AIMTo study the effects of protease inhibitors on the large and small intestinal absorption of insulin in rats and to explore the mechanism of various protease inhibitors in different intestinal regions.

METHODSThe intestinal absorption of insulin was evaluated by its hypoglycemic effect and serum insulin level using an in situ loop method with the washing treatment.

RESULTSAdministration of insulin alone did not decrease the glucose level at either intestinal region with or without the washing treatment. With the unwashing treatment, there were no hypoglycemic effects in small intestinal loop when coadministration of insulin with protease inhibitors. With the washing treatment, the biological effects of insulin were amplified a little in small intestinal loop; obvious hypoglycemic effects were found in large intestinal loop with or without the washing treatment. The effectiveness of protease inhibitors was susceptible to their categories, concentrations and activities of proteolytic enzymes in different regions. The efficacy order of various protease inhibitors for enhancing hypoglycemic response of insulin was: leupeptin > sodium glycocholate > bacitracin > bestatin > cystatin; the percutaneous enhancement effects were observed in the presence of either sodium glycocholate or bacitracin.

CONCLUSIONCoadministration of protease inhibitors could increase the insulin efficacy more effectively in the large intestine than in the small intestine.

Animals ; Bacitracin ; pharmacology ; Biological Availability ; Blood Glucose ; metabolism ; Colon ; metabolism ; Glycocholic Acid ; pharmacology ; Insulin ; pharmacokinetics ; Intestinal Absorption ; drug effects ; Intestine, Small ; metabolism ; Leupeptins ; pharmacology ; Male ; Protease Inhibitors ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar

AIMTo investigate the degradation of recombinant hirudin-2 (rHV2) in nasal mucosa of rabbit.

METHODSThe specific and accurate HPLC method was developed for analyzing rHV2; The degrading ratios of rHV2 at different concentrations and at pH conditions in rabbit nasal mucosa homogenate were determined; The results in nasal mucosa homogenate were compared with that in small intestinal mucosa homogenate of rabbits. The stability of rHV2 in the enzyme extract of nasal mucosa surface and the effect of proteolysis inhibitor bacitracin on the degradation of rHV2 in nasal mucosa homogenate were also estimated.

RESULTSThe degradation of rHV2 in rabbit nasal mucosa homogenate showed concentration- and pH-dependence; rHV2 in nasal mucosa homogenate was more stable than that in intestinal mucosa homogenate. Also rHV2 was more stable in the enzyme extracts of nasal serosal surface than that of mucosa surface. Addition of bacitracin was able to inhibit the degradation to some degree.

CONCLUSIONComparing with oral administration, rHV2 nasal delivery was a more tolerant route.

Animals ; Bacitracin ; pharmacology ; Chromatography, High Pressure Liquid ; Female ; Hirudins ; genetics ; metabolism ; pharmacokinetics ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intestinal Mucosa ; drug effects ; metabolism ; Kinetics ; Nasal Mucosa ; drug effects ; metabolism ; Rabbits ; Recombinant Proteins ; metabolism ; pharmacokinetics

Not only is Group A beta-hemolytic Streptococcus (GAS) the most frequent cause of bacterial pharyngitis, it is also the culprit in various skin and systemic infections, acute rheumatic fever, post streptococcal glomerulonephritis, and other disorders and complications. A new, ready-to-use media, Dio-Bacit, in a two section plate containing 5% sheep blood agar on one side and sheep blood agar with bacitracin (2microgram/ml) on the other was compared for its efficiency in identifying GAS with bacitracin and bacitracin + sulphamethaxazole / trimethoprim disk tests applied after isolation of beta-hemolytic colonies. We also used the latex-agglutination test as the gold standard method for differentiating GAS from streptococci belonging to other groups. Compared with the latex-agglutination test, we found the sensitivity and specificity of the Dio-Bacit method to be 92.0% and 96.9%, respectively. Dio-Bacit plates provide an easy and very useful way to identify GAS within one day, saving time, labor, and money for routine diagnostic microbiology laboratories.
Adult ; Anti-Bacterial Agents/pharmacology ; Anti-Infective Agents/pharmacology ; Bacitracin/pharmacology ; Bacteriological Techniques ; Child ; Comparative Study ; Culture Media ; Female ; Human ; *Latex Fixation Tests ; Male ; *Microbial Sensitivity Tests ; Pharyngitis/*diagnosis/microbiology ; Sensitivity and Specificity ; Streptococcal Infections/*diagnosis ; Streptococcus pyogenes/drug effects/*isolation & purification ; Support, Non-U.S. Gov't ; Trimethoprim-Sulfamethoxazole Combination/pharmacology