Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter

The effect of inhibition of nitric oxide synthase on nonadrenergic, noncholinergic nerve-mediated responses in circular smooth muscle of the human esophageal body and lower esophageal sphincter (LES) was examinedin vitro. Tissues were obtained from 10 patients (eight esophageal resection for cancer, two transplant donors). Muscle strips from the LES developed significant spontaneous tension (11.6 ± 2.1 mN/mm²,N=6) and relaxed in response to electrical stimulation. The nitric oxide synthase inhibitor,N -nitro-l-arginine (NNA), at 10^–5 M, inhibited the relaxation, but had no significant effect on the spontaneous tension (13.0 ± 2.6 mN/mm²,P=0.07). Esophageal body strips developed little spontaneous tension, demonstrated an off contraction following the cessation of the electrical stimulus, and when contracted with 10^–5 M carbachol, relaxed during electrical stimulation. NNA (10^–5 M) inhibited the off contraction and the relaxation seen after carbachol and unmasked a prominent intrastimulus contraction. This intrastimulus contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin. NNA showed similar potency in the esophageal body and LES and its effects were reversed byl-arginine, but notd-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.This research was supported in part by an ICI Pharma/Medical Research Council of Canada Research Fellowship grant awarded to H.G. Preiksaitis and a Medical Research Council Program Grant PG8.     

A Field Test of the Sweat Patch

The sweat patch is a new, noninvasive method designed to estimate the ethanol consumption of drinking subjects. It consists of salt-impregnated absorbent pads protected by a plastic chamber with attached water-tight adhesive. The patch reportedly collects transepidermal fluid at a steady rate for up to 10 days. Recent laboratory research has indicated a linear relationship between the concentration of ethanol in transepidermal fluid and mean concentration of ethanol in blood. Levels of ethanol in the sweat patch allowed identification of persons drinking at least 0.5 g of ethanol/kg/day with 100% sensitivity and specificity. The study reported here was conducted to test the field effectiveness of this sweat patch in normal, active research subjects. First, several pretests were conducted to determine the optimal location of the patch on the body and its fluid uptake at various sites. A laboratory experiment using nonalcoholic subjects was conducted to replicate previous work, and methods of measuring ethanol concentration in the patch were refined. A field test of the patch was then carried out. Healthy active volunteers drank a single "moderate" dose of ethanol (0.5 g of ETOH/kg of body weight) and then remained abstinent for the next 3 days. A week later, a "heavy" dose (1.0/kg of body weight) was consumed. Only a trace of ethanol was detected in any of the patches worn in either experiment. The patch did not measure ethanol in the transepidermal fluid under field conditions. Thus, further design modifications and pilot testing are required before the full benefits of this unobtrusive measure of drinking can be realized.     

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain acetylcholinesterase activity in forest songbirds exposed to a new method of UULV fenitrothion spraying

Brain acetylcholinesterase (AChE) activity was measured in forest songbirds exposed to Ultra Ultra Low Volume (UULV) aerial spraying of fenitrothion in New Brunswick for spruce budworm control. Brain AChE activity was determined in 324 songbirds from the sprayed blocks and 47 from an unsprayed control area, and represented four species. In most cases, more than half of the individuals of any species sampled were diagnosed as exposed (20% inhibition) to the fenitrothion sprays and had a mean percent level of inhibition of 40% or greater, relative to mean control values. The proportion of birds with life-threatening levels of inhibition (50%) was usually less than 20%. The largest proportion of birds with life-threatening inhibition was found after the first 210 g AI/ha spray. The White-throated Sparrow had the highest proportion (25–55%) of individuals with life-threatening inhibition after all sprays. Brain AChE inhibition was greater in exposed birds collected after the first 210 g AI/ha spray than after the second one. Variation among species' responses to the sprays is discussed in relation to habitat and foraging preferences. Several sampling biases which may contribute to underestimation of the impact of fenitrothion spraying on birds are identified.     

Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node.

AIMS: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (相似文献   

Udp-glucuronosyltransferase 2b7 is the major enzyme responsible for gemcabene glucuronidation in human liver microsomes.

The predominant metabolic pathway of gemcabene in humans is glucuronidation. The principal human UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of gemcabene were determined in this study. Glucuronidation of gemcabene was catalyzed by recombinant UGT1A3, recombinant UGT2B7, and recombinant UGT2B17, as well as by human liver microsomes (HLM). Gemcabene glucuronidation in recombinant UGTs and HLM followed non-Michaelis-Menten kinetics consistent with homotropic activation, but pharmacokinetics in humans were linear over the dose range tested (total plasma C(max), 0.06-0.88 mM). Gemcabene showed similar affinity (S(50)) for recombinant UGTs (0.92-1.45 mM) and HLM (1.37 mM). S-Flurbiprofen was identified as a more selective inhibitor of recombinant UGT2B7-catalyzed gemcabene glucuronidation (>23-fold lower IC(50)) when compared with recombinant UGT1A3- or recombinant UGT2B17-catalyzed gemcabene glucuronidation. The IC(50) for S-flurbiprofen inhibition of gemcabene glucuronidation was similar in HLM (60.6 microM) compared with recombinant UGT2B7 (27.4 microM), consistent with a major role for UGT2B7 in gemcabene glucuronidation in HLM. In addition, 5,6,7,3',4',5'-hexamethoxyflavone inhibited recombinant UGT1A3 and recombinant UGT2B17-catalyzed gemcabene glucuronidation (with 4-fold greater potency for recombinant UGT1A3) but did not inhibit gemcabene glucuronidation in HLM, suggesting that UGT1A3 and UGT2B17 do not contribute significantly to gemcabene glucuronidation. Reaction rates for gemcabene glucuronidation from a human liver bank correlated well (r(2)=0.722, P<0.0001; n=24) with rates of glucuronidation of the UGT2B7 probe substrate 3'-azido-3'-deoxythymidine. In conclusion, using the three independent experimental approaches typically used for cytochrome P450 reaction phenotyping, UGT2B7 is the major enzyme contributing to gemcabene glucuronidation in human liver microsomes.     

Reasons for Teachers' Adaptation of Substance Use Prevention Curricula in Schools with Non-White Student Populations

In this study we investigate reasons why teachers adapt substance use prevention curricula in the nation's middle schools. We hypothesize that these reasons will be most salient in schools with racially and ethnically diverse student populations, for whom teachers may believe it appropriate to tailor their curricula. The study sample comprised a nationally representative sample of lead substance use prevention teachers in the nation's middle schools. Respondents answered questions concerning eight student problems or needs that constituted reasons why they might adapt their prevention lessons. Controlling for a variety of school and teacher characteristics, we found that teachers in high minority schools were more likely to adapt curricula in response to three of the eight characteristics presented: youth violence, limited English proficiency, and various racial/ethnic or cultural groups. We suggest that curriculum developers make a systematic effort to understand how teachers are adapting their curricula in high minority schools and incorporate these modifications, if found effective, into their curricula.     

Is there a relationship between overweight and obesity and mental health problems in 4- to 5-year-old Australian children?

OBJECTIVE: To investigate the relationship between overweight and obesity, and mental health problems in Australian 4- to 5-year-old children. METHODS: The study used data from wave 1 (2004) of the Longitudinal Study of Australian Children (LSAC). The participants were 4983 4- to 5-year-old children (2537 boys and 2446 girls) with a mean age of 56.9 months (standard deviation 2.6 months; range 51-67 months). Children were classified as nonoverweight, overweight, and obese on the basis of International Obesity Task Force definitions. Mental health problems were assessed by the Strengths and Difficulties Questionnaire (SDQ) completed by parents and teachers. RESULTS: Although obese 4- to 5-year-old boys had more mental health problems than nonoverweight boys, differences between the groups were small and substantially reduced when analyses controlled for children's sociodemographic characteristics. Parents reported that overweight/obese girls had more peer problems, whereas teachers reported they had more conduct problems. Children in all weight groups had mean scores within the normal range of scores on all the SDQ subscales. CONCLUSIONS: Differences in rates of mental health problems experienced by young children of different weight status appear relatively small. Higher rates of mental health problems experienced by more obese boys may reflect differences in their sociodemographic characteristics rather than their weight status per se. Policies that reduce the number of young children living in poverty or experiencing other adverse social circumstances have the potential to reduce rates of mental health problems experienced by older children with overweight/obesity.