Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.     

Overexpression of the 18A2/mts1 gene and down–regulation of the TIMP–2 gene in invasive human glioma cell lines in vitro

Invasion of the reconstituted extracellular matrix composite, Matrigel, by eight human glioma–derived cell lines and human fetal brain cells was assessed in vitro using 8 um polycarbonate filters in a modified Boyden migration chamber. With the exception of one low grade glioma derived cell line, all lines studied proved to be invasive while normal fetal brain cells failed to invade. This invasive potential was independent of the histological grade of the tumour from which the cell lines originated. In addition, the expression of the metastasis–associated gene 18A2lmts1 as well as the tissue inhibitor of metalloproteinases–2 (TIMP–2) was analysed in each of the glioma–derived cell lines. The 18A2/mtsl was expressed in all the cells studied with the exception of fetal brain cells and the low grade non–invasive glioma derived IPRK–7 cell line. The 18A2/mtsl related genes coding for the S100 subfamily of calcium binding proteins were found to be differentially and overexpressed in invasive cell lines. TIMP–2 was expressed only in noninvasive cell lines. These results suggest that the 18A2/ mtsl and TIMP–2 genes could play an important role in the invasive behaviour of human glioma cells in vitro. .     

Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells.

NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis.     

短暂性脑缺血发作患者血浆中TXB2和PGF1α含量检测

本文用放射免疫法测定47例短暂性脑缺血发作(TIA)患者血浆中血栓素B_2(TXB_2)和6酮-前列腺F_(1α)(PGF_(1α))的含量。结果发现TIA患者血浆中TXB_2含量增高,PGF_(1α)降低;头颅CT或MRI示有小灶性梗塞者及TIA发作持续时间长于30min者TXB_2升高和PGF_(1α)降低更显著。治疗3个月后,血浆PGF_(1α)显著增高。TXB_2和PGF_(1α)在体内的失平衡是急性脑血管疾病发病的重要机理之一。     

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.