Clustering of Y chromosome deletions in subinterval E of interval 6 supports the existence of an oligozoospermia critical region outside the DAZ gene.

Y chromosome molecular analysis was performed using the STS-PCR technique in 50 patients with oligozoospermia. Microdeletions of interval 6 of the Y chromosome were detected in seven patients, in six of whom subinterval E was affected. All patients retained the RBM1 and DAZ genes, while in one deletion involved the SPGY gene. The size of the deletion was not apparently related to the severity of the disease. These results suggest the presence of an oligozoospermia critical region on the Y chromosome within subinterval E of interval 6.     

Model of intersegmental coordination in the leech heartbeat neuronal network

We have created a computational model of the timing network that paces the heartbeat of the medicinal leech, Hirudo medicinalis. The rhythmic activity of this network originates from two segmental oscillators located in the third and fourth midbody ganglia. In the intact nerve cord, these segmental oscillators are mutually entrained to the same cycle period. Although experiments have shown that the segmental oscillators are coupled by inhibitory coordinating interneurons, the underlying mechanisms of intersegmental coordination have not yet been elucidated. To help understand this coordination, we have created a simple computational model with two variants: symmetric and asymmetric. In the symmetric model, neurons within each segmental oscillator called oscillator interneurons, inhibit the coordinating interneurons. In contrast, in the asymmetric model only the oscillator interneurons of one segmental oscillator inhibit the coordinating interneurons. In the symmetric model, when two segmental oscillators with different inherent periods are coupled, the faster one leads in phase, and the period of the coupled system is equal to the period of the faster oscillator. This behavior arises because, during each oscillation cycle, the oscillator interneurons of the faster segmental oscillator begin to burst before those of the slower oscillator, thereby terminating spike activity in the coordinating interneurons. Thus there is a brief period of time in each cycle when the oscillator interneurons of the slower segmental oscillator are relieved of inhibition from the coordinating interneurons. This "removal of synaptic inhibition" allows, within certain limits, the slower segmental oscillator to be sped to the period of the faster one. Thus the symmetric model demonstrates a plausible biophysical mechanism by which one segmental oscillator can entrain the other. In general the asymmetric model, in which only one segmental oscillator has the ability to inhibit the coordinating interneurons, behaves similarly, except only one segmental oscillator can control the period of the system. In addition, we simulated physiological experiments in which a "driving" stimulus, consisting of alternating positive and negative current steps, was used to control a single oscillator interneuron and thereby entrain the activity of the entire timing network.     

FMRFamide effects on membrane properties of heart cells isolated from the leech, Hirudo medicinalis.

1. The effects of the cardioactive peptide FMRFamide were tested on enzymatically dissociated muscle cells isolated from hearts of the leech. These cells were normally quiescent, with resting potentials near -60 mV. 2. Superfusion of FMRFamide induced a strong depolarization in isolated heart cells (e.g., greater than 40 mV with 10(-6) M FMRFamide). The depolarization was maintained in the continued presence of peptide and persisted long after its removal. Less frequently, FMRFamide superfusion elicited an episodic polarization rhythm. 3. The response of isolated heart cells to bath-applied FMRFamide showed a 1- to 2-min latency. The latency decreased with repeated applications of FMRFamide. 4. The FMRFamide response was diminished by Na+ replacement but persisted with Ca2+ channel blockade. 5. In voltage-clamped heart cells (-60 mv), superfusion of FMRFamide elicited a slow inward current with a transient and a sustained component. 6. Current-voltage (I-V) curves during FMRFamide superfusion in normal leech saline showed that FMRFamide also enhanced voltage-dependent outward currents activated at depolarized levels. 7. Under conditions in which K+ currents were substantially blocked, the FMRFamide-dependent I-V curve was net inward from -90 to +50 mV. A voltage-dependent component was blocked by Co2+ and a linear component by Na+ replacement. 8. We conclude that FMRFamide elicits a persistent inward current with a Na+ component and in addition modulates both voltage-dependent Ca2+ and K+ currents that may contribute to the normal myogenic activity of leech heart muscle cells.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

T cell subpopulations in myocardial inflammatory infiltrates detected by confocal microscopy: dose dependence in mice treated with cyclophosphamide during acute Trypanosoma cruzi infection

In this article, we have characterized cell subpopulations found in the hearts of mice presenting acute Chagas' disease by immunocytochemistry and subjected to different schedules of an immunosuppressive therapy with cyclophosphamide (CY). In this comparative study, CY treatment with different doses was carried out before or after infection with Trypanosoma cruzi Y strain trypomastigotes, enabling us to discriminate the parasitemic kinetics and inflammatory processes in the heart, 12 d after infection. Animals treated with 200 mg/kg of CY 2 d before infection presented high parasitaemia as well as heavy inflammation and low parasite loads in the heart. Mice treated 5 d after infection with the same dose, developed the same parasitaemic peak but were not able to control it. Their heart did not present inflammation, but a high number of parasites could be seen. Animals treated with five 3 mg/kg doses of CY every other day presented heavy inflammatory reaction and low parasitaemia. In this group, as well as the one treated before infection, immunocytochemistry studies have shown predominance of CD8(+) T cells in the myocardium. On the other hand, mice treated with 200 mg/kg of CY 5 d after infection, presented small amounts of CD4(+) T cells while no CD8(+) could be found. These results have confirmed the dose dependence influence of this drug on the T cell populations in the inflammatory infiltrates as well as the importance of the schedule employed.     

Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine

Chronic alcoholism is a major public health problem and causes multiorgan diseases and toxicity. Although the majority of ethanol ingested is metabolized by the liver, it has intoxicating effects in the brain. Evidence is accumulating that intermediates of oxygen reduction may be associated with the development of alcoholic disease. Several studies have shown the capacity of carnitine and its derivatives to influence ethanol metabolism. We have previously demonstrated that preadministration of L-carnitine to rats receiving ethanol significantly reduced fatty acid ethyl esters in different organs and that the carnitine/acylcarnitine system is crucial for maintaining a functional acetyl-CoA/CoA ratio under conditions in which cellular homeostasis is exposed to the deleterious effects of accumulating organic acids. Ethanol, administered to rats for 20 months, induced significant changes in the status of glutathione, primarily in the brain regions of hippocampus and cerebellum, followed by cortex and striatum, where a decrease in reduced glutathione (GSH) and the GSH/oxidized glutathione ratio was found. The same brain regions showed a significant increase in free radical-induced luminescence and hydroxynonenal (HNE), which were associated with decreased GSH reductase activity. Long-term supplementation with acetyl carnitine significantly reduced GSH depletion, particularly in the brain regions of hippocampus, an effect associated with decreased luminescence and HNE formation. In addition, acetyl carnitine treatment increased GSH reductase and arginase activities. Our results indicate that decreased GSH reductase activities associated with thiol depletion are important factors sustaining a pathogenic role in alcohol-related pathologies. Administration of acetyl carnitine greatly reduces these metabolic abnormalities. This evidence supports the pharmacological potential of acetyl carnitine in the management of alcoholic disturbances.