Sympathoinhibition by rilmenidine in conscious rabbits: involvement of α2-adrenoceptors

Summary Cardiovascular and sympathetic nervous system effects of the mixed ₂-adrenoceptor and imidazoline receptor agonist rilmenidine were studied in conscious rabbits chronically instrumented for the recording of the firing rate of renal sympathetic fibers. Separate experiments were carried out on pithed rabbits with electrically stimulated (2 Hz) sympathetic outflow. Drugs were administered intravenously in a cumulative manner.In conscious rabbits, rilmenidine 0.1, 0.3 and 1.0 mg kg^–1 dose-dependently lowered blood pressure, renal sympathetic nerve activity, heart rate and the plasma concentration of noradrenaline and adrenaline. The effect on blood pressure and plasma catecholamines was maximal after 0.3 mg kg^–1 whereas heart rate and renal sympathetic nerve activity decreased further after rilmenidine 1.0 mg kg^–1. Yohimbine 0.1 and 0.5 mg kg^–1, when injected subsequently, attenuated and at the higher dose abolished all effects of rilmenidine. The effects of rilmenidine were also antagonized by the ₂-adrenoceptor antagonist 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imidazole HCl (RX821002; 0.1 and 0.5 mg kg^–1). Yohimbine 0.1 and 0.5 mg kg^–1 did not attenuate or attenuated only slightly the decrease of heart rate and renal sympathetic nerve activity produced by infusion of vasopressin. In pithed rabbits with electrically-stimulated sympathetic outflow, yohimbine 0.1 submaximally and yohimbine 0.5 mg kg^–1 maximally increased the plasma noradrenaline concentration.The experiments show by direct measurement of sympathetic nerve firing and plasma catecholamines that rilmenidine causes sympathoinhibition in conscious rabbits, presumably through central sites of action. The antagonism by yohimbine, at doses which are selective for ₂-adrenoceptors (vs. imidazoline receptors), demonstrates the involvement of ₂-adrenoceptors in the sympatho-inhibition.Correspondence to: B. Szabo at the above address     

Urinaryα 1 as an index of proximal tubular function in early infancy

Urinary ₁-microglobulin (U-A₁M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A₁M was high until day 14 and declined thereafter. It was significantly correlated with urinary ₂-microglobulin (U-B₂M) throughout the study, but not with serum A₁M on days 1 or 7. Similar to U-B₂M, U-A₁M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A₁M as well as U-B₂M was high on days 1–7 and then decreased to normal levels, suggesting that U-A₁M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A₁M is a useful index of proximal tubular function in early infancy.     

Transmission of antibodies to Chlamydia Psittaci and Coxiella Burnetii through eggs and “crop milk” in pigeons

Young semi-domesticated pigeons captured or hatched from eggs gathered in Bratislava during 1989–1991 were examined for complement fixing antibodies to Chlamydia psittaci and agglutinating antibodies to Coxiella burnetii. Antibodies to Ch. psittaci were present in 76% of birds younger than 24 h, in 47.7% between 1 and 10 days of age and in 12% of nestlings over 10 days old. Antibodies to Ch. psittaci were also detected in crop milk of 4.1% of 1 to 10 day old birds and in 4.5% of specimens older than 10 days. Antibodies to C. burnetii were not found in juvenile birds under 24 h old, but antibodies against this agent were present in 16.4% birds between 1 and 10 days old and in 18% over 10 days old. Antibodies to C. burnetii were also detected in crop milk collected from crops of 2% of the young birds between 1 and 10 days.     

Recent advances in understanding the pathogenesis of the hemolytic uremic syndromes

One of the requirements for an agent to cause hemolytic uremic syndrome (HUS) is its ability to injure endothelial cells. Shiga-like toxin (SLT) can do this. SLT is produced byEscherichia coli andShigella dysenteriae serotype 1; both have been implicated as causes of typical HUS. Endothelial cells have receptors (GB₃) for SLT and the toxin can inhibit eukaryotic protein synthesis, thereby causing cell death. Glomerular endothelial cell injury or death results in a decreased glomerular filtration rate and many of the perturbations seen in HUS. It is no longer certain that hemolysis is the result of a microangiopathy. Cell injury results in release of von Willebrand multimers; if these are ultra-large, thrombosis may ensue. There is also increasing evidence that neutrophils have a role in the pathogenesis of typical HUS.Streptococcus pneumoniae can also cause HUS and care must be taken to avoid giving plasma to patients withS. pneumoniae-associated HUS. There is compelling evidence that types of HUS are inherited by autosomal recessive and autosomal dominant modes. Patients with autosomal recessive HUS may have recurrent episodes. Mortality and morbidity rates are high for the inherited forms.     

Depression of drug metabolizing activity in the human liver by interferon-α

Summary The depressant effect of interferon- on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol·g^–1 liver·min^–1, and from 3.22 to 2.16 nmol·g^–1 liver·min^–1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon- can impair the activity of drug metabolizing enzymes in the human liver.     

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin > imipramine > desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verified that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.     

肝细胞癌上皮细胞白蛋白和CK7的表达

目的 探讨人类肝癌肝组织是否存在小上皮细胞（small epithelial cell,SEC),这类细胞是否表达白蛋白CK7抗体,对30例人肝细胞肝癌的手术标本材料作免疫组化染色,对其中10例作超微结构观察和白蛋白及CK7的免疫电镜标记。结果 30例中有20例在肝癌肿瘤边缘和增生的小胆管发现有少量SEC。这类细胞既表达白蛋白,又表达CK7。电镜下,这类SEC体积较小,核大,胞质少胞质内主要为游离核糖体,并有胞质内张力微丝及细胞间连接结构。免疫电镜下,10例中有5例可显示在同一SEC同时表达白蛋白和CK7。结论 人肝细胞癌肝中确实存在SEC。这类SEC具有与人肝母细胞瘤和胆道闭锁肝组织中的SEC一样的形态和免疫表型特点。     

共刺激分子CD28和B7在关节炎发病中的作用

目的：探讨Ｂ７;ＣＤ２８共刺激信号在关节炎发病机制中的作用。方法：经牛Ⅱ型的（ＢⅡＣ）诱导ＳＤ大鼠建立关节炎动物模型,分析抗Ｂ７－１和抗Ｂ７－２抗体对关节炎大鼠临床症状和特异性免疫反应的影响。结果：抗Ｂ７－１抗体可阻止ＳＤ大鼠发生胶原诱地性关节炎,降低大鼠对ＢⅡＣ的体液免疫反应。结论：Ｂ７;ＣＤ２８共刺激信号在诱发Ｔ细胞介导的自身免疫疾病中起作用,抗Ｂ７－１抗体具有潜在的治疗作用。     

γ射线诱导人肝癌细胞表达B7-1共刺激分子的研究

目的　研究电离辐射与肿瘤细胞B7- 1分子表达之间的关系 ,探讨肿瘤细胞辐照后免疫原性增强的机制。方法　采用间接免疫荧光 -流式细胞仪分析技术 ,研究在用不同剂量γ射线照射SMMC - 772肝癌细胞后、培养不同时间内SMMC - 772细胞B7- 1共刺激分子的表达水平。并用3H -TdR释放法测定照射和未照射肿瘤细胞与淋巴细胞共反应后的细胞毒活性。结果　未照射和经 10、2 0、30Gy照射的人肝癌细胞不表达B7- 1分子。经 40、5 0、6 0Gy剂量照射后 ,SMMC - 772肝癌细胞表达B7- 1分子 ,最高达 6 6 .8± 1.3% ,与对照组比有非常显著性差异 (P <0 .0 1)。表达时间的高峰在照射后培养 72h时 ,最低在照射后培养 2 4h时 (P <0 .0 5 )。细胞毒活性测定结果表明 ,表达B7- 1分子的SMMC - 72肝癌细胞与淋巴细胞共反应后 ,细胞毒活性明显高于未照射组 (P <0 .0 1)。结论　γ射线可诱导肝癌细胞表达B7- 1分子 ,从而增强肿瘤细胞的免疫性     

7-硝基吲唑对大鼠脑缺血再灌流保护作用的研究

目的：探讨神经元型一氧化氮合酶抑制剂（ｎＮＯＳＩ）７－硝基吲唑（７－ｎｉｔｒｏｉｎｄａｚｏｌｅ,７－ＮＩ）对脑缺血再灌流保护作用的机理。方法：选用体重１８０－２２０ｇ的雌性Ｗｉｓｔａｒ大鼠,随机分组,左颈外动脉管腔内置渔线经颈内动脉送至大脑中动脉内,使之闭塞。