Colon-specific delivery of budesonide with azopolymer-coated pellets: therapeutic effects of budesonide with a novel dosage form against 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats.

The objective of this study was to achieve colon-specific delivery of budesonide using azopolymer-coated pellets and to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. After oral administration of azopolymer-coated pellets containing budesonide, a significant increase was observed in the therapeutic effects of the drug accompanied by a decrease in its systemic adverse effects when compared with oral administration in saline or rectal administration by enema. In addition, with the use of the colon-specific oral dosage form the dose of budesonide could be reduced. These results suggested that azopolymer-coated pellets may be a useful dosage form for the colon-specific delivery of budesonide as an anti-inflammatory steroid drug to bring about the healing of TNBS-induced colitis in rats.     

K+ loading, but not Na+ loading, and blockade of ATP-sensitive K+ channels augment renal kallikrein secretion

This study aimed to examine whether K+ loading or Na+ loading augments renal kallikrein (KK) secretion. It also investigated the effect of blockade of renal ATP-sensitive K+ channels on renal KK secretion. Rats were administered 50 mmol/kg body weight of KCl. Twelve-hour collected urine was measured for urinary excretion of K+ and Na+ and urinary activity of renal KK. Increases in urinary excretion of K+ and Na+ by K+ loading accompanied an increase in renal KK secretion. In another experiment, rats were infused intravenously with a solution of 75 mM K+ and 75 mM Na+, 150 mM Na+ or 300 mM Na+ for 150 min under anesthesia. Urinary KK activity was measured in urine collected every 30 min. Renal KK secretion began to increase within the 30 min infusion of K+ solution and persisted at more elevated levels during the infusion with K+ solution than with Na+ solutions. Furthermore, rats were given intravenous injection of ATP-sensitive K+ channel blocker, either PNU-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl) at a concentration of 10 mg/kg or glibenclamide at 30 mg/kg. Renal KK secretion increased 30 min after administration of both PNU-37883A and glibenclamide. In conclusion, it may be that augmentation of renal KK secretion by K+ loading occurred through an increase in urinary K+ excretion followed by the inhibition of K+ transport from ATP-sensitive K+ channels.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.     

Prospective comparison of open<Emphasis Type="Italic">vs</Emphasis>. laparoscopic colon surgery for carcinoma

Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. METHODS: In 1990, we began a comparative study of open (OCR)vs.laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. RESULTS: Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7vs.9.7 days), less blood loss, less wound problems (1vs.14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. CONCLUSION: After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.     

The von-Hippel-Lindau (VHL) tumor suppressor gene is not mutated in sporadic ovarian carcinomas

The von Hippel-Lindau (VHL) tumor suppressor gene has been shown to be mutated frequently not only in neoplasms from von Hippel-Lindau disease, but also in sporadic clear cell renal carcinoma. In order to reveal the possible role of the VHL tumor suppressor gene in the development of ovarian carcinoma, a total of 71 primary sporadic ovarian carcinomas were analyzed for the presence of mutations in the exon 2 and 3 of the VHL tumor suppressor gene, using the polymerase chain reaction with single strand conformation polymorphism analysis. No mutations in the VHL gene were found in any of the tumors analyzed. This result shows that the VHL tumor suppressor gene does not play a major role in the tumorigenesis of sporadic ovarian carcinoma.     

Distribution of endogenous and exogenous carnitine in rats with sepsis and acute liver failure

The distribution of carnitine was investigated in male Wistar rats with sepsis or acute liver failure. Sepsis was produced by cecal ligation and puncture, while acute liver failure was induced by intraperitoneal injection of carbon tetrachloride. Then 14C-carnitine or L-carnitine was injected intravenously. In healthy control rats and rats with sepsis, both 14C-radioactivity and carnitine were increased in the liver and kidneys. When the carnitine fractions were investigated, it was found that free carnitine and short-chain acylcarnitine were increased. In the rats with acute liver failure, 14C-radioactivity decreased in the liver, but carnitine increased, with free carnitine and short-chain acylcarnitine levels rising. These findings suggested that exogenous free carnitine accumulated directly in the organs with carnitine deficiency in rats with sepsis and acute liver failure. In addition, there was differential regulation of the fractions of both exogenous and endogenous carnitine (free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine). Furthermore, the distribution of exogenous carnitine differed between sepsis and acute liver failure.     

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time

Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [¹²³I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.     

Iridoid glucosides of Melampyrum laxum

From the aerial part of MALAMPYRUM LAXUM, M IQ. three iridoid glucosides were isolated and identified as melampyroside, mussaenoside and aucubin.     

Comparative epidemiology of cancer between the United States and Japan. A second look

Vital statistics were examined for the years 1955 through 1985 for Japanese natives and United States whites to elucidate changes in cancer mortality and related antecedent patterns of life-style in these two populations. Results show that lung cancer rates are rapidly accelerating among Japanese males as a consequence of their prior history of heavy cigarette smoking. Oropharyngeal cancer rates are also rising in Japan paralleling increases in alcohol and tobacco utilization. As the Japanese life-style and diet continue to become more "westernized," the rates of malignancies of the breast, ovary, corpus uteri, prostate, pancreas, and colon also continue to rise. Nevertheless, the mortality patterns of certain malignancies, viz., laryngeal, esophageal, and urinary bladder cancer, are discrepant with their established risk factor associations, suggesting the existence of other differences in risk factor exposure between the two countries. Epidemiologists and health educators need to develop innovative international programs of investigation and health promotion with preventive impact on common malignancies associated with risk factors of life-style.     

The application of population pharmacokinetic analysis to large scale clinical efficacy trials

Summary Results have been presented that demonstrate the ability to conduct population pharmacokinetic analysis as a component of clinical efficacy and safety trials. This method of analysis offers the potential to determine the pharmacokinetics of a drug in the actual patients receiving medication and to evaluate relationships between pharmacokinetics and drug action. However, active involvement in the protocol design, and data collection process are required to ensure the quality of the resultant data set.