Role of increased peripheral vascular resistance in burn shock

In intact rabbits and rabbits with exclusion of the aortic and carotid sinus reflexogenic zones the effects of lethal burn trauma were studied on indices of the hemodynamics and respiration. Similar changes were found in the cardiac output and total oxygen consumption in the rabbits of the two groups. By contrast with intact animals, in rabbits with exclusion of the reflexogenic zones burns did not lead to any sharp rise of peripheral vascular resistance. The systemic arterial pressure fell correspondingly in these animals by a much greater degree than in the intact rabbits. The survival period of the denervated rabbits after burns was shorter than that of the intact rabbits. It is concluded that the increase in the peripheral vascular resistance in burn shock is of a reflex compensatory nature.Department of Experimental and Clinical Physiology, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 400–402, May, 1979.     

Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy

The main objective of the present study was to determine alterations of calcium handling in the diabetic rat heart during the transition from adaptive to maladaptive phase of cardiomyopathy. By inhibiting the nuclear enzyme poly(ADP-ribose) polymerase (PARP), we also investigated the possible role of this enzyme in the sequence of pathological events. Six weeks after induction of type I diabetes by injection of streptozotocin in rats, the hearts were perfused according to Langendorff. Intracellular-free calcium (Ca(2+)(i)) levels were measured by surface fluorometry using Indo-1 AM. Cyclic changes in Ca(2+)(i) concentrations and hemodynamic parameters were measured simultaneously. The hearts were challenged by infusion of isoproterenol. Six weeks of diabetes resulted in reduced inotropy and lusitropy. The diabetic hearts (DM) expressed a significantly elevated end-diastolic Ca(2+)(i) level (control, 111-/+20 vs DM, 221-/+35 nM). The maximal transport capacity of SERCA2a and conductance of RyR2 were reduced. These changes were not accompanied by major alterations in the tissue content of SERCA2a, RyR2, phospholamban and Na(+)/Ca(2+) exchanger. In response to beta-adrenergic activation, SERCA2a transport capacity and RyR2 conductance were stunted in the DM hearts. Inhibition of PARP induced minor changes in the mechanical function and calcium handling of the DM hearts. In conclusion, the observed changes in contractility and in Ca(2+)(i) handling are most likely attributable to functional disturbances of SERCA2a and RyR2 in this transitional phase of diabetes. At this stage of diabetes, PARP does not appear to play a significant pathogenetic role in the alterations in contractile function and calcium handling.     

Altered arachidonic acid metabolism and platelet size in atopic subjects

The release and metabolism of endogenous arachidonic acid (AA) in physiologically activated platelets obtained from 11 atopic patients with allergic rhinitis and/or asthma was compared to that of sex- and age-matched nonatopic controls. Prelabeled [3H]AA platelets were stimulated with thrombin or collagen and the amount of free [3H]AA and radiolabeled metabolites released were measured by high-performance liquid chromatography. The results obtained indicate that although the incorporation of [3H]AA into platelet phospholipids and total release of 3H-radioactivity upon stimulation were comparable in the two groups, the percentage of 3H-radioactivity released from platelets as free AA was significantly lower (P less than 0.01) in the atopic group. The reduction in free [3H]AA was accompanied by an increase (P less than 0.01) in the percentage of 3H-radioactivity released as cyclooxygenase products in atopic platelets (compared to nonatopic cells) after stimulation with 10 and 25 micrograms/ml collagen. The amount of platelet lipoxygenase product released was comparable between the two groups. Although the blood platelet counts were similar, the mean platelet volume was statistically higher (P less than 0.01) in the atopic group. These results indicate that arachidonic acid metabolism in atopic platelets is altered, the pathophysiological significance of which remains to be clarified.     

Postprandial lipemia as an early predictor of cardiovascular complications in childhood obesity

Abstract. The growing trend of childhood overweight and obesity is a major health concern worldwide. Although obesity is a key risk factor for cardiovascular disease, the etiologic link between obesity and the progression of vascular disease remains unknown. Traditionally, lowering fasting blood cholesterol concentration has been the main interventional target for decreasing the risk of heart disease. However, there is increasing evidence that elevated concentrations of intestinally-derived chylomicron particles are associated with cardiovascular disease risk and that this is particularly evident in insulin-resistance and obesity in adulthood. In this review we comment on recent evidence suggesting that overweight children have fasting chylomicron concentrations equivalent to that found in adults diagnosed with cardiovascular disease. Further, we consider the hypothesis that fasting and postprandial chylomicron metabolism has a central role in the genesis of cardiovascular disease during childhood obesity.     

Prenatal maternal personality as an early predictor of vulnerable parenting style

Archives of Women's Mental Health - Perinatal mental health problems, particularly depression, are prevalent and have been a central focus of prevention initiatives. The greater proportion of...     

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.     

妊高征患者胎盘血循环中血管舒、缩物质水平的改变及意义

目的　通过测定胎盘部位子宫静脉血中一氧化氮 (nitricoxide,NO)及内皮素 (endothelin ,ET)的浓度 ,并与外周血中同类物质的对比 ,了解妊高征时胎盘血管的病变程度及其与外周血中血管活性物质浓度改变的关系。方法　分别于剖宫产手术前及手术中抽取胎盘部位子宫静脉血和外周静脉血 ,应用硝酸根还原酶与Griess反应相结合的方法测定NO ;应用放射免疫分析法测定ET。结果　妊高征组胎盘部位子宫静脉血中NO2 -/NO3 -为 (70 2 6± 12 6 0 ) μmol/l,外周血清NO-2 /NO-3 为 (6 5 5 2± 14 88) μmol/l,二者之间无显著差异。妊高征组外周血浆ET水平为 (5 3 72± 15 2 8)ng/L ,胎盘部位子宫静脉血浆ET水平为 (5 2 80± 14 19)ng/L ,两者之间无显著性差异 (P >0 .0 1)。与正常晚孕组比较 ,妊高征组血中ET、NO-2 /NO-3 水平均显著增高 (P <0 .0 1)。结论　妊高征患者的子宫、胎盘循环系统血管舒、缩物质平衡失调 ,血管内皮系统的功能亦遭到破坏 ;妊高征患者胎盘血循环ET、NO水平升高 ,但与外周血中ET、NO水平的升高无关。     

Continuous measurement of peripheral vascular resistance and circulatory function

Peripheral vascular resistance, stroke volume, cardiac output and maximum acceleration were computed in ‘real-time’ using aortic pressure and flow signals processed by simple analogue circuits incorporated into a multichannel recording system. The use of the system was exemplified by records of the haemodynamic effects of methoxamine and adrenaline in anaesthetized dogs and noradrenaline, isoprenaline and ephedrine in unanaesthetized dogs. These analogue techniques are applicable to circulatory studies in man.     

Early-onset increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in SHR versus WKY.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p < 0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.     

绝经前后妇女载脂蛋白E基因多态性及血脂代谢的分析

为探讨绝经期妇女载脂蛋白E(ApoE)基因多态性的分布情况 ,以及载脂蛋白E基因多态性对绝经期妇女血脂代谢的影响。选取 10 4例绝经后妇女及 92例绝经前妇女 ,采用聚合酶链反应———限制片段长度多态性技术(PCR RFLP)来分析ApoE的基因型 ,并按常规酶法及免疫法测定血脂和载脂蛋白及脂蛋白 (a)。结果显示E3 3基因型及ε3等位基因频率在两组人群中均为最高 ,且在绝经后组中E3 2频率较普通人群明显低 ,在绝经后组中胆固醇(TC)甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)、载脂蛋白B(ApoB)及脂蛋白 (a) (Lp(a) )均显著高于绝经前组 (P<0 0 5 ,P <0 0 1)且在绝经后组中ε4携带者TC ,LDL C ,ApoB明显高于ε3携带者 (P <0 0 5 )。表明载脂蛋白E基因多态性对绝经期妇女血脂的代谢有一定的影响。     

Skin and platelet alpha-synuclein as peripheral biomarkers of Parkinson's disease

Parkinson's disease (PD) is a heterogeneous disease that can be difficult to diagnose, and for which we have no simple effective biomarker. In this study we have investigated whether peripheral alpha-synuclein might represent a useful biomarker given that it has a central role in the pathogenesis of PD. We found that full length and truncated alpha-synuclein is present in platelets, but the amount is very variable and does not correlate with disease presence or severity. Furthermore, we show that alpha-synuclein can be detected by immunoblotting in some, but not all, human skin biopsies, but again its level does not correlate with disease presence or severity. We conclude that skin or platelet alpha-synuclein would not be an appropriate diagnostic biomarker for PD.