Satoru Mineshita

Preventive Effects of Unsei‐in and Oren‐gedoku‐to, Chinese Traditional Medicines, Against Rat Paw Oedema and Abdominal Constriction in Mice

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 Behçets 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.

Serum Albumin for Estimating Creatinine Clearance in the Elderly with Muscle Atrophy

The present study was conducted to develop a special formula to predict creatinine clearance (CCr, ml/min) in the elderly with chronic muscle atrophy using serum albumin (Alb, g/dl). We obtained 90 data sets including actual body weight (BW, kg), urinary creatinine excretion (UCr, mg/24 h), serum creatinine (SCr, mg/dl), and Alb from 90 inpatients aged 60-92 years. Regression equations were determined between the dependent variable of UCr/BW and the explanatory variable of Alb as follows: For males Ucr/BW = 2.695 Alb + 4.665 For females Ucr/BW = 1.827 Alb + 4.146. Then, the new predictive formula was derived from the equations: For males CCr = (19Alb + 32)BW/(100 x SCr) For females CCr = (13Alb + 29)BW/(100 x SCr). Evaluations for the predictive error (predicted CCr- measured CCr) showed that the new formula could provide more accurate and less biased estimates of CCr than the Cockcroft and Gault formula could, even in patients with renal insufficiency and in those with Alb < or = 2.8 g/dl.

The effect of Oren-gedoku-to on experimental colitis in rats.

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 Crohns disease in man.

Use of salivary acetaminophen concentration to assess gastric emptying rate of liquids

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 (tmax), the concentration at 0.75 h (C0.75), the area under the curve from 0 to 1.0 h (AUC1.0), and the AUC0.5/AUC2.0 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 tmax, 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 tmax with minimal distress to the patient.

Intestinal Behçet's disease associated with non-Hodgkin's lymphoma.

A 45-year-old man with intestinal Behçets disease noticed an enlarged right cervical lymph node, and was diagnosed with diffuse large cell type, non-Hodgkins lymphoma. The intrapelvic lymph tract was markedly deformed because of recurrent ileocecal ulceration, and conventional lymphoscintigraphy with a common tracer did not abolish the suspicion that lymphoma cells may have invaded the lymph nodes. Dynamic lymphoscintigraphy with a new tracer,99mtechnetium-diethylene triamine pentaacetic acid-human serum albumin, because of its high detection sensitivity, was very useful for excluding this suspicion, and for determining the clinical stage of lymphoma. Combination induction chemotherapy led to complete remission without any adverse effects, but subsequent supportive therapy with same protocol could not be completed because of progression of the intestinal lesions. Special management for the intestinal lesions, such as bowel rest, may be essential with chemotherapy for patients with intestinal Behçets disease.

Effects of Oren‐gedoku‐to and Unsei‐in, Chinese Traditional Medicines, on Interleukin‐8 and Superoxide Dismutase in Rats

This study was conducted to elucidate the mechanisms of action of two Chinese traditional drugs, Oren‐gedoku‐to and Unsei‐in, which have been used for many years in the treatment of inflammatory disorders.

Pharmacokinetic interaction between acetaminophen and lansoprazole

Because of its minimal gastric toxicity, acetaminophen is the analgesic of choice for patients with gastric acid-related disorders. Because proton pump inhibitors are widely used, concomitant prescription of acetaminophen and lansoprazole would be prevalent. This crossover study was conducted to investigate an acetaminophen-lansoprazole interaction. On one occasion, each of six healthy, fasted, male volunteers ingested 1.0 g acetaminophen dissolved in 200 mL water. On another occasion, at least 1 week apart, 30 mg lansoprazole was administered orally, simultaneously with acetaminophen, after pretreatment with the same dose of lansoprazole once daily for 2 days. Plasma acetaminophen concentrations were measured at 0, 0.25, 0.5, 0.75, 1, 2, 3, 5, and 8 hours after dosing. The peak plasma concentration of acetaminophen and the time to its occurrence were significantly higher and shorter, respectively, during the lansoprazole session than during the control session. Neither the elimination half-life nor the area under the curve was significantly different between the two sessions. Lansoprazole hastens the absorption of acetaminophen solution, but little modifies its elimination rate and bioavailability.

Gastric emptying of liquids is delayed by co-ingesting solids: a study using salivary paracetamol concentrations.

Background: Paracetamol concentrations in plasma, a frequently used index of gastric emptying (GE) of liquids, are closely correlated with those in saliva. GE of liquids is delayed by co-ingesting solids. No researchers have used salivary paracetamol concentrations to show this phenomenon. The aim of this study was to elucidate whether salivary paracetamol concentrations can detect the food-induced delay in liquid GE. Methods: Paracetamol absorption was measured twice in five healthy male volunteers. Following an overnight fast, they received 10 mg/kg paracetamol in 200 ml water alone on one occasion, and received this solution after consuming a 400 kcal-containing cookie on another occasion. After thorough rinsing of the month, 1 ml saliva was obtained, simultaneously with 2 ml blood, at 0, 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, and 6.0 h after paracetamol intake. The peak concentration (Cmax), the time to Cmax (tmax), the area under the curve (AUC), and Cmax/AUC in plasma were calculated. Salivary Cmax and tmax were also determined. Results: Plasma Cmax and AUC were not significantly different between the two occasions. In contrast, significant differences in plasma tmax and Cmax/AUC (P < 0.05) established the food-induced delay in GE. Salivary tmax could detect the delayed GE, whereas salivary Cmax could not. Conclusions: Salivary tmax can document the solid meal-induced delay in liquid GE.

The role of an uncommon type of oral streptococcus sanguis in the etiology of behcet's disease.

The relationships of Behcet’s disease (BD) with oral diseases and the prevalence of an uncommon type of oralStreptococcus sanguis (Str. sanguis) in the oral cavity were investigated in a case-control study. BD patients were compared to patient controls (collagen disease) and healthy controls.An interview questionnaire survey of BD and oral diseases showed that during the pre-onset, onset, and post-onset periods, the incidences of tonsillitis and dental caries, or the history of dental treatment, were greater in BD cases. Typological analysis showed a higher prevalence of an uncommon type ofStr. sanguis, differing from the common type, among BD cases compared to control groups. These results, showing a higher incidence of tonsillitis and dental caries during the presymptomatic period, a greater frequency of dental treatments during the symptomatic period, and the presence of an uncommon type ofStr. sanguis, indicate thatStr. sanguis of an uncommon type is related to increased risk of BD, and the possibility of a causal role is suggested.

Prevention by Minaprine of Ischemic Neuronal Damage and Memory Impairment in Mongolian Gerbils

This study examines the effect of the psychotropic drug minaprine on memory impairment in Mongolian gerbils subjected to a 5-min bilateral common carotid artery occlusion, as assessed by their performance in an 8-arm radial maze task. Gerbils were initially trained on the 8-arm radial maze until their mean error was 0-1 for 5 days. This task was repeated before the ischemia was performed and again 7 days after it. Then the animals were immediately sacrificed for histopathological examination. Severe memory impairment occurred in the control gerbils; whereas when minaprine 75 mg/kg was given orally 30 min before the 5-min occlusion, memory impairment was significantly reduced. Histopathological analysis of the control gerbils showed nearly complete loss of the pyramidal neurons in the CA1 region of the hippocampus, whereas the minaprine-treated gerbils showed complete preservation of the pyramidal neurons. These findings suggest that minaprine has memory-impairment-prevention and neuroprotective effects against short-term ischemia in gerbils.