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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potential behavioral and teratogenic effects of caffeine were studied in Charles River CD albino rats. Caffeine in distilled water was given by gavage to pregnant rats (dams) at doses of 5, 25, 50 or 75 mg/kg on Days 3-19 of gestation. Concurrent controls received distilled water gavage (10 ml/kg) on the same days. Dams were allowed to deliver normally. Physical and behavioral observations were made on dams during gestation and lactation and on F1 offspring through 9 weeks of age. Caffeine decreased body weights and food intake and increased water intake in gestating dams but these effects dissipated during lactation. Spontaneous locomotor activity (PAC) and open field (OF) were increased immediately after caffeine gavage but not before. Parturition was slightly delayed. With analyses of data based on individual pups the following effects were noted. Pre- and post-weaning offspring body weights were decreased in females at 50 and 75 mg/kg and in males at 75 mg/kg. Incisor eruption was delayed in females at 5, 50 and 75 mg/kg and in males at all doses. Auditory startle developed earlier in the 5 mg/kg dose group but was delayed at 75 mg/kg for males only. Eye opening was delayed in both sexes at 25, 50 and 75 mg/kg. In females, vaginal opening was delayed at 5, 25 and 75 mg/kg and 9-week ovary weights were increased at 75 mg/kg. In postweaning males, food intake was decreased and water intake was increased with increasing dose. In males, PAC was decreased at 75 mg/kg only on Day 12. At 7 weeks of age, step-down passive avoidance was decreased at 5 and 25 mg/kg but increased at 50 and 75 mg/kg, and at 8 weeks of age, shuttlebox active avoidance was decreased with increasing dose. Maternal and offspring behaviors were only weakly correlated. Correction for litter effect in developmental data yielded fewer significant results and only at 50 and 75 mg/kg. The issue of whether it is always appropriate to correct for "litter effect" is discussed.
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PMID:Postnatal neurobehavioral development in rats exposed in utero to caffeine. 370 93

The cardiotoxic potential of the phenothiazine neuroleptic thioridazine and five of its metabolites, including two stereoisomeric forms of thioridazine 5-sulfoxide (ring sulfoxide), was characterized in the isolated perfused rat heart. Hearts from male Sprague-Dawley rats were perfused using a modified Langendorff technique. After a 30-min control period, hearts were perfused for 30 min with 15 or 30 microM thioridazine, racemic and isomeric forms of thioridazine 5-sulfoxide, or thioridazine 2-sulfoxide. Thioridazine disulfoxide, thioridazine 2-sulfone, and desmethylthioridazine 2-sulfoxide were perfused at 15 microM. Thioridazine (15 microM) severely reduced contractile tension and the rate of tension development (dT/dt), transiently increased coronary flow rate but prolonged conductance through the AV node. No arrhythmias were seen. At 30 microM, ventricular premature contractions and irregular rhythms occurred, progressing to asystole. Thioridazine 5-sulfoxide was arrhythmogenic at 15 and 30 microM. Atrial premature contractions and paroxysmal atrial tachycardia progressed to second degree AV block. Contractile tension and dT/dt declined although not as quickly when compared to thioridazine. Each isomeric form of thioridazine 5-sulfoxide was also cardiotoxic at 15 and 30 microM. There were minor differences in the onset and degree of toxicity but the overall results did not suggest a stereoselective effect. Lactic dehydrogenase and aspartate aminotransferase concentrations were unchanged after thioridazine 5-sulfoxide perfusion indicating no direct tissue damage. Thioridazine 5-sulfoxide induced arrhythmias could not be prevented or reversed by treatment with adrenergic agonists. They were reversible upon washout, however. The other metabolites were not arrhythmogenic at 15 microM. Racemic thioridazine 5-sulfoxide appears to be qualitatively and quantitatively more arrhythmogenic than thioridazine, an action that does not appear to be stereoselective.
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PMID:Cardiotoxicity of thioridazine and two stereoisomeric forms of thioridazine 5-sulfoxide in the isolated perfused rat heart. 376 35

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
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PMID:Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts. 1611 32

Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.
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PMID:New pharmacological strategies in rheumatic diseases. 2797 25