Effects of sex and age on strength-duration properties.

OBJECTIVE: To evaluate the possible effects of sex and age on strength-duration time constant (SDTC). METHODS: The SDTC of 126 healthy volunteers was measured following stimulation of right median nerve at the wrist. Variations in values were evaluated according to sex and age. RESULTS: The SDTC was 438.6+/-114.5 micros in women and 396.2+/-90.3 in men (P=.023). In men, as age increased, so did SDTC. However, this was not true in women. Comparing the values of women and men, aged below 40, demonstrated a difference in excitability, confined to younger patients. CONCLUSIONS: As SDTC depends on the biophysical properties of the axonal membrane and can provide some information about Na(+) channel function, these data raise the possibility of a difference in Na(+) channel function between men and women and a difference in the conductance with age. SIGNIFICANCE: The age- and sex-related differences shown in this study suggest a possible biochemical or hormonal influence on axonal excitability.     

Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine.

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.     

The <Emphasis Type="Italic">Arg</Emphasis>194<Emphasis Type="Italic">Trp</Emphasis> polymorphism in DNA repair gene XRCC1 and the risk for sporadic late-onset Alzheimer's disease

Abstract Alzheimer's disease (AD) is defined pathologically by the presence of β-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically significant (OR=1.95, 95% CI 0.88–4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96–4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the development of AD.     

Contradictory effects of chlorpromazine on endothelial cells in a rat model of endotoxic shock in association with its actions on serum TNF-alpha levels and antioxidant enzyme activities.

We examined the effects of the phenothiazine derivative, chlorpromazine on thoracic aortic endothelial cell histology (14 h after LPS challenge) in a model of endotoxic shock in rats. Since excessive formation of tumor necrosis factor-alpha (TNF-alpha) and oxygen-derived free radicals contribute to endothelial injury in endotoxemia, we also evaluated the effect of the drug on the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase in liver tissue in this model and tried to find out whether this possible effect was associated with a change in serum TNF-alpha levels (measured 90 min after chlorpromazine administration). Endotoxemia was induced by a single i.p. injection of lipopolysaccharide (LPS) (5 mg kg(-1) in 1.5 ml of saline; LPS from Escherichia coli serotype 055:B5, L-2880, Sigma Chemical Company). Electron microscopic evaluation of the aortas revealed that chlorpromazine (administered 30 min prior to LPS challenge), in smaller doses (3 mg kg(-1)) ameliorated the endothelial cell injury caused by LPS, whereas it caused deterioration of endothelial cell morphology in higher doses (10 and 25 mg kg(-1)). Chlorpromazine administration caused a significant reduction in serum TNF-alpha levels, which was correlated well with an increase in SOD activity in all drug doses (3, 10 and 25 mg kg(-1)). Catalase activity was increased only in the 25 mg kg(-1) chlorpromazine group.     

Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis

The goal of this investigation was to study the protective effects of thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in rats. On day 0 under ether anesthesia, the experimental groups were immunized with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and emulsified in Freund's incomplete adjuvant. Control rats were gavaged with vehicle, whereas CII was administered intradermally. In addition, arthritis treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3 weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a week for 3 weeks starting on day 0). A significant decrease in the incidence and severity of arthritis by clinical and radiographic assessments was found in recipients of therapy, compared with that of controls. The MTX treatment significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in arthritic rats. Likewise, TQ treatment was also able to reduce significantly (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The histopathologic abnormalities are consistent with the hydropic epithelial cell degenerations and moderate tubular dilatation in the some proximal and distal tubules. The severity of the degenerative changes in most of the shrunken glomerules and vascular congestion were also observed in arthritic animals. Preventive treatment of TQ and especially MTX significantly inhibited kidney dysfunction and this histopathologic alterations. These studies indicate that TQ can be used similar to MTX as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.     

A comparison of double single suture-button fixation,suture-button fixation,and screw fixation for ankle syndesmosis injury: A retrospective cohort study

Different methods have been used throughout the years for syndesmotic injury but there is no consensus on the ideal treatment. Some methods are expensive and some have more complications. The aim of this study is to compare single suture endobutton with double suture endobutton and screw fixation for syndesmotic injury.Sixty nine patients with syndesmotic injury with fibular fractures whom were treated with a single interosseous suture endobutton system (ZipTight^TM, Zimmer Biomet), a double interosseous suture endobutton system (ZipTight^TM, Zimmer Biomet) and 1 syndesmotic screw (TST, Istanbul, Turkey) were included in this study. Functional and radiological results from patient records between 2015 and 2018 were retrospectively evaluated.Twenty patients were treated with the double interosseous suture endobutton, 23 were treated with the single interosseous suture endobutton, and 26 were treated with traditional AO screw fixation. Three patients from the screw fixation group (11.5%) required revision surgery (P < .05). All the radiologic and clinical outcomes were statistical similar in all 3 groups.Our findings showed that the interosseous suture endobutton system is at least as safe as the screw fixation technique for treatment of syndesmosis joint injuries and can be used as an alternative to the screw method. The interosseous suture endobutton system eliminates the need for a second surgery to remove the hardware, which minimizes the probability of re-diastasis. Since our results showed no statistical difference between single and double interosseous suture endobutton systems, the less costly single endobutton system may be the better alternative.     

Peroxynitrite induced decrease in Na^＋, K^＋-ATPase activity is restored by taurine

AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In the present study, the effect of taurine on changes of liver plasma membrane Na+, K+-ATPase induced by ONOO- was investigated. METHODS: Liver plasma membrane was exposed to ONOO-with or without taurine. Na+, K+-ATPase activity and lipid peroxidation as thiobarbituric acid reactive substances (TBARS) levels were measured. RESULTS: Different concentrations of ONOO- (100, 200, 500, and 1 000 μmol/L) were found to decrease liver plasma membrane Na+, K+-ATPase activity significantly. The depletion of enzyme activity was not concentration dependent. Effects of different concentrations of taurine on liver plasma membrane Na+, K+-ATPase activity were also measured. Taurine did not cause any increase in enzyme activity. When plasma membranes were treated with 200 μmol/L ONOO- with different concentrations of taurine, a restoring effect of taurine on enzyme activity was observed. TBARS levels were also measured and taurine was found to decrease the elevated values. CONCLUSION: Taurine is observed to act as an antioxidant of ONOO- to decrease lipid peroxidation and thus affect liver plasma membrane Na+, K+-ATPase by restoring its activity.     

Amlodipine and glutathione cycle in hypercholesterolaemia

OBJECTIVE: Effects of amlodipine on lipid peroxidation and alterations in glutathione and related enzymes in blood and aortic tissue were investigated in a cholesterol-induced atherosclerotic rabbit model. METHODS AND RESULTS: New Zealand white male rabbits were fed with regular chow (group I), chow supplemented with I% cholesterol (group II), regular chow plus amlodipine 5 mg/kg/day p.o. (group III) and I% cholesterol diet supplemented with amlodipine (group IV) for 8 weeks. Cholesterol, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-Rd) were determined in blood samples drawn before and after the experimental period. Aortic tissue was examined morphologically for atherosclerotic changes and tissue cholesterol, MDA, GSSG, GSH-PX, GSH-Rd and glutathione-S-transferase (GST) were measured. After 8 weeks, blood cholesterol, MDA, GSSG and GSH-PX were elevated in groups II and IV; GSH was reduced in group IV; MDA levels were higher in group II than in group IV. Aortic tissue investigations revealed higher cholesterol and MDA concentrations in group II than in group IV. Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group II. Histopathological alterations related to atherogenesis were less in group IV than in group II. CONCLUSIONS: Amlodipine reduced the increase in oxidative stress by inhibiting excessive MDA production. Accelerated glutathione redox cycle activity of erythrocytes from animals supplemented with amlodipine suggests that this drug may reduce oxidative stress by enhancing the glutathione system. However, this drug does not seem to affect the glutathione redox cycle in the aortic tissue.