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%.

     

Radioimmunoassay for amatoxins by use of a rapid, 125I-tracer-based system

In this new radioimmunoassay system for determination of amatoxins in urine and plasma, a novel chemical approach is used for antigen and 125I-tracer production, based on a detoxified alpha-amanitin derivative (aldoamanitin). Total assay time, including data processing, is less than 100 min. The lowest detectable concentration is 1 microgram/L for urine, 0.1 microgram/L for plasma. In the clinically significant range, within-run CVs are less than 8%. This new 125I-based assay is a significant improvement over existing 3H technology in terms of speed, precision, and freedom from interference.     

Opportunistic intracranial infection in AIDS detection by technetium-99m DTPA brain scintigraphy

Radionuclide brain scintigraphy and computed tomography (CT) demonstrated cerebral lesions in two patients with acquired immunodeficiency disease syndrome (AIDS) complicated by opportunistic infection of the brain. In the detection of these cerebral lesions, [99mTc]DTPA radionuclide scintigraphy was as reliable as CT. Since malignant lymphoma involving the brain has been seen with increasing frequency in patients with AIDS, the positive brain scan alone is nonspecific and should be correlated appropriately with the clinical setting.     

Anleitung für eine vollständige Kehlkopfpräparation

Zusammenfassung Anhand von 9 Abbildungen wird eine Methode zur Kehlkopfpräparation beschrieben, bei der sämtliche Knorpel, Gelenke und Muskeln dargestellt werden. Nach Ablösung des Schildknorpels und des Hypopharynx werden die Mm. postici und arytaenoidei isoliert, die Cricoarytaenoidgelenke sowie die Arytaenoidknorpel präpariert und die Mm. laterales eingeschnitten. Ein Horizontalschnitt durch den Ringknorpel und die median-sagittale Spaltung des proximalen Fragmentes liefern schließlich den Zugang zu den inneren Kehlkopfweichteilen.     

Localization of acetylcholine receptors and cholinesterase on nerve-contacted and noncontacted muscle cells grown in the presence of agents that block action potentials

The possible role of nerve activity in triggering changes in the localization of acetylcholine receptors (AChRs) and cholinesterase (ChE) on nerve-contacted Xenopus muscle cells has been assessed. The localization of these molecules was examined on nerve-contacted and noncontacted muscle cells in cultures of spinal cord and myotomal muscle derived from Xenopus embryos. Sites of high AChR density were revealed by staining with fluorescent alpha-bungarotoxin and sites of ChE localization were revealed histochemically. Localization of AChRs and ChE at sites of nerve-muscle contact occurred when the culture medium contained 1.2 micron tetrodotoxin (TTX), 1.2 micron TTX, 10 mM magnesium, and no calcium salts, 1.2 micron TTX and 2 mM manganese, or 106 mM potassium methyl sulfate instead of sodium chloride. The nerve-contacted muscle cells in each of these modified culture media also exhibited a reduced incidence of AChR and ChE patches away from the site of contact. It is concluded that the neural factor(s) that triggers the local and remote changes in AChR and ChE distribution can be supplied to the neurites and externalized in the absence of nerve impulses, and that the nerve and muscle cells can interact even when they are largely depolarized.     

Localized osteolysis in stable, non-septic total hip replacement

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.     

Computerized tomography diagnosis of diffuse intraperitoneal metastases after retroperitoneal lymphadenectomy for testicular carcinoma

We report 2 cases of diffuse intraperitoneal metastases from testicular carcinoma following transabdominal retroperitoneal lymphadenectomy. This is an unusual pattern of metastasis for nonseminomatous germ cell tumors and it is believed to be the result of direct seeding from lymphatic leakage secondary to surgery. The value of computerized tomography in diagnosing this entity is emphasized.     

Neuronal activity evoked by chronically implanted intracortical microelectrodes

The averaged evoked compound action potentials (AECAPs) were recorded from the ipsilateral pyramidal tract of awake, unrestrained cats before, during, and after continuous electrical stimulation of the cerebral cortex via chronically implanted activated iridium or platinum-30% iridium (Pt30%Ir) microelectrodes. After stimulating 24 h at 20 pulses per second (pps), using charge-balanced, 200-microseconds pulse pairs of 40 to 80 microA (400 to 800 microC/cm2, 8 to 16 nC/phase (ph), 2 to 4 A/cm2), there was a transient elevation of the threshold of the early (direct) and of the alte (transynaptic) components of the AECAP. After cessation of continuous stimulation at 80 microA, the threshold of the early component of the AECAP remained elevated for as long as 24 h and the late component as long as 4 days, indicating significant but reversible depression of the electrical excitability of cortical neurons close to the microelectrodes. In three cats stimulated 23 h/day for 1 week, the AECAP also recovered to their prestimulus threshold. In contrast, pulsing for 24 h at 320 microA (3200 microC/cm2, 64 nC/ph, 16 A/cm2) produced marked elevation of the threshold of the AECAPs which was not reversed by 7 to 12 days after termination of intracortical stimulation. The electrical excitability of neurons adjacent to (unpulsed) microelectrodes 2 mm from the pulsed electrode was not affected. The observations reported here, in conjunction with the histologic results reported in the companion paper, indicate that both the Pt30%Ir and the iridium microelectrodes can be operated safely at currents to at least 80 microA, charge/ph of 16 A/cm2, and a charge density of 800 microC/cm2 X ph. However, on the basis of the electrophysiologic criteria, both types appear to be unsafe when pulsed at 320 microA (64 nC/ph, 3200 microC/cm2 X ph, 16 A/cm2).