Changes in the biliary excretion of organic anions following exhaustive exercise in rats

The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked reduction of glycogen concentration in the liver (-72%). When bromosulphthalein was administered i.v., its maximal biliary excretion (Tm) was significantly reduced (-30%), and plasma and liver concentrations of the dye were increased (+31% and +56%, respectively). The decrease corresponded both to the excretion of the conjugated and unconjugated dye (-30% and -33%, respectively). Cytosolic glutathione S-transferase activity in the liver was not affected by exercise, but there was a significant reduction in the hepatic concentration of glutathione (-50%). The Tm of dibromosulphthalein was also significantly reduced (-36%) and its plasma and liver concentrations increased (+67% and +33%, respectively) in exercised rats. The results suggest that, in addition to the direct effect of liver glutathione depletion, other factors must be involved in the impairment of the biliary excretion of organic anions caused by exercise.     

Preliminary experience with new bioactive prosthetic material for repair of hernias in infected fields

Surgisis (Cook Surgical, Bloomington, Ind., USA) is a new four-ply bioactive, prosthetic mesh for hernia repair derived from porcine small-intestinal submucosa. It is a naturally occurring extracellular matrix which is easily absorbed, supports early and abundant new vessel growth, and serves as a template for the constructive remodeling of many tissues. As such, we believe that Surgisis mesh is ideal for use in contaminated or potentially contaminated fields in which ventral, incisional, or inguinal hernia repairs are required. From November 2000 through May 2002, 25 patients (11 male, 14 female) underwent placement of Surgisis mesh for a variety of different hernia repairs. A total of 25 hernia repairs were performed in our patient population. Fourteen procedures (56%) were performed in a potentially contaminated setting (i.e. with incarcerated/strangulated bowel within the hernia or coincident with a laparoscopic cholecystectomy/colectomy). Eleven repairs (44%) were performed in a grossly contaminated field, including one in which an infected polypropylene mesh from a previous inguinal hernia repair was replaced with Surgisis and one in which necrotic bowel was discovered within the hernial sac. Median follow-up was 15 months with a range of 1–20 months. Of the 25 total repairs, there was one wound infection complicated by enterocutaneous fistula in a patient originally operated on for ischemic bowel. The fistula was in a location independent of the Surgisis mesh. There were no mesh-related complications or recurrent hernias in our early postoperative follow-up period. Surgisis mesh appears to be a promising new prosthetic material for hernia repair, especially in contaminated or potentially contaminated fields. Obviously, long-term follow-up is still required. Electronic Publication     

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.     

Composite tissue (limb) allografts in rats. III. Development of donor-host lymphoid chimeras in long-term survivors

Eight LEW rat recipients possessing long-term-surviving (206-701 days) LBN vascularized hind limb allografts (CTAs) were tested for donor-host lymphoid chimerism. The recipients received various cyclosporine (CsA) treatment protocols in order to induce indefinite CTA acceptance. Histological examination of long-term-surviving CTAs demonstrated normal-appearing bone marrow in the donor limb. Lymphocytes isolated from host hemopoietic tissues (peripheral blood and/or spleen) by ficoll-hypaque density gradient centrifugation were tested against LEW-anti-BN antisera. Comparisons were made to standard curves employing various known concentrations of LBN and LEW cell combinations. The level of lymphocyte agglutination (dependent variable) showed a significant (P less than 0.025-0.005) linear relationship to the concentration of LBN donor cells (independent variable) present. Lymphocyte suspensions isolated from long-term CTA host peripheral blood and/or spleen showed a mean of 19.7% (+/- 9.7-95% confidence interval) donor LBN mononuclear cells present. Thus, it appeared that lymphoid cells originated from, and/or were released from LBN donor bone marrow into the circulation, resulting in chimeric repopulation of hemopoietic tissues. The presence of donor immunocytes in these limb allograft recipients may have been beneficial, and thus could have helped contribute to the long-term CTA survival observed.     

Spontaneous hypertriglyceridemic obesity and hyperglycemia in an inbred line of rats

A genetically mild obesity syndrome of pubertal onset in a highly inbred line of rats differentiated as beta (beta) has been described. It was discovered in both sexes fed a stock diet for rodents. Hyperphagia was not noticeable. Total fat content reached 31 percent of total body weight in mature males. Obesity was associated with normal plasma cholesterol values and hypertriglyceridemia. Fasting blood sugar levels at maturity were within the normal range for rats, but significantly higher than in lean alpha (alpha) controls. This syndrome developed into a mild glucose intolerance and glucosuria in older obese rats.     

Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis

Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca²⁺ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca²⁺, which was more effective than increasing [Ca²⁺]_i through elevating extracellular Ca²⁺ or the addition of forskolin which increased [Ca²⁺]_i but desensitized the myofilaments to Ca²⁺.