McCully JD, Cowan DB, Pacak CA, Toumpoulis IK, Dayalan H, Levitsky S. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am J Physiol Heart Circ Physiol 296: H94 -H105, 2009. First published October 31, 2008 doi:10.1152/ajpheart.00567.2008.-Previously, we demonstrated that ischemia induces mitochondrial damage and dysfunction that persist throughout reperfusion and impact negatively on postischemic functional recovery and cellular viability. We hypothesized that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, would enhance postischemic functional recovery and limit infarct size. New Zealand White rabbits (n ϭ 52) were subjected to 30 min of equilibrium and 30 min of regional ischemia (RI) induced by snaring the left anterior descending coronary artery. At 29 min of RI, the RI zone was injected with vehicle (sham control and RI vehicle) or vehicle containing mitochondria (7.7 ϫ 10 6 Ϯ 1.5 ϫ 10 6 /ml) isolated from donor rabbit left ventricular tissue (RI-Mito). The snare was released at 30 min of RI, and the hearts were reperfused for 120 min. Our results show that left ventricular peak developed pressure and systolic shortening in RI-Mito hearts were significantly enhanced (P Ͻ 0.05 vs. RI-vehicle) to 75% and 83% of equilibrium value, respectively, at 120 min of reperfusion compared with 57% and 62%, respectively, in RI-vehicle hearts. Creatine kinase-MB, cardiac troponin I, and infarct size relative to area at risk were significantly decreased in RI-Mito compared with RI-vehicle hearts (P Ͻ 0.05). Confocal microscopy showed that injected mitochondria were present and viable after 120 min of reperfusion and were distributed from the epicardium to the subendocardium. These results demonstrate that viable respiration-competent mitochondria, isolated from tissue unaffected by ischemia and then injected into the ischemic zone just before reperfusion, significantly enhance postischemic functional recovery and cellular viability. ischemia; infarct; apoptosis PREVIOUSLY, WE AND OTHERS demonstrated that myocardial ischemia initiates a succession of events resulting in alterations of mitochondrial volume, mitochondrial structure, mitochondrial oxidative phosphorylation, mitochondrial oxygen consumption, and mitochondrial calcium accumulation that extend into reperfusion to severely compromise myocardial postischemic functional recovery and significantly increase infarct size (IS) (11,15,30).We and others attempted to modulate the effects of ischemia on mitochondrial structure and function by pharmaceutical and/or exogenous substrate intervention alone or in combination with procedural techniques to provide cardioprotection (2,11,15,16,30,36). These protocols, for the most part, provided only limited cardioprotection, and mitochondrial damage and dysfunction remained after myocardial ischemia and continued to impact negatively on postischemic functional recovery and cellular viability. T...

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Methotrexate (MTX), a cytotoxic chemotherapeutic agent, is considered an effective drug in the treatment of psoriasis. The aim of this study was to find out whether the effect of MTX treatment in psoriasis is due to oxidative stress-induced apoptosis. Psoriasis vulgaris patients (58 in number) were recruited for this study. Healthy volunteers (45 in number) served as control. Samples of psoriatic patients were collected and analyzed for total reactive oxygen species (ROS), malondialdehyde (MDA) levels, nitrite, nitrate levels and the activities of antioxidants like superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) and also the protein expression of caspase-3, before (Day 0) and after (at the end of 6 and 12 weeks) MTX treatment. Our results show a significant increase in tissue ROS and plasma MDA after MTX treatment when compared with before MTX treatment in psoriasis patients (p < 0.001). The levels of serum nitrite and nitrate were decreased significantly after MTX treatment (p < 0.001). The activities of plasma SOD, TAS and serum CAT levels were decreased, but not significantly after 12 weeks of treatment. The expression of caspase-3 was increased after MTX treatment. In conclusion, MTX induce apoptosis through oxidative stress by reducing NO and increasing caspase-3 levels. MTX-induced apoptosis may account for the beneficial effect of MTX treatment in psoriasis patients, which is characterized by acanthosis.

Background:Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis.Aim:Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters.Materials and Methods:Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals.Results:ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels.Conclusion:Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters.

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