Pharmacokinetics of a new histamine H2-receptor antagonist,Z-300, in rat and dog

1. The plasma level of Z-300 reached a maximum (C_max) at 30?min after the oral administration of Z-300 to dog, and disappeared from the systemic circulation with a halflife of 8-9 h. The bioavailability of Z-300 was 52% after the oral administration of Z-300, 3?mg/kg. At doses ranging from 3 to 30?mg/kg, C_max and AUC (area under the plasma concentration-time curve) were proportional to the dose. 2. The plasma level of Z-300 reached C_max at 10?min after the oral administration of Z-300 to rat, and disappeared from the systemic circulation with a half-life of 0.8-1.6 h. The bioavailability of Z-300 was 39% after the oral administration of Z-300, 10?mg/kg, and there was a non-linear relationship between the plasma level-time profile of Z-300 and the administered dose (3-50?mg/kg). 3. The binding of Z-300 to plasma protein was 92% in man, 65% in dog and 25% in rat. It is suggested that these species differences were due to the content of α₁-acid glycoprotein (α₁-AG), because Z-300 bound more strongly to α₁-AG than to albumin.     

[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole

Background  ¹³CO₂ is produced on metabolism of ¹³C-labelled-pantoprazole ([¹³C]-pantoprazole) by CYP2C19.
Aim  To investigate whether the [¹³C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese.
Methods  We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [¹³C]-pantoprazole. Changes in the carbon isotope ratios (¹³CO₂/¹²CO₂) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio (‰). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole.
Results  The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve ( AUC )_20–60 min of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC _20–60 min of DOB.
Conclusions  [¹³C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI.     

A Case of Pneumatosis Cystoides Intestinalis Associated with Trichlor-oethylene Developing Typical Features during the Follow-up of Undetermined Sigmoid Lesions

Abstract: A 64-year-old male lens grinder with a 43-year history of occupational exposure to trichloroethylene (TCE) visited Shinshu University Hospital in December 1988 complaining of distention of the lower abdomen. A barium enema study and endoscopic examination showed rosary-like semilunar folds and edematous mucosa of undetermined etiology in the sigmoid colon. Three months later, the patient visited the hospital again complaining of blood in the stool. An endoscopic examination performed at this time revealed numerous broad-based, smooth-surfaced, protruding lesions in the sigmoid colon. A diagnosis of pneumatosis cystoides intestinalis (PCI) associated with TCE was made. After 4-days treatment with 50% oxygen given by inhalation, the patient's symptoms were completely relieved, and a colonoscopy revealed no evidence of PCI. He returned to his job at the factory which involved dealing with TCE and because of adequate ventilation and a shorter work-day he has been free of recurrence during a year follow-up period. The finding of rosary-like semilunar folds, as demonstrated by the initial endoscopic and barium enema studies in our patient, is a peculiar one in the incipient stage of PCI.     

Changes in work performances in obstructive sleep apnea patients after dental appliance therapy

Abstract The effects of dental appliances on work performances of obstructive sleep apnea syndrome (OSAS) is not well examined. This study evaluated the polysomnographic and psychological findings before and after therapy. Nine patients were diagnosed OSAS by nocturnal polysomnography. The psychological battery was performed from 13:00 to 14:00, which consisted of Uchida-Kraepelin psychodiagnostic test (U-K's test) and Bourdon's cancellation test (Bourdon's test). Approximately 3 months after the treatment, the examinations were performed. Apnea and desaturation index decreased significantly after the therapy. In addition, sleep architecture improved after the therapy compared with that before the therapy. Dysfunction of task performances, such as mean level of work amounts in U-K's test, mean error, mean performance time and mean deviation in Bourdon's test improved after therapy. We conclude that dental appliances therapy is effective not only to apnea but also to work performance in OSAS.     

Relation of dietary preference to bite force and occlusal contact area in Japanese children

Summary  The purpose of this study was to examine the relationship of dietary preference to bite force and occlusal contact area in Japanese elementary school children. A total of 348 children, aged 7–12 years, from two public elementary schools located in Okayama Prefecture, Japan, participated in the study. Clinical examination included decayed, missing and filled teeth (dmft and DMFT), and total numbers of deciduous and permanent teeth. Bite force and occlusal contact area were measured using a pressure-detecting sheet. Dietary preference was assessed using a questionnaire in which the answers were given in like/dislike form. Mann–Whitney U- test and multiple logistic regression analysis were applied to analyse the data. In multiple logistic regression analysis after adjustment for age, gender and total number of teeth present, children who liked cabbage and celery showed significantly higher bite force ( P  =   0·05 and P  <   0·01, respectively) than those who disliked these. Children who liked cabbage and celery also showed higher occlusal contact area ( P  <   0·05 and P  <   0·01, respectively) than those who disliked these. The Japanese elementary school children who liked hard foods such as cabbage and celery showed higher bite force and higher occlusal contact area than those who disliked these foods. A positive attitude towards harder food items might contribute to healthy development of the masticatory apparatus.