Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role?

Secondary adrenal insufficiency (SAI) is a potentially life-threatening endocrine disorder due to an impairment of corticotropin (ACTH) secretion from any process affecting the hypothalamus or pituitary gland. ACTH deficit can be isolated or associated with other pituitary failures (hypopituitarism). An increased mortality due to cardiovascular, metabolic, and infectious diseases has been described in both primary and secondary adrenal insufficiency. However, few studies have provided compelling evidences on the underlying mechanism in SAI, because of the heterogeneity of the condition. Recently, some studies suggested that inappropriate glucocorticoid (GCs) replacement therapy, as for dose and/or timing of administration, may play a role. Hypertension, insulin resistance, weight gain, visceral obesity, increased body mass index, metabolic syndrome, impaired glucose tolerance, diabetes mellitus, dyslipidemia have all been associated with GC excess. These conditions are particularly significant when SAI coexists with other pituitary alterations, such as growth hormone deficiency, hypogonadism, and residual tumor. Novel regimen schemes and GC preparations have been introduced to improve compliance and better mimick endogenous cortisol rhythm. The controlled trials on the improved replacement therapies, albeit in the short-term, show some beneficial effects on cardiovascular risk, glucose metabolism, and quality of life. This review examines the current evidence from the available clinical trials investigating the association between different glucocorticoid replacement therapies (type, dose, frequency, and timing of treatment) and glycometabolic alterations in SAI

Estrogenic activity and cytotoxicity of six anticancer drugs detected in water systems

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Eco-genotoxicity of six anticancer drugs using comet assay in daphnids

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Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans

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Androgen modulation of pro-inflammatory and antiinflammatory cytokines during preadipocyte differentiation

Background: Macrophages and adipocytes contribute to release of cytokines resulting in the chronic inflammatory profile of the metabolic syndrome. The local increase of proinflammatory cytokines impairs adipogenesis, resulting in formation of dysfunctional adipocytes that are unable to store and handle lipids. The altered lipid fluxes in/from adipocytes affect whole-body metabolism. We investigated the role of androgens on adipocyte-derived proinflammatory and anti-inflammatory cytokines during preadipocyte differentiation. Materials and methods: Various differentiation methods were used to obtain full conversion of 3T3-L1 into mature adipocytes. The degree of adipocyte conversion in the presence/absence of dihydrotestosterone (DHT) was analyzed by measuring intracellular triglycerides (Oil Red O staining). The effects of DHT administration on interleukin 1Β (IL-1Β), IL-2, IL-6, IL-10, IL-12, interferon γ (IFNΓ) and tumor necrosis factor α (TNFα) secretion was measured at days 0, 4, 6 and 8 of differentiation using the SearchLight multiplex protein array. Results: DHT regulates a number of cytokines in committed and mature 3T3-L1 adipocytes. IL-1Β and TNFα were readily suppressed at the very early stages of differentiation. IFNΓ release was inhibited at day 4, but the effect was no longer detectable on day 8. IL-6 and IL-12 were significantly reduced at day 8 of differentiation. Conversely, the differentiation-dependent increase of IL-2 and IL-10 was further stimulated by DHT since day 0. Conclusions: We provide evidence that androgens promote an anti-inflammatory profile that parallels the acquisition of a functional adipocyte phenotype. The crosstalk between androgens, adipocyte-derived mediators of inflammation and intracellular lipid fluxes could have profound implications on metabolism of men with obesity and metabolic syndrome. © 2010, by Walter de Gruyter Berlin New York. All rights reserved

Theobromacacao Criollo var. Beans: Biological Properties and Chemical Profile

Abstract: Theobroma cacao provides precious products such as polyphenol-rich beans that are useful for nutraceutical purposes. The geographical area may influence the chemical composition of raw cocoa beans in terms of the polyphenols and biological qualities of the products. This work aimed to investigate the biological properties and the chemical composition of two different samples of Criollo var. cocoa raw beans coming from two areas (Indonesia; Peru). Beans underwent biphasic extraction obtaining lipophilic and hydroalcoholic extracts. The extracts were tested for antiradical, antimutagenic, and antigenotoxic effects. Cell viability inhibition toward breast, gastric/esophageal colorectal adenocarcinoma, and hepatoblastoma human cell lines was evaluated. Extracts were chemically investigated through UV-Vis spectroscopy and ultra-high-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QqTOF MS/MS). Results showed that the Indonesian bean hydroalcoholic extracts were able to scavenge 20 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cation radical better than the Peruvian hydroalcoholic extracts (ECs50: 72.63 vs. 322.20 µg/mL). Extracts showed antimutagenic and antigenotoxic activity. The viability inhibitory effect on breast and hepatic cancer cells was reached only for the Indonesian hydroalcoholic extracts at hundreds of µg/mL. Phenylpropenoyl-Lamino acids, hydroxycinnamoyl aminoacids conjugates, and procyanidin compounds were found mainly in the hydroalcoholic extracts, whereas fatty acids and lyso-phospholipids were found mainly in lipophilic fractions. Fatty acid and (epi)catechins appeared to be affected by different environmental conditions of the geographical areas

Antioxidant activity of coatings containing eugenol for flexible aluminium foils to preserve food shelf-life

Active food packaging is an innovative system that avoids food deterioration ensuring quality, safety and shelf-life extension of food. Herein, two novel eugenol vinyl-based resins were used for coating flexible aluminium foils with potential packaging applications. Coatings were prepared with single eugenol or loaded eugenol in Santa Barbara Amorphous15 (SBA-15) mesoporous silica nanoparticles, and their antioxidant activity was investigated by DPPH, ABTS, ORAC, TBARS assays and by the hydroxyl free radicals’ generator method with HPLC analysis. Antioxidant activity was also evaluated exposing the coatings to various food simulants. Both coatings revealed adequate antioxidant capacity when exposed to fatty food simulants and to vapour phase hydroxyl free radicals (scavenging > 50%). The incorporation of eugenol in SBA-15 reduced its release to 65%, promoting eugenol beneficial antioxidant effects over time. The release of eugenol from the coatings into food simulants is not required for the activity of free radical scavenging

Ecotoxic effects of loratadine and its metabolic and light-induced derivatives

Loratadine and desloratadine are second-generation antihistaminic drugs. Because of human administration, they are continuously released via excreta into wastewater treatment plants and occur in surface waters as residues and transformation products (TPs). Loratadine and desloratadine residues have been found at very low concentrations (ng/L) in the aquatic environment but their toxic effects are still not well known. Both drugs are light-sensitive even under environmentally simulated conditions and some of the photoproducts have been isolated and characterized. The aim of the present study was to investigate the acute and chronic ecotoxicity of loratadine, desloratadine and their light-induced transformation products in organisms of the aquatic trophic chain. Bioassays were performed in the alga Pseudokirchneriella subcapitata, the rotifer Brachionus calyciflorus and in two crustaceans, Thamnocephalus platyurus and Ceriodaphnia dubia. Loratadine exerted its acute and chronic toxicity especially on Ceriodaphnia dubia (LC50: 600 mu g/L, EC50: 28.14 mu g/L) while desloratadine showed similar acute toxicity among the organisms tested and it was the most chronically effective compound in Ceriodaphnia dubia and Pseudokirchneriella subcapitata. Generally, transformation products were less active in both acute and chronic assays.Peer reviewe

Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer

Familial aggregation is a significant risk factor for the development of thyroid cancer and Familial Non-Medullary Thyroid Cancer (FNMTC) accounts for 5-7% of all NMTC. Whole Exome Sequencing analysis in the family affected by FNMTC with oncocytic features where our group previously identified a predisposing locus on chromosome 19p13.2, revealed a novel heterozygous mutation (c.400G>A, NM_012335; p.Gly134Ser) in exon 5 of MYO1F, mapping to the linkage locus. In the thyroid FRTL-5 cell model stably expressing the mutant MYO1F p.Gly134Ser protein we observed an altered mitochondrial network, with increased mitochondrial mass and a significant increase of both intracellular and extracellular Reactive Oxygen Species, compared to cells expressing the wild-type protein or carrying the empty vector. The mutation conferred a significant advantage in colony formation, invasion and anchorage independent growth. These data were corroborated by in vivo studies in zebrafish, since we demonstrated that the mutant MYO1F p.Gly134Ser, when overexpressed, can induce proliferation in whole vertebrate embryos, compared to the wild-type one. MYO1F screening in additional 192 FNMTC families identified another variant in exon 7, which leads to exon skipping, and is predicted to alter the ATP-binding domain in MYO1F. Our study identified for the first time a role for MYO1F in NMTC. This article is protected by copyright. All rights reserved

Cardiac magnetic resonance reveals biventricular impairment in Cushing’s syndrome: a multicentre case-control study

Purpose: Cushing’s syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. Methods: This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. Results: Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. Conclusion: CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors