Synaptic modifications accompanying epileptogenesis in vitro: long-term depression of GABA-mediated inhibition

We used an in vitro model similar to kindling to examine the processes underlying epileptogenesis. A 60 Hz train was applied every 5–10 min to the Schaffer collateral pathways in guinea pig hippocampal slices until epileptiform bursting was elicited in the CA3 region. The resultant alterations in both spontaneous and evoked activities were studied using intracellular recordings from CA3 pyramidal cells. An attempt was made to elucidate the synaptic modifications responsible for the conversion to this state of enhanced excitability. Analyses revealed that the emergence of epileptiform discharge was accompanied by a long-term depression of evoked inhibitory conductances. This tetanus-induced reduction of inhibition involved both the early and late phases of the evoked hyperpolarization, suggesting modification of both the GABA_A and GABA_B receptor-mediated events. Previous studies have suggested that NMDA receptor activation plays an important role in the induction of epileptiform activity in this model. Our data, showing that depression of inhibition can be induced in the presence of CNQX, is consistent with this hypothesis. The parallel development of long-term depression of inhibition and epileptiform bursting following tetanic stimulation suggests that plasticity of the inhibitory transmission process is a potential source of vulnerability contributing to epileptogenesis.     

2型糖尿病对扩张型心肌病患者预后的影响研究

背景 2型糖尿病可增加患者心血管疾病的早发风险,对健康构成重大威胁。阐明2型糖尿病对扩张型心肌病患者预后的影响,有利于指导患者的管理。目的 探讨2型糖尿病对扩张型心肌病患者预后的影响。方法 回顾性选取广西医科大学第一附属医院心血管内科2015年1月至2020年5月收治的313例扩张型心肌病患者为研究对象。根据患者是否罹患2型糖尿病将患者分为糖尿病组（n=66）和非糖尿病组（n=247）,收集患者一般资料、实验室检查指标并进行随访,随访终点事件为全因死亡,随访日期截至2021-12-31。采用landmark比较两组患者的生存率。建立多因素Cox比例风险回归模型,探究扩张型心肌病患者全因死亡的影响因素。结果 Landmark分析结果显示,糖尿病组和非糖尿病组扩张型心肌病患者随访1年内的生存率比较,差异无统计学意义（χ2=1.520,P=0.218）;随访1年后,糖尿病组扩张型心肌病患者的生存率低于非糖尿病组（χ2=4.414,P=0.036）。分段拟合法构建的多因素Cox比例风险回归分析显示,收缩压[HR=0.965,95%CI(0.948,0.982)]、N末端B型利钠肽原[HR=9....     

Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression

Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4⁺ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4⁺ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.     

Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses

Bath application of the inhibitors of phospholipases, nordihydroguaiaretic acid (NDGA) and p-bromophenacyl bromide (BPB), to the rat hippocampal slices suppressed long-term potentiation (LTP) in Schaffer/commissural-CA1 pyramidal synapses. On the other hand, neither of the two inhibitors suppressed LTP in mossy fiber-CA3 pyramidal cell synapses. BPB did not suppress phosphatidylinositol-specific phospholipase C (PI-PLC) activity of the slices. These results suggested that the mechanisms of LTP were quite different in the CA1 and CA3 subfields of rat hippocampus: in CA1, the involvement of an arachidonate metabolism was strongly suggested, whereas in CA3, an arachidonic acid cascade may not be necessary for LTP.     

Temporal discrimination in the cerebellar cortex during conditioned eyelid responses

Little is known about mechanisms used by the nervous system to encode time. In light of recent evidence, cerebellar cortex involvement in the learned timing of conditioned eyelid responses shows promise as an area of investigation into neural timing mechanisms. Lesion studies indicate that the cerebellar cortex is necessary for response timing, but do not rule out the possibility that response timing is encoded afferent to the cerebellum. To differentiate between precerebellar and cerebellar cortical timing mechanisms, rabbits were trained by pairing direct stimulation of mossy fibers in the cerebellum as the conditioned stimulus (CS) with an eyeshock unconditioned stimulus (US). We find that individual animals can produce diffently timed conditioned responses when trained with a mossy fiber CS that has been paired with the US at various interstimulus intervals. The fact that differently timed responses can be conditioned using constant-frequency stimulation of an invariant subset of mossy fibers as the CS suggests that timing information in the afferent input to the cerebellum is not essential. Two rabbits trained with single-pulse stimulation in the cerebellum as the CS also learned differently timed conditioned responses; suggesting that fiber recruitment during a stimulus train does not convey the necessary temporal coding to the cerebellar cortex. Together with the lesion data, these findings suggest that the learned timing of conditioned eyelid responses occurs in the cerebellar cortex. Received: 25 August 1997 / Accepted: 12 January 1998     

Trends in pubertal development in Europe

The secular changes in growth and maturation can be seen as indicators of socio-economic and health status. In most European countries the age of onset of puberty and of menarcheal age has been decreasing during the past few decades. The duration of puberty seems also to decrease, though few studies provide sufficient data to support this postulation. The four Dutch nationwide growth surveys are useful examples assessing the secular trend in pubertal development over the past 45 years. Genetic and environmental factors contribute to the secular changes. Environmental factors seem to be the most important. Recently, attention has been given to substances with oestrogen-like actions that are present in nutrients. The possible role of these substances in growth and maturation is discussed.     

Evaluation of in vivo and in vitro repopulation assays for murine haemopoietic stem cells

Three assays to determine the repopulation potential of stem cells in murine bone marrow grafts were evaluated on their reliability with regard to the ranges in graft size. In vivo, marrow repopulating ability, as calculated from the number of in vitro clonable progenitors (colony-forming units in culture, CFU-C) generated by the graft in the femur of an irradiated recipient, appeared to be independent of the input over a wide range of cell numbers grafted. A second assay, erythroid repopulating ability is a measure of the number of new reticulocytes or erythrocytes in the blood generated by the graft, and significantly underestimates stem cell activity of the graft. The third assay measures the long-term repopulating ability of bone marrow cells in vitro on pre-established stromal cell layers by determination of the number of CFU-C produced in these cultures. Calculations of short-term in vitro repopulating ability, done from measurements of the production of non-adherent CFU-C in the first week of culture, appeared to be independent of cell input. Long-term in vitro repopulating potential, measured by the CFU-C content of the adherent layer at 4 weeks, is also independent of the numbers of cell input.     

Accuracy and choice of procedures in 24-hour oesophageal pH monitoring with monocrystalline antimony electrodes

In 24 h pH monitoring, the evaluation is dependent on the absolute accuracy of the pH measurements. Several sources of error exist, such as the chemical composition of calibration buffers and reference electrode gel and the effect of temperature on both the pH and the reference electrodes. We investigated the magnitude of these errors for the monocrystalline antimony electrode. Similar analysis applies to other types of pH electrodes. The errors we found are important when choosing a calibration procedure. We recommend a calibration procedure in which the pH and reference electrodes are both put in a beaker with the calibration buffers prior to and after the 24 h measurements. The calibration buffers and the electrode gel should have a specially selected ion composition where, for example, the Cl-ion concentration is critical. Corrections for differences in temperature between the calibration and the in situ measurements must be added. The pH measurements can be checked by performing in situ calibration.     

Predominance of methicillin-resistant Staphylococcus aureus in the residents and environments of long-term care facilities in Taiwan

Background/purpose

This study investigated the distribution and persistence of multidrug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and multidrug-resistant Acinetobacter baumannii (MDRAB) in six long-term care facilities (LTCFs).