Selective inhibition of human cyclo-oxygenase-2 by meloxicam

Human cyclo-oxygenase-1 (hCOX-1) and-2 were expressed in stable transfected COS A.2 cells and in insect cells using a Sf9 baculovirus expression system. Inhibition of COX activity was examined using both whole cell and microsomal assays. Ibuprofen, naproxen, 6-MNA, diclofenac and indomethacin were selective for hCOX-1 or were equipotent inhibitors for COX-1 and COX-2. Piroxicam was equally inhibitory for both enzymes in the whole cell assay while it preferentially inhibited hCOX-2 in the microsomal assay. However, maximal inhibition of hCOX-2 by piroxica plateaued at 60%. Nimesulide was equipotent in the whole-cell assay but was five-fold selective for hCOX-2 in the microsomal assay. Meloxicam preferentially inhibited hCOX-2 in the whole cell assay at concentrations of 0.01 to 1 μmol/L but was an equipotent inhibitor of both enzymes at higher concentrations. In the microsomal assay, meloxicam exhibited high selectivity for hCOX-2 (75-fold). The preferential inhibition of hCOX-2 by meloxicam may explain the favourable gastrointestinal profile observed for meloxicam compared with other NSAIDs.     

Risk of iatrogenic human immunodeficiency virus infection through transfusion of blood tested by inappropriately stored or expired rapid antibody assays in a Zambian hospital

BACKGROUND: The purpose of this study was to estimate the risk of human immunodeficiency virus (HIV) infection via the transfusion of blood tested by inappropriately stored or expired rapid antibody assays in Zambia. STUDY DESIGN AND METHODS: Surgical patients (n = 370) were tested with antibody assays (HIV-spot and HIV 1+2) that had expired 3 to 6 months previously. Blood donors (n = 211) were tested by inappropriately stored but non-expired HIV-spot assay. Serum samples from both groups were retested with enzyme immunoassays, and the seropositivity of samples was confirmed by immunoblotting. RESULTS: Seroprevalence in surgical patients and blood donors was 19.8 and 11.6 percent, respectively. Sensitivity and specificity of HIV-spot (expired) were 88.2 and 98.1 percent; those of HIV 1+2 (expired) were 82.1 and 94.7 percent; and those of HIV-spot (non-expired) were 91.7 and 98.8 percent, respectively. The risk of HIV infection via the transfusion of blood tested by HIV-spot (expired), HIV-spot (nonexpired), or HIV 1+2 (expired) was calculated to be 1.4, 1.0, and 3.2 percent, respectively. CONCLUSION: Manufacturers of the HIV-spot and HIV 1+2 assays claim sensitivity and specificity of 98.8 and 100 percent and 100 and 99.5 percent, respectively. In this study, sensitivity and specificity were 11 to 18 percent lower. Moreover, in- date reagents also performed less well than the manufacturers claimed, but the worst results were with expired or improperly stored reagents. According to the manufacturers of HIV-spot and HIV 1+2, the risk of HIV infection would be 0.2 and 0 percent, respectively. However, the risk of contracting HIV through transfusion is at least six times higher than expected.     

Lactate and glucose minimum speeds and running performance

This study aimed to analyse the validity of glucose minimum speed (GMS) for lactate minimum speed (LMS) assessment during running and their relationship to endurance performance. Eight male trained runners (28.7 +/- 9.0 years) volunteered to take part in this study and underwent an official 10-km road race and a track lactate minimum test (LMT) (0.5-km sprint plus 6 x 800 m from 87 to 98% of maximal 3-km speed). Lactate and glucose minimum speeds were considered those related to the minimum blood lactate and glucose concentrations respectively attained during the graded phase of LMT. Significant correlations (p < 0.05) were found between LMS and GMS (r = 0.72) and LMS and 10-km performance (r = 0.83), but not between GMS and 10-km performance (r = 0.49). No significant differences (p > 0.05) were found between LMS (4.75 +/- 0.08 m/s), GMS (4.73 +/- 0.07 m/s) and 10-km mean speed (4.79 +/- 0.17 m/s). In conclusion, we found GMS to be a good predictor of LMS during track LMT, LMS being well related to endurance running performance.     

Characterization of purified rabbit uterine renin: influence of pregnancy on uterine inactive renin

Using specific antibody raised against renal renin, we have documented that the majority of the uterine renin-like activity in gravid and nongravid uteri is immunoreactive renin. To characterize its physiochemical properties, we obtained highly purified uterine renin by two affinity chromatographic steps, pepstatin and antirenin. Uterine renin has a pH optimum of 6, an apparent mol wt of 38K, and a Km of 1.7 microM for homologous substrate. These properties are identical to those of renal renin and are not influenced by the pregnant state. In the basal state, an inactive form of the uterine enzyme constitute 55 +/- 10% of the total uterine renin. During pregnancy, active renin increased 40-fold as inactive renin fell to 4 +/- 3% of the total renin concentration. The renal renin concentration fell as plasma renin increased during pregnancy. These data suggest that the increased uterine renin concentrations during pregnancy are probably due to increased local production and conversion of renin precursor to the active enzyme. This stimulation of the uterine renin level appears to be independent of renal renin.     

A randomized trial of perioperative hemodilution versus transfusion of preoperatively deposited autologous blood in elective surgery

Hemodilution, one of several methods proposed to decrease homologous blood transfusion in elective surgery, has not been studied in a prospective controlled trial to determine if it is successful. A prospective, randomized controlled study was conducted to determine if hemodilution can serve as an alternative to preoperative autologous blood donation. Fifty patients were randomized to preoperatively deposit 3 units of autologous blood or to undergo hemodilution immediately before elective radical retropubic prostatectomy. All patients were treated under a standard protocol, including surgery performed by a single surgeon. The preoperative deposit groups received a mean of 2.44 +/− 1.0 units of blood; 2 of 25 patients required homologous blood transfusion for blood loss of 2600 mL and 1700 mL. The hemodilution group received a mean of 2.88 +/− 0.4 units of autologous blood: no hemodilution patient received homologous blood. At discharge, the mean hematocrit for the preoperative deposit group was 35.5 +/− 4.9 (0.35 +/− 0.05), and that for the hemodilution group was 31.8 +/− 4.7 (0.32 +/− 0.05) (p less than 0.001). There were no differences in perioperative morbidity in the treatment groups. The best predictor of discharge hematocrit was the initial hematocrit of the patient. It can be concluded that hemodilution can safely replace or at least augment preoperative autologous donations as a means of decreasing homologous blood transfusion in study patients. These results can be applied to any elective surgery procedure in which a 1000-mL blood loss is anticipated. Other advantages of hemodilution, including convenience, lower cost, and better preservation of all components of autologous blood, suggest that this practice deserves wider application.