In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.     

Interactions between colour and luminance contrast in the perception of motion

It has been demonstrated widely that at isoluminance moving chromatic stimuli are seen to be stationary or moving more slowly than their luminance counterparts. We have examined the effect on perceived velocity of adding luminance contrast to an isoluminant chromatic stimulus. We show that moving luminance contrast 'captures' colour so that a combined colour and luminance stimulus is seen moving as a unified percept. However, in the presence of colour contrast, significantly higher levels of luminance contrast are required to achieve a veridical velocity than for monochromatic stimuli with only luminance contrast. We show that this interactive effect between colour and luminance contrast cannot be fully explained by a threshold masking of luminance by colour contrast. The effect suggests that a breakdown in the veridical perception of velocity should be expected for colours with a wide range of associated luminance contrasts and not just for those at the point of isoluminance.     

Studies on antifungal agents. In vitro activity of novel cis-5-alkoxy (or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine derivatives

The synthesis and in vitro antifungal activity of a novel series of cis-5-alkoxy(or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)- 2-methylisoxazolidine derivatives (6a-n) are described. The 5-[(4-chlorobenzyloxy)methyl] analogue 6h and the two 5-acyloxymethyl derivatives 6k,l demonstrated the best overall potency. Against Candida stellatoidea, the minimum inhibitory concentrations (MIC's) for 6h,k,l ranged between 0.7 and 2.0 micrograms/ml. The corresponding value for the standard drug ketoconazole was 7-20 micrograms/ml.     

Fetal pancreas transplantation in miniature swine. IV. Suppression of DTH and MLR responses by treatment with ultraviolet light-irradiated peripheral blood lymphocytes

Irradiation of peripheral blood lymphocytes of miniature swine with ultraviolet light prevented them from initiating proliferative responses in allogeneic mixed lymphocyte reactions and also reduced IL-2 production in these MLRs. When pigs were injected in a series of 4-5 weekly transfusions with UV-irradiated allogeneic PBL differing at the MHC, PBL of recipient pigs progressively responded less strongly to donor PBL in MLRs over the treatment period. These pigs also gave negligible delayed-type hypersensitivity responses to donor PBL at the end of the treatment period. Of the seven UV-irradiated PBL-treated pigs, four produced no antidonor PBL antibody and three produced antibody. Serum from the three antibody-producing pigs also suppressed MLRs of unrelated PBL. By contrast, pigs that received a series of injections of untreated allogeneic PBL gave strong DTH responses to donor PBL and heightened proliferation in MLRs with donor PBL, and all produced antidonor PBL antibody.     

Selected predictors of health promotion counseling by three groups of allied health professionals

Three groups of allied health professionals, including dental hygienists, dietitians, and certified nurse-midwives, were surveyed to determine current practice, beliefs, and attitudes regarding health promotion and disease prevention. The study aimed to explore the power of selected variables drawn from social learning theory in predicting self-reported level of counseling. We conducted separate analyses for 10 areas of health promotion and disease prevention: high blood pressure, smoking, lack of exercise, overweight, high-fat diet, alcohol abuse, illicit drug use, stress, isolation and loneliness, and nonuse of safety belts. The predictor variables were respondents' professional group membership, confidence that they possess appropriate skills and knowledge to counsel patients (self-efficacy), belief that patients will follow through on recommendations (adherence expectation), and belief that reduction of risk will improve patients' health status (expectation of health impact). The level of counseling activity varied markedly across the risk areas, with blood pressure and weight receiving the most emphasis on average and isolation and loneliness and nonuse of safety belts receiving markedly less attention. There also was variation across the professional groups. Certified nurse-midwives had higher mean counseling scores in all topics except those related to diet, where the dietitians' mean scores were approximately the same. Of all the areas about which counseling might be increased, use of safety belts stands out as having the lowest reported prevalence, the least complexity in terms of implementation, and the most relevance to at least two of the professional groups. These findings suggest the importance of skills training, including the provision of actual or simulated counseling experience and modeling by others in the same professional group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of propranolol on nitrogen and energy metabolism in sepsis

Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.