ABSTRACT
OBJECTIVE: The morphology of lesions in mouse models of osteoarthritis (OA) has not been comprehensively characterized, in part because current histological assessments of OA focus primarily on articular cartilage (AC). In the present study, sections of murine stifle joints with naturally occurring (aged animals) and surgically induced (destabilized medial meniscus, DMM) OA were examined using a newly developed histological grading scheme that includes quantitative measurements and semiquantitative grades to evaluate multiple joint tissues. DESIGN: The data collected was analyzed using Principal Components Analysis (PCA); factor scores for each joint were generated. Individual parameters and factor scores were compared between surgical groups and among age groups. For comparison, the original Mankin Histological-Histochemical Grading System (HHGS) also was applied. RESULTS: Overall, lesions were most severe in the medial tibial plateaus. Significant changes in AC and neighboring bone were identified in surgically induced models and in naturally occurring disease. Mean factor scores provided a comprehensive evaluation of joint changes. An important new finding was that chondrocyte cell death within the AC was a commonly identified lesion and its extent significantly increased with age. While the Mankin HHGS detected significant overall differences in OA severity between surgical groups, it was not sensitive in detecting age-related differences, nor did it provide information regarding changes in individual tissues. CONCLUSION: These results demonstrate the utility of this newly developed murine OA grading scheme in identifying lesions in AC and in other joint tissues. Surgically induced changes were similar to those occurring naturally with aging.
Subject(s)
Arthritis, Experimental/pathology , Cartilage, Articular/pathology , Chondrocytes/pathology , Osteoarthritis/pathology , Aging/pathology , Animals , Male , Menisci, Tibial/pathology , Mice , Mice, Inbred C57BL , Osteoarthritis/diagnosis , Stifle/pathologyABSTRACT
The specificity of benzodiazepine pretreatment on the reinforcing efficacy of cocaine was investigated using a multiple schedule of cocaine and food presentation. Cocaine was available under a fixed-ratio 4 schedule of reinforcement during 1 h of the session, while food was delivered under a discrete-trial, fixed-ratio 10 schedule during the other. Following initial exposure to alprazolam, responding maintained by both cocaine and food was significantly reduced. However, tolerance quickly developed to the sedative effects of alprazolam on food-maintained responding, while no reduction in the effects of the drug on cocaine self-administration was observed. Alprazolam (0.5 to 4.0 mg/kg, IP) significantly reduced cocaine intake without affecting food-maintained responding following subsequent testing with the drug. These data suggest a potential specific effect (e.g., anxiolytic) of alprazolam in cocaine reinforcement.
Subject(s)
Alprazolam/pharmacology , Cocaine/antagonists & inhibitors , Reinforcement Schedule , Animals , Cocaine/administration & dosage , Conditioning, Operant/drug effects , Drug Tolerance , Feeding Behavior/drug effects , Male , Rats , Rats, Inbred F344 , Self AdministrationABSTRACT
Intrauterine insemination by itself for multiple and/or severe infertility factors had no benefit over cervical cap with whole ejaculate or coitus in this study. The PRs for IUI and cervical cap with whole ejaculate or coitus were similar and low, suggesting that IUI by itself has limited, if any, utility in enhancing PRs in this type of infertility population. Couples attempting IUI should be advised about the low probability of achieving pregnancy. Ovulation stimulation and/or heterologous donor insemination, IVF, or gamete intrafallopian transfer may be beneficial therapeutic options.
Subject(s)
Infertility, Female/therapy , Insemination, Artificial, Homologous/methods , Adult , Coitus , Female , Humans , Pregnancy , Prospective Studies , UterusABSTRACT
This investigation was designed to examine the effects of benzodiazepines on intravenous cocaine self-administration in rats. Pretreatment with low doses of the benzodiazepine receptor agonist, chlordiazepoxide (0.3 to 1.0 mg/kg, IP), resulted in small but nonsignificant increases in drug intake with 0.5 mg/kg cocaine, while higher doses (10 mg/kg, IP) significantly decreased drug intake in all rats tested. The effects of chlordiazepoxide on self-administration were attenuated when the concentration of cocaine was increased to 1.0 mg/kg, suggesting that chlordiazepoxide was opposing rather than augmenting the pharmacological actions of cocaine. Pretreatment with the benzodiazepine receptor antagonist, Ro 15-1788 (1.0 to 10 mg/kg, IP), had no effect on self-administration, suggesting that the reinforcing properties of cocaine do not result from direct interactions with benzodiazepine receptors. The result of this investigation demonstrate that chlordiazepoxide alters intravenous cocaine self-administration in rats. Although additional research will be necessary to confirm these data, the results of this investigation suggest that chlordiazepoxide may decrease the reinforcing efficacy of cocaine through indirect actions on dopaminergic neuronal activity potentially mediated through GABAergic mechanisms via benzodiazepine receptor activation.
