pharm Sci. 2014;63:113-23.

3. Expert Opin Investig Drugs. 2013;22(2):245-57.

4. Chin Med J. (Engl) 2014;127(23):4001-5.

5. J Agric Food Chem. 2007;55(5):1737-42

6. Phytother Res. 2005;19(4):303-9.

7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.

8. Iran J Pharm Res. 2013 Summer;12(3):307-16.

9. Pak J Pharm Sci. 2013;26(6):1173-9.

10. Bioinformation 2013;9(6):321-4.

11. Zhong Yao Cai. 2008;31(11):1721-4

12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders¹.

Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities².In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function³. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)^4.

After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment³. It is thought to have some antiacne properties as well¹. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance¹.

In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity⁵.

In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans¹.

Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-3².

Antimicrobial and mosquito repellent activity

In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency⁶.

Photoaging

Forest & Kim Starr/Wikimedia Commons/CC BY 3.0

Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents⁷.

In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity⁸. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol⁹. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response¹⁰.

The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use⁴.

Transdermal delivery

A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin¹¹. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.¹².

Conclusion

Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.

References

1. J Ethnopharmacol. 2014;154(2):408-18.

2. Eur J Pharm Sci. 2014;63:113-23.

3. Expert Opin Investig Drugs. 2013;22(2):245-57.

4. Chin Med J. (Engl) 2014;127(23):4001-5.

5. J Agric Food Chem. 2007;55(5):1737-42

6. Phytother Res. 2005;19(4):303-9.

7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.

8. Iran J Pharm Res. 2013 Summer;12(3):307-16.

9. Pak J Pharm Sci. 2013;26(6):1173-9.

10. Bioinformation 2013;9(6):321-4.

11. Zhong Yao Cai. 2008;31(11):1721-4

12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders¹.

Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities².In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function³. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)^4.

After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment³. It is thought to have some antiacne properties as well¹. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance¹.

In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity⁵.

In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans¹.

Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-3².

Antimicrobial and mosquito repellent activity

In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency⁶.

Photoaging

Forest & Kim Starr/Wikimedia Commons/CC BY 3.0

Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents⁷.

In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity⁸. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol⁹. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response¹⁰.

The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use⁴.

Transdermal delivery

A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin¹¹. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.¹².

Conclusion

Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.

References

1. J Ethnopharmacol. 2014;154(2):408-18.

2. Eur J Pharm Sci. 2014;63:113-23.

3. Expert Opin Investig Drugs. 2013;22(2):245-57.

4. Chin Med J. (Engl) 2014;127(23):4001-5.

5. J Agric Food Chem. 2007;55(5):1737-42

6. Phytother Res. 2005;19(4):303-9.

7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.

8. Iran J Pharm Res. 2013 Summer;12(3):307-16.

9. Pak J Pharm Sci. 2013;26(6):1173-9.

10. Bioinformation 2013;9(6):321-4.

11. Zhong Yao Cai. 2008;31(11):1721-4

12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.