The role of α2-adrenoceptors of the medullary lateral reticular nucleus in spinal antinociception in rats

We attempted to find out the role of α₂-adrenoceptors of the medullary lateral reticular nucleus (LRN) in antinociception in rats. Spinal antinociception was evaluated using the tail-flick test, and supraspinal antinociception using the hotplate test. Antinociceptive effects were determined following local electric stimulation of the LRN, and following microinjections of medetomidine (an α₂-adrenoceptor agonist; 1–10 μg), atipamezole (an α₂-adrenoceptor antagonist; 20 μg) or lidocaine (4%) into the LRN. The experiments were performed using intact and spinalized Hannover-Wistar rats with a unilateral chronic guide cannula. Electric stimulation of the LRN as well as of the periaqueductal gray produced a significant spinal antinociceptive effect in intact rats. Medetomidine (1–10 μg), when microinjected into the LRN, produced no significant antinociceptive effect in the tail-flick test in intact rats. However, following spinalization, medetomidine in the LRN (10 μg) produced a significant atipamezole-reversible antinociceptive effect in the tail-flick test in the hot-plate test, medetomidine (10 μg) in the LRN produced a significant atipamezole-reversible increase of the paw-lick latency in intact rats. Microinjection of atipamezole (20 μg) or lidocaine alone into the LRN produced no significant effects in the tail-flick test. The results are in line with the previous evidence indicating brat the LRN and the adjacent ventrolateral medulla is involved in descending inhibition of spinal nocifensive responses. However, α₂-adrenoceptors in the LRN do not mediate spinal antinociception but, on the contrary, their activation counteracts antinociception at the spinal cord level. The spinal aninociceptive effect of supraspinally administered medetomidine in spinalized rats can be explained by a spread of the drug (e.g., via circulation) which then directly activates α₂-adrenoceptors at the spinal cord level.     

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。     

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。     

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.