PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients.

Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in the liver, skeletal muscle, and adipose tissue, among others. As a leading cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cause a significant burden worldwide and therapeutic strategies are needed. This review provides an overview of the evidence on PPAR-targeted treatment of NAFLD and NASH in individuals with type 2 diabetes mellitus. We considered current evidence from clinical trials and observational studies as well as the impact of treatment on comorbid metabolic conditions such as obesity, dyslipidemia, and cardiovascular disease. Future areas of research, such as possible sexually dimorphic effects of PPAR-targeted therapies, are briefly reviewed.

Dapsone in a Large Tertiary Center: Outdated Therapeutic Option or Timeless Agent?

BACKGROUND: The ancient drug dapsone has antimicrobial and anti-inflammatory features. In dermatology, dapsone is primarily used for neutrophil-dominant skin diseases. However, real-life data assessing the long-term efficacy of dapsone across multiple dermatological diseases is missing. -Objectives: To determine the efficacy and safety of dapsone in patients with inflammatory skin diseases treated at the Department of Dermatology of the University Hospital Zurich. METHODS: The hospital database was searched for patients treated with dapsone in the last 20 years (from January 1, 1998, to December 31, 2017). Overall, 175 patients were included in our study. RESULTS: Thirty-four patients received dapsone for eosinophilic dermatoses, 82 for neutrophilic dermatoses and 59 for other dermatoses. After 3 months, 8% of all patients reached complete remission, 40.6% showed improvement, 30.3% had stable disease, and only 9.1% had disease progression. Final treatment evaluation revealed complete response in 13.2%, disease improvement in 47.4%, stable disease in 25.7% and disease progression in only 12.0%. Patients who showed remission or improvement after 3 months were significantly older than patients with stable or progressive disease. In addition, remission after 3 months was associated with a significantly lower dose of dapsone compared to improvement only. Hemolysis was the most common adverse event (21.7%). CONCLUSIONS: Our data show that dapsone is a valid treatment option in various dermatological diseases, leading to a favorable response in the vast majority of patients. In addition, it is well tolerated, safe and inexpensive. Randomized, controlled trials are needed to further elucidate the role of this high-potential drug.

Efficacy and safety of colchicine in inflammatory skin diseases: a retrospective, monocentric study in a large tertiary center.

Introduction: Colchicine is an ancient, but rarely used drug. Little data exist on its efficacy and safety in patients suffering from skin diseases. The objective of our study was to determine whether colchicine showed favorable efficacy and safety in our patients during the last 20 years.Methods: The hospital database was searched for patients treated with colchicine in the last 20 years (January 1, 1998 to December 31, 2017). Overall, total of 41 patients were included in our study.Results: In 63.4% of all patients, either a complete response or an improvement of disease was observed. Adverse events occurred rarely.Discussion: Colchicine is an effective and safe treatment.

Sex-related differences in wall remodeling and intraluminal thrombus resolution in a rat saccular aneurysm model.

OBJECTIVE: Intracranial aneurysms (IAs) are more often diagnosed in women. Hormones and vessel geometry, which influences wall shear stress, may affect pathophysiological processes of the arterial wall. Here, the authors investigated sex-related differences in the remodeling of the aneurysm wall and in intraluminal thrombus resolution. METHODS: A well-characterized surgical side-wall aneurysm model was used in female, male, and ovariectomized rats. Decellularized grafts were used to model highly degenerated and decellularized IA walls and native grafts to model healthy IA walls. Aneurysm growth and thrombus composition were analyzed at 1, 7, 14, and 28 days. Sex-related differences in vessel wall remodeling were compared with human IA dome samples of men and pre- and postmenopausal women. RESULTS: At 28 days, more aneurysm growth was observed in ovariectomized rats than in males or non-ovariectomized female rats. The parent artery size was larger in male rats than in female or ovariectomized rats, as expected. Wall inflammation increased over time in all groups and was most severe in the decellularized female and ovariectomized groups at 28 days compared with the male group. Likewise, in these groups the most elastin fragmentation was seen at 28 days. In female rats, on days 1, 7, and 14, the intraluminal thrombus was mainly composed of red blood cells and fibrin. On days 14 and 28, macrophage and smooth muscle cell invasion inside the thrombus was shown, leading to the removal of red blood cells and deposition of collagen and elastin. On days 14 and 28, similar profiles of thrombus reorganization were observed in male and ovariectomized female rats. However, collagen content in thrombi and vessel wall macrophage content were higher in aneurysms of male rats at 28 days than in those of female rats. On day 28, thrombus coverage by endothelial cells was lower in ovariectomized than in female or male rats. Finally, analysis of human IA domes showed that endothelial cell coverage was lower in men and postmenopausal women than in younger women. CONCLUSIONS: Aneurysm growth and intraluminal thrombus resolution show sex-dependent differences. While certain processes (endothelial cell coverage and collagen deposition) point to a strong hormonal dependence, others (wall inflammation and aneurysm growth) seem to be influenced by both hormones and parent artery size.