In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

Anti-allergic effect of bryonolic acid from Luffa cylindrica cell suspension cultures.

The anti-allergic activity of bryonolic acid (1) isolated from the cultured cells of Luffa cylindrica L. (Cucurbitaceae) was compared with that of glycyrrhetinic acid (2), the aglycone of glycyrrhizin from licorice. Compound 1, when administered to rats intraperitoneally at a dose of 600 mg/kg, inhibited homologous passive cutaneous anaphylaxis more strongly than 2 at the same dose. Compound 1 also significantly inhibited delayed hypersensitivity in mice which could not be inhibited by 2. In contrast to 2, 1 showed not only little toxicity but no visible side effects on mice, without impairing the activity of the hepatic enzyme (4,5 beta-dihydrocortisone:NADP+ delta 4-oxidoreductase) involved in steroid catabolism.     

Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

Correlation of functional parameters derived by equilibrium radionuclide angiocardiography and left ventricular size in patients with old myocardial infarction

A total of 131 patients with old (over 6 months) myocardial infarction (MI) and 18 normal subjects underwent equilibrium radionuclide angiocardiography at rest (rERNA). The following rERNA parameters were assessed: left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), regional wall motion and a left ventricular size index. The patients with old MI were divided into four groups (I to IV) according to increasing left ventricular (LV) size, and the behaviour of the numerical parameters (LVEF, PER, PFR) was evaluated in each group. LVEF proved to be the most sensitive numerical parameter of overall LV performance. PFR decreased significantly from group I to group III but not from group III to group IV, suggesting that for extreme degrees of left ventricular enlargement some compensatory mechanism acts to prevent a too large fall in LV compliance. The effects of the site of the previous MI on LV performance were also evaluated. Both LV size and performance were least affected by postero-inferior MI. The LVEF was, however, a better predictor of LV size than the site of the MI.     

Cross-linking of atrial natriuretic peptide to binding sites in rat olfactory bulb membranes

Binding sites for 125I-atrial natriuretic peptide (ANP)2 in rat olfactory bulb membranes have been studied using pharmacological and biochemical methods. Various unlabeled ANP-related peptides were tested for the ability to inhibit the binding of the radioligand in membrane binding assays. ANP(92-126) and ANP(99-126) were the most potent inhibitors tested, both exhibiting an IC50 value of 0.40 nM. ANP(103-126) and ANP(103-123) were 3 and 70 times less potent, respectively. ANP(111-126) was unable to inhibit the binding of the radioligand at a concentration of 1 microM. Several peptides unrelated to ANP were unable to inhibit the binding of the radioligand to rat olfactory bulb membranes. Membranes labeled with 125I-ANP were incubated with cross-linking agents and subjected to SDS-PAGE followed by autoradiography. A band possessing an apparent molecular mass of 116 kDa was identified. The labeling of this band was progressively decreased by increasing concentrations of unlabeled ANP(99-126) (IC50 = 0.6 nM) and by several other ANP-related peptides at nanomolar concentrations. For comparison purposes, ANP binding sites in rat aorta membranes were labeled with 125I-ANP and cross-linked using identical techniques. Three bands possessing molecular masses of 120, 72, and 62 kDa were identified. These results indicate that the ANP binding site in rat olfactory bulb membranes displays pharmacological and biochemical properties similar to peripheral ANP receptors.     

The influence of alcohol on the outcome of automated static perimetry

It is well known that perimetric findings fluctuate within a single examination. There is additional fluctuation between perimetric examinations. The cause of this fluctuation is not yet fully understood, but such things as changes in attention, patient cooperation, or drugs have been discussed. To study such possible factors, we carried out perimetry on subjects who had consumed alcohol and who had not. The results indicate that alcohol, at a blood concentration of approximately 0.08%, barely influences the results of static automated perimetry. Differential light sensitivity remained unchanged by alcohol at all eccentricities tested. A decrease in the ability to cooperate was manifested by a significant higher score of false-positives in catch trials. There was also a tendency toward an increase in false-negative responses in catch trials, an increase in the number of stimuli presentations required, and higher short-term fluctuation. Lack of the influence of alcohol on the differential light threshold does not necessarily mean that alcohol has no influence on visual function. It indicates, however, that differential light sensitivity, as measured with the automated perimeter Octopus, is not influenced by moderate alcohol ingestion.