The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine

Sarcosine is an amino acid involved in one-carbon metabolism and a promising therapy for schizophrenia because it enhances NMDA receptor (NMDAR) function by inhibiting glycine uptake. The structural similarity between sarcosine and glycine led us to hypothesize that sarcosine is also an agonist like glycine. We examined this possibility using whole-cell recordings from cultured embryonic mouse hippocampal neurons. We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist. This finding led us to examine whether the physiological effects of NMDAR activation with these two co-agonists are the same. The difference in desensitization probably accounts for rises in intracellular Ca²⁺, as assessed by the fluorescent indicator fura-FF, being larger when NMDAR activation occurred with sarcosine than with glycine. In addition, Ca²⁺-activated K⁺ currents following NMDAR activation were larger with sarcosine than with glycine. Compared to glycine, NMDAR-mediated autaptic currents decayed faster with sarcosine suggesting that NMDAR deactivation also differs with these two co-agonists. Despite these differences, NMDAR-dependent neuronal death as assessed by propidium iodide was similar with both co-agonists. The same was true for neuronal bursting. Thus, sarcosine may enhance NMDAR function by more than one mechanism and may have different effects from other NMDAR co-agonists.     

Elevated plasma Met-enkephalin levels in the human newborn are a poor indicator of perinatal stress.

OBJECTIVE: This study was designed to investigate whether plasma Met-enkephalin peptides could serve as markers of physiologic stress in the neonate. STUDY DESIGN: Infants (n = 115) between 1.2 and 4.7 kg and 28 and 42 weeks of gestation were studied at birth. Seventy-four infants were delivered by the vaginal route, 31 by cesarean section after labor, and 10 by cesarean section before labor. Correlations were sought between plasma enkephalin peptides and epinephrine, norepinephrine, and arterial blood gases with linear regression analysis. Various clinical data were also analyzed. RESULTS: Plasma Met-enkephalin levels were significantly greater in infants exposed to labor (440 +/- 36 vs 260 +/- 30 pg/ml, p less than 0.05). The large-molecular-weight forms of enkephalin peptides were also greater in these infants (approximately 50 +/- 4 vs 23 +/- 2 ng/ml). There was no correlation between plasma enkephalin peptides and catecholamines, arterial pH, or Apgar scores. There was a significant but weak correlation between plasma Met-enkephalin levels and birth weight (r = 0.34, p = 0.03) and PaO2 (r = -0.28, p less than 0.05). CONCLUSION: The lack of correlation between Met-enkephalin plasma levels and umbilical plasma catecholamine concentrations, acid-base status, or Apgar scores suggests that circulating Met-enkephalin is a poor indicator of stress in the newborn.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

The equivalence of English and Chinese SF-36 versions in bilingual Singapore Chinese

Objective: To assess the equivalence of English and Chinese versions of the SF-36. Methods: Using a crossover design with block randomisation and stratification by age, identical English or Chinese questionnaires containing the English (UK) and Chinese (HK) SF-36 versions were administered 3–16 days apart to 168 free-living, bilingual, ethnic Chinese volunteers in Singapore. Item level equivalence of both versions was assessed by comparing item means and orderings within each scale. Scale level equivalence was assessed by comparing internal consistency (Cronbach's ), results of factor analysis and mean scale scores (using paired t-tests and intra-class correlations). Results: Item and scale level comparisons supported the equivalence of both versions. For both the versions, item means, item ordering and Cronbach's were similar, and factor analysis yielded two factors with similar factor loadings. There was no clinically important difference in mean scale scores for seven of eight scales, and intra-class correlations were excellent/good for five scales (0.69–0.77) and moderate for three scales (0.55–0.57). Conclusion: English (UK) and Chinese (HK) SF-36 versions are equivalent in bilingual Singapore Chinese. Our data suggest that SF-36 scores from English- and Chinese-speaking subjects may be combined in studies using the SF-36, increasing the power and representativeness of such studies.     

The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog

We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the neuroprotection was more robust than with 17beta-estradiol. The effect of ZYC-5 was not mediated by the classical estrogen receptor, because it was unaffected by the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against excitotoxicity was not directly mediated through the NMDA receptor, because there was no effect of ZYC-5 on NMDA current or the intracellular calcium increase induced by NMDA. Results obtained with the free-radical-sensitive dye, dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related to its radical scavenging properties. Although some of estrogen's neuroprotective effects may depend upon the estrogen receptor, our results suggest the possibility of neuroprotection without hormonal side effects.     

A descriptive study of youth risk behavior in urban and rural secondary school students in El Salvador

Background  

Adolescence is an important stage of life for establishing healthy behaviors, attitudes, and lifestyles that contribute to current and future health. Health risk behavior is one indicator of health of young people that may serve both as a measure of health over time as well as a target for health policies and programs. This study examined the prevalence and distribution of youth health risk behaviors from five risk behavior domains–aggression, victimization, depression and suicidal ideation, substance use, and sexual behaviors–among public secondary school students in central El Salvador.     

Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.