Use of Enzymatic Activity for Design of Orally Administered Enteric Dosing Forms

Abstract— Liquid and semi-solid enteric dosage forms were prepared by entrapping drug with an appropriate partition coefficient in a lipid base vehicle which would then be released by the action of intestinal enzymes. Lipid ester derivatives such as glyceryl monocaprylate and polysorbate 80 were used as vehicles. These vehicles readily dissolved the poorly water-soluble compounds used in the study, itazigrel, indomethacin and the dye, sudan II, and were digested by lipase and esterase, releasing the test drugs with time profiles similar to those observed in dissolution studies. The vehicles released little or only a small amount of the drugs into aqueous medium in the absence of an appropriate enzyme. The enzyme-sensitive enteric vehicles when containing sudan II did not release the dye in the stomach of rats after oral administration, but released significant amounts of the dye in the small intestine.     

Smoking behaviour and personality: a population-based study in Japan

Abstract Aims . The aim of our study was to determine whether the previously reported findings also apply to a general population in Japan and whether, among current smokers, such personality characteristics can be correlated with the age they started to smoke and their present daily consumption of cigarettes . Design . Cross-sectional survey . Setting . Miyagi prefecture, in northern Japan . Participants . 20 538 residents in Miyagi, aged 40-64 years . Measurement . A self-administered questionnaire involving smoking status (current, ex- and non-smokers) and patterns and the Japanese version of the short-form Eysenck Personality QuestionnaireRevised (EPQ-R) . Findings . (1) Current and ex-smokers were higher on Extraversion and Psychoticism than non-smokers for both genders. (2) Heavy smokers were higher on Psychoticism than light smokers and those who started to smoke prior to the legally permitted age were higher on Psychoticism than those who did not . Conclusions . (1) Our study confirmed that the findings which had been previously reported in selected samples in western countries also apply to a general population in Japan; (2) current smokers were found to be heterogeneous in terms of Psychoticism when the age they started to smoke and their present daily consumption of cigarettes were taken into account.     

A Case of Widely Split Double P Waves with Marked Intra-Atrial Conduction Delay

Widely Split Double P Wave. We report a 78-year-old man as the first documented case of double P waves separated by 400 msec on 12-lead ECG. These P waves had different polarities on lead V₁. The first P wave represented activation of the lateral wall of the right atrium, and the latter P wave represented activation of the nudial right atrium and the left atrium. Widely spaced double potentials were recorded craniocaudally along the line, presumably corresponding to the crista terminalis during sinus rhythm. For this to occur, conduction disturbance has to be present both in the upper and lower right atrium. Conduction disturbance in the upper right atrium would interrupt excitation from the sinus node to the medial wall, and conduction disturbance in the lower right atrium would interrupt excitation spreading from the lower lateral right atrium to the isthmus area where fragmented potentials were recorded. These multiple discrete lesions appear to constitute a unique electrical atriopathy in this patient.     

The Inhibitory Effects of Cephalosporin and Dipeptide on Ceftibuten Uptake by Human and Rat Intestinal Brush-border Membrane Vesicles

Abstract— The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H⁺-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent K_m and V_max values of 0·35 min and 2·052 nmol (mg protein)^?1 min^?1 for human BBMV, and 0·50 mm and 3·056 nmol (mg protein)^?1 min^?1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver–Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.     

A rupture of lung metastasis of hepatocellular carcinoma causing haemothorax

A 67 year old male with non-resectable hepatocellular carcinoma (HCC) in both lobes and liver cirrhosis was treated with transcatheter arterial embolization and regional chemotherapy. He was doing well for 18 months. He was readmitted for fever, chest pain and multiple pulmonary metastases. During interleukin-2 therapy, he suddenly developed dyspnoea and palpitation, and was in shock. Left-sided haemothorax was confirmed by draining 3 L of fresh blood. In spite of intensive care, he died within 36 h. Autopsy showed that the haemothorax was caused by rupture of one of the metastases in the upper lobe of the left lung, and that the primary HCC was totally necrotic. Survey of the literature failed to find a report of fatal bleeding from a lung metastasis of HCC.     

Electrostimulation of sympathetic nerve fibers during nerve-sparing laparoscopic retroperitoneal lymph node dissection in testicular tumor

A long-handled pair of electrodes with sufficient length to allow stimulation during laparoscopic retroperitoneal lymph node dissection (RPLND) was designed at our institute. We clinically utilized this electrode in the treatment of a 37-year-old patient with testicular tumor who underwent right orchidectomy and nerve-sparing laparoscopic RPLND. During laparoscopic RPLND, sympathetic nerve fibers relevant to ejaculation were electrically stimulated and changes in pressure at the bladder neck were observed. Nerve preservation was confirmed by increased pressure at the bladder neck and ejaculation immediately after the electrostimulation. The application of laparoscopic electrostimulation may become widespread, particularly since it meets the increasing demand for minimally invasive surgery.