A study was conducted to form a unified hypothesis regarding the gonadotropin-related mechanisms that underlie alterations in the male reproductive system in individuals with diabetes. Streptozotocin-induced diabetes resulted in reduced fertility, prolificacy, and libido. Testes showed a marked decrease in the number and function of Leydig cells, the latter manifested as changes in the expression of biochemical markers, including the GLUT-3 hexose transporter, c-kit, insulin-like growth factor I (IGF-I), androgen receptors, and overall tyrosine phosphorylation, as assessed by Western blot and immunocytochemical analyses. The expression of c-kit, IGF-I, insulin, and follicle-stimulating hormone (FSH) receptors in the seminiferous tubules was also affected. Serum levels of luteinizing hormone (LH), FSH, and testosterone significantly decreased. There was a significant (P <.05) correlation between the serum levels of insulin and FSH. No significant correlation was found between the serum levels of insulin or glucose and LH. On the basis of our results, we conclude that, in insulin-dependent diabetes, 1) Leydig cell function and testosterone production decrease because of the absence of the stimulatory effect of insulin on these cells and an insulin-dependent decrease in FSH, which, in turn, reduces LH levels; and 2) sperm output and fertility are reduced because of a decrease in FSH caused by a reduction in insulin.

The aims of the present study were first to compare the effects of melatonin and vitamin E on the cholestasis syndrome and their protective effect on liver injury, and second, to evaluate the activity of antioxidant enzymes after treatment with these antioxidant drugs. Cholestasis was achieved in adult male Wistar rats by double ligature and section of the extra-hepatic biliary duct. Hepatic and plasma oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and reduced glutathione (GSH) in plasma and homogenates of hepatic tissue. Serum bilirubin, alkaline phosphatase (AP), and gamma-glutamyl-transpeptidase (GGT) were used to evaluate the severity of cholestasis, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Both vitamin E and melatonin were administrated 1 day before and 7 days after bile duct ligation. Acute ligation of the bile duct was accompanied by a significant increased in MDA and a decrease in GSH levels in both plasma and liver, as well as a significant reduction in antioxidant enzymes activities. The overall analysis of both treatments showed that melatonin (500 microg/kg daily) offered significantly better protection against cholestasis and a superior protective effect on hepatic injury than did vitamin E (15 mg/kg daily). Although vitamin E treatment resulted in a reduction of parameters of oxidative stress, the results were significantly better after a much lower daily dose of melatonin. Moreover, melatonin treatment was associated with a significant recovery of antioxidative enzymes. In conclusion, the present paper demonstrates a correlation between the intensity of biliary tract obstruction and increased free radical generation, as well as a direct correlation between the level of oxidative stress and the biochemical markers of liver injury. Melatonin (at a much lower dose than vitamin E) was much more efficient than vitamin E in reducing the negative parameters of cholestasis, the degree of oxidative stress and provided a significantly greater hepatoprotective effect against the liver injury secondary to the acute ligation of the biliary duct.

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Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 ± 16 mg/dl). The animals became normoglycemic for ~10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 ± 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liverpyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity. Diabetes 50:131-138, 2001P revious results from our group showed that oral administration of sodium tungstate to rats made insulin deficient and diabetic by streptozotocin (STZ) injection caused a dramatic decrease in their blood glucose concentration (1,2). Two animal models of diabetes, STZ (corresponding to type 1 diabetes model) and neonatally injected STZ (nSTZ) rats (resembling a type 2 diabetes model) were tested. In the first case, the main action of tungstate appears to be the restoration of the hepatic glucose metabolism by increasing the capacity of the liver to utilize glucose through glycolysis and glycogenesis, and to decrease its potential for glucose output (1). However, this does not appear to be the case in rats with diabetes induced by nSTZ; in these rats, the normoglycemic effect of tungstate cannot be attributed to the small changes observed in hepatic glucose metabolism. Moreover, the main action of tungstate appears to be correlated with an increase in insulin content and ␤-cell mass, which leads to an improvement in the ability of ␤-cells to respond to glucose (2). ...

The peculiar features of domain walls observed in ferroelectrics make them promising active elements for next-generation non-volatile memories, logic gates and energy-harvesting devices. Although extensive research activity has been devoted recently to making full use of this technological potential, concrete realizations of working nanodevices exploiting these functional properties are yet to be demonstrated. Here, we fabricate a multiferroic tunnel junction based on ferromagnetic LaSrMnO electrodes separated by an ultrathin ferroelectric BaTiO tunnel barrier, where a head-to-head domain wall is constrained. An electron gas stabilized by oxygen vacancies is confined within the domain wall, displaying discrete quantum-well energy levels. These states assist resonant electron tunnelling processes across the barrier, leading to strong quantum oscillations of the electrical conductance.

No abstract

The effect of melatonin (MEL) on the nephropathy and the oxidative stress induced by a single and high dose of Adriamycin (AD) has been studied in Wistar male rats. MEL (50 μg/kg/day) was injected intraperitoneally 3 and 7 days, respectively, before and after AD injection (20 mg/kg i.p.). Trunk blood was drawn and triglycerides, total cholesterol, phospholipids, high-density lipoprotein cholesterol, urea, creatinine, total protein, lipoperoxides, and reduced glutathione (GSH) levels and catalase activity (CAT) were determined in serum. In kidney homogenates, lipoperoxides, GSH, and CAT were measured as well as total protein in urine. AD administration resulted in hyperlipidemia and high-grade proteinuria and a marked increase in serum lipoperoxides, urea, and creatinine. In the kidney, the increase in lipoperoxides was accompanied by a significant decrease of GSH and CAT. The efficiency of MEL was specially remarkable in restoring GSH, CAT, and proteinuria to the levels of controls. These results confirm the involvement of free radicals in the pathogenesis of nephrotoxicity induced by AD. Likewise, they show the high antioxidative power of MEL and its marked effect on the prevention and suppression of this nephropathy.

Lu et al. Reply:The authors of the preceding Comment [1] argue that the patterns we measured on highly oriented pyrolytic graphite (HOPG) by electric field microscopy (EFM) [2] were a result of surface contamination (e.g., water film) and cannot be attributed to the potential fluctuations of graphite. We disagree with their arguments.The method we used is indeed suitable to measure absolute contact potential differences (CPD), and the voltage dependence shown in Fig. 1 in Ref.[2] is necessary for the calibration. The curves shown in that figure are normalized at the minimum; that is why they coincide. Even if they were not normalized, the difference in CP between the two chosen areas in that figure is about 0.1 V, which in the scale of Fig. 1(a) is within the order of the symbol width [2]. We measured relative values of potentials with the same calibration in a surface region atomically flat as observed by atomic force microscopy. In a homogeneous metal there are no CP fluctuations, neither in a HOPG sample of 0.8 mosaicity measured under similar conditions [2] as the 0.4 -HOPG, a fact that speaks against contamination. Independently done measurements using Kelvin force microscopy in HOPG as well as in Pd-Au structures provide the same CPD as the EFM parabola shift, supporting our interpretation.The authors [1] do not seem to be aware of a key point to understand the EFM experiments. Graphite is not a metal; it conducts in-plane but is practically insulating normal to the planes [3]. Therefore, ideal graphite screens poorly [4] and has a positive dielectric constant [5], an insulator property. Therefore, the applied electric field penetrates 100 nm, and the potential information is not only from the surface but from far inside the bulk. Imagine a condenser consisting of an air gap and 100 nm graphite. In EFM, we are measuring the fluctuation in the energy of this condenser. In this case, it is clear that the role played by an impurity dielectric layer of 1 nm thickness is irrelevant. In particular, one should understand the point of the screening of the electric field. The fluctuation patterns observed are a consequence of regions with different graphite structures or defect densities, which also may link graphite planes changing the density of states at Fermi level.Although the regions with different potentials appear rounded, they are not circles but nearly polygons. Electron backscatter diffraction (EBSD) provides an independent confirmation of the observed patterns on a similar HOPG sample; see Fig. 1. The EBSD patterns look similar to the EFM ones [2] and are related to different dislocation or crystallographic defect density and orientation, which originate the CPD.There have been recent angle-resolved photoemission spectroscopy experiments [6] on clean surfaces of graphite samples in UHV, etc., where regions with a different density of states at the Fermi level were clearly observed. These results provide an indication for the existence of fluctuations of the potential on the sample surface, in agreement w...