Bioavailability of mefenamic acid: influence of food and water intake

The influence of food and water intake on mefenamic acid (N-2,3-xylylanthranilic acid) bioavailability from commercial capsules of high bioavailability was studied in four healthy male volunteers. The drug was administered as a single oral dose of 250 mg, under fasting or nonfasting conditions, and a 4 X 4 Latin-square design was used. Eight blood samples were collected over a 24-h period following drug administration, and the drug plasma concentrations were determined by HPLC. The bioavailability of mefenamic acid from capsules was markedly influenced in the fasting subjects by the water but not by the food intake. A good correlation was found between the bioavailability and amount of water ingested with the drug in the fasting subjects. The area under the plasma concentration-time curve (AUC0-infinity) of mefenamic acid was highest when the capsule was taken with 50 mL of water or immediately after a meal. Increasing the amount of water from 50 to 500 mL in the fasting subjects caused a significant reduction in AUC0-infinity.     

Five percent, 7.5% or 10% hypertonic saline prevents delayed neuronal death in gerbils

PURPOSE: To clarify the appropriate concentration and dose of hypertonic saline solution (HSS) for preventing delayed neuronal death in the hippocampal CA1 subfield after transient forebrain ischemia in gerbils. METHODS: Thirty gerbils were randomly assigned to five groups: physiological saline solution (PSS) group, ischemia/reperfusion treated with PSS 2 mL x kg(-1); 5% HSS group, treated with 5% HSS 2 mL x kg(-1); 7.5% HSS group, treated with 7.5% HSS 2 mL x kg(-1); 10% HSS group, treated with 10% HSS 2 mL x kg(-1); 20% HSS group, treated with 20% HSS 2 mL x kg(-1). Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for four minutes. Five days later, histopathological changes in the hippocampal area were examined, and the degenerative ratio of the pyramidal cells were measured according to the following formula: (number of degenerative pyramidal cells/total number of pyramidal cells per 1 mm of hippocampal CA1 subfield) x 100. RESULTS: In PSS and 20% groups, neuronal cell damage was observed five days after ischemia. In the other three groups, these changes were not observed. The degenerative ratios of pyramidal cells were as follows; PSS group: 91.6 +/- 5.6%, 5% HSS group: 7.2 +/- 1.6%, 7.5% group: 8.3 +/- 1.4%, 10% HSS group: 6.2 +/- 1.1%, 20% HSS group: 85.8 +/- 8.7% (P < 0.05; PSS and 20% HSS vs three other groups). CONCLUSION: This study demonstrates that 5, 7.5 or 10% HSS 2 mL x kg(-1) may prevent delayed neuronal death in the hippocampal CA1 subfield after cerebral ischemia/reperfusion in gerbils.     

Drug-induced hypersensitivity nephritis: lymphocyte stimulation testing and renal biopsy in 10 cases

The pathomorphological and clinical findings were investigated in 10 cases of drug-induced hypersensitivity nephritis. Hypersensitivity due to drugs was strongly suggested by the lymphocyte stimulation test in all patients. The offending drugs included penicillin, cephem derivatives, nonsteroidal anti-inflammatory drugs, and minocycline. All patients developed acute renal failure shortly after administration of regular doses of the drugs. Allergic symptoms plus a raised level of serum IgE or eosinophilia were seen in 7 patients. The remaining 3 patients receiving nonsteroidal anti-inflammatory drugs had no allergic symptoms, but developed severe proteinuria. Eight patients without severe glomerular damage recovered after withdrawal of the offending drugs and temporal dialysis and/or steroid therapy. Renal biopsies revealed tubulitis and tubular epithelial degeneration with interstitial edema as the common characteristic findings. Granulomatous lesions were occasionally observed. Multinucleated giant cells found in the granulomas were positive for LN-3 which is compatible with HLA-DR antigen. The glomeruli appeared normal, except in 2 cases in whom crescentic glomerulonephritis and thrombotic microangiopathy were seen. Our study suggests that the lymphocyte stimulation test and renal biopsy are the most useful means to confirm the diagnosis and provides further evidence for the participation of cell-mediated immunity in the pathogenesis of drug-induced hypersensitivity nephritis.     

Tissue distribution and excretion of hexabromobenzene and its debrominated metabolites in the rat

Tissue distribution and excretion of hexabromobenzene (HBB) and some metabolites were studied in male Wistar rats administered a single oral dosage of HBB.Most of the HBB dosage was absorbed by the intestinal tract and it was rapidly metabolized and distributed throughout the body as the debrominated metabolites, pentabromobenzene (PeBB), tetrabromobenzene (TeBB) and tribromobenzene (TrBB). The time courses of HBB, PeBB and TeBB concentrations in the tissues were roughly classified into several types, and debromination of HBB was found to take place stepwise.The reductive debromination of HBB occurs by metabolic enzymes in the liver rather than microbes in the intestine.     

Rapid spontaneous postpartum remission in a case of chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy]

A 28-year-old woman developed numbness and weakness of the hands and arms when she was 8 months pregnant, and weakness worsened gradually. However, weakness started to spontaneously subside immediately after delivery and she felt almost recovered several hours later. But weakness and numbness recurred one week after delivery and she was admitted to our hospital. Neurological examination revealed moderate weakness and disturbance of the deep and cutaneous sensations in the upper and lower extremities, and marked decrease of the deep tendon reflexes. The upper extremities were more severely affected. Nerve conduction study showed marked decrease in the motor conduction velocities. Cerebrospinal fluid showed increase of protein without pleocytosis. Teased preparation of the biopsied sural nerve showed occasional internodal segments with thin myelination, indicating demyelination and remyelination. A diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was made. Treatment with prednisolone markedly improved the weakness and hyporeflexia as well as the cerebrospinal fluid protein. Postpartum rapid remission may have been produced by rapid increase of endogenous steroid hormone in the blood by its massive excretion during delivery.     

Seborrhoeic Dermatitis: Treatment with Anti-Mycotic Agents

In order to elucidate the effectiveness of anti-mycotics in treating seborrhoeic dermatitis, an attempt was made to isolate Malassezia from seborrhoeic lesions of patients of seborrhoeic dermatitis. The results revealed that, in male patients, 46/49 cases were positive for Malassezia furfur on the face and 30/48 cases were positive for M. furfur on the scalp. In female patients, 7/13 cases were positive for M. furfur on the face, and 6/17 cases were positive for M. furfur on the scalp. Anti-mycotic agents were excellent in 50% and good in 31% of the spore-positive cases, yielding an overall efficacy rate of 81%. In contrast, the treatment of the face with vehicle alone showed only one excellent result out of 8 cases. Although clinical improvement was rapid on the side treated with a topical corticosteroid in the half-side-test, numerous fungal elements remained. While the improvement with anti-mycotic agents was slower than that with the corticosteroid, clinical improvement became evident by the third week of administration and fungal elements disappeared.     

Mucin-producing Bile Duct Tumor of the Caudate Lobe Protruding into the Common Hepatic Duct

Mucin-producing tumor in the bile duct is referred to clinically as mucin-producing bile duct tumor (MPBT). Intraductal papillary neoplasm of the biliary tract that resembles an intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a rare category of MPBT and is not well characterized. We, herein, report a case of MPBT of the caudate lobe of the liver that showed papillary growth and communicated with the bile duct of the caudate lobe and protruded into the common hepatic duct. Histologically, MPBT cells showed papillary overgrowth with abundant mucinous secretions, resembling an IPMN of the pancreas. The MPBT cells showed the same immunostaining pattern as that of cells from IPMN of the pancreas.     

Chromosomal Mapping of Genetic Locus Associated with Thymus-size Enlargement in BUF/Mna Rats

The thymoma-prone rat of the BUF/Mna strain is a useful model for human thymoma. In this strain thymoma development is regulated by a single autosomal susceptible gene, Tsr-1. At pre-thymoma age, BUF/Mna rats have extremely large thyrauses, when compared to those of other strains of rats. Genetic studies in crosses between BUF/Mna rats with large thymuses and WKY/NCrj rats with small thymuses suggested the presence of a major autosomal gene, Ten-1 , which contributes to thymus enlargement in a backcross population. Linkage studies between Ten-1 and microsatellite markers in backcross rats of (WKY/NCrj×BUF/Mna)Fl×BUF/Mna have led to the localization of Ten-1 in chromosome 1. This result may provide an approach to clone Tsr-1 , which could be allelic to Ten-1.     

Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic,renal, cerebral,and coronary circulation of dogs anesthetized with enflurane

Summary In beagle dogs anesthetized with enfluranenitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1–10 g/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3–10 g/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs.