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[Possibilities and results of using clopidogrel (Listab) in comprehensive treatment of patients with crural deep veins thrombosis].
Gavrilenko, AV, Voronov, DA
Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery. 2015;(1):91-4; 96-8
Abstract
The authors carried out a prospective non-randomized controlled study including patients undergoing conservative treatment for acute thrombosis of crural deep veins with a stable course of the disease. A total of 60 patients discharged from hospital for further outpatient follow up and treatment were subdivided into two groups: Group I (study group, "Listab" group) composed of 35 patients who immediately began taking prescribed clopidogrel ("Listab") at a dose of 75 mg a day, and Group II (first control group, "VKA" group) comprising 25 patients receiving vitamin K antagonists (VKA) at various doses according to the generally accepted recommendations. We retrospectively formed Group III consisting of 21 patients (second control group, "ASA or VKA" group) who despite initial prescription of VKA either received them interruptedly and only for a short time after discharge from hospital or took preparations of acetylsalicylic acid (ASA) alone. The cumulative index of freedom from negative clinical outcomes after 12 months of follow up in the "Listab" group amounted to 0.9143, in the "VKA" group to 0.9600, and in the "ASA or VKA" group to 0.7619. The cumulative index of freedom from negative clinical and/or ultrasound outcomes after 12 months of follow up amounted to 0.8571, 0.8400, and 0.6190, respectively. In the "Listab" group the relative incidence of adverse events while taking the drug as calculated per 100 patient-months amounted to 1.79 and in the "VKA" group to 2.95. Administration of Listab was associated with the best patient compliance as compared to other drugs (VKA and ASA). The proportion of patients reporting regular taking of the drug in the "Listab" group amounted to 91.4%. A conclusion was drawn that in patients with crural deep vein thrombosis with a stable course of the acute period of the disease Listab may be used effectively and safely in comprehensive ambulatory treatment of patients having low adherence to taking VKA and to regular laboratory monitoring of the coagulation level (or if such monitoring is impossible), as well as in cases of high risk of haemorrhage while taking VKA. The final determination of the possibility of using clopidogrel-containing drugs and their place in treatment of the pathology concerned requires larger clinical trials.
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The effects of resistance exercise training on macro- and micro-circulatory responses to feeding and skeletal muscle protein anabolism in older men.
Phillips, BE, Atherton, PJ, Varadhan, K, Limb, MC, Wilkinson, DJ, Sjøberg, KA, Smith, K, Williams, JP
The Journal of physiology. 2015;(12):2721-34
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Abstract
KEY POINTS Increases in limb blood flow in response to nutrition are reduced in older age. Muscle microvascular blood flow (MBF) in response to nutrition is also reduced with advancing age and this may contribute to age-related 'anabolic resistance'. Resistance exercise training (RET) can rejuvenate limb blood flow responses to nutrition in older individuals. We report here that 20 weeks of RET also restores muscle MBF in older individuals. Restoration of MBF does not, however, enhance muscle anabolic responses to nutrition. ABSTRACT The anabolic effects of dietary protein on skeletal muscle depend on adequate skeletal muscle perfusion, which is impaired in older people. This study explores fed state muscle microvascular blood flow, protein metabolism and exercise training status in older men. We measured leg blood flow (LBF), muscle microvascular blood volume (MBV) and muscle protein turnover under post-absorptive and fed state (i.v. Glamin to double amino acids, dextrose to sustain glucose ∼7-7.5 mmol l(-1) ) conditions in two groups: 10 untrained men (72.3 ± 1.4 years; body mass index (BMI) 26.5 ± 1.15 kg m(2) ) and 10 men who had undertaken 20 weeks of fully supervised, whole-body resistance exercise training (RET) (72.8 ± 1.4 years; BMI 26.3 ± 1.2 kg m(2) ). We measured LBF by Doppler ultrasound and muscle MBV by contrast-enhanced ultrasound. Muscle protein synthesis (MPS) was measured using [1, 2-(13) C2 ] leucine with breakdown (MPB) and net protein balance (NPB) by ring-[D5 ] phenylalanine tracers. Plasma insulin was measured via ELISA and indices of anabolic signalling (e.g. Akt/mTORC1) by immunoblotting from muscle biopsies. Whereas older untrained men did not exhibit fed-state increases in LBF or MBV, the RET group exhibited increases in both LBF and MBV. Despite our hypothesis that enhanced fed-state circulatory responses would improve anabolic responses to nutrition, fed-state increases in MPS (∼50-75%; P < 0.001) were identical in both groups. Finally, whereas only the RET group exhibited fed-state suppression of MPB (∼-38%; P < 0.05), positive NPB achieved was similar in both groups. We conclude that RET enhances fed-state LBF and MBV and restores nutrient-dependent attenuation of MPB without robustly enhancing MPS or NPB.
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Ascorbate improves circulation in postural tachycardia syndrome.
Stewart, JM, Ocon, AJ, Medow, MS
American journal of physiology. Heart and circulatory physiology. 2011;(3):H1033-42
Abstract
Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.
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Improvement in systemic endothelial condition following amputation in patients with critical limb ischemia.
Newton, DJ, Khan, F, Kennedy, G, Belch, JJ
International angiology : a journal of the International Union of Angiology. 2008;(5):408-12
Abstract
AIM: Most patients with critical limb ischemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality. Peripheral ischemic tissue produces circulating toxic molecules, which may worsen endothelial function systemically and contribute to the general atherosclerotic process within the body. We looked at whether markers of endothelial function improve after amputation of the ischemic limb, when this potential source of toxins has been removed. METHODS We measured blood levels of vascular endothelial growth factor (VEGF), homocysteine, endothelin-1, vascular cell adhesion molecule-1, E-selectin, thrombomodulin and von Willebrand factor (vWF) in 40 patients with CLI. We also assessed peripheral microvascular function in forearm skin by measuring responses to iontophoresis of acetylcholine and sodium nitroprusside. The measurements were repeated 6 months after amputation. RESULTS We found abnormally high levels of endothelial products in the patients, and 6 months later VEGF and vWF had both reduced significantly from previous values (by 70% and 40%, respectively; P<0.01 in both cases). CONCLUSION Improvements in these two markers after amputation are consistent with the hypothesis that peripheral ischemic tissue has a systemic effect on the vascular endothelium and may contribute to the progression of coronary heart disease in patients with CLI.
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The effect of 6 months training on leg power, balance, and functional mobility of independently living adults over 70 years old.
Ramsbottom, R, Ambler, A, Potter, J, Jordan, B, Nevill, A, Williams, C
Journal of aging and physical activity. 2004;(4):497-510
Abstract
Where strength training has been used in conjunction with functional-task training in older people, not only have there been improvements in leg strength but also improved function has been measured (e.g., Skelton & McLaughlin, 1996). Many studies use participants from care homes rather than community dwellers. We investigated changes in leg power, balance, and functional mobility in community-dwelling sedentary men and women over 70 years of age (n = 6 for training group [TR]; n = 10 for control group [CN]). Progressive training took place over 24 weeks using seated and nonseated exercise. For TR, leg power increased 40%, from 108 +/- 40 to 141 +/- 53 W (p < .01); dynamic balance increased 48%, from 22.3 +/- 7.9 to 33.1 +/- 6.1 cm (p < .01; functional reach); and functional mobility increased 12%, from 7.46 +/- 1.32 to 6.54 +/- 1.41 s (p < .05; timed walk). CN showed no significant change. In conclusion, a community-based exercise program led to large improvements in leg-extensor power, dynamic balance, and functional mobility.
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Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease.
Gokce, N, Vita, JA, Bader, DS, Sherman, DL, Hunter, LM, Holbrook, M, O'Malley, C, Keaney, JF, Balady, GJ
The American journal of cardiology. 2002;(2):124-7
Abstract
Aerobic exercise training improves endothelial vasomotor function in the coronary circulation of patients with coronary artery disease (CAD), an effect that has been attributed to local repetitive increases in shear stress on the endothelium. To study the effects of exercise on endothelial function in the peripheral circulation, we used vascular ultrasound to examine flow-mediated dilation and nitroglycerin-mediated dilation in the brachial and posterior tibial arteries of 58 subjects with CAD. Studies were performed at baseline and after 10 weeks in 40 subjects (aged 59 +/- 10 years) who participated in a supervised cardiac rehabilitation program that predominantly involved moderate intensity leg exercise (three 30-minute sessions/week), and 18 matched patients who did not exercise and maintained a sedentary lifestyle. Exercise was associated with a 29% increase in functional capacity (7.3 +/- 2.2 vs 9.4 +/- 2.7 METs, p <0.001), and significant improvement in endothelium-dependent, flow-mediated dilation in a conduit artery of the leg, but not the arm. Nitroglycerin-mediated dilation in the upper arm and lower extremity was unaffected. These findings suggest that exercise improves endothelial function in peripheral conduit arteries of patients with CAD and that the beneficial effect may be more marked in the vascular beds of the exercised limbs.