Pharmacological and morphological differences between X- and Y-type ganglion cells in the cat's retina

Pharmacological and morphological differences between X- and Y-cells of the cat's retina were studied using extracellular as well as intracellular recordings of the ganglion cells in the perfused eye-cup preparations. First, the effects of strychnine and bicuculline on the center and the surround responses were investigated. Strychnine blocked the surround inhibition of on-center X-cells, whereas bicuculline blocked that of on-center Y-cells, suggesting that these two-types of cells have different inhibitory interneurons which employ different neurotransmitters. In contrast, the center and the surround responses of off-center cells were reduced by bicuculline, leaving brief transient excitations, irrespective of whether the cells were X- or Y-type. Second, cells whose responses were studied intracellularly and classified as X- or Y-type, were stained with Lucifer yellow CH and observed in whole-mount preparations. It was found that X-cells have morphological characteristics of β-cells, and Y-cells those of α-cells.     

Toxicity studies on tetramethylthiuram monosulfide

Tetramethylthiuram monosulfide (TMTM), when given in a small dose of 26 mg/kg po, caused prolongation of the hexobarbital sleeping time in female Wistar rats. This effect was enhanced by increasing the dose to 867 mg/kg po and was associated with a lengthening of the zoxazolamine paralysis time. Both effects are causally related to an inhibition of the microsomal monooxygenases. One of the reasons for this inhibition conceivably is the concomitant decrease in the conversion of palmitic acid (incorporation of ¹⁴C radioactivity) into the phospholipids of the microsomal membrane. In contrast, other clinicochemical parameters of liver function detectable in the blood remained normal even after oral doses of 26 mg/kg TMTM administered on 5 consecutive days per week over a period of 4 weeks. However, this treatment caused a decrease in the erythrocyte count and hemoglobin content in the blood, together with a reduction of the relative liver weight, body weight, and the intake of food, while the consumption of drinking water was increased. Histologically, there was evidence of hepatocellular and renal tubular swelling. In female mice given acute oral doses of TMTM, the LD₅₀ was calculated as 818 (583–995) mg/kg. In mutagenicity tests, TMTM caused point mutations in strains TA 100 and TA 1535 (Salmonella typhimurium LT 2). The results indicate that the toxic potential of TMTM is comparable to that of other thiurams. A tentative hygienic threshold limit of 5 mg/m³ is proposed for the working environment.     

The cardiac responses of schizophrenics to orienting, signal and non-signal tones.

The cardiac responses of schizophrenics were examined under three conditions: (1) to repeated 75 dB, 1000 Hz (orienting) tones of no attentional significance; (2) to 75 dB, 1000 and 2000 Hz tones presented randomly and requiring a motor response to the 1000 Hz (signal) tone; (3) to 85 dB, 1000 Hz orienting tones. Responses of non-psychotic psychiatric patients were examined to the 75 dB tones. All patients were subdivided upon the basis of electrodermal responsivity during conditions (1) and (3), into groups of responders - no habituation of responses; non-responders - no responses; habituators - responses habituated to criterion. All groups exhibited a decelerative response with a latency of less than 1 sec. The groups were differentiated by the second component of the response to the orienting tones: responders - acceleration; habituators - deceleration; non-responders - predominantly no response. All exhibited accelerative responses to the signal tones. Parallels between cardiac and electrodermal responsivity are outlined.     

Free radical metabolism of hydralazine. Binding and degradation of nucleic acids

The binding of hydralazine, a hydrazine-containing hypotensive drug, to nucleic acids has been studied. Binding of this drug to biopolymers was assayed using spin-trapping techniques in the presence of various metal ions, which produce free radical intermediates from hydralazine [B. K. Sinha and A. G. Motten, Biochem, biophys. Res. Commun. 105, 1044 (1982)]. Some interaction was detected with the single-stranded nucleic acids. Hydralazine binds strongly to the native DNA, most likely by intercalation of the drug into DNA bases. In the presence of nucleic acids and metal ions, hydralazine stimulated the production of OH(.) radicals which was inversely proportional to the degree of binding. Aldehyde formation in DNA was also induced by hydralazine which was stimulated by superoxide dismutase and inhibited by catalase.     

Metabolic effects of acarbose administration in normal and diabetic rats

The effect of acarbose on cardiac and hepatic metabolism was investigated in normal and diabetic rats. Groups of rats were fed one of the three following diets for 7 days: (1) ground Purina chow, (2) ground Purina chow fortified with raw corn starch and sucrose, and (3) the above high carbohydrate diet, with added acarbose (40 mg/100 g food). At the end of the dietary period the rats were decapitated, and a sample of liver tissue was removed and frozen in liquid nitrogen. The heart was extirpated for subsequent perfusion by the Langendorff technique. Increases in liver and heart glycogen produced by the high carbohydrate diet in the normal rats were prevented completely when acarbose was incorporated into the food. In diabetic animals, liver glycogen was uniformly lower than normal, irrespective of the diet or the presence of acarbose. With animals fed the control diet, cardiac glycogen was higher in diabetic than in normal rats. The high carbohydrate diet caused a lowering of heart glycogen in diabetic rats and this reduction in glycogen content was reversed by including acarbose in the diet. Effects of isoproterenol on myocardial phosphorylase a activity were determined in hearts from normal and diabetic rats given one of the three diets. The high carbohydrate diet decreased the enzymatic response to the catecholamine in hearts from both normal and diabetic animals, and this phenomenon was prevented by the presence of acarbose in the diet. In diabetic rats fed any of the three diets, the activation of cardiac phosphorylase by isoproterenol was greatly accentuated. Measurements of heart uridine kinase showed that the activity of this enzyme was lower than normal in hearts from diabetic rats given either the control or the high carbohydrate diet. The presence of acarbose in the latter diet resulted in a significant decrease in cardiac uridine kinase activity in hearts from normal rats. The results of this study demonstrate the effectiveness of acarbose in modulating tissue metabolism in normal and diabetic animals.     

Hexadecane enhances non-biliary,intestinal excretion of stored hexachlorobenzene by rats

[¹⁴C] Hexachlorobenzene (100 mg/kg) was orally administered to 4 groups of rats. Ten days later the effects of hexadecane (3 × 5 ml/kg by gavage) and/or bile duct ligation on urinary and fecal excretion and tissue levels of hexachlorobenzene, were examined. Hexadecane did not affect urinary excretion of hexachlorobenzene, whereas bile duct ligation tripled it. Each of the 3 treatments (n-hexadecane, bile duct ligation and the combination of the two) resulted in a significant increase in fecal excretion of hexachlorobenzene. Moreover, the combination of hexadecane and bile duct ligation produced a greater increase in fecal excretion of hexachlorobenzene in blood, fat and kidney were not affected by any of the treatments, but liver concentrations were reduced significantly by bile duct ligation. Concentrations of hexachlorobenzene in intestinal contents indicate that intestinal-wall passage is the primary route of elimination from the body and that enhancement of elimination occurs mostly distal to the jejunum.     

Survey on the pharmacodynamics of the new antipsychotic risperidone

This review reports on the pharmacodynamics of the new antipsychotic risperidone. The primary action of risperidone is serotonin 5-HT₂ receptor blockade as shown by displacement of radioligand binding (K_i: 0.16 nM), activity on isolated tissues (EC₅₀:0.5 nM), and antagonism of peripherally (ED₅₀: 0.0011 mg/kg) and centrally (ED₅₀:0.014 mg/kg) acting 5-HT₂ receptor agonists in rats. Risperidone is at least as potent as the specific 5-HT₂ receptor antagonist ritanserin in these tests. Risperidone is also a potent dopamine D₂ receptor antagonist as indicated by displacement of radioligand binding (K_i: 1.4 nM), activity in isolated striatal slices (IC₅₀: 0.89 nM), and antagonism of peripherally (ED₅₀: 0.0057 mg/kg in dogs) and centrally acting D₂ receptor agonists (ED₅₀: 0.056–0.15 mg/kg in rats). Risperidone shows all effects common to D₂ antagonists, including enhancement of prolactin release. However, some central effects such as catalepsy and blockade of motor activity occur at high doses only. Risperidone is 4–10 times less potent than haloperidol as a central D₂ antagonist in rats and it differs from haloperidol by the following characteristics: predominant 5-HT₂ antagonism; LSD antagonism; effects on sleep; smooth dose-response curves for D₂ antagonism; synergism of combined 5-HT₂/D₂ antagonism; pronounced effects on amphetamine-induced oxygen consumption; increased social interaction; and pronounced effects on dopamine (DA) turnover. Risperidone displays similar activity at pre- and postsynaptic D₂ receptors and at D₂ receptors from various rat brain regions. The binding affinity for D₄ and D₃ receptors is 5 and 9 times weaker, respectively, than for D₂ receptors; interaction with D₁ receptors occurs only at very high concentrations. The pharmacological profile of risperidone includes interaction with histamine H₁ and -adrenergic receptors but the compound is devoid of significant interaction with cholinergic and a variety of other types of receptors. Risperidone has excellent oral activity, a rapid onset, and a 24-h duration of action. Its major metabolite, 9-hydroxyrisperidone, closely mimics risperidone in pharmacodynamics. Risperidone can be characterized as a potent D₂ antagonist with predominant 5HT₂ antagonistic activity and optimal pharmacokinetic properties.Unpublished research reports are available from Documentation Service, Janssen Pharmaceutica, B-2340 Beerse, Belgium     

硫酸软骨素膜剂制备及对口腔粘膜损伤防治作用研究

探讨制备硫酸软骨素膜剂的方法及其对大鼠口腔粘膜损伤的药理作用。方法：依据医院制剂规范要求,以ＰＶＡ为包衣材料制备性质均一、溶出度较好的硫酸软骨素膜剂剂型;利用大鼠口腔粘膜损伤模型,通过病理观察比较其对粘膜损伤的防治作用。结果：硫酸软骨素膜剂的平均含量为 ６． ０５ ｍｇ／片,重量差异与卫生度均符合规范要求,适于口腔、皮肤等组织粘膜给药。实验证明硫酸软骨素膜剂具有减轻大鼠口腔粘膜损伤程度,提前修复等作用。结论：硫酸软骨素可制成一种新型粘膜保护剂型,并具有一定的粘膜保护作用。     

痛风宁消炎镇痛的实验研究

目的：评估痛风宁对急性痛风的抗炎镇痛药效。方法：２４只雄性Ｗｉｓｔａｒ大鼠随机分成模型组、中药组、西药组,分别灌胃蒸馏水、痛风宁溶液、秋水仙碱溶液,于第３天将０．２ｍｌ尿酸钠溶液注入右侧踝关节腔造成急性痛风模型,２４ｈ后观察步态,７２ｈ后测量关节周径,观察受试关节周围软组织炎症病理及滑膜细胞超微结构变化。结果：中药组和西药组受试关节周径增大值明显比模型组小（Ｐ＜０．０１）;中药组和西药组受试关节周围软组织炎性细胞浸润、水肿、毛细血管充血及滑膜细胞线粒体、内质网肿胀均比模型组轻,痛行为步态均得到明显改善（Ｐ＜０．０１）。结论：痛风宁与秋水仙碱一样是治疗急性痛风有效的抗炎镇痛药。