Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems

Background

Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.

Neuroprotective effects of metformin on traumatic brain injury in rats is associated with the AMP-activated protein kinase signaling pathway

Metabolic Brain Disease - Metformin is an activator of AMP-activated protein kinase (AMPK). Thus, it has the potential to restore energy in damaged neurons and attenuate secondary brain damage due...     

A High-Throughput,Precipitating Colorimetric Sandwich ELISA Microarray for Shiga Toxins

Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC) bacteria were simultaneously detected with a newly developed, high-throughput antibody microarray platform. The proteinaceous toxins were immobilized and sandwiched between biorecognition elements (monoclonal antibodies) and pooled horseradish peroxidase (HRP)-conjugated monoclonal antibodies. Following the reaction of HRP with the precipitating chromogenic substrate (metal enhanced 3,3-diaminobenzidine tetrahydrochloride or DAB), the formation of a colored product was quantitatively measured with an inexpensive flatbed page scanner. The colorimetric ELISA microarray was demonstrated to detect Stx1 and Stx2 at levels as low as ~4.5 ng/mL within ~2 h of total assay time with a narrow linear dynamic range of ~1–2 orders of magnitude and saturation levels well above background. Stx1 and/or Stx2 produced by various strains of STEC were also detected following the treatment of cultured cells with mitomycin C (a toxin-inducing antibiotic) and/or B-PER (a cell-disrupting, protein extraction reagent). Semi-quantitative detection of Shiga toxins was demonstrated to be sporadic among various STEC strains following incubation with mitomycin C; however, further reaction with B-PER generally resulted in the detection of or increased detection of Stx1, relative to Stx2, produced by STECs inoculated into either axenic broth culture or culture broth containing ground beef.     

The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I‐MIBG accompanied by ASCT for high‐risk and relapsed neuroblastoma: A pilot study

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant ¹³¹I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day ?30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m²), carboplatin (1500 mg/m²), and melphalan (210 mg/m²). Non‐MIBG‐avid subgroup received etoposide (600 mg/m²), carboplatin (1200 mg/m²), and melphalan (150 mg/m²). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.     

Characterization of pressure changes in the lower urinary tract during coughing with special reference to the demands on the pressure recording equipment

The exact demands on urodynamic equipment for measurement of coughs and cough associated pressure changes in the lower urinary tract have been analyzed from high-speed pressure recordings using a double microtip transducer and a storage oscilloscope. The equipment was tested in vitro by the step-test method. The natural frequency response was 175.6 Hz and the rise-time 2.5 ms, resulting in accurate measurements of frequencies up to about 60 Hz which is way above the clinically measured frequencies. Four men and 2 women, all of whom were healthy volunteers, were examined in the supine position with an empty bladder. Pressures were measured in the bladder and in the external sphincter zone of the urethra. The spectral power density of the bladder and urethral pressures were calculated by Fourier analysis. The pressure changes in the urethra were in all volunteers equal to or slower than in the bladder. The analysis of the spectral power density showed that 99% of the pressure changes could be recorded with an instrument capable of recording 9 Hz frequencies, i.e., with a sampling rate of 18 Hz or more. © 1994 Wiley-Liss, Inc.     

New trends in the development of oral antidiabetic drugs

A large number of oral antidiabetic agents are available today. This article provides a short review of the pharmacology and some clinical aspects of various oral antidiabetic drugs. It focuses mainly on the newest developing drugs (therapy of the near future) and on the most commonly used older groups for the common approach of every-day practice (sulphonylureas). The primary goal of this review is to compare the electrophysiological effects of glibenclamide in isolated normal and streptozotocin induced diabetic rats and alloxan induced rabbits ventricular preparations, while on the other hand to differentiate the hypoglycaemic sulphonylureas (0.1-1000 mmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 micromol/l) as well as chronically treated (5 mg/kg for 10 weeks) glibenclamide prolonged the action potential duration in normal but failed to affect it in diabetic ventricular preparations. Our results suggest that the sensitivity to glibenclamide of K(ATP) channels in diabetic ventricular fibers is drastically decreased. The effects of different sulphonylureas (tolbutamide, glibenclamide, gliclazide, glimepiride) on ventricular ectopic beats as well as the duration of ventricular fibrillation induced by 10 min ischemia/50 min reperfusion in healthy and diabetic rats were compared. Tolbutamide and gliclazide dose-dependently enhanced both parameters both in healthy and diabetic groups. Glibenclamide in healthy rats increased, while in diabetic rats it decreased the arrhythmogenicity. Glimepiride depressed the arrhythmogenicity in both healthy and diabetic animals. Glimepiride proved to dose-dependently enhance the myocardial tissue flow in dog in contrast to glibenclamide. These results confirm that glimepiride has less cardiovascular actions than other sulphonylureas. From the newest oral antidiabetics this review tries to emphasize the most important basic pharmacological properties, mechanism of action, therapeutic use.     

Total mesorectal excision with ultrasonic coagulation knife ("UltraCision") in surgery of rectal cancer

The authors report a total of 62 middle and low third rectal cancer cases operated on by total mesorectal excision by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The total mesorectal excision facilitates, the low anterior resections and preservation of sphincter with an ultra-low colorectal, or coloanal anastomosis using the double stapling technique. In the authors' experience, the "UltraCision" cutting-coagulating device permits an atraumatic, bloodless and oncologically correct dissection. Using the double stapling technique, we succeeded in 60% of our middle- and low-third rectal cancer patients to perform a sphincter preserving low anterior resection. In 9 (28%) of the low third rectal cancer patients, preservation of the sphincter was possible with oncologically correct anterior resection and an ultra-low colo-anal anastomosis. Three anastomotic insufficiencies occurred, two of them healed on lotion-suction drainage, and one on the application of transient protective ileostomy. The literature data suggest a lower local recurrency rate after radical rectal cancer surgery, if total mesorectal excision is performed.     

Cardiac electrophysiological effects of citalopram in guinea pig papillary muscle comparison with clomipramine

The effect of citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant, was studied on cardiac action potential configuration and compared with that of the tricyclic antidepressant (TCA) clomipramine. Conventional microelectrode techniques were used in right ventricular papillary muscle preparations of the guinea pig. Citalopram caused a concentration-dependent (10-100 microM) shortening of action potential duration (APD), depression of plateau and overshoot potential, and reduction of maximum velocity of depolarization (V(max)). No significant changes in resting membrane potential were observed. Similar results were obtained with clomipramine; however, reduction of V(max) and overshoot was more pronounced with clomipramine, whereas citalopram caused relatively greater shortening of APD. Effects of both drugs were partly reversible. The results indicate that the SSRI antidepressant citalopram, similarly to TCA compounds, alters cardiac action potential configuration in guinea pig ventricular muscle, probably owing to inhibition of cardiac Na(+) and Ca(2+) channels. Differences in cardiac side effects of the two drugs may be related to their different actions on cardiac action potential configuration.