Sensitive fluorescence assay for d,l-methadone.

d,l-Methadone forms a fluorophore when reacted with paraformaldehyde in concentrated sulfuric acid. Based on this reaction, a fluorescence assay suitable for quantitative d,l-methadone analysis from plasma and other tissues was developed. d,l-Methadone was extracted at pH 9.2 from the deproteinized filtrate of plasma or of aqueous tissue homogenate into an organic phase of 25% isobutanol in ethylene dichloride. After an aliquot of the organic phase was evaporated to dryness at 50--55 degrees with an air jet, paraformaldehyde (0.1%, in concentrated sulfuric acid) was added, and fluorescence was read at 450 nm with excitation at 275 nm. By this method, d,l-methadone can be assayed in the presence of its metabolites, morphine, diacetylmorphine (heroin), codeine, and cocaine; however, amphetamine, meperidine, and quinine interfere.     

Effect of cadmium on hepatic mixed-function oxidases during the early development of rats: Possible protective role of metallothionein

Hepatic metallothionein contents and activities of mixed function oxidases in control and cadmium-treated rats (1.2 mg Cd²⁺/kg) of various age groups (7-, 14-, 21- and 90-days-old) were determined. A significantly high concentration of native metallothionein was noticed in immature rats (7- and 14-days-old). Cadmium administration induced metallothionein only in 21- and 90-day-old rats, while the basal level of native metallothionein of immature rats was not altered. Activity of certain mixed-function oxidases (MFO) such as aryl hydrocarbon hydroxylase, aminopyrine-N-demethylase, and benzphetamine-N-demethylase was inhibited significantly only in 21- and 90-day-old rats. Microsomal cadmium accumulation was significantly higher in adult as compared to immature rats. Results suggest a protective role of metallothionein against cadmium-induced inhibition of mixed-function oxidases in immature rats.     

HBsAg Seropositive Status and Survival After Renal Transplantation: Meta-Analysis of Observational Studies

The natural history of hepatitis B virus (HBV) infection after renal transplantation (RT) remains unclear. We conducted a systematic review of the published medical literature on the impact of HBV surface antigen (HBsAg) seropositivity on survival of RT recipients. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality and graft loss in HBsAg positive RT recipients across the published studies. We identified six observational studies (6050 unique patients); all of them being cohort, retrospective studies. Pooling of study results demonstrated that HBsAg in serum was an independent and significant risk factor for death after RT; the summary estimate for relative risk was 2.49 with a 95% confidence interval (95% CI) of 1.64-3.78. A test for homogeneity of the relative risk across the studies gave a p-value of <0.0001. HBsAg seropositivity was an independent and significant risk factor for graft failure after RT; the summary estimate was 1.44 with a 95% CI of 1.02-2.04 (homogeneity test, p <0.0001). This meta-analysis shows that HBsAg positive RT recipients have an increased risk for mortality and graft failure compared to seronegative patients.     

Grass aeropollen of the western United States Gulf Coast.

Volumetric air sampling was performed at Corpus Christi, Tex., September 1987 to August 1989. Grass aeropollen during all of 1988 accounted for 15.3% of total pollen captured during two major peaks, one in May and another during September and October. The remaining grass pollen, about one-quarter of the total, was found throughout the year with low levels in the winter and mid-summer. This bimodal pollen release corresponds to the flowering of two major types of grasses occurring in the western Gulf Coast region, the cool temperate species which are predominantly spring flowering in response to long-day photoperiodicity, and the more common warm temperate and subtropical species flowering by and large in the fall as short-day plants. Supplementing the already rich grass flora and adding to the high proportion of total aeropollen was the long distance dispersal of grass pollen found perhaps in sufficiently high quantities to trigger allergic symptoms and to cause grass pollinosis out of season, at least in acutely sensitive individuals. This occurred in late March, well before the spring peak in May. Correlations existed between near-drought conditions and reduced pollen shed in 1988, and normal precipitation and much higher pollen shed during parts of 1987 and 1989, illustrating the importance of environmental factors such as moisture on annual pollen frequency and level of pollinosis which can be variable and annually unpredictable. What is predictable is the genetically controlled timing of pollen maturation and release which will be generally the same year by year.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of a Bioartificial Liver Using Isolated Hepatocytes

Abstract: Severe liver disease is very often life-threatening and dramatically diminishes quality of life. Liver support systems based on detoxification alone have been proved ineffective because they cannot correct biochemical disorders. An effective artificial liver support system should be capable of carrying out the liver's essential processes, such as synthetic and metabolic functions, detoxification, and excretion. It should be capable of sustaining patients with fulminant hepatic failure, preparing patients for liver transplantation when a donor liver is not readily available (i.e., bridge to transplantation), and improving the survival and quality of life for patients for whom transplantation is not a therapeutic option. Recent advances in cell biology, tissue culture techniques, and biotechnology have led the way for the potential use of isolated hepatocytes in treating an array of liver disorders. Isolated hepatocytes may be transplanted to replace liver-specific deficiencies or as an important element of an auxiliary hybrid, bioartificial extracorporeal liver support device, which are important therapeutic applications for treating severe liver disease. Recently, several hepatocyte-based liver support systems have been proposed. Although there is no current consensus on its eventual design configuration, the hollow fiber hepatocyte bioreactor shows the greatest promise. Furthermore, application of tissue engineering technology, based on cellsurface interaction studies proposed by our group and others, has enhanced interest in the development of highly efficient hybrid, bioartificial, liver support devices.     

Preparation, characterization and performance evaluation of neomycin-HSA microspheres

Human serum albumin microspheres containing neomycin sulphate were prepared using emulsion polymerization and polymer dispersion techniques. The many variables which may affect the shape, size, stability, release of the drug from the microspheres such as internal phase to external phase volume ratio, human serum albumin content, stirring rate, polymer content and stabilizing agent concentration, were studied. Unlike the microspheres prepared by the emulsion polymerization technique, polymer dispersion stabilised microspheres were uniform in size and shape with a narrow range of size distribution. In vitro release of neomycin sulphate from albumin microspheres was studied using the dialysis cell method. The drug release from microspheres followed Q versus (t)-1/2 linear relationship. The in vivo distribution studies on prepared microspheres revealed that the localization takes place preferably in lung tissues, liver, spleen and kidney and is found to be dependent on the microsphere size. On administration of microspheres of 3-6 microns size, approximately 55 per cent of administered drug could be localized in the lungs.     

Reversal of diabetes by the isotransplantation of nicotinamide-streptozotocin-induced islet adenoma in rats

The effect of syngeneic transplantation of islet tumors induced by streptozotocin-nicotinamide treatment into Fisher inbred diabetic rats was studied. Transplantation of 10 mg of tumor tissue under the kidney capsule of severely diabetic animals resulted in complete amelioration in 9 of 14 animals. Partial improvement was noted in three animals, whereas only one animal showed no change in diabetic condition within 4 months. Improvement in diabetes was accompanied by gain in body weight, decrease in blood sugar level and urinary glucose excretion, and normalization of glucose tolerance. After removal of the kidney containing the tumor grafts, the animals reverted to a severe diabetic condition, suggesting that the tumor graft supplied the insulin needs of the diabetic animals. The graft tissue exhibited in vitro insulin synthesis and secretion in response to 16.7 mM glucose.