Synthesis of antimicrobial agents. 3. Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.     

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.     

Klinische Erfahrungen mit der Knorpel-Knochen-Transplantation

The treatment of deep cartilage defects in load-bearing joints is a problem that still has no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously, usually leaving damage that can lead to early arthrosis. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, transplantation of tissue autografts and allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation of genuine hyaline articular cartilage and its retention at least in the medium term. The Draenert method, in which a water-cooled diamond bone-cutting system is used, is an effective procedure for resurfacing the joints affected by localised cartilaginous defects, even when there is also severe bone loss. Donor-side morbidity can be kept to a minimum by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone covered with periosteum for protection.     

De-novo expression of vascular ecto-5′-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure

Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.     

The concept of culture: A core issue in health disparities

Contemporary discourse contains numerous examples of use of the concept of culture by social and behavioral scientists. Simple reification, where the speaker makes culture into a thing capable of action exemplifies one usage in public discourse. Some quantitative social scientists attempt to characterize people’s cultural identities by means of a single categorical variable, which often “lumps” people into categories such as “Hispanic” or “Black” that in fact have numerous culturally bounded subcategories. Approaches that emphasize cultural process are preferable to those who attempt to categorize; more complex measures of acculturation help investigators to make convincing analyses of circumstances in which health disparities occur. Examples in which investigators make appropriate use of cultural characterizations demonstrate their utility in investigating health disparities in Haitian American women, injecting and noninjecting drug users, Hispanic youth, and adult Hispanics at risk of HIV infection. Focus on culture in the study of health disparities can identify entanglements between structural factors such as poverty and lack of education and cultural factors such as beliefs about health. Qualitative methods coupled with quantitative methods have great potential to improve investigators’ grasp of cultural nuance while capturing the distribution of qualitatively derived behaviors.