Context:
The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of ...patients at metabolic risk.
Objective:
The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly.
Patients:
Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%).
Outcome Measures:
Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUCGH) during the oral glucose tolerance test, AUCCpeptide during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6.
Results:
The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUCGH (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUCCpeptide (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = −0.766; P < 0.001), M value (ρ = −0.818; P < 0.001), and DIo (ρ = −0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUCGH (P = 0.047), IGF-I (P = 0.047), AUCCpeptide (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUCGH proved to be the main independent factor influencing VAI.
Conclusions:
In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegaly.
Age at first calving (AFC) represents the nonproductive period of ∼2 yr in Holstein cows, and thus, it has a relevant effect on the cost of rearing replacements in the dairy herd. In the present ...study, we aimed to evaluate genetic and genomic aspects of AFC in the Italian Holstein population. Data of 4,206,218 heifers with first calving between 1996 and 2020 were used. Age at first calving averaged 26.09 ± 3.07 mo and decreased across years. Heritability was estimated using a linear animal model which included the fixed effects of herd-year-season of birth and classes of gestation length, and the random animal additive genetic effect fitted to a pedigree-based relationship matrix. The EBV and genomically EBV (GEBV) were obtained, and they were standardized to mean 100 and standard deviation 5, where animals above the mean are those contributing to reduce AFC. Heritability estimates of AFC ranged from 0.031 to 0.045. The trend of sires' GEBV was favorable and indicated a reduced AFC across years. Approximate genetic correlations between GEBV of AFC and GEBV of other economically important traits were calculated on a subset of genotyped females born after 2015. Moderate favorable associations of AFC with production traits (0.39–0.51), udder depth (0.40), interval from first to last insemination in heifer (−0.43), and longevity (0.34) were assessed. Overall, the greatest lifetime productive performances and most favorable days open in first lactation were observed when heifers calved at 22 to 23 mo. In contrast, progeny of sires with GEBV of AFC above the mean yielded more milk, fat, and protein in first lactation, and had shorter days open than progeny of sires with GEBV of AFC below the mean. Results suggested that breeding strategies to improve AFC should be pursued, also considering genetic correlations between AFC and traits which are already part of the Italian Holstein breeding objective. The inclusion of AFC in an aggregate index is expected to contribute to enhance farm income.
Aliment Pharmacol Ther 2012; 35: 238–247
Summary
Background Metabolic factors have been associated with liver damage in patients with non‐alcoholic fatty liver disease (NAFLD).
Aims To test a new ...marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings.
Methods One hundred and forty‐two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL‐6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner).
Results By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003–1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023–2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771–8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231–6.757, P = 0.01) were correlated with significant fibrosis (F2–F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%).
Conclusions In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.
Background
Treatment of moderate‐to‐severe atopic dermatitis (AD) in the elderly may be challenging, due to side‐effects of traditional anti‐inflammatory drugs and to comorbidities often found in ...this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known.
Objectives
A multicentre retrospective, observational, real‐life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined.
Methods
Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P‐NRS, S‐NRS and DLQI) scores at baseline and after 16 weeks of treatment.
Results
Two hundred and seventy‐six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16‐week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18–64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty‐one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event.
Conclusions
Therapy with dupilumab led to a significant improvement of AD over a 16‐week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.
Gestation length (GL) can potentially affect health and performance of both the dam and the newborn calf, and it is controlled by two genetic components, direct and maternal. This means that both the ...calf (direct effect) and the cow (maternal effect) genotypes contribute to determine GL and its variability. The aims of the present study were to estimate direct and maternal variance components of GL, develop a routine genetic evaluation of GL in Italian Holstein and evaluate potential (un)favourable associations with traits for which selection is undertaken in this population. A multiple-trait repeatability linear animal model was employed for the estimation of variance components considering GL in first and later parities as different traits. The posterior mean (PM) of heritability of the direct effect was 0.43 for first parity and 0.35 for later parities. The PM of heritability of the maternal effect was lower, being 0.08 for primiparae and 0.06 for pluriparae. The posterior standard deviation (PSD) of the heritability estimates was small, ranging from 0.001 to 0.005. The relationship of direct and maternal effects with important traits such as milk yield and fertility indicated that selecting for extreme GL, longer or shorter, may have negative consequences on several traits, suggesting that GL has an intermediate optimum in dairy cattle. In conclusion, this study reveals that selecting an intermediate GL in the Italian Holstein population is advisable. Although scarcely variable compared to other conventional traits for which Italian Holstein is selected, GL is heritable and a deeper knowledge can be useful for decision-making at the farm level.
The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated target in the development of therapeutics against HIV ...infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the beta-diketo acids (DKAs) represent a major lead for anti-HIV-1 drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized, and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3'-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-cross-linking experiments.
BACKGROUND
Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidemia and hypertension, which are characteristic features of a ...condition of cardiometabolic risk. Our objective was to investigate the relationship between visceral adiposity index (VAI) and phenotypic characteristics in women with PCOS.
METHODS
We conducted a cross-sectional case–control study in our Endocrinology Outpatients Clinic. A total of 220 women with PCOS (Rotterdam definition) and 144 age- and BMI-matched healthy women were studied. We evaluated hyperandrogenemia and clinical hyperandrogenism, ovarian morphology, hypothalamic–hypophyseal axis and metabolic syndrome parameters. An oral glucose tolerance test (75 g glucose) measured areas under the curve (AUC) for insulin (AUC2h-insulin) and for glucose (AUC2h-glucose). Homeostasis model assessment of insulin resistance, the Matsuda index of insulin resistance and VAI were determined.
RESULTS
Of all the variables examined, at multivariate analysis, only AUC2h-insulin odds ratio (OR): 1.00; 95% confidence interval (CI): 1.00–1.00; P = 0.003 and VAI score (OR: 1.81; 95% CI: 1.20–2.73; P = 0.005) showed an independent association with PCOS. All phenotypes with oligomenorrhea showed a higher VAI score than the control group (oligomenorrhea + hyperandrogenism: 2.49 ± 1.46 versus 1.62 ± 0.84, P < 0.001; oligomenorrhea + polycystic ovary morphology: 2.25 ± 1.4 versus 1.62 ± 0.84, P = 0.001; complete phenotype: 2.45 ± 1.63 versus 1.62 ± 0.84, P < 0.001).
CONCLUSIONS
Our data suggest that VAI could be an easy and useful tool in daily clinical practice and in population studies for the assessment of cardiometabolic risk associated with PCOS.
GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the ...question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children.
This was a 1-year prospective study. Thirty-four GHD children (11.6 +/- 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement therapy and again at 12 months.
At the beginning of the study, total and LDL cholesterol were higher in GHD children than in controls (P<0.001), whereas HDL cholesterol, triglycerides, insulin, HOMA-IR, leptin, and adiponectin were similar. At 12 months of continuous GH replacement therapy in the GHD group, there was a significant increase in both auxological data and IGF-I (P<0.001); total cholesterol (P<0.001), LDL (P<0.001), triglycerides (P<0.005), and leptin (P<0.001) decreased significantly; HDL (P<0.003), insulin (P<0.001), HOMA-IR (P<0.001) increased while adiponectin was unmodified. Furthermore, IGF-IDelta showed an inverse correlation with leptin Delta (rho = -0.398, P = 0.02).
In GHD children, the evaluation of metabolic parameters proves to be a useful tool for the evaluation of auxological parameters during GH replacement therapy. In our study, GH replacement therapy in GHD children improved final height, restored IGF-I levels, reduced leptin levels, and improved the lipid profile, without producing any unfavorable effects on glucose metabolism.
The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral ...therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20 %) was used for data interpretation. At baseline, 9/12 subjects (75.0 %) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5–X4, one X4–R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism.
To determine factors associated with < 2.5 copies/ml plasma HIV RNA in subjects treated with highly active antiretroviral therapy (HAART) and with viraemia < 50 copies/ml.
Cross-sectional analysis of ...84 HIV-positive patients taking HAART with plasma HIV RNA < 50 copies/ml for at least 6 months and no history of virological failure.
Current HAART therapy was based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 66%, a protease inhibitor in 26% and nucleoside reverse transcriptase inhibitors in 7%. Viraemia levels were measured using a modified ultrasensitive Roche Amplicor HIV-1 Monitor test able to quantify plasma HIV RNA to a lower limit of 2.5 copies /ml; proviral DNA was measured with a real-time polymerase chain reaction assay. Analysis of variance and multiple logistic regression analysis were utilized to test for associations between residual replication and other variables.
Residual HIV viraemia > 2.5 copies/ml was found in 50% of subjects; 94% of subjects had detectable proviral DNA (>or= 20 copies/10(6) peripheral blood mononuclear cells) and 21% had archived mutations. Usage of a NNRTI-based HAART was the only independent predictor of viral suppression below the cut-off value of the modified ultrasensitive assay.
In our population, NNRTI-based HAART seems to have a stronger impact on residual replication than protease inhibitor-based HAART. This finding may be considered in therapeutic decisions such as the choice of initial HAART regimen and the interruption or simplification of treatment.
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