Effect of Central Muscarine Receptor Blockade with DKJ-21 on the Blood Pressure and Heart Rate in Stress-Induced Hypertensive Rats

Da-Nian Zhu, Long-Mei Xue, Peng Li. Effect of central muscarine receptor blockade. with DKJ-21 on the blood pressure and heart rote in stress-induced hypertensive rats.

The experiments were performed on Wistar or Sprague-Dawley rats of both sexes divided at random into stress and control groups. The rats in the stress groups were put into cages and subjected to electric foot-shocks and noises for 9-15 days, which caused an increase in blood pressure (BP) and heart rate (HR). In hypertensive rats DKJ-21 (4mg/lml) was injected intravenously (i.v.), and 0.5-1.0h after administration the BP and HR dropped from the high level to normotensive level. In normotensive rats, however, administration of DKJ-21 had no effect on BP or HR. In separate groups of normotensive rats, pretreatment of DKJ-21 (4 mg/l ml, i.v.) blocked the pressor and tachycardiac effect induced by microinjection of physostigmine (0.4μg/0.1 /μl/site), corticosterone (40μg/0.1μl/site) or aldosterone (40 μg/0.1 μl/site) into the rostral ventrolateral medulla (rVLM). Furthermore, DKJ-21 also attenuated the enhancement of the pressor response to stimulation of the defense area in the midbrain, which was induced by microinjection of drugs (mentioned above) into the rVLM. These results indicate that i.v. DKJ-21 can selectively block the muscarinic receptors in the rVLM in stress-induced hypertensive rats, which suggests that abnormal enhancement of cholinergic mechanism in the rVLM may be related to hypertensive effects of corticoids in this area.     

微小病变型肾病综合征患者IL－2的检测及其意义

３２例微小病变型肾病综合征（ＭＣＮＳ）患者，采用￣３Ｈ－ＴｄＲ掺入法测定其外周血Ｔ淋巴细胞产生白介素２（ＩＬ＿２）的浓度，结果显示本病患者Ｔ细胞产生ＩＬ＿２的能力显著降低，与对照组相比差异非常显著（Ｐ＜０．０１），故认为ＭＣＮＳ的发生与Ｔ细胞功能异常有关。     

Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brain.

The inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to the GABA_A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC₅₀ from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC₅₀ values found in the literature. IC₅₀ values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [³⁵S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.     

Reversible low-molecular-weight proteinuria in patients with distal renal tubular acidosis

Four patients with untreated renal tubular acidosis had a urinary excretion of low-molecular-weight (LMW) proteins which was restored to normal by alkali therapy. Hypokalaemic proximal tubular damage in untreated patients with distal renal tubular acidosis is believed to be the cause of LMW proteinuria. An examination of urinary excretion of LMW proteins is useful for determining hypokalaemic proximal tubular dysfunction, as well as the efficiency of alkali therapy.     

Channges in regional cerebral blood flow after hyperventilation in the pig with an induced focal cerebral contusion

Summary Changes in regional cerebral blood flow in anaesthetized pigs with an induced focal cerebral contusion were studied before and after two grades of hyperventilation. A reduction in arterial tension of CO₂ with 0.70mmHg and a further reduction of 0.55mmHg did not change the CO₂ reactivity. Reactivity in both injured and macroscopically normal regions was the same, revealing an average of 39.3% flow change per kPa change in CO₂ tension. Regions with low flow after the contusion had an equally big reduction apparently leading to hypoxia because global metabolic rate was unchanged.     

Stability studies of the components of a prototype penicillinase (β-lactamase)-linked ELISA kit

Penicillinase (β-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37°C and 2-8°C). Stability studies were conducted on previously validated assay for pregnanediol-3α-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37°C for 1 week and at 2-8°C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37°C up to 1 week and at room temperature up to 2 weeks and at 2-8°C for a period of 6 months, during which the stability was studied. © 1993 Wiley-Liss, Inc.     

Endotoxin-induced uveitis (EIU) in the rat: A study of inflammatory and immunological mechanisms

Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B₂, prostaglandin E₂, leukotriene B₄ and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B₂ was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E₂ & leukotriene B₄ peaks and a second peak of thromboxane B₂ were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothetized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.     

THE EFFECT OF SOME α2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

1. The effects of graded doses of the α₂-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the α₂-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.     

Comparison of the use of bulk to micro culture of cell preparations for lymphokine-activated cytotoxicity assays.

Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells.