ABSTRACT
Sepsis is a critical illness with high morbidity and mortality. Anaerobic glycolysis plays an important role in the pathogenesis of sepsis. Pyruvate dehydrogenase complex (PDHC) serves as a key regulator during sepsis. With PDHC dephosphorylation and deacetylation, PDHC activity is upregulated, allowing pyruvate translocate to mitochondria in aerobic condition, preceding the production of acetyl-CoA to accelerate aerobic oxidation. Activation of PDHC improves the prognosis of sepsis through regulating the balance of lactate, release of inflammatory factors and energy metabolism. A variety of remedies can improve the prognosis of patients with sepsis by up-regulating the activity of PDHC, including dichloroacetate (DCA), vitamin B1, milrinone, tumor necrosis factor binding protein, and ciprofloxacin.This article reviews the role and the regulatory mechanism of PDHC and signal pathway in the sepsis metabolism, in order to innovate treatment for sepsis and multiple organ dysfunction.
ABSTRACT
Objective To investigate the hemodynamic parameters to stabilize cerebral blood flow within limits of cerebral autoregualtion. Methods We assessed the flow velocity of middle cerebral artery using transcranial Doppler and recorded invasively the blood pressure simultaneously. We then analyzed the curves of cerebral blood flow autoregulation (CBFA) and calculated upper limit of autoregulation (ULA) and lower limit of autoregulation (LLA). The values of critical closing pressue (CCP) and resistance area product (RAP) were calculated according to previous theory. The relationship between CCP, RAP and MABP were analyzed. Results In the process of increasing or decreasing blood pressure, ULA and LLA of normal rats were 148.12 ± 7.49 mmHg or 62.96 ± 3.34 mmHg, respectively. When mean artery blood pressue (MABP) changed within limits of cerebral autoregulation, the cerebral blood flow velocity changed little (increasing:0.65± 0.27 cm/s/10mmHg MABP, decreasing:0.43±0.23cm/s/10 mmHg MABP), while CCP and RAP changed significantly (in?creasing: 4.60 ± 1.06 mmHg/10mmHg MABP and 0.11 ± 0.04/10 mmHg MABP, decreasing: 6.74 ± 0.59 mmHg/10 mmHg MABP and 0.09 ± 0.02/10mmHg MABP). After fixing change of blood flow velocity, CCP and RAP were correlated with MABP more remarkablely, although all blood flow velocity, CCP and RAP were significantly correlated with MABP. Conclusion Within limits of cerebral autoregulation, stable cerebral blood flow is mainly achieved by the change of CCP and RAP against blood pressure changing on normal rats, especially the increasing or de?creasing of CCP.
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[ ABSTRACT] Myosin light chain kinase ( MLCK) activates the regulatory light chain of myosin II, and the phos-phorylated myosin light chain leads to actomyosin contractile activity, as well as the cell contraction and increasing intercel-lular gap, which finally results in endothelial barrier dysfunction.MLCK-dependent hyperpermeability occurs in response to multiple cell signaling molecules and signaling pathways, including Ca2+, Src, PKC, NO, cGMP and mitogen activated protein kinases ( MAPK) .In this review, different mechanisms of endothelial hyperpermeability mediated by MLCK are discussed.
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Objective To investigate the correlation between the measurement methods of carotidcerebral pulse wave velocity (ccPWV) and the traditional method of brachial-ankle pulse wave velocity (baPWV).Methods A total of 136 healthy volunteers were divided into a youth group (20-39 years),a middleaged group (40-59 years),and an elderly group (more than 60 years) according to their ages.While detecting baPWV,transcranial Doppler ultrasound was used to simultaneously monitor the ipsilateral common carotid artery and the terminal segment of internal carotid artery.The time differences of the beating points of their cardiac cycles and the distanceses of the skin surfaces between the 2 probes were measured and ccPWV was calculated.Results The systolic blood pressure,pulse pressure and mean arterial pressure in the elderly group were signifificantly higher than those in the middle-aged group and the young group.The ccPWVs in the youth,middle-aged and elderly groups were 418 ± 52 cm/s,489 ±54 cm/s,and 599 ± 58 cm/s,respectively.The elderly group was significantly faster than the middle-aged group (t =7.308,P ＜0.001),and the middle-aged group was significantly faster than the youth group (t=6.758,P＜0.001).A Pearson correlation analysis showed that ccPWV was significantly positively associated with the age (r=0.847,P＜0.001) and baPWV (r =0.548,P ＜0.001).The multiple linear regression analysis showed that ccPWV was significantly positively associated with the age and diastolic blood pressure (partial correlation coefficients were 0.742 and 0.293respectively,P ＜0.001 and ＜0.010 respectively).Conchlusions ccPWV is a new measurement method for cerebrovascular stiffneas,and it has a good correlation with the traditional measurement method.
