Subchronic Oral Toxicity of Glyoxal via Drinking Water in Rats

Subchronic Oral Toxicity of Glyoxal via Drinking Water in Rats.Ueno, H., Segawa, T., Hasegawa, T., Nakamuro, K., Maeda, H.,Hiramatsu, Y., Okada, S., and Sayato, Y. (1991). Fundam. Appl.Toxicol. 16, 763–772. The subchronic oral toxicity ofglyoxal via drinking water and the effect on in vivo proteinsynthesis in tissues following a single treatment with thissubstance were assessed in Sprague–Dawley male rats. Animalsreceived drinking water containing glyoxal levels of 2000, 4000,and 6000 mg/liter ad libitum for 30, 60, and 90 days in PhaseI. In Phase II, the high-dose and control-1 groups fed the dietad libitum, and a diet-limited control-2 group given the sameamount of diet as consumed by the high-dose group were maintainedfor 90 and 180 days. The study designs included observationsof clinical signs, body weights, major organ weights, grossand histopathological examinations, serum clinical chemistry,and biochemical examinations such as glyoxalase activity andglutathione content in selected tissues. Body weight gain andorgan weights significantly decreased with dosage. Althoughconsumption of food and water was also depressed in the exposedgroup, the reduction of body weight gain was greater in thehigh-dose group than in the diet-limited control 2 group. Histopathologicalexaminations revealed only a slight papillary change in thekidneys from the high-dose group at both 90 and 180 days terminationsin Phase II. The induction of both glyoxalase I and II was observedin liver and erythrocytes at 30-day termination of the exposedgroups. Serum enzyme and protein levels were significantly reducedby the mid- and/or high-dose exposures. With a single oral high-dosetreatment of glyoxal, a great decline in the incorporation ofL-[³H]leucine was shown particularly in the liver, and thisprobably led in part to a reduction in the serum protein levelsin rats following subchronic exposure to glyoxal. These dataindicated an overall low degree of systemic toxicity to ratsexposed subchronically to glyoxal via drinking water.     

Membrane-bound complement regulatory activity is decreased on vaccinia virus-infected cells

Decay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 and mouse Crry are cell surface-bound complement regulatory proteins capable of inhibiting C3 convertase activity on cell membranes, and therefore provide a substantial protection from attack by homologous complement activated either by the classical or by the alternative pathway. Decrease in complement regulatory activity might lead to spontaneous complement deposition and subsequent cell injury. MoAb 512 can inhibit the complement regulatory activity of molecules on rat cells, resulting in deposition of homologous complement. The antigen recognized by 512 MoAb in rats is homologous to mouse Crry. Fifteen to 20 h after infection with vaccinia virus, in vitro cultured KDH-8 rat hepatoma cells show a strong decrease in expression of Crry-like antigen, and proved to be sensitive to complement deposition when 1:5 diluted normal rat serum was added to the culture medium as a source of complement. Addition of complement to the cultured KDH-8 cells infected with a very low dose of vaccinia virus (1 plaque-forming unit (PFU)/1000 cells) substantially reduced spreading of virus infection in the cell culture, while inactivation of complement by heat or zymozan treatment abrogated the protective effect.     

PROTO-ONCOGENE EXPRESSION IN HUMAN GLOMERULAR DISEASES

The expression of the protein products and mRNA of c- fos , c- myc , p53, and c- raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c- fos and c- myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.     

Accelerated ventricular rhythm in the newborn

Accelerated ventricular rhythm was observed in two newborn infants. Neither of them had any causative clinical symptoms for the ventricular arrhythmia. The arrhythmia disappeared when the infants were 18 days and 45 days old, respectively. Arrhythmia was noted in the fetal period, especially in case 1.     

Fetal valproate syndrome with reduction deformity of limb

A case is reported of a female infant having multiple anomalies, including epicanthic folds, hypertelorism, bifid nasal bridge, shallow philtrum, low-set ears, brain atrophy, cleft palate, hemangioma on the chest, and reduction deformity of the left upper limb. This is the first case where an infant who was exposed to sodium valproate intra-uterine has a reduction deformity of the upper limb.     

Hypertrophic cardiomyopathy in Noonan syndrome

Noonan syndrome, a well-known multiple congenital anomalies syndrome, is frequently accompanied by cardiovascular diseases including hypertrophic cardiomyopathy (HCM). The incidence of HCM in Noonan syndrome is approximately 20–30% and one-third of cases reveal ventricular outflow obstruction. HCM in Noonan syndrome is occasionally associated with a congenital heart defect, whereas classic HCM seldom accompanies cardiac malformations. Asymmetric septal hypertrophy and symmetric septal hypertrophy (concentric hypertrophy) can be observed both in HCM with Noonan syndrome and in classic HCM. but apical hypertrophy has not been reported in Noonan syndrome yet, although it appears in classic HCM. Congestive heart failure is the major cause of death in patients with HCM in Noonan syndrome, but cases of sudden death have also been reported. The histopathologic findings of ventricular myocardial tissue in HCM with Noonan syndrome are similar to those in classic HCM.     

Laparoscopy Assisted Colectomy with Extracorporeal Anastomosis

Abstract: Laparoscopy assisted colectomy with extracorporeal anastomosis was carried out in five patients. In three patients, the lesions were carcinoma with submucosal invasion and the histological results of the polypectomy specimen indicated the necessity of the subsequent colectomy. In the other two patients the lesions were either adenoma or carcinoma in adenoma. Under pneumoperitoneum, mobilization of the colon was performed using the laparoscopic technique. In three patients the mesenteric vessels of a segment of the colon were ligated and divided extracorporeally. In two patients the mesenteric vessels were clipped and divided intracorporeally. In all cases, extracorporeal resection of the colon and hand suture anastomosis were performed. Surgery time ranged from 3 hours and 20 minutes to 4 hours and 50 minutes. No postoperative complications were experinced. Four patients began to walk on the first postoperative day. Postoperative administration of analgesics was needed in four patients for two days or less after the operation. In all but one case, bowel sounds were audible from the first post-operative day onwards. In only one patient was the postoperative recovery delayed. Although sufficient future studies should be accumulated to confirm the advantages of this procedure, we can expect that laparoscopy assisted colectomy will become a useful procedure for benign and early malignant lesions in which colonoscopic removal was not possible or was suspected to be insufficient. (Dig Endosc 1944; 6 : 52–58)     

Thrombocytopenia associated with platelet-associated immunoglobulin G in alcoholic hepatitis

Abstract A 45 year old Japanese man with alcoholic hepatitis developed thrombocytopenia together with an increase in the level of platelet-associated immunoglobulin G (PAIgG). Bone marrow aspiration revealed a normal nucleated cell count and a slight increase of megakaryocytes. After abstinence from alcohol, laboratory and symptomatic improvement occurred in association with a prompt increase in the platelet count and a corresponding decrease of PAIgG. These findings suggest that PAIgG may have been involved in the development of thrombocytopenia in this patient.     

Hepatocellular carcinoma in 13 patients with hepatitis C virus-associated chronic hepatitis

Abstract Thirteen of 81 patients with chronic hepatitis and positive hepatitis C virus (HCV) antibody developed hepatocellular carcinoma (HCC) during a follow-up period of 54 ± 38 months. The histopathological findings in HCC-bearing liver in these patients included six cases of chronic persistent hepatitis [CPH; mean hepatitis activity index (HAI) score: 5.8] and seven cases of chronic aggressive hepatitis (CAH) 2A, or 2B (HAI) score: 13.6). Multiple biopsies of the liver in six cases revealed that five cases, including four with CPH at the time of HCC diagnosis, previously had histopathological findings identical to CAH 2A, and another case constantly had CPH during the 8-year follow-up. These findings suggest that HCV-associated HCC can occur even in patients with HCV antibody positivity and inactive or mild chronic hepatitis. This is of interest in the pathogenetic mechanisms of HCV-associated HCC.