Effect of adenosine on atrioventricular conduction. II: Modulation of atrioventricular node transmission by adenosine in hypoxic isolated guinea pig hearts

Adenosine as well as hypoxia and ischemia are known to cause atrioventricular conduction block. To test the hypothesis that adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay in isolated perfused guinea pig hearts, we characterized a) the time courses of hypoxia-induced adenosine release and delay in atrioventricular conduction, b) the relationships between oxygen tension, adenosine concentration in the effluent, and atria-to-His-bundle interval, and c) the adenosine receptor mediating the negative dromotropic effect of hypoxia. Oxygen tension and effluent adenosine levels were linearly related with a correlation coefficient (r) of -0.85 and a slope of -6.3 +/- 0.37 pmol/min/g/torr. Likewise, oxygen tension and atria-to-His-bundle interval prolongation were linearly related with r = -0.85 and a slope of -0.180 +/- 0.013 msec/torr. The EC50 of effluent adenosine in causing atria-to-His-bundle prolongation was 0.26 +/- 0.02 microM. Adenosine deaminase, an enzyme that deaminates adenosine to inosine and is limited to the extracellular space, significantly attenuated (61%) the atria-to-His-bundle interval prolongation caused by hypoxia. This prolongation was further reduced (81%) by a combination of adenosine deaminase and theophylline, an adenosine receptor blocker. Adenosine deaminase also reduced (by 95%) the atria-to-His-bundle interval prolongation in normoxic recipient hearts caused by the effluent of hypoxic donor hearts. Several adenosine antagonists, i.e., theophylline, 8-phenyltheophylline, and 8-(p-sulfophenyl)theophylline antagonized in a dose-dependent manner the negative dromotropic effect of exogenous adenosine and hypoxia. Schild analysis of the antagonism of hypoxia-induced atria-to-His-bundle interval prolongation by 8-(p-sulfophenyl)theophylline yielded the following pA2 values: 5.30 +/- 0.25 and 5.28 +/- 0.31 using oxygen tension and effluent adenosine vs. AH interval prolongation, respectively. 8-(p-Sulfophenyl)theophylline also antagonized to an equal extent atria-to-His-bundle interval prolongations of similar magnitude caused either by adenosine or hypoxia. We conclude that 1) adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay, and 2) the adenosine receptor that mediates the negative dromotropic effect of hypoxia is similar to that of exogenous adenosine.     

Association of hemoglobin H disease with Hb J-Iran (beta 77 His---- Asp): impact on subunit assembly

A young Iranian female was found to be heterozygous for hemoglobin (Hb) J-Iran (beta 77 His----Asp) in combination with Hb H disease. The proportion of Hb J in the patient's hemolysate was surprisingly high: 65% Hb J, 30% Hb A. Thus, the interaction of a negatively charged beta subunit variant of Hb with alpha-thalassemia leads to a marked increase in the relative amount of the variant Hb within red cells. This observation provides further support for an electrostatic model of Hb subunit assembly.     

Neutralization of heparin activity by neutrophil lactoferrin

Lactoferrin is a prominent component of neutrophil secondary granules, and its blood concentration is increased in certain inflammatory diseases. In contrast to the well-described biochemical characterization of lactoferrin as an iron-binding protein, its physiologic role in the regulation of inflammation and other host defense mechanisms is unclear. In this report, we provide evidence that lactoferrin has a potent heparin-neutralizing activity during thrombin inhibition by the serine proteinase inhibitors (serpins) antithrombin and heparin co-factor II. Activated neutrophil supernatant, which contains lactoferrin and other heparin-binding proteins, could neutralize the heparin-dependent antithrombin-thrombin inhibition reaction. The addition of lactoferrin to plasma corrected the heparin- induced prolongation of blood plasma coagulation as measured by the activated partial thromboplastin time (aPTT). Treatment of whole blood with specific inflammatory mediators, fMLP, lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) increased the concentration of both plasma lactoferrin and platelet factor 4 while inhibiting the blood anticoagulant activity of heparin as measured by the aPTT. These results suggest that the prothrombotic sequelae of some inflammatory processes may be partly due to various agonists that release neutrophil lactoferrin, which can then neutralize glycosaminoglycan-dependent serpin-thrombin inhibition reactions.     

Long‐term leisure‐time physical activity has a positive effect on bone mass gain in girls

The purpose of this 7‐year prospective longitudinal study was to examine whether the level and consistency of leisure‐time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L₂–L₄) were assessed by dual‐energy X‐ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (G_LL), consistently high (G_HH), and changed from low to high (G_LH) and from high to low (G_HL) during 7 years of follow‐up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the G_LL group, the G_HH group had higher BMC (11.7% in the TF, p < .05) and BMD at the TB (4.5%) and the TF (12.2%, all p < .05) at age 18. Those in the G_LH group also had higher a BMC at each site (8.5% to 9.4%, p < .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of G_LL (all p < 0.05) at the age 18. Our results suggest that long‐term leisure‐time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain. © 2010 American Society for Bone and Mineral Research     

Sensory and multisensory representations within the cat rostral suprasylvian cortex

Because the posterior limb of the rostral suprasylvian sulcus (RSp) of the cat resides in close proximity to representations of the somatosensory, auditory, and visual modalities, the surrounding cortices would be expected to be a region where a high degree of multisensory convergence and integration is found. The present experiments tested this notion by using anatomical and electrophysiological methods. Tracer injections into somatosensory, auditory, and visual cortical areas almost all produced terminal labeling within the RSp, albeit at different locations and in different proportions. Inputs from somatosensory cortices primarily targeted the inner portion of the anterior RSp; inputs from auditory cortices generally filled the outer portion of the middle and posterior RSp; inputs from visual cortices terminated in the inner portion of the posterior RSp. These projections did not have sharp borders but often overlapped one another, thereby providing a substrate for multisensory convergence. Electrophysiological recordings confirmed this anatomical organization as well as identifying the presence of multisensory (bimodal) neurons in the areas of overlap between representations. Curiously, however, the proportion of bimodal neurons was only 24% of the neurons sampled in this region, and the majority of these did not show multisensory interactions when combined-modality stimuli were presented. In summary, these experiments indicate that the RSp is primarily auditory in nature, but this representation could be further subdivided into an outer sulcal anterior auditory field (sAAF) and an inner field of the rostral suprasylvian sulcus (FRS).     

Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

Background  

The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl₂) in rats subjected to the forced swimming test (FST).     

Cross-modal circuitry between auditory and somatosensory areas of the cat anterior ectosylvian sulcal cortex: a 'new' inhibitory form of multisensory convergence

Examples of convergence of visual and auditory, or visual and somatosensory, inputs onto individual neurons abound throughout the brain, but substantially fewer incidences of auditory-somatosensory neurons have been reported. The present experiments sought to examine auditory-somatosensory convergence to assess whether there is a feature of this type of convergence that might obscure it from conventional methods of multisensory detection. Auditory-somatosensory convergence was explored in cat anterior ectosylvian sulcus (AES) cortex, where higher-order somatosensory area IV (SIV) and auditory field of the anterior ectosylvian sulcus (FAES) share a common border. While neuroanatomical tracers documented a projection from FAES to SIV, physiological studies failed to reveal the bimodal neurons expected from such cross-modal connectivity. Stimulation of FAES through indwelling electrodes also failed to excite any of the SIV neurons examined. However, when stimulation of auditory FAES was combined with somatosensory stimulation, a large majority (66%) of SIV neurons showed a significant response attenuation. FAES-induced response suppression was specific to SIV, could not be elicited by activating other auditory regions and was blocked by the microiontophoretic application of the GABAergic antagonist bicuculline methiodide. Based on these data, a novel, cross-modal circuit is proposed involving projections from auditory FAES to somatosensory SIV, where local inhibitory interneurons 'reverse the sign' of the cross-modal signals to produce auditory-somatosensory suppression. This form of excitatory-inhibitory multisensory convergence has not been reported before and suggests that the level of interaction between auditory and somatosensory modalities has been substantially underestimated.     

先天性无肛直肠舟状窝瘘手术186例

1临床资料1988-06/2003-12我院共186例,均为女性,无肛门,其中0～6月龄21例,0.5～1岁96例,1～3岁53例,3～8岁15例,13岁1例.以大便从会阴部舟状窝瘘口处排出而就诊,患儿有不同程度的排便困难,严重时伴腹胀呕吐,多数患儿有营养不良性贫血.瘘口直径0.3～0.6 cm,直肠盲端到肛穴皮肤之间的距离1.0～2.5 cm,属于中、低位肛门直肠畸形.本组有3例合并先天性心脏病-室间隔缺损,2例合并骶前囊肿,1例合并脐疝.     

血清HBV-DNA水平的变化与慢性乙型活动性肝炎的关系

目的:研究慢性肝炎患者HBV-DNA水平与病情变化的关系. 方法:采用荧光标记定量PCR的方法,测定慢性乙型肝炎急性发作患者(HBeAg阳性45例,抗HBe阳性30例)其活动期和恢复期的血清HBV-DNA含量. 结果:HBeAg阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(10.2±1.6) vs (5.3±2.1), P<0.05],抗-HBe阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(7.6±1.3) vs (4.0±2.0), P<0.05]. 另外,活动期血清HBV-DNA含量(Logarrithm copy/mL)在HBeAg阳性组显著高于抗HBe阳性组[(10.2±1.6) vs (7.6±1.3), P<0.05]. 血清HBV-DNA水平与丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)及总胆红素(T-BLLI)之间无相关性. 结论:HBV-DNA复制水平与慢性乙型病毒性肝炎的活动密切相关.