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Biomedical subjects

H Guenther

Publications and source records attributed to H Guenther.

10 recordsLinked to original sources
PubMed1998

Pharmacokinetic interaction between ritonavir and clarithromycin.

BACKGROUND: Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes. OBJECTIVE: To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin. METHODS: This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin. RESULTS: Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin. CONCLUSIONS: No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.

AIDS-Related Opportunistic Infections↗
PubMed1976

Matrix vesicle heterogeneity: possible morphogenetic functions for matrix vesicles.

Extracellular membranous matrix vesicles were localized and described using electronmicroscopy during chondrogenesis, osteogenesis, and dentinogenesis. Evidence indicates that matrix vesicles in each of these specific tissue types function to concentrate and transport ions and enzymes which serve as nucleation sites for the mineralization of hydroxylapatite. We have examined different developmental stages of Meckel's cartilage, alveolar bone and epithelial-mesenchymal interactions associated with tooth formation in newborn mice. These ultrastructural studies indicate matrix vesicle heterogeneity. Whereas most matrix vesicles contain alkaline phosphatase activity during cartilage, bone and dentine mineralization, in earlier developmental stages matrix vesicles contain acid phosphatase activities and little, if any, alkaline phosphatase. Tissue type, specific developmental stage, and ultrastructural criteria indicate various "classes" of matrix vesicles. During epithelial-mesenchymal interactions in tooth development, mesenchymal cells (preodontoblasts) appear to be the source of matrix vesicles as indicated by the complementarity between H-2 histocompatibility alloantigen specificity on the cell surface and that of the matrix vesicle outer surface; matrix vesicles are limited by a trilaminar membrane derived from the mesenchymal cells. Some of the vesicles located adjacent to dividing inner enamel epithelial cells contain RNA's as determined by electron microscopic autoradiography in situ, as well as by direct biochemical assays. We postulate that matrix vesicles have many different and important biological functions, one of which may be to mediate developmental information from mesenchyme to epithelia during "instructive" stages of tooth development.

Animals↗
PubMedDate not supplied

Fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro.

OBJECTIVES: To define the release of nitric oxide (NO), prostaglandin E2 (PGE2), and the neutral metalloproteinases (NMPs) in horses with subchondral cystic lesions (SCL) and to study bone resorption triggered by conditioned media of fibrous tissue of SCL in vitro. STUDY DESIGN: Equine explant cultures of fibrous tissue of SCL, and synovial membrane and articular cartilage of normal horses and horses affected with moderate and severe osteoarthritis were performed. NO, PGE2, and NMP concentrations of media samples were measured, and osteoclast formation and activation was studied in vitro. ANIMALS: Experiment 1: 32 horses with SCL (n = 8), normal joints (7), and joints with moderate (7) and severe (10) osteoarthritis (OA). Experiment 2: 22 horses with SCL (n = 3), normal joints (7), and chip fractures (12). Experiment 3: Conditioned media of fibrous tissue from 3 horses with SCL of the medial femoral condyle (n = 1), distal metacarpal bone (1), and tarsal bone (1). METHODS: Determinations of local mediator concentrations were made with the Griess assay for NO and an enzyme immunoassay kit for PGE2 concentrations in biological fluids. Enzyme activities were assessed with radiolabeled substrates indicating collagenolytic, gelatinolytic, and caseinolytic activities. The resorption pit assay was used to assess osteoclast recruitment and activity. RESULTS: Fibrous tissue of SCL produced NO, PGE2, and NMPs. Of all the variables measured, PGE2 concentrations were the highest in cystic tissue of SCL compared with synovial membrane and articular cartilage from normal joints and joints with chip fractures, indicating that this mediator may play an important role in pathological bone resorption associated with SCL. These findings were supported by the observation that conditioned media of SCL tissue were capable of recruiting osteoclasts and increasing their activity. CONCLUSION: Fibrous tissue of SCL released NO, PGE2, and NMPs into the culture media. It is suspected that intralesional fibrous tissue may play an active role in the pathological process of bone resorption occurring in SCL in horses and may be partly responsible for the maintenance, slow healing rate, and expansion of these lesions. CLINICAL RELEVANCE: Understanding the pathogenesis of SCL will help to establish successful therapy in horses affected with SCL.

Analysis of Variance↗