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.     

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.     

重症肌无力病人乙酰胆碱受体抗体的测定及临床意义

用ＥＬＩＳＡ（固相酶联免疫吸附）法测定１７２例ＭＧ病人血清乙酰胆碱受体抗体（ＡｃｈＲａｂ），结果显著高于健康献血员组和非ＭＧ病人组。不同性别、病程及临床类型与ＡｃｈＲａｂ无相关性，但４１～５０岁组的显著高于其他年龄组。６７例类固醇激素治疗组、２２例大剂量两种球蛋白治疗组、１２例胸腺切除术组及３例ＭＧ危象病人２４次血浆交换疗法（ＰＥ）组，治疗后伴随肌无力症状的好转，ＡｃｈＲａｂ均显著低于治疗前。结果表明：ＡｃｈＲａｂ测定为ＭＧ诊断提供了可靠的实验依据，为类固醇激素、大剂量丙种球蛋白、胸腺切除术和ＰＥ等治疗ＭＧ提供理论依据和疗效评定的实验指标，进一步证实了ＭＧ免疫学发病机理。     

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.     

Involvement of glutamate receptors,lipases, and phospholipases in long-term potentiation and neurodegeneration

Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Normal excitation of glutamate receptors initiates the stimulation of phospholipases and lipases with the generation of second messengers that are necessary for normal cell function. The overstimulation of glutamate receptors can initiate a cascade of biochemical events including stimulation of membrane phospholipid turnover, excessive calcium entry, abnormal phosphorylation, and proteolysis. These events may be responsible for neuronal injury and degeneration found in Alzheimer disease, ischemia, spinal cord trauma, epilepsy, and Huntington disease.     

Thrombosis triggered by severe arterial lesions is inhibited by oral administration of a glycoprotein IIb/IIIa antagonist

Platelet aggregation and thrombosis play an important role in the onset of acute coronary events. Regardless of the stimulus for activation, platelet thrombus formation is ultimately regulated through the IIb/IIIa receptor complex. The effects of oral administration of xemilofiban, a non-peptide mimetic of the RGDF sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated in a canine model. Xemilofiban significantly reduced platelet deposition on severely damaged arterial wall. Platelet deposition was reduced at both low (13 ± 1 from 56 ± 18 × 10⁶ platelets cm⁻²; P  < 0.05) and high (23 ± 2 from 111 ± 21 × 10⁶ platelets cm⁻²; P  < 0.01) shear rates. Platelet deposition was reduced to a monolayer as seen by electron microscopy (platelet–vessel wall interaction). Therefore, the availability of an orally active IIb/IIIa antagonist for chronic use may have significant value in preventing thrombus formation in those clinical situations associated with severe arterial injury, such as atherosclerotic plaque disruption.     

Dystonia gravidarum: a new case with a long follow-up.

We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia.     

Acetylcholine receptor antibody in myasthenia gravis

Radioimmunoassay techniques were used to detect antibodies to the acetylcholine receptor (AAChR) in 164 patients with adult-onset myasthenia gravis. AAChR levels above 0.6 nM/l were considered pathological and were found in 67% of the patients with an average value of 58.99 +/- 125.02 nM/l (0.6-900.0). Correlation, with clinical functional status, the histopathological thymus alterations and the different therapeutics used did not disclose any statistically significant differences.     

重症肌无力患者泼尼松治疗前后免疫学指标的变化

探讨泼尼松治疗重症肌无力（MG）免疫学机制。对382例MG患者在漏尼松中剂量冲击，小剂量维持疗法治疗前后，检测酰胆碱受体抗炎（AchRab)，突触前膜抗体（PsMab)，单个核细胞亚群（PBMC），肿瘤坏死因子（TNF），可溶性白介素－2受体（SIL－2R），β2－微球蛋白（β2－m)，以及红细胞免疫功能的变化。结果表明：MG患者在泼尼松治疗前后多项免疫指标有显著性的变化。为泼尼松治疗MG提供了评定疗效的免疫学指标，进一步阐明了MG发病的免疫学机制。     

Quantitative autoradiographic study of L-glutamate binding sites in normal and atrophic human cerebellum.

In the present work the distribution of L-glutamate binding sites in the different layers of human cerebellum of normal individuals and of seven patients who died with olivopontocerebellar atrophy (OPCA) was examined with the technique of quantitative autoradiography. Specific L-[3H]glutamate binding was higher in the molecular than in the granule cell layer of normal cerebellar tissue. A significant decrease of L-[3H]glutamate specific binding was observed in the molecular layer of all OPCA tissues. In the granule cell layer L-[3H]glutamate binding was decreased only in two patients who suffered from late-onset sporadic OPCA and in one patient who suffered from a form of OPCA inherited in a dominant manner. Quisqualate-sensitive binding sites were the most abundant binding sites in the molecular layer of normal cerebella, whereas N-methyl-D-aspartic acid (NMDA)-sensitive binding sites were the most abundant type in the granule cell layer. A significant decrease of quisqualate-sensitive and an increase in NMDA-sensitive binding sites were observed in the molecular layer of OPCA cerebellar tissues. No significant changes were observed in the granule cell layer of these tissues.