Presynaptic Mechanism of Action of 4-Aminopyridine: Changes in Intracellular Free Ca2+ Concentration and Its Relationship to B-50 (GAP-43) Phosphorylation

Abstract: Recently we have shown that 4-aminopyridine (4-AP), a drug known to enhance transmitter release, stimulates the phosphorylation of the protein kinase C substrate B-50 (GAP-43) in rat brain synaptosomes and that this effect is dependent on the presence of extracellular Ca²⁺. Hence, we were interested in the relationship between changes induced by 4-AP in the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) and B-50 phosphorylation in synaptosomes. 4-AP (100 μ M ) elevates the [Ca²⁺]_i (as determined with fura-2) to approximately the same extent as depolarization with 30 m M K⁺ (from an initial resting level of 240 n M to ∼480 n M after treatment). However, the underlying mechanisms appear to be different: In the presence of 4-AP, depolarization with K⁺ still evoked an increase in [Ca²⁺]_i, which was additive to the elevation caused by 4-AP. Several Ca²⁺ channel antagonists (CdCl₂, LaCl₃, and diphenylhydantoin) inhibited the increase in B-50 phosphorylation by 4-AP. It is interesting that the increase in [Ca²⁺]_i and the increase in B-50 phosphorylation by 4-AP were attenuated by tetrodotoxin, a finding pointing to a possible involvement of Na⁺ channels in this action. These results suggest that 4-AP (indirectly) stimulates both Ca²⁺ influx and B-50 phosphorylation through voltage-dependent channels by a mechanism dependent on Na⁺ channel activity.     

Pathology of pulmonary parasitic migration: morphological and bronchoalveolar cellular responses following Nippostrongylus brasiliensis infection in rats

Nippostrongylus brasiliensis has an obligatory migratory phase through the lungs during its development in rats. This migration is associated with marked tissue damage and pronounced cellular reaction. Given that cells from the lower respiratory tract, especially alveolar macrophages, can adhere to and kill larvae of N. brasiliensis in vitro, we studied the time course of morphological changes associated with parasitic migration. Compared to a primary infection, a secondary infection resulted in significant changes in the pulmonary tissue characterized by an early acute inflammation leading to granulomatous reaction in the parenchyma and a leucocytosis in the bronchoalveolar lavage fluids with an anamnestic increase in absolute numbers of neutrophils, alveolar macrophages, eosinophils, and lymphocytes. Scanning electron microscopy showed that inflammatory cells, especially alveolar macrophages, granulocytes, lymphocytes, erythrocytes, and platelets, adhered to the larvae following secondary infection and this adhesion was associated with disruption of cuticular surface in some larvae. Secondary infection also resulted in retention of larvae in granulomatous lesions in the lungs even up to 21 days postinfection. There was mast cell and type II pneumocyte hyperplasia and these cells appeared to be activated. Thus, the histopathological changes in lungs correlated with the bronchoalveolar cellular responses and further document the inflammatory and immunological reactions during the migration of N. brasiliensis larvae.     

厉螨科二新种（蜱螨亚纲：革螨股）

本文绘图描述了厉螨科二新种:拟单阳厉螨Androlaelaps singuloides sp.nov.与陇川下盾螨Hypoaspis longchuanensis sp.nov.,标本分别采自蟋蟀与独角仙体上,采集地同为云南陇川县,文中还列举了它们与相近种类的鉴别要点。     

下盾螨属二新种（蜱螨亚纲：厉螨科）

本文绘图描述了下盾螨属Hypoaspis二新种,订名为拟小下盾螨Hypoaspis subminor sp.nov.与邓氏下盾螨H.tengi sp.nov.。模式标本分别采自宁夏自治区中宁县的黑线仓鼠Cricetulus barabensis Pallas与小毛足鼠Phodopus roborovskii Satunin体上,保存在宁夏自治区地方病防治所与贵阳医学院。     

Effects of growth conditions on exopolysaccharide production by Cyanospira capsulata

Batch cultures of Cyanospira capsulata, a heterocystous cyanobacterium possessing a thick polysaccharidic capsule, were characterized by increasing viscosity owing to the continuous release of a soluble polysaccharide (EPS) into the culture medium. Both capsulated trichomes and solubilized EPS contributed to the flow properties of whole cultures. A typical pseudoplastic behaviour, the more marked the more aged were the cultures, was evidenced.The production of EPS was investigated under different growth conditions by changing some nutritional and physical parameters known to affect the synthesis of exopolysaccharides in algae and cyanobacteria. Among the factors tested (Ca²⁺, Mg²⁺ or PO₄⁻⁴ deficiencies, salinity and pH) only Mg²⁺ shortage caused a significant enhancement of the EPS production. Under continuous illumination in open ponds, the EPS productivity of batch cultures on standard mineral medium was about 5·8 g m⁻² day⁻¹, whereas under Mg²⁺ deficiency with a consequent increase of the cultures' viscosity     

Genetic counseling of a couple presenting respectively terminal transverse defects and congenital arthrogryposis.

A 29-year-old woman consulted together with her husband for a problem of congenital joint contractures. Clinical findings in the woman were characteristic of "amyoplasia congenita". In view of the severe distal limb involvement, the possibility of a distal arthrogryposis was also considered. Unexpectedly, the husband presented terminal transverse defects, mainly of the feet, suggestive of Adams-Oliver syndrome, an autosomal dominant condition with variable expression. This discovery significantly altered the counseling given to the couple, i.e. they had to be given a high recurrence risk for congenital limb malformations in their offspring and rigorous echographic monitoring of future pregnancies was advised.     

Oculocerebral syndrome with hypopigmentation (Cross syndrome): the mixed pattern of hair pigmentation as an important diagnostic sign.

The present report describes two female siblings of mixed ancestry (Cape Coloured) with consanguineous parents as further examples of Cross oculocerebral hypopigmentation syndrome. The mixed pattern of hair pigmentation as an important diagnostic sign is emphasized.     

Inhibition of Microsomal Lipid Peroxidation and Cytochrome P-450-Catalyzed Reactions by Nitrofuran Compounds

(5-Nitro-2-furfuryliden)amino compounds bearing triazol-4-yl, benzimidazol-l-yl, pyrazol-l-yl, triazin-4-yl or related groups (a) stimulated superoxide anion radical generated by rat liver microsomes in the presence of NADPH and oxygen; (b) inhibited the NADPH-dependent, iron-catalyzed microsomal lipid peroxidation; (c) prevented the NADPH-dependent destruction of cytochrome P-450; (d) inhibited the NADPH-dependent microsomal aniline 4-hydroxylase activity; (e) failed to inhibit either the cumenyl hydroperoxide-dependent lipid peroxidation or the aniline-4-hydroxylase activity, except for the benzimidazol-l-yl and the substituted triazol-4-yl derivatives, which produced minor inhibitions. Reducing equivalents enhanced the benzimidazol-l-yl derivative inhibition of the cumenyl hydroperoxide-induced lipid peroxidation. The ESR spectrum of the benzimidazol-l-yl derivative, reduced anaerobically by NADPH-supplemented microsomes, showed characteristic spin couplings. Compounds bearing unsaturated nitrogen heterocycles were always more active than those bearing other groups, such as nifurtimox or nitrofurazone. The energy level of the lowest unoccupied molecular orbital was in fair agreement with the capability of nitrofurans for redox-cycling and related actions. It is concluded that nitrofuran inhibition of microsomal lipid peroxidation and cytochrome P-450-catalyzed reactions was mostly due to diversion of reducing equivalents from NADPH to dioxygen. Trapping of free radicals involved in propagating lipid peroxidation might contribute to the overall effect of the benzimidazol-l-yl and substituted triazol-4-yl derivitives.