The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 1

Repeated oral doses of di-n-butyl phthalate (DBP) to male rats caused a decrease in testicular fructose and glucose and a sloughing of the germ cells on the first day of treatment. On day 2, more severe sloughing was seen and was accompanied by decreases in testicular iron and zinc levels and increases in the level of inositol and cholesterols. The sloughing was followed by atrophy, accompanied by dissociation of the germ cells from the Sertoli cells and reduction of triglycerides, cholesterols and phospholipids containing choline and ethanolamine residues in the testis.     

Mechanisms of the biphasic responses to endothelin-3 in dog coronary arteries.

1. Endothelin-3 (ET-3) elicited relaxations at low concentrations (up to 10(-8) M) and contractions at higher concentrations in dog isolated coronary arteries precontracted with prostaglandin F2 alpha (PGF2 alpha). The relaxation by ET-3 was not affected by endothelium denudation nor treatment with NG-nitro-L-arginine, but was abolished or reversed to a contraction by treatment with indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthetase inhibitor, or diphloretin phosphate, a prostaglandin receptor antagonist. ET-1 produced only concentration-dependent contractions. 2. BQ-123, a new selective ETA receptor antagonist, caused relaxation of the strips contracted with ET-3 in a dose-dependent manner and prevented the ET-3-induced contraction but did not affect the contraction produced by PGF2 alpha. The relaxation caused by ET-3 was enhanced by treatment with BQ-123. 3. It is concluded that the relaxations elicited by ET-3 in dog coronary arteries are mediated via liberation of PGI2 by activation of non-ETA receptors, located in subendothelial tissues, possibly smooth muscle cells, whereas the peptide-induced contractions are mediated via ETA receptors.     

Sandwich radioimmunoassay of human plasma renin using two monoclonal antibodies

Plasma immunoreactive renin was measured by sandwich radioimmunoassay, under various physiological and pathological conditions. Enzymatic activities of active renin and trypsin-activatable inactive renin were also measured. There was a significant correlation between plasma immunoreactive renin concentration (IRRC) and total (active plus inactive) renin concentration, as estimated by enzymatic activity. In plasma from normotensive volunteers and hypertensive patients, the IRRC were 279 +/- 37 pg/ml and 268 +/- 29 pg/ml, respectively. After the intravenous injection of furosemide, the plasma IRRC in normotensive volunteers increased significantly. IRRC was significantly higher in plasma from juvenile diabetics than in plasma from age-matched disease-free children. Thus, renin secretion in children with diabetes mellitus is increased.     

Changes in serum myoglobin levels caused by tourniquet ischemia under normothermic and hypothermic conditions

Serum myoglobin levels have been found to be elevated for a few hours after removal of a tourniquet. In the present study, levels of serum myoglobin were measured by radioimmunoassay from local blood samples in patients who were treated with surgery of the hand in a bloodless field. After removal of the tourniquet blood samples were obtained from the antecubital vein of each patient immediately after release, five minutes, one hour, and 24 hours later. In these samples the serum myoglobin levels were not influenced by the mode of anesthesia, tourniquet time, or specific type of surgery. When the upper extremity was cooled with ice water before application of the tourniquet, however, the increase of serum myoglobin was statistically significantly inhibited when compared with the normothermic condition. Muscle injury due to tourniquet ischemia may be decreased by cooling of the upper extremity prior to tourniquet application.     

GABA affects the glutamate receptor-chloride channel complex in mechanically isolated and internally perfused Aplysia neurons.

The effects of gamma-aminobutyric acid (GABA) on the glutamate receptor chloride ion (Cl-) channel complex were examined in mechanically isolated and internally perfused Aplysia neurons using a concentration clamp technique. GABA at concentrations of 3 x 10(-6) M or more, concentration dependently delayed the recovery of the glutamate response from desensitization. This effect was independent of the GABA response and Cl- redistribution. Muscimol (10(-4) M) mimicked the effect of GABA. However, this was not the case for baclofen (10(-3) M). In some isolated neurons, GABA at concentrations of more than 10(-4) M clearly induced an additional Cl- current, the current kinetics of which were different from those induced by lower concentrations of GABA. Even in the continued presence of 10(-4) M GABA, which desensitized the fast GABA response, higher concentrations of GABA (3 x 10(-4) M to 10(-2) M) elicited the additional current in a concentration-dependent manner. The presence of 10(-4) M glutamate completely abolished this current, indicating cross-desensitization between the glutamate and slow GABA responses. High concentrations of GABA (3 x 10(-2) M) did not activate the glutamate receptor coupled to the large cation channel. The results suggest that, in Aplysia neurons, the glutamate receptor-Cl- channel complex has some similarities to the GABA receptor-Cl- channel complex.     

Force-time parameters during explosive isometric grip correlate with muscle power

Although explosive isometric contraction provides little work toward the outside, force-time parameters of the rising phase of the force-time curve may be able to predict muscle power. The purpose of this study was to examine the relationship between muscle power with work (power grip) and force-time parameters during the rising phase in explosive isometric grip. Fifteen healthy young adult males participated in this study. Power grip was measured using loads of 20%–50% of maximal voluntary contraction (MVC) (peak isometric force). Subjects pulled explosively on a grip bar held with the second digital joints without the thumb. Peak power was calculated from peak velocity and load. Explosive isometric grip was measured using a hand dynamometer. Time-series data of both tests were sampled by an analog-to-digital interface. Both tests were performed with the subjects seated with a sagittal and horizontal position of the arm supported by an armrest. Peak power in the power grip test tended to be larger with an increase of the load, but there was no significant difference between 40% and 50% MVC. Only the peak power in 50% MVC significantly correlated with peak grip force (r=0.52, p<0.05). The force-time parameters related to the peak rate of the rising force phase in explosive isometric grip significantly correlated with the peak powers (30%–50% MVC, r=|0.58−0.78|). Peak rate of the rising force phase in explosive isometric grip may be useful for predicting muscle power with loads between 30%–50% MVC.     

A 6-day subrenal capsule assay for predictive testing of primary esophageal cancers

Subrenal Capsule Assay (SRCA) as a chemosensitivity test was performed on 14 esophageal squamous cell carcinomas in order to select a more effective form of chemotherapy. Of the 14 assays, 12 were evaluable. Mice were treated with anticancer agents (e.g. Cisplatin, Bleomycin, Methotrexate, Vindesine) on days 1 and 3 after transplantation, and on day 6, the sensitivities were determined. Fresh esophageal cancers yielded an evaluable assay rate of 74%. The implant grew progressively for six days in the remaining group of control mice. Histologically, host cell infiltration at the border of the implant was observed from day 3 after transplantation, and cells had degenerated or had been partially replaced by scar tissue by day 6. The results of chemosensitivity tests differed according to the anticancer agent used or from case to case. Clinically, correspondence between the assay results and clinical results was obtained in 5 out of 7 cases. SRCA is a new promising chemosensitivity test which is clinically useful, and the present results indicated the feasibility of its use in developing an effective chemotherapy for esophageal cancer.     

The male reproductive function in patients with spinal cord injury

Seminal findings and blood hormone levels were studied for evaluating the male reproductive function in patients with spinal cord injury. The patients were divided into 3 groups, namely, 18 patients with complete injury, 5 patients with incomplete injury and 3 patients with dyspermatism. The number of sperms, the rate of movement and rate of deformation were measured for semen obtained by forced ejaculation. The number of sperms was kept at a relatively high level in the three groups, while the rate of movement fell off in all of the three groups. The rate of deformation was highest in the patients with complete injury and lowest in the patients with dyspermatism. As for blood hormone levels, LH, FSH and Testosterone (hereinafter referred to as TES) were determined by the RIA. The cases were classified into those in the acute stage and those in the chronic stage 3 months after sustaining injury for a comparative study. The subjects consisted of 27 cases in the acute stage and 47 cases in the chronic stage. For 8 patients in the acute stage, the blood hormone levels were determined even in the chronic stage and follow-up observations were made on the changes in the levels. The FSH level was low in both stages, while LH and TES tended to increase in the chronic stage. Particularly, the TES level was elevated in all the cases in the follow-up observations made in 8 patients. From the results mentioned above, transient disturbance of the interstitial function is suggested as the mechanism of male gonadal disturbance due to spinal cord injury.     

Point mutation in the band 4.2 gene associated with autosomal recessively inherited erythrocyte band 4.2 deficiency

Abstract: A patient who represented acute hemolytic crisis was studied. Analysis of the erythrocyte membrane proteins by SDS-PAGE revealed a deficiency of band 4.2. In the family, the sister of the patient who had been clinically normal was also shown to be deficient in band 4.2. Binding studies showed that the propositus' membranes were able to bind normal band 4.2 protein as much as control. It was suggested that the binding sites for the protein were prepared on the membrane. We analyzed the band 4.2 cDNA of the propositus and detected a mutation that changes a codon for alanine to one for threonine at residue 142. Band 4.2 exon III of genomic DNA which included the mutation site was amplified and sequenced directly in the family members, and it was revealed that only the homozygotes of the mutation allele manifested band 4.2 deficiency and the parents, who were heterozygotes, showed normal amounts of band 4.2. Recently, the same mutation was reported as Protein 4.2^NIPPON in another 4 cases (Bouhassira et al. Blood 1992: 79: 1846–1854). This study supports the hypothesis that this mutation is the pathogenetic cause of band 4.2 deficiency and not a polymorphism.