Enhanced charge-independent mitochondrial free Ca2 + and attenuated ADP-induced NADH oxidation by isoflurane: Implications for cardioprotection

Modulation of mitochondrial free Ca^2 + ([Ca^2 +]_m) is implicated as one of the possible upstream factors that initiates anesthetic-mediated cardioprotection against ischemia–reperfusion (IR) injury. To unravel possible mechanisms by which volatile anesthetics modulate [Ca^2 +]_m and mitochondrial bioenergetics, with implications for cardioprotection, experiments were conducted to spectrofluorometrically measure concentration-dependent effects of isoflurane (0.5, 1, 1.5, 2 mM) on the magnitudes and time-courses of [Ca^2 +]_m and mitochondrial redox state (NADH), membrane potential (ΔΨ_m), respiration, and matrix volume. Isolated mitochondria from rat hearts were energized with 10 mM Na⁺- or K⁺-pyruvate/malate (NaPM or KPM) or Na⁺-succinate (NaSuc) followed by additions of isoflurane, 0.5 mM CaCl₂ (≈ 200 nM free Ca^2 + with 1 mM EGTA buffer), and 250 μM ADP. Isoflurane stepwise: (a) increased [Ca^2 +]_m in state 2 with NaPM, but not with KPM substrate, despite an isoflurane-induced slight fall in ΔΨ_m and a mild matrix expansion, and (b) decreased NADH oxidation, respiration, ΔΨ_m, and matrix volume in state 3, while prolonging the duration of state 3 NADH oxidation, respiration, ΔΨ_m, and matrix contraction with PM substrates. These findings suggest that isoflurane's effects are mediated in part at the mitochondrial level: (1) to enhance the net rate of state 2 Ca^2 + uptake by inhibiting the Na⁺/Ca^2 + exchanger (NCE), independent of changes in ΔΨ_m and matrix volume, and (2) to decrease the rates of state 3 electron transfer and ADP phosphorylation by inhibiting complex I. These direct effects of isoflurane to increase [Ca^2 +]_m, while depressing NCE activity and oxidative phosphorylation, could underlie the mechanisms by which isoflurane provides cardioprotection against IR injury at the mitochondrial level.     

WRKY transcription factors: evolution,regulation, and functional diversity in plants

Protoplasma - The recent advancements in sequencing technologies and informatic tools promoted a paradigm shift to decipher the hidden biological mysteries and transformed the biological issues...     

Diurnal variation and oscillatory patterns in physiological responses and HSP70 profile in heat stressed yaks at high altitude

The present study was carried out at altitude of 3000 m above sea level (asl) to evaluate the impact of heat stress on yak adaptability. Sixteen healthy yaks of different age were randomly divided into two groups, calf (GI; n = 8) and adult (GII; n = 8). Experimental yaks were exposed to heat stress in the open paddock. THI ranged between 61.60 and 64.17 which were beyond the comfortable limit for yak. Post-exposure, rectal temperature increased (p < 0.01) by 2.97 °F and 2.42 °F in calf and adult yaks as compared to pre-exposure (100.08 ± 0.04 °F, 100.06 ± 0.05 °F). Respiration rate increased (p < 0.01) by 2.96 and 2.40 fold in calf and adult yaks with increased pulse rate on post-exposure to heat stress. The oscillatory patterns of physiological responses indicated that the level of heat stress increment was higher (p < 0.05) in calves than adult yaks. Plasma HSP70 increased (p < 0.01) by 7 fold in calf and 5 fold in adult yaks in comparison to pre-exposure level of 83.67 ± 1.11pg/ml and 80.65 ± 1.35 pg/ml. Thus, the yaks were experiencing heat stress at high altitude of 3000 m asl during the warmer months of the year and calves were more prone to heat stress as compared to adults.     

Myeloid metaplasia in aspirates from enlarged spleens: a clue in the absence of peripheral blood findings characteristic of myelofibrosis

OBJECTIVE: To assess the significance of finding myeloid metaplasia in splenic aspirates from patients presenting with mild to moderate firm splenomegaly, in the absence of characteristic peripheral blood findings, in diagnosing idiopathic myelofibrosis. STUDY DESIGN: Archival records pertaining to 14 patients diagnosed as having myeloid metaplasia on splenic aspirates performed between September 2000 and April 2004 were analyzed. RESULTS: The relevant findings in these 9 women and 5 men were: splenic enlargement 17-21 cm with homogeneous echotexture on ultrasonography, hemoglobin 4-10 g/dL, variable pattern of anemia, total leukocyte count 6,300-28,800/ mm3 with neutrophilia and a few late myeloid precursors on the differential count, normal platelet counts, dry bone marrow tap in 10 patients and cellular marrow aspirate with prominence of megakaryocytes dispersed in a maturing cell population of myeloid and erythroid series in 4 patients. Splenic aspirates yielded foci of trilineage hematopoiesis suggestive of myeloid metaplasia, possibly due to myelofibrosis of idiopathic type, as confirmed on trephine biopsy in all cases. CONCLUSION: Splenic aspirates may be a useful tool for detecting myeloid metaplasia suggesting myelofibrosis when peripheral blood findings are not yet characteristic of the same. The procedure was not associated with any complications.