Mivazerol, a new α2-adrenergic agonist, blunts cardiovascular effects following surgical stress in pentobarbital-anesthetized rats

Background: Mivazerol is a new and selective α₂-adrenoceptor agonist, devoid of hypotensive effects, which has been designed to prevent adverse cardiac outcome in perioperative patients with, or at risk of coronary artery disease. Methods: In the present study, the effects of mivazerol on hemodynamic changes induced by trachea-exposure surgery stress were investigated in pentobarbital-anesthetized rats, and compared to those of dexmedetomidine. Results: Intravenous infusion of 3 different doses of mivazerol (3.75, 7.5 and 15 μg kg^-1 h^-1) did not significantly alter BP but caused a dose-related decrease in HR. The maximal decrease in HR was approximately 87 beats/min. Contrary to mivazerol, dexmedetomidine (7.5 μg kg^-1 h^-1, i.v.) decreased both BP (11±3.2 mmHg) and HR. The maximum decrease in HR was approximately 104 beats/min. Surgical stress produced a rapid increase in BP (maximal increase of 50 mmHg) and HR (maximal increase of 100 beats/min), which lasted for at least 15 min. Constant infusion of mivazerol, at a dose of 15 μg kg^-1 h^-1, beginning 20 min prior to surgery and lasting for 35 min, significantly inhibited surgical stress-induced increases in BP (P < 0.05) and HR (P < 0.001). Dexmedetomidine, at a dose which produced hypotension and profound bradycardia prior to surgery, did not have any effect on the surgical stress-induced elevation in BP (P>0.05), but prevented the increase in HR (P < 0.05). Pretreatment with the α₂-adrenoceptor antagonist rau-wolscine (0.5 mg/kg, i.v.) blocked the bradycardia induced by mivazerol as well as the inhibitory effect of mivazerol on surgical stress-induced elevations in HR and BP. Conclusion: Mivazerol attenuates surgical stress-induced elevations in BP and HR during pentobarbital anesthesia in rats, and these effects are mediated by stimulation of α₂-adrenoceptors. Unlike dexmedetomidine, mivazerol does not reduce BP, and is also more potent than dexmedetomidine in blunting surgical stress-induced increases in BP in pentobarbital-anesthetized rats.     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

小檗碱对大鼠再灌心律失常及钙调节的作用

小檗碱（Ｂｅｒ，１０ｍｇ·ｋｇ－１）使缺血／再灌后ＶＴ发生率明显降低，持续时间明显缩短，无１例发生ＶＦ及死亡，与对照组比较差异有显著性。离体实验表明：小檗碱（３０μｍｏｌ·Ｌ－１），能抑制高钙条件下Ｃａ２＋内流，而增加低钙条件下的Ｃａ２＋内流。结果表明：小檗碱具有预防再灌心律失常作用；不同Ｃａ２＋浓度能够影响心肌４５Ｃａ内流；小檗碱对心肌Ｃａ２＋内流有双向调节作用，尤其在高Ｃａ２＋条件下，降低４５Ｃａ内流可能是其抗心律失常作用机制之一。     

儿童边缘性锌缺乏症综合判断的研究

对沈阳市某幼儿园９９例３～６岁锌缺乏儿童的营养调查和生物样品（血液、尿液和毛发）的分析发现：同对照组儿童相比，锌缺乏儿童除Ｆｅ、维生素Ａ外，其他主要营养素的摄入明显不足；缺锌儿童的发锌、ＲＢＣ锌水平、血清ＡＬＰ活性、尿锌／尿肌酐比值均明显低于对照组。经补锌治疗后血浆锌水平、血清ＡＬＰ活性、尿锌／尿肌酐比值显著升高。应用临床诊断实验的评价方法分析发现结合血浆锌水平，联合使用发锌，血清ＡＬＰ和尿锌／尿肌酐比值３项指标可以准确判断儿童边缘性锌缺乏，这时并联的灵敏度为９６．１８％，串联的特异度可高达到１００％（血清ＡＬＰ活性＜１０４ＩＵ／Ｌ，同时发锌含量＜１１０ｐｐｍ．尿锌／尿肌酐比值＜０．３μｇ／ｇ）。     

An experimental model for canine visceral leishmaniasis

Seven mixed-breed dogs were challenged with either promastigotes or amastigotes of Leishmania donovani infantum strains recently isolated from naturally infected dogs. Different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. Anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and Western blotting on crude antigen. Western blotting on two pure parasite proteins, dp72 and gp70-2, was also done. Mitogenic and antigen-specific stimulation of peripheral blood lymphocytes was monitored; and the haematological, clinical and parasitological parameters measured. Dogs challenged with amastigotes exhibited a more pronounced humoral response to leishmanial antigens. Only in one case was strong antigen-specific proliferation detected. Clinical signs of disease, including hypergammaglobulinaemia, enlarged lymph nodes and the presence of parasites, were also more apparent in the dogs challenged with amastigotes. None of the seven dogs died. Serum antibodies to leishmanial antigens were apparent between 1.5 to 3 months following challenge and correlated with the appearance of enlarged lymph nodes, hypergammaglobulinaemia and the presence of parasites in tissue biopsies. Serum antibodies remained chronically high in these dogs throughout the period of the study. Only one dog (1/3) challenged intravenously with promastigotes and the dog challenged intradermally with amastigotes produced transient antibody responses to leishmanial antigen.     

组织胺诱导胸腺细胞凋亡的研究

用苔盼蓝及吖啶橙染色，ＤＮＡ片段检定与ＤＮＡ电泳等方法进行组织胺诱导胸腺细胞凋亡的研究，旨在探讨其可能机制及其在胸腺细胞负选择中的作用。结果表明，组织胺诱导使体外培养的胸腺细胞出现典型的细胞调亡。雷尼替丁可阻断上述作用，提示胸腺细胞存在Ｈ＿２受体，活化该受体可能在胸腺细胞的负选择中起重要作用。     

脐动脉血流速波、产前胎心监护及脐动脉血气分析与新生儿结局的对比研究

测定１１５例足月妊娠者（正常妊娠６２例，高危妊娠５３例）脐动脉血流速波（ＵｍＡＳ／Ｄ），同时作产前胎心电子监护（ＮＳＴ），其中３７例于分娩时抽取脐动脉血作血气分析。对上述三种方法预测新生儿结局的效果进行比较。结果表明：ＵｍＡＳ／Ｄ、脐动脉血的ｐＨ值较ＮＳＴ对新生儿结局不良有较好的预测性，异常ＵｒｎＡＳ／Ｄ与新生儿酸中毒有密切关系。     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.