Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

Advances in understanding the molecular basis of the first steps in color vision

Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.     

几种介质在精子毛细管穿透试验中的比较研究

目的:①新鲜的BCM和冰冻BCM能否用来评价人精子的功能;②降低pH（7.6）的HEW能否用来评价人精子功能。方法:以毛细管穿透试验评价人精子功能。应用人宫颈粘液（HCM）、新鲜和冷冻牛宫颈粘液（BCM）和鸡蛋清（HEW）作为精子穿透介质,对35例生育男子与66例不育男子的精液样本进行了宫颈粘液毛细管穿透试验（CMPT）。结果:生育男子精子分别在HCM、BCM（新鲜和冷冻）和HEW（pH 7.6）中穿透高度相近,无明显统计学意义（P>0.05）;生育男子与不育男子精子在新鲜BCM和HEW中穿透率也无显著差异（P>0.05〕,但他们在HCM和冷冻BCM中,则差异非常显著（P<0.001）。结论:BCM（新鲜和冷冻）和 HEW可代替HCM作为毛细管穿透介质来评价生育男子精子功能;冷冻BCM也可代替HCM来评价不育男子精子功能,而新鲜BCM和HEW则不能用来评价不育男子的精子功能。     

Antenatal presentation of biliary atresia

OBJECTIVES: To investigate the incidence, presence of associated anomalies, type of malformation, and natural history of children with biliary atresia (BA) who presented antenatally.Study design The database of 194 infants diagnosed with BA at our tertiary referral unit between 1991 and 2002 was reviewed for infants in whom routine antenatal ultrasound had revealed biliary cystic malformations (BCMs). A retrospective analysis of their medical records was undertaken. RESULTS: Nine infants (six girls) with BCM were identified (4.6% of total referred patients with BA); all were born after 37 weeks' gestational age and presented to us at a median age of 4 weeks (range, 1-14 weeks). The presence of the BCM was confirmed on postnatal ultrasonography. Median age at corrective surgery was 5 weeks (range, 2-16 weeks). At surgery, six patients had type III BA, including one with the biliary atresia-splenic malformation syndrome; two had type II BA; and one had type I BA. Postoperatively, the infants were followed for a median of 2 years (range, 6 months to 11 years). All infants successfully cleared their jaundice. CONCLUSIONS: Improved techniques in routine antenatal ultrasonography can allow early recognition of BCM. This study suggests that BCM noted antenatally may represent early presentation of both biliary atresia-splenic malformation and nonsyndromic BA.     

Rivastigmine reduces “likely to use methamphetamine” in methamphetamine-dependent volunteers

We previously reported that treatment with the cholinesterase inhibitor rivastigmine (3 mg, PO for 5 days) significantly attenuated “Desire for METH”. Given that higher dosages of rivastigmine produce greater increases in synaptic ACh, we predicted that 6 mg should have more pronounced effects on craving and other subjective measures. In the current study, we sought to characterize the effects of short-term exposure to rivastigmine (0, 3 or 6 mg) on the subjective and reinforcing effects produced by administration of methamphetamine (METH) in non-treatment-seeking, METH-dependent volunteers. This was a double-blind, placebo-controlled, crossover study. Participants received METH on day 1, and were then randomized to placebo or rivastigmine on day 2 in the morning and treatment continued through day 8. METH dosing was repeated on day 6. The data indicate that METH (15 and 30 mg), but not saline, increased several positive subjective effects, including “Any Drug Effect”, “High”, “Stimulated”, “Desire METH”, and “Likely to Use METH” (all p's < 0.0001). In addition, during self-administration sessions, participants were significantly more likely to choose METH over saline (p < 0.0001). Evaluating outcomes as peak effects, there was a trend for rivastigmine to reduce “Desire METH” (p = 0.27), and rivastigmine significantly attenuated “Likely to Use METH” (p = 0.01). These effects were most prominent for rivastigmine 6 mg when participants were exposed to the low dose (15 mg, IV), but not high dose (30 mg, IV), of METH. The self-administration data reveal that rivastigmine did not alter total choices for METH (5 mg, IV/choice). Overall, the results indicate some efficacy for rivastigmine in attenuating key subjective effects produced by METH, though additional research using higher doses and longer treatment periods is likely needed. These data extend previous findings and indicate that cholinesterase inhibitors, and other drugs that target acetylcholine systems, warrant continued consideration as treatments for METH dependence.