ABSTRACT
The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.
Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Neuropeptides/pharmacology , Optic Nerve/blood supply , Substance P/analogs & derivatives , Sumatriptan/adverse effects , Animals , Arterioles/drug effects , Blood-Retinal Barrier/drug effects , Calcitonin Gene-Related Peptide/antagonists & inhibitors , Capsaicin/antagonists & inhibitors , Capsaicin/pharmacology , Dose-Response Relationship, Drug , Female , Male , Microinjections , Neurokinin A/antagonists & inhibitors , Neurokinin A/pharmacology , Neurokinin B/pharmacology , Neurokinin-1 Receptor Antagonists , Optic Nerve/drug effects , Optic Nerve/physiopathology , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/pharmacology , Rabbits , Receptors, Calcitonin Gene-Related Peptide , Receptors, Neurokinin-1/physiology , Receptors, Neurokinin-2/antagonists & inhibitors , Receptors, Neurokinin-2/physiology , Retinal Vessels/drug effects , Retinal Vessels/physiology , Substance P/pharmacology , Sumatriptan/administration & dosage , Sumatriptan/pharmacokinetics , Vasodilation/drug effects , Vasodilation/physiologyABSTRACT
Antimicrobial susceptibility testing of pneumococci is now essential to monitor for the presence of resistance to agents such as the penicillins, macrolides, lincomycins, chloramphenicol, and tetracycline. In this study, clinical isolates of a selection of resistant South African strains were tested for antimicrobial susceptibility by minimal inhibitory concentration (MIC) determination and by a modified Kirby-Bauer disk diffusion technique, using Mueller-Hinton medium supplemented with 5% horse blood. Disk diffusion breakpoints were determined for penicillin G, erythromycin, clindamycin, tetracycline, chloramphenicol, and rifampin. Reliable results were obtained on disk diffusion for all these agents except for penicillin G. With 6-mug penicillin G disks, zones of strains with intermediate penicillin susceptibility overlapped those of sensitive and resistant strains. With 5-mug methicillin disks, clearer separation of strains based on susceptibility to penicillin G occurred. Strains with zones of <35 mm around penicillin G disks and <25 mm around methicillin disks should have penicillin G MICs determined to confirm their resistance to penicillin G. In view of the potential for pneumococci to be resistant to the agents used in this study, antimicrobial susceptibility of all clinically significant isolates should be determined.
Subject(s)
Streptococcus pneumoniae/drug effects , Chloramphenicol/pharmacology , Clindamycin/pharmacology , Erythromycin/pharmacology , Humans , Microbial Sensitivity Tests , Penicillin G/pharmacology , Penicillin Resistance , Rifampin/pharmacology , Tetracycline/pharmacologyABSTRACT
Strains of Streptococcus pneumoniae resistant to penicillin have been reported from several countries around the world. Many South African isolates, in addition, exhibit resistance to tetracycline, chloramphenicol, erythromycin, clindamycin, and cotrimoxazole in varying patterns. A qualitative test of the ability of antibiotic-resistant pneumococci to inactivate penicillin, oxacillin, cephalothin, cefoxitin, chloramphenicol, tetracycline, minocycline, erythromycin, clindamycin, streptomycin, gentamicin, and cotrimoxazole revealed that only chloramphenicol was degraded. This finding was confirmed in a quantitative test in which the residual antimicrobial activity of broth containing chloramphenicol in subinhibitory concentrations was determined after incubation with antibiotic-resistant bacteria. Chloramphenicol resistance was shown to be associated with the production of inducible chloramphenicol acetyltransferase. No beta-lactamase activity was demonstrated. Plasmid deoxyribonucleic acid was not demonstrable in partially purified lysates of antibiotic-resistant strains of S. pneumoniae.
