The influence of endogenous dopamine levels on the density of [3H]SCH23390-binding sites in the brain of the honey bee, Apis mellifera L

This paper examines the relationship between endogenous dopamine (DA) levels and the density of [3H]SCH23390-binding sites in the brain of the adult worker honey bee. DA levels were reduced pharmacologically using a single 10 microl injection of either alpha-methyl-DL-p-tyrosine (AMT; 250 microg or 500 microg) or alpha-methyl-DL-tryptophan (AMTP; 250 or 500 microg) into the haemolymph of the bee. In all cases, maximum depletion of DA was observed 3 h after treatment, but in bees treated with AMTP (250 or 500 microg) or with 250 microg AMT, DA levels returned to normal within 24 h of treatment. Neither AMT nor AMTP was selective for DA: both drugs also reduced serotonin (5-hydroxytryptamine, 5HT) levels in the brain. However, AMTP was more effective than AMT at depleting 5HT, whereas for DA, the reverse was true. Depletion of DA levels, using 250 microg AMT, led to a dramatic decline in the levels of specific binding of [3H]SCH23390, defined in this study as binding in the presence of 5x10(-6) M cis-(Z)-flupentixol (see Ref. [28] ). In contrast, naturally occurring diel fluctuations in DA levels, identified in the optic lobes of the brain, and changes in brain DA levels resulting from queenlessness, had no significant effect on the density of [3H]SCH23390-binding sites in the brain of the bee. Overall, these results indicate that under normal physiological conditions, there is no direct link in honey bees between changes in endogenous brain DA levels and the density of D(1)-like receptors labelled by [3H]SCH23390.     

Functional and phenotypic characterization of peptide-vaccine-induced HCV-specific CD8+ T cells in healthy individuals and chronic hepatitis C patients

Only very limited information on phenotype and function of vaccine-induced CD8+ T cells is available for humans. We investigated hepatitis C virus-specific CD8+ T cells after vaccination with the HCV peptide-vaccine IC41 which includes 5 MHC-class I and 3 MHC class-II-restricted epitopes. In healthy subjects, IC41 induced both HCV-specific central memory as well as effector CD8+ T cells which rapidly expanded upon antigen exposure in vitro. IFNgamma production was dependent on formulation of the synthetic peptides with the adjuvant poly-l-arginine. In chronic HCV patients, the frequency of HCV-specific CD8+ T cells increased after vaccination with a decline of CD45RA-positive effector memory cells in some but not all patients. Thus, this study suggests that HCV-specific memory cells can be induced by peptide vaccination and that a reversion of functional impaired phenotypes by therapeutic vaccination is possible in chronic HCV infection.     

Research priorities for australian critical care nurses: do we need them?

The development of research priorities for critical care nurses has been previously examined from the perspective of both Australian and international critical care nursing experts. A variety of techniques have been used to determine research priorities for critical care nursing, however, a clear articulation of research priorities for Australian critical care nurses, which are both timely and encompass all aspects of critical care nursing practice, is lacking. Research priorities previously determined in Australia and elsewhere identify similar clinical research priorities such as nutritional support, infection control, supporting respiratory and cardiac function, and follow-up of critically ill patients. However, differences between the few available studies exist, possibly because of the changing nature of critical care nursing practice. Despite the identification of research priorities for critical care nursing in the past, there is little evidence to demonstrate a direct effect on research output in these areas. Future development of research priorities for Australian critical care nurses needs to be carefully considered. It is essential that identification of such research priorities be done within the context of their intended use.     

Differential sensitivity of specific neuronal populations of the rat hypothalamus to prolactin action

Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA) neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum prolactin. Elevated prolactin levels during pregnancy and lactation may mediate actions in other hypothalamic regions such as the paraventricular nucleus (PVN) and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more sensitive prolactin targets than neurons in other regions because they are required to regulate basal prolactin secretion. Moreover, differences in the accessibility of the ARC to prolactin in blood may influence the responsiveness of this population. Therefore, we compared prolactin-induced signaling in different hypothalamic neuronal populations following either systemic or intracerebroventricular (icv) prolactin administration. Phosphorylation of the signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin-responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were widely observed in the ARC but absent from the rPOA and PVN. Many of these responsive cells in the ARC were identified as NEDA neurons. The lowest icv prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng) pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and appeared to be more sensitive than dopaminergic neurons in the rPOA. Subpopulations of oxytocin neurons in the hypothalamus were also found to be differentially sensitive to prolactin. These data suggest that differences in the accessibility of the arcuate nucleus to prolactin, together with intrinsic differences in the NEDA neurons, may facilitate homeostatic feedback regulation of prolactin release.     

Screening of anti-dengue activity in methanolic extracts of medicinal plants

Background  

Dengue fever regardless of its serotypes has been the most prevalent arthropod-borne viral diseases among the world population. The development of a dengue vaccine is complicated by the antibody-dependent enhancement effect. Thus, the development of a plant-based antiviral preparation promises a more potential alternative in combating dengue disease.     

Introduction of a Day-Case Laparoscopic Cholecystectomy Service in the UK: A Critical Analysis of Factors Influencing Same-Day Discharge and Contact with Primary Care Providers

INTRODUCTION

The objective of this study was to determine the safety and acceptability of the implementation of a day-case laparoscopic cholecystectomy (LC) service in a large UK teaching hospital, and analyse factors influencing contact with primary care providers. Wide-spread introduction of day-case LC in the UK is a major target of healthcare providers. However, few centres have reported their experience. In the US, out-patient surgery for LC has been reported, though many groups have utilised 24-h observation units to facilitate discharge. Concerns remain amongst surgeons regarding the feasibility and acceptability of the introduction of day-case LC in the UK.

PATIENTS AND METHODS

Comprehensive care and operative data were prospectively collected on the first 106 consecutive day-case procedures in our hospital. Postoperative recovery was monitored by telephone questionnaire on days 2, 5 and 14, including complications, satisfaction and general practitioner consultation.

RESULTS

A total of 106 patients were admitted for day-case LC, of whom 84% were discharged on the day of surgery. Patient satisfaction rate was 94% in both the successful day-case and the admitted patients. Mean operation time was 62 min, with an average total stay on the day-care unit of 426 min. Training-grade surgeons performed 31% of operations. Both the re-admission rate after surgery and rate of conversion to open surgery were 2%. Advice from primary healthcare providers was sought by 33% of patients within the first 14 postoperative days.

CONCLUSIONS

Introduction of day-case LC in the UK is feasible and acceptable to patients. The potential burden to primary care providers needs further study.     

Assessment of examiner leniency and stringency ('hawk-dove effect') in the MRCP(UK) clinical examination (PACES) using multi-facet Rasch modelling

Background

A potential problem of clinical examinations is known as the hawk-dove problem, some examiners being more stringent and requiring a higher performance than other examiners who are more lenient. Although the problem has been known qualitatively for at least a century, we know of no previous statistical estimation of the size of the effect in a large-scale, high-stakes examination. Here we use FACETS to carry out a multi-facet Rasch modelling of the paired judgements made by examiners in the clinical examination (PACES) of MRCP(UK), where identical candidates were assessed in identical situations, allowing calculation of examiner stringency.

Methods

Data were analysed from the first nine diets of PACES, which were taken between June 2001 and March 2004 by 10,145 candidates. Each candidate was assessed by two examiners on each of seven separate tasks. with the candidates assessed by a total of 1,259 examiners, resulting in a total of 142,030 marks. Examiner demographics were described in terms of age, sex, ethnicity, and total number of candidates examined.

Results

FACETS suggested that about 87% of main effect variance was due to candidate differences, 1% due to station differences, and 12% due to differences between examiners in leniency-stringency. Multiple regression suggested that greater examiner stringency was associated with greater examiner experience and being from an ethnic minority. Male and female examiners showed no overall difference in stringency. Examination scores were adjusted for examiner stringency and it was shown that for the present pass mark, the outcome for 95.9% of candidates would be unchanged using adjusted marks, whereas 2.6% of candidates would have passed, even though they had failed on the basis of raw marks, and 1.5% of candidates would have failed, despite passing on the basis of raw marks.

Conclusion

Examiners do differ in their leniency or stringency, and the effect can be estimated using Rasch modelling. The reasons for differences are not clear, but there are some demographic correlates, and the effects appear to be reliable across time. Account can be taken of differences, either by adjusting marks or, perhaps more effectively and more justifiably, by pairing high and low stringency examiners, so that raw marks can be used in the determination of pass and fail.     

A COMPARATIVE STUDY OF THE EFFICACY AND TOXICITY OF ETODOLAC AND NAPROXEN IN THE TREATMENT OF OSTEOARTHRITIS

SUMMARY In a two-period, double-blind, crossover study, patients with osteoarthritis of the knee and/or hip received etodolac 300 mg twice daily for 4 weeks and naproxen 500 mg twice daily for 4 weeks in random order. The assessment of efficacy showed that naproxen and etodolac were equally effective in the management of pain and stiffness in osteoarthritis. However, a significantly higher proportion of patients preferred naproxen to etodolac for the relief of pain intensity. The incidence of adverse events caused by either drug was the same.     

Establishment of an early liver fibrosis model by the hydrodynamics-based transfer of TGF-β1 gene

Background  

Liver fibrosis represents a significant and severe health care problem and there are no efficient drugs for therapy so far. Preventing the progression of fibrogenesis and revival endogenous repair activities is an important strategy for both current and future therapies. Many studies of liver fibrosis consist of animal testing with various hepatotoxins. Although this method is often used, the model at which cirrhosis or extensive fibrosis becomes irreversible has not been well defined and is not representative of early-stage fibrogenesis. We here report the establishment of a transient and reversible liver fibrosis animal model which may better represent an early and natural fibrotic event. We used a high-speed intravenous injection of naked plasmid DNA of transforming growth factor-β1 (TGF-β1) gene which is under the control of a metallothionein-regulated gene in a pPK9A expression vector into the tail vein (the hydrodynamics-based transfer) and fed the mouse with zinc sulfate (ZnSO₄)-containing water simultaneously.