Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults.

Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults. Strong positive correlations with fat mass were observed for cystine and mixed disulfides (r ≥ 0.61, P < 0.001), but not the quantitatively major form, bCys. Primary human preadipocytes were differentiated in media containing cystine concentrations varying from 10-50 µM, a range similar to that in plasma. Increasing extracellular cystine (10-50 µM) enhanced mRNA expression of PPARG2 (to sixfold), PPARG1, PLIN1, SCD1 and CDO1 (P = 0.042- < 0.001). Adipocyte lipid accumulation and lipid-droplet size showed dose-dependent increases from lowest to highest cystine concentrations (P < 0.001), and the malonedialdehyde/total antioxidant capacity increased, suggesting increased oxidative stress. In conclusion, increased cystine concentrations, within the physiological range, are positively associated with both fat mass in healthy adults and human adipogenic differentiation in vitro. The potential role of cystine as a modifiable factor regulating human adipocyte turnover and metabolism deserves further study.

Does Serum Visfatin Represent a Biochemical Marker to an Experimental Peripheral Neuropathic Pain in Mice.

The effects of pregabalin on neuropathic pain relief and the serum visfatin level were assessed using an experimental model of neuropathy in a study conducted on 40 male mice with sciatic nerve constriction. The mice were randomly assigned to 4 groups, each with 10 mice. The mice were subjected to experimental chronic partial constriction of the sciatic nerve and compared to sham-operated, saline-treated control mice (group I). The experimental groups (II-IV) were subjected to partial constriction of the left sciatic nerve. A series of behavioral tests, electrophysiological studies and biochemical measures were performed after 3 weeks of daily oral treatment with pregabalin (20 and 40 mg/kg in groups III and IV, respectively). The study revealed the actions of pregabalin against the nociceptive effects of chronic sciatic nerve constriction in mice (p < 0.01), including replenishment of the glutathione level (p < 0.05) and reduction of the serum visfatin level. No significant effect on the tissue malondialdehyde level was found for any of the pregabalin doses. The percentage differences in the maximum tetanic force between the ipsilateral and contra lateral legs were significant in both pregabalin-treated groups (p < 0.05). We concluded that pregabalin reduced the serum visfatin level and produced a dose-dependent antinociceptive antioxidant effect.

Potential Neuroprotective Role of Verapamil in Experimentally- Induced Chronic Sciatic Nerve Constriction in Mice.

Objectives: The aim of the current study was to evaluate of three dose levels of verapamil; as a calcium channel blocker that could confer an anti-inflammatory efficacy, in an experimental model of neuropathy in mice that had been subjected to chronic partial constriction of the sciatic nerve. Materials and Methods: Six groups; each of 10 mice as follows: Oral saline treated control (group I), sham operated (group II), groups subjected to partial constriction of left sciatic nerve (groups III-VI); oral saline control group, groups treated with oral verapamil 15, 30 and 60 mg/kg respectively. Time course behavioral tests were observed namely noxious thermal and non noxious response as well as cold allodynia response at 0, 1,7,14 and 21 day of study. Serum visfatin and serum leptin levels, nerve reduced glutathione, spinal cord brain derived neurotrophic factor as end point biochemical measurements were assessed. All were done after three weeks of oral treatment. Results: The study revealed significant antinociceptive effect of verapamil (P<0.001) with replenishment of reduced glutathione (P<0.01), significant increase in spinal cord levels of brain derived neurotrophic factor (P<0.001) and reduction of mean serum visfatin levels. No significant effect on mean serum leptin in any treated groups was observed. Conclusions: Verapamil 60 mg, 30 mg/kg oral dose had the highest significant antinociceptive, regenerative and as well as ability to reduce serum visfatin level after three week therapy.

Further studies on autoclaved cercarial vaccine against schistosomiasis: safety, longevity and stability.

The autoclaved cercarial vaccine (ACV) which is a special type of killed vaccine has been reported to induce experimental high level of homologous protective immunity. This study was to adjust the dose and to assess vaccine safety, longevity and stability as well as the possibility of transplacental transmission of immune response from pregnant mice to their offspring. The results showed that two doses of the lowest most effective concentration of ACV that achieved the high percentage reduction of worm burden is safe as demonstrated by absence of any local or systemic side effects, normal blood picture and normal liver and kidney function tests. ACV is stable when kept either at 4 degrees C for six months or at -35 degrees C for up to 12 months and it offered considerable duration of longevity. Offspring of vaccinated mothers didn't show any signs of protection against challenge infection.