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.     

Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible nitinol stent

In order to treat fistulated esophageal cancer using a flexible stent, a covered flexible stent was constructed by wrapping a nitinol stent with a thin sheet of Gore-Tex, preserving the stents original advantages of flexibility and a low-profile introducer system. This stent was used to perform standard radiotherapy in a case of fistulated esophageal cancer.     

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.     

Effects of Zinc on Production of Active Oxygen Species by Rat Neutrophils

Abstract: The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemilumi-nescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O₂^? and H₂O₂ production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O₂^? and H₂O₂ production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O₂^? production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O₂^? production through the classical signal transduction pathway, and by increasing H₂O₂ not via O₂^?.     

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.     

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.     

Effects of multipurpose solutions (MPS) for hydrogel contact lenses on gap-junctional intercellular communication (GJIC) in rabbit corneal keratocytes

To ensure the effects of multipurpose solutions (MPS) for hydrogel contact lenses on the cornea, the inhibitory activity of three types of MPS on corneal cells has been evaluated with the use of scrape loading and dye transfer assay (SLDT assay) and Western blotting on rabbit corneal keratocytes (RC4). In SLDT assay, MPS-A and poloxamine showed dose-dependent inhibitory activity, suggesting the inhibitory action of MPS-A and poloxamine to gap junctional intercellular communication (GJIC) in the tested cells. Moreover, after treatment with MPS-A, the GJIC was initially inhibited within 4 h, and thereafter gradually turned to an approximately 60% level of the initial value. When MPS-A was removed from the incubation media after exposure of the cells, the recovery of GJIC was time dependent and returned to approximately initial levels at 8 h. Complete recovery was established after approximately 24 h. These findings suggested that the inhibitory action of MPS-A on corneal keratocytes was reversible. This inhibition was accompanied by a decrease in the quantity of connexin-43, which is a major protein constituting the gap junctional channel of these cells, and its change in the phosphorylation state. Taken together, it was suggested that MPS-A interacts with connexin-43, inducing an inhibitory action on GJIC.