Sex-related Differences in Rat Liver Microsomal Enzymes and Their Induction by Doxapram

Abstract— The effects of doxapram on the hepatic microsomal mono-oxygenase system of male and female rats were investigated. Male and female rats were administered doxapram (10–120 mg kg^?1 day^?1, i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg^?1) elevated the parameters in a dose-dependent manner while doxapram (100 and 120 mg kg^?1) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg^?1) caused induction of hepatic drug metabolism typified by an increase of hepatic microsomal cytochrome P450 content and activities of hexobarbitone hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demethylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. However, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrome c reductase and NADH-cytochrome c reductase activities, and cytochrome b₅ content were unaffected in rats of both sexes. The sex-dependent cytochrome P450 species may be selectively sensitive to the action of doxapram.     

Occupational scleroderma. A 17-year follow-up study

Summary Two patients with a scleroderma-like disorder induced by epoxy resins were reported from the Department of Dermatology, Gunma University School of Medicine, Japan in 1980. Here, we describe the clinical and laboratory characteristics of these patients after 17 years' follow-up from 1976 to 1993. Their systemic manifestations and indurated sclerotic skin changes disappeared within 5 years. No internal organ involvement has developed during the period of follow-up. On routine laboratory tests, no abnormalities have been found in the peripheral blood or in the blood chemistry or serology. Histological examination revealed atrophy of the dermis and restoration of the normal pattern of fine collagen bundles, when compared ulth the previous skin biopsy specimens. This scleroderma-like disorder induced by epoxy resins is considered to be different from systemic sclerosis: it has an acute onset and a fairly good prognosis, and does not show involvement of the internal organs.     

Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) Elα gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.     

Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea:Analysis by sleep position

Abstract Fifteen patients with obstructive sleep apnea were treated using prosthetic mandibular advancement (PMA). Each patient was evaluated in the supine and lateral decubitus positions with and without PMA. After PMA treatment, the mean intraesophageal pressure (Peso) in the supine position improved from -42.6 to -27.3 cmH₂O and the mean apnea + hypopnea index (AHI) decreased from 48.8/h to 23.7/h. The mean Peso in the lateral decubitus position improved from -27.9 to -18.6 cmH₂O and the mean AHI decreased from 9.6/h to 6.6/h. With PMA, respiratory disturbance during sleep further improved by changing the body position from the supine to lateral decubitus position.     

Antibodies to hepatitis C virus and elevated transaminase levels in a town of hyperendemicity in Iwate, Japan

In an annual survey for liver function tests in persons aged > xs35 years in Iwate Prefecture, Japan, a town was identified where high levels of alanine aminotransferase abounded. Of 5152 inhabitants aged > 35 years in this town, antibodies to hepatitis C virus (HCV) determined by enzyme-linked immunosorbent assay with HCV core peptides were detected in 798 (15.5%) people, hepatitis B surface antigen was detected in 47 (0.9%) people and antibodies to hepatitis B surface antigen and/or hepatitis B core antigen unaccompanied by surface antigenaemia were detected in 1748 (33.9%) people. Antibodies to HCV core peptides correlated closely with the antibodies detected by passive haem-agglutination with recombinant HCV proteins of the second generation. Antibodies to HCV core peptides were particularly common in one of the nine districts of the town (district 8), where 276 (45.3%) of 609 inhabitants tested positive; there were no differences in the frequency of serological markers of hepatitis B virus (HEV) infection among residents in the nine districts. Of the 798 individuals with antibodies to HCV core peptides, 257 (32.2%) were found to have elevated transaminase levels. A history of transfusion was associated with a high frequency of antibodies to HCV core peptides, except in district 8 where such antibodies were equally frequent in residents irrespective of transfusions. These results indicate an epidemiology of HCV distinct from that of HBV in this town and a very local spread of HCV, as well as a high frequency of hepatic injuries in individuals with antibodies to HCV.     

Functional and phenotypical activation of leucocytes in inflamed human colonic mucosa

Infiltrating leucocytes are activated to generate reactive oxygen species or to produce several molecules in inflamed colonic mucosa. To clarify the phenotypical and functional properties of activating cells in colitic mucosa, 23 patients with ulcerative colitis and 13 controls were studied using a combined method for determining in situ nitroblue tetrazolium reducing activity and immunohisto-chemical characterization. Antibodies 25F9 (anti-macrophage), EG2 (anti-eosinophil cationic protein), MAC387 (anti-calprotectin, expressed by activated myeloid-histiocytes lineage), and MAC-1 (anti-CD11b) were used. The proportion of EG2, calprotectin, and CD11b-positive cells were significantly increased in inflamed mucosa. The proportion of EG2, calprotectin, and CD11b-positive cells significantly correlated with the histological degree of inflammation. Proportion of EG2-positive cells but not calprotectin nor CD11b-positive cells was significantly correlated with nitroblue tetrazolium reducing activity. Aggregated cells reducing nitroblue tetrazolium seen in severely inflamed mucosa were found to be EG2 positive. Most of the calprotectin-positive cells were 25F9 negative. In addition to activation of neutrophils and macrophages, eosinophil activation has been shown to be involved in inflamed colonic mucosa.     

Effect of testosterone on the mucosal defence against intestinal helminths in Indian soft-furred rats, Millardia meltada with reference to goblet and mast cell responses

Effects of testosterone on the mucosal defence mechanisms against intestinal helminths were examined in Millardia meltada. When female M. meltada were treated with testosterone at the pharmacological dose, Nippostrongy-lus brasiliensis infection persisted for over seven weeks with prominent biphasic pattern of faecal egg production, whereas almost complete expulsion was observed by two weeks in untreated controls. In spite of a biphasic pattern of faecal egg production, the worm burden of testosterone-treated animals remained constant up to three weeks and then slowly decreased by seven weeks. To see whether or not this delayed expulsion in testosterone treated animals was due to altered cellular responses of the intestinal mucosa, goblet and mast cell responses were examined histologically. At two weeks post-infection, goblet cell responses at the infected site were significantly lower in testosterone-treated animals than in controls. In contrast mast cell hyperplasia was comparable between testosterone-treated and control animals. When Strongyloides venezuelensis, in which expulsion is dependent on mucosal mast cells, were infected concurrently with N. brasiliensis, testosterone-treated animals could expel S. venezuelensis worms by Day 18, but failed to expel N. brasiliensis. Histologically, mast cell hyperplasia was associated with expulsion ofS. venezuelensis, while goblet cell responses were suppressed. From these results, testosterone seems to suppress proliferation/function of goblet cells but does not affect mast cells ofM. meltada.     

Induction of Suppressor T Cells by Anti-Globoside Antibodies in Cancer Sera

T cells treated with cancer sera frequently suppressed immunoglobulinproduction by autologous lymphocytes stimulated with pokeweedmitogen. Sera from healthy individuals did not induce suppressoractivity. This suppression is not caused by T_G cells (T cellsbearing receptors for the Fc portion of immunoglobulin G [IgG])interacting with immune complexes, because we used T cells depletedof T_G cells. The suppressor-inducing factors were separatedinto an IgG-containing fraction and a fraction with a smallermolecular weight. IgG fractions from all sera that were positivefor anti-globoside antibody induced suppressor T cells, andelimination of the anti-globoside antibody from these IgG fractionsreduced the ability to induce suppressor T cells. T cells treatedwith rabbit anti-globoside antiserum also activated suppressorT cells. These observations indicate that the antibodies directedto the globoside antigen on suppressor T cells stimulate thesuppressor T cells, and that anti-globoside antibody in cancersera may play a role in causing immunodeficiency in cancer patients.     

CASE REPORT: Insulin - like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.