Amenorrea primaria in una adolescente con iperprolattinemia: mancato riconoscimento di una sindrome di Turner

We report a case of a 14-year-old girl with primary amenorrhoea and hyperprolactinaemia. One year treatment with cabergoline – a dopamine agonist – caused a significant reduction in serum prolactin (PRL) concentration without a normalisation of menstrual cycle. After our examination, Turner’s syndrome (45X0/46XY mosaicism) was diagnosed. Turner’s syndrome (TS) is characterised by short stature, streak gonads, infertility, and hearth and kidney malformations. The presence of Y chromosome fragments in patients with TS is known to increase the risk of gonadoblastoma. The patient underwent prophylactic gonadectomy and received substitutive estrogenic therapy

Porcine derived relaxin stimulates new vessel formation and improves the disturbed wound healing of the genetically diabetic mice

Diabetic mice are characterized by an altered expression pattern of VEGF, and impaired vasculogenesis during healing. We investigated the effects of porcine derived relaxin in diabetes-related wound healing defects in genetically diabetic mice. An incisional wound model was produced on the back of female diabetic C57BL/KsJm+/+ Leptdb (db+/db+) mice and their normal littermates (db+/+m). Animals were treated daily with RLX (25μg mouse/day subcutaneously) or its vehicle. Mice were killed on days 3, 6 and 12 after skin injury for measurements of vascular-endothelial-growth-factor (VEGF) mRNA and protein synthesis. Furthermore, we evaluated wound-breaking strength, histological changes, and angiogenesis at day 12. At day 6, RLX administration resulted in an increase in VEGF mRNA expression and protein wound content. Furthermore the histological evaluation indicated that RLX improved the impaired wound healing, and increased wound breaking strength at day 12 in diabetic mice. Immunohistochemistry showed that RLX in diabetic animals augmented new vessel formation. These data strongly suggest that RLX may have a potential application in diabetes-related wound disorders

Anti-obesity drug therapy in clinical practice: Evidence of a poor prescriptive attitude

Obesity is a worldwide growing problem for the health care systems and its treatment is strongly recommended. Orlistat, naltrexone/bupropion, and liraglutide are approved for weight loss in Italy in patients with a Body Mass Index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 with concomitant diseases. However, the prescription of these drugs is significantly low worldwide. General practitioners (GPs) play a key role in the early diagnosis and appropriate management of obesity. The aim of the study was to investigate the management of obesity and the prescriptive attitude of anti-obesity drugs in a general practice setting.All patients registered in lists of 8 GPs with a recorded diagnosis of obesity or BMI values ≥ 30 kg/m2 in the period 2017–2018, were recruited. A descriptive analysis of demographic and clinical characteristic was carried out. The Spearman's correlation rank test was applied to identify correlations between BMI and all the variables of interest.Among 1301 obese patients, only 66.1 % had been diagnosed and 29.4 % had no registered BMI value. Patients with recorded BMI, were overweight (7.8 %) or in the obesity class I (38.8 %), class II (14.1 %), and class III (7.1 %), respectively.The obese patients (class 1–3) were older [66 (55–76) vs 49 (32–59); p < 0.01], and had more concurrent diseases [5 (3−8) vs 4 (2–6); p < 0.01] than patients who reached a BMI < 30 Kg/m2. Moreover, most of obese were high cardiovascular risk (HCVr) patients (67.0 % vs 31.9 %; p < 0.01). The BMI was directly related to age (rs 0.14; p < 0.01), diabetes (rs 0.19; p < 0.01), hypertension (rs 0.14; p < 0.01), heart failure (rs 0.09; p < 0.01), HCVr (rs 0. 12; p < 0.01) and number of comorbidities (rs 0.08; p = 0.01). No prescriptions of orlistat or naltrexone/bupropion were found. Liraglutide was prescribed only in 7 patients because of the concomitant presence of diabetes.Our results suggest a low adherence to guide line recommendations for obesity management and confirm an under-prescription of anti-obesity drugs in Italy

Levels of Heavy Metals in Adolescents Living in the Industrialised Area of Milazzo-Valle del Mela (Northern Sicily)

In the Milazzo-Valle del Mela area, the presence of industrial plants and the oil refinery make local residents concerned for their health. For this reason, we evaluated the levels of heavy metals in 226 children aged 12–14 years, living in the 7 municipalities of the area. A control age-matched population (n=29) living 45 km far from the industrial site was also enrolled. Arsenic, cadmium, chromium, mercury, nickel, and vanadium were analysed in 24 h urine samples, while lead concentration was evaluated in blood samples. A questionnaire regarding life style and risk perception was also administered. Adolescents from Milazzo-Valle del Mela had cadmium levels significantly higher compared to either controls  (P<0.0001) or the reference values of the European Germany Environmental Survey (GerES-IV) and the American National Health and Nutrition Examination Survey (NHANES). Furthermore, children had higher perception of living in a high-risk environment. The present data, for the first time, clearly indicate that adolescents living in Milazzo-Valle del Mela have increased body concentration of cadmium, which may be harmful to human health. These results deserve particular attention by the local and regional government to initiate prevention programmes in this susceptible population

Role of NLRP3 in an experimental model of testicular ischemia and reperfusion in mice

Inflammasomes are multi-protein complexes composed of one of several leucinerich repeat receptors (NLRs) including NLRP1, NLRP3, NLRC4 and AIM2: NLRP3 is currently the most fully characterized inflammasome. Testicular torsion leads to tissue degeneration and, after reperfusion, results in production of reactive oxygen species and triggers the apoptosis machinery. To better understand the role of NLRP3 during testicular ischemia/reperfusion (TI/R), we investigated the morphological aspects of spermatogenesis underlying the effects of inflammasome in KO mice during TI/R. KO (Nlrp3tm1bhk) and wild-type (WT: C57Bl6) animals underwent 1h testicular-ischemia followed by reperfusion. The mice were killed after 1 day and 7 days of reperfusion and the determination of caspase-3 activity was executed. Furthermore, both the tubular (mean seminiferous tubule diameter and Johnsen’s scoring system [1]) and extratubular (edema, hemorrhagic extravasation, vessels dilation, and Leydig cells changes [2]) compartments were evaluated. The TUNEL assay for apoptosis was also performed. After 1 and 7 days of reperfusion in WT mice an increase of caspase-3 was observed. Structurally, marked histological damages characterized by altered spermatogenesis, evident extratubular changes and increased TUNEL activity were observed. In KO mice caspase-3 was inhibited. Histological damages were significantly decreased, TUNEL activity was reduced and extratubular changes were significantly milder. We suggest that NLRP3 inhibition might have a protective role on spermatogenesis and it can be proposed in patients with unilateral testicular torsion

CO 2

Laparoscopy (LS) has been shown to decrease the inflammatory sequelae of endotoxemia. β-arrestin 2 plays an important function in signal transduction pathway of TLR4. High mobility group box-1 (HMGB-1) is involved in the delayed systemic inflammatory response. We investigated the effects of CO2 insufflation on liver, lung, and kidney expression of both β-arrestin 2 and HMGB-1 during sepsis. Cecal ligation and puncture (CLP) was performed in male rats and 6 h later the animals were randomly assigned to receive a CO2 pneumoperitoneum or laparotomy. Animals were euthanized; liver, lung, and kidney were removed for the evaluation of β-arrestin 2 and HMGB-1 expression. Immunohistochemical detection of myeloperoxidase (MPO) was investigated in lung and liver and bacterial load was determined in the peritoneal fluid. CO2 pneumoperitoneum reduced peritoneal bacterial load, increased the expression of β-arrestin 2, and blunted the expression of the potent proinflammatory HMGB-1 in liver, lung, and kidney compared with laparotomy. Liver and lung MPO was markedly reduced in rats subjected to LS compared with laparotomy. We believe that CO2 exerts an early protective effect by reducing bacterial load and likely toll-like receptor activation which in turn leads to a preserved β-arrestin 2 expression and a reduced HMGB-1 expression

Beta-caryophyllene exhibits anti-proliferative effects through apoptosis induction and cell cycle modulation in multiple myeloma cells

Cannabinoid receptors, which are widely distributed in the body, have been considered as possible pharmacological targets for the management of several tumors. Cannabinoid type 2 receptors (CB2Rs) belong to the G protein-coupled receptor family and are mainly expressed in hematopoietic and immune cells, such as B-cells, T-cells, and macrophages; thus, CB2R activation might be useful for treating cancers affecting plasma cells, such as multiple myeloma (MM). Previous studies have shown that CB2R stimulation may have anti-proliferative effects; therefore, the purpose of the present study was to explore the antitumor effect of beta-caryophyllene (BCP), a CB2R agonist, in an in vitro model of MM. Dexamethasone-resistant (MM.1R) and sensitive (MM.1S) human multiple myeloma cell lines were used in this study. Cells were treated with different concentrations of BCP for 24 h, and a group of cells was pre-incubated with AM630, a specific CB2R antagonist. BCP treatment reduced cell proliferation through CB2R stimulation; notably, BCP considerably increased the pro-apoptotic protein Bax and decreased the anti-apoptotic molecule Bcl-2. Furthermore, an increase in caspase 3 protein levels was detected following BCP incubation, thus demonstrating its anti-proliferative effect through apoptosis activation. In addition, BCP regulated AKT, Wnt1, and beta-catenin expression, showing that CB2R stimulation may decrease cancer cell proliferation by modulating Wnt/β-catenin signaling. These effects were counteracted by AM630 co-incubation, thus confirming that BCP’s mechanism of action is mainly related to CB2R modulation. A decrease in β-catenin regulated the impaired cell cycle and especially promoted cyclin D1 and CDK 4/6 reduction. Taken together, these data revealed that BCP might have significant and effective anti-cancer and anti-proliferative effects in MM cells by activating apoptosis, modulating different molecular pathways, and downregulating the cell cycle

Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes

Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdb mice (db+/db+) and their normoglycemic littermates (db+/+m). In the db+/db+ mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase

Flavocoxid mitigates cadmium-induced toxicity: structural, immunohistochemical and molecular analysis in mice kidney

Background: Cadmium (Cd), a diffused environmental pollutant, has adverse effects on urinary apparatus [1]. The role of flavocoxid, a flavonoid with antioxidant activity [2], on the morphological and biochemical changes induced in vivo by Cd in mice kidneys was evaluated. Methods: C57 BL/6J mice received 0.9% NaCl alone, flavocoxid (20 mg/kg/day i.p.) alone, Cd chloride (CdCl2) (2 mg/kg i.p.) alone, or CdCl2 plus Flavocoxid (2 mg/kg i.p. plus 20 mg/kg/day i.p.) for 14 days. At the end of experiment, the mice were killed with an overdose of ketamine and xylazine and the kidneys were collected and processed for structural, immunohistochemical and biochemical analysis. Results: Cd treatment alone significantly increased iNOS, TNF-α and MMP-9 expression, induced structural damages in the glomeruli and in the proximal tubule epithelium, and reduced claudin-11, occludin and N-cadherin immunoreactivity. Flavocoxid administration reduced iNOS, TNF-α and MMP-9 expression, ameliorated glomerular and tubular changes and enhanced claudin-11, occludin and N-cadherin immunoreactivity. Conclusions: We demonstrated for the first time that flavocoxid has a protective role against Cd-induced damages in mice kidney. Therefore, flavocoxid may have a promising role against environmental Cd, in particular against its harmful effects on glomerular and tubular lesions