Blockade of dopamine D1 receptors by SCH 23390 antagonizes discriminative stimulus effects of pentazocine

The purpose of this investigation was to test the hypothesis that the discriminative stimulus properties of pentazocine are mediated through an interaction with dopamine receptors. Rats were trained to discriminate s.c. injections of pentazocine (3.0 mg/kg) from vehicle in a two-choice discrete trial avoidance paradigm. SCH 23390 (0.003–0.056 mg/kg), a selective antagonist of dopamine D₁ receptors, inhibited the discriminative stimulus effects of pentazocine in a dose-dependent fashion, whilst the selective D₂ receptor antagonist sulpiride (20.0–80.0 mg/kg) did not antagonize them. It appears that the dopamine D₁ receptors play an important role in the discriminative stimulus effects of pentazocine.     

Regeneration of myelinated fiber after crush injury is retarded in sciatic nerves of mutant Japanese quails deficient in neurofilaments

Regeneration of myelinated fibers in the sciatic nerve 2 weeks after crush injury was studied morphometrically in mutant Japanese quails deficient in neurofilaments and in normal quails (controls). There were fewer regenerated myelinated fibers per nerve at 10 mm (R₁) and 20 mm (R₂) distal to the crush site in mutants than in controls (P < 0.05). Both median and maximum diameters were smaller (P < 0.01) in mutants than in controls. On electron microscopy, transverse axonal area and axonal circumference were smaller (P < 0.001) at both R₁ and R₂ in mutants than in controls. The number of myelin lamellae was less (P < 0.01) in mutants than in controls at R₁, but was similar at R₂. There were fewer myelin lamellae in relation to axonal area in mutants than in controls at R₁ (P < 0.0001) and R₂ (P = 0.0032). The results indicate a retardation of both radial growth of axons and myelination around axons of the same size in mutants compared with controls. Such retardation may be explained by the deficiency of neurofilaments and the altered relationship between Schwann cell and axon in the mutant. Received: 18 December 1995 / Revised, accepted: 20 May 1996     

PLANTAR MALIGNANT MELANOMA

Among 51 cases of malignant melanoma seen at the Department of Dermatology, Tohoku University School of Medicine, from 1966 to 1978, 16 cases had had the primary lesion on the sole. The average age of these 16 cases was 63 and the sex ratio (M:F) was 11:5. The common sites of involvement on the sole were the heel (in 9 cases) and the toes and metatarsal region (in 5 cases). In 14 cases the lesions arose on the right sole; furthermore, 6 cases had had histories of trauma before or after the development of tumor and 7 cases had received insufficient excisions of their lesions, all of which showed a recurrence and/or lymph node metastasis within a year. These data suggest that traumatic stimulation may have some effect up on the pathogenesis of plantar melanoma. The clinicopathological features of plantar malignant melanoma in Japan are also described.     

High single-dose alternate-day corticosteroid regimens in treatment of polymyositis

Summary High single-dose alternate-day prednisolone therapy (ADT) was compared with daily-dose prednisolone therapy (DDT) for treatment of polymyositis. Thirty patients with polymositis were treated with ADT for an average of 33.9 months. The combined number of improvements was 21 out of 30, a response rate of 70%. Side-effects were very rare and mild. On the other hand, 9 of 17 patients treated with DDT for an average 18.5 months improved, a response rate of 53%. The incidence of side-effects was strikingly higher than with ADT. ADT is therefore strongly advocated for treatment of polymyositis to avoid infectious complications and lessen cushingoid side-effects.     

An improved method for determination of the total kininogen in rabbit and human plasma

The method described by Diniz and Carvalho has been widely used for determination of the total kininogen (KGN) in plasma, but this method is also reported to produce bradykinin (BK) potentiators besides BK after incubation of the pretreated plasma with trypsin. The present experiments aim to establish a method to induce the full conversion of KGN into BK without potentiators and kininase. The pretreatment of plasma with heat (98°) and acetic acid (pH 3.5) used in Diniz's method was compared with five other pretreatments, namely non-treated, two ways of heating (at 98 or 60°) and two ways of acidification (at pH 3.5 or 2.0). The pretreated plasmas were incubated with trypsin in 0.2 M Tris buffer, pH 7.8. BK released was assayed on the isolated rat uterus. The full conversion of KGN into BK by trypsin was tested, comparing it with the amounts of BK released by highly purified hog pancreas kallikrein and highly purified snake venom kininogenase. Trypsin (200 μg) and 30 min of the incubation were sufficient to convert KGN into BK up to plateau level in non-treated and treated plasmas. The results indicated that the pretreatments of Diniz and 98° produced BK potentiators, and the non-treated and the pH 3.5-treated plasmas showed lesser amounts of BK formed, even in the presence of o-phenanthroline. The pretreatments of pH 2.0 and 60° produced no potentiators and caused the full conversion of KGN into BK, but the latter treatment did not inactivate kininase in rabbit plasma. Thus, it is concluded that the pretreatment of plasma with HCl (pH 2.0) was most suitable for the determination of total KGN in rabbit plasma. For human plasma, pretreatment by heating (60°) was also suitable, besides the pH 2.0 treatment.     

A case of advanced gastric cancer with pulmonary carcinomatous lymphangiosis responding remarkably to combination chemotherapy of docetaxel (TXT) and TS-1

A 51-old-female patient was admitted because of dyspnea. This case was diagnosed inoperable advanced gastric cancer and pulmonary carcinomatous lymphangiosis. She was treated by combination of docetaxel (TXT) and TS-1. TXT (40 mg/m2) was administered on day 1, and TS-1 (80 mg/body/day) was then administered for 14 days followed by a 7-day interval as one course. After two courses of chemotherapy, carcinomatous lymphangiosis declined, tumor markers decreased, and dyspnea improved. Administration of oxygen was thus discontinued. No side effects appeared (hematological or non-hematological).