In vitro effect of zinc on oxidative changes in human semen

Summary The in vitro effect of zinc on superoxide anion (O₂^?) generation and on experimentally induced lipid peroxidation (LPO) in spermatozoa of infertile men was investigated. Washed spermatozoa pre-incubated for 30 min at 37°C in the presence of 1 or 3 mmol l^-1 zinc, released less superoxide anions (P<0.03 and P<0.02, respectively; n=9) than the untreated spermatozoa. Similar results were obtained using activated polymorphonuclear leukocytes (1 times 10⁶ cells ml^-1) in the presence of 1 or 3 mmol l^-1 Zn (P<0.001 and P<0.0002, respectively; n=9). The in vitro evidence of the inhibitory effect of zinc on O₂^? generation by human spermatozoa and leukocytes indicates that zinc may act in vivo as a scavenger of excessive O₂^? production by defective spermatozoa and/or leukocytes in semen after ejaculation. A significant stimulatory effect of Zn (3 mmol l^-1) on iron-induced lipid peroxidation, measured by the formation of thiobarbituric acid reactive substances (TBARS), was detected in the spermatozoa of 16 normo- and 17 asthenozoospermic males (P<0.0001 and P<0.001, respectively). In 11 samples with sperm concentration 20.3±2.1 times 10⁶ ml^-1, exhibiting initial TBARS concentration two times higher than in normo-and asthenozoospermic samples (40.5±2.4 vs. 17.1±1.1 and 28.5±4.1 nmoles TBARS 10^-8 spermatozoa), no effect of zinc on the LPO rate was found. The observed inhibitory effect of zinc on superoxide anion regardless of the initial O₂^? level and stimulatory effect of zinc depending on the initial LPO rate in human spermatozoa suggests that this metal ion participates in the oxidative changes occurring after ejaculation and thus may modulate the properties of germ cells.     

Relationship of sperm superoxide dismutase-like activity with other sperm-specific enzymes and experimentally induced lipid peroxidation in infertile men

Summary. Superoxide dismutase-like activity (SOD-like), isoenzyme lactate dehydrogenase-C4 (LDH-C4) and NADH-diaphorase activities in spermatozoa have been investigated from 58 normozoospermic and 27 oligozoospermic men. Significantly higher SOD-like, LDH-C4 and diaphorase activities ( P <0.01, P <0.005 and P <0.0001, respectively) were detected in spermatozoa from oligozoospermic men, compared to the activities found in normozoospermic samples. SOD-like activity (mean±SE) in oligozoospermic samples amounted to 8.3±1.6 U 10⁻⁸ spermatozoa, while in spermatozoa in normozoospermic men with a sperm concentration above 20 million of spermatozoa per ml amounted to 4.2±0.5 U 10⁻⁸. There was a close correlation between the SOD-like activity and biochemical indicators of the presence of residual cytoplasm i.e. isoenzyme LDH-C4 and NADH-diaphorase (r = 0.53 and r = 0.66 in normozoospermic and r = 0.63 and r = 0.54 in oligozoospermic men, respectively). A positive relationship between SOD-like activity and experimentally-induced lipid peroxidation was detected in 54 infertile men (r = 0.30; P <0.05). These findings suggest that a higher level of superoxide dismutase-like activity may reflect a defect in the development or maturation of spermatozoa and, thereby, a decreased fertility potential. Hence, determination of SOD-like activity may give information on the state of maturity of human spermatozoa, while its role in the antioxidative protection remains to be determined.     

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.     

Cirrhotic cardiomyopathy: a specific entity

Cirrhosis is a frequent and severe condition, which is the late stage of numerous chronic liver diseases. It is associated with major hemodynamic alterations characteristic of hyperdynamic circulation and with a series of structural, functional, electrophysiological and biological heart abnormalities termed cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial. It is usually clinically latent or mild, likely because the peripheral vasodilatation significantly reduces the left ventricle afterload. However, sudden changes of hemodynamic state (vascular filling, surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts and orthotopic liver transplantation) or myocardial contractility (introduction of beta-blocker therapy) can unmask its presence, and sometimes convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. This entity has been described recently, and its diagnostic criteria are still under debate. To date, current management recommendations are empirical, nonspecific measures. Recognition of cirrhotic cardiomyopathy depends on a high level of awareness for the presence of this syndrome, particularly in patients with advanced cirrhosis who undergo significant surgical, pharmacological or physiological stresses.     

Serum sialic acid in subjects with impaired glucose tolerance and in newly diagnosed type 2 diabetic patients

Several general population studies and those carried out in diabetic patients with complications have pointed to serum sialic acid as a marker of inflammation in atherosclerosis. In this study we examined whether total sialic acid (TSA) was changed in the sera of 28 newly diagnosed subjects with type 2 diabetes (type 2 DM), 47 subjects with impaired glucose tolerance (IGT) and 72 subjects with normal glucose tolerance (NGT). The associations between sialic acid and other atherosclerotic risk factors such as lipid profile, baseline diene conjugates in low-density lipoproteins (LDL-BDC) and fasting insulin were also investigated. We found a trend to TSA increase in subjects with impaired glucose tolerance and a significant increase in TSA in newly diagnosed patients with type 2 DM (2.2±0.3 vs. 1.9±0.3 mmol/l; p<0.03) when compared to subjects with NGT. Lipid profile and LDL-BDC, as a marker of circulating oxidized LDL, did not differ among glucose tolerance categories. Significant associations between total sialic acid and 2-h post-load glucose level, fasting insulin, insulin sensitivity, HDL-cholesterol and log of triglycerides were found in the examined subjects. Multiple regression analysis showed significant correlations between serum sialic acid and 2-h post-load glucose levels and insulin sensitivity. This study indicates that measurement of TSA as a marker of subclinical inflammation may be valuable as an independent parameter in identifying subjects at higher risk of developing type 2 diabetes and those who might benefit from anti-inflammatory treatment. Received: 10 May 2002 / Accepted in revised form: 15 April 2003 Correspondence to M. Gavella     

Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid.

OBJECTIVE: To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent urinary tract infections. METHODS: Twenty women with a history of recurrent urinary tract infections each received 9 intravesical instillations of hyaluronic acid over 6 months. Their status was assessed prospectively over 47.6 weeks and compared with a retrospective review of patient charts covering 36.2+/-6.2 weeks. RESULTS: The total numbers of urinary tract infections were 67 before and 10 after treatment (p<0.001). Thirteen patients (65%) were free of recurrences until the end of the study. One had a recurrence during treatment, and 6 (30%) during follow-up. The number of infections per year per patient was reduced from 4.99+/-0.92 to 0.56+/-0.82 (p<0.001). In women with recurrences, time to recurrence was 178.3+/-25.5 days, compared with 76.7+/-24.6 days before treatment (p<0.001). CONCLUSION: Intravesical instillation of hyaluronic acid is effective in preventing recurrent urinary tract infections.     

Oral contraception, mechanical contraception, and carbohydrate and lipid metabolism: a two-year study.

The carbohydrate and lipid metabolism of 100 women using an oral contraceptive (0.5 mg norgestrel + 0.05 mg ethinyl estradiol) and of 96 women using mechanical contraceptives was monitored over a 2-year period. The women had been screened for factors known to adversely affect carbohydrate and lipid metabolism. Two-hour oral glucose tolerance tests were performed at 6-month intervals during the study; serum insulin was determined at the same intervals in half the women. Triglycerides, total cholesterol, free fatty acids, and body weight were also measured. The study showed no significant differences in lipid metabolism nor in weight gain between women using oral or mechanical contraceptives. After 6 months the fasting glucose of women using oral contraceptives was significantly decreased; at 120 minutes, glucose and insulin levels were significantly increased in comparison to women using mechanical contraceptives. A greater percentage of oral contraceptive users had borderline-abnormal oral glucose tolerance tests but the abnormalities did not persist in the same individuals during the study. The incidence of a pathological oral glucose tolerance with oral contraceptives was 1%.     

A saturable mechanism for transport of immunoglobulin G across the blood-brain barrier of the guinea pig.

The existence of an immunological blood-brain barrier to homologous blood-borne immunoglobulin G (IgG) was investigated in the guinea pig using a vascular brain perfusion technique in situ. Cerebrovascular unidirectional transfer constants (Kin) for 125I-labeled IgG (2.5 micrograms/ml) estimated from the multiple-time brain uptake data, ranged from 0.53 to 0.58 ml min-1 g-1 X 10(3) in the parietal cortex, hippocampus, and caudate nucleus, the transfer rate being some 10 times higher than that for [3H]dextran (MW 70,000). In the presence of 4 mg/ml unlabeled IgG, unidirectional blood to brain transfer of 125I-IgG was markedly inhibited. Immunohistochemical analysis of the brain tissue after vascular perfusion with unlabeled IgG revealed a distribution of the blood-borne immunoglobulin in the endothelial cells of microvessels and in the surrounding perivascular tissue. It is concluded that there is a specific transfer mechanism for IgG at the blood-brain barrier in the guinea pig, which is saturated at physiological plasma levels of IgG.     

A liver urocanase deficiency

Two sisters with a rare inborn error of histidine metabolism resulting from urocanase deficiency are being presented. The more common form of familial histidinemia due to histidase deficiency is excluded. The urocanase deficiency is proven by demonstrating increased excretion of metabolites of the product of the urocanase enzyme action. Further, the strongest evidence for the urocanase defect rests on the demonstration of urocanase deficiency and normal histidase activity in liver.