Decreased G-protein coupling of serotonin 5-HT(1A) receptors in the brain of 5-HT(1B) knockout mouse

The firing of central serotonin (5-hydroxytryptamine, 5-HT) neurons and their capacity to release 5-HT are subjected to a receptor-mediated auto-control via 5-HT(1A) and 5-HT(1B) receptors respectively located on the somata/dendrites (5-HT(1A) autoreceptors) and preterminal axon arborizations (5-HT(1B) autoreceptors) of these neurons. To further characterize mutual adaptations of these two receptor subtypes in the absence of one of them, activation of G-protein coupling by agonist was measured and compared to wild-type (WT) in 5-HT(1A) and 5-HT(1B) homozygous knockout (KO) mice. As expected, in WT, the non-selective 5-HT(1A/1B) receptor agonist 5-carboxyamidotryptamine (5-CT) stimulated guanosine 5'-O-(gamma-[(35)S]thio)triphosphate ([(35)S]GTP(gamma)S) incorporation in many brain regions endowed with one and/or the other receptor. In the respective KOs, no stimulation was measured in regions known to express only or mainly the deleted receptor. In the 5-HT(1A) KOs, the amplitude of G-protein activation in regions endowed with 5-HT(1B) receptors was unchanged by comparison to WT. In the 5-HT(1B) KOs, the magnitude of the 5-CT stimulation was the same as WT in all regions containing 5-HT(1A) receptors, except in the amygdala, where it was significantly lower, even if this region was one of the most strongly activated in the WT. A similar result was obtained in the amygdala of 5-HT(1B) KOs after activation by the selective 5-HT(1A) receptor agonist R-(+)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Under these conditions, however, there was in addition a significant lowering of the stimulated (but not basal) [(35)S]GTP(gamma)S incorporation by comparison to WT in all regions endowed with 5-HT(1A) receptors, including the dorsal raphe nucleus. Thus, eventhough agonist radioligand binding to either 5-HT(1A) or 5-HT(1B) receptors is unchanged in the reciprocal KOs, it appears that a compensatory decrease in the efficiency of G-protein coupling to 5-HT(1A) receptors has developed in the 5-HT(1B) mutant. This could represent the first indication of a cross-talk between these two 5-HT receptor subtypes, at least in brain regions where they are co localized in the same neurons.     

Sleep-wake patterns in children with intrauterine growth retardation

The purpose of this study was to characterize the sleep patterns of children with intrauterine growth retardation, known to be at risk for neurodevelopmental disorders, and seek a possible correlation with behavior, concentration, and attention problems. The sleep patterns of 26 children with intrauterine growth retardation aged 4 to 7 years were compared with those of 47 control children using activity monitors (actigraphs). In addition, data were collected from the parents regarding sleep habits, behavior, concentration, and attention. Children with intrauterine growth retardation aged 4 to 7 years were found to have a tendency toward poorer quality of sleep than their matched controls. This inclination was statistically significant only for one sleep measure, the true sleep time. A tendency toward increased fragmentation of sleep, prolonged waking, and decreased sleep efficiency, although not statistically significant in this study, was demonstrated. Our results showed that 58% of the children with intrauterine growth retardation, compared with 40% of the children in the control group, could be defined as "poor sleepers" (sleep efficiency lower than 90% or three or more waking episodes per night). This disturbed sleep profile is probably an integral part of the neurodevelopmental profile typical of these at-risk children. No significant correlations were found between sleep quality and behavior, concentration, and attention problems.     

Halichondramine,a new tetracyclic bipiperidine alkaloid from the marine sponge Halichondria sp

Halichondramine (1), a new tetracyclic alkylbipiperidine alkaloid, has been isolated from the marine sponge Halichondria sp., collected in the Dahlak archipelago (the Red Sea), Eritrea. The structure of halichondramine was elucidated by interpretation of MS, COSY, HMQC, HMBC, TOCSY, and HSQC-TOCSY data.     

Nucleus accumbens dopamine and learned fear revisited: a review and some new findings

A role for the nucleus accumbens (NAcc) and its dopamine (DA) innervation in fear and fear learning is supported by a large body of evidence, which has challenged the view that the NAcc is solely involved in mediating appetitive processes. Unfortunately, due to conflicting findings in the aversive conditioning literature the role of the NAcc in aversive conditioning remains unclear. This review focuses on the results of recent in vivo microdialysis studies that have examined the release of NAcc DA during Pavlovian aversive conditioning. In addition, we present additional new findings, which re-examine the involvement of NAcc DA in aversive conditioning. DA release was measured in the NAcc core using in vivo microdialysis during discrete cue Pavlovian aversive conditioning in four experiments. In all cases no change in DA levels was observed either during training or in response to the CS presentations despite robust behavioural evidence of discrete cue Pavlovian aversive conditioning. These findings contrast with some previous studies that show that primary and conditioned aversive stimuli increase DA release in the NAcc. We suggest that the inconsistencies in the literature might be due to procedural differences in the measurement of aversive conditioning, and the precise location of the probe in the NAcc region. Hence, rather than discount an involvement of NAcc DA in affective processes, we propose that functionally dissociable sub-regions of the NAcc may contribute to different aspects of Pavlovian aversive learning.     

Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.     

MMP-9与TIMP-1在肾小管上皮细胞转分化中的作用

目的研究结扎大鼠单侧输尿管(UUO)制备的实验性肾纤维化模型梗阻肾基质金属蛋白酶9(MMP-9)和组织金属蛋白酶抑制剂1(TIMP-1)表达的动态变化,探讨MMP-9和TIMP-1在肾小管上皮细胞转分化中的作用。方法将64只雄性大鼠随机分为假手术组和UUO组(n=32),UUO组结扎单侧输尿管,术后3d、7d、14d、21d每组各处死8只大鼠,用免疫组化法检测大鼠梗阻肾组织MMP-9、TIMP-1、α-平滑肌肌动蛋白(α-SAM)及纤维连接蛋白(FN)的表达。结果UUO术后3d,PAS染色见少量肾小管基底膜(TBM)局灶性断裂。术后7d,TBM断裂程度加重,基底膜断裂的肾小管数增多。术后14d直至术后21d,可见部分TBM增厚、扭曲,基底膜断裂程度和基底膜断裂的肾小管数较7d时略减轻和减少。与假手术组相较,UUO组随着梗阻时间的延长,肾间质中α-SMA、FN、TIMP-1蛋白表达逐渐增多。UUO组术后3d可见MMP-9在肾小管间质有强阳性表达,术后7d达高峰,14～21d呈下降趋势。α-SMA、MMP-9、TIMP-1主要表达于肾小管上皮和肾间质。MMP-9阳性染色面积与α-SMA阳性染色面积、TBM的断裂程度、基底膜断裂的肾小管个数均呈正相关(r分别为0.894,0.854,0.821,P均<0.05)。结论肾小管间质MMP-9和TIMP-1蛋白表达的动态变化影响TBM完整性与ECM堆积。MMP-9与TIMP-1相互拮抗调节肾小管基底膜代谢,参与肾小管上皮细胞转分化,影响肾纤维化进展。     

Epidemiologic increase of various genotypes of vancomycin-resistant Enterococcus faecium in a university hospital

After a report of a possible relationship between an outbreak of vancomycin-resistant enterococci (VRE) in a nearby hospital and earlier admission of two of the patients with this VRE in the University Medical Centre of Utrecht (UMCU), the Netherlands, an extensive search for VRE carriers was started in the UMCU. In the study period of two months, VRE carriership was diagnosed in 51 patients in nine of the 11 wards investigated. Twenty-six patients in eight wards were colonized with the same VRE genotype as in the nearby hospital; spread was demonstrated in three wards. In addition, six patients of one ward were colonized with a second genotype and seven other patients with a third genotype, while 12 patients were carriers of a unique genotype. Most carriers were found in the internal medicine/nephrology and dialysis ward. Far-reaching measures (such as cohort nursing, admission stops, use of gowns and gloves, disinfection and restriction of use of vancomycin) taken in the four wards where spread was demonstrated, appeared effective but in three wards, spread was again demonstrated later. Frequent readmissions and transfers of patients appear to play an important part in this matter. None of the 51 colonized patients developed a serious VRE infection.     

Daclizumab and basiliximab: monoclonal mouse-man antibodies with effective immunosuppression without side effects

Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab, when added to an immunosuppressive regimen consisting of cyclosporin and prednisone, reduce the incidence of acute rejections after kidney transplantation by 30-40%, during the first 6 months. Daclizumab and basiliximab are monoclonal antibodies of which the variable parts are of mouse origin and the other components of human origin. The addition of the interleukin-2 receptor antagonists was not accompanied by extra side effects. Ongoing clinical trials aim at answering the question whether the addition of daclizumab and basiliximab will allow to avoid or decrease the use of more toxic immunosuppressive drugs.     

睫状沟重建Ⅱ期小切口人工晶状体植入术

目的 评价睫状沟重建Ⅱ期小切口人工晶状体植入术的临床效果。方法 采用弦长5.5mm反眉状巩膜隧道切口,对39例39眼白内障术后、后囊膜破损无晶状体眼患者施行睫状沟重建Ⅱ期小切口人工晶状体植入术,观察术中时间,术后视力,术中、术后并发症。结果 平均手术时间20min,术后1周裸眼视力,0.1～0.3者3眼(8％),0.5～0.9者25眼(64％),1.0～1.5者11眼(28％)。除瞳孔欠圆外,其它术中、术后并发症经常规治疗1周内痊愈,人工晶状体无脱位及移位现象。结论 睫状沟重建Ⅱ期小切口人工晶状体植入术具有切口小、手术时间短、操作简单、术后视力恢复迅速而且稳定等优点,值得在基层医院推广使用。     

Cystic fibrosis and neonatal calcified scrotal masses

We report a case of an infant who presented with failure to thrive and in whom the identification of calcified scrotal masses led us to the diagnosis of cystic fibrosis.