Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development.

Metabolism is one of the major determinants for age-related changes in susceptibility to chemicals. Aldehydes are highly reactive molecules present in the environment that also can be produced during biotransformation of xenobiotics and endogenous metabolism. Although the lung is a major target for aldehyde toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been poorly studied. The expression of ALDH in liver and lung across ages (postnatal day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity was the highest contributor in lung. Total aldehyde oxidation capability in liver increases with age, but stays constant in lung. These overall developmental profiles of ALDH expression in a tissue appear to be determined by the different composition of ALDH isoforms within the tissue and their independent temporal and tissue-specific development. ALDH2 showed the most notable tissue-specific development. Hepatic ALDH2 was increased with age, while the pulmonary form did not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased thereafter both in liver and lung. ALDH3 increased with age in liver and lung, although ALDH3A1 was only detectible in lung. Collectively, the present study indicates that, in the case of aldehyde exposure, the in vivo responses would be tissue and age dependent.     

Pharmacodynamic Modeling for Change of Locomotor Activity by Methylphenidate in Rats

Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (K_i) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model. Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine.     

Modulation of cytokine production from an EpiOcular corneal cell culture model in response to Staphylococcus aureus superantigen

The present study investigated the hypothesis that Staphylococcus aureus enterotoxin B (SEE) produces epithelial cell death and releases inflammatory cytokines that produce stromal infiltration during contact lens induced peripheral ulceration. Epithelial cells were incubated with different doses of SEB for various time periods. Culture supernatants were assayed for cytokines IL- lo, IL-6 and chemotactic agents IL-8 and LTB,. SEE induced the production of IL- I p and IL-8. Epithelial cells exposed for longer periods (48 h) with low concentrations of SEB produced significantly higher levels (N0.02) of IL-Ip and IL-8 (P<0.05) compared t o a 24 h exposure. SEB did not induce the production o f IL-6 and     

Implication of the systolic hump in systemic arterial pressure waves

The systolic hump in the aortic blood pressure wave is defined as the aorticresistance component proportional to the aortic blood flow superimposed on the windkessel component. An electrical analogue comprising a series resistance (aortic resistance) plus a resistance (peripheral resistance) and capacitance (aortic compliance) in parallel (i.e. windkessel component) is used for analysis. Curve fitting using the leastsquares method is performed on calculated and measured blood pressure waves from dogs under haemodynamical conditions induced by infusion of three drugs (noradrenaline, isoproterenol and acetylcholine). The curve fitting RMS (root mean square) errors are <3% for blood pressure waves and <30% for blood flow waves, with good agreement between measured and calculated blood flow waveforms. Infusion of noradrenaline and acetylcholine is found to induce a significant decrease and increase in the aortic resistance, respectively. Although only a small fraction of the blood pressure wave, the systolic hump has a marked effect on the systolic pressure waveform.     

The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy

Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.     

补碘对7～12岁轻度碘缺乏病儿童脑功能及生长、发育的影响

通过半年对３５名７～１２岁轻度碘缺乏病儿童进行补碘，并与同龄、同地的正常儿童和缺碘未补碘儿童进行比较，以观察补碘对儿童脑功能及生长发育的影响。结果发现：①补碘可使儿童碘营养状况恢复正常，尿碘值由（８３．２±３．５）μｇ／Ｌ上升到（１６２．２±１．６）μｇ／Ｌ，血清Ｔ４、ＦＴ４Ｉ和ｒＴ３：也与正常儿童一致而与未补碘儿童有显著性差异（Ｐ＜０．０５）．②轻度碘缺乏病儿童智商低于正常儿童（Ｐ＜０．０１），补碘在一定程度上改善其智商水平。③轻度碘缺乏病及补碘未能明显影响儿童的生长发育，可能与儿童总营养水平较差有关。     

Development of neurochemical separation of ON and OFF channels at retinal ganglion cells

Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development.     

Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co-activation of NMDA and 5HT Receptors

The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg²⁺ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT_1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT₁, a selective 5HT_1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg²⁺, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg²⁺ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg²⁺ block. When the membrane potential was depolarized by ～20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg²⁺ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg²⁺ through activation of receptors with 5HT_1a-like pharmacology.     

A preliminary statistical model for identifying repeaters of parasuicide

This paper presents a statistical model constructed using logisticregression to identify those at high-risk of repeating parasuicide. Thesubjects in the study are Cork city residents who exhibited parasuicidalbehaviour between 1 January and 30 June 1995. Repetition of the behaviourwithin six months of the index episode distinguishes repeaters fromnon-repeaters. The model was designed so that it could be used bynon-clinicians and hence does not require information relating topsychiatric diagnosis or use of psychiatric services. The proportion ofsubjects correctly classified remained stable across a range of cut-pointprobabilities (mean = 86%, range: 83.9–87.5%). Using acut-point of 0.2, 96% of repeaters and 81% of non-repeaters were correctly classified. Using 0.45 led to the correct identification of81% of repeaters and 90% of non-repeaters. If these highlevels of sensitivity and specificity are maintained in validation tests onfuture cohorts in Cork city then the model could form the basis of anintervention programme designed to prevent the repetition of parasuicide.     

上海城乡儿童智力发育调查

为探索着力低下早期发现的途径和方法，对上海城乡4546名0～12岁）儿童进行了智力发育测查。首先用DDST或绘人测验进行智力筛查，筛查阳性者按不同年龄用儿——心量表、WPPSI或WISC—R进行测试。DQ或IQ低于70者以婴幼儿一初中生社会生活量表进行社会适应能力评估。测查结果共发现智力低下42例，占调查儿童总数的9．24％。城乡相比，农村智力低下现患率（16．13‰）明显高于城市（4．19‰），P＜0．01。从性别来分，男孩现患率（11．36‰）高于女孩（6．91‰）。智力低下患病率有随年龄增加而上升的趋势。因素分析与配对研究显示智力低下与父母文化素质有密切关系，父母文化程度小学以下者其子女智力低下患病率高。智力低下的发生还与高危因素有关。