Systemic oxytocin increases glutamate efflux in the nucleus accumbens core of cocaine-experienced male and female rats but only increases dopamine efflux in males.

Oxytocin attenuates cocaine-seeking when administered both systemically and directly into the nucleus accumbens core. This effect is blocked by intra-accumbens antagonism of mGlu2/3 and, together with our finding that intra-accumbens oxytocin increases glutamate concentrations in this brain region, indicates that pre-synaptic regulation of glutamate release by oxytocin influences cocaine relapse. However, mGlu2/3 receptors also regulate dopamine release in the nucleus accumbens. Here we aimed to determine whether systemic oxytocin increases glutamate and dopamine concentrations in the nucleus accumbens core of cocaine-experienced and cocaine-naïve male and female rats. A subset of rats self-administered cocaine (0.5 mg/kg/infusion) and then underwent extinction training for 2-3 weeks. Rats were implanted with microdialysis probes in the accumbens core and samples were collected for a baseline period, and following saline (1 mL/kg), and oxytocin (1 mg/kg, IP) injections. Locomotion was assessed during microdialysis. In cocaine-experienced rats, oxytocin increased glutamate concentrations in the accumbens core to the same extent in males and females but only increased dopamine concentrations in male rats. Oxytocin did not alter glutamate levels in cocaine-naïve rats. Oxytocin did not produce sedation. These results extend previous findings that systemic oxytocin increases nucleus accumbens dopamine in a sex-specific manner in cocaine-experienced rats. These data are the first to find that systemic oxytocin increases nucleus accumbens glutamate after cocaine experience, providing a mechanism of action by which oxytocin attenuates the reinstatement of cocaine seeking in both male and female rats.

Antenatal betamethasone and favourable outcomes in fetuses with 'poor prognosis' diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a common abnormality affecting 1 in 2,000 gestations. The mortality exceeds 50% despite recent advances in postnatal treatment. The widespread antenatal use of glucocorticoids to induce lung maturation in fetuses at risk of premature delivery suggests a potential for a therapeutic effect in other fetuses with impaired lung development. The parents of three fetuses referred with CDH and features suggesting a poor postnatal prognosis (early diagnosis, liver herniation, and lung area-to-head circumference ratio <1.0, or associated abnormalities) elected to receive maternal betamethasone starting at 24 to 26 weeks' gestation rather than undergo a fetal tracheal plug. All three infants survived and were extubated within 10 days. The long-term use of antenatal steroids in the treatment of CDH may thus be of benefit and warrants further study.

The identification of alpha-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase.

Peptides based upon the non-prime side residues of the NS4A-4B cleavage site of hepatitis C virus (HCV) NS3-4A proteinase containing an alpha-ketoamide moiety in place of the scissile amide bond are potent inhibitors of this enzyme.

Nurse-physician collaborative relationship on nurses' self-perceived job satisfaction in ambulatory care.

The dynamic restructuring of the healthcare environment from a primary acute care focus to an ambulatory care focus has prompted a migration of nurses to the ambulatory care setting. The predication of nursing job satisfaction is a complex process that has received little attention in the ambulatory care setting. The purpose of this study was to determine if a relationship existed between the nurse-physician relationship and nurses' self-perceived job satisfaction in the ambulatory care setting. While study findings demonstrated there was no significant relationship between the nurse-physician relationship and nurses' self-perceived job satisfaction in the ambulatory care setting, it did confirm that registered nurses working in the ambulatory setting have a moderate level of job satisfaction. The lack of correlation between the nurse-physician relationship and job satisfaction may have been attributed to limitations such as a limited sample size and the nurses having a relationship with a smaller number of physicians in the ambulatory care setting. Recommendations to further understanding of the nurse-physician relationship included further descriptive studies of nurses working in the ambulatory care setting and further studies on job satisfaction of nurses.

Peritoneal non-closure at caesarean section.

BACKGROUND: It has been suggested that the peritoneal suture might be omitted during caesarean section without adverse effects. OBJECTIVES: The objective of this review was to assess the effects of non-closure as an alternative to closure of the peritoneum at caesarean section on intra-operative and immediate postoperative outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Controlled trials comparing leaving the visceral and/or parietal peritoneum unsutured at caesarean section with a technique which involves suturing the peritoneum in women undergoing elective or emergency caesarean section. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted by two reviewers. MAIN RESULTS: Four trials involving 1194 women were included. Non-closure of the peritoneum saved operating time (weighted mean difference of -6.12 minutes, 95% confidence interval -8.00 to -4.27) with no significant differences in postoperative morbidity, analgesic requirements and length of hospital stay. There was a consistent, although nonsignificant, trend for improved immediate postoperative outcome if the peritoneum was not closed. REVIEWER'S CONCLUSIONS: There seems to be no significant difference in short term morbidity from non-closure of the peritoneum at caesarean section.

The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase.

Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.

Self-reported abuse history and pain complaints among young adults.

OBJECTIVE: Considerable evidence suggests that a self-reported history of physical and/or sexual abuse is more frequently reported among chronic pain populations and is associated with poorer adjustment to pain. However, previous research has typically included patients seeking treatment for pain, whereas few population-based studies have explored the association between abuse history and pain. This purpose of this study was to examine the association between self-reported history of sexual or physical abuse and recent pain complaints, health-related variables, and psychological disturbance among a nonclinical sample of young adults. DESIGN: Subjects were 426 (275 female, 151 male) college students who completed a series of questionnaires assessing abuse history, recent pain, health care utilization, perceived health, and psychological variables. RESULTS: Females reported a positive history of abuse (PHA) more frequently than males (43.5% vs. 23.8%), and females reported significantly higher rates for all types of abuse except physical abuse during childhood (p < 0.05). PHA subjects reported experiencing pain in more sites and pain of higher severity over the past month compared to subjects with a negative history of abuse (NHA) (p < 0.05). PHA subjects also reported more health care utilization and greater psychological disturbance, including depression, somatization, negative temperament, and higher levels of catastrophizing (p < 0.05). Interestingly, when somatization and depression scale scores were used as covariates, group differences in pain complaints and health care utilization became nonsignificant (p > 0.10). CONCLUSION: These findings suggest that a self-reported history of physical or sexual abuse is associated with increased pain complaints, health care utilization, and psychological disturbance even among young adults from a nonclinical population. Moreover, the association between abuse and pain complaints appears to be moderated at least in part by the higher levels of somatization and depression observed in the PHA group.

Pregnancies complicated by retained placenta: sex ratio and relation to pre-eclampsia.

Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's Hospital, covering 8549 births between 1993 and 1995, were used to ascertain the sex ratios in singleton pregnancies and the sex ratios in those pregnancies in which there was retained placenta, hypertension in pregnancy, or pre-eclampsia. The likelihood of independence of occurrence or mutual exclusivity of retained placenta and hypertension in pregnancy or pre-eclampsia were also examined. The male:female sex ratio in the South Australian population was 1.077. In pregnancies with hypertension in pregnancy it was 1.165 (P<0.001) and in pregnancies with retained placenta it was 0.883 (P<0.0001). There was a trend to an increased sex ratio in pre-eclamptic pregnancy (1.248 in primigravid and 1.092 in multigravid women) but there was insufficient power to detect significance (P=0.207 and 0.470, respectively). Neither hypertension in pregnancy nor pre-eclampsia were mutually exclusive of placenta accreta: hypertensive disorders of pregnancy and placenta accreta occurred independently of each other. Our findings suggest that sex-linked antigens are unlikely to influence maternofetal interactions consistently to give rise to one but not the other pregnancy complication.