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Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition sustained by the reduced function of one of the enzymes involved in the adrenal steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of enzyme activity impairment determine different clinical pictures, with childhood or post-pubertal onset. The aim of this study was to evaluate the relationship between genotype, phenotype, and adrenal hormonal levels in a group of 66 patients affected by NCAH attending outpatient pediatric or endocrinological Clinics. Our findings show that age at pubarche/menarche was significantly younger, height SD score) and Δ bone age-chronological age were significantly higher in patients with a more severe enzyme activity impairment, while cutaneous androgenization and menstrual irregularities in post-pubertal girls were not related to the grading of genotype.

Congenital adrenal hyperplasia, both in its classic (CCAH) and non-classic form (NCAH), is a morbid condition sustained by the absent or reduced function of one of the enzymes involved in cortisol biosynthesis - mainly 21 hydroxylase - associated with different levels of clinical androgenization. In a wide group of relatives of patients affected by CCAH and NCAH (no.=222) and healthy volunteers (no.=30), a clinical, hormonal and genetic evaluation was performed in order to differentiate between the condition of heterozygous mutation carrier and non-carrier of any among 21-hydroxylase gene (CYP21) mutations. This study shows that clinical presentation and basal 17α-hydroxyprogesterone (17α-OHP) are not able to differentiate between heterozygous carriers and non-carriers, whereas 17α-OHP value after ACTH bolus is significantly different between heterozygous carriers and non-carriers: p<0.001 with a cut-off value of 3 ng/ml (90% sensitivity and 74,3% specificity). Moreover, our data indicate that 17α-OHP response to ACTH may be a useful tool to select subjects for genetic analysis.

Diabetics have at least twice the risk of stroke and may show performance deficit in a wide range of cognitive domains. The mechanisms underlying this gradually developing end-organ damage may involve both vascular changes and direct damage to neuronal cells as a result of overproduction of superoxide by the respiratory chain and consequent oxidative stress. The study aimed to assess the role of oxidative stress on the aldose reductase-polyol pathway, on advanced glycated end-product (AGE)/AGE-receptor interaction, and on downstream signaling in the hippocampus of streptozotocin-treated rats. Data show that, in diabetic rats, levels of prooxidant compounds increase, whereas levels of antioxidant compounds fall. Receptor for AGE and galectin-3 content and polyol flux increase, whereas glyceraldehyde-3-phosphate dehydrogenase activity is impaired. Moreover, nuclear factor kappaB (p65) transcription factor levels and S-100 protein are increased in the hippocampus cytosol, suggesting that oxidative stress triggers the cascade of events that finally leads to neuronal damage. Dehydroepiandrosterone, the most abundant hormonal steroid in the blood, has been reported to possess antioxidant properties. When dehydroepiandrosterone was administered to diabetic rats, the improved oxidative imbalance and the marked reduction of AGE receptors paralleled the reduced activation of nuclear factor kappaB and the reduction of S-100 levels, reinforcing the suggestion that oxidative stress plays a role in diabetes-related neuronal damage.

Background/aims: In liver cirrhosis atrial natriuretic peptide (ANP) decreases portal vascular resistance and tributary flow. The enzyme neutral endopeptidase (NEP) degrades ANP and bradykinin and generates endothelin-1 from big-endothelin. We determined the effects of NEP inhibition by candoxatrilat on hormonal status, liver function and arterial and portal pressures in rats with CCl4-induced cirrhosis., Methods: Two groups of seven control rats received 1 ml 5% glucose solution alone or containing 10 mg/kg candoxatrilat; three groups of 10 ascitic cirrhotic rats received placebo, 5 or 10 mg/kg candoxatrilat. NEP protein concentration and immunostaining were analyzed in normal and cirrhotic livers., Results: In cirrhotic rats 10 mg/kg candoxatrilat significantly increased steady-state indocyanine green clearance (a parameter reflecting liver plasma flow) (P<0.01), decreased portal pressure (P<0.01), had no effect on arterial pressure and plasma renin activity but increased ANP plasma levels (P<0.05) and urinary excretions (P<0.01) of ANP and cGMP. In the cytosol fraction of rat cirrhotic livers a 280% increase in NEP content was found (P<0.01), chiefly localized in desmin-positive myofibroblast-like cells of fibrous septa., Conclusions: Candoxatrilat has few effects on systemic hemodynamics and hormonal status; its portal hypotensive action depends on effects exerted on intrahepatic vascular resistance.

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.

Background: The pathogenesis of ischemia/reperfusion (I/R) involves generation of reactive oxygen and nitrogen species. This in vivo study investigates the effect of dehydroepiandrosterone (DHEA), a physiologic steroid with antioxidant properties, on oxidative balance and renal dysfunctions induced by monolateral I/R., Methods: Normal and DHEA-treated rats (4 mg/day x 21 days, orally) were subjected to monolateral renal I/R (30 minutes/6 hours). The oxidative state was determined by measuring hydrogen peroxide level and activities of glutathione-peroxidase, catalase, and superoxide dismutase. Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production and inducible nitric oxide synthase (iNOS) levels were also measured. Hydroxynonenal content was used to probe lipid peroxidation. Functional parameters determined were creatinine levels and Na/K-ATPase activity. Immunohistochemical and morphologic studies were also performed., Results: A markedly pro-oxidant state was evident in the kidney of rats subjected to I/R. Both hydrogen peroxide and reactive nitrogen species (nitric oxide and iNOS) increased, whereas antioxidants decreased. Oxidant species induce TNF-alpha increase, which, in turn, produces lipoperoxidative processes, as documented by the increased hydroxynonenal (HNE) level. As final result, impaired renal functionality, hydropic degeneration, and vacuolization of proximal convolute tubules were observed in kidneys of I/R rats. DHEA pretreatment improved the parameters considered., Conclusion: I/R induces oxidative stress and consequently damages the proximal convolute renal tubules. Rats supplemented with DHEA and subjected to I/R had reduced pro-oxidant state, oxidative damage, and improved renal functionality, indicating an attenuation of oxidative injury and dysfunctions mediated by I/R.

The data obtained analyzing generation time, cell yield and their variability in different culture media in diploid strains of Saccharomyces cerevisiae demonstrate the existence of a biochemically determined heterotic effect, that could be of some relevance for the study of yeast population genetics, as well as for the improvement of microbial fermentation processes.

The authors report their experience of 11 cases of hemoperitoneum due to hemorrhagic endoabdominal neoformation, diagnosed through laparoscopy, and the diagnosis of which was confirmed by the biopsy under the sight. They describe the casuistry observed: 4 hepatic neoplasms (11,9%); 4 ovary neoplasmus (12,1%); 1 neuroblastoma (10%); 2 ovary endometriosic cysts (16,6%). They, at last, emphasize the usefulness of laparoscopy as an investigating mean offering a sure diagnostical reliability.