Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life

Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome

Background: Women with polycystic ovary syndrome (PCOS) exhibit elevated serum advanced glycation end-products (AGE) compared with healthy subjects. Short-term administration of orlistat has been shown to reduce the postmeal increase in serum AGE levels in women with PCOS and in controls. Objective: To evaluate the long-term effect of orlistat and a low-calorie diet on serum AGE levels, and on the hormonal and metabolic profile of obese PCOS and normal women. Design: A clinical trial of 6 months of orlistat administration with an energy-restricted diet [basic metabolic rate (BMR) 600 kcal/day] in all subjects. Subjects: Twenty-nine women with PCOS [aged 27.52 ± 5.77 years; body mass index (BMI) 35.43 ± 5.31 kg/m2] and 18 controls (aged 32.06 ± 5.64 years; BMI 36.39 ± 6.47 kg/m2). Measurements: Serum AGE levels (U/ml), hormonal and metabolic profile. Results: PCOS and controls did not differ in BMI (P = 0.58), waist-to-hip ratio (WHR) (P = 0.44), fasting insulin concentration (P = 0.45) and glucose-to-insulin ratio (GIR) (P = 0.34). PCOS women exhibited statistically higher AGE (P < 0.001) and testosterone levels (P < 0.001) compared with controls. After 6 months of orlistat treatment, AGE levels showed a statistically significant decrease in both groups (PCOS: baseline 9.08 ± 1.84, post-orlistat 8.56 ± 1.95, P = 0.001; controls: baseline 5.02 ± 0.62, post-orlistat 4.91 ± 0.69, P = 0.03), independently of the BMI reduction in the PCOS group. A significant reduction was observed in BMI (PCOS: P < 0.001; controls: P < 0.001), WHR (PCOS: P = 0.002; controls: P = 0.04), fasting insulin (PCOS: P < 0.001; controls: P = 0.008), and testosterone concentrations in PCOS (P < 0.001). SHBG concentration (PCOS: P = 0.004; controls: P = 0.008) and GIR (PCOS: P < 0.001; controls: P = 0.03) were significantly increased. A significant improvement was also observed in insulin resistance indices post-treatment in both groups. Conclusions: Our data suggest that orlistat has a beneficial effect in reducing elevated AGE levels and improving the hormonal and metabolic profile in women with PCOS after 6 months of treatment, independently of BMI changes. © 2006 The Authors

The prognostic role of micronutrient status and supplements in COVID-19 outcomes: A systematic review

Micronutrients constitute an adjuvant treatment for respiratory viral infections. Since there is no effective antiviral therapy for COVID-19 yet, adjuvant intervention for the survival of critically ill patients may be significant. Search of the PubMed, CINAHL and Cochrane databases was carried out to find human studies investigating the prognostic role of micronutrient status and the effects of micronutrient supplementation intervention in COVID-19 outcomes of adult patients. Patients with certain comorbidities (diabetes mellitus type 2, obesity, renal failure, liver dysfunction etc.) or pregnant women were excluded. 31 studies (27 observational studies and 4 clinical trials) spanning the years 2020–2021, pertaining to 8624 COVID-19 patients (mean age±SD, 61 ± 9 years) were included in this systematic review. Few studies provided direct evidence on the association of serum levels of vitamin D, calcium, zinc, magnesium, phosphorus and selenium to patients' survival or death. Vitamin D and calcium were the most studied micronutrients and those with a probable promising favorable impact on patients. This review highlights the importance of a balanced nutritional status for a favorable outcome in COVID-19. Micronutrients’ deficiency on admission to hospital seems to be related to a high risk for ICU admission, intubation and even death. Nevertheless, evidence for intervention remains unclear. © 2022 Elsevier Lt

The prognostic role of micronutrient status and supplements in COVID-19 outcomes: A systematic review

Micronutrients constitute an adjuvant treatment for respiratory viral infections. Since there is no effective antiviral therapy for COVID-19 yet, adjuvant intervention for the survival of critically ill patients may be significant. Search of the PubMed, CINAHL and Cochrane databases was carried out to find human studies investigating the prognostic role of micronutrient status and the effects of micronutrient supplementation intervention in COVID-19 outcomes of adult patients. Patients with certain comorbidities (diabetes mellitus type 2, obesity, renal failure, liver dysfunction etc.) or pregnant women were excluded. 31 studies (27 observational studies and 4 clinical trials) spanning the years 2020–2021, pertaining to 8624 COVID-19 patients (mean age±SD, 61 ± 9 years) were included in this systematic review. Few studies provided direct evidence on the association of serum levels of vitamin D, calcium, zinc, magnesium, phosphorus and selenium to patients' survival or death. Vitamin D and calcium were the most studied micronutrients and those with a probable promising favorable impact on patients. This review highlights the importance of a balanced nutritional status for a favorable outcome in COVID-19. Micronutrients’ deficiency on admission to hospital seems to be related to a high risk for ICU admission, intubation and even death. Nevertheless, evidence for intervention remains unclear. © 2022 Elsevier Lt

Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean ± standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 ± 9.6 μg/ml and 5.6 ± 5.0 μg/ml, respectively, in serum and 10.8 ± 5.7 μg/ml and 6.1 ± 4.2 μg/ml, respectively, in CSF. The mean ± SD areas under the concentration-time curves (AUCs) were 128.7 ± 83.9 μg·h/ml for serum and 101.6 ± 59.6 μg·h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 ± 19.0 h and 6.5 ± 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 μg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens. Copyright © 2006, American Society for Microbiology. All Rights Reserved

ECATS - Mission of Association for an environmentally compatible air transport system

After 5 years of operation and collaboration the ECATS Network of Excellence (NoE) will now transform itself into a registered Association of European Research Establishments and Universities leading in the field of aeronautics and the environment. The transition from NoE to the Association will take place during 2010 and 2011. This future ECATS Association has the vision to support endeavours to make aviation more sustainable focussing on scientific expertise and exchange of information. ECATS’ Virtual Fuel Centre focusses on alternative fuel characterisation allowing operating a premix burner, measuring flame velocities, expanding kinetic schemes and spray characterisation. ECATS’ Airport Air Quality (AAQ) focus area povides an assessment of this highly interdisciplinary research field, and develops improved characterisation and approximation specifications for aviation particulate matter emissions. ECATS’ third focus area is dealing with global impact of aviation and green flight. Close collaboration is exploited in order to provide updated estimates and synergies with other programmes established. The future ECATS Association provides an efficient framework for collaboration between universities and research establishments and helps making aviation more sustainable