HIV and Vertebral Fractures: a Systematic Review and Metanalysis.

The survival of HIV-infected patients has increased with the advent of antiretroviral therapy with the emergence of new comorbidities. Vertebral fracture is a manifestation of reduced bone strength and osteoporosis. This study aims to assess the frequency of spine fractures in HIV-positive men and women aged over 18 years. We performed a systematic review of randomized controlled trials, cohort studies, cross-sectional studies, and case-control studies. Studies that evaluated morphometric and/or clinical vertebral fracture were included. In total 488 studies were found, of which 53 had their full texts evaluated. A total of 85,411 HIV positive individuals were identified in 26 studies. The meta-analysis of the prevalence of vertebral fractures included 12 studies with 10,593 subjects. The prevalence was 11.1% [95% confidence interval (95% CI) 4.5%, 25.0%, I2 98.2% p < 0.00001]. When we evaluated independently studies of clinical vertebral fracture and morphometric vertebral fracture, the prevalence was 3.9% (95% CI 0.9, 15.8, I2 96.4% p < 0.00001) and 20.2% (95% CI 15.7%, 25.6%, I2 69.9% p = 0.003) respectively. HIV-infected individuals had an odds ratio of vertebral fractures of 2.3 (95% CI 1.37, 3.85, I2 98.2% p < 0.00001) when compared with HIV-uninfected patients (n = 9 studies). In conclusion, HIV-positive subjects had a higher risk of vertebral fractures when compared with HIV-negative subjects

Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

<div><p>Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS.</p> </div

Effects of the adipokines resistin, visfatin, leptin, and adiponectin on androstenedione production <i>in</i><i>vitro</i> in the presence of LH: compared to control cells, adiponectin treatment (3μg/mL) decreased levels of androstenedione in medium (****p= <0.0001) when bovine theca cells were treated with LH and insulin (both at 100 ng/mL).

<p>Small stimulatory effects of leptin and visfatin were also observed. The concentrations of adipokines were chosen on the basis of the relative serum levels in normal women. Data shown are mean+SD. </p

Gene expression of LH receptor (LHR), steroid acute regulatory protein (STAR) and key steroidogenic enzymes (CYP11A1, CYP17) after treatment with adiponectin.

<p>Cells were cultured in the presence of LH (10 ng/mL). The effect of adiponectin is expressed as a proportion of gene expression in control (non-treated) bovine theca cells. Marked decreases in the gene expression of (a) LHR (*p=0.02) (b), STAR (**p=0.028) (c) CYP11A1 (***p=0.02) and (d) CYP17 (****p=0.012) were observed in bovine theca cells after a 24-h treatment with adiponectin (3 μg/mL). Data are shown as the mean (95% CI).</p

Expression of adiponectin receptors in follicles from normal and polycystic human ovaries.

<p>Both AdipoR1 (Figure 1a) and AdipoR2 (Figure 1b) were detected in granulosa (G) and theca (T) of antral follicles (insets show control [negative] sections). The proportions of theca and granulosa cells expressing protein for adiponectin receptor I & 2 (AdipoR1 and AdipoR2) in follicles from normal and polycystic ovaries are shown in the bar graphs. A total of 920 follicles were analysed. A significant reduction in the proportion of TCs labelled for (c) AdipoR1 and (d) AdipoR2 was demonstrated in polycystic ovaries compared with normal ovaries from healthy women (*p=0.002, **p=0.049, Mann-Whitney). No differences between PCO and control tissue were detected in the proportion of granulosa cells labelling for AdipoR1 (e) or AdipoR2 (f). Data shown are mean + SEM in up to 7 normal and 15 polycystic ovaries.</p

Fruit and vegetable intake and bones: A systematic review and meta-analysis.

BackgroundAlthough intake of fruits and vegetables seemed to have a protective effect on bone metabolism, its effect on fractures remains uncertain.MethodsA systematic review of randomized controlled trials (RCTs) and cohort studies (PROSPERO: CRD42016041462) was performed. RCTs and cohort studies that evaluated the combined intake of fruits and vegetables in men and women aged over 50 years were included. We considered fractures as a primary outcome measure. Changes in bone markers were considered as secondary outcomes. The search strategy included the following descriptors: fruit, vegetables, vegetable products, bone and bones, bone fractures, postmenopausal osteoporosis, and osteoporosis. PubMed, Embase, and Cochrane Library were the databases used. The appraisal of the studies was performed by two independent reviewers, and discussed and agreed upon by both examiners. The data extracted from the RCTs and cohort studies were summarized separately. The risks of fractures were combined across studies using random models. Bone resorption marker (CTx) was summarized with standardized mean differences. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate the strength of recommendations.ResultsOf the 1,192 studies screened, 13 articles were included in the systematic review and 10 were included in the pooled analysis (6 cohort studies and 4 RCTs). The six cohort studies included in the meta-analysis included a population of 225,062. The pooled hazard ratio (HR) (95% confidence interval (CI)) of the hip in five studies was 0.92 (0.87, 0.98). Its heterogeneity was moderate (I2 = 55.7%, p = 0.060), GRADE (⊕⊕⊕O). Two cohort studies evaluated the risk of any fracture; the HR was 0.90 (95% CI: 0.86-0.96), with aheterogeneity of 24.9% (p = 0.249, GRADE (⊕⊕⊕O)). There was no association between the bone resorption marker CTx and 3 months of fruit and vegetable intake evaluated by four RCTs, GRADE (⊕⊕O O).ConclusionThere was an association between the increase of at least one serving of fruits and vegetables per day and decreases in the risk of fractures. The level of evidence for this association is moderate

High Serum Uric Acid Is Associated with Tubular Damage and Kidney Inflammation in Patients with Type 2 Diabetes

Background. Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). Methods. Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. Results. Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations≥6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). Conclusions. High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results

Effects of the different doses of adiponectin on markers of direct oxidative stress (AOPP)(A) and anti-oxidant capacity (FRAP and Nox)(B and C).

<p>(A)Compared to control cells, adiponectin treatment (in all doses tested) decreased the AOPP levels (ANOVA, P = 0.0003). (B and C) No differences were seen in terms of anti-oxidant capacity markers, namely FRAP and NoX. Data shown represents mean ± SEM (A) or median (IQ 25–75%) (B and C).</p

Effect of adiponectin on reduction of androstenedione serum levels (24h).

<p>Mice previously synchronized with equine gonadotropin chorionic (eCG), were submitted to one of the four different treatments: 1) Group 1- control (PBS), Group 2—adiponectin 0.1 μg/mL, Group 3—adiponectin 1 μg/mL, and Group 4—adiponectin 5 μg/mL. After 24 h the animals were euthanized and serum levels of androstenedione evaluated (mean ± SEM). There was a statistically significant reduction in adiponectin treated groups (ANOVA p = 0.01).</p