Prolactin responses to haloperidol in drug-free and treated schizophrenic patients

Summary The prolactin response to 5 mg haloperidol i.m. was studied in 12 schizophrenic patients in a drug-free state and after a month treatment with haloperidol, as a possible index of dopamine receptor sensitivity and occupancy. Blood samples were taken at times 0, 60, 90 and 120 minutes. The increase in PRL observed in the drug-free state disappeared after drug treatment. The PRL plasma levels after treatment with 60 mg haloperidol per os were higher than the maximal PRL responses after 5 mg i.m. The increases in baseline PRL caused by the treatment correlated positively to the reduction in the BPRS score. The test was also performed in a group of 11 patients chronically treated with haloperidol during a daily dose of 60 mg, and 15 days after reduction of the dose to 30 mg. PRL increases after 5 mg haloperidol i.m. were observed only after reduction of the dose. It is suggested that the prolactin response to haloperidol is an index of the occupancy of receptors that are involved in the PRL releasing mechanisms, and could be used to verify their blockade by the neuroleptics, especially in patients that do not respond positively to drug treatment.     

Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response

Coronavirus MHV-JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV-JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG + B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down-regulation of this protein, possibly mediated by anti-S antibodies.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

解耦联蛋白在心肌中的表达与心力衰竭

位于心肌线粒体内膜上的解耦联蛋白 (UCPs) ,作为质子通道驱散氧化呼吸时形成的H 梯度 ,使产能转化为产热 ,从而增加呼吸 ,阻止ATP形成 ,并抑制活性氧族的产生 ,最终阻止了心肌细胞的程序性死亡。脂肪酸、寒冷、甲状腺激素、肾上腺素等能调控UCPs的浓度和活性。UCPs在心力衰竭中的作用仍然不清楚 ,有待进一步研究     

神经活素对Pc12细胞作用的初步观察

从胎脑、颌下腺、肌肉组织中制备神经活素。其性能同脑活素一样：可促进Ｐｃ１２细胞的突起生长，提高其胞浆内乳酸脱氢酶活性，电泳显示二者有相同的三条带。提示：神经活素有可能替代脑活素应用于临床。     

Monoclonal antibodies to canine intra-acrosomal sperm proteins recognizing acrosomal status during capacitation and acrosome reaction

Summary.  Monoclonal antibodies Ds-1 and Ds-2 specifically labelling dog sperm acrosome were prepared by immunization of mice with acetic acid extracts of dog spermatozoa. Electron microscopy and indirect immunofluorescence localized the site of Ds-1 and Ds-2 proteins inside the acrosomal vesicle. Ds-1 antibody detected 55, 76, 115, 120 and 190kDa proteins under non-reducing conditions, and 73 kDa and 54 kDa proteins after reduction (p73/Ds-1 and p54/Ds-1). 92 kDa and 40 kDa proteins recognized by Ds-2 (p92/Ds-2 and p40/Ds-2) migrated at > 200 kDa in the absence of reducing agent. In vivo , p73/Ds-1 and p54/Ds-1 are therefore likely to be present both in free and complexed form, while all of p92/Ds-2 and p40/Ds-2 form disulfide-bonded complexes. Decrease in the rate of acrosomes stained with Ds-1 and Ds-2 was correlated with the progress of capacitation resulting in the increased rate of spontaneous acrosome reactions, as suggested by a dramatic effect of A23187. Monoclonal antibody to boar acrosin (ACR-2) recognized dog sperm acrosin homologue. A higher rate of ACR-2-negative spermatozoa was observed after capacitation and A23187 treatment compared to Ds-1 and Ds-2, indicating that proteins recognized by Ds-1 and Ds-2 are localized in a specific compartment of acrosome, distinct from acrosin and possibly representing fraction of acrosomal matrix.     

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-γ (IFNγ) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid^® and thiopentone on Th1/Th2 balance, measurements of IFNγ and IL-4 production by mononuclear leucocytes were carried out in vitro . As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 μg.ml⁻¹, Intralipid^® 35 or 100 μg.ml⁻¹, or thiopentone 3 μg.ml⁻¹. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFNγ (p <0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid^® had no effects on IFNγ, IL-2 or IL-4 concentrations. Propofol 10 μ.ml⁻¹ increased the IFNγ/IL-4 ratio from the control value median 243 (162–562) (25th–75th percentile) to 363 (195–1028) (p < 0.01), but thiopentone decreased it to 145 (60–214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.     

胃恶性上皮核仁组成区相关蛋白的研究

用嗜银染色技术对34例良性胃溃疡、40例胃粘膜异型增生、46例胃腺癌组织石蜡切片中的核仁组成相关蛋白(AgNOR)进行研究,25例正常胃粘膜组织作对照。发现对照组、良性溃疡组,异型增生组和腺癌组的细胞核AgNOR平均计数差异有显著性(P<0.01)。恶性细胞中AgNOR的体积、形状及在细胞核内的位置也不相同。作者认为此法有助于区别胃的良性和恶性病变。     

临床肿瘤用药的统计分析

[目的]了解肿瘤用药的消费现状及发展趋势，为临床合理用药提供依据。[方法]对本院1996年-2002年抗肿瘤药、生物反应调节剂和升白细胞药的用药情况进行统计分析，以药品的年消耗金额作统计。[结果]抗肿瘤药、生物反应调节剂和升白细胞药分别占全部药品年消耗总金额的24．24％～33．73％、15．80％～23．33％和5．86％～9．11％。[结论]抗肿瘤药、生物反应调节剂和升白细胞药是用于肿瘤治疗的主要药品，尤其是抗肿瘤天然药物有着广阔的应用前景。