Increased muscular phospholipase A2 activity in diabetic rats.

Anomalies in prostaglandin (PG) synthesis have been suggested in both experimental and human diabetes mellitus; increased levels of plasma and tissue eicosanoids has been recently reported by several investigators. One step in prostaglandin synthesis is the enzymatic hydrolysis of membrane phospholipids by Phospholipase A2 (PLA2). Nevertheless the alternative pathway involving Phospholipase C must be considered. An evaluation of PLA2 activity is therefore a useful method for studying prostaglandin synthesis in the peripheral target tissues of insulin activity. We studied PLA2 activity in normal and diabetic rat muscle. Streptozotocin-induced diabetic rats showed significantly higher muscular PLA2 activity when compared with controls (3.04 x 10(-2) +/- 0.50 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1 (p less than 0.01). This effect was not observed in diabetic animals successfully treated with insulin (1.78 x 10(-2) +/- 0.5 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1), and a significant correlation was found between blood glucose and muscular PLA2 activity (r = 0.42; p less than 0.05). Our results clearly show that in streptozotocin-induced diabetic rats muscular PLA2 activity is significantly higher. The relationship between blood glucose levels and muscular PLA2 activity and the decrease of PLA2 activity after insulin treatment suggest that these changes may be related to a defect in insulin effect.     

Preliminary evaluation of particle systems visualization on the skin surface by scanning electron microscopy and transparency profilometry

Background: There is a rising debate concerning the possible side effects arising from the use of particles at nanosize since the production of nanomaterials is increasing worldwide. Nanoparticles are able to enter the body through the skin, lungs or intestinal tract, depositing in several organs, and the risk associated with exposure to them, the routes of entry and the molecular mechanisms of any cytotoxicity need to be well understood. The aim of this work was to evaluate the suitability of skin replica as a method to study the colloidal systems visualization and distribution on skin surface. Methods: Solid lipid nanoparticles (SLN) were used as carrier systems. Skin replicas on healthy volunteers, before and after SLN application, were prepared and visualized using profilometry and scanning electron microscopy (SEM). Results: The results obtained in our study show that skin replica represents a suitable method to study the colloidal systems and their interaction with the skin surface. Conclusion: Profilometry enabled us to observe the systems distribution on a cutaneous texture. In addition, SEM, thanks to its high magnifications and field depth, allowed us to evaluate particles' distribution on the skin texture and the interaction between particles of different compositions and replica silicone.     

Relation between leptin and the metabolic syndrome in elderly women

BACKGROUND: Leptin has been shown to be linked to adiposity and insulin resistance in middle-aged participants. However, the association between leptin and metabolic syndrome independently of body fat and body fat distribution has not been evaluated in healthy elderly people. METHODS: We studied the independent relation between leptin and the components of the metabolic syndrome in 107 women aged 67-78 years with body mass index (BMI) ranging from 18.19 to 36.16 kg/m2. In all participants, we evaluated BMI, waist and hip circumferences, body composition by dual energy X-ray absorptiometry, fasting, and 2-hour glucose, lipids, insulin, homeostasis model assessment of insulin resistance (HOMA), systolic (SBP), diastolic blood pressure (DBP), and leptin. RESULTS: Significant correlation was found between leptin, BMI, waist circumference, fat mass, DBP, SBP, cholesterol, triglycerides, insulin, and HOMA. After adjusting for age and waist circumference, as well for age and fat mass, leptin was significantly related to insulin levels, HOMA, and cholesterol. In a stepwise multiple regression analysis using insulin levels or HOMA as dependent variables and age, waist circumference, fat mass, leptin, SBP, DBP, cholesterol, and triglycerides as independent variables, leptin entered the regression first, waist circumference second, and age third. CONCLUSION: Our study shows that leptin is significantly related to indices of adiposity in elderly women, and leptin is significantly associated with insulin levels, HOMA, and cholesterol independent of age, body fat, and fat distribution. Leptin, waist circumference, and age together explained 31% and 33% of insulin levels and HOMA variance, respectively, in healthy elderly women.     

Alström Syndrome: Mutation Spectrum of ALMS1

Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone‐rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world‐wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.     

Relationship between leptin levels and bone mineral density in the elderly

OBJECTIVE: To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly. DESIGN: A cross-sectional study. PATIENTS: A cohort of 92 men and 171 women, with ages ranging from 68 to 75 years, selected as a healthy and normal functioning group, in the city centre of Verona. MEASUREMENTS: Plasma leptin levels were determined in each participant. Body composition was evaluated with dual energy X-ray absorptiometry (DXA). Bone mineral content (BMC) and bone mineral density (BMD) were measured at whole-body, hip and femoral neck level in all subjects. RESULTS: In both men and women a significant relationship between fat mass and whole-body BMC or BMD was found. The strength of this association was consistently reduced after adjustment for plasma leptin. A significant association between circulating leptin levels, whole-body, total hip and femoral neck BMC and BMD was found in both sexes. This association retained the statistical significance after adjustment for fat mass percentage, especially in women. In stepwise multiple linear regression analyses, leptin was shown to be a significant predictor of whole-body, total hip and femoral neck BMC and BMD, independently of age and the percentage of body fat in both sexes. The circulating levels of leptin accounted for a variance in whole-body BMC of 8.9% in men and 18.2% in women, and in whole-body BMD of 10.6% in women. CONCLUSION: Our data show a significant relationship between leptin, bone mineral mass and density in healthy elderly men and women.     

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.     

Do oestrogen receptors play a role in the pathogenesis of HIV-associated lipodystrophy?

Epidemiological data show an increased risk of HIV-associated lipodystrophy in women, and sex hormone abnormalities have been reported with highly active antiretroviral therapy (HAART). This study, which demonstrates that oestrogen receptor beta expression is significantly reduced in the subcutaneous adipose tissue of HIV-infected lipodystrophic patients, downregulated by HAART regimens including protease inhibitors (PI), and restored after switching from PI, opens perspectives for the investigation of selective oestrogen receptor modifiers for the management of this syndrome.