Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

BACKGROUND: Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. METHODS: Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Then, rats with testicular atrophy (AT) were divided into two groups (n = 10 each): untreated rats (AT) receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g b.w.(-1).day(-1), sc.) for 28d. Healthy controls (CO, n = 10) were studied in parallel. Animals were sacrificed on day 29(th). Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx) were assessed. RESULTS: Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p < 0.05). Interestingly, plasma IGF-I did not augment in rats with testicular atrophy treated with IGF-I, while IGFBP3 levels, that reduces IGF-I availability, was increased in this group (p < 0.05). CONCLUSION: In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrom or liver cirrhosis)

Human influence on growing-period frosts like the early April 2021 in Central France

International audienceAbstract. In early April 2021 several days of harsh frost affected central Europe. This led to very severe damage in grapevine and fruit trees in France, in regions where young leaves had already unfolded due to unusually warm temperatures in the preceding month (March 2021). We analysed with observations and 172 climate model simulations how human-induced climate change affected this event over central France, where many vineyards are located. We found that, without human-caused climate change, such temperatures in April or later in spring would have been even lower by 1.2 ∘C (0.75 to 1.7 ∘C). However, climate change also caused an earlier occurrence of bud burst that we characterized in this study by a growing degree day index value. This shift leaves young leaves exposed to more winter-like conditions with lower minimum temperatures and longer nights, an effect that overcompensates the warming effect. Extreme cold temperatures occurring after the start of the growing season such as those of April 2021 are now 2 ∘C colder (0.5 to 3.3 ∘C) than in preindustrial conditions, according to observations. This observed intensification of growing-period frosts is attributable, at least in part, to human-caused climate change with each of the five climate model ensembles used here simulating a cooling of growing-period annual temperature minima of 0.41 ∘C (0.22 to 0.60 ∘C) since preindustrial conditions. The 2021 growing-period frost event has become 50 % more likely (10 %–110 %). Models accurately simulate the observed warming in extreme lowest spring temperatures but underestimate the observed trends in growing-period frost intensities, a fact that yet remains to be explained. Model ensembles all simulate a further intensification of yearly minimum temperatures occurring in the growing period for future decades and a significant probability increase for such events of about 30 % (20 %–40 %) in a climate with global warming of 2 ∘C

A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury

Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine, which displays potent profibrogenic effects and is highly expressed in fibrotic livers. For this reason, development of TGF-B1 inhibitors might be of great importance to control liver fibrogenesis as well as other undesired side effects due to this cytokine. Potential peptide inhibitors of TGF-beta1 (derived from TGF-beta1 and from its type III receptor) were tested in vitro and in vivo using different assays. Peptides P11 and P12, derived from TGF-beta1, and P54 and P144, derived from its type III receptor, prevented TGF-beta1-dependent inhibition of MV1Lu proliferation in vitro and markedly reduced binding of TGF-beta1 to its receptors. P144 blocked TGF-beta1-dependent stimulation of a reporter gene under the control of human alpha2(I) collagen promoter. Intraperitoneal administration of P144 also showed potent antifibrogenic activity in vivo in the liver of rats receiving CCl4. These rats also showed a significant decrease in the number of activated hepatic stellate cells as compared with those treated with saline only. These results suggest that short synthetic peptides derived from TGF-beta1 type III receptor may be of value in reducing liver fibrosis in chronic liver injury