No abstract

The gastric emptying rate (GER) of liquids can be quantified by calculating the rate of acetaminophen absorption from serial plasma concentrations. As acetaminophen concentrations in saliva are well correlated with those in plasma, the salivary concentrations may be suitable for use in GER measurement. To evaluate such suitability, salivary and plasma samples were simultaneously obtained from seven healthy volunteers at 0, 0.25, 0.5, 0.75, 1.0, 1.5, and 2.0 h after they had ingested 20 mg/kg of acetaminophen mixed with a 200-ml liquid meal (200 kcal). Commonly used parameters for the rate of acetaminophen absorption were calculated from the salivary and plasma data, including the maximum concentration (Cmax), the time to Cmax (t(max)), the concentration at 0.75 h (C0.75), the area under the curve from 0 to 1.0 h (AUC1.0), and the AUC(0.5)/AUC(2.0) ratio. The mean (SD) salivary/plasma concentration ratio was 2.48 (1.47) at 0.25 h, and the means were almost unity afterwards. Significant correlations between saliva and plasma were found in all parameters studied (r = 0.77-0.90; P < 0.05). However, except for t(max), the salivary parameters overestimated those of plasma. The present results suggest that: (1) the salivary acetaminophen concentration at 0.25 h (C0.25) is a poor reflection of plasma C0.25 (2) thereby the parameters embodying salivary C0.25 such as AUC1.0 and the AUC0.5/AUC2.0 ratio, are unreliable, and (3) liquid GER can be assessed by salivary t(max) with minimal distress to the patient.

Serum interleukin-8 (IL-8) production was measured in 43 Adamantiades-Behçet's disease (A-BD) patients and in 46 healthy volunteers using a sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the patients (14.6 +/- 3 pg/ml) was significantly higher than that of controls (10.8 +/- 3 pg/ml, P < 0.05). Since IL-8 is known to have proinflammatory properties, it may play some role in the pathogenesis of A-BD. We also investigated the activity of serum superoxide dismutase (SOD) in the 43 patients with A-BD and in the 46 healthy volunteers. Serum SOD activity was markedly increased in the patients with A-BD (13.1 +/- 3%), especially in active A-BD, compared with that in the healthy volunteers (6.7 +/- 3%, P < 0.01). Our results suggest the involvement of IL-8 and SOD in the pathogenesis of A-BD as seen in other inflammatory diseases.

The effects of antipyrine (1200 mg day‐1), phenobarbitone (100 mg day‐ 1) and rifampicin (600 mg and 1200 mg day‐1, respectively) administration for 7 days on sparteine metabolism and 6 beta‐ hydroxycortisol excretion were studied in panels of extensive (EM) and poor metaboliser (PM) subjects. Drug metabolism was induced in both EM and PM subjects by antipyrine and rifampicin pretreatment as indicated by increased excretion of 6 beta‐hydroxycortisol. A 30% increase in metabolic clearance of sparteine was observed in EM subjects following rifampicin administration whereas in PM subjects no effect on the overall elimination of the drug was seen. The data indicate that the regulation of cytochrome P‐450 isozyme involved in polymorphic debrisoquine/sparteine metabolism is predominantly under genetic control and that enzyme induction exerts only a marginal effect.

Endothelin (ET)-1, a potent vasoconstrictor peptide derived from the endothelium, is markedly increased in endotoxic shock, although the pathophysiological role of ET-1 under septic conditions remains obscure. To delineate the role of ET-1 and its receptor subtype in endotoxic shock, we here attempted to determine the changes of circulating levels of ET-1 and its biosynthetic intermediate big ET-1 in endotoxic shock rats, to evaluate the gene expression of ET-1 as well as the ET-1 receptor subtypes (ETA and ETB) in the heart, lung and liver, and to study the effects of ET receptor antagonists on systemic arterial blood pressure, heart rate and survival rate. Administration of bacterial lipopolysaccharide (LPS) caused profound hypotension, increased heart rate and death, and these effects were blocked by a nonselective ETA/ETB receptor antagonist (TAK044), but not by an ETA selective antagonist (BQ123). Administration of exogenous ET-1 caused a profound pressor response in control rats, but not in the LPS-pretreated rats. Injection of LPS caused marked elevation of plasma levels of both ET-1 and big ET-1, which were not affected by treatment with either ET receptor antagonist. Administration of LPS caused up-regulation of ET-1 and ETB receptor mRNA in the heart, whereas ETA receptor mRNA was markedly down-regulated in the heart, lung and liver. These data suggest differential gene regulation of ET-1 and its receptor subtypes in various organs from endotoxic shock rats, and that nonselective ETA/ETB receptor antagonist, but not ETA receptor antagonist, ameliorates endotoxin-induced hypotension and death.

No abstract

Oren-gedoku-to and Unsei-in are complex mixtures of ingredients derived from plants. These two drugs are clinically most frequently used in the treatment of Behçet's disease, we have investigated the anti-inflammatory and analgesic actions of Oren-gedoku-to and Unsei-in using a battery of tests; rat paw oedema induced by five different agents; abdominal constriction; mouse ear swelling; and dye leakage tests, designed to clarify the therapeutic potential of these medicines. The findings in this study that these medicines are able to inhibit the rat paw oedema, suppress the abdominal constriction and inhibit the increased dye permeability confirm the analgesic and anti-inflammatory effects of these compounds. From these results there seems a clear rationale for exploring the effectiveness of these Chinese medicines in the treatment of chronic and acute inflammatory diseases.

In Japan and China, Oren-gedoku-to (a complex mixture of ingredients derived from plants) has been used as a herbal medicine in the treatment of inflammatory and ulcerative diseases. In other countries salicylazosulfapyridine has been used to treat inflammatory bowel disease. In this study, we have compared the effect of Oren-gedoku-to with salicylazosulfapyridine on trinitrobenzene-sulphonic acid-induced colonic damage in rats, a model representative of ulcerative colitis and Crohn's disease in man. Oren-gedoku-to was administered orally for one or two weeks over a range of doses. Tissue damage scores, body weight, spleen weight, colon wet weight and colon wall thickness were measured, and colonic tissue levels of interleukin-8 (IL-8), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and myeloperoxidase activity were examined. The results indicated that Oren-gedoku-to was effective in the treatment of inflammatory bowel disease in the rat model. Histological observation showed a quicker healing process of the lesions, and a reduction of inflammatory cell infiltration following administration of Oren-gedoku-to. The precise mechanism of action for Oren-gedoku-to is still unclear; however, the reduction of IL-8, LTB4, and PGE2 observed suggests that the mechanism may be different from salicylazosulfapyridine (which has no effect on IL-8). There may be a potential benefit in offering combination therapy for the treatment of inflammatory bowel disease.