Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro

Abstract— We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin » clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.     

Short-period Double-dosing for Simultaneous Evaluation of Intestinal Absorption and Hepatic Disposition in a Single Conscious Rat Using Cephalexin as Test Drug

A new method has been developed for simultaneous evaluation of local absorption from the intestine into the portal system and local disposition through the liver, and for assessment of the bioavailability of a drug in a single conscious rat. The method is based on the difference between plasma concentrations in portal and systemic blood (PS method). Because cephalexin is known to be absorbed completely from the intestine and not to be eliminated through the liver, it was used as test drug to confirm the validity of the new method. The portal vein and the femoral artery of a rat were simultaneously cannulated and blood samples were obtained from both sites. Two methods of administration, single-dosing and double-dosing, were investigated and the efficacy of double-dosing (DD) was demonstrated. Rats received an intra-arterial (group A) or oral (group B) dose in single-dosing, whereas rats used for double-dosing received an oral dose 3 h after an intra-arterial dose (group C). After administration of cephalexin, the portal and arterial plasma concentrations were determined by HPLC. Groups A and B were monitored for 4 h and group C for 8 h. The portal-blood flow rate was measured by means of an electromagnetic flow-meter. Global and local moments were calculated by trapezoidal integration with extrapolation to infinite time. On the basis of the PS method, the local absorption ratio (F_a) and the mean local absorption time (t?_a) were estimated to be 0.975 ± 0.104 and 2.19 ± 0.51 h, respectively, in group B. By comparing the averaged moments between groups A and B, the extent of bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F_H) were calculated to be 1.01, 1.92 h and 1.04, respectively. The mean hepatic transit time (t?_H) was negligible. In group C, F_a = 0.936 ± 0.107, t?_H = 1.55 ± 0.32 h, F = 1.08 ± 0.07, MAT = 1.55 ± 0.40 h and F_H = 1.17 ± 0.14 h, the mean values being close to those from groups A and B. In conclusion, the PS method with short-period double-dosing (PS-DD method) can offer an effective means of evaluating the local absorption kinetics of drugs, because F, MAT and F_H are obtained from a single conscious rat, and consequently the standard deviations of the quantities can be quickly estimated.     

Case Report: Fibrolamellar hepatocellular carcinoma in a Japanese woman: A case report and review of Japanese cases

Fibrolamellar hepatocellular carcinoma (FLHCC) is an entity distinct from ordinary hepatocellular carcinoma and is very rare in Oriental countries. We present here a Japanese case of FLHCC in a 25 year old woman, and review Japanese cases of FLHCC. The patient had mild abdominal pain when the hepatic tumour was revealed by ultrasonography. Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody were negative and serum alpha-fetoprotein (AFP) was within the normal limit. Ultrasound-guided fine needle biopsy was performed and the tumour was histologically diagnosed as FLHCC. A right lobectomy of the liver was then performed. Macroscopically, the tumour (10 × 10 times 8 cm) was circumscribed, rather hard and yellowish white. Microscopically, neoplastic hepatocytes were polygonal and large with eosinophilic cytoplasm, which contained pale bodies. A number of fibrous stroma were arranged in thin parallel bands. Consequently, the case was diagnosed as FLHCC. In Japan, approximately 18 000 people die of ordinary hepatocellular carcinoma annually, while only nine cases (including the present case; six males, three females) of FLHCC in Japanese subjects have been reported previously. The mean age of the Japanese cases of FLHCC is 20.9 years old. One case with positive HBsAg, liver cirrhosis and high level of AFP was observed of nine cases. The nature of FLHCC in Japanese subjects may not be significantly different from that in Caucasians, except for male predominance.     

Endoscopic retrograde cholangiopancreatography in paediatric patients with biliary disorders

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty-two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.     

The Role of Mammalian Intestinal Bacteria in the Reductive Metabolism of Zonisamide

Zonisamide (1,2-benzisoxazole-3-methanesulphonamide), a new anticonvulsant, is mainly metabolized to 2-sulphamoylacetylphenol by reduction of the benzisoxazole ring. Recent studies have shown that mammalian liver enzymes are responsible for the reduction of zonisamide. Because intestinal bacteria can also mediate the reduction of xenobiotics, this study was designed to evaluate the role of intestinal bacteria in in-vivo reductive metabolism of zonisamide. Treatment of rats with antibiotics significantly reduced the urinary and faecal excretion of 2-sulphamoylacetylphenol after oral administration of zonisamide. Re-contamination of the antibiotic-treated rats with microflora restored the excretion of the metabolite. The caecal contents of the control rats had significant zonisamide reductase activity, whereas little or no zonisamide reductase activity was observed with the caecal contents of the antibiotic-treated rats. Eight pure strains of intestinal bacteria were tested for zonisamide reductase activity and the highest was observed in Clostridium sporogenes. We concluded that intestinal bacteria play a major role in the reductive metabolism of zonisamide to 2-sulphamoylacetylphenol in-vivo.     

Screening for depression among first-visit psychiatric patients: Comparison of different scoring methods for the Center for Epidemiologic Studies Depression Scale using receiver operating characteristic analyses

Abstract The present paper aims to compare the ability of eight scoring methods for the Center for Epidemiologic Studies Depression Scale (CES-D), one of the most widely used self-report inventories for depression, to screen for a major depressive episode. The subjects were 591 patients who constituted representative samples of the first-visit patients to 23 psychiatric hospitals and clinics all over Japan. The criterion diagnoses were given by a semi-structured interview with established inter-rater reliability. The eight alternative scoring methods included the conventional Likert method, which gives the weights 0,1,2 and 3 to the four anchor points of the CES-D; the presence method, which gives the weights 0, 1, 1 and 1, respectively; the GHQ method, which gives the weights 0, 0, 1 and 1, respectively; the persistence method, which gives the weights 0, 0, 0 and 1, respectively; 10-item version, 5-item version, single-item version and the algorithmic method. On the basis of the receiver operating characteristic (ROC) analyses, it was found that the traditional Likert scoring method of the full CES-D performed best in detecting major depressive episodes among first-visit psychiatric patients. The presence method, the GHQ method and the 10-item version appeared to have a similar ability. The persistence method, the 5-item version and the single-item version resulted in significantly worse performance.     

Development of a Compact, Highly Efficient, Totally Implantable Motor–Driven Assist Pump System

Abstract: We have developed a compact, highly efficient, totally implantable assist pump system, which consists of a motor–driven assist pump and a transcutaneous energy and optical information transmission system. The motor–driven assist pump consists of ad. c. brushless motor and a specially designed miniature ball screw. A magnetic coupling mechanism between the blood pump and an actuator provides active blood filling via mild suction force. The controller consists of a PID follow–up controller using an 8–bit one–chip microcomputer. The volume of the pump is 350 ml, and its controller is 210 ml. Pump outflow of 5. 8 L/min was obtained against a mean afterload of 100 mm Hg. The pump showed a high efficiency rate and good durability. An efficiency rate of 19–21% (pump output/motor input) was obtained during 87 days of continuous pumping. No mechanical trouble occurred for an accumulated period of 6 months.     

Morphological changes of basophils in immunological reactions—effect of sodium cromoglycate

The morphological changes in blood basophils, from patients with bronchial asthma, were studied in vitro during immunological reactions, with particular reference to interaction with anti-IgE. Anti-human IgE results in an absolute reduction in basophil numbers in buffy coat preparations as well as basophil cytoplasmic degranulation. An increase in the numbers of pear-shaped (A-form) basophils is also observed. Sodium cromoglycate impairs all these anti-IgE induced basophil changes, providing further insight into the mechanism of action of this compound in bronchial asthma.