Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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Liu, Penghao; Xie, Qihai; Wei, Tong; Chen, Yichen; Chen, Hong; Shen, Weili

2015-01-01

Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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Liu, Penghao [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Xie, Qihai [Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai (China); Wei, Tong [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Yichen [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Hong, E-mail: hchen100@shsmu.edu.cn [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Shen, Weili, E-mail: wlshen@sibs.ac.cn [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2015-12-04

Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

Prevention of cardiac complications in peripheral vascular surgery

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Cutler, B.S.

1986-01-01

The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. Complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. To reduce the incidence of cardiac complications, it is first necessary to identify patients at risk through screening tests. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise

Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus

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Torimoto Keiichi

2013-01-01

Full Text Available Abstract Background Fluctuations in blood glucose level cause endothelial dysfunction and play a critical role in onset and/or progression of atherosclerosis. We hypothesized that fluctuation in blood glucose levels correlate with vascular endothelial dysfunction and that this relationship can be assessed using common bedside medical devices. Methods Fluctuations in blood glucose levels were measured over 24 hours by continuous glucose monitoring (CGM on admission day 2 in 57 patients with type 2 diabetes mellitus. The reactive hyperemia index (RHI, an index of vascular endothelial function, was measured using peripheral arterial tonometry (EndoPAT on admission day 3. Results The natural logarithmic-scaled RHI (L_RHI correlated with SD (r=−0.504; PPP=0.001 and percentage of time ≥200 mg/dl (r=−0.292; P=0.028. In 12 patients with hypoglycemia, L_RHI also correlated with the percentage of time at hypoglycemia (r=−0.589; P=0.044. L_RHI did not correlate with HbA1c or fasting plasma glucose levels. Furthermore, L_RHI did not correlate with LDL cholesterol, HDL cholesterol, and triglyceride levels or with systolic and diastolic blood pressures. Finally, multivariate analysis identified MAGE as the only significant determinant of L_RHI. Conclusions Fluctuations in blood glucose levels play a significant role in vascular endothelial dysfunction in type 2 diabetes. Trial registration UMIN000007581

Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

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Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

2002-01-01

cardiovascular risk factors. CONCLUSIONS: These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium.......BACKGROUND: It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life...... ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. METHODS: We included in the study 131 patients with documented ischemic heart disease and a serum cholesterol level of > or =5 mmol/L before the institution of lipid-lowering treatment and dietary intervention...

Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

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Sankrityayan, Himanshu; Majumdar, Anuradha S

2016-01-01

Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers.

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Stirban, Alin; Nandrean, Simona; Kirana, Stanley; Götting, Christian; Veresiu, Ioan Andrei; Tschoepe, Diethelm

2012-01-01

Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7-10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% ((∗∗)P benfotiamine treatment to 25%(∗§) ((∗)P benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

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Goulopoulou, Styliani; Davidge, Sandra T

2015-02-01

In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of the erectile dysfunction of vascular origin by means of the ultrasound Doppler Duplex

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Varon, Claudia; Aponte, Hernan Alonso; Poveda, Alvaro; Rubiano, Nicolas; Serrano, Adolfo

1996-01-01

We studied 20 patients with erectile dysfunction of vascular origin and 10 patients with psychological erectile dysfunction with Doppler ultrasound before and after injection of intra cavernous vasoactive substances. We observed that psychological erectile dysfunction, is characterized by normal vascular velocities in cavernous arteries (control group). In patients with vascular aetiology we obtained abnormal registrations that differentiated arterial from venous pathology. There was a significant difference in the diameter of the cavernous artery and the systolic flow after the injection of vasoactive substances

Down-regulation of vascular PPAR-γ contributes to endothelial dysfunction in high-fat diet-induced obese mice exposed to chronic intermittent hypoxia.

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Zhang, Yanan; Zhang, Chunlian; Li, Haiou; Hou, Jingdong

2017-10-14

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is associated with endothelial dysfunction. The prevalence of OSA is linked to an epidemic of obesity. CIH has recently been reported to cause endothelial dysfunction in diet-induced obese animals by exaggerating oxidative stress and inflammation, but the underlying mechanism remains unclear. PPAR-γ, a ligand-inducible transcription factor that exerts anti-oxidant and anti-inflammatory effects, is down-regulated in the peripheral tissues in diet-induce obesity. We tested the hypothesis that down-regulation of vascular PPAR-γ in diet-induced obesity enhances inflammation and oxidative stress in response to CIH, resulting in endothelial dysfunction. Male C57BL/6 mice were fed either a high-fat diet (HFD) or a low-fat diet (LFD) and simultaneously exposed to CIH or intermittent air for 6 weeks. An additional HFD group received a combination of CIH and PPAR-γ agonist pioglitazone for 6 weeks. Endothelial-dependent vasodilation was impaired only in HFD group exposed to CIH, compared with other groups, but was restored by concomitant pioglitazone treatment. Molecular studies revealed that vascular PPAR-γ expression and activity were reduced in HFD groups, compared with LFD groups, but were reversed by pioglitazone treatment. In addition, CIH elevated vascular expression of NADPH oxidase 4 and dihydroethidium fluorescence, and increased expression of proinflammatory cytokines TNF-α and IL-1β in both LFD and HFD groups, but these increases was significantly greater in HFD group, along with decreased vascular eNOS activity. Pioglitazone treatment of HFD group prevented CIH-induced changes in above molecular markers. The results suggest that HFD-induced obesity down-regulates vascular PPAR-γ, which results in exaggerated oxidative stress and inflammation in response to CIH, contributing to endothelial dysfunction. This finding may provide new insights into the mechanisms by which OSA

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

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Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

Benfotiamine Counteracts Smoking-Induced Vascular Dysfunction in Healthy Smokers

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Alin Stirban

2012-01-01

Full Text Available Background. Smoking induces endothelial dysfunction (ED mainly by exacerbating oxidative stress (OS and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day. Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM. Smoking acutely induced a decrease in FMD by 50% (∗∗P<0.001 versus baseline an effect significantly reduced by benfotiamine treatment to 25%∗§ (∗P<0.05 versus baseline, §P<0.05 versus smoking alone. Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

A Ten Year Analysis of Fatal Peripheral Vascular Injuries Autopsy Study

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Salim Tuncer

2016-04-01

Full Text Available Aim: Peripheral vascular injuries are usually associated with fatal injuries. Early diagnosis and intervention are so vital for improving a favorable outcome for traumatic vascular injuries. As a preventable cause of death, we aimed to evaluate peripheral vascular injuries in overall deaths in ten year period, 2003-2012. Material and Method: A retrospective evaluation was made of 2845 death cases which had post-mortem examination and autopsy from the 10-year period of 2003-2012 in Eskisehir, Turkey. The mean age of the cases included in the study was 32.5±7.9 years with the highest rate of cases occurring in the 30-39 years age group. Males constituted 89.2% of the victims. The most frequent manner of death was homicide 83.8%.The femoral artery was the most commonly injured vessel 29 cases (78.4%. In this study it was identified that, 33 patients (89.3% died before any medical intervention could be performed. Discussion: Our study shows that, peripheral vascular injuries most commonly caused by sharp objects. The injuries have a low mortality rate when early intervention is made. Autopsies are conducted is very important to explain not only the cause of death but also the treatment process, which would clear the cases of any potential malpractice or negligence claims.

Effects of diabetic peripheral neuropathy on gait in vascular trans-tibial amputees.

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Nakajima, Hiroshi; Yamamoto, Sumiko; Katsuhira, Junji

2018-07-01

Patients with diabetes often develop diabetic peripheral neuropathy, which is a distal symmetric polyneuropathy, so foot function on the non-amputated side is expected to affect gait in vascular trans-tibial amputees. However, there is little information on the kinematics and kinetics of gait or the effects of diabetic peripheral neuropathy in vascular trans-tibial amputees. This study aimed to clarify these effects, including the biomechanics of the ankle on the non-amputated side. Participants were 10 vascular trans-tibial amputees with diabetic peripheral neuropathy (group V) and 8 traumatic trans-tibial amputees (group T). Each subject's gait was analyzed at a self-selected speed using a three-dimensional motion analyzer and force plates. Ankle plantarflexion angle, heel elevation angle, and peak and impulse of anterior ground reaction force were smaller on the non-amputated side during pre-swing in group V than in group T. Center of gravity during pre-swing on the non-amputated side was lower in group V than in group T. Hip extension torque during loading response on the prosthetic side was greater in group V than in group T. These findings suggest that the biomechanical function of the ankle on the non-amputated side during pre-swing is poorer in vascular trans-tibial amputees with DPN than in traumatic trans-tibial amputees; the height of the center of gravity could not be maintained during this phase in vascular trans-tibial amputees with diabetic peripheral neuropathy. The hip joint on the prosthetic side compensated for this diminished function at the ankle during loading response. Copyright © 2018 Elsevier Ltd. All rights reserved.

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

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Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

2016-01-01

This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812

THE INFLUENCE OF PERIPHERAL NEUROPATHY AND PERIPHERAL VASCULAR DISEASE IN THE OUTCOME OF DIABETIC FOOT MANAGEMENT – A PROSPECTIVE STUDY

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Sundar Prakash S, Krishnakumar, Chandra Prabha

2015-04-01

Full Text Available Objective: Peripheral neuropathy and Peripheral Vascular Disease are the risk factors for the development of diabetic foot. The aim of this study was to evaluate differences and predictors of outcome parameters in patients with diabetic foot by stratifying these subjects according to the severity of these risk factors. Materials and methods: This is a prospective study conducted in 70 patients in the age group of 30-90 years diagnosed as Type II Diabetes with foot ulcers. After detailed clinical examination the following tests were conducted in all the patients: Complete blood count (CBC, Haemoglobin (Hb, Random Blood Sugar (RBS, Erythrocyte Sedimentation rate (ESR, Chest X-ray(CXR, Electrocardiography (ECG, foot X-ray, pus culture, Neuropathy testing by Semmes Weinstein Monofilament Test and Vibration Perception Threshold and Peripheral vascularity assessment by Duplex Doppler. Then grading of the ulcers was done using Wagner’s Grade. The outcome of the patients was assessed by recording the healing time, mode of surgery and amputation rates of the patients. Results: A total of 70 patients with diabetic foot were consecutively included into the study (65.7% male, age (31% in 51-60 years, mean diabetes duration (5.2 years, Ulcer Grade (37% in Grade IV, Foot lesions (45.7% in toe, Blood sugar levels (64% in 300-400 mg/dl, Neuropathy (84%, Peripheral vascular disease (67%, major amputation (7% and mortality (1.4%. Conclusion: All diabetic patients should undergo testing for neuropathy and peripheral vascular disease apart from doing other tests.

Warfarin accelerated vascular calcification and worsened cardiac dysfunction in remnant kidney mice

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Ming-Tsun Tsai

2018-04-01

Full Text Available Background: Vascular calcification is highly prevalent in end-stage renal disease (ESRD and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model. Methods: Human aortic smooth muscle cells (HASMC were cultured in medium supplemented with warfarin and phosphate to investigate the potential role of this drug in osteoblast transdifferentiation. For in vivo study, adult male C57BL/6 mice underwent 5/6 nephrectomy were treated with active vitamin D3 plus warfarin to determine the extent of vascular calcification and parameters of cardiovascular function. Results: We found that the expressions of Runx2 and osteocalcin in HASMC were markedly enhanced in the culture medium containing warfarin and high phosphate concentration. Warfarin induced calcification of cultured HASMC in the presence of high phosphate levels, and this effect is inhibited by vitamin K2. Severe aortic calcification and reduced left ventricular ejection fractions were also noted in 5/6 nephrectomy mice treated with warfarin and active vitamin D3. Conclusion: Warfarin treatment contributes to the accelerated vascular calcification in animal models of advanced chronic kidney disease. Clinicians should therefore be aware of the profound risk of warfarin use on vascular calcification and cardiac dysfunction in patients with ESRD and atrial fibrillation. Keywords: Left ventricular dysfunction, Uremia, Vascular calcification, Warfarin

Determination of cardiac risk by dipyridamole-thallium imaging before peripheral vascular surgery

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Boucher, C.A.; Brewster, D.C.; Darling, R.C.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1985-01-01

To evaluate the severity of coronary artery disease in patients with severe peripheral vascular disease requiring surgery, preoperative dipyridamole-thallium imaging was performed in 54 stable patients with suspected coronary artery disease. Of the 54 patients, 48 had peripheral vascular surgery as scheduled without coronary angiography, of whom 8 (17 per cent) had postoperative cardiac ischemic events. The occurrence of these eight cardiac events could not have been predicted preoperatively by any clinical factors but did correlate with the presence of thallium redistribution. Eight of 16 patients with thallium redistribution had cardiac events, whereas there were no such events in 32 patients whose thallium scan either was normal or showed only persistent defects (P less than 0.0001). Six other patients also had thallium redistribution but underwent coronary angiography before vascular surgery. All had severe multivessel coronary artery disease, and four underwent coronary bypass surgery followed by uncomplicated peripheral vascular surgery. These data suggest that patients without thallium redistribution are at a low risk for postoperative ischemic events and may proceed to have vascular surgery. Patients with redistribution have a high incidence of postoperative ischemic events and should be considered for preoperative coronary angiography and myocardial revascularization in an effort to avoid postoperative myocardial ischemia and to improve survival. Dipyridamole-thallium imaging is superior to clinical assessment and is safer and less expensive than coronary angiography for the determination of cardiac risk

Usefulness of peripheral vascular function to predict functional health status in patients with Fontan circulation.

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Goldstein, Bryan H; Golbus, Jessica R; Sandelin, Angela M; Warnke, Nicole; Gooding, Lindsay; King, Karen K; Donohue, Janet E; Gurney, James G; Goldberg, Caren S; Rocchini, Albert P; Charpie, John R

2011-08-01

After the Fontan operation, patients are at a substantial risk of the development of impaired functional health status. Few early markers of suboptimal outcomes have been identified. We sought to assess the association between peripheral vascular function and functional health status in Fontan-palliated patients. Asymptomatic Fontan patients (n = 51) and age- and gender-matched healthy controls (n = 22) underwent endothelial pulse amplitude testing using a noninvasive fingertip peripheral arterial tonometry (PAT) device. Raw data were transformed into the PAT ratio, an established marker of vascular function. Cardiopulmonary exercise testing was performed using the Bruce protocol. In the Fontan cohort, 94% of patients were New York Heart Association functional class I and 88% had a B-type natriuretic peptide level of interquartile range 1.96 to 4.13 vs median 1.86, interquartile range 1.14 to 2.79, p = 0.03). The PAT ratio, a measure of reactive hyperemia, was lower in Fontan patients (median 0.17, interquartile range -0.04 to 0.44, vs median 0.50, interquartile range 0.27 to 0.74, p = 0.002). The key parameters of exercise performance, including peak oxygen consumption (median 28.8 ml/kg/min, interquartile range 25.6 to 33.2 vs median 45.5 ml/kg/min, interquartile range 41.7 to 49.9, p interquartile range 150 to 246 vs median 330, interquartile range 209 to 402 W, p <0.0001), were lower in Fontan patients than in the controls. The PAT ratio correlated with the peak oxygen consumption (r = 0.28, p = 0.02) and peak work (r = 0.26, p = 0.03). In conclusion, in an asymptomatic Fontan population, there is evidence of reduced basal peripheral arterial tone and vasodilator response, suggesting dysfunction of the endothelium-derived nitric oxide pathway. Vasodilator function appears to correlate with exercise performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

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Upa Kukongviriyapan

2014-03-01

Full Text Available Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L in drinking water for eight weeks. Curcumin (50 or 100 mg/kg was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan.

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San-Ni Chen

Full Text Available This is an observational study of fluorescein angiography (FA in consecutive patients with rhegmatogenous retinal detachment (RRD in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL, and refraction status (RF recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8% in group 1, 3 eyes (4.1% in group 2, 40 eyes (54.8% in group 3 and 17 eyes (23.3% in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion.

Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

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Melemedjian Ohannes K

2008-03-01

Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

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Ekatherina Stoyanova

Full Text Available The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1.

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Bhatta, Anil; Yao, Lin; Xu, Zhimin; Toque, Haroldo A; Chen, Jijun; Atawia, Reem T; Fouda, Abdelrahman Y; Bagi, Zsolt; Lucas, Rudolf; Caldwell, Ruth B; Caldwell, Robert W

2017-11-01

Elevation of arginase activity has been linked to vascular dysfunction in diabetes and hypertension by a mechanism involving decreased nitric oxide (NO) bioavailability due to L-arginine depletion. Excessive arginase activity also can drive L-arginine metabolism towards the production of ornithine, polyamines, and proline, promoting proliferation of vascular smooth muscle cells and collagen formation, leading to perivascular fibrosis. We hypothesized that there is a specific involvement of arginase 1 expression within the vascular endothelial cells in this pathology. To test this proposition, we used models of type 2 diabetes and metabolic syndrome. Studies were performed using wild type (WT), endothelial-specific arginase 1 knockout (EC-A1-/-) and littermate controls(A1con) mice fed high fat-high sucrose (HFHS) or normal diet (ND) for 6 months and isolated vessels exposed to palmitate-high glucose (PA/HG) media. Some WT mice or isolated vessels were treated with an arginase inhibitor, ABH [2-(S)-amino-6-boronohexanoic acid. In WT mice, the HFHS diet promoted increases in body weight, fasting blood glucose, and post-prandial insulin levels along with arterial stiffening and fibrosis, elevated blood pressure, decreased plasma levels of L-arginine, and elevated L-ornithine. The HFHS diet or PA/HG treatment also induced increases in vascular arginase activity along with oxidative stress, reduced vascular NO levels, and impaired endothelial-dependent vasorelaxation. All of these effects except obesity and hypercholesterolemia were prevented or significantly reduced by endothelial-specific deletion of arginase 1 or ABH treatment. Vascular dysfunctions in diet-induced obesity are prevented by deletion of arginase 1 in vascular endothelial cells or arginase inhibition. These findings indicate that upregulation of arginase 1 expression/activity in vascular endothelial cells has an integral role in diet-induced cardiovascular dysfunction and metabolic syndrome. Published

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents

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Natália Portela

Full Text Available Abstract Background: A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. Objective: To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. Methods: The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years and 14 without (FH-; 27 ± 5 years a family history of hypertension. Blood pressure, heart rate (DIXTAL®, forearm blood flow (Hokanson®, and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®. Results: At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96, heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18, forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16, and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21, respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86, heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86, and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25, respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03. Conclusion: Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

Relation of Mitochondrial Oxygen Consumption in Peripheral Blood Mononuclear Cells to Vascular Function in Type 2 Diabetes Mellitus

Science.gov (United States)

Hartman, Mor-Li; Shirihai, Orian S.; Holbrook, Monika; Xu, Guoquan; Kocherla, Marsha; Shah, Akash; Fetterman, Jessica L.; Kluge, Matthew A.; Frame, Alissa A.; Hamburg, Naomi M.; Vita, Joseph A.

2014-01-01

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMC’s) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to ATP production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMC’s that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMC’s and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192±47 vs. 161±44 pMoles/min, P=0.01), uncoupled (64±16 vs. 53±16 pMoles/min, P=0.007), and maximal (795±87 vs. 715±128 pMoles/min, P=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1±6.6 vs. 15.8±4.8%, P=0.03) and correlated with maximal oxygen consumption (R= −0.64, P=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for assessment of mitochondrial function in larger scale observational and interventional studies in humans. PMID:24558030

Endurance exercise training increases peripheral vascular response in human fingers.

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Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

1998-10-01

The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, ppressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

DEFF Research Database (Denmark)

Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

2011-01-01

for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

Effect of agmatine on experimental vascular endothelial dysfunction.

Science.gov (United States)

Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

2016-05-01

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

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Farjam, Reza [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pramanik, Priyanka; Aryal, Madhava P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Srinivasan, Ashok [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Chapman, Christopher H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

2015-11-15

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans}, and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

International Nuclear Information System (INIS)

Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.; Srinivasan, Ashok; Chapman, Christopher H.; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue

2015-01-01

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K"t"r"a"n"s, and the fraction of blood plasma volume, V_p. The temporal changes in the means of hippocampal transfer constant K"t"r"a"n"s and V_p after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K"t"r"a"n"s Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

Science.gov (United States)

Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, ppulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

Postpartum Vascular Dysfunction in the Reduced Uteroplacental Perfusion Model of Preeclampsia.

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Lesley Brennan

Full Text Available Preeclampsia is a disorder affecting 2-8% of all pregnancies, characterized by gestational hypertension (≥ 140/90 mmHg and proteinuria (≥300 mg over 24 hours diagnosed following the 20th week of pregnancy, and for which there is currently no available treatment. While the precise cause of preeclampsia is unknown, placental ischemia/hypoxia resulting from abnormal trophoblast invasion and maternal endothelial dysfunction are central characteristics. Preeclampsia is a major cause of both maternal and fetal morbidity and mortality in the perinatal period. In addition, women who have experienced preeclampsia are more likely to suffer cardiovascular disease later in life. The cause of this elevation in cardiovascular risk postpartum, however, is unknown. We hypothesize that there may be lasting vascular dysfunction following exposure to reduced uteroplacental perfusion during pregnancy that may contribute to increased cardiovascular risk postpartum. Using the rat reduced utero-placental perfusion pressure (RUPP model of preeclampsia, blood pressure was assessed in dams at gestational day 20, one and three months postpartum. Mesenteric artery and aortic function were assessed using wire myography. We demonstrated hypertension and increased mesenteric artery responses to phenylephrine at gestational day 20, with the latter due to a decreased contribution of nitric oxide without any change in methylcholine-induced relaxation. At one month postpartum, we demonstrated a small but significant vasoconstrictive phenotype that was due to an underlying loss of basal nitric oxide contribution. At three months postpartum, endothelium-dependent relaxation of the aorta demonstrated sensitivity to oxLDL and mesenteric arteries demonstrated decreased nitric oxide bioavailability with impaired methylcholine-induced relaxation; indicative of an early development of endothelial dysfunction. In summary, we have demonstrated impaired vascular function following

Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

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Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

2013-12-01

We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

LENUS (Irish Health Repository)

Saeed, A

2012-01-31

Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

Usefulness of magnetic resonance angiography in diagnosis of peripheral vascular disease

International Nuclear Information System (INIS)

Kuga, Takayuki; Akiyama, Norio; Takenaka, Hiroaki; Fujioka, Kentaro; Zempo, Noriya; Esato, Kensuke

1992-01-01

The diagnostic usefulness of magnetic resonance angiography (MRA) was evaluated in 19 patients with peripheral vascular disease. It takes thirty minutes or less to perform this test, without any complications. The percent of correct diagnosis on obstructive and stenotic region was 75% in cases of deep vein thrombosis. In addition, it was easy to diagnose an existence of a graft patent. However, it was unsatisfactory to understand morphologic changes of an iliac artery and to determine the position of grafting. The position and size of dilatation and existence of thrombus were easily evaluated in patients with venous aneurysm and varicose vein. MRA was a non-invasive, short spending time imaging. It was available for pregnant women and people with drug allergy, heart failure or renal failure. We believe that MRA can be used in the preoperative examination and the evaluation of the postoperative complications in the peripheral vascular diseases. (J.P.N.)

Usefulness of magnetic resonance angiography in diagnosis of peripheral vascular disease

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Kuga, Takayuki; Akiyama, Norio; Takenaka, Hiroaki; Fujioka, Kentaro; Zempo, Noriya; Esato, Kensuke (Yamaguchi Univ., Ube (Japan). School of Medicine)

1992-03-01

The diagnostic usefulness of magnetic resonance angiography (MRA) was evaluated in 19 patients with peripheral vascular disease. It takes thirty minutes or less to perform this test, without any complications. The percent of correct diagnosis on obstructive and stenotic region was 75% in cases of deep vein thrombosis. In addition, it was easy to diagnose an existence of a graft patent. However, it was unsatisfactory to understand morphologic changes of an iliac artery and to determine the position of grafting. The position and size of dilatation and existence of thrombus were easily evaluated in patients with venous aneurysm and varicose vein. MRA was a non-invasive, short spending time imaging. It was available for pregnant women and people with drug allergy, heart failure or renal failure. We believe that MRA can be used in the preoperative examination and the evaluation of the postoperative complications in the peripheral vascular diseases. (J.P.N.).

Discussion of vascular vagovagal reflexes in interventional approach of peripheral arterial diseases

International Nuclear Information System (INIS)

Zhuang Baixi; Yu Chunli; Ma Lubo; Yang Miao; Shi Bo

2007-01-01

Objective: To investigate the vascular vagovagal reflexes (VVRs) during interventional approach of peripheral arterial disease (PAD). Methods: Twelve patients with VVRs during intervention of 528 patients with peripheral arterial diseases were analyzed retrospectively. Results: The 12 patients with VVRs belonging to mixed type, included 2 cases of occurrence during intervention and 10 cases after intervention. All patients recovered well without adverse reaction. Conclusion: VVRs should always be looking after and prompt management be ready in hand. (authors)

Clinical Significance of the Presence of Autonomic and Vestibular Dysfunction in Diabetic Patients with Peripheral Neuropathy

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Soo Kyoung Kim

2012-02-01

Full Text Available BackgroundWe investigated the prevalence of diabetic autonomic neuropathy (DAN and vestibular dysfunction (VD in diabetic patients with peripheral neuropathy.MethodsThirty-five diabetic patients with peripheral neuropathy were enrolled from August 2008 to July 2009. All subjects underwent autonomic function tests. Nineteen of the patients (54.3% underwent videonystagmography.ResultsDiabetic autonomic neuropathy was observed in 28 patients (80%. A mild degree of autonomic failure was observed in 18 patients (64.3%, and a moderate degree of autonomic failure was observed in ten patients (35.7%. Factors related to DAN included diabetic nephropathy (P=0.032, degree of chronic kidney disease (P=0.003, and duration of diabetes (P=0.044. Vestibular dysfunction was observed in 11 of 19 patients (57.9%. There was no significant association between DAN and VD.ConclusionDiabetic autonomic neuropathy was observed in 28 diabetic patients (80% with peripheral neuropathy. Vestibular dysfunction was observed in nearly 60% of diabetic patients with peripheral neuropathy who complained of dizziness but showed no significant association with DAN. Diabetic patients who complained of dizziness need to examine both autonomic function and vestibular function.

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Science.gov (United States)

Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer's disease

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Ilaria eCanobbio

2015-03-01

Full Text Available Alzheimer’s disease (AD is the most common neurodegenerative cause of dementia in the elderly. AD is accompanied by the accumulation of amyloid peptides in the brain parenchyma and in the cerebral vessels. The sporadic form of the AD accounts for about 95% of all cases. It is characterized by a late onset, typically after the age of 65, with a complex and still poorly understood aetiology. Several observations point towards a central role of cerebrovascular dysfunction in the onset of sporadic AD. According to the vascular hypothesis, AD may be initiated by vascular dysfunctions that precede and promote the neurodegenerative process. In accordance to this, AD patients show increased hemorragic or ischemic stroke risks. It is now clear that multiple bidirectional connections exist between AD and cerebrovascular disease, and in this new scenario, the effect of amyloid peptides on vascular cells and blood platelets appear to be central to AD. In this review we analyse the effect of amyloid peptides on vascular function and platelet activation and its contribution to the cerebrovascular pathology associated with AD and the progression of this disease.

Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness.

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Yurie Obata

Full Text Available Pulse wave velocity (PWV has been recommended as an arterial damage assessment tool and a surrogate of arterial stiffness. However, the current technology does not allow to measure PWV both continuously and in real-time. We reported previously that peripherally measured ejection time (ET overestimates ET measured centrally. This difference in ET is associated with the inherent vascular properties of the vessel. In the current study we examined ETs derived from plethysmography simultaneously at different peripheral locations and examined the influence of the underlying arterial properties on ET prolongation by changing the subject's position. We calculated the ET difference between two peripheral locations (ΔET and its corresponding PWV for the same heartbeat. The ΔET increased with a corresponding decrease in PWV. The difference between ΔET in the supine and standing (which we call ET index was higher in young subjects with low mean arterial pressure and low PWV. These results suggest that the difference in ET between two peripheral locations in the supine vs standing positions represents the underlying vascular properties. We propose ΔET in the supine position as a potential novel real-time continuous and non-invasive parameter of vascular properties, and the ET index as a potential non-invasive parameter of vascular reactivity.

Early experience of endovascular treatment of peripheral vascular disease

International Nuclear Information System (INIS)

Ashraf, T.; Yousuf, K.; Karim, M.T.

2015-01-01

Atherosclerotic peripheral arterial disease (PAD) is prevalent affecting up to 16% of the population aged 55 years or older. Endovascular intervention for the treatment of limb ischemia has become the first line therapy but in Pakistan it is in embryonic stage due to dearth of trained persons and dedicated centres. This study was conducted to evaluate procedural success and early outcome of endovascular treatment of peripheral vascular disease. Methods: A prospective single arm multicentre study was conducted at the National Institute of Cardiovascular Disease and National Medical Centre, Karachi, Pakistan from January 2013 to June 2014. A total of 25 patients were enrolled in the study that underwent endovascular treatment. Out of 25 patients 23 (92%) had critical limb ischemia (CLI) as per TASC II classification (A to D) and 2 (8%) had carotid lesion with history of TIA. Patients of acute limb ischemia and stroke were excluded. Ankle brachial index (ABI) was classified as normal (0.9-1.3), mild (0.7-0.9), moderate (0.4-0.69), severe (<0.4). Outcome was taken as immediate success and symptoms, amputation of limb among CLI patients and incidence of stroke in patients with carotid artery lesion at end of six months. Results: Among aortoiliac, femoropopliteal and tibioperoneal lesions, tibioperoneal lesions at six months were found to be more symptomatic 6 (86%) and amputation 4 (57%). Two carotid lesions at follow up were asymptomatic without stroke. Conclusion: Endovascular treatment of peripheral vascular lesions, i.e., aortoiliac, femoropopliteal tibioperoneal and carotid lesions were satisfactory in immediate outcome. Tibioperoneal lesions were more symptomatic and limb amputation at six months. (author)

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

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Annalisa Canta

2015-06-01

Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Science.gov (United States)

Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

2015-01-01

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice

Science.gov (United States)

Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications. PMID:22474522

Evaluation of age and peripheral vascular disease as risk factors for ...

African Journals Online (AJOL)

Results: Among the 120 diabetic participants, peripheral vascular disease (PVD) was detected only in those aged 50 years and above and all the three diagnostic methods detected PVD increasingly with advancing age. Clinical criteria detected PVD in 4.7% of those aged 50-59 years and 26.3% of those aged .70years.

Arterial stiffness and peripheral vascular resistance in offspring of hypertensive parents

DEFF Research Database (Denmark)

Buus, Niels Henrik; Carlsen, Rasmus K; Khatir, Dinah S

2018-01-01

AIM: Established essential hypertension is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for essential hypertension is uncertain. METHODS: Participants from the Danish Hypertension Prevention Project...... (DHyPP) (both parents hypertensive) (n = 95, 41 ± 1 years, 53% men) were compared with available spouses (n = 45, 41 ± 1 years) using measurements of ambulatory blood pressure (BP), left ventricular mass index (LVMI), pulse wave velocity, central BP and augmentation index (AIx) in addition to forearm...... than men (P hypertension display increased AIx and LVMI, although vascular stiffness...

Association between plantar fascia vascularity and morphology and foot dysfunction in individuals with chronic plantar fasciitis.

Science.gov (United States)

Chen, Hongying; Ho, Hok-Ming; Ying, Michael; Fu, Siu Ngor

2013-10-01

Single-cohort laboratory-based study. To identify whether plantar fascia vascularity and thickness are associated with foot pain and dysfunction in individuals with chronic plantar fasciitis. Background Altered plantar fascia vascularity and thickening of the fascia have been identified in individuals with chronic plantar fasciitis. Thirty-eight patients with chronic unilateral plantar fasciitis and 21 controls participated in this study. Proximal plantar fascia vascularization and thickness were assessed using ultrasound imaging, and pain and foot dysfunction were quantified with a visual analog scale and the Chinese version of the Foot Function Index, respectively. Paired t tests were used to assess the side-to-side differences in fascia thickness and vascularity index (VI) in the control and patient groups, and an unpaired t test was used to make comparisons with the patient group. Multiple regression analysis was performed to identify whether the VI and fascia thickness were associated with pain and foot dysfunction. There were significantly higher VI (mean ± SD, 2.4% ± 1.4%) and fascia thickness (5.0 ± 1.3 mm) values in the affected feet when compared with the unaffected feet in the patient group (VI, 1.4% ± 0.5%; fascia thickness, 3.3 ± 0.7 mm) and with the dominant side of the controls (VI, 1.6% ± 0.4%; fascia thickness, 2.9 ± 0.6 mm). After accounting for age, gender, body mass index, and duration of symptoms, the VI explained 13% and 33% of the variance in pain scores measured with a visual analog scale and the pain subscale of the Foot Function Index, respectively; the VI and fascia thickness explained 42% of the variance in the Foot Function Index. Individuals with unilateral chronic plantar fasciitis demonstrated significantly greater vascularity and thickened fascia on the affected side compared to the unaffected side and also to healthy controls. Fascia vascularity was associated independently with self-perceived pain, and both fascia

Significant complications occurred in the perioperative period of peripheral vascular interventions:an analysis of 1620 consecutive procedures

International Nuclear Information System (INIS)

Yan Zicai; Liu Li; Zhang Haibo; Wang Ning; Li Yu; Yan Ying

2010-01-01

Objective: To categorize the significant complications occurred in the perioperative period of peripheral vascular interventions and to analyze their causes, outcomes and managements in order to make a further understanding of the cause of occurrence and to improve the handling ability. Methods: Over the past five years a total of 1620 consecutive peripheral vascular interventions were carried out in our institute. Significant complications, which occurred in the perioperative period, and the clinical data were carefully examined. The occurrence, treatment, consequence and final outcome of each complication were retrospectively analyzed. Results: Of 1620 consecutive peripheral interventional procedures, significant complication which developed during the operation or within one week after the treatment was seen in 76 (4.69%). The significant complications could be classified into twelve kinds. After proper management most complications were cured without leaving any sequelae. Nevertheless, in some patients permanent damages such as paraplegia, lower limb paralysis, necrosis of gluteus, etc. were left over. Death occurred in six patients. Of the six patients, four died of concomitant hepatic failure and agranulocytosis, one of retroperitoneal hematoma and hemoperitoneum, and another one of pulmonary embolism. Conclusion: (1) Significant complications may occur in most peripheral vascular interventional therapies, which, in most cases, are mainly related to the insufficient understanding of the disease and improper manipulation. (2) A comprehensive and solid fundamental knowledge of the disease, strictly following the indications and careful handling the operation are the key points to reduce the occurrence of severe complications in the perioperative period of peripheral vascular interventions. (authors)

Asymptomatic carotid artery stenosis in patients with severe peripheral vascular diseases

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Rasoul Mirsharifi

2009-04-01

Full Text Available

• BACKGROUND: The prevalence of carotid artery stenosis (CAS in the  eneral population is not high enough to justify screening programs. This study was done to determine the prevalence of asymptomatic carotid artery stenosis (ACAS among patients with severe peripheral vascular disease (PVD.
• METHODS: Between March 2005 and February 2006, 54 consecutive  atients with severe PVD admitted at a vascular surgery unit and underwent carotid duplex scanning in a prospective study. A  uestionnaire was used to collect data concerning known risk factors. Significant CAS was defined as a stenosis of 70% or greater.
• RESULTS: The mean age was 62.5 years (51-72. Out of 54 patients, 2 (3.7% had an occluded internal carotid artery. Significant CAS was found in 9 (16.7% and its presence was correlated with diabetes, hypertension, hypercholesterolemia, hypertriglyceridemia, coronary artery disease, severity of symptoms, ankle-brachial index, and carotid bruit. On multivariate analysis, only hypercholesterolemia and carotid bruit seemed to have independent influence.
• CONCLUSION: The prevalence of significant ACAS is higher among  atients with severe PVD. This patient population may indicate a  uitable subgroup for screening of ACAS, especially when hypercholesterolemia and carotid bruit are present.
• KEYWORDS: Carotid artery stenosis, duplex ultrasound scanning, peripheral vascular disease, carotid endarterectomy,
• cerebrovascular accident.

Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients

NARCIS (Netherlands)

Diekman, M. J.; Harms, M. P.; Endert, E.; Wieling, W.; Wiersinga, W. M.

2001-01-01

Total peripheral vascular resistance (TPR) decreases in thyrotoxicosis and increases in hypothyroidism. Several mechanisms may be involved, including adaptation to changes in heat production and direct non-genomic effects of tri-iodothyronine (T3) on vascular smooth muscle cells. The aim of this

Peripheral vascular effects on auscultatory blood pressure measurement.

Science.gov (United States)

Rabbany, S Y; Drzewiecki, G M; Noordergraaf, A

1993-01-01

Experiments were conducted to examine the accuracy of the conventional auscultatory method of blood pressure measurement. The influence of the physiologic state of the vascular system in the forearm distal to the site of Korotkoff sound recording and its impact on the precision of the measured blood pressure is discussed. The peripheral resistance in the arm distal to the cuff was changed noninvasively by heating and cooling effects and by induction of reactive hyperemia. All interventions were preceded by an investigation of their effect on central blood pressure to distinguish local effects from changes in central blood pressure. These interventions were sufficiently moderate to make their effect on central blood pressure, recorded in the other arm, statistically insignificant (i.e., changes in systolic [p cooling experiments was statistically significant (p < 0.001). Moreover, both measured systolic (p < 0.004) and diastolic (p < 0.001) pressure decreases during the reactive hyperemia experiments were statistically significant. The findings demonstrate that alteration in vascular state generates perplexing changes in blood pressure, hence confirming experimental observations by earlier investigators as well as predictions by our model studies.

Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Chi, Liyi; Hu, Xiaojing; Zhang, Wentao; Bai, Tiao; Zhang, Linjing; Zeng, Hua; Guo, Ruirui; Zhang, Yanhai; Tian, Hongyan

2017-01-01

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II (Ang

The role of vegetative and vascular disturbances in development of sexual dysfunctions. Chapter 11

International Nuclear Information System (INIS)

2000-01-01

It is well known that in clinics of late consequences of low radiation doses action the principle place takes vegetative and vascular dysfunctions. For estimation of vegetative-vascular system tone the Danini-Ashner of eye-heard reflex is studied. Status of the reflex for 120 examined patients was studied. Results of investigation of Danini-Ashner reflex in relation of received dose of radiation, as well as results of skin temperature of sicks with different levels of low radiation doses late consequences are presented. For study of vegetative-vascular system the electro-skin resistance method was used as well

Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

Science.gov (United States)

Miller, Tracie L.; Borkowsky, William; DiMeglio, Linda A.; Dooley, Laurie; Geffner, Mitchell E.; Hazra, Rohan; McFarland, Elizabeth J.; Mendez, Armando J.; Patel, Kunjal; Siberry, George K.; Van Dyke, Russell B.; Worrell, Carol J.; Jacobson, Denise L.

2011-01-01

Objectives Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. Design Prospective cohort study Methods Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. Results The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). Conclusions HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication. PMID:22136114

Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults.

Science.gov (United States)

van Schaardenburgh, Michel; Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J R

2016-01-01

Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. ClinicalTrials.gov NCT01842412.

Quantitative near-infrared spectroscopy on patients with peripheral vascular disease

OpenAIRE

Franceschini, MA; Fantini, S; Palumbo, R; Pasqualini, L; Vaudo, G; Franceschini, E; Gratton, E; Palumbo, B; Innocente, S; Mannarino, E

1997-01-01

We have used near-infrared spectroscopy to measure the hemoglobin saturation at rest and during exercise on patients affected by peripheral vascular disease (PVD). The instrument used in our study is a frequency-domain tissue oximeter which employs intensity modulated (110 MHz) laser diodes. We examined 9 subjects, 3 of which were controls and 6 were patients affected by stage II PVD. The optical probe was located on the calf muscle of the subjects. The measurement protocol consisted of: (1) ...

Peripheral vascular disease in patients with coronary artery disease

International Nuclear Information System (INIS)

Bashir, E. A.; Aslam, N.

2001-01-01

Objective: The prevalence of peripheral vascular disease (PVD) in patients with coronary artery disease (CAD) has been investigated in many different ways. It depends on the diagnostic methods used and definition of atherosclerotic manifestations in the different vascular beds. This study was carried out to determine the prevalence of PVD in the lower limbs in group of patients with CAD. Design: This is a prospective observational study. Place and duration of study: The study was conducted at Combined Military Hospital/Armed Forces institute of Cardiology, Rawalpindi, over a period of one year (January 1998 to January 1999). Subjects and methods: A total number of 200 patient (171 male and 29 females) aged 55-77 years with CAD. Diagnosed by coronary angiography were included in the study. In all patients blood pressure was recorded in both arms by sphygmomanometer and ankle systolic pressure by Doppler ultrasound. Ankle branchial index was calculated. Demographic data were obtained from the patient's hospital files. Results: The prevalence of PVD was 22.5% in patients with CAD in agreement with the results of most previous investigation. There was tendency towards increasing prevalence of PVD with more advanced CAD. Thirty patients (27%) showed evidence of triple vessel disease as compared to 13 patient (18%) with double vessel and 2 patients (1%) with single vessel disease. Conclusion: A non-invasive investigation of peripheral arterial circulation should be included early in the clinical consideration of patients with chest pain or similar symptoms suggesting coronary artery disease. Ankle systolic pressure appears to be simple and cheap technique for evaluation of results. (author)

A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

DEFF Research Database (Denmark)

Olsen, M H; Andersen, U B; Wachtell, K

2000-01-01

We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension....

Central and peripheral fat and subclinical vascular damage in older women.

Science.gov (United States)

Fantin, Francesco; Rossi, Andrea P; Cazzadori, Marco; Comellato, Gabriele; Mazzali, Gloria; Gozzoli, Maria Paola; Grison, Elisa; Zamboni, Mauro

2013-05-01

the aim of this study was to evaluate the relationship between fat distribution and arterial compliance in a group of elderly women, in particular to test a possible independent role of abdominal fat mass and peripheral fat mass on subclinical vascular damage, defined by a pulse wave velocity (PWV) >12 m/s. in 96 women with age range 60-80 years (68.65 ± 4.98 years) and BMI range from 18.8 to 41.2 kg/m(2) (27.07 ± 4.61 kg/m(2)), we evaluated the body mass index, waist circumference, systolic and diastolic blood pressure, fasting glucose, cholesterol, LDL and HDL cholesterol, triglycerides and body composition by dual energy X-ray absorptiometry (DXA). Arterial stiffness was assessed by carotid-femoral (PWVcf) and carotid-radial pulse wave velocity (PWVcr). significant associations were found between PWVcf, age, waist circumference, BMI and trunk fat assessed by DXA, as well as TG and HDL cholesterol. After adjustment for the total fat mass a negative statistically significant association between PWVcf and leg fat mass was shown. In multiple regression analyses the mean arterial pressure, trunk fat mass and leg fat mass were significant predictors of vascular damage with OR, respectively, of 1.06 (CI: 1.01-1.11), 1.25 (CI: 1.06-1.48) and 0.73 (CI: 0.53-0.99). the results of this study show, in a sample of apparently healthy elderly women, that central and peripheral adiposity are independent predictors, with an opposite effect on subclinical vascular damage, confirming and strengthening the protective role of the gluteal-femoral fat on cardiovascular risk even in elderly.

Peripheral vascular insufficiency impairs functional capacity in patients with heart failure

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Renato Murayama

2014-04-01

Full Text Available INTRODUCTION: Heart failure (HF is a complex syndrome in which effort limitation is associated with deterioration of peripheral musculature. Improving survival rates among these patients have led to the appearance of cases in which other pathologies are associated with HF, such as peripheral vascular insufficiency (PVI. The combination of these two pathologies is common, with significant repercussions for affected patients. OBJECTIVE: To compare functional limitations and quality of life between patients with HF in isolation or HF + PVI. METHOD: Twelve patients with HF+PVI were paired to 12 patients with HF in isolation. All had ejection fraction 0.05. CONCLUSIONS: The study participants who had mixed disease exhibited a greater degree of functional impairment than the group with HF, without reporting worsened quality of life.

Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

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Marcondes Alves Barbosa Da Silva

2015-10-01

Full Text Available Type 2 diabetes (DM2 increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR with spironolactone decreases ROS-associated vascular dysfunction and improves vascular NO signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+ mice] received spironolactone (50 mg/kg body weight/day or vehicle (ethanol 1% via oral per gavage for 6 weeks. Spironolactone treatment abolished the endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS phosphorylation (Ser1177, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 (SOD1 and catalase expression, improved sodium nitroprusside (SNP and BAY 41-2272-induced relaxation, as well as increased soluble guanylyl cyclase (sGC subunit β protein expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes.

Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

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Alessia Nicotra

Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

Tirapazamine causes vascular dysfunction in HCT-116 tumour xenografts

International Nuclear Information System (INIS)

Huxham, Lynsey A.; Kyle, Alastair H.; Baker, Jennifer H.E.; McNicol, Krista L.; Minchinton, Andrew I.

2006-01-01

Background and purpose: Tirapazamine is a hypoxic cytotoxin currently undergoing Phase II/III clinical evaluation in combination with radiation and chemotherapeutics for the treatment of non-hematological cancers. Tissue penetration studies using multicellular models have suggested that tirapazamine exposure may be limited to cells close to blood vessels. However, animal studies show tirapazamine enhances the anti-tumour activity of radiation and chemotherapy and clinical studies with tirapazamine, so far, are promising. To investigate this apparent paradox we examined the microregional effects of tirapazamine in vivo by mapping drug effects with respect to the position of blood vessels in tumour cryosections. Patients and methods: Tirapazamine was administered i.p. to mice bearing HCT-116 tumours, which were excised at various times after treatment. Images of multiple-stained cryosections were overlaid to provide microregional information on the relative position of proliferating cells, hypoxia, perfusion and vasculature. Results: We observed extensive and permanent vascular dysfunction in a large proportion of tumours from mice treated with tirapazamine. In the affected tumours, blood flow ceased in the centrally located tumour vessels, leaving a rim of functional vessels around the periphery of the tumour. This vascular dysfunction commenced within 24 h after tirapazamine administration and the areas affected appeared to be replaced by necrosis over the following 24-48 h. Conclusions: Because the majority of hypoxic cells are located in the center of tumours we propose that the activity of tirapazamine in vivo may be related to its effects on tumour vasculature and that its activity against hypoxic cells located distal to functional blood vessels may not be as important as previously believed

Peripheral atherectomy practice patterns in the United States from the Vascular Quality Initiative.

Science.gov (United States)

Mohan, Sathish; Flahive, Julie M; Arous, Edward J; Judelson, Dejah R; Aiello, Francesco A; Schanzer, Andres; Simons, Jessica P

2018-06-21

Peripheral atherectomy has been shown to have technical success in single-arm studies, but clinical advantages over angioplasty and stenting have not been demonstrated, leaving its role unclear. We sought to describe patterns of atherectomy use in a real-world U.S. cohort to understand how it is currently being applied. The Vascular Quality Initiative was queried to identify all patients who underwent peripheral vascular intervention from January 2010 to September 2016. Descriptive statistics were performed to analyze demographics of the patients, comorbidities, indication, treatment modalities, and lesion characteristics. The intermittent claudication (IC) and critical limb ischemia (CLI) cohorts were analyzed separately. Of 85,605 limbs treated, treatment indication was IC in 51% (n = 43,506) and CLI in 49% (n = 42,099). Atherectomy was used in 15% (n = 13,092) of cases, equivalently for IC (15%; n = 6674) and CLI (15%; n = 6418). There was regional variation in use of atherectomy, ranging from a low of 0% in one region to a high of 32% in another region. During the study period, there was a significant increase in the proportion of cases that used atherectomy (11% in 2010 vs 18% in 2016; P < .0001). Compared with nonatherectomy cases, those with atherectomy use had higher incidence of prior peripheral vascular intervention (IC, 55% vs 43% [P < .0001]; CLI, 47% vs 41% [P < .0001]), greater mean number of arteries treated (IC, 1.8 vs 1.6 [P < .0001]; CLI, 2.1 vs 1.7 [P < .0001]), and lower proportion of prior leg bypass (IC, 10% vs 14% [P < .0001]; CLI, 11% vs 17% [P < .0001]). There was lower incidence of failure to cross the lesion (IC, 1% vs 4% [P < .0001]; CLI, 4% vs 7% [P < .0001]) but higher incidence of distal embolization (IC, 1.9% vs 0.8% [P < .0001]; CLI, 3.0% vs 1.4% [P < .0001]) and, in the CLI cohort, arterial perforation (1.4% vs 1.0%; P = .01). Despite a lack of evidence for atherectomy over angioplasty and stenting, its use has

Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study

Directory of Open Access Journals (Sweden)

Cassidy Roslyn

2007-06-01

Full Text Available Abstract Background Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats. Methods Male Wistar rats (n = 6/group were fed diets providing varying percentages of energy from fat and carbohydrate (CHO. For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO, chow supplemented with chocolate biscuit (30% fat; 56% CHO or a high-fat diet (45% fat; 35% CHO. Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA. Results Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p p p p p Conclusion Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.

Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

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Naoyuki eSato

2013-11-01

Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

Science.gov (United States)

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

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Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats.

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Bridges, Jason P; Gilbert, Jeffrey S; Colson, Drew; Gilbert, Sara A; Dukes, Matthew P; Ryan, Michael J; Granger, Joey P

2009-05-01

Recent evidence indicates that both increased oxidative stress and an altered balance between pro- and anti-angiogenic factors such as vascular-endothelial growth factor (VEGF) and the soluble VEGF receptor (sFlt-1) contribute to endothelial dysfunction in preeclampsia. We hypothesized that chronic infusion of sFlt-1 to mimic the increase observed in preeclamptic patients would reduce plasma VEGF concentrations, increase blood pressure (BP) and vascular superoxide levels, and cause endothelial dysfunction in the pregnant rat. Recombinant sFlt-1 was infused (500 ng/h) during days 13-18 of pregnancy. BP, fetal and placental weight, oxidative stress and vessel vasorelaxation were determined on day 18 of pregnancy. Plasma sFlt-1 concentrations (299 +/- 33 vs. 100 +/- 16 pg/ml; P 570 +/- 77 vs. 780 +/- 48 pg/ml; P < 0.01) were decreased when compared to vehicle infused dams. sFlt-1 rats had smaller fetuses (1.3 +/- 0.03 vs. 1.5 +/- 0.04 g, P < 0.01) and placentas (0.41 +/- 0.01 vs. 0.47 +/- 0.02 g; P < 0.05). Placental (180 +/- 66 vs. 24 +/- 2.3 RLU/min/mg; P < 0.05) and vascular (34 +/- 8 vs. 12 +/- 5 RLU/min/mg; P < 0.05) superoxide production was increased in the sFlt-1 compared to vehicle infused rats. Vasorelaxation to acetylecholine (ACh) and sodium nitroprusside (SNP) were both decreased (P < 0.05) in the sFlt-1 infusion group compared to the vehicle and this decrease was attenuated (P < 0.05) by the superoxide scavenger Tiron. These data indicate elevated maternal sFlt-1 and decreased VEGF concentrations results in increased oxidative stress that contributes to vascular dysfunction during pregnancy.

Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

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Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

2010-11-02

Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; Pwomen with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

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Portela, Natália; Amaral, Josária Ferraz; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; Martinez, Daniel Godoy; Laterza, Mateus Camaroti

2017-07-10

A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. O histórico familiar para hipertensão arterial está relacionado a anormalidades vasculares e autonômicas, bem como disfunções no comportamento neuro-hemodinâmico durante o exerc

A serving of blueberry (V. corymbosum) acutely improves peripheral arterial dysfunction in young smokers and non-smokers: two randomized, controlled, crossover pilot studies.

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Del Bo', Cristian; Deon, Valeria; Campolo, Jonica; Lanti, Claudia; Parolini, Marina; Porrini, Marisa; Klimis-Zacas, Dorothy; Riso, Patrizia

2017-11-15

Several studies have documented the important role of polyphenol-rich foods in the modulation of vascular remodelling and function. This study aimed to evaluate the capacity of a single portion of blueberry (V. corymbosum) to acutely improve peripheral arterial dysfunction in a group of young volunteers. Twenty-four healthy males (12 non-smokers and 12 smokers) were recruited for two different randomized, controlled, crossover pilot acute studies. In the first study, non-smokers were exposed to a control treatment (C; 300 mL of water with sugar) and a blueberry treatment (BB; 300 g of blueberry). In the second study, smokers underwent 3 different protocols: (1) - smoking treatment (S); (2) - control treatment (CS; 300 mL of water with sugar + smoking); (3) - blueberry treatment (BS; 300 g of blueberry + smoking). Each treatment (1 day long) was separated by a one week washout period. Blood pressure, peripheral arterial function (reactive hyperemia index, RHI, a marker of endothelial function) and arterial stiffness (digital augmentation index, dAix and dAix normalized by considering a heart rate of 75 bpm, dAix@75) were measured before and after each treatment. In the first study, the consumption of blueberry and control treatment acutely increased peripheral arterial function in the group of non-smokers. The improvement in RHI was higher and significantly different after blueberry treatment compared to the control treatment (54.8 ± 8.4% BB vs. 28.2 ± 8.3% C; p = 0.01). No effects were observed for markers of arterial stiffness, blood pressure and heart rate. Acute cigarette smoke significantly increased blood pressure and heart rate, while no significant effect was registered in peripheral arterial function and stiffness. The intake of blueberry and control treatment before a cigarette did not counteract the increase in blood pressure and heart rate, while it significantly improved peripheral arterial function. In particular, a significant increase was observed

Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

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Roquer, J; Segura, T; Serena, J; Castillo, J

2009-01-01

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (ARTICO study will increase the knowledge of patient outcome after ischemic stroke and may help to improve our ability to detect patients at high risk of stroke recurrence or major cardiovascular events. (c) 2009 S. Karger AG, Basel.

Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

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Weissgerber, Tracey L

2014-11-01

Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

Development of a sirolimus-eluting poly (L-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention.

Science.gov (United States)

Grabow, Niels; Bünger, Carsten M; Kischkel, Sabine; Timmermann, J Hinrich; Reske, Thomas; Martin, David P; Williams, Simon F; Schareck, Wolfgang; Sternberg, Katrin; Schmitz, Klaus-Peter

2013-10-01

Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0 × 20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50 ± 25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

International Nuclear Information System (INIS)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

2014-01-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

Energy Technology Data Exchange (ETDEWEB)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

2014-10-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Interarm Difference in Blood Pressure: Reproducibility and Association with Peripheral Vascular Disease

OpenAIRE

Mehlsen, Jesper; Wiinberg, Niels

2014-01-01

The present study aimed at examining the interarm difference in blood pressure and its use as an indicator of peripheral arterial disease (PAD). Data were included from consecutive patients referred from their general practitioner to our vascular laboratory for possible PAD aged 50 years or older without known cardiac disease, renal disease, or diabetes mellitus. 824 patients (453 women) with mean age of 72 years (range: 50–101) were included. 491 patients had a diagnosi...

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

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Yong Guan

2015-10-01

Full Text Available ABSTRACT Erectile dysfunction (ED is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5 questionnaire. Nocturnal penile tumescence (NPT testing confirmed the occurrence of ED in 96 (80% patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30% were demonstrated only with vascular abnormality, 41 (42.7% were detected only with neural abnormality, 26 (27.1% revealed mixed abnormalities. Of the 55 patients (29+26 with vascular problems, 7 patients (12.7% with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine, 31 (56.4% with corporal veno-occlusive dysfunction and 17 (30.9% had both problems. Of the 67 (41+26 patients with abnormal neurophysiological outcomes, 51 (76.1% with abnormal bulbocavernosus reflex (BCR, 20 (29.9% with pathological pudendal nerve evoked potentials (PDEPs and 25 (37.3% with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs. Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

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Domenico, T D; Joelsons, G; Montenegro, R M; Manfro, R C

2017-04-03

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (Ptransplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Peripheral neuromuscular dysfunction and falls in an elderly cohort.

Science.gov (United States)

Sorock, G S; Labiner, D M

1992-09-01

In a prospective study of 169 tenants of senior citizen housing in New Jersey in 1986-1987, the relations between tests of peripheral sensory and motor functions in the lower extremities and the rate of first falls were evaluated. The mean age of the cohort was 79.8 years. Fifty-seven persons fell at least once during the follow-up period (mean, 5.6 months). After adjustment for history of stroke, heart failure, emphysema, and use of a walker or cane, rate ratios for first falls were elevated in subjects with reduced toe joint position sense (rate ratio (RR) = 2.2) and sharp-dull discrimination (RR = 2.0), but to a lesser extent for reduced ankle strength (RR = 1.5). Presence of one or more of these three deficits was defined as a peripheral neuromuscular dysfunction and was associated with first falls after adjustment for multiple covariates (RR = 2.4, 95% confidence interval 1.3-4.5). Having two or all three sensory or motor deficits increased the rate of falling 3.9 times (95% confidence interval 2.1-7.0) compared with persons without these deficits. These data suggest that impaired sensory and motor function of the lower extremities plays an important role in falls in the elderly.

Inhibition of Vascular c-Jun N-Terminal Kinase 2 Improves Obesity-Induced Endothelial Dysfunction After Roux-en-Y Gastric Bypass.

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Doytcheva, Petia; Bächler, Thomas; Tarasco, Erika; Marzolla, Vincenzo; Engeli, Michael; Pellegrini, Giovanni; Stivala, Simona; Rohrer, Lucia; Tona, Francesco; Camici, Giovanni G; Vanhoutte, Paul M; Matter, Christian M; Lutz, Thomas A; Lüscher, Thomas F; Osto, Elena

2017-11-14

Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity-induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. After 7 weeks of a high-fat high-cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D-TAT or the JNK peptide inhibitor D-JNKi-1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D-JNKi-1 treatment improved endothelial vasorelaxation in response to insulin and glucagon-like peptide-1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D-JNKi-1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon-like peptide-1-mediated signaling. The inhibitory phosphorylation of insulin receptor substrate-1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity-induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Achados de imagem e alternativas terapêuticas das malformações vasculares periféricas Imaging findings and therapeutic alternatives for peripheral vascular malformations

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Lucas Moretti Monsignore

2010-06-01

Full Text Available As malformações vasculares periféricas compreendem um espectro de lesões que se tornam aparentes no decorrer da vida e podem ser encontradas em praticamente todo o corpo. São pouco comuns e frequentemente confundidas com o hemangioma infantil. Estas doenças são completamente distintas tanto em relação à história clínica como ao prognóstico e às formas de tratamento. Nestas lesões, a história evolutiva e as características do exame físico são de extrema importância para o adequado diagnóstico clinicorradiológico, que guiará a melhor alternativa terapêutica. As classificações mais recentes dividem as malformações vasculares periféricas levando em consideração o fluxo sanguíneo (alto e baixo e os componentes vasculares envolvidos (arteriais, capilares, linfáticos e venosos. As malformações vasculares periféricas representam um desafio diagnóstico e terapêutico, e exames complementares como tomografia computadorizada, ultrassonografia com Doppler e ressonância magnética, em conjunto com a história clínica, podem trazer informações quanto às características de fluxo e à extensão das lesões. Arteriografia e flebografia confirmam o diagnóstico, avaliam a sua extensão e orientam a decisão terapêutica. Malformações de baixo fluxo geralmente são tratadas por abordagem percutânea e injeção de agente esclerosante, enquanto para as malformações de alto fluxo o acesso é endovascular com uso de agentes embolizantes permanentes líquidos ou sólidos.Peripheral vascular malformations represent a spectrum of lesions that appear through the lifetime and can be found in the whole body. Such lesions are uncommon and are frequently confounded with infantile hemangioma, a common benign neoplastic lesion. In the presence of such lesions, the correlation between the clinical and radiological findings is extremely important to achieve a correct diagnosis, which will guide the best therapeutic approach. The

Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure

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Jablonski, Kristen L.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; McQueen, Matthew B.; Seals, Douglas R.

2013-01-01

Objectives We determined the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130–159 mmHg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11M/6F; 62±7 yrs, mean±S.D.) completed a randomized, crossover study of 4 weeks of both low and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary sodium excretion was reduced by ~50% (to 70±30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following the low sodium diet (psodium markedly enhanced NO- mediated EDD (greater ΔFBFACh with endothelial NO synthase [eNOS] inhibition) without changing eNOS expression/activation (Ser1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (p<0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reverses both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects. PMID

Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise.

Science.gov (United States)

Rundell, Kenneth W; Steigerwald, Michelle D; Fisk, Michelle Z

2010-08-01

Associations between high particulate matter (PM) pollution and increased morbidity and mortality from coronary heart disease have been identified. This study assessed leukotriene (LT) participation in PM-induced vascular endothelial dysfunction. Ten healthy males exercised 4 times for 30 min in both high PM (550,286 +/- 42,004 particles x cm(-3)) and low PM (4571 +/- 1922 particles x cm(-3)) after ingesting placebo (PL) or 10 mg montelukast (MK; half-life 3-6 h), a leukotriene receptor antagonist. Brachial artery flow-mediated dilation (FMD) was measured pre- and 30 min, 4 h, 24 h post-exercise. No basal brachial artery vascoconstriction was evident from high PM exercise. High PM blunted FMD, whereas high PM MK, low PM PL, and low PM MK demonstrated normal FMD (p < .003). Change in FMD (pre- to post-exercise) for high PM PL was different than for high PM MK, low PM PL, and low PM MK at 30 min post-exercise (p < .007). At 4 h, high PM MK FMD blunting increased (p = .1). At 24 h, high PM FMD blunting persisted (p < .05); no difference was observed between high PM PL or MK treatment, but was different that low PM PL/MK treatments (p < .05). MK blocked high PM post-exercise FMD blunting and maintained normal response, suggesting that leukotrienes are involved in PM-initiated vascular endothelial dysfunction.

Role of Peripheral Vascular Resistance for the Association Between Major Depression and Cardiovascular Disease

DEFF Research Database (Denmark)

Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

2015-01-01

Major depression and cardiovascular diseases are 2 of the most prevalent health problems in Western society, and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial....... The changes in arterial structure, contractile and relaxing functions associated with depression symptoms are discussed, and the role of these abnormalities for the pathology of major depression and cardiovascular diseases are suggested....... character including a number of neuronal, humoral, immune, and circulatory pathways. Depression-associated cardiovascular abnormalities associate with cardiac dysfunctions and with changes in peripheral resistance. Although cardiac dysfunction in association with depression has been studied in detail...

Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

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Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

2014-09-01

The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

Peripheral Circulatory Features during High-Frequency Jet Ventilation

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M. B. Kontorovich

2010-01-01

Full Text Available The paper gives the results of a study of peripheral circulatory features during high-frequency jet ventilation (HFJV. The main specific features of peripheral circulation and oxygen transport during HFJV are formulated on the basis of a study of cardiac output (impedance cardiography, peripheral vascular resistance, peripheral vascular blood filling (photoplethysmogram analysis, adaptive peripheral blood flow reactions (spectral analysis of peripheral vascular pulsation. HFJV gives rise to the peculiar pattern of peripheral hemodynamics and tissue gas exchange, which is characterized by higher oxygen uptake without a decrease in mixed venous blood saturation, with normal extraction coefficient and preserved low peripheral vascular resistance. During HFJV, unlike traditional ventilation, the main peripheral hemodynamic feature is the increased capillary bed blood volume caused by the blood flow involvement of reserve capillaries under control of volume (parasympathetic regulation of adaptive peripheral hemodynamic reactions. Key words: high-frequency jet ventilation, oxygen transport, peripheral hemodynamics.

Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

LENUS (Irish Health Repository)

Walsh, Sarah K

2012-01-31

Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

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Maskomani Silambarasan

2016-04-01

Full Text Available Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose and at various time intervals (6, 12, 24 and 48 h. miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

Increased expression of matrix metalloproteinase-1 in systemic vessels of preeclamptic women: a critical mediator of vascular dysfunction.

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Estrada-Gutierrez, Guadalupe; Cappello, Renato E; Mishra, Nikita; Romero, Roberto; Strauss, Jerome F; Walsh, Scott W

2011-01-01

This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type 1α, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor α. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the imbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor α, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Vascular remodeling versus amyloid beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease.

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Tong, Xin-Kang; Nicolakakis, Nektaria; Kocharyan, Ara; Hamel, Edith

2005-11-30

The roles of oxidative stress and structural alterations in the cerebrovascular dysfunctions associated with Alzheimer's disease (AD) were investigated in transgenic mice overexpressing amyloid precusor protein (APP+) or transforming growth factor-beta1 (TGF+). Age-related impairments and their in vitro reversibility were evaluated, and underlying pathogenic mechanisms were assessed and compared with those seen in AD brains. Vasoconstrictions to 5-HT and endothelin-1 were preserved, except in the oldest (18-21 months of age) TGF+ mice. Despite unaltered relaxations to sodium nitroprusside, acetylcholine (ACh) and calcitonin gene-related peptide-mediated dilatations were impaired, and there was an age-related deficit in the basal availability of nitric oxide (NO) that progressed more gradually in TGF+ mice. The expression and progression of these deficits were unrelated to the onset or extent of thioflavin-S-positive vessels. Manganese superoxide dismutase (SOD2) was upregulated in pial vessels and around brain microvessels of APP+ mice, pointing to a role of superoxide in the dysfunctions elicited by amyloidosis. In contrast, vascular wall remodeling associated with decreased levels of endothelial NO synthase and cyclooxygenase-2 and increased contents of vascular endothelial growth factor and collagen-I and -IV characterized TGF+ mice. Exogenous SOD or catalase normalized ACh dilatations and NO availability in vessels from aged APP+ mice but had no effect in those of TGF+ mice. Increased perivascular oxidative stress was not evidenced in AD brains, but vascular wall alterations compared well with those seen in TGF+ mice. We conclude that brain vessel remodeling and associated alterations in levels of vasoactive signaling molecules are key contributors to AD cerebrovascular dysfunctions.

Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease

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E.M. McCarthy

2017-06-01

The association between circulating MP levels and objective assessment of macro- and microvascular dysfunction within these disease areas suggests that MPs might have a useful role as novel circulating biomarkers of vascular disease within the CTDs.

Polyarteritis nodosa presenting as peripheral vascular disease and acute limb ischemia

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A Shukla

2017-01-01

Full Text Available Acute limb ischemia and peripheral vascular disease (PVD are unusual presentations of polyarteritis nodosa (PAN. Here, we present a case with PVD of both lower limbs leading to foot claudication. Digital subtraction angiography showed narrowing, irregularity, and occlusion of both lower limb arteries with no involvement of the abdomen visceral arteries. Based on significant weight loss, diastolic blood pressure >90 mmHg, myalgia, testicular pain, and angiographic abnormalities in medium-sized arteries, he was diagnosed as having PAN. He was treated with corticosteroid and bolus intravenous cyclophosphamide following which he had prompt and near-complete recovery of the symptoms without any tissue loss.

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

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Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

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Mostafa Wanees Ahmed El husseny

2017-01-01

Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

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Rexhaj, Emrush; Pireva, Agim; Paoloni-Giacobino, Ariane; Allemann, Yves; Cerny, David; Dessen, Pierre; Sartori, Claudio; Scherrer, Urs; Rimoldi, Stefano F

2015-10-01

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans. Copyright © 2015 the American Physiological Society.

Alzheimer's disease, cerebrovascular dysfunction and the benefits of exercise: from vessels to neurons.

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Lange-Asschenfeldt, Christian; Kojda, Georg

2008-06-01

Exercise training promotes extensive cardiovascular changes and adaptive mechanisms in both the peripheral and cerebral vasculature, such as improved organ blood flow, induction of antioxidant pathways, and enhanced angiogenesis and vascular regeneration. Clinical studies have demonstrated a reduction of morbidity and mortality from cardiovascular disease among exercising individuals. However, evidence from recent large clinical trials also suggests a substantial reduction of dementia risk - particularly regarding Alzheimer's disease (AD) - with regular exercise. Enhanced neurogenesis and improved synaptic plasticity have been implicated in this beneficial effect. However, recent research has revealed that vascular and specifically endothelial dysfunction is essentially involved in the disease process and profoundly aggravates underlying neurodegeneration. Moreover, vascular risk factors (VRFs) are probably determinants of incidence and course of AD. In this review, we emphasize the interconnection between AD and VRFs and the impact of cerebrovascular and endothelial dysfunction on AD pathophysiology. Furthermore, we describe the molecular mechanisms of the beneficial effects of exercise on the vasculature such as activation of the vascular nitric oxide (NO)/endothelial NO synthase (eNOS) pathway, upregulation of antioxidant enzymes, and angiogenesis. Finally, recent prospective clinical studies dealing with the effect of exercise on the risk of incident AD are briefly reviewed. We conclude that, next to upholding neuronal plasticity, regular exercise may counteract AD pathophysiology by building a vascular reserve.

Relaxin as a natural agent for vascular health

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Daniele Bani

2008-06-01

Full Text Available Daniele BaniDepartment of Anatomy, Histology and Forensic Medicine, Sect. Histology, University of Florence, ItalyAbstract: Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral vascular disease, and renal failure are the main manifestations of cardiovascular disease (CVD, the leading cause of death and disability in developed countries. Continuing insight into the pathophysiology of CVD can allow identification of effective therapeutic strategies to reduce the occurrence of death and/or severe disabilities. In this context, a healthy endothelium is deemed crucial to proper functioning and maintenance of anatomical integrity of the vascular system in many organs. Of note, epidemiologic studies indicate that the incidence of CVD in women is very low until menopause and increases sharply thereafter. The loss of protection against CVD in post-menopausal women has been chiefly attributed to ovarian steroid deficiency. However, besides steroids, the ovary also produces the peptide hormone relaxin (RLX, which provides potent vasoactive effects which render it the most likely candidate as the elusive physiological shield against CVD in fertile women. In particular, RLX has a specific relaxant effect on peripheral and coronary vasculature, exerted by the stimulation of endogenous nitric oxide (NO generation by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX inhibits the activation of inflammatory leukocytes and platelets, which play a key role in CVD. Experimental studies performed in vascular and blood cell in vitro and in animal models of vascular dysfunction, as well as pioneer clinical observations, have provided evidence that RLX can prevent and/or improve CVD, thus offering background to clinical trials aimed at exploring the broad therapeutic potential of human recombinant RLX as a new cardiovascular drug.Keywords: relaxin, blood vessels, endothelial cells, vascular smooth muscle, nitric oxide

Phlebitis and infiltration: vascular trauma associated with the peripheral venous catheter

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Braga, Luciene Muniz; Parreira, Pedro Miguel; Oliveira, Anabela de Sousa Salgueiro; Mónico, Lisete dos Santos Mendes; Arreguy-Sena, Cristina; Henriques, Maria Adriana

2018-01-01

ABSTRACT Objective: to determine the incidence rate and risk factors for the nursing-sensitive indicators phlebitis and infiltration in patients with peripheral venous catheters (PVCs). Method: cohort study with 110 patients. Scales were used to assess and document phlebitis and infiltration. Socio-demographic variables, clinical variables related to the PVC, medication and hospitalization variables were collected. Descriptive and inferential analysis and multivariate logistic models were used. Results: the incidence rate of phlebitis and infiltration was respectively 43.2 and 59.7 per 1000 catheter-days. Most PVCs with these vascular traumas were removed in the first 24 hours. Risk factors for phlebitis were: length of hospital stay (p=0.042) and number of catheters inserted (p<0.001); risk factors for infiltration were: piperacillin/tazobactan (p=0.024) and the number of catheters inserted (p<0.001). Conclusion: the investigation documented the incidence of nursing-sensitive indicators (phlebitis and infiltration) and revealed new risk factors related to infiltration. It also allowed a reflection on the nursing care necessary to prevent these vascular traumas and on the indications and contraindications of the PVC, supporting the implementation of the PICC as an alternative to PVC. PMID:29791668

Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.

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Mo, Jiao; Yang, Renhua; Li, Fan; Zhang, Xiaochao; He, Bo; Zhang, Yue; Chen, Peng; Shen, Zhiqiang

2018-03-15

Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats. Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H 2 O 2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD). Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H 2 O 2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin. Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases

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Giulio Illuminati, MD

2016-01-01

Conclusions: These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions.

Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

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E.R. Parra

2012-07-01

Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

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Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

2018-07-01

Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

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Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

2017-01-01

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Massage Therapy Restores Peripheral Vascular Function following Exertion

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Franklin, Nina C.; Ali, Mohamed M.; Robinson, Austin T.; Norkeviciute, Edita; Phillips, Shane A.

2014-01-01

Objective To determine if lower extremity exercise-induced muscle injury (EMI) reduces vascular endothelial function of the upper extremity and if massage therapy (MT) improves peripheral vascular function after EMI. Design Randomized, blinded trial with evaluations at 90 minutes, 24 hours, 48 hours, and 72 hours. Setting Clinical research center at an academic medical center and laboratory Participants Thirty-six sedentary young adults were randomly assigned to one of three groups: 1) EMI + MT (n=15; mean age ± standard error (SE): 26.6±0.3), 2) EMI only (n=10; mean age ± SE: 23.6±0.4), and 3) MT only (n=11; mean age ± SE: 25.5 ± 0.4). Intervention Participants were assigned to either EMI only (a single bout of bilateral, eccentric leg-press exercise), MT only (30-minute lower extremity massage using Swedish technique), or EMI + MT. Main outcome measures Brachial artery flow-mediated dilation (FMD) was determined by ultrasound at each time point. Nitroglycerin-induced dilation was also assessed (NTG; 0.4 mg). Results Brachial FMD increased from baseline in the EMI + MT group and the MT only group (7.38±0.18 to 9.02±0.28%, p<0.05 and 7.77±0.25 to 10.20±0.22%, p < 0.05, respectively) at 90 minutes remaining elevated until 72 hrs. In the EMI only group FMD was reduced from baseline at 24 and 48 hrs (7.78±0.14 to 6.75±0.11%, p<0.05 and 6.53±0.11, p<0.05, respectively) returning to baseline after 72 hrs. Dilations to NTG were similar over time. Conclusions Our results suggest that MT attenuates impairment of upper extremity endothelial function resulting from lower extremity EMI in sedentary young adults. PMID:24583315

Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

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Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

2008-01-01

The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD: a meta-analysis.

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Linying Peng

Full Text Available BACKGROUND: Postoperative cognitive dysfunction (POCD is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12.The standardized mean difference (SMD and the 95% confidence interval (95%CI were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI] (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies, and interleukin(IL-6 (SMD[95%CI] (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies, but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies. CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

Vascular corrosion casting of normal and pre-eclamptic placentas.

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Yin, Geping; Chen, Ming; Li, Juan; Zhao, Xiaoli; Yang, Shujun; Li, Xiuyun; Yuan, Zheng; Wu, Aifang

2017-12-01

Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality that is associated with decreased placental perfusion. In the present study, vascular corrosion casting was used to investigate the differences in structural changes of the fetoplacental vasculature between normal and pre-eclamptic placentas. An improved epoxy resin vascular casting technique was used in the present study. Casting media were infused into 40 normal and 40 pre-eclamptic placentas through umbilical arteries and veins in order to construct three dimensional fetoplacental vasculatures. The number of branches, diameter, morphology and peripheral artery-to-vein ratio were measured for each specimen. The results indicated that the venous system of normal placentas was divided into 5-7 grades of branches and the volume of the vascular bed was 155.5±45.3 ml. In severe pre-eclamptic placentas, the volume was 106.4±36.1 ml, which was significantly lower compared with normal placentas (P<0.01). The venous system of pre-eclamptic placentas was divided into 4-5 grades of branches, which was much more sparse compared with normal placentas. In additions, the diameters of grade 1-3 veins and grade 2-3 arteries were significantly smaller in severe pre-eclampsia (P<0.05). In conclusion, pre-eclamptic placentas displayed a decreased volume of vascular bed, smaller diameters of grade 1-3 veins and grade 2-3 arteries, and an increased peripheral artery-to-vein ratio, which may be a cause of the placental dysfunction during severe pre-eclampsia.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

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T.D. Domenico

Full Text Available We analyzed microRNA (miR-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23, acute tubular necrosis group (n=18 and stable patients group used as a control for gene expression (n=8. Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05 and urine (P<0.001 compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05. Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001 but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079. miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

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Ziegler, Matthew A; Distasi, Matthew R; Bills, Randall G; Miller, Steven J; Alloosh, Mouhamad; Murphy, Michael P; Akingba, A George; Sturek, Michael; Dalsing, Michael C; Unthank, Joseph L

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats.

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Si, Lislivia Yiang-Nee; Kamisah, Yusof; Ramalingam, Anand; Lim, Yi Cheng; Budin, Siti Balkis; Zainalabidin, Satirah

2017-07-01

Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) C max = 234.5 ± 3.9%, Endo-(-) C max = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) C max = 264.5 ± 6.9%, Endo-(-) C max = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) R max = 73.2 ± 2.1%, Endo-(-) R max = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) R max = 57.8 ± 1.7%, Endo-(-) R max = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

Vascular access in neonatology: peripherally inserted central catheter and peripheral venous catheter

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Marcia Lienemann

2014-04-01

The objective of this paper is to present aspects of peripherally inserted central catheter and peripheral venous catheter, highlighting important points in choosing the type of access. For the passage of peripherally inserted central catheter is previously performing specific course necessary, while the primary indication occurs when it is necessary to access the patient's stay for a long period of time. Whereas peripheral venipuncture is the most appropriate in cases of needing an IV line quickly and safely, for the administration of fluids, blood collection, blood transfusion and other.

Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity.

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Rivera, José Carlos; Madaan, Ankush; Zhou, Tianwei Ellen; Chemtob, Sylvain

2016-12-01

Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder. Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Quantitative near-infrared spectroscopy on patients with peripheral vascular disease

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Franceschini, Maria-Angela; Fantini, Sergio; Palumbo, Renato; Pasqualini, Leonella; Vaudo, Gaetano; Franceschini, Edoardo; Gratton, Enrico; Palumbo, Barbara; Innocente, Salvatore; Mannarino, Elmo

1998-01-01

We have used near-infrared spectroscopy to measure the hemoglobin saturation at rest and during exercise on patients affected by peripheral vascular disease (PVD). The instrument used in our study is a frequency-domain tissue oximeter which employs intensity modulated (110 MHz) laser diodes. We examined 9 subjects, 3 of which were controls and 6 were patients affected by stage II PVD. The optical probe was located on the calf muscle of the subjects. The measurement protocol consisted of: (1) baseline (approximately 5 min); (2) stationary bicycle exercise (approximately 5 min); (3) recovery (approximately 15 min). The change in hemoglobin saturation during exercise ((Delta) Y) and the recovery time after exercise (trec) were significantly greater in the PVD patients ((Delta) Y equals -21 +/- 3%, trec equals 5.9 +/- 3.8 min) than in the control subjects ((Delta) Y equals 2 +/- 3%, trec equals 0.6 +/- 0.1 min).

Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK phosphorylation in renal and vascular dysfunction

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Gupta Akanksha

2005-03-01

Full Text Available Abstract Background In the present study we tested the hypothesis that progression of streptozotocin (STZ-induced diabetes (14-days to 28-days would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK phosphorylation in kidneys and thoracic aorta. Methods Male Sprague Dawley rats (350–400 g were randomized into three groups: sham (N = 6, 14-days diabetic (N = 6 and 28-days diabetic rats (N = 6. Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V. on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat. Results The diabetic rats lost body weight at both 14-days (-10% and 28-days (-13% more significantly as compared to sham (+10% group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS, prepro endothelin-1 (preproET-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. Conclusion The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

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Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Interarm Difference in Blood Pressure: Reproducibility and Association with Peripheral Vascular Disease

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Jesper Mehlsen

2014-01-01

Full Text Available The present study aimed at examining the interarm difference in blood pressure and its use as an indicator of peripheral arterial disease (PAD. Data were included from consecutive patients referred from their general practitioner to our vascular laboratory for possible PAD aged 50 years or older without known cardiac disease, renal disease, or diabetes mellitus. 824 patients (453 women with mean age of 72 years (range: 50–101 were included. 491 patients had a diagnosis of hypertension and peripheral arterial disease (PAD was present in 386 patients. Systolic blood pressure was 143 ± 24 mmHg and 142 ± 24 mmHg on the right and left arm, respectively (P=0.015. The interarm difference was greater in patients with hypertension (P=0.002 and PAD (P20 mmHg. This study confirmed the presence of a systematic but clinically insignificant difference in systolic blood pressure between arms. The interarm difference was larger in hypertension and PAD. Consistent lateralisation is present for differences ≥20 mmHg and an interarm difference >25 mmHg is a reliable indicator of PAD in the legs.

BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

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Thapa, Lekhjung; Rana, P V S

2016-01-01

Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

Molecular mechanisms of circulatory dysfunction in cirrhotic portal hypertension

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Hsin-Ling Ho

2015-04-01

Full Text Available Acute or chronic insults to the liver are usually followed by a tissue repairing process. Unfortunately, this action, in most cases, is not effective enough to restore the normal hepatic structure and function. Instead, fibrogenesis and regenerative nodules formation ensue, which are relatively nonfunctioning. The common final stage of the process is liver cirrhosis with increased intrahepatic resistance to portal venous blood flow. Throughout the entire course, the extrahepatic circulatory dysfunction, including increased splanchnic blood flow, elevated portal venous blood flow and pressure, decreased splanchnic and peripheral vascular resistance, tachycardia, and increased cardiac output, are noted and denoted as portal hypertension with hyperdynamic circulatory dysfunction. When such a condition is established, patients may suffer from fatal complications such as gastroesophageal variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome. The cause of such a circulatory dysfunction is not fully elucidated. Nevertheless, clarification of the pathophysiology definitely contributes to the control of portal hypertension-related complications. Herein, the molecular mechanism of this intriguing disaster is reviewed and discussed.

Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

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Huang, Alex L; Silver, Annemarie E; Shvenke, Elena; Schopfer, David W; Jahangir, Eiman; Titas, Megan A; Shpilman, Alex; Menzoian, James O; Watkins, Michael T; Raffetto, Joseph D; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M; Dhadly, Mandeep; Eberhardt, Robert T; Keaney, John F; Gokce, Noyan; Vita, Joseph A

2007-10-01

Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Review of gestational diabetes mellitus effects on vascular structure and function.

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Jensen, Louise A; Chik, Constance L; Ryan, Edmond A

2016-05-01

Vascular dysfunction has been described in women with a history of gestational diabetes mellitus. Furthermore, previous gestational diabetes mellitus increases the risk of developing Type 2 diabetes mellitus, a risk factor for cardiovascular disease. Factors contributing to vascular changes remain uncertain. The aim of this review was to summarize vascular structure and function changes found to occur in women with previous gestational diabetes mellitus and to identify factors that contribute to vascular dysfunction. A systematic search of electronic databases yielded 15 publications from 1998 to March 2014 that met the inclusion criteria. Our review confirmed that previous gestational diabetes mellitus contributes to vascular dysfunction, and the most consistent risk factor associated with previous gestational diabetes mellitus and vascular dysfunction was elevated body mass index. Heterogeneity existed across studies in determining the relationship of glycaemic levels and insulin resistance to vascular dysfunction. © The Author(s) 2016.

The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

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Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

2017-01-01

Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized

Antioxidant Enzymes Activity in Patients with Peripheral Vascular Disease, with and without Presence of Diabetes Mellitus

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Jandrić-Balen, Marica; Božikov, Veljko; Bistrović, Dragica; Jandrić, Ivan; Božikov, Jadranka; Romić, Željo; Balen, Ivan

2003-01-01

The study evaluated antioxidant status in patients with peripheral vascular disease (PVD), with and without concomitant diabetes mellitus (DM). 211 participants were divided into standardized 4 groups: patients with PVD and DM (PVD+DM+), patients with PVD without DM (PVD+DM-), patients without PVD with DM (PVD-DM+) and patients without PVD and DM (PVD-DM-). The diagnosis of PVD was established by Doppler sonography analysis, including determination of the ankle brachial index (...

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

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Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

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Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

2011-01-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

Nitric Oxide Manipulation: A Therapeutic Target for Peripheral Arterial Disease?

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Gareth Williams

2012-01-01

Full Text Available Peripheral Arterial Disease (PAD is a cause of significant morbidity and mortality in the Western world. Risk factor modification and endovascular and surgical revascularisation are the main treatment options at present. However, a significant number of patients still require major amputation. There is evidence that nitric oxide (NO and its endogenous inhibitor asymmetric dimethylarginine (ADMA play significant roles in the pathophysiology of PAD. This paper reviews experimental work implicating the ADMA-DDAH-NO pathway in PAD, focussing on both the vascular dysfunction and effects within the ischaemic muscle, and examines the potential of manipulating this pathway as a novel adjunct therapy in PAD.

Prophylactic effects of elastin peptide derived from the bulbus arteriosus of fish on vascular dysfunction in spontaneously hypertensive rats.

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Takemori, Kumiko; Yamamoto, Ei; Ito, Hiroyuki; Kometani, Takashi

2015-01-01

To determine the prophylactic effects of an elastin peptide derived from the bulbus arteriosus of bonitos and prolylglycine (PG), a degradation product of elastin peptide, on vascular dysfunction in spontaneously hypertensive rats (SHRs). Male 15-week-old SHR/Izm rats were fed without (control group) or with elastin peptide (1 g/kg body weight) for 5 weeks (EP group), or were infused via an osmotic mini-pump for 4 weeks with PG (PG group) or saline (control group). Using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension was compared. mRNA production levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. Aortas of the EP group displayed limited endothelial damage compared with that in the control group. Under treatment of SHRs with elastin peptide, the effect of phenylephrine returned closer to the normal level observed in normotensive Wistar-Kyoto (WKY/Izm) rats. mRNA production of eNOS (but not ICAM-1) was greater in the EP group than in the control group. Endothelial damage was suppressed and pressure-induced vascular distension was greater in the PG group than in the corresponding control group. These results suggest that elastin peptide from bonitos elicits prophylactic affects hypertension-associated vascular dysfunction by targeting the eNOS signaling pathway. PG may be a key mediator of the beneficial effects of elastin peptide. Copyright © 2014 Elsevier Inc. All rights reserved.

The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

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Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

2010-10-01

The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction

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Lamping, KL; Nuno, DW; Coppey, LJ; Holmes, AJ; Hu, S; Oltman, CL; Norris, AW; Yorek, MA

2013-01-01

Aims The ability of dietary enrichment with monounsaturated (MUFA), n-3, or n-6 polyunsaturated fatty acids (PUFA) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO). Material and Methods We fed mice a high saturated fat diet (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signaling and reactivity of isolated pressurized gracilis arteries. Results After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance, and indices of insulin signaling (phosphorylated Akt) to normal whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine reduced in MO fed mice compared to normal. Conclusion We conclude that short term enrichment of an ongoing high fat diet with n-3 PUFA rich MO but not MUFA rich OO or n-6 PUFA rich SO reverses glucose tolerance, insulin signaling, and vascular dysfunction. PMID:22950668

Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension.

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Trebicka, Jonel; Wix, Cyrus; von Heydebrand, Matthias; Hittatiya, Kanishka; Reiberger, Thomas; Klein, Sabine; Schierwagen, Robert; Kristiansen, Glen; Peck-Radosavljevic, Markus; Fischer, Hans-Peter; Møller, Søren; Bendtsen, Flemming; Krag, Aleksander; Sauerbruch, Tilman

2015-04-01

Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels. Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot. The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa. This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia

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Felipe A. Zuniga

2014-01-01

Full Text Available The bioavailability of nitric oxide (NO represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE. PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1, which induces endothelial dysfunction by increasing reactive oxygen species (ROS and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

Prevalence of erectile dysfunction and associated factors among diabetic men attending diabetic clinic at Muhimbili National Hospital in Dar-es-Salaam, Tanzania.

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Mutagaywa, Reuben Kato; Lutale, Janeth; Aboud, Muhsin; Kamala, Benjamin Anathory

2014-01-01

There has been an increase in the prevalence of erectile dysfunction (ED) in the general population especially among Diabetic patients. This seems to be neglected problem in low-income countries. This study aims at establishing the prevalence of ED and associated risk factors in diabetic patients attended at Diabetic Clinic at Muhimbili National Hospital. A cross-sectional hospital based study was conducted among 312 diabetic patients attending diabetic clinic at Muhimbili National Hospital between May and December 2011. More than half (55.1%) of the patients were found to have some form of ED (12.8% had mild dysfunction, 11.5% moderate and 27.9% severe dysfunction). The severity of ED was correlated with increased age. Multivariate logistic regression revealed that ED was significantly predicted by old age (odds ratio (OR) = 7.1, 95% CI 1.2-40.7), evidence of peripheral neuropathy (OR) =5.9, 95% CI 1.6-21.3), and evidence of peripheral vascular disease (OR =2.5, 95% CI 1.2-5.3). Also longer duration of DM was marginally associated with ED (p=0.056). Patients with ED were also more likely to suffer other sexual domains (perectile dysfunction.

Peripheral artery disease: potential role of ACE-inhibitor therapy

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Giuseppe Coppola

2008-12-01

Full Text Available Giuseppe Coppola, Giuseppe Romano, Egle Corrado, Rosa Maria Grisanti, Salvatore NovoDepartment of Internal Medicine, Cardiovascular and Nephro-Urological Diseases, Chair of Cardiovascular Disease, University of Palermo, Palermo, ItalyAbstract: Subjects with peripheral arterial disease (PAD of the lower limbs are at high risk for cardiovascular and cerebrovascular events and the prevalence of coronary artery disease in such patients is elevated. Recent studies have shown that regular use of cardiovascular medications, such as therapeutic and preventive agents for PAD patients, seems to be promising in reducing long-term mortality and morbidity. The angiotensin-converting-enzyme (ACE system plays an important role in the pathogenesis and progression of atherosclerosis, and ACE-inhibitors (ACE-I seem to have vasculoprotective and antiproliferative effects as well as a direct antiatherogenic effect. ACE-I also promote the degradation of bradykinin and the release of nitric oxide, a potent vasodilator; further, thay have shown important implications for vascular oxidative stress. Other studies have suggested that ACE-I may also improve endothelial dysfunction. ACE-I are useful for reducing the risk of cardiovascular events in clinical and subclinical PAD. Particularly, one agent of the class (ie, ramipril has shown in many studies to able to significantly reduce cardiovascular morbidity and mortality in patients with PAD.Keywords: atherosclerosis, peripheral arterial disease, endothelial dysfunction, ACE-inhibitors

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

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Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

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Fetterman, Jessica L; Holbrook, Monica; Westbrook, David G; Brown, Jamelle A; Feeley, Kyle P; Bretón-Romero, Rosa; Linder, Erika A; Berk, Brittany D; Weisbrod, Robert M; Widlansky, Michael E; Gokce, Noyan; Ballinger, Scott W; Hamburg, Naomi M

2016-03-31

Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy

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Zhang, Lu, E-mail: chaperones@163.com [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Guo, YuQi [Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China)

2016-03-05

Highlights: • B-Fe{sub 3}O{sub 4}NPs did not induce cell apoptosis or necrosis in HUVECs within 24 h. • B-Fe{sub 3}O{sub 4}NPs induced HUVEC dysfunction and inflammation. • B-Fe{sub 3}O{sub 4}NPs induced enhanced autophagic activity and blockade of autophagy flux. • Suppression of autophagy dysfunction attenuated B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. - Abstract: Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe{sub 3}O{sub 4}NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe{sub 3}O{sub 4}NPs (B-Fe{sub 3}O{sub 4}NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe{sub 3}O{sub 4}NPs did not induce cell death within 24 h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe{sub 3}O{sub 4}NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe{sub 3}O{sub 4}NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe{sub 3}O{sub 4}NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe{sub 3}O{sub 4}NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe{sub 3}O{sub 4}NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.

International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection

DEFF Research Database (Denmark)

Behrendt, Christian-Alexander; Bertges, Daniel; Eldrup, Nikolaj

2018-01-01

intervention; (ix) complications; and (x) follow up. CONCLUSION: A modified Delphi study allowed 25 international vascular registry experts to achieve a consensus recommendation for a minimum core data set and an optimum data set for peripheral arterial revascularisation registries. Continued global...... via internet exchange and face to face discussions. In total, 187 different items from the various registry data forms were identified for potential inclusion in the recommended data set. Ultimately, 79 items were recommended for inclusion in minimum core data sets, including 65 items in the level 1...... data set, and an additional 14 items in the more specific level 2 and 3 recommended data sets. Data elements were broadly divided into (i) patient characteristics; (ii) comorbidities; (iii) current medications; (iv) lesion treated; (v) procedure; (vi) bypass; (vii) endarterectomy (viii) catheter based...

N-Acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs.

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Herrera, Emilio A; Cifuentes-Zúñiga, Francisca; Figueroa, Esteban; Villanueva, Cristian; Hernández, Cherie; Alegría, René; Arroyo-Jousse, Viviana; Peñaloza, Estefania; Farías, Marcelo; Uauy, Ricardo; Casanello, Paola; Krause, Bernardo J

2017-02-15

Intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial epigenetic programming of the umbilical vessels. There is no evidence that this epigenetic programming is occurring on systemic fetal arteries. In IUGR guinea pigs we studied the functional and epigenetic programming of endothelial nitric oxide synthase (eNOS) (Nos3 gene) in umbilical and systemic fetal arteries, addressing the role of oxidative stress in this process by maternal treatment with N-acetylcysteine (NAC) during the second half of gestation. The present study suggests that IUGR endothelial cells have common molecular markers of programming in umbilical and systemic arteries. Notably, maternal treatment with NAC restores fetal growth by increasing placental efficiency and reverting the functional and epigenetic programming of eNOS in arterial endothelium in IUGR guinea pigs. In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetylcysteine (NAC) on fetal endothelial function and endothelial nitric oxide synthase (eNOS) programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, half of the sows receiving NAC in the drinking water (from day 34 until term). Fetal biometry and placental vascular resistance were followed by ultrasound throughout gestation. At term, umbilical arteries and fetal aortae were isolated to assess endothelial function by wire-myography. Primary cultures of endothelial cells (ECs) from fetal aorta, femoral and umbilical arteries were used to determine eNOS mRNA levels by quantitative PCR and analyse DNA methylation in the Nos3 promoter by pyrosequencing. Doppler ultrasound measurements showed that NAC reduced placental vascular resistance

Altered protein expression profiles in umbilical veins: insights into vascular dysfunctions of the children born after in vitro fertilization.

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Gao, Qian; Pan, Hai-Tao; Lin, Xian-Hua; Zhang, Jun-Yu; Jiang, Ying; Tian, Shen; Chen, Lu-Ting; Liu, Miao-E; Xiong, Yi-Meng; Huang, He-Feng; Sheng, Jian-Zhong

2014-09-01

Cardiovascular dysfunction and remodeling have been found in some children conceived by in vitro fertilization (IVF). However, the underlying mechanisms remain unclear. In this study, the retrospective investigation showed that the blood pressure of IVF-conceived Chinese children was higher than that of naturally conceived (NC) children at ages 3-13 yr. We analyzed the expression profile of proteins in the umbilical veins of IVF and NC newborns by proteomic techniques. Using iTRAQ (isobaric tags for relative and absolute quantitation), 47 differentially expressed proteins (DEPs) were identified by feature selection in IVF umbilical veins compared with NC. Ingenuity Pathway Analysis, which is used to explore the signaling pathways of DEPs, revealed that these DEPs played important roles in vascular system development and carbon metabolism, implying that these DEPs might be potential candidates for further exploration of the mechanism(s) of vascular dysfunction in IVF children. We found that the serum estradiol (E₂) level in the cord blood of IVF newborns was significantly higher than that of NC newborns. High concentrations of E₂ induced alteration of lumican and vimentin expression in human umbilical vein endothelial cells, which was consistent with the proteomic results. These findings suggested that abnormal expression of proteins in umbilical veins might be related to the cardiovascular dysfunction and remodeling in IVF offspring. In conclusion, our data for the first time reveal the protein expression profile in blood vessels of IVF offspring and provide information for further mechanism study and evaluation of risks of cardiovascular abnormality in IVF children. © 2014 by the Society for the Study of Reproduction, Inc.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy.

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Emter, Craig A; Tharp, Darla L; Ivey, Jan R; Ganjam, Venkataseshu K; Bowles, Douglas K

2011-10-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ET(A)) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K(+) currents (I(K(+))) in coronary smooth muscle cells. Raising internal Ca(2+) from 200 to 500 nM increased Ca(2+)-sensitive K(+) current in HF-TR and control, but not HF animals. In conclusion, an ET(A)-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca(2+)-sensitive I(K(+)) was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca(2+)-sensitive I(K(+)), illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy.

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

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Maseroli, Elisa; Scavello, Irene; Vignozzi, Linda

2018-05-02

Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International

Neuro-otological and peripheral nerve involvement in Fabry disease

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Sergio Carmona

2017-07-01

Full Text Available Fabry disease (FD is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain, vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%, vertigo (27.8% or both (25%. An involvement of either cochlear or vestibular function was identified in most patients (75%. In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neurootological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

Application of DCE-MRI in evaluating lower extremity capillary endothelial function in patients with diabetes mellitus complicated by peripheral vascular disease after PTA

International Nuclear Information System (INIS)

Tian Hao; Zhao Jinli; Chen Xiaohua; Wu Xianhua; Li Yuehua

2014-01-01

Objective: To quantify endothelial function of lower extremity capillary in patients with peripheral vascular disease associated with diabetes mellitus by using DCE-MRI, and to explore the feasibility of DCE-MRI in predicting vascular restenosis in lower extremity after PTA. Methods: During the period form May 2009 to Jan. 2012, a total of 51 patients (study group) with diabetic lower extremity vascular diseases (77 diseased legs in total) were admitted to the hospital and were treated with PTA. Another 20 volunteers were used as control group. K-trans values were measured in soleus muscle using DCE-MRI. Based on the results after 6 months follow-up, the patients were classified into restenosis group and non-restenosis group. The K -trans values and others clinical data were compared between the two groups. Results: Although clinical symptoms and signs were improved in both groups after the treatment, K-trans value of restenosis group showed no obvious changes after PTA, while K-trans value of non-restenosis group was improved significantly. Before PTA, the difference in K -trans value between the two groups was not statistically significant, while K-trans values of the two groups were significantly lower than that of the control group (P<0.05). Conclusion: K-trans value can reflect the endothelial function in diabetes mellitus patients with peripheral vascular disease, and it can also predict the occurrence of restenosis, providing a useful evidence for clinical. therapy. (authors)

Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study

Directory of Open Access Journals (Sweden)

Patino-Alonso Maria C

2011-04-01

Full Text Available Abstract Background Ambulatory blood pressure monitoring (ABPM shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index. Methods/Design A cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group. Main measurements: age, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA and pulse wave velocity (PWV with the Sphigmocor

Assessment of the quality of life of patients with peripheral vascular diseases

International Nuclear Information System (INIS)

Wohlgemuth, W.A.; Bayreuth Univ.; Niechzial, M.; Nagel, E.; Bohndorf, K.

2003-01-01

The Medical Outcome Short Form 36 is commonly used as a generic quality of life measure in the assessment of vascular disease. The Claudication Scale CLAU-S, the PAVK-86 Fragebogen, and the Walking Impairment Questionnaire WIQ are validated disease-specific questionnaires for intermittent claudication. A disease specific tool for critical ischaemia is lacking. Quality of life of patients with peripheral arterial occlusive disease is not only impaired in the physical functioning domains (mobility, self care, activities of daily living), but moreover in their social and emotional wellbeing. This situation worsens under conservative treatment. Angioplasty and operation procedure similar improvements in all dimensions of hrQOL. As radiological interventional procedures just aim to improve hrQOL and do not bring a definite cure for the underlying disease, patients perception of their quality of life should be taken into account both in the indication for angioplasty and for the scientific evaluation of new treatment modalities. (orig.) [de

Ocular vestibular evoked myogenic potential elicited from binaural air-conducted stimulations: clinical feasibility in patients with peripheral vestibular dysfunction.

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Iwasaki, Shinichi; Egami, Naoya; Inoue, Aki; Kinoshita, Makoto; Fujimoto, Chisato; Murofushi, Toshihisa; Yamasoba, Tatsuya

2013-07-01

Ocular vestibular evoked myogenic potentials (oVEMPs) to binaural air-conducted stimulation (ACS) may provide a convenient way of assessing the crossed vestibulo-ocular reflex in patients with vestibular dysfunction as well as in healthy subjects. To investigate the clinical feasibility of using oVEMPs in response to binaural ACS to assess normal subjects and patients with vestibular dysfunction. The study investigated 24 normal subjects (14 men and 10 women, aged from 23 to 60 years) and 14 patients with unilateral peripheral vestibular dysfunction. Each subject underwent oVEMP testing in response to monaural ACS and binaural ACS (500 Hz tone burst, 135 dBSPL). In normal subjects, bilateral oVEMPs were elicited in 75% of subjects in response to monaural ACS and in 91% in response to binaural ACS. Asymmetry ratios (ARs) of the responses to binaural ACS were significantly smaller than those of the responses to monaural ACS (p binaural ACS. Approximately 30% of patients showed reduced ARs to binaural ACS relative to monaural ACS, primarily due to contamination by uncrossed responses elicited in healthy ears.

Noninvasive studies of peripheral vascular disease

International Nuclear Information System (INIS)

Yao, J.S.T.

1987-01-01

Plethysmography probably is the oldest method for measuring blood flow. In this method, measurements are made of changes in volume of an organ or region of tissue. In the modern practice of vascular surgery, the use of plethysmography has been expanded to include detection of not only arterial occlusive disease but also carotid artery disease and venous problems. Several types of plethysmographs are now available for clinical use in the evaluation of arterial occlusions. These are volume, strain-gauge, and photoelectric plethysmographs. The water-filled volume recorder, popular in the early use of plethysmography, is now obsolete and has been replaced by the air-filled volume plethysmograph, notably, the pulse-volume recorder. For clinical application, the newer plethysmographs, such as the strain-gauge, photopletyhsmograph, and pulse-volume recorder, are now standard equipment in many vascular laboratories. They are discussed in this article

[Infectious risk related to the formation of multi-species biofilms (Candida - bacteria) on peripheral vascular catheters].

Science.gov (United States)

Seghir, A; Boucherit-Otmani, Z; Sari-Belkharroubi, L; Boucherit, K

2017-03-01

The Candida yeasts are the fourth leading cause of death from systemic infections, the risk may increase when the infection also involves bacteria. Yeasts and bacteria can adhere to medical implants, such as peripheral vascular catheters, and form a multicellular structures called "mixed biofilms" more resistant to antimicrobials agents. However, the formation of mixed biofilms on implants leads to long-term persistent infections because they can act as reservoirs of pathogens that have poorly understood interactions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Signs of maternal vascular dysfunction precede preeclampsia in women with type 1 diabetes

DEFF Research Database (Denmark)

Clausen, Peter; Ekbom, Pia; Damm, Peter

2007-01-01

Aim This study aims to test the hypothesis that vascular dysfunction is present early in pregnancy in women with type 1 diabetes who subsequently develop preeclampsia. Methods Eighty-three women with type 1 diabetes of more than 10 years duration were followed up prospectively during pregnancy...... women developed preeclampsia. NID was significantly impaired at Week 29 in women prone to preeclampsia (108.8±7.0% vs. 116.8±8.9%, mean±S.D., P...±57 µg/l, Ppreeclampsia were also characterized by higher UAE, higher BP, and higher HbA1C than women who did not [Gestational Week 11: 194 (3–1104) vs. 7 (0–412) mg/24 h, median (range), P=.0003; 122±12/75±6 vs. 111±11/69±9 mmHg, mean±S.D., P

Ultrasound-Guided Angioplasty of Dysfunctional Vascular Access for Haemodialysis. The Pros and Cons

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García-Medina, J., E-mail: josegmedina57@gmail.com [“Reina Sofia” University Hospital, Vascular and Interventional Radiology Unit, Department of Radiology (Spain); García-Alfonso, J. J., E-mail: juanjozarandieta@gmail.com [University of Murcia, Faculty of Medicine (Spain)

2017-05-15

PurposeTo describe the benefits and the disadvantages of angioplasty in dialysis fistulas using only ultrasound guidance.Materials and MethodsThis is a prospective study in 132 failing or non-maturing arteriovenous accesses that underwent 189 ultrasound-guided balloon angioplasties. The technical success was defined as non-use of X-ray fluoroscopy during the procedure.Results127 procedures (67%) were successfully completed without fluoroscopy. Most failures were due to difficulty to traverse aneurismal segments, as well as anastomotic stenoses. Including initial failures, the primary patency rates at 6, 12 months and 2 years were 75 ± 3, 41 ± 3 and 14 ± 2%, respectively.ConclusionEndovascular repair of the dysfunctional vascular access for haemodialysis under ultrasound guidance is feasible and safe in roughly two-thirds of cases.

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

Science.gov (United States)

Roll, Stephanie; Müller-Nordhorn, Jacqueline; Keil, Thomas; Scholz, Hans; Eidt, Daniela; Greiner, Wolfgang; Willich, Stefan N

2008-01-01

Background In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE) or polyester (Dacron®) grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE). Methods We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results Nine randomized controlled trials (RCT) were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 = 14%)). Similarly, there were no significant differences with regard to secondary patency rates. Conclusion Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other. PMID:19099583

Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold-Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.

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Xiong, Shiqiang; Wang, Bin; Lin, Shaoyang; Zhang, Hexuan; Li, Yingsha; Wei, Xing; Cui, Yuanting; Wei, Xiao; Lu, Zongshi; Gao, Peng; Li, Li; Zhao, Zhigang; Liu, Daoyan; Zhu, Zhiming

2017-08-02

Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca 2+ homeostasis and the vascular function in cold-induced hypertension. Primary vascular smooth muscle cells from wild-type or Trpm8 -/- mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular and mitochondrial Ca 2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species-triggered Ca 2+ influx and the activation of RhoA/Rho kinase pathway. In vivo, long-term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of menthol were further validated in angiotensin II-induced hypertensive mice. Long-term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold-induced hypertension. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Evaluating Peripheral Vascular Injuries: Is Color Doppler Enough for Diagnosis?

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Mohd Lateef Wani

2014-03-01

Full Text Available Background:: Vascular injury poses a serious threat to limb and life. Thus, diagnosis should be made immediately with minimally invasive methods. Doppler is a good aid in diagnosis of vascular injury. Methods:: The present prospective study was conducted on 150 patients who presented with soft signs (the signs which are suggestive but not confirmatory of vascular injury. They were subjected to color Doppler examination before exploration. The patients with the features of vascular injury on color Doppler were subjected to exploration. On the other hand, those who had normal Doppler were subjected to CT- angiography. Then, the findings of the exploration were matched with those of color Doppler. The data were analyzed using the SPSS statistical software. Results:: Out of the 150 Doppler examinations, 110 (73.33% were reported as positive, while 40 were reported as negative for vascular injury. These were subjected to CT-angiography and seven of them had the features of vascular injury on CT-angiography. All the patients with positive Doppler or CT angiography findings were subjected to exploration. Doppler had a sensitivity of 94% and specificity of 82.5% in diagnosis of vascular injury using Binary classification test. Conclusions:: Color Doppler is an easily available, reliable, and handy method of diagnosing a vascular injury. It has a very high sensitivity and specificity in diagnosis of vascular injuries.

The relationship between vascular endothelial dysfunction and treatment frequency in neovascular age-related macular degeneration.

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Ueda-Consolvo, Tomoko; Hayashi, Atsushi; Ozaki, Mayumi; Nakamura, Tomoko; Yagou, Takaaki; Abe, Shinya

2017-07-01

To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections.

The Effect of Clinical Care Location on Clinical Outcomes After Peripheral Vascular Intervention in Medicare Beneficiaries.

Science.gov (United States)

Turley, Ryan S; Mi, Xiaojuan; Qualls, Laura G; Vemulapalli, Sreekanth; Peterson, Eric D; Patel, Manesh R; Curtis, Lesley H; Jones, W Schuyler

2017-06-12

Modifications in reimbursement rates by Medicare in 2008 have led to peripheral vascular interventions (PVI) being performed more commonly in outpatient and office-based clinics. The objective of this study was to determine the effects of this shift in clinical care setting on clinical outcomes after PVI. Modifications in reimbursement have led to peripheral vascular intervention (PVI) being more commonly performed in outpatient hospital settings and office-based clinics. Using a 100% national sample of Medicare beneficiaries from 2010 to 2012, we examined 30-day and 1-year rates of all-cause mortality, major lower extremity amputation, repeat revascularization, and all-cause hospitalization by clinical care location of index PVI. A total of 218,858 Medicare beneficiaries underwent an index PVI between 2010 and 2012. Index PVIs performed in inpatient settings were associated with higher 1-year rates of all-cause mortality (23.6% vs. 10.4% and 11.7%; p index revascularization and geographic region on the occurrence of all-cause hospitalization, repeat revascularization, and lower extremity amputation. Index PVI performed in office-based settings was associated with a higher hazard of repeat revascularization when compared with other settings. Differences in clinical outcomes across treatment settings and geographic regions suggest that inconsistent application of PVI may exist and highlights the need for studies to determine optimal delivery of PVI in clinical practice. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

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Luciana Teofili

2015-05-01

Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-α-induced vascular endothelial dysfunction

International Nuclear Information System (INIS)

Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.; Chen, J.-W.; Chiang, H.-C.

2007-01-01

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-α)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-α induces various biological effects on vascular cells, TNF-α dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-α concentrations, we adopted the lower TNF-α (0.2 ng/ml) to rule out the possible involvement of other TNF-α-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-α-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-α-induced nuclear factor-kappaB (NF-κB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-α. Inhibition of ERK, JNK, or NF-κB attenuates TNF-α-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-α induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-κB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-α. Although AP-1 activation by the lower TNF-α was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-α-induced adhesion molecule expression

Association between glycemic control and morning blood surge with vascular endothelial dysfunction in type 2 diabetes mellitus patients

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Rama Kumari Nuthalapati

2016-01-01

Full Text Available Objective: Morning blood pressure surge (MBPS is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and MBPS, and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM. The current study examined the association between glycemic control and MBPS and the involvement of MBPS in the development of vascular dysfunction in T2DM patients. Materials and Methods: One hundred and twenty-two consecutive T2DM outpatients from the Department of Cardiology and Endocrinology were enrolled in this study. We did MBPS in T2DM patients, 85 (male (69.7% patients and 37 (female patients (30.3%; mean age 60.1 ± 9.39; (n = 122 using 24 h ambulatory blood pressure monitoring and assessed vascular function by brachial artery flow-mediated dilation (FMD and nitroglycerin-mediated dilation (NMD. Results: The correlation between MBPS and various clinical variables were examined by single regression analysis in all subjects. MBPS showed significant and positive correlation with pulse rate (P = 0.01, fasting blood sugar (P = 0.002, and postprandial blood sugar (P = 0.05. To further confirm the association of insulin resistance (IR with MBPS in T2DM patients, we examined the correlation between homeostasis model assessment-IR (HOMA-IR, an established marker of IR and MBPS in diabetic (DM patients who were not taking insulin no significant association with MBPS in T2DM patients (P = 0.41, angiotensin-converting enzyme/angiotensin receptor blocker (P = 0.07. We examined the relationship between MBPS and vascular injury by measuring endothelium-dependent FMD and endothelium-independent NMD in T2DM patients. Among the various traditional risk factors for atherosclerosis such as DM duration (P = 0.04, platelet reactivity (P = 0.04 and morning surge (P = 0.002 emerged as significant factors. HOMA-IR was a negative correlation with FMD. Conclusions: The current study demonstrated that

The inter-arm blood pressure difference and peripheral vascular disease: cross-sectional study.

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Clark, Christopher E; Campbell, John L; Powell, Roy J; Thompson, John F

2007-10-01

A blood pressure (BP) difference between the upper limbs is often encountered in primary care. Knowledge of its prevalence and importance in the accurate measurement of BP is poor, representing a source of error. Current hypertension guidelines do not emphasize this. To establish the prevalence of an inter-arm blood pressure difference (IAD) and explore its association with other indicators of peripheral vascular disease (PVD) in a hypertensive primary care population. This was a cross-sectional study. Primary care, one rural general practice, was the setting of the study. The methods were controlled simultaneous measurement of brachial BPs, ankle-brachial pressure index (ABPI) and tiptoe stress testing in 94 subjects. In all, 18 of 94 [19%, 95% confidence interval (CI) 11-27%] subjects had mean systolic inter-arm difference (sIAD) > or =10 mmHg and seven of 94 (7%, 95% CI 2-12%) had mean diastolic inter-arm difference (dIAD) > or =10 mmHg. Nineteen of 91 (20%, 95% CI 12-28%) had a reduced ABPI pressure drop > or =20%. An IAD and asymptomatic PVD are common in a primary care hypertensive population. Magnitude of the IAD is inversely correlated with ABPI, supporting the hypotheses that IADs are causally linked to PVD, and that IAD is a useful marker for the presence of PVD. Consequently, detection of an IAD should prompt the clinician to screen subjects for other signs of vascular disease and target them for aggressive cardiovascular risk factor modification.

Autonomic dysfunction in cirrhosis and portal hypertension

DEFF Research Database (Denmark)

Dümcke, Christine Winkler; Møller, Søren

2008-01-01

Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases...

Atrial fibrillation and vascular disease-a bad combination

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Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2012-01-01

This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2

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Lindegaard Pedersen, Brian; Bækgaard, Niels; Quistorff, Bjørn

2017-01-01

BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests...... were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function...... group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P

TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

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Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

2014-06-15

Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

International Nuclear Information System (INIS)

Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y

2014-01-01

Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

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Eidt Daniela

2008-12-01

Full Text Available Abstract Background In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE or polyester (Dacron® grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE. Methods We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results Nine randomized controlled trials (RCT were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28], no significant heterogeneity (p = 0.32, I2 = 14%. Similarly, there were no significant differences with regard to secondary patency rates. Conclusion Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other.

ORIGINAL ARTICLES Assessing peripheral arteries in South African ...

African Journals Online (AJOL)

Enrique

2004-05-02

May 2, 2004 ... No data are available on this topic in African black diabetic patients, where the ..... peripheral vascular disease in the university based Vascular Surgical Service in Durban. MD thesis, University of Natal, 1999. 5. Brooks B ...

Reconstructive vascular surgery below the knee

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Rasmussen, L B; Jelnes, R; Sager, P

1986-01-01

In a series of 38 consecutive patients with advanced peripheral vascular disease (i.e. rest pain) reconstructive vascular surgery was performed with the distal anastomosis below the knee. Ankle/arm pressure index (AAI) was 0.28 (0.11-0.47) preoperatively; accumulated graft patency rate was 0.47 (SD...

[Recent advances on pericytes in microvascular dysfunction and traditional Chinese medicine prevention].

Science.gov (United States)

Liu, Lei; Liu, Jian-Xun; Guo, Hao; Ren, Jian-Xun

2017-08-01

Pericytesis a kind of widespread vascular mural cells embedded within the vascular basement membrane of blood microvessels, constituting the barrier of capillaries and tissue spaces together with endothelial cells. Pericytes communicate with microvascular endothelial cells through cell connections or paracrine signals, playing an important role in important physiological processes such as blood flow, vascular permeability and vascular formation. Pericytes dysfunction may participate in some microvascular dysfunction, and also mediate pathological repair process, therefore pericytes attracted more and more attention. Traditional Chinese medicine suggests that microvascular dysfunction belongs to the collaterals disease; Qi stagnation and blood stasis in collaterals result in function imbalance of internal organs. Traditional Chinese medicine (TCM) has shown effects on pericytes in microvascular dysfunction, for example qi reinforcing blood-circulation activating medicines can reduce the damage of retinal pericytes in diabetic retinopathy. However, there are some limitations of research fields, inaccuracy of research techniques and methods, and lack of mechanism elaboration depth in the study of microvascular lesion pericytes. This paper reviewed the biological characteristics of pericytes and pericytes in microvascular dysfunction, as well as the intervention study of TCM on pericytes. The article aims to provide reference for the research of pericytes in microvascular dysfunction and the TCM study on pericytes. Copyright© by the Chinese Pharmaceutical Association.

Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus.

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Sheshah, Eman; Madanat, Amal; Al-Greesheh, Fahad; Al-Qaisi, Dalal; Al-Harbi, Mohammad; Aman, Reem; Al-Ghamdi, Abdul Aziz; Al-Madani, Khaled

2015-01-01

Sudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus. This cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan. Feet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC peripheral neuropathy were 67.5 and 58.9 % respectively. Sudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted.

Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo.

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Itani, Nozomi; Skeffington, Katie L; Beck, Christian; Niu, Youguo; Giussani, Dino A

2016-01-01

There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy. © 2015 The Authors. Journal of Pineal Research. Published by John Wiley & Sons Ltd.

Gastrin-releasing peptide induces monocyte adhesion to vascular endothelium by upregulating endothelial adhesion molecules

International Nuclear Information System (INIS)

Kim, Mi-Kyoung; Park, Hyun-Joo; Kim, Yeon; Kim, Hyung Joon; Bae, Soo-Kyung; Bae, Moon-Kyoung

2017-01-01

Gastrin-releasing peptide (GRP) is a neuropeptide that plays roles in various pathophysiological conditions including inflammatory diseases in peripheral tissues; however, little is known about whether GRP can directly regulate endothelial inflammatory processes. In this study, we showed that GRP promotes the adhesion of leukocytes to human umbilical vein endothelial cells (HUVECs) and the aortic endothelium. GRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by activating nuclear factor-κB (NF-κB) in endothelial cells. In addition, GRP activated extracellular signal-regulated kinase 1/2 (ERK1/2), p38MAPK, and AKT, and the inhibition of these signaling pathways significantly reduced GRP-induced monocyte adhesion to the endothelium. Overall, our results suggested that GRP may cause endothelial dysfunction, which could be of particular relevance in the development of vascular inflammatory disorders. - Highlights: • GRP induces adhesion of monocytes to vascular endothelium. • GRP increases the expression of endothelial adhesion molecules through the activation of NF-κB. • ERK1/2, p38MAPK, and Akt pathways are involved in the GRP-induced leukocyte adhesiveness to endothelium.

Endothelial dysfunction in the regulation of portal hypertension

Science.gov (United States)

Iwakiri, Yasuko

2013-01-01

Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions. PMID:21745318

Hospital Readmissions in Diabetic Kidney Transplant Recipients with Peripheral Vascular Disease.

Science.gov (United States)

Lubetzky, Michelle; Kamal, Layla; Ajaimy, Maria; Akalin, Enver; Kayler, Liise

2018-04-28

The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed. We performed a retrospective review of adult diabetic kidney-only transplant recipients with and without PVD transplanted from January 2012 until June 30, 2015. Of 203 diabetic kidney transplant recipients, 56 (27.6%) had PVD and 147 (72.4%) had no PVD. At a median of 3.14 years follow up there were no significant differences in 30-, 90-, or 1-year readmission rates. At 1 year after transplant, PVD patients were significantly more likely to have a greater sum of unplanned inpatient days (44.6% versus 27.9% with ≥10 inpatient days, p=0.03) and at least one reoperation (28.6% vs. 8.7%, pPVD had significantly increased rates of non-graft related operations of which 31.2% were PVD related. Diabetic patients with PVD utilize more resources after kidney transplant, spending more time in the hospital and undergoing more post-transplant operations. The causes of readmission are predominantly related to progression of PVD rather than allograft complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Vascular pathology: Cause or effect in Alzheimer disease?

Science.gov (United States)

Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

2018-03-01

Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Efficacy of intra-meibomian gland injection of the anti-VEGF agent bevacizumab for the treatment of meibomian gland dysfunction with lid-margin vascularity

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Jiang X

2018-05-01

Full Text Available Xiaodan Jiang,* Yuexin Wang,* Huibin Lv, Yan Liu, Mingzhou Zhang, Xuemin Li Department of Ophthalmology, Peking University Third Hospital, Beijing, China *These authors contributed equally to this work Purpose: To investigate the efficacy of a novel treatment – intra-meibomian gland (MG injection of the anti-VEGF agent bevacizumab – for MG dysfunction (MGD with eyelid-margin vascularity. Methods: A total of 26 eyes from 13 patients diagnosed with MGD and eyelid-margin vascularity were included in our study. Patients received intra-meibomian gland injections of bevacizumab (150 µL, 2.5 mg/0.1 mL at multiple sites with a 29 G needle where telangiectasia was severe. The Ocular Surface Disease Index (OSDI, tear film, tear-breakup time (TBUT, eyelid-margin features, MG features, conjunctiva, and corneal staining were assessed at 1 day before injection and 1 week, 1 month, and 3 months after injection. Blood pressure, best-corrected visual acuity, intraocular pressure, and slit lamp examinations were performed to assure the safety of patients at 1 day before and 1 day, 1 week, 1 month, and 3 months after injection. Results: Lid-margin vascularity, conjunctival injection, expressed secretion quality, expressivity of the MG, TBUT, corneal staining, and OSDI were significantly improved 1 week, 1 month, and 3 months after injection compared to baseline values. Lid-margin vascularity, conjunctival injection, meibomian gland expressivity, TBUT, and OSDI continued to improve; the greatest improvements were observed at 1 month and sustained for 3 months. Spearman’s correlation analysis indicated that age and sex significantly influenced TBUT improvement. Females and older patients tended to have shorter baseline TBUT that followed a different trend from that of males and younger patients during postinjection visits, revealed by subgroup analysis. No local or systemic side effects were observed at follow-up visits. Conclusion: This study is the first to

The effects of vasoactive agents on flow through saphenous vein grafts during lower-extremity peripheral vascular surgery.

Science.gov (United States)

Maslow, Andrew D; Bert, Arthur; Slaiby, Jeffrey; Carney, William; Marcaccio, Edward

2007-06-01

The purpose of this study was to assess the effects of hemodynamic alterations on vein graft flow during peripheral vascular surgery. It was hypothesized that vasopressors can be administered without compromising flow through the vein grafts. Tertiary care center, university medical center. Randomized placebo-controlled double-blinded study. The effects of phenylephrine, epinephrine, milrinone, intravenous fluid, and placebo on newly constructed peripheral vein grafts were assessed in 60 patients (12 patients in each of 5 groups). Systemic and central hemodynamics were measured by using intra-arterial and pulmonary artery catheters. Vein graft flow was measured by using a transultrasonic flow probe (Transultrasonic Inc, Ithaca, NY). Phenylephrine increased systemic mean blood pressure (mBP) (68.2-94.0 mmHg, p < 0.01), systemic vascular resistance (SVR) (1,091-1,696 dynes x sec x cm(-5), p < 0.001), and vein graft flow (39.5-58.9 mL/min, p < 0.01), whereas cardiac output remained unchanged. Epinephrine resulted in increased cardiac output (4.4-6.9 L/min, p < 0.01) and mBP (72.7-89.1 mmHg, p < 0.01), whereas vein graft flow was reduced in 6 of 12 patients. Intravenous fluid administration resulted in a relatively smaller increase in graft flow (37.6-46.0 mL/min, p < 0.05), an increase in cardiac output, and an insignificant decrease in SVR. Other treatments had either little or no effect on vein graft flow. The study hypothesis was partly supported. Although both phenylephrine and epinephrine increased blood pressure, only the former increased vein graft flow in all patients. In conjunction with increases in graft flow after fluid administration, these data suggest that factors affecting vein graft flow are not just simply related to systemic hemodynamics.

Estudo de associação entre anticorpos anticardiolipinas e fenômenos vasculares periféricos em pacientes com esclerodermia sistêmica Study about the association between anticardiolipin antibodies and peripheral vascular phenomena in patients suffering from systemic scleroderma

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Ana Paula Torres Liberati

2010-06-01

Full Text Available Isquemia é comum em esclerodermia sistêmica e é causada por vasoespasmo e trombose. As autoras analisaram a associação de eventos vasculares periféricos e anticorpos anticardiolipinas (aCl em 54 esclerodérmicos. Em 100% deles existia Raynaud; 59,2% apresentaram cicatrizes estelares; 43,3%, telangiectasias; 14,8%, fenômenos tromboembólicos periféricos. ACl IgG foram positivos em 9,2% dos casos e o IgM, em 7,4%. Fenômenos embólicos periféricos estão associados a aCl IgG (p=0,03, não se encontrando associação com demais manifestações.Ischemia is common in systemic scleroderma and it is caused by vasospasm and thrombosis. In the present study we analyzed the association of peripheral vascular events and anticardiolipin (aCl antibodies in 54 patients suffering from systemic scleroderma. The results showed that 100% of the patients presented Raynaud; 59.2% presented digital micro scars; 43.3%, presented teleangiectasies and 14.8%, presented peripheral thromboembolism. ACl IgG were positive in 9.2% and IgM, in 7.4%. Peripheral tromboembolic phenomena had a positive association with aCl IgG (p=0.03. No other associations were found.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

International Nuclear Information System (INIS)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

2017-01-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

Energy Technology Data Exchange (ETDEWEB)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

2017-05-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Diagnosis and treatment of vascular damage in dementia.

Science.gov (United States)

Biessels, Geert Jan

2016-05-01

This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Transfemoral transcatheter aortic valve implantation in patients with small diseased peripheral vessels

International Nuclear Information System (INIS)

Ruparelia, Neil; Buzzatti, Nicola; Romano, Vittorio; Longoni, Matteo; Figini, Fillipo; Montorfano, Matteo; Kawamoto, Hiroyoshi; Miyazaki, Tadashi; Spagnolo, Pietro; Alfieri, Ottavio; Colombo, Antonio; Latib, Azeem

2015-01-01

Objectives: The aim of this study was to assess the feasibility, safety and short-term outcomes of transfemoral transcatheter aortic valve implantation (TF-TAVI) in patients with small diseased peripheral vessels. Background: The transfemoral (TF) route for transcatheter aortic valve (TAVI) is the default option due to associated advantages. However, this is limited due to the high prevalence of significant peripheral arterial disease and increased risk of vascular complications. Methods: Of 539 consecutive patients undergoing TAVI in a single Italian center, 23 patients underwent TF-TAVI in the presence of small peripheral vessels as defined by a minimal luminal diameter (MLD) of ≤ 5.5 mm [by computed tomography (CT)] and/or the inability to advance a large-bore sheath. Calcification was defined as being concentric if calcium extended more than 270° around the circumference of the artery. All patients underwent 30-day clinical follow-up. Results: 17 (73.9%) patients underwent peripheral vessel pre-dilatation with a semi-compliant balloon and 6 (26.1%) patients with a Solopath sheath. 6 (26.1%) patients suffered a peri-procedural complication, with 1 patient requiring surgical embolectomy for thrombotic occlusion and the remaining patients successfully managed percutaneously in the catheter laboratory. No patient suffered a vessel perforation or required implantation of a covered stent. At 30-day follow-up, all patients were free of symptoms and signs or symptoms of peripheral vascular disease, with well-functioning TAVI prostheses as evaluated by echocardiography. Conclusions: Performing TF-TAVI is feasible in patients with no other viable vascular access option in the presence of small MLD and calcification of the peripheral vasculature, with any anticipated acute vascular complication managed in the catheter laboratory with established percutaneous techniques. - Highlights: • Small peripheral vessels is regarded as contraindication to transfemoral TAVI. �

Transfemoral transcatheter aortic valve implantation in patients with small diseased peripheral vessels

Energy Technology Data Exchange (ETDEWEB)

Ruparelia, Neil [San Raffaele Scientific Institute, Milan (Italy); Imperial College, London (United Kingdom); Buzzatti, Nicola; Romano, Vittorio; Longoni, Matteo; Figini, Fillipo; Montorfano, Matteo; Kawamoto, Hiroyoshi; Miyazaki, Tadashi; Spagnolo, Pietro; Alfieri, Ottavio; Colombo, Antonio [San Raffaele Scientific Institute, Milan (Italy); Latib, Azeem, E-mail: info@emocolumbus.it [San Raffaele Scientific Institute, Milan (Italy)

2015-09-15

Objectives: The aim of this study was to assess the feasibility, safety and short-term outcomes of transfemoral transcatheter aortic valve implantation (TF-TAVI) in patients with small diseased peripheral vessels. Background: The transfemoral (TF) route for transcatheter aortic valve (TAVI) is the default option due to associated advantages. However, this is limited due to the high prevalence of significant peripheral arterial disease and increased risk of vascular complications. Methods: Of 539 consecutive patients undergoing TAVI in a single Italian center, 23 patients underwent TF-TAVI in the presence of small peripheral vessels as defined by a minimal luminal diameter (MLD) of ≤ 5.5 mm [by computed tomography (CT)] and/or the inability to advance a large-bore sheath. Calcification was defined as being concentric if calcium extended more than 270° around the circumference of the artery. All patients underwent 30-day clinical follow-up. Results: 17 (73.9%) patients underwent peripheral vessel pre-dilatation with a semi-compliant balloon and 6 (26.1%) patients with a Solopath sheath. 6 (26.1%) patients suffered a peri-procedural complication, with 1 patient requiring surgical embolectomy for thrombotic occlusion and the remaining patients successfully managed percutaneously in the catheter laboratory. No patient suffered a vessel perforation or required implantation of a covered stent. At 30-day follow-up, all patients were free of symptoms and signs or symptoms of peripheral vascular disease, with well-functioning TAVI prostheses as evaluated by echocardiography. Conclusions: Performing TF-TAVI is feasible in patients with no other viable vascular access option in the presence of small MLD and calcification of the peripheral vasculature, with any anticipated acute vascular complication managed in the catheter laboratory with established percutaneous techniques. - Highlights: • Small peripheral vessels is regarded as contraindication to transfemoral TAVI. �

Oral Health and Erectile Dysfunction

OpenAIRE

Singh, Vijendra P.; Nettemu, Sunil K.; Nettem, Sowmya; Hosadurga, Rajesh; Nayak, Sangeeta U.

2017-01-01

Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP) and erectile dysfunction (ED) by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this...

/sup 99m/Tc radionuclide angioscintigraphic perfusion analysis in the assessment and follow-up of peripheral vascular diseases of the lower limbs

International Nuclear Information System (INIS)

Bencini, C.; Mazzuca, N.; Bertelli, P.; Pulera, N.; Mariani, G.

1986-01-01

Peripheral arterial diseases (PADs) of the lower limbs such as thromboangitis obliterans (TAO) (Buerger's disease), arteriosclerosis obliterans (ASO) and diabetes mellitus, produce trophic disturbances occurring most often in the toes. Perfusion analysis of the foot and toes was previously reported. The analysis utilized radionuclide arteriography (RNA) during reactive hyperaemia to obtain peak activity in RNA time-activity curves (TACs). RNA was also used to assess healing capability of skin ulcers of the calf and ankle, which depends on localized enhancement of capillary blood flow. On these bases, detection of capillary blood flow assumes primary importance in the assessment of peripheral vascular disease (PVD). The purpose of this study was to determine whether RNA of the toes at rest could provide adequate assessment of microcirculation in PVD and of microcirculatory changes induced by lumbar sympathectomy (LS)

Body Mass Index and Operating Times in Vascular Procedures

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M. Durup-Dickenson

Full Text Available : Introduction: The influence of body mass index (BMI on operating times in central and peripheral vascular surgical procedures was investigated. Report: A national cohort of Danish patients who underwent a vascular procedure between 1983 and 2012 was used for analysis. Data were analysed with pairwise comparisons of BMI groups for operating times using the independent samples Kruskall–Wallis test. Discussion: A total of 3,255 carotid endarterectomies; 6,885 central vascular procedures; and 4,488 peripheral bypasses were included for the analysis. Median operating times for carotid endarterectomy and central vascular procedures were, respectively, 5 and 15 minutes longer in obese patients than in normal weight patients. This represents a 7% and 10% increase in median operating times, respectively. Linear and multi-adjusted linear regressions were conducted adjusting for confounders, showing a significant correlation between BMI and operating time. Obesity significantly increased the operating times in carotid endarterectomy and central vascular procedures. These may have ramifications for the individual operative stress but not necessarily on logistical operation planning. Keywords: Body mass index (BMI, Obesity, Operating time, Surgery, Vascular surgical procedures

Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

OpenAIRE

Flatters, Sarah J.L.; Bennett, Gary J.

2006-01-01

Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

Science.gov (United States)

Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

2015-01-01

To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

A new therapeutic approach for erectile dysfunction: Low intensity shockwaves

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García-Perdomo, Herney Andrés

2015-07-01

Full Text Available Erectile dysfunction is the inability to achieve or sustain a penile erection for vaginal penetration and satisfactory sexual performance. It is the second most frequent problem of sexual dysfunction in men, after premature ejaculation, with an approximate prevalence rate of 30%. Most cases of erectile dysfunction have an organic origin, mostly vascular diseases, but it is also associated with psychological, neurological, and hormonal factors, or with structural alterations of the penis. Therapy with 5-phosphodiesterase inhibitors has been clinically effective, but some patients do not respond to it. Lowintensity shock waves may improve penile vascularity and blood flow, leading to better erections, and improvement of the quality of sexual performance. In this review several studies are included that show the effectiveness of this treatment for erectile dysfunction.

Development and Validation of a Preprocedural Risk Score to Predict Access Site Complications After Peripheral Vascular Interventions Based on the Vascular Quality Initiative Database

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Daniel Ortiz

2016-01-01

Full Text Available Purpose: Access site complications following peripheral vascular intervention (PVI are associated with prolonged hospitalization and increased mortality. Prediction of access site complication risk may optimize PVI care; however, there is no tool designed for this. We aimed to create a clinical scoring tool to stratify patients according to their risk of developing access site complications after PVI. Methods: The Society for Vascular Surgery’s Vascular Quality Initiative database yielded 27,997 patients who had undergone PVI at 131 North American centers. Clinically and statistically significant preprocedural risk factors associated with in-hospital, post-PVI access site complications were included in a multivariate logistic regression model, with access site complications as the outcome variable. A predictive model was developed with a random sample of 19,683 (70% PVI procedures and validated in 8,314 (30%. Results: Access site complications occurred in 939 (3.4% patients. The risk tool predictors are female gender, age > 70 years, white race, bedridden ambulatory status, insulin-treated diabetes mellitus, prior minor amputation, procedural indication of claudication, and nonfemoral arterial access site (model c-statistic = 0.638. Of these predictors, insulin-treated diabetes mellitus and prior minor amputation were protective of access site complications. The discriminatory power of the risk model was confirmed by the validation dataset (c-statistic = 0.6139. Higher risk scores correlated with increased frequency of access site complications: 1.9% for low risk, 3.4% for moderate risk and 5.1% for high risk. Conclusions: The proposed clinical risk score based on eight preprocedural characteristics is a tool to stratify patients at risk for post-PVI access site complications. The risk score may assist physicians in identifying patients at risk for access site complications and selection of patients who may benefit from bleeding avoidance

Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients

DEFF Research Database (Denmark)

Olivarius, Niels de Fine; Holstein-Rathlou, N H; Siersma, V

2004-01-01

was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p...). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria...... as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function...

Vascular nitric oxide: Beyond eNOS

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Yingzi Zhao

2015-10-01

Full Text Available As the first discovered gaseous signaling molecule, nitric oxide (NO affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC to produce cyclic guanosine monophosphate (cGMP, although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA or production of cyclic inosine monophosphate (cIMP] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

Science.gov (United States)

Mendes Garrido Abregú, Facundo; Gobetto, María Natalia; Juriol, Lorena Vanesa; Caniffi, Carolina; Elesgaray, Rosana; Tomat, Analía Lorena; Arranz, Cristina

2018-06-01

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life. Copyright © 2018 Elsevier Inc. All rights reserved.

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

Energy Technology Data Exchange (ETDEWEB)

Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents--a phantom study.

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Bunck, Alexander C; Jüttner, Alena; Kröger, Jan Robert; Burg, Matthias C; Kugel, Harald; Niederstadt, Thomas; Tiemann, Klaus; Schnackenburg, Bernhard; Crelier, Gerard R; Heindel, Walter; Maintz, David

2012-09-01

4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n=14) than by 2D phase contrast flow imaging (n=10). 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

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Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

2013-10-01

Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Overview of vascular disease

International Nuclear Information System (INIS)

Bisset, G.S. III

1998-01-01

Vascular disease in the pediatric population is a poorly understood process which is often underestimated in its incidence. The common beginnings of such ubiquitous diseases as atherosclerosis manifest themselves at a cellular level shortly after birth. Other common systemic disorders, including congestive heart failure and sepsis, are also intricately associated with dysfunctional vasculature. Progress in the understanding of normal and pathophysiologic processes within the vascular system begins with the 'control center' - the endothelial cell. The purpose of this review is to consolidate a body of knowledge on the processes that occur at the cellular level within the blood vessel wall, and to simplify the understanding of how imbalances in these physiologic parameters result in vascular disease. (orig.)

Mitochondrial dysfunction in obesity.

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de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

2018-01-01

Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral surgical wounding and age-dependent neuroinflammation in mice.

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Zhipeng Xu

Full Text Available Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, Iba1 positive cells (the marker of microglia activation, CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

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Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

2015-07-01

Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial

Atherectomy in Peripheral Artery Disease: A Review.

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Bhat, Tariq M; Afari, Maxwell E; Garcia, Lawrence A

2017-04-01

Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.

Quantification of periodontal pathogens in vascular, blood, and subgingival samples from patients with peripheral arterial disease or abdominal aortic aneurysms.

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Figuero, Elena; Lindahl, Christeel; Marín, María José; Renvert, Stefan; Herrera, David; Ohlsson, Ola; Wetterling, Thomas; Sanz, Mariano

2014-09-01

The aim of this investigation is to quantify periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, and Tannerella forsythia) in vascular, blood, and subgingival samples. As a secondary objective, two molecular bacterial identification methods (nested polymerase chain reaction [PCR] and quantitative PCR [qPCR]) are compared. Seventy consecutive patients provided a vascular lesion, a blood sample, and 36 subgingival samples. Bacterial DNA was extracted, and qPCR was used to determine the prevalence and amounts of the target pathogens in each sample. Nested PCR was performed only in the samples from vascular lesions. Periodontal examination was performed in 42 patients. Mann-Whitney U or χ(2) tests were used to compare microbiologic results according to periodontal diagnosis. All targeted periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, T. forsythia, or C. rectus) were detected in subgingival samples, with a prevalence rate of 72.2%, 47.2%, 74.3%, and 82.9%, respectively. In 7.1% and 11.4% of vascular and blood samples, bacterial DNA was detected. One patient was positive for A. actinomycetemcomitans in the three types of samples. No differences were found in the levels of targeted bacteria when comparing patients with and without periodontitis. Prevalence rates obtained with nested PCR were significantly higher than those obtained with qPCR. The presence of A. actinomycetemcomitans was demonstrated in vascular, blood, and subgingival samples in one of 36 patients. These results, although with a very low frequency, may support the hypothesis of a translocation of periodontal pathogens from subgingival microbiota to the bloodstream and then to atheromatous plaques in carotid or other peripheral arteries. Nested PCR is not an adequate method for identifying DNA of periodontal pathogens in low quantities because of the high number of false-negative results.

Oxidative and inflammatory signals in obesity-associated vascular abnormalities.

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Reho, John J; Rahmouni, Kamal

2017-07-15

Obesity is associated with increased cardiovascular morbidity and mortality in part due to vascular abnormalities such as endothelial dysfunction and arterial stiffening. The hypertension and other health complications that arise from these vascular defects increase the risk of heart diseases and stroke. Prooxidant and proinflammatory signaling pathways as well as adipocyte-derived factors have emerged as critical mediators of obesity-associated vascular abnormalities. Designing treatments aimed specifically at improving the vascular dysfunction caused by obesity may provide an effective therapeutic approach to prevent the cardiovascular sequelae associated with excessive adiposity. In this review, we discuss the recent evidence supporting the role of oxidative stress and cytokines and inflammatory signals within the vasculature as well as the impact of the surrounding perivascular adipose tissue (PVAT) on the regulation of vascular function and arterial stiffening in obesity. In particular, we focus on the highly plastic nature of the vasculature in response to altered oxidant and inflammatory signaling and highlight how weight management can be an effective therapeutic approach to reduce the oxidative stress and inflammatory signaling and improve vascular function. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Atherectomy for peripheral arterial disease].

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Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

2015-04-13

Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

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Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

2017-01-01

Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

Autonomic and Vascular Control in Prehypertensive Subjects with a Family History of Arterial Hypertension

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Josária Ferraz Amaral

2018-02-01

Full Text Available Abstract Background: Individuals with a family history of systemic arterial hypertension (FHSAH and / or prehypertension have a higher risk of developing this pathology. Objective: To evaluate the autonomic and vascular functions of prehypertensive patients with FHSAH. Methods: Twenty-five young volunteers with FHSAH, 14 normotensive and 11 prehypertensive subjects were submitted to vascular function evaluation by forearm vascular conductance(VC during resting and reactive hyperemia (Hokanson® and cardiac and peripheral autonomic modulation, quantified, respectively, by spectral analysis of heart rate (ECG and systolic blood pressure (SBP (FinometerPRO®. The transfer function analysis was used to measure the gain and response time of baroreflex. The statistical significance adopted was p ≤ 0.05. Results: Pre-hypertensive individuals, in relation to normotensive individuals, have higher VC both at rest (3.48 ± 1.26 vs. 2.67 ± 0.72 units, p = 0.05 and peak reactive hyperemia (25, 02 ± 8.18 vs. 18.66 ± 6.07 units, p = 0.04. The indices of cardiac autonomic modulation were similar between the groups. However, in the peripheral autonomic modulation, greater variability was observed in prehypertensive patients compared to normotensive individuals (9.4 [4.9-12.7] vs. 18.3 [14.8-26.7] mmHg2; p < 0.01 and higher spectral components of very low (6.9 [2.0-11.1] vs. 13.5 [10.7-22.4] mmHg2, p = 0.01 and low frequencies (1.7 [1.0-3.0] vs. 3.0 [2.0-4.0] mmHg2, p = 0.04 of SBP. Additionally, we observed a lower gain of baroreflex control in prehypertensive patients compared to normotensive patients (12.16 ± 4.18 vs. 18.23 ± 7.11 ms/mmHg, p = 0.03, but similar delay time (-1.55 ± 0.66 vs. -1.58 ± 0.72 s, p = 0.90. Conclusion: Prehypertensive patients with FHSAH have autonomic dysfunction and increased vascular conductance when compared to normotensive patients with the same risk factor.

MIAMI cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease

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Grau-Monge, Cristina; Delcroix, Gaëtan J.-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F.; Armour, Maxime R.; Montero, Ramon B.; Schiller, Paul C.; Andreopoulos, Fotios M.; D’Ippolito, Gianluca

2017-01-01

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of 2 layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration. PMID:28211362

4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents – A phantom study

International Nuclear Information System (INIS)

Bunck, Alexander C.; Jüttner, Alena; Kröger, Jan Robert; Burg, Matthias C.; Kugel, Harald; Niederstadt, Thomas; Tiemann, Klaus; Schnackenburg, Bernhard; Crelier, Gerard R.

2012-01-01

Purpose: 4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. Materials and methods: 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. Results: In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n = 14) than by 2D phase contrast flow imaging (n = 10). Conclusions: 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type

The influence of perivascular adipose tissue on vascular homeostasis

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Szasz T

2013-03-01

Full Text Available Theodora Szasz,1 Gisele Facholi Bomfim,2 R Clinton Webb1 1Department of Physiology, Georgia Regents University, Augusta, USA; 2Department of Pharmacology, University of São Paulo, São Paulo, Brazil Abstract: The perivascular adipose tissue (PVAT is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT. Keywords: adipokines

Imaging of peripheral arteries by 16-slice computed tomography angiography: a valuable tool

International Nuclear Information System (INIS)

Mishra, A.; Ehtuish, Ehtuish F.

2007-01-01

To evaluate the efficacy of multidetector (16-row) computed tomography (MDCT) in imaging the upper and lower limb arterial tree in trauma and peripheral vascular disease. Thirty three patients underwent multislice computed tomography angiography (MSCTA) of the upper or the lower limb on multislice (16-slice) CT scanner between November 2004 and July 2005 in the Department of Radiology, National Organ Transplant Center, Tripoli, Libya. The findings were retrospectively compared with the surgical outcome in cases of trauma with suspected arterial injuries; or color Doppler correlation was obtained, for patients of peripheral vascular disease. Multislice computed tomography angiography allows a comprehensive diagnostic work-up in all trauma cases with suspected arterial injuries. In 23 cases of peripheral vascular diseases, MSCTA adequately demonstrated the presence of any stenosis or occlusion, its degree and extent, the presence of collaterals and distal reformation if any; the presence of plaques. Our experience of computed tomography angiography with 16-row MDCT scanner has clearly demonstrated its efficacy as a promising, new, fast, accurate, safe and non-invasive imaging modality of choice in cases of trauma with suspected arterial injuries; and as a useful screening modality in cases of peripheral vascular disease for diagnosis and for grading. (author)

Future Targets for Female Sexual Dysfunction.

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Farmer, Melissa; Yoon, Hana; Goldstein, Irwin

2016-08-01

Female sexual function reflects a dynamic interplay of central and peripheral nervous, vascular, and endocrine systems. The primary challenge in the development of novel treatments for female sexual dysfunction is the identification and targeted modulation of excitatory sexual circuits using pharmacologic treatments that facilitate the synthesis, release, and/or receptor binding of neurochemicals, peptides, and hormones that promote female sexual function. To develop an evidence-based state-of-the-art consensus report that critically integrates current knowledge of the therapeutic potential for known molecular and cellular targets to facilitate the physiologic processes underlying female sexual function. State-of-the-art review representing the opinions of international experts developed in a consensus process during a 1-year period. Expert opinion was established by grading the evidence-based medical literature, intensive internal committee discussion, public presentation, and debate. Scientific investigation is urgently needed to expand knowledge and foster development of future treatments that maintain genital tissue integrity, enhance genital physiologic responsiveness, and optimize positive subjective appraisal of internal and external sexual cues. This article critically condenses the current knowledge of therapeutic manipulation of molecular and cellular targets within biological systems responsible for female sexual physiologic function. Future treatment targets include pharmacologic modulation of emotional learning circuits, restoration of normal tactile sensation, growth factor therapy, gene therapy, stem cell-based therapies, and regenerative medicine. Concurrent use of centrally and peripherally acting therapies could optimize treatment response. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Advanced Maternal Age Worsens Postpartum Vascular Function

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Jude S. Morton

2017-06-01

Full Text Available The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin, previously pregnant (postpartum and previously mated but never delivered (nulliparous rats at approximately 13.5 months of age (3 months postpartum or equivalent. Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6% vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively; suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.

What Is Peripheral Artery Disease?

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... or bluish color to the skin A lower temperature in one leg compared to the other leg Poor nail growth on the toes and decreased hair growth on the legs Erectile dysfunction, especially among men who have diabetes Diagnosis Peripheral artery disease (P.A.D.) is diagnosed based ...

Aerobic exercise and other healthy lifestyle factors that influence vascular aging

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Santos-Parker, Jessica R.; LaRocca, Thomas J.

2014-01-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote “resistance” against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

Science.gov (United States)

Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

2014-12-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. Copyright © 2014 The American Physiological Society.

Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

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Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

2013-01-01

In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Endothelial dysfunction: a unifying hypothesis for the burden of cardiovascular diseases in sub-Saharan Africa.

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Sampson, Uchechukwu K A; Engelgau, Michael M; Peprah, Emmanuel K; Mensah, George A

2015-01-01

It is well established that the leading causes of death and disability worldwide are cardiovascular diseases (CVD), chief among which is ischaemic heart disease. However, it is also recognised that ischaemic heart disease frequently coexists with other vascular conditions, such as cerebrovascular, renovascular and peripheral vascular disease, thus raising the notion of a common underlying pathobiology, albeit with differing manifestations, dictated by the implicated vascular bed. The understanding that common metabolic and behavioural risk factors as well as social determinants and drivers are convergent in the development of CVD evokes the idea that the dysfunction of a common bio-molecular platform is central to the occurrence of these diseases. The state of endothelial activation, otherwise known as endothelial dysfunction, occurs when reactive oxygen signalling predominates due to an uncoupled state of endothelial nitric oxide synthase (eNOS). This can be a physiological response to stimulation of the innate immune system or a pathophysiological response triggered by cardiovascular disease risk factors. The conventional wisdom is that the endothelium plays an important role in the initiation, progression and development of CVD and other non-communicable diseases. Consequently, the endothelium has remarkable relevance in clinical and public health practice as well as in health education, health promotion, and disease- and risk-factor prevention strategies. It also presents a plausible unifying hypothesis for the burden of CVD seen globally and in sub-Saharan Africa. Importantly, the heterogeneity in individual responses to metabolic, behavioural, and social drivers of CVD may stem from a complex interplay of these drivers with genomic, epigenetic and environmental factors that underpin eNOS uncoupling. Therefore, further biomedical research into the underlying genetic and other mechanisms of eNOS uncoupling may enlighten and shape strategies for addressing the

Biology of Sexual Dysfunction

Directory of Open Access Journals (Sweden)

Anil Kumar Mysore Nagaraj

2009-05-01

Full Text Available Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic difficulties more often than not coexist, suggesting an integration of phases. Sexual dysfunction can result from a wide variety of psychological and physiological causes including derangements in the levels of sex hormones and neurotrensmitters. This review deals with the biology of different phases of sexual function as well as implications of hormones and neurotransmitters in sexual dysfunction

Cortical capillary dysfunction in patients suspected of Alzheimer’s disease

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Eskildsen, Simon Fristed; Gyldensted, Louise; Nagenthiraja, Kartheeban

Vascular risk factors are suspected to play a role in the etiology of Alzheimer’s disease. Recently, a model that relates capillary dysfunction to the development of AD was proposed[1]. The model predicts that capillary dysfunction in form of increased capillary transit time heterogeneity (CTH...

NF1 Signal Transduction and Vascular Dysfunction

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2015-05-01

microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

Vascular aspects of multiple sclerosis

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D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques

Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial

Evaluation of peripheral vasodilative indices in skin tissue of type 1 diabetic rats by use of RGB images

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Tanaka, Noriyuki; Nishidate, Izumi; Nakano, Kazuya; Aizu, Yoshihisa; Niizeki, Kyuichi

2016-04-01

We investigated a method to evaluate the arterial inflow and the venous capacitance in the skin tissue of streptozotocin-induced type 1 diabetic rats from RGB digital color images. The arterial inflow and the venous capacitance in the dorsal reversed McFarlane skin flap are calculated based on the responses of change in the total blood concentration to occlusion of blood flow to and from the flap tissues at a pressure of 50 mmHg. The arterial inflow and the venous capacitance in the skin flap tissue were significantly reduced in type 1 diabetic rat group compared with the non-diabetic rat group. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular dysfunctions in diabetes mellitus.

Diabetes, vestibular dysfunction, and falls: analyses from the National Health and Nutrition Examination Survey.

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Agrawal, Yuri; Carey, John P; Della Santina, Charles C; Schubert, Michael C; Minor, Lloyd B

2010-12-01

Patients with diabetes are at increased risk both for falls and for vestibular dysfunction, a known risk factor for falls. Our aims were 1) to further characterize the vestibular dysfunction present in patients with diabetes and 2) to evaluate for an independent effect of vestibular dysfunction on fall risk among patients with diabetes. National cross-sectional survey. Ambulatory examination centers. Adults from the United States aged 40 years and older who participated in the 2001-2004 National Health and Nutrition Examination Survey (n = 5,86). Diagnosis of diabetes, peripheral neuropathy, and retinopathy. Vestibular function measured by the modified Romberg Test of Standing Balance on Firm and Compliant Support Surfaces and history of falling in the previous 12 months. We observed a higher prevalence of vestibular dysfunction in patients with diabetes with longer duration of disease, greater serum hemoglobin A1c levels and other diabetes-related complications, suggestive of a dose-response relationship between diabetes mellitus severity and vestibular dysfunction. We also noted that vestibular dysfunction independently increased the odds of falling more than 2-fold among patients with diabetes (odds ratio, 2.3; 95% confidence interval, 1.1-5.1), even after adjusting for peripheral neuropathy and retinopathy. Moreover, we found that including vestibular dysfunction, peripheral neuropathy, and retinopathy in multivariate models eliminated the significant association between diabetes and fall risk. Vestibular dysfunction may represent a newly recognized diabetes-related complication, which acts as a mediator of the effect of diabetes mellitus on fall risk.

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

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Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

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Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A. [AJ Drexel Plasma Institute, Drexel University, Camden, New Jersey 08103 (United States); Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M. [Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 (United States)

2015-12-15

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

Peripheral arterial disease and revascularization of the diabetic foot.

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Forsythe, R O; Brownrigg, J; Hinchliffe, R J

2015-05-01

Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi-level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised--treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non-revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell-based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches. © 2014 John Wiley & Sons Ltd.

Vacuum assisted closure in vascular surgery.

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Beno, M; Martin, J; Sager, P

2011-01-01

Vacuum assisted closure (VAC-therapy) is a well established method in nearly all surgical disciplines. The aim is to present the efficiency of vacuum assisted closure in the treatment of acute and chronic wounds in patients admitted in the department of vascular surgery. Within the year 2008 there were 59 patients (44 men, 15 women) treated with VAC therapy in our Department of Vascular surgery (Landshut, Germany). VAC was used 22x (37.28 %) in therapy of ulcus cruris (venous, arterial, mixed genesis), 15x (25.42%) in patients with diabetic foot syndrome, 12x (20.33%) in secondary healing wounds and infected wounds, 5x (8.47%) in wounds after several injuries and soft skin tissue infections and 5x (8.47%) in wound infections connected with vascular graft infections after vascular revascularization. VAC therapy seems to be very effective in the management of patients with venous ulcers, especially after a proper surgical treatment (100%), patients with soft skin tissue infections (100%) and secondary healing wounds (100%) especially in combination with MESH-Grafting. In patients with diabetic foot syndrome (80%) and peripheral arterial occlusive disease (72.7%), an evaluation of peripheral blood perfusion and revascularization prior to VAC therapy is often necessary. Although VAC was used 5x in the therapy of infected vascular grafts, successful preservation of infected graft material was observed in only one case (infection of PTFE femoro-popliteal bypass graft). Vacuum assisted closure in vascular surgery proved to be simple and efficient method in therapy of acute and chronic wounds. The efficiency of VAC systems in therapy of infected graft material after revascularization needs further studies (Tab. 3, Ref. 10).

Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life.

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Hildreth, Kerry L; Ozemek, Cemal; Kohrt, Wendy M; Blatchford, Patrick J; Moreau, Kerrie L

2018-04-09

The menopausal transition is associated with somatic symptoms and increased rates of depression, which can impair quality of life (QOL) and increase cardiovascular disease (CVD) risk. This period is also associated with accelerated vascular aging (arterial stiffening and endothelial dysfunction), an antecedent to CVD. This secondary analysis sought to explore associations between depression, menopausal symptoms and QOL, and vascular aging across menopause stages. Arterial stiffness (carotid artery compliance), endothelial function (brachial artery flow-mediated dilation [FMD]), menopausal symptoms (Menopausal Symptom List [MSL]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), and QOL (Utian QOL Scale [UQOL]) were measured in 138 women (19-70 years) classified as premenopausal (n = 41, 34 ± 8 years; mean ± SD), early (n = 25, 49 ± 3 years), or late perimenopausal (n = 26, 50 ± 4 years), or early (n = 22, 55 ± 4 years) or late postmenopausal (n = 24, 61 ± 5 years). Differences across menopause stages were determined using one-way analysis of variance; associations between vascular measures and MSL, CES-D, and UQOL were tested using Pearson's correlation analyses. Menopausal symptoms, depression, and QOL worsened across menopause stages, particularly in late perimenopausal women. Vasosomatic symptom frequency, and general somatic symptom frequency and severity were inversely correlated with carotid artery compliance and FMD (r = -0.27 to -0.18, all P stages of menopause was associated with greater frequency and severity of menopausal symptoms, and lower QOL, but not depression. Mechanisms underlying these associations (eg, inflammation, oxidative stress) should be explored.

The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells.

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Han, Jingyan; Weisbrod, Robert M; Shao, Di; Watanabe, Yosuke; Yin, Xiaoyan; Bachschmid, Markus M; Seta, Francesca; Janssen-Heininger, Yvonne M W; Matsui, Reiko; Zang, Mengwei; Hamburg, Naomi M; Cohen, Richard A

2016-10-01

Oxidative stress is implicated in increased vascular permeability associated with metabolic disorders, but the underlying redox mechanism is poorly defined. S-glutathionylation, a stable adduct of glutathione with protein sulfhydryl, is a reversible oxidative modification of protein and is emerging as an important redox signaling paradigm in cardiovascular physiopathology. The present study determines the role of protein S-glutathionylation in metabolic stress-induced endothelial cell permeability. In endothelial cells isolated from patients with type-2 diabetes mellitus, protein S-glutathionylation level was increased. This change was also observed in aortic endothelium in ApoE deficient (ApoE -/- ) mice fed on Western diet. Metabolic stress-induced protein S-glutathionylation in human aortic endothelial cells (HAEC) was positively correlated with elevated endothelial cell permeability, as reflected by disassembly of cell-cell adherens junctions and cortical actin structures. These impairments were reversed by adenoviral overexpression of a specific de-glutathionylation enzyme, glutaredoxin-1 in cultured HAECs. Consistently, transgenic overexpression of human Glrx-1 in ApoE -/- mice fed the Western diet attenuated endothelial protein S-glutathionylation, actin cytoskeletal disorganization, and vascular permeability in the aorta. Mechanistically, glutathionylation and inactivation of Rac1, a small RhoGPase, were associated with endothelial hyperpermeability caused by metabolic stress. Glutathionylation of Rac1 on cysteine 81 and 157 located adjacent to guanine nucleotide binding site was required for the metabolic stress to inhibit Rac1 activity and promote endothelial hyperpermeability. Glutathionylation and inactivation of Rac1 in endothelial cells represent a novel redox mechanism of vascular barrier dysfunction associated with metabolic disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

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Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

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Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

2010-05-15

BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

Endothelial dysfunction after non-cardiac surgery

DEFF Research Database (Denmark)

Søndergaard, E S; Fonnes, S; Gögenur, I

2015-01-01

was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment...

UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes.

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Adler, Amanda I; Stevens, Richard J; Neil, Andrew; Stratton, Irene M; Boulton, Andrew J M; Holman, Rury R

2002-05-01

To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors. Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index < 0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3-4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined. Hyperglycemia, assessed as HbA(1c), was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12-46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10-43). Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.

MRI for peripheral artery disease: Introductory physics for vascular physicians.

Science.gov (United States)

Roy, Trisha L; Forbes, Thomas L; Dueck, Andrew D; Wright, Graham A

2018-04-01

Magnetic resonance imaging (MRI) has advanced significantly in the past decade and provides a safe and non-invasive method of evaluating peripheral artery disease (PAD), with and without using exogenous contrast agents. MRI offers a promising alternative for imaging patients but the complexity of MRI can make it less accessible for physicians to understand or use. This article provides a brief introduction to the technical principles of MRI for physicians who manage PAD patients. We discuss the basic principles of how MRI works and tailor the discussion to how MRI can evaluate anatomic characteristics of peripheral arterial lesions.

Vascular quality of care pilot study: how admission to a vascular surgery service affects evidence-based pharmacologic risk factor modification in patients with lower extremity peripheral arterial disease

Directory of Open Access Journals (Sweden)

Steenhof N

2014-06-01

Full Text Available Naomi Steenhof,1,2 Francesca Le Piane,1 Kori Leblanc,1–3 Naomi R Eisenberg,4 Yvonne Kwan,1 Christine Malmberg,1,6 Alexandra Papadopoulos,5,7 Graham Roche-Nagle4,7,8 1Department of Pharmacy, University Health Network, 2Leslie Dan Faculty of Pharmacy, University of Toronto, 3Centre for Innovation in Complex Care, University Health Network, 4Division of Vascular Surgery, University Health Network, 5Faculty of Nursing, University of Toronto, Toronto, ON, 6Victoria General Hospital, Vancouver Island Health Authority, Victoria, BC, 7Peter Munk Cardiac Centre, University Health Network, 8Faculty of Medicine, University of Toronto, Toronto, ON, Canada Background: Peripheral arterial disease (PAD guidelines recommend aggressive risk factor modification to improve cardiovascular outcomes. Recommended pharmacologic therapies include antiplatelets, angiotensin converting enzyme (ACE inhibitors, and HMG-CoA-reductase inhibitors (statins. Purpose: We studied the degree to which patient admission to a vascular surgery service increased the use of these therapies. Patients and methods: The authors conducted a retrospective chart review of 150 patients with PAD admitted to the vascular surgery service at a large Canadian tertiary care hospital. The use of recommended pharmacologic therapies at the time of admission and discharge were compared. A multidisciplinary clinical team established criteria by which patients were deemed ineligible to receive any of the recommended therapies. Angiotensin receptor blockers (ARBs were considered an alternative to ACE inhibitors. Results: Prior to hospital admission, 64% of patients were on antiplatelet therapy, 67% were on an ACE inhibitor or ARB, and 71% were on a statin. At the time of discharge, 91% of patients were on an antiplatelet (or not, with an acceptable reason, 77% were on an ACE inhibitor or an ARB (or not, with an acceptable reason, and 85% were on a statin (or not, with an acceptable reason. While new

Absence of resting cardiovascular dysfunction in middle-aged endurance-trained athletes with exaggerated exercise blood pressure responses.

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Currie, Katharine D; Sless, Ryan T; Notarius, Catherine F; Thomas, Scott G; Goodman, Jack M

2017-08-01

Untrained individuals with exaggerated blood pressure (EBP) responses to graded exercise testing are characterized as having resting dysfunction of the sympathetic and cardiovascular systems. The purpose of this study was to determine the resting cardiovascular state of endurance-trained individuals with EBP through a comparison of normotensive athletes with and without EBP. EBP was defined as a maximal systolic blood pressure (SBP) at least 190 mmHg and at least 210 mmHg for women and men respectively, in response to a graded exercise test. Twenty-two life-long endurance-trained athletes (56 ± 5 years, 16 men) with EBP (EBP+) and 11 age and sex-matched athletes (55 ± 5 years, eight men) without EBP (EBP-) participated in the study. Sympathetic reactivity was assessed using BP responses to a cold pressor test, isometric handgrip exercise, and postexercise muscle ischemia. Resting left ventricular structure and function was assessed using two-dimensional echocardiography, whereas central arterial stiffness was assessed using carotid-to-femoral pulse wave velocity. Calf vascular conductance was measured at rest and peak postexercise using strain-gauge plethysmography. All sympathetic reactivity, left ventricular, and arterial stiffness indices were similar between groups. There was no between-group difference in resting vascular conductance, whereas peak vascular conductance was higher in EBP+ relative to EBP- (1.81 ± 0.65 vs. 1.45 ± 0.32 ml/100 ml/min/mmHg, P < 0.05). Findings from this study suggest that athletes with EBP do not display the resting cardiovascular state typically observed in untrained individuals with EBP. This response in athletes, therefore, is likely a compensatory mechanism to satisfy peripheral blood-flow demands rather than indicative of latent dysfunction.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

Science.gov (United States)

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Perioperative smoking cessation in vascular surgery

DEFF Research Database (Denmark)

Kehlet, M.; Heesemann, Sabine; Tonnesen, H.

2015-01-01

Background: The effect of intensive smoking cessation programs on postoperative complications has never before been assessed in soft tissue surgery when smoking cessation is initiated on the day of surgery. Methods: A single-blinded randomized clinical trial conducted at two vascular surgery...... departments in Denmark. The intervention group was offered the Gold Standard Program (GSP) for smoking cessation intervention. The control group was offered the departments' standard care. Inclusion criteria were patients with planned open peripheral vascular surgery and who were daily smokers. According...

Usefulness of abdominal aortic calcification for screening of peripheral vascular disease

International Nuclear Information System (INIS)

Park, Chul Hi; Kim, Jeong Ho; Choi, Soo Jin; Kim, Hyung Sik; Jin, Wook; Yang, Dal Mo

2006-01-01

We wanted to evaluate the value of abdominal aortic calcification (AAC), as detected on CT, as a predictor of atherosclerotic stenotic disease of the lower extremity arteries. One hundred three patients who had CT angiography performed for the evaluation of peripheral vascular disease were enrolled in this retrospective study. The volume (mm 3 ) of the AAC was measured on CT. Each lower extremity was divided into 8 segments. The extent of stenosis of the lower extremity artery was manifested as the sum of the stenosis scores for 16 segments (total stenosis score: TSS). The significant stenosis scores (SSS-50 and SSS-75) were defined as the sum of scores for the lower extremity artery segments that had significant stenosis of more than 50% and 75%, respectively. AAC was correlated to the TSS, SSS-50 and SSS-75 with using Spearman's correlation coefficient. The diagnostic performance of AAC for stenosis of a lower extremity artery of more than 50% and 75%, respectively, was evaluated by using the receiver operating characteristic (ROC) curve. The Spearman's correlation coefficients were 0.728 (AAC vs. TSS), 0.662 (AAC vs. SSS-50), and 0.602 (AAC vs. SSS-75), respectively. For significant stenosis more than 50% and 75%, the areas under the ROC curve were 0.898 and 0.866, respectively. The cutoff value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 1030 mm 3 , 87%, 88%, 89%. 86% and 87% for stenosis more than 50% and 1030 mm 3 , 87%, 80%, 79%, 88% and 84% for stenosis more than 75%, respectively. Abdominal aortic calcification detected on CT may be a useful predictor of atherosclerotic stenotic disease of lower extremity arteries

Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

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Zitouni, Karima; Tinworth, Lorna; Earle, Kenneth Anthony

2017-06-29

There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for

Dual-energy CT based vascular iodine analysis improves sensitivity for peripheral pulmonary artery thrombus detection: An experimental study in canines

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Tang, Chun Xiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Han, Zong Hong; Zhou, Chang Sheng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Krazinski, Aleksander W.; Silverman, Justin R. [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

2013-12-01

Purpose: To evaluate the performance of dual-energy CT (DECT) based vascular iodine analysis for the detection of acute peripheral pulmonary thrombus (PE) in a canine model with histopathological findings as the reference standard. Materials and methods: The study protocol was approved by our institutional animal committee. Thrombi (n = 12) or saline (n = 4) were intravenously injected via right femoral vein in sixteen dogs, respectively. CT pulmonary angiography (CTPA) in DECT mode was performed and conventional CTPA images and DECT based vascular iodine studies using Lung Vessels application were reconstructed. Two radiologists visually evaluated the number and location of PEs using conventional CTPA and DECT series on a per-animal and a per-clot basis. Detailed histopathological examination of lung specimens and catheter angiography served as reference standard. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of DECT and CTPA were calculated on a segmental and subsegmental or more distal pulmonary artery basis. Weighted κ values were computed to evaluate inter-modality and inter-reader agreement. Results: Thirteen dogs were enrolled for final image analysis (experimental group = 9, control group = 4). Histopathological results revealed 237 emboli in 45 lung lobes in 9 experimental dogs, 11 emboli in segmental pulmonary arteries, 49 in subsegmental pulmonary arteries, 177 in fifth-order or more distal pulmonary arteries. Overall sensitivity, specificity, accuracy, PPV, and NPV for CTPA plus DECT were 93.1%, 76.9%, 87.8%, 89.4%, and 84.2% for the detection of pulmonary emboli. With CTPA versus DECT, sensitivities, specificities, accuracies, PPVs, and NPVs are all 100% for the detection of pulmonary emboli on a segmental pulmonary artery basis, 88.9%, 100%, 96.0%, 100%, and 94.1% for CTPA and 90.4%, 93.0%, 92.0%, 88.7%, and 94.1% for DECT on a subsegmental pulmonary artery basis; 23.8%, 96.4%, 50.4%, 93

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

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Cheng-Jui Lin

2016-12-01

Full Text Available Background/Aims: Indoxyl sulfate (IS is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD. We explored the effect of IS on human early endothelial progenitor cells (EPCs and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD, pulse wave velocity (PWV, ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS and free IS (F-IS were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR, hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

Nitric oxide bioavailability dysfunction involves in atherosclerosis.

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Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long

2018-01-01

The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

Contemporary vascular smartphone medical applications.

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Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

2013-08-01

Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

Peripheral blood flow control in diabetes mellitus

DEFF Research Database (Denmark)

Hilsted, Jannik

1991-01-01

Long term diabetes has a profound effect on the peripheral circulation. This has been demonstrated to be due to the presence of angiopathy and autonomic neuropathy, affecting autoregulation and distensibility of the vessels as well as local and central reflex regulation of the vascular resistance...

Gene transfer therapy in vascular diseases.

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McKay, M J; Gaballa, M A

2001-01-01

Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid.

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Tian, Rong; Ding, Yun; Peng, Yi-Yuan; Lu, Naihao

2017-03-11

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ), have emerged as important molecules in the pathogenesis of diabetic endothelial dysfunction. Additionally, neutrophils-derived myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) play important roles in the vascular injury. However, it is unknown whether MPO can use vascular-derived ROS to induce diabetic endothelial dysfunction. In the present study, we demonstrated that NADPH oxidase was the main source of ROS formation in high glucose-cultured human umbilical vein endothelial cells (HUVECs), and played a critical role in high glucose-induced endothelial dysfunction such as cell apoptosis, loss of cell viability and reduction of nitric oxide (NO). However, the addition of MPO could amplify the high glucose-induced endothelial dysfunction which was inhibited by the presence of apocynin (NADPH oxidase inhibitor), catalase (H 2 O 2 scavenger), or methionine (HOCl scavenger), demonstrating the contribution of NADPH oxidase-H 2 O 2 -MPO-HOCl pathway in the MPO/high glucose-induced vascular injury. In high glucose-incubated rat aortas, MPO also exacerbated the NADPH oxidase-induced impairment of endothelium-dependent relaxation. Consistent with these in vitro data, in diabetic rat aortas, both MPO expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired. The results suggested that vascular-bound MPO could amplify high glucose-induced vascular injury in diabetes. MPO-NADPH oxidase-HOCl may represent an important pathogenic pathway in diabetic vascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin D in Vascular Calcification: A Double-Edged Sword?

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Jeffrey Wang

2018-05-01

Full Text Available Vascular calcification (VC as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification. Therefore, more complex underlying processes involving physiochemical changes to mineral balance, vascular remodelling and perturbed hormonal responses such as parathyroid hormone (PTH and fibroblast growth factor 23 (FGF-23 are likely to contribute to VC. In particular, VC resulting from modifications to calcium, phosphate and vitamin D homeostasis has been recently elucidated. Notably, deregulation of vitamin D metabolism, dietary calcium intake and renal mineral handling are associated with imbalances in systemic calcium and phosphate levels and endothelial cell dysfunction, which can modulate both bone and soft tissue calcification. This review addresses the current understanding of VC pathophysiology, with a focus on the pathogenic role of vitamin D that has provided new insights into the mechanisms of VC.

Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

LENUS (Irish Health Repository)

O'Sullivan, Eoin P

2010-12-01

Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)\\/RANKL\\/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.

The influence of perivascular adipose tissue on vascular homeostasis.

Science.gov (United States)

Szasz, Theodora; Bomfim, Gisele Facholi; Webb, R Clinton

2013-01-01

The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.

Erectile dysfunction in the cardiovascular patient.

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Vlachopoulos, Charalambos; Jackson, Graham; Stefanadis, Christodoulos; Montorsi, Piero

2013-07-01

Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

Endothelial dysfunction: a comprehensive appraisal

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Vilariño Jorge O

2006-02-01

Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.

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Jain, Swati; Sharma, Bhupesh

2015-12-01

Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. Copyright © 2015 Elsevier Inc. All rights reserved.

Vascular Remodeling in Experimental Hypertension

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Norma R. Risler

2005-01-01

Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

Vascular function in health, hypertension, and diabetes

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

2015-01-01

muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular......, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

Endothelial function and dysfunction: clinical significance and assessment

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Shaghayegh Haghjooyejavanmard

2008-08-01

Full Text Available

• Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
•  KEYWORDS: Endothelial function, endothelium, Disease.

A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.

Science.gov (United States)

Del Bo', Cristian; Porrini, Marisa; Fracassetti, Daniela; Campolo, Jonica; Klimis-Zacas, Dorothy; Riso, Patrizia

2014-12-01

Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p blueberry treatment vs. -42.8 ± 20.0% smoking treatment, p blueberry treatment vs. +13.1 ± 0.02% smoking treatment, mmHg, p blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved.

The course of peripheral vascular disease in non-insulin-dependent diabetes.

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Kreines, K; Johnson, E; Albrink, M; Knatterud, G L; Levin, M E; Lewitan, A; Newberry, W; Rose, F A

1985-01-01

The present report is an analysis of the course of peripheral vascular disease (PVD) in 619 patients with non-insulin-dependent diabetes (NIDDM) recruited within 1 yr of diagnosis and followed quarterly for up to 14 yr (X = 10.5 yr). At 13 yr duration, the actuarially determined cumulative risks for intermittent claudication (IC), nonpalpable dorsalis pedis pulse (NPUL), and arterial calcification (CALC) were, respectively, 37.9%, 34.5%, and 60.9% for men and 24.3%, 37.6%, and 32.2% for women. Major amputations (AMP) occurred in only 1.3% of the patients, equivalent to approximately one case per 1000 patients per year. The corresponding incidences of IC, NPUL, and CALC were, respectively, 29, 27, and 47 per 1000 men and 19, 27, and 25 per 1000 women per year. CALC and NPUL were strongly related to mortality. Baseline risk factors with probability levels that suggest a relationship to PVD were, in women, age versus CALC (P less than 0.01), age versus NPUL (P less than 0.05), weight versus NPUL (P less than 0.05), systolic BP versus CALC (P less than 0.01), summed glucose tolerance test versus CALC (P less than 0.01), and triglyceride level versus CALC (P less than 0.05). In men, the only significant risk factors were diminished vibration perception, which was related to NPUL (P less than 0.05), and the serum triglyceride level, which was related to IC (P less than 0.05). In patients who are carefully followed prospectively, IC is far more common, but AMP is far less common than has been generally appreciated. Further studies are needed to clarify the roles of the diverse risk factors that are possibly related.

Time course of arterial vascular adaptations to inactivity and paralyses in humans.

NARCIS (Netherlands)

Groot, P.C.E. de; Kuppevelt, D. van; Pons, C.; Snoek, G.V.E.; Woude, L.H.V. van der; Hopman, M.T.E.

2003-01-01

PURPOSE: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction

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Yves eLecarpentier

2014-11-01

Full Text Available Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta and gamma play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998. PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction

Adherence to standard precaution in the peripheral vascular access Siguiendo las precauciones padrón para procedimiento de inserción vascular periférico Adesão às precauções padrão no acesso vascular periférico

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Melissa Alves Cirelli

2007-06-01

Full Text Available This prospective and quantitative study was carried out in a small private general hospital, where the adherence to standard precaution in the peripheral vascular access was evaluated. The data were collected through a questionnaire aiming to characterize the nursing team's knowledge and opinion about standard precautions and the availability of materials. In addition, a systemized observation of the procedures of vein puncture and medicine administration was performed. It was identified that 84.4% of the punctures had been carried out without gloves or previous hand washing; in 29.7% of the procedures, needles were recapped and 93.2% of the professionals reported adequate material supply. Concluding, the professionals expose themselves and patients to unnecessary risks of infection. The nursing team must be the focus of continuous interventions and future actions in order to minimize the risk of infection in the procedure of peripheral vascular access.Estudio prospectivo, cuantitativo, realizado en un hospital general privado de poca complejidad, donde fue evaluado el seguimiento de las precauciones patrón para realizar inserción vascular periférica. Los datos fueron recolectados por medio de un cuestionario, con el objetivo de determinar las características del conocimiento y de opinión del equipo de enfermería sobre los temas de adhesión, precauciones patrón, disponibilidad de materiales; y por observación sistémica de los procedimientos de punción venosa y administración de medicamentos. Se identificó que 84,4% de las punciones fueron realizadas sin guantes y sin lavado previo de manos, 29,7% de las veces hubo reutilización de agujas y 93,2% de los profesionales afirmó tener una adecuada cantidad de materiales. Se concluyó que los profesionales exponen a sus pacientes y a sí mismos a riesgos de infección innecesaria. El equipo de enfermería debe enfocar su intervención y actividades futuras con el objetivo de minimizar el

Percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease using a transluminal endatherectomy catheter (TEC): Initial results and angiographic follow-up

International Nuclear Information System (INIS)

Rilinger, Norbert; Goerich, Johannes; Scharrer-Pamler, Reinhard; Vogel, Jochen; Tomczak, Reinhard; Merkle, Elmar; Sokiranski, Roman; Brambs, Hans-Juergen

1997-01-01

Purpose. To evaluate the clinical results of percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease. Methods. Rotational atherectomy was performed in 39 patients aged 39-87 years (mean 66.6 years). A total of 71 lesions (43 stenoses and 28 occlusions) were treated in 40 limbs. Additional balloon angioplasty was required in 54% of lesions. Fifteen patients (37.5%) presented in Fontaine stage II, 10 patients (25%) in Fontaine stage III and 15 patients (37.5%) in Fontaine stage IV. Rotational atherectomy at 750 rpm was carried out over a 0.014-inch guidewire with continuous aspiration into a vacuum, bottle. Follow-up angiography and color flow Doppler examinations were performed in 22 patients (23 limbs) after a mean period of 6 months (range 2-14 months). Results. There was one primary technical failure. In 36 of 40 lesions there was a good angiographic result with residual stenoses in less than 30%. In 70 lesions treated by rotational atherectomy, however, 54% showed residual stenoses of 30%-50% and these cases required additional balloon angioplasty. The mean ankle-brachial index improved significantly (p<0.001), from 0.49 before the procedure to 1.01 after the procedure. A single distal embolus, related to primary recanalization, occurred and there were two large inguinal hematomas. Cumulative clinical patency after 6 months was 83.8% and cumulative angiographic patency after 6 months was 79.1%. Conclusion. Percutaneous rotational atherectomy is a promising approach for the treatment of chronic peripheral vascular disease. Further prospective, randomized studies are necessary to compare percutaneous transluminal angioplasty with this new technical approach

75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-12-06

...] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...) and/or abnormal vascularity (abnormal blood supply and circulation) of the central nervous system. The...

Attenuated flow‐induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short‐term high salt diet

Science.gov (United States)

Cosic, Anita; Jukic, Ivana; Stupin, Ana; Mihalj, Martina; Mihaljevic, Zrinka; Novak, Sanja; Vukovic, Rosemary

2016-01-01

Key points Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress.The objective of this study was to assess vascular response to flow‐induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS‐fed rats in vitro.The novelty of this study is in demonstrating impaired flow‐induced dilatation of MCAs and down‐regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID.In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake.Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo. Abstract The aim of this study was to determine flow‐induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)‐fed rats. Healthy male Sprague‐Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10–Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N ω‐nitro‐l‐arginine methyl ester (l‐name). mRNA levels of antioxidative enzymes, NAPDH‐oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real‐time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

Directory of Open Access Journals (Sweden)

Ryuji Sakakibara

2011-01-01

Full Text Available Bladder dysfunction (urinary urgency/frequency, bowel dysfunction (constipation, and sexual dysfunction (erectile dysfunction (also called “pelvic organ” dysfunctions are common nonmotor disorders in Parkinson's disease (PD. In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

Science.gov (United States)

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Microcirculatory disorders in scleroderma systematica: an association with vascular wall stiffness

Directory of Open Access Journals (Sweden)

Ulyana Yuryevna Ruzhentsova

2013-01-01

Full Text Available Objective: to study the specific features of regulation of peripheral vascular tone and their association with the endothelial structure and function of large vessels in patients with scleroderma systematica (SDS. Subjects and methods. The investigation enrolled 25 patients with SDS (mean age, 47±2.6 years; mean disease duration, 8.3+1.7 years and 15 apparently healthy individuals matched for age and gender. Comprehensive examination involved laboratory and instrumental studies, laser Doppler study to evaluate endothelium-dependent and endothelium-independent vasodilation, as well as applanation tonometry calculating the pulse wave velocity and augmentation index. Results. All the patients were found to have impaired peripheral vascular responsiveness as compared to the controls. The examination established a relationship between the magnitude of endothelium-dependent vasodilation and the stiffness index of large vessels. There was no association between endothelium-independent vasodilation and vascular elasticity parameters.

NEURO-VASCULAR INJURIES ASSOCIATED WITH LIMB ...

African Journals Online (AJOL)

hi-tech

2000-12-01

Dec 1, 2000 ... Subjects: Forty three patients with bone fractures associated with vascular and peripheral nerve injury seen at the Emergency Room of Assir Central Hospital from 1990 to 1999. There were 39 males and four females. Thirty five of these patients (81.4%) were Saudi nationals and the rest were non-Saudi.

Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

Science.gov (United States)

Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

2016-03-01

Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Factors predicting walking intolerance in patients with peripheral ...

African Journals Online (AJOL)

Objective. To determine which physiological variables conduce to walking intolerance in patients with peripheral arterial disease (PAD). Design. The physiological response to a graded treadmill exercise test (GTT) in patients with PAD was characterised. Setting. Patients were recruited from the Department of. Vascular ...

Insulin resistance: vascular function and exercise

Directory of Open Access Journals (Sweden)

Moon-Hyon Hwang

2016-09-01

Full Text Available Insulin resistance associated with metabolic syndrome and Type 2 diabetes mellitus is an epidemic metabolic disorder, which increases the risk of cardiovascular complications. Impaired vascular endothelial function is an early marker for atherosclerosis, which causes cardiovascular complications. Both experimental and clinical studies indicate that endothelial dysfunction in vasculatures occurs with insulin resistance. The associated physiological mechanisms are not fully appreciated yet, however, it seems that augmented oxidative stress, a physiological imbalance between oxidants and antioxidants, in vascular cells is a possible mechanism involved in various vascular beds with insulin resistance and hyperglycemia. Regardless of the inclusion of resistance exercise, aerobic exercise seems to be beneficial for vascular endothelial function in both large conduit and small resistance vessels in both clinical and experimental studies with insulin resistance. In clinical cases, aerobic exercise over 8 weeks with higher intensity seems more beneficial than the cases with shorter duration and lower intensity. However, more studies are needed in the future to elucidate the physiological mechanisms by which vascular endothelial function is impaired in insulin resistance and improved with aerobic exercise.

Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

Science.gov (United States)

Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

2014-04-01

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

Science.gov (United States)

2009-12-01

diabetic retinopathy . Therefore, se- lectively targeting existing blood vessels (vascular- disrupting therapy) and/or inhibiting the forma- tion of new...adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at...tumor sections (Fig. 4). However, viable tumor cells were commonly detected at tumor periphery. Because of the existence of viable peripheral tumor cells

Vascular access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

Science.gov (United States)

Doherty, Daniel J; Pottle, Alison; Malietzis, George; Hakim, Nadey; Barbir, Mahmoud; Crane, Jeremy S

2018-01-01

Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

[Vascular access guidelines for hemodialysis].

Science.gov (United States)

Rodríguez Hernández, J A; González Parra, E; Julián Gutiérrez, J M; Segarra Medrano, A; Almirante, B; Martínez, M T; Arrieta, J; Fernández Rivera, C; Galera, A; Gallego Beuter, J; Górriz, J L; Herrero, J A; López Menchero, R; Ochando, A; Pérez Bañasco, V; Polo, J R; Pueyo, J; Ruiz, Camps I; Segura Iglesias, R

2005-01-01

Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

Biomarkers of inflammation and endothelial dysfunction as predictors of pulse pressure and incident hypertension in type 1 diabetes

DEFF Research Database (Denmark)

Ferreira, Isabel; Hovind, Peter; Schalkwijk, Casper G

2018-01-01

AIMS/HYPOTHESIS: Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes. METHODS: We investigated, in an inception cohort of 277 individuals...... with type 1 diabetes, the course, tracking and temporal inter-relationships of BP, specifically pulse pressure (a marker of arterial stiffening) and hypertension, and the following biomarkers of systemic and vascular inflammation/endothelial dysfunction: C-reactive protein (CRP), soluble intracellular...... endothelial dysfunction and inflammation in the development of premature arterial stiffening and hypertension in type 1 diabetes....

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Directory of Open Access Journals (Sweden)

Candice G. T. Tahimic

2017-10-01

Full Text Available Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Science.gov (United States)

Tahimic, Candice; Globus, Ruth K.

2018-01-01

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

Proposed protocols for peripheral and renal Doppler

International Nuclear Information System (INIS)

Fonseca Portuguez, Adriana

2009-01-01

A literature review was performed in order to prepare a summary of the important concepts of Doppler and applications in peripheral vascular evaluation and renal. The normal characteristics are summarized and explained in each vascular system and diagnostic criteria of the disorders frequently encountered in practice. Requested more studies have been identified and proposed protocols and report sheets have been developed to standardize the methodology of realization of several Doppler studies. The variability between operators has been treated to reduce as much as possible and follow-up studies have provided in patients who need. (author) [es

Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications.

Science.gov (United States)

Domingueti, Caroline Pereira; Dusse, Luci Maria Sant'Ana; Carvalho, Maria das Graças; de Sousa, Lirlândia Pires; Gomes, Karina Braga; Fernandes, Ana Paula

2016-01-01

Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

[The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

Science.gov (United States)

Fischer, Tamás

2015-03-01

The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

Vascular training and endovascular practice in Europe

DEFF Research Database (Denmark)

Liapis, C.D.; Avgerinos, E.D.; Sillesen, H.

2009-01-01

specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. RESULTS: Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1....... Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted......% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral...

Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism.

Science.gov (United States)

Zhou, Bo; Li, Huixia; Liu, Jiali; Xu, Lin; Zang, Weijin; Wu, Shufang; Sun, Hongzhi

2013-06-15

The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in cardiovascular disease (CVD) is not fully understood. In the present study, we investigated the effect of osteocalcin on autophagy and endoplasmic reticulum (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and in vascular cell models and clarified the intracellular events responsible for osteocalcin-mediated effects. The evidences showed that intermittent injections of osteocalcin in mice fed the high-fat diet were associated with a reduced body weight gain, decreased blood glucose and improved insulin sensitivity compared with mice fed the high-fat diet receiving vehicle. Simultaneously, the administration of osteocalcin not only attenuated autophagy and ER stress but also rescued impaired insulin signaling in vascular tissues of mice fed a high-fat diet. Consistent with these results in vivo, the addition of osteocalcin reversed autophagy and ER stress and restored defective insulin sensitivity in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the presence of tunicamycin or in knockout XBP-1 (a transcription factor which mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects of osteocalcin were nullified by suppression of Akt, mammalian target of rapamycin (mTOR) or nuclear factor kappa B (NFκB), suggesting that osteocalcin inhibits autophagy, ER stress and improves insulin signaling in the vascular tissue and cells under insulin resistance in a NFκB-dependent manner, which may be a promising therapeutic strategies of cardiovascular dysfunction secondary to obesity.

Vascular disease in cocaine addiction.

Science.gov (United States)

Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

2017-07-01

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Vascular injuries of the upper extremity Lesões vasculares de membros superiores

Directory of Open Access Journals (Sweden)

Raafat Shalabi

2006-12-01

Full Text Available OBJECTIVE: This study analyzes the causes of injuries, presentations, surgical approaches, outcome and complications of vascular trauma of the upper limbs, in spite of limited hospital resources. METHODS: A 5-year retrospective analysis. From 01/01/2001 to 31/12/2005, 165 patients were operated for vascular injuries at King Fahd Hospital, Medina, Saudi Arabia. Of all peripheral vascular trauma patients (115, upper limb trauma was present in 58. Diagnosis was made by physical examination and hand-held Doppler alone or in combination with Doppler scan/angiography. Primary vascular repair was performed whenever possible; otherwise, the interposition vein graft was used. Fasciotomy was considered when required. Patients with unsalvageable lower extremity injury requiring primary amputation were excluded from the study. RESULTS: Fifty patients were male (86% and eight were female (14%, aged between 2.5-55 years (mean 23 years. Mean duration of presentation was 8 h after the injury. The most common etiological factor was road traffic accidents, accounting for 50.5% in the blunt trauma group and 33% among all penetrating and stab wound injuries. Incidence of concomitant orthopedic injuries was very high in our study (51%. The brachial artery was the most affected (51%. Interposition vein grafts were used in 53% of the cases. Limb salvage rate was 100%. CONCLUSION: Patients who suffer vascular injuries of the upper extremities should be transferred to vascular surgery centers as soon as possible. Decisive management of peripheral vascular trauma will maximize patient survival and limb salvage. Priorities must be established in the management of associated injuries, and delay must be avoided when ischemic changes are present.OBJETIVO: Este estudo analisa as causas de lesões, apresentação, abordagens cirúrgicas, desfechos e complicações do trauma vascular de membros superiores, apesar de recursos hospitalares limitados. MÉTODOS: An

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

Science.gov (United States)

Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

2011-08-01

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

Tumor vascularity evaluated by transrectal color Doppler US in predicting therapy outcome for low-lying rectal cancer

International Nuclear Information System (INIS)

Barbaro, Brunella; Valentini, Vincenzo; Coco, Claudio; Mancini, Anna Paola; Gambacorta, Maria Antonietta; Vecchio, Fabio Maria; Bonomo, Lorenzo

2005-01-01

Purpose: To evaluate the impact on T downstaging of the vasculature supplying blood flow to rectal cancer evaluated by color Doppler ultrasound. Methods and Materials: Color Doppler images were graded in 29 T3-staged rectal carcinoma patients sonographically just before chemoradiation. Any arterial vessels detected in rectal masses were assigned one of two grades: vascularity was considered as grade 1 for vessels feeding the periphery and as grade 2 for vessels coursing in all rectal masses within its peripheral and central portions. The pulsatility indices (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) were calculated in the central and peripheral portions. Results: The pathologic observations showed a change in stage in 15 of the 23 patients graded 2, positive predictive value 65.2% (p = 0.047), and in one of the six rectal cancers graded 1 (negative predictive value, 83.3%). The minimal peripheral PI values in rectal cancer graded 2 were higher in nonresponding (2.2 ± 1.3) than in responding lesions (1.6 ± 0.7) p = 0.01. Conclusion: Vascularity graded 2 associated with low peripheral PI values are indicators of therapy outcome. Vascularity graded 1 and high peripheral PI values in graded 2 have negative predictive value

Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease.

Science.gov (United States)

Grau-Monge, Cristina; Delcroix, Gaëtan J-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F; Armour, Maxime R; Montero, Ramon B; Schiller, Paul C; Andreopoulos, Fotios M; D'Ippolito, Gianluca

2017-02-17

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of two layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration.

The role of inflammation in vascular insulin resistance with focus on IL-6

DEFF Research Database (Denmark)

Andersen, Kirsten; Pedersen, B.K.

2008-01-01

The present review focuses on the possible role of interleukin-(IL)-6 in vascular insulin resistance. The endothelium plays an important role in regulating the tone of the vasculature by releasing nitric oxide (NO) to the smooth muscles of the vessels, thereby regulating the distribution of blood....... It is likely that chronic low-level inflammation plays an important role in developing endothelial dysfunction mainly through proinflammatory actions of tumor necrosis factor alpha (TNF-alpha). TNF-alpha induces production of IL-6 and it has been suggested that a causal relationship exists between endothelial...... dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions Udgivelsesdato: 2008/9...

The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

Science.gov (United States)

Schwabl, Philipp; Hambruch, Eva; Seeland, Berit A; Hayden, Hubert; Wagner, Michael; Garnys, Lukas; Strobel, Bastian; Schubert, Tim-Lukas; Riedl, Florian; Mitteregger, Dieter; Burnet, Michael; Starlinger, Patrick; Oberhuber, Georg; Deuschle, Ulrich; Rohr-Udilova, Nataliya; Podesser, Bruno K; Peck-Radosavljevic, Markus; Reiberger, Thomas; Kremoser, Claus; Trauner, Michael

2017-04-01

Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl 4 , 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged. We then measured portal pressure, intrahepatic vascular resistance, liver fibrosis and bacterial translocation. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl 4 (15.2±0.5 vs. 11.8±0.4mmHg; p=0.001) rats. In PPVL animals, we observed less bacterial translocation (-36%; p=0.041), a decrease in lipopolysaccharide binding protein (-30%; p=0.024) and splanchnic tumour necrosis factor α levels (-39%; p=0.044) after PX treatment. In CCl 4 rats, PX decreased fibrotic Sirius Red area (-43%; p=0.005), hepatic hydroxyproline (-66%; pportal pressure (-14%; p=0.041) by restoring endothelial function, 14week PX therapy additionally inhibited sinusoidal remodelling and decreased portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut. Copyright �

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

Science.gov (United States)

Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

2018-02-01

 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Initial experience with the Cardiva Boomerang vascular closure device in diagnostic catheterization.

Science.gov (United States)

Doyle, Brendan J; Godfrey, Michael J; Lennon, Ryan J; Ryan, James L; Bresnahan, John F; Rihal, Charanjit S; Ting, Henry H

2007-02-01

The authors studied the safety and efficacy of the Cardiva Boomerang vascular closure device in patients undergoing diagnostic cardiac catheterization. Conventional vascular closure devices (sutures, collagen plugs, or metal clips) have been associated with catastrophic complications including arterial occlusion and foreign body infections; furthermore, they cannot be utilized in patients with peripheral vascular disease or vascular access site in a vessel other than the common femoral artery. The Cardiva Boomerang device facilitates vascular hemostasis without leaving any foreign body behind at the access site, can be used in peripheral vascular disease, and can be used in vessels other than the common femoral artery A total of 96 patients undergoing transfemoral diagnostic cardiac catheterization were included in this study, including 25 (26%) patients with contraindications to conventional closure devices. Femoral angiography was performed prior to deployment of the Cardiva Boomerang closure device. Patients were ambulated at 1 hr after hemostasis was achieved. The device was successfully deployed and hemostasis achieved with the device alone in 95 (99%) patients. The device failed to deploy in 1 (1%) patient and required conversion to standard manual compression. Minor complications were observed in 5 (5%) patients. No patients experienced major complications including femoral hematoma > 4 cm, red blood cell transfusion, retroperitoneal bleed, arteriovenous fistula, pseudoaneurysm, infection, arterial occlusion, or vascular surgery. The Cardiva Boomerang device is safe and effective in patients undergoing diagnostic cardiac catheterization using the transfemoral approach, facilitating early ambulation with low rates of vascular complications. (c) 2006 Wiley-Liss, Inc.

Auditory system dysfunction in Alzheimer disease and its prodromal states: A review.

Science.gov (United States)

Swords, Gabriel M; Nguyen, Lydia T; Mudar, Raksha A; Llano, Daniel A

2018-04-06

Recent findings suggest that both peripheral and central auditory system dysfunction occur in the prodromal stages of Alzheimer Disease (AD), and therefore may represent early indicators of the disease. In addition, loss of auditory function itself leads to communication difficulties, social isolation and poor quality of life for both patients with AD and their caregivers. Developing a greater understanding of auditory dysfunction in early AD may shed light on the mechanisms of disease progression and carry diagnostic and therapeutic importance. Herein, we review the literature on hearing abilities in AD and its prodromal stages investigated through methods such as pure-tone audiometry, dichotic listening tasks, and evoked response potentials. We propose that screening for peripheral and central auditory dysfunction in at-risk populations is a low-cost and effective means to identify early AD pathology and provides an entry point for therapeutic interventions that enhance the quality of life of AD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Peripheral neuropathy: an often-overlooked cause of falls in the elderly.

Science.gov (United States)

Richardson, J K; Ashton-Miller, J A

1996-06-01

Peripheral neuropathy is common in the elderly and results in impairments in distal proprioception and strength that hinder balance and predispose them to falls. The loss of heel reflexes, decreased vibratory sense that improves proximally, impaired position sense at the great toe, and inability to maintain unipedal stance for 10 seconds in three attempts all suggest functionally significant peripheral neuropathy. Physicians can help their patients with peripheral neuropathy to prevent falls by teaching them and their families about peripheral nerve dysfunction and its effects on balance and by advising patients to substitute vision for the lost somatosensory function, correctly use a cane, wear proper shoes and orthotics, and perform balance and upper extremity strengthening exercises.

The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.

Science.gov (United States)

Rezende, Flávia; Moll, Franziska; Walter, Maria; Helfinger, Valeska; Hahner, Fabian; Janetzko, Patrick; Ringel, Christian; Weigert, Andreas; Fleming, Ingrid; Weissmann, Norbert; Kuenne, Carsten; Looso, Mario; Rieger, Michael A; Nawroth, Peter; Fleming, Thomas; Brandes, Ralf P; Schröder, Katrin

2018-05-01

NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes. In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice. ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery

DEFF Research Database (Denmark)

Storkebaum, Erik; Ruiz de Almodovar, Carmen; Meens, Merlijn

2010-01-01

BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( ...

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

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A.P. Davel

2011-09-01

Full Text Available The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Oral Health and Erectile Dysfunction.

Science.gov (United States)

Singh, Vijendra P; Nettemu, Sunil K; Nettem, Sowmya; Hosadurga, Rajesh; Nayak, Sangeeta U

2017-01-01

Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP) and erectile dysfunction (ED) by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions.

Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

NARCIS (Netherlands)

Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

2008-01-01

Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

PET/CT and vascular disease: Current concepts

Energy Technology Data Exchange (ETDEWEB)

Cavalcanti Filho, Jose Leite Gondim; Souza Leao Lima, Ronaldo de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Souza Machado Neto, Luiz de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Kayat Bittencourt, Leonardo, E-mail: lkayat@terra.com.br [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Cortes Domingues, Romeu [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Fonseca, Lea Mirian Barbosa da [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil)

2011-10-15

Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

Conditional Müllercell ablation causes independent neuronal and vascular pathologies in a novel transgenic model.

Science.gov (United States)

Shen, Weiyong; Fruttiger, Marcus; Zhu, Ling; Chung, Sook H; Barnett, Nigel L; Kirk, Joshua K; Lee, SoRa; Coorey, Nathan J; Killingsworth, Murray; Sherman, Larry S; Gillies, Mark C

2012-11-07

Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood-retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor. Intravitreal injection of ciliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuroprotective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the CNS associated with glial dysfunction.

Cardiovascular autonomic dysfunction due to diabetes mellitus: An ...

African Journals Online (AJOL)

Cardiovascular autonomic neuropathy (CAN) is a common form of diabetes autonomic neuropathy, causes abnormalities in heart rate control as well as central and peripheral vascular dynamics, and may carry an increased risk of mortality. The aim of this article was to review the importance of identifying CAN and ...

Pathogenesis of vascular leak in dengue virus infection.

Science.gov (United States)

Malavige, Gathsaurie Neelika; Ogg, Graham S

2017-07-01

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

Risk indicators in coronary cardiac disease and occlusive disease of the peripheral arteries

International Nuclear Information System (INIS)

Roth, H.

1982-01-01

In 160 patients with clinically confirmed coronary heart diseases, angiograms of the coronary vessels, the left ventricle, the abdominal aorta, the pelvic and femoral arteries and the supra-aortic vessels were taken. At the same time the incidence of the risk indicators overweight, hypercholesterinaemia, hypertriglyceridaemia, hyperuricaemia, diabetes mellitus, hypertension and cigarette smoking was established and compared with the angiograms. Hypercholesterinaemia, hypertriglyceridaemia, diabetes mellitus and hypertension are found to be in a clearly positive correlation with the frequency and severity of coronary and peripheral vascular diseases. For hyperuricaemia and overweight a relation to the frequency and severity of peripheral but not coronary vascular stenoses is outlined. Cigarette smoking, again, proves to be a clear risk indicator. (orig./MG) [de

Vascular mechanism of axonal degeneration in peripheral nerves in hemiplegic sides after cerebral hemorrhage: An experimental study

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Bayram Ednan

2008-04-01

Full Text Available Abstract Background Though retrograde neuronal death and vascular insufficiency have been well established in plegics following intracerebral hemorrhage, the effects of plegia on arterial nervorums of peripheral nerves have not been reported. In this study, the histopathological effects of the intracerebral hemorrhage on the dorsal root ganglions and sciatic nerves via affecting the arterial nervorums were investigated. Methods This study was conducted on 13 male hybrid rabbits. Three animals were taken as control group and did not undergo surgery. The remaining 10 subjects were anesthetized and were injected with 0.50 ml of autologous blood into their right sensory-motor region. All rabbits were followed-up for two months and then sacrificed. Endothelial cell numbers and volume values were estimated a three dimensionally created standardized arterial nervorums model of lumbar 3. Neuron numbers of dorsal root ganglions, and axon numbers in the lumbar 3 nerve root and volume values of arterial nervorums were examined histopathologically. The results were analyzed by using a Mann-Whitney-U test. Results Left hemiplegia developed in 8 animals. On the hemiplegic side, degenerative vascular changes and volume reduction in the arterial nervorums of the sciatic nerves, neuronal injury in the dorsal root ganglions, and axonal injury in the lumbar 3 were detected. Statistical analyses showed a significant correlation between the normal or nonplegic sides and plegic sides in terms of the neurodegeneration in the dorsal root ganglions (p Conclusion Intracerebral hemorrhage resulted in neurodegeneration in the dorsal root ganglion and axonolysis in the sciatic nerves, endothelial injury, and volume reduction of the arterial nervorums in the sciatic nerves. The interruption of the neural network connection in the walls of the arterial nervorums in the sciatic nerves may be responsible for circulation disorders of the arterial nervorums, and arterial

The first report of CADASIL in Peru: Olfactory dysfunction on initial presentation

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Anastasia Vishnevetsky

2016-12-01

Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL is a rare, heritable, small vessel vascular disease caused by mutations in the Notch3 gene that is characterized by migraines, subcortical vascular events, cognitive decline, and mood disturbances. However, many CADASIL cases present with unusual symptoms such as status epilepticus, a movement disorder, or sensory dysfunction. This study describes the clinical, genetic, and radiologic characteristics of a Peruvian family with CADASIL in which multiple family members presented with severe olfactory deficits. Seven members of the family have symptoms suggestive of CADASIL, with genetic testing revealing R133C mutations in the two patients who underwent genetic testing. Cognitive testing and olfactory identification testing (Smell Identification Test were performed in three CADASIL patients revealing total anosmia in two tested patients and severe hyposmia in the other. Olfactory dysfunction has been associated with various neurologic and psychiatric conditions, though few studies have linked it with neurovascular disorders such as CADASIL. This first reported case of CADASIL in Peru emphasizes that symptomatic olfactory dysfunction may be an unusual presentation of CADASIL and that olfactory dysfunction is important to evaluate in CADASIL patients.

Diverse Imaging characteristics of a mandibular intraosseous vascular lesion

International Nuclear Information System (INIS)

Handa, Hina; Naidu, Giridhar S.; Dara, Balaji Gandhi Babu; Deshpande, Ashwini; Raghavendra, Raju

2014-01-01

Intraosseous vascular lesions of the maxillofacial region are rare, and the differential diagnosis of intraosseous vascular malformations from other jaw lesions can be challenging. In the present case, magnetic resonance imaging and three-dimensional computed tomographic angiography (CTA) was used for diagnosis, and the lesion was treated with surgical excision. Diverse characteristics such as the 'honeycomb' and 'sunburst' radiographic appearances and the absence of major peripheral feeder vessels in the CTA were noted. Intraosseous vascular malformations have a varied radiographic appearance, and the nomenclature of these lesions is equally diverse, with several overlapping terms. Pathologists do not generally differentiate among intraosseous vascular lesions on the basis of histopathology, although these lesions may present with contrasting immunohistochemical and clinical behaviors requiring varied treatment strategies. This case report highlights the need for multiple imaging modalities to differentiate among vascular lesions, as well as to better understand the behaviors of these unique lesions.

Arginase promotes skeletal muscle arteriolar endothelial dysfunction in diabetic rats.

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Fruzsina K. Johnson

2013-05-01

Full Text Available Endothelial dysfunction is a characteristic feature in diabetes that contributes to the development of vascular disease. Recently, arginase has been implicated in triggering endothelial dysfunction in diabetic patients and animals by competing with endothelial nitric oxide synthase for substrate L-arginine. While most studies have focused on the coronary circulation and large conduit blood vessels, the role of arginase in mediating diabetic endothelial dysfunction in other vascular beds has not been fully investigated. In the present study, we determined whether arginase contributes to endothelial dysfunction in skeletal muscle arterioles of diabetic rats. Diabetes was induced in male Sprague Dawley rats by streptozotocin injection. Four weeks after streptozotocin administration, blood glucose, glycated hemoglobin, and vascular arginase activity were significantly increased. In addition, a significant increase in arginase I and II mRNA expression was detected in gracilis muscle arterioles of diabetic rats compared to age-matched, vehicle control animals. To examine endothelial function, first-order gracilis muscle arterioles were isolated, cannulated in a pressure myograph system, exposed to graded levels of luminal flow, and internal vessel diameter measured. Increases in luminal flow (0-50µL/min caused progressive vasodilation in arterioles isolated from control, normoglycemic animals. However, flow-induced vasodilation was absent in arterioles obtained from streptozotocin-treated rats. Acute in-vitro pretreatment of blood vessels with the arginase inhibitors Nω-hydroxy-nor-L-arginine or S-(2-boronoethyl-L-cysteine restored flow-induced responses in arterioles from diabetic rats and abolished differences between diabetic and control animals. Similarly, acute in-vitro pretreatment with L-arginine returned flow-mediated vasodilation in vessels from diabetic animals to that of control rats. In contrast, D-arginine failed to restore flow

Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality.

Science.gov (United States)

Alzamora, María Teresa; Baena-Díez, José Miguel; Sorribes, Marta; Forés, Rosa; Toran, Pere; Vicheto, Marisa; Pera, Guillem; Reina, María Dolores; Albaladejo, Carlos; Llussà, Judith; Bundó, Magda; Sancho, Amparo; Heras, Antonio; Rubiés, Joan; Arenillas, Juan Francisco

2007-12-11

The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of

Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results.

Science.gov (United States)

Lammer, Johannes; Bosiers, Marc; Deloose, Koen; Schmidt, Andrej; Zeller, Thomas; Wolf, Florian; Lansink, Wouter; Sauguet, Antoine; Vermassen, Frank; Lauwers, Geert; Scheinert, Dierk; Popma, Jeffrey J; McGreevy, Robert; Rapoza, Richard; Schwartz, Lewis B; Jaff, Michael R

2016-06-13

This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). Drug-eluting BVS has shown promise in coronary arteries. The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 ± 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 ± 0.14 improved from pre-procedure to 0.96 ± 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Vascular Cognitive Impairment: risk factors and brain MRI correlates

NARCIS (Netherlands)

Reijmer, Y.D.

2012-01-01

Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of

NON-PHARMACOLOGICAL CONCEPTS OF ENDOTHELIAL DYSFUNCTION IMPROVEMENT

Directory of Open Access Journals (Sweden)

Mirjana Bakic

2007-04-01

Full Text Available Endothelium plays an important role in maintaining normal vascular tonus and blood fluidity reducing thrombocyte activity and adhesion of leukocytes as well as limiting response of vascular inflammation. However, in certain pathological conditions such as hypercholesterolemia, hypertension, and diabetes, endothelium improves vasoconstriction, inflammation and thrombocytic events.Non-pharmacological concept is based on recognition of genetic factors, environmental factors, or combination of risk factors for the occurrence of endothelial dysfunction, general and individual education of the significance of adequate nutrition, physical activity and regulation of body weight, regular check-ups and the application of antioxidants which can regulate and protect several aspects of endothelial functions.

Vascular Endothelial Dysfunction in Inflammatory Bowel Diseases: Pharmacological and Nonpharmacological Targets

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Antonietta Gerarda Gravina

2018-01-01

Full Text Available Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions involving primarily the gastrointestinal tract. However, they may be also associated with systemic manifestations and comorbidities. The relationship between chronic inflammation and endothelial dysfunction has been extensively demonstrated. Mucosal immunity and gastrointestinal physiology are modified in inflammatory bowel diseases, and these modifications are mainly sustained by alterations of endothelial function. The key elements involved in this process are cytokines, inflammatory cells, growth factors, nitric oxide, endothelial adhesion molecules, and coagulation cascade factors. In this review, we discuss available data in literature concerning endothelial dysfunction in patients affected by inflammatory bowel disease and we focus our attention on both pharmacological and nonpharmacological therapeutic targets.

CURRENT METHODS OF ENDOTHELIAL DYSFUNCTION ASSESSMENT AND THEIR POSSIBLE USE IN THE PRACTICAL MEDICINE

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A. V. Shabrov

2016-01-01

Full Text Available A review contains a description of the most common methods of evaluation and monitoring of "endothelial dysfunction" that are assessed in terms of their information content and applicability in the practice of medicine. The term "endothelial function" is interpreted primarily as a function of the regulation of capillary blood flow, carried out by the expense of the dynamic change of the phase of vasoconstriction and vasodilatation in vessels of resistive type (in accordance with the changing needs of cellular metabolism. Assessment of endothelial dysfunction is understood as a generalized indicator of the extent and nature of violations of the regulation of peripheral circulation. It includes an assessment of imbalances between endotheliumdependent vasoconstrictor and vasodilating factors or mismatch of the local and central regulation of capillary blood flow in response to various functional tests or other effects (eg, cold test, or test with local ischemia. All methods of endothelial dysfunction assessment in the survey are divided into invasive and non-invasive. The main feature of invasive methods lies in the direct effect on the endothelium of the coronary or other vessels by introducing into these vessels vasoactive substances such as acetylcholine. Response to the test (vasoconstriction or vasodilation is evaluated by coronary angiography or by ultrasound. Non-invasive methods of the assessment of endothelial dysfunction or functions of regulation of the peripheral circulation are regarded as the most promising for widespread use. There are two basic methods that underlie functional tests: methods PAT (peripheral arterial tone and PHG (polyhepatography. Assessment of endothelial dysfunction in many modern scientific researches is important. They are regarded as the causative factors of many different diseases. Such assessments can be useful in everyday medical practice. Assessment of endothelial function provides the clinician with

Peripheral and central vascular conductance influence on post-exercise hypotension

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Endo Masako Y

2012-12-01

Full Text Available Abstract Background Post-exercise hypotension (PEH following prolonged dynamic exercise arises from increased total vascular conductance (TVC via skeletal muscle vasodilation. However, arterial vasodilation of skeletal musculatures does not entirely account for the rise in TVC. The aim of the present study was to determine the contribution of vascular conductance (VC of the legs, arms, kidneys and viscera to TVC during PEH. Methods Eight subjects performed a single period of cycling at 60% of heart rate (HR reserve for 60 minutes. Blood flow in the right renal, superior mesenteric, right brachial and right femoral arteries was measured by Doppler ultrasonography in a supine position before exercise and during recovery. HR and mean arterial pressure (MAP were measured continuously. MAP decreased significantly from approximately 25 minutes after exercise cessation compared with pre-exercise baseline. TVC significantly increased (approximately 23%; P Conclusion PEH was not induced by decreased cardiac output, but by increased TVC, two-thirds of the rise in which can be attributed to increased VC in active and inactive limbs.

Percutaneous Treatment of Peripheral Vascular Malformations in Children: Long-Term Clinical Outcome

International Nuclear Information System (INIS)

Linden, Edwin van der; Otoide-Vree, Marleen; Pattynama, Peter M. T.

2012-01-01

Purpose: This study was designed to assess the rate of complications and clinical failure at 3 and 12 months after percutaneous treatment of vascular malformations in children. Furthermore, we describe patient satisfaction of treatment results during 5 years of follow-up. Methods: In a retrospective cohort study, we evaluated 26 patients younger than aged 19 years who were treated for symptomatic vascular malformations. Data on treatment outcomes and patient satisfactions were obtained with a precoded structured questionnaire. Patient files and imaging data were retrieved to obtain information regarding the vascular malformations and treatment. Clinical success was defined as disappearance or partial improvement of the complaints. Patient satisfaction was declared whenever patients answered in the questionnaire that they were satisfied with the treatment results. Results: Of 26 eligible patients, we included 23 (88%). The mean follow-up was 36 (range, 15–127) months. Posttreatment, 87% (20/23; 95% confidence interval (CI), 66–97%) of patients reported clinical success at 3 months. At 1, 2, 3, 4, and 5 years of follow-up this percentage was 74%, 59%, 59%, 59%, and 59%, respectively. Eleven (48%, 95% CI 27–69%) patients had experienced complications and 22% (95% CI 7–44%) had major complications, of which 5 had required additional treatment. In all, 83% (19/23) of the patients reported satisfaction with the treatment. Conclusions: Percutaneous treatment of vascular malformations improved clinical symptoms in 87% of the patients at 3 months and were sustainable for half of all patients during a 5-year follow-up period. However, major complications were seen in 22%.

Oral health and erectile dysfunction

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Vijendra P Singh

2017-01-01

Full Text Available Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP and erectile dysfunction (ED by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions.

[Fistulae or catheter for elderly who start hemodialysis without permanent vascular access?].

Science.gov (United States)

García Cortés, Ma J; Viedma, G; Sánchez Perales, M C; Borrego, F J; Borrego, J; Pérez del Barrio, P; Gil Cunquero, J M; Liébana, A; Pérez Bañasco, V

2005-01-01

Autologous access is the best vascular access for dialysis also in older patients and it should be mature when patient needs hemodialysis. It is not always possible. Surgeon availability and demographic characteristics of patients (age, diabetes, vascular disease...) are factors that determine primary vascular access. To analyse outcome and vascular access complications in elderly who start hemodialysis without vascular access. All patients older than 75 years who initiated hemodialysis without vascular access between January 2000 and June 2002 were included, They were divided en two groups depending on primary vascular access. GI: arterio-venous fistulae. GIIl: Tunnelled cuffed catheter. Epidemiological and analytical data, vascular access complications related, as well as patient and first permanent vascular access survival from their inclusion in dialysis up to December 2002 were analysed and compared in both groups. 32 patients were studied. GI: n = 17 (4 men) and GIIl: n =1 5 (8 men), age: 79.9 +/- 3.8 and 81.7 +/- 4 years respectively (ns). There were no differences in sex and comorbidity (diabetes, ischemic heart disease, peripheral vascular disease and hypertension). It took GI 3 months to get a permanent vascular access suitable for using, while it took GIIl 1.3 months (p catheters was higher in GI (3.35 vs 1.87 p central venous thrombosis happen in GI (I: 25 CVT/100 patients-year) vs 30% in GIIl (I = 14.4/100 patients-year) (ns). No significant differences neither in bleeding (66.7% vs 33.3%) nor ischemia (75% vs 25%) were found. Dialysis dose (Kt/V) as well as anaemia degree were similar in both groups. Permanent vascular access survival after 2 years was 45.8% in GI and 24% in GII (ns). Patient survival was similar in GI and GII (72% vs 51% ns). Elderly who start hemodialysis without vascular access took longer to get a suitable permanent vascular access when arterio-venous fistulae is placed than with a tunnelled cuffed hemodialysis catheter. As a

A case of William's syndrome associated peripheral pulmonary arterial stenosis

International Nuclear Information System (INIS)

Jung, Kyung Hwa; Hwang, Mi Soo; Kim, Sun Yong; Chang, Jae Chun; Park, Bok Hwan

1988-01-01

William's syndrome, in order to more completely delineate the total spectrum of the disorder, indicates that 'infantile hypercalcemia', 'peculiar facies' and 'supravalvular aortic stenosis.' In has other many vascular anomalies, such as peripheral pulmonary arterial stenosis, coronary arterial stenosis, celiac arterial stenosis, and renal aterial stenosis. Only 32% of the patients have evidence of supravalvular aortic stenosis. And it is very rare disease entity that has been reported rarely in Korea. Recently authors experienced a case that was questioned William's syndrome with peripheral pulmonary arterial stenosis, clinically and preliminary radiologically and this case was confirmed by operation. Here we report a case of William's syndrome with peripheral pulmonary arterial stenosis and reviewed literatures

Obesity-induced vascular inflammation involves elevated arginase activity.

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Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

2017-11-01

Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-( S )-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

Preoperative evaluation of cardiac risk using dobutamine-thallium imaging in vascular surgery

International Nuclear Information System (INIS)

Zellner, J.L.; Elliott, B.M.; Robison, J.G.; Hendrix, G.H.; Spicer, K.M.

1990-01-01

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery

Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

Science.gov (United States)

2016-10-01

accompanied by injuries to peripheral nerves; if not repaired, the trauma can lead to significant dysfunction and disability . While nerves have the ability to...recovery, minimized disability , and increased quality of life for our wounded warriors. 2. KEYWORDS: Stem Cell, Nerve Conduit, Peripheral Nerve...would be a paradigm shift away from ordering X-rays at 10-12 weeks and only ordering a CT scan. It has the potential to change the standard of care

Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

DEFF Research Database (Denmark)

Jensen, Tonny Joran

1997-01-01

that albuminuria is a marker of widespread vascular dysfunction. Increased transport of macromolecules across the vascular wall, elevated plasma levels of von Willebrand factor, and impaired fibrinolytic capacity have been demonstrated in albuminuric patients. The cause of this vascular vulnerability...... problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?...

Surgical revascularization versus amputation for peripheral vascular disease in dialysis patients: a cohort study

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Ramkumar Nirupama

2005-03-01

Full Text Available Abstract Background Surgical treatment of peripheral vascular disease (PVD in dialysis patients is controversial. Methods We examined the post-operative morbidity and mortality of surgical revascularization or amputation for PVD in a retrospective analysis of United States Renal Data System. Propensity scores for undergoing amputation were derived from a multivariable logistic regression model of amputation. Results Of the Medicare patients initiated on dialysis from Jan 1, 1995 to Dec 31, 1999, patients underwent surgical revascularization (n = 1,896 or amputation (n = 2,046 in the first 6 months following initiation of dialysis were studied. In the logistic regression model, compared to claudication, presence of gangrene had a strong association with amputation [odds ratio (OR 19.0, 95% CI (confidence interval 13.86–25.95]. The odds of dying within 30 days and within1 year were higher (30 day OR: 1.85, 95% CI: 1.45–2.36; 1 yr OR: 1.46, 95% CI: 1.25–1.71 in the amputation group in logistic regression model adjusted for propensity scores and other baseline factors. Amputation was associated with increased odds of death in patients with low likelihood of amputation (rd percentile of propensity score and moderate likelihood of amputation (33rd to 66th percentile but not in high likelihood group (>66th percentile. The number of hospital days in the amputation and revascularization groups was not different. Conclusion Amputation might be associated with higher mortality in dialysis patients. Where feasible, revascularization might be preferable over amputation in dialysis patients.

Study of peripheral circulation in non-pregnant, pregnant and pre-eclamptic women using applied potential tomography.

Science.gov (United States)

Ahmed, Badreldeen

2004-08-01

Profound changes are known to occur in the cardiovascular system during pregnancy, involving an increase in cardiac output and a fall in peripheral resistance. In some women these adaptations may be inappropriate and this may result in pregnancy-induced hypertension and pre-eclampsia. The aims of the study were to evaluate the relatively new, non-invasive technique of applied potential tomography (APT) in measurements of peripheral blood flow, to study peripheral blood flow in a sample of non-pregnant, pregnant and pre-eclamptic women, and to investigate whether the adaptive changes in the peripheral circulation are different in pre-eclampsia compared with normal pregnancy. Applied potential tomography was used to assess peripheral vascular reactivity, by monitoring fluid distribution in calf muscles during postural change. The APT technique was able to detect peripheral vasoconstriction in response to an increase in intramural pressure brought about by passive lowering of the leg (peripheral mechanisms). The peripheral vasoconstriction response was found to be more prominent in woman with pre-eclampsia. The presence of a local reflex in the lower limb had been postulated and the effect of this reflex on the peripheral circulation could be detected using APT, regardless of how it was initiated. In normal pregnant women this reflex was diminished when compared to non-pregnant women, which might contribute to the reduction in peripheral vascular resistance seen in normal pregnancy. This reflex was defective in pre-eclampsia and this lack of adaptation may be a local reflex contributing to the raised peripheral resistance, which in turn may be a factor in high blood pressure in pre-eclampsia.

Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease.

Science.gov (United States)

Gelinas, Jinelle C; Lewis, Nia C; Harper, Megan I; Melzer, Bernie; Agar, Gloria; Rolf, J Douglass; Eves, Neil D

2017-11-01

What is the central question of this study? Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD. What is the main finding and its importance? Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short-term training programmes may not be long enough to improve vascular-related cardiovascular risk in COPD. Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV 1 %pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV 1 %pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow-mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima-media thickness, carotid compliance, distensibility and β-stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power (V̇O2 peak ) was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular

VASCULAR REMODELING IN HYPERTENSION: ANGIOGENESIS FEATURES

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L. A. Haisheva

2014-07-01

Full Text Available Aim — cross-sectional study of changes in various segments of the vascular bed in arterial hypertension (AH, defining the role of inducers and inhibitors of angiogenesis in these processes.Materials and methods. The study included 99 patients with arterial hypertension of I–II degree, average age of 63.2 ± 2.6 years, diseaseduration 9.2 ± 7.2 years.Results. It was found that patients with arterial hypertension have disorders in all segments of vascular bed: endothelial dysfunction (highvWF, microcirculatory disorders, and increased pulse wave velocity (PWV of elastic-type vessels. The level of angioginesis factors doesnot depend on such parameters as gender, age, body mass index. Smoking and duration of hypertension influence on vascular endothelialgrowth factor raise and endostatin levels are higher in patients with family history of cardiovascular diseases. Duration of disease is directlycorrelated with microcirculatory disorders and the PWV, correlation between microcirculatory disorders and pulse wave velocity indicatetheir common processes.

Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

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da Silva Gonçalves Bós, Denielli; Van Der Bruggen, Cathelijne E E; Kurakula, Kondababu; Sun, Xiao-Qing; Casali, Karina R; Casali, Adenauer G; Rol, Nina; Szulcek, Robert; Dos Remedios, Cris; Guignabert, Christophe; Tu, Ly; Dorfmüller, Peter; Humbert, Marc; Wijnker, Paul J M; Kuster, Diederik W D; van der Velden, Jolanda; Goumans, Marie-José; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; de Man, Frances S; Handoko, M Louis

2018-02-27

PYR treatment in PH rats normalized the cardiovascular autonomic function, demonstrated by an increase in parasympathetic activity and baroreflex sensitivity. PYR improved survival, increased RV contractility, and reduced RV stiffness, RV hypertrophy, RV fibrosis, RV inflammation, and RV α-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression, as well. Furthermore, PYR reduced pulmonary vascular resistance, RV afterload, and pulmonary vascular remodeling, which was associated with reduced local and systemic inflammation. RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH. © 2017 American Heart Association, Inc.

Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

OpenAIRE

Fidanboylu, Mehmet; Griffiths, Lisa A.; Flatters, Sarah J. L.

2011-01-01

Paclitaxel (Taxol (R)) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS...

Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.

Science.gov (United States)

Shinagawa-Kobayashi, Yoko; Kamimura, Kenya; Goto, Ryo; Ogawa, Kohei; Inoue, Ryosuke; Yokoo, Takeshi; Sakai, Norihiro; Nagoya, Takuro; Sakamaki, Akira; Abe, Satoshi; Sugitani, Soichi; Yanagi, Masahiko; Fujisawa, Koichi; Nozawa, Yoshizu; Koyama, Naoto; Nishina, Hiroshi; Furutani-Seiki, Makoto; Sakaida, Isao; Terai, Shuji

2018-02-05

Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow. Copyright © 2018 Elsevier Inc. All rights reserved.

Randomized controlled trial to evaluate the effect of canola oil on blood vessel function in peripheral arterial disease: rationale and design of the Canola-PAD Study

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Enns JE

2014-10-01

Full Text Available Jennifer E Enns,1,2 Peter Zahradka,1–3 Randolph P Guzman,4,5 Alanna Baldwin,1 Brendon Foot,1 Carla G Taylor1–31Canadian Centre for Agri-Food Research in Health and Medicine, St Boniface Research Centre, Winnipeg, Canada; 2Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; 3Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 4IH Asper Clinical Research Institute, St Boniface Hospital, Winnipeg, Canada; 5Section of Vascular Surgery, Department of Surgery, St Boniface Hospital, Winnipeg, CanadaBackground: Individuals with peripheral arterial disease (PAD are at high risk for cardiac events due to atherosclerosis. Dietary fatty acid composition has been shown to modulate blood vessel properties, but whether a diet enriched in conventional canola oil can improve clinical endpoints in PAD is not known.Purpose: To describe the rationale and design of a clinical trial testing the effect of canola oil consumption on vascular function and cardiovascular risk factors in an 8-week dietary intervention in individuals with PAD.Methods: The Canola-PAD Study was a single center, prospective, double-blind, randomized controlled trial in 50 patients over 40 years old with PAD. Participants were randomized into two groups and consumed food items containing either conventional canola oil (25 g/day or an oil mixture representing the Western diet (25 g/day for 8 weeks as part of their usual diet. The primary outcome was vascular function (ankle-brachial index, arterial stiffness, endothelial dysfunction, walking capacity, and cognitive function. Secondary measurements included anthropometrics, serum lipid profile and fatty acid composition, markers of inflammation and glycemic control, and serum metabolite profile.Discussion: The Canola-PAD Study uses an innovative and noninvasive approach to evaluate the effect of canola oil on clinically relevant outcomes in individuals with PAD, including

Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players.

Science.gov (United States)

Alexandru, Nicoleta; Badila, Elisabeta; Weiss, Emma; Cochior, Daniel; Stępień, Ewa; Georgescu, Adriana

2016-03-25

The recognition of the importance of diabetes in vascular disease has greatly increased lately. Common risk factors for diabetes-related vascular disease include hyperglycemia, insulin resistance, dyslipidemia, inflammation, hypercoagulability, hypertension, and atherosclerosis. All of these factors contribute to the endothelial dysfunction which generates the diabetic complications, both macro and microvascular. Knowledge of diabetes-related vascular complications and of associated mechanisms it is becoming increasingly important for therapists. The discovery of microparticles (MPs) and their associated microRNAs (miRNAs) have opened new perspectives capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. MPs known as submicron vesicles generated from membranes of apoptotic or activated cells into circulation have the ability to act as autocrine and paracrine effectors in cell-to-cell communication. They operate as biological vectors modulating the endothelial dysfunction, inflammation, coagulation, angiogenesis, thrombosis, subsequently contributing to the progression of macro and microvascular complications in diabetes. More recently, miRNAs have started to be actively investigated, leading to first exciting reports, which suggest their significant role in vascular physiology and disease. The contribution of MPs and also of their associated miRNAs to the development of vascular complications in diabetes was largely unexplored and undiscussed. In essence, with this review we bring light upon the understanding of impact diabetes has on vascular biology, and the significant role of MPs and MPs associated miRNAs as novel mediators, potential biomarkers and therapeutic targets in vascular complications in diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

Science.gov (United States)

Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

2015-12-01

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

International Nuclear Information System (INIS)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael; Bartok, Eva; Werner, Nikos; Bauernfeind, Franz; Latz, Eicke; Nickenig, Georg; Hornung, Veit; Ghanem, Alexander

2011-01-01

Highlights: → NLRP3 is not required for systemic cardiovascular function in healthy mice. → NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. → NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1β is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

Energy Technology Data Exchange (ETDEWEB)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bartok, Eva [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bauernfeind, Franz [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Latz, Eicke [Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Hornung, Veit [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Ghanem, Alexander, E-mail: ghanem@uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

2011-08-05

Highlights: {yields} NLRP3 is not required for systemic cardiovascular function in healthy mice. {yields} NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. {yields} NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). IL-1{beta} is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1{beta} is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Intraarterial digital subtraction angiography of peripheral arteries with isotonic contrast material

International Nuclear Information System (INIS)

Yashiro, Naobumi; Itai, Yuji; Ohtomo, Kuni; Furui, Shigeru; Iio, Masahiro

1984-01-01

Intraarterial digital subtraction angiography (IADSA) of peripheral arteries with isotonic contrast material, which was prepared by diluting meglumine amidotrizoate (65% Angiografin), was performed in ten patients. In six, both IADSA and conventional screen-film arteriography were performed for comparison. Painless peripheral arteriography was achieved by IADSA with isotonic contrast material. Five IADSAs were safely done on an outpatient basis. Visualization of arteries by IADSA was satisfactory, but the details of smaller arteries were better shown by screen-film arteriography. Visualization of faint stains was better in IADSA. The authors believe that IADSA with isotonic contrast material is a method of choice for the diagnosis of vascular diseases and tumorous conditions of extremities, as well as for the purpose of preoperative vascular mapping. It is safely performed with smaller dose of contrast material on outpatient basis, and with less discomfort and cost for the patient. (author)

Indication, procedure, and choice of the embolisation material in transcatheteral vascular occlusion

International Nuclear Information System (INIS)

Vogel, H.; Niemeier, J.; Hamburg Univ.

1985-01-01

If it is planned to effect transcatheteral occlusion of vessels, it must be examined whether the relevant vessel should be occluded permanently or temporarily and whether the occlusion should be located centrally in the vascular trunk or in a major twig, or peripherally in the region of the capillaries, arterioles and small vessels. Temporary occlusion with fibrospum is usually sufficient for treating a haemorrhage. Ethibloc or Bucrylate can be employed to shut off an organ and to achieve partial organ necrosis. Arteriovenous connections with a large vascular lumen can be occluded by means of metal particles. Peripherally occluding substances should not be used for embolisations in the gastrointestinal range because of the risk of local necrosis and possible dangerous infection resulting therefrom. To the present day hardly any indications have been found for the use of absolute alcohol. Bucrylate has the drawback, compared against Ethibloc, that the catheter may adhere to the vascular wall. Vessels with a low flow rate should be occluded either by means of balloon catheter or a coaxial catheter system because of the risk of reflux. (orig.) [de

Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma?

Directory of Open Access Journals (Sweden)

Danny Moore

2008-04-01

Full Text Available Danny Moore, Alon Harris, Darrell WuDunn, Nisha Kheradiya, Brent Siesky1Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Primary open angle glaucoma (OAG is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP. Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction.Keywords: glaucoma, autoregulation, blood flow, atherosclerosis, vasospasm, endothelial dysfunction

Anti-Inflammatory Effects of Interleukin-19 in Vascular Disease

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Ross N. England

2012-01-01

Full Text Available Despite aggressive dietary modification, lipid-lowering medications, and other interventional medical therapy, vascular disease continues to be a leading cause of mortality in the western world. It is a significant medical and socioeconomic problem contributing to mortality of multiple diseases including myocardial infarction, stroke, renal failure, and peripheral vascular disease. Morbidity and mortality of vascular disease are expected to worsen with the increasing number of patients with comorbid conditions such as obesity, metabolic syndrome, and diabetes mellitus type 2. Vascular diseases such as atherosclerosis, restenosis, and allograft vasculopathy are recognized to be driven by inflammation, and as such, cytokines which mediate inflammation not only represent important targets of rational therapy, but also can be considered as possible therapeutic modalities themselves. In this paper, we will examine the role of inflammatory cytokines and lymphocyte Th1/Th2 polarity in vascular inflammation, with a focus on atherosclerotic vascular disease. We will then introduce a recently described Th2 interleukin, interleukin-19 (IL-19, as a previously unrecognized mediator of vascular inflammatory disorders. We will review our current understanding of this interleukin in health and disease and present the possibility that IL-19 could represent a potential therapeutic to combat vascular inflammatory disease.

The role of atherectomy in the treatment of lower extremity peripheral artery disease

Science.gov (United States)

2012-01-01

Background The incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons. Method Typical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis. Conclusions This review summarizes the features and the current applications of new debulking devices. PMID:23173800

Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor

DEFF Research Database (Denmark)

Trøstrup, Hannah; Lerche, Christian J; Christophersen, Lars J

2018-01-01

-wounded, infection-susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB....../c wounds but increased peripheral levels 4-7 days post-infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S......100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central...

Vascular dysfunction associated with major depression-like symptoms: monoamine homeostasis and endothelial dysfunction

DEFF Research Database (Denmark)

Bouzinova, Elena; Andresen, Jørgen; Wiborg, Ove

Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In Chronic Mild Stress (CMS) model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS...... and reduced expression of extra-neuronal transporter (OCT-2) in anhedonic arteries. The contractility of middle cerebral arteries to 5-HT was reduced by CMS but recovered by anti-depressant treatment. Resistance arteries from anhedonic rats were less sensitive to acetylcholine compared to non......-like response) was significantly reduced in anhedonic rats. This was associated with decreased transcription of intermediate-conductance Ca2+-activated K+ channels. Our results indicate that CMS-induced depression-like symptoms in rats are associated with changes in monoamine uptake and endothelial dysfunctions...

Cortical capillary dysfunction in patients suspected of Alzheimer’s disease

DEFF Research Database (Denmark)

Eskildsen, Simon Fristed; Gyldensted, Louise; Nagenthiraja, Kartheeban

) leads to inefficient oxygen extraction and eventually to tissue hypoxia. In this study we investigated regional cerebral blood flow (CBF) and CTH in cortical gray matter of AD patients and controls using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and surface based statistics.......Vascular risk factors are suspected to play a role in the etiology of Alzheimer’s disease. Recently, a model that relates capillary dysfunction to the development of AD was proposed[1]. The model predicts that capillary dysfunction in form of increased capillary transit time heterogeneity (CTH...

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

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Sin Bond Leung

2013-01-01

Full Text Available Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction.

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

Science.gov (United States)

Leung, Sin Bond; Zhang, Huina; Lau, Chi Wai; Huang, Yu; Lin, Zhixiu

2013-01-01

Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS) level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO) bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction. PMID:23589720

Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML in human brain: relation to vascular dementia

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Williams Jonathan

2007-10-01

Full Text Available Abstract Background Advanced glycation end-products (AGEs and their receptor (RAGE occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1 those with dementia have higher levels of neuronal and vascular AGEs and (2 if cognitive dysfunction depends on neuronal and/or vascular AGE levels. Methods Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology were immunostained for Nε-(carboxymethyl-lysine (CML, the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures. Results The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01 or a history of hypertension (p = 0.028. Additionally, vascular CML staining related to cognitive impairment (p = 0.02 and a history of diabetes (p = 0.007. Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002. Conclusion CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.

Microalbuminuria, endothelial dysfunction and cardiovascular risk

DEFF Research Database (Denmark)

Feldt-Rasmussen, B

2000-01-01

Microalbuminuria was originally considered to be an important new risk factor for diabetic nephropathy. More recently, it has been convincingly shown that microalbuminuria is also an independent risk factor for cardiovascular morbidity and mortality in Type 1 and Type 2 diabetic patients. Even...... in the non-diabetic background population, microalbuminuria is a risk factor for cardiovascular mortality. What is the link between increased loss of albumin in urine and cardiovascular disease and mortality? As microalbuminuria is apparently associated with increased universal vascular sieving of albumin...... evidence of endothelial dysfunction in patients with microalbuminuria, which may be the common link accounting for the associations mentioned above. In this context, a number of markers of endothelial cell dysfunction have been found to be increased in patients with microalbuminuria. In addition, a number...

Evaluation of the psychometric properties of the phlebitis and infiltration scales for the assessment of complications of peripheral vascular access devices.

Science.gov (United States)

Groll, Dianne; Davies, Barbara; Mac Donald, Joan; Nelson, Susanne; Virani, Tazim

2010-01-01

To prevent complications from peripheral vascular access device (PVAD) therapy, the Infusion Nurses Society (INS) developed 2 scales to measure the extent and severity of phlebitis and infiltration in PVADs. This study evaluated the psychometric properties of these scales to validate them with respect to their interrater reliability, concurrent validity, feasibility, and acceptability. A total of 182 patients at 2 sites were enrolled, and 416 observations of PVAD sites were made. Two nurses independently rated each PVAD site for the presence or absence of phlebitis and/or infiltration by using the INS scales. The interrater reliability was calculated, as was the agreement of the observed versus charted incidence of phlebitis and infiltration (concurrent validity) and the ease of use of the scales (feasibility, acceptability). Interrater reliability for both the Phlebitis and Infiltration scales and concurrent validity were found to be statistically significant (P Phlebitis and Infiltration scales have been shown to be easy to use, valid, and reliable scales.

Near-infrared vascular imaging in peripheral venous and arterial access

OpenAIRE

Cuper, N.J.

2012-01-01

Venous and arterial access are among the most widespread medical procedures performed in children. Especially in young children venous and arterial access can be problematic due to tiny blood vessels that are difficult to localize beneath a layer of baby fat. This thesis describes the development and clinical evaluation of the VascuLuminator, a guidance tool for peripheral venous and arterial access by visualizing blood vessels underneath the skin with near-infrared light. In a third to a fif...

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

Science.gov (United States)

Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

2017-10-01

Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.

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Alaa Alkhalaf

Full Text Available Formation of advanced glycation endproducts (AGEs, endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h were randomized to receive benfotiamine (n = 39 or placebo (n = 43. Plasma and urinary AGEs (N(ε-(carboxymethyl lysine [CML], N(ε-(Carboxyethyl lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1] and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO] were measured at baseline and after 6 and 12 weeks.Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation.Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications. TRIAL REGRISTRATION: ClinicalTrials.gov NCT00565318.

Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.

Science.gov (United States)

Alkhalaf, Alaa; Kleefstra, Nanne; Groenier, Klaas H; Bilo, Henk J G; Gans, Reinold O B; Heeringa, Peter; Scheijen, Jean L; Schalkwijk, Casper G; Navis, Gerjan J; Bakker, Stephan J L

2012-01-01

Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy. Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (N(ε)-(carboxymethyl) lysine [CML], N(ε)-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks. Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation. Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications. TRIAL REGRISTRATION: ClinicalTrials.gov NCT00565318.

Neuro-vascular injuries associated with limb fractures | Mirdad | East ...

African Journals Online (AJOL)

Subjects: Forty three patients with bone fractures associated with vascular and peripheral nerve injury seen at the Emergency Room of Assir Central Hospital from 1990 to 1999. There were 39 males and four females. Thirty five of these patients (81.4%) were Saudi nationals and the rest were non-Saudi. The age range was ...

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Nielsen, F S; Bang, L E

1996-01-01

of ischaemic heart disease (ECG reading) (49/20/5)% and peripheral vascular disease as indicated by reduced systolic blood pressure on big toe (69/30/ 14)% was significantly higher in group 1 vs group 2 (p

Clinical impact of exercise in patients with peripheral arterial disease.

Science.gov (United States)

Novakovic, Marko; Jug, Borut; Lenasi, Helena

2017-08-01

Increasing prevalence, high morbidity and mortality, and decreased health-related quality of life are hallmarks of peripheral arterial disease. About one-third of peripheral arterial disease patients have intermittent claudication with deleterious effects on everyday activities, such as walking. Exercise training improves peripheral arterial disease symptoms and is recommended as first line therapy for peripheral arterial disease. This review examines the effects of exercise training beyond improvements in walking distance, namely on vascular function, parameters of inflammation, activated hemostasis and oxidative stress, and quality of life. Exercise training not only increases walking distance and physiologic parameters in patients with peripheral arterial disease, but also improves the cardiovascular risk profile by helping patients achieve better control of hypertension, hyperglycemia, obesity and dyslipidemia, thus further reducing cardiovascular risk and the prevalence of coexistent atherosclerotic diseases. American guidelines suggest supervised exercise training, performed for a minimum of 30-45 min, at least three times per week, for at least 12 weeks. Walking is the most studied exercise modality and its efficacy in improving cardiovascular parameters in patients with peripheral arterial disease has been extensively proven. As studies have shown that supervised exercise training improves walking performance, cardiovascular parameters and quality of life in patients with peripheral arterial disease, it should be encouraged and more often prescribed.

Treatment of peripheral vestibular dysfunction using photobiomodulation

Science.gov (United States)

Lee, Min Young; Hyun, Jai-Hwan; Suh, Myung-Whan; Ahn, Jin-Chul; Chung, Phil-Sang; Jung, Jae Yun; Rhee, Chung Ku

2017-08-01

Gentamicin, which is still used in modern medicine, is a known vestibular toxic agent, and various degrees of balance problems have been observed after exposure to this pharmacologic agent. Photobiomodulation is a candidate therapy for vertigo due to its ability to reach deep inner ear organs such as the cochlea. Previous reports have suggested that photobiomodulation can improve hearing and cochlea function. However, few studies have examined the effect of photobiomodulation on balance dysfunction. We used a rat model to mimic human vestibulopathy resulting from gentamicin treatment and evaluated the effect of photobiomodulation on vestibular toxicity. Slow harmonic acceleration (SHA) rotating platform testing was used for functional evaluation and both qualitative and quantitative epifluorescence analyses of cupula histopathology were performed. Animals were divided into gentamicin only and gentamicin plus laser treatment groups. Laser treatment was applied to one ear, and function and histopathology were evaluated in both ears. Decreased function was observed in both ears after gentamicin treatment, demonstrated by low gain and no SHA asymmetry. Laser treatment minimized the damage resulting from gentamicin treatment as shown by SHA asymmetry and recovered gain in the treated ear. Histology results reflected the functional results, showing increased hair cell density and epifluorescence intensity in laser-treated cupulae.

Increased subsequent risk of erectile dysfunction among middle and old age males with chronic osteomyelitis: a nationwide population-based cohort study.

Science.gov (United States)

Wang, H-Y; Chao, C-H; Lin, C-L; Tseng, C-H; Kao, C-H

2016-07-01

Chronic inflammation may cause endothelial dysfunction and atherosclerosis, resulting in subsequent erectile dysfunction (ED). We examined the relationship between chronic osteomyelitis, which is a chronic inflammatory disease, and ED. A retrospective cohort study was conducted using data from the National Health Insurance Research Database. After excluding patients <40 years of age, 677 male patients newly diagnosed with chronic osteomyelitis (COM) from 1 January 2000 to 31 December 2011 were identified for the study. The non-osteomyelitis comparison cohort consisted of 2706 male participants. The incidence of ED was 2.66-fold higher in the COM cohort than in the non-osteomyelitis cohort (4.01 vs 1.51 per 10 000 person-years). After adjusting for age and comorbidities of coronary heart disease, hypertension, hyperlipidemia, depression, stroke, diabetes, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease and asthma, the patients with COM had a 2.82-fold risk of ED (95% confidence interval=1.44-5.56). The incidence of ED increased with that of comorbidities in both cohorts. The highest hazard ratio was in patients between 40 and 59 years of age who had COM. Our data showed, for the first time, that COM is a possible risk factor for the development of ED.

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats.

Science.gov (United States)

Gun, Aburrahman; Ozer, Mehmet Kaya; Bilgic, Sedat; Kocaman, Nevin; Ozan, Gonca

2016-01-01

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

Directory of Open Access Journals (Sweden)

Aburrahman Gun

2016-01-01

Full Text Available Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS. HFCS (6 weeks, 30% fed with drinking water caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

Red cell 2, 3-diphosphoglycerate levels among diabetic patents with and without vascular complications.

Science.gov (United States)

Kanter, Y; Bessman, S P; Bessman, A

1975-08-01

There have been differences of opinion among authors concening in the levels of red cell 2,3-diphosphoglycerate (2,3-DPG) and nucleotides in nonacidotic diabetic patients. Our data suggest that abnormal levels of 2, 3-DPG in diabetic patients are related to the presence of vascular complications and not to the duration of the disease per sec. 2,3-DPG levels are normal in diabetic patients with no evidence of vascular complications (group A). In ambulatory patients with vascular complications (group B), significantly higher levels of 2,3-DPG are found than in normal subjects and patients in group A. In hospitalized diabetic patients with active peripheral vascular complications (group C), levels of 2,3-DPG are likewise significantly increased over those of normal subjects and patients of group A. 2,3-DPG was found to be significantly elevated in patients of group C as compared with group B. 2,3-DPG levels in venous blood from infected legs as compared with those of the peripheral venous blood were not significantly different, thereby ruling out local factors. There were no differences in the blood lactate levels in any of the group studied. The elevation of the 2,3-DPG levels may be a reflection of attempted red blood cell compensation for tissue hypoxia in the diabetic with vascular disease.

Differences in Blood Pressure and Vascular Responses Associated with Ambient Fine Particulate Matter Exposures Measured at the Personal Versus Community Level

Science.gov (United States)

Background Higher ambient fine particulate matter (PM2.5) levels can be associated with increased blood pressure and vascular dysfunction. Objectives To determine the differential effects on blood pressure and vascular function of daily changes in community ambient-...

Minimum training requirement in ultrasound imaging of peripheral arterial disease.

Science.gov (United States)

Eiberg, J P; Hansen, M A; Grønvall Rasmussen, J B; Schroeder, T V

2008-09-01

To demonstrate the minimum training requirement when performing ultrasound of peripheral arterial disease. Prospective and blinded comparative study. 100 limbs in 100 consecutive patients suffering from peripheral arterial disease, 74% suffering critical limb ischemia, were enrolled during a 9 months period. One physician with limited ultrasound experience performed all the ultrasound examinations of the arteries of the most symptomatic limb. Before enrolling any patients 15 duplex ultrasound examinations were performed supervised by an experienced vascular technologist. All patients had a digital subtraction arteriography performed by an experienced vascular radiologist, unaware of the ultrasound result. The number of insufficiently insonated segments (non-diagnostic segments) was significantly reduced during the study; from 9% among the initial 50 limbs to 2% among the last 50 limbs (Pultrasound and arteriography from the initial 50 patients (overall Kappa=0.66, (95%-CI: 0.60-0.72); supragenicular Kappa=0.73 (95%-CI: 0.64-0.82); infragenicular Kappa=0.61 (95%-CI: 0.54-0.69)) to the last 50 patients (overall Kappa=0.66 (95%-CI: 0.60-0.72), supragenicular Kappa=0.67 (95%-CI: 0.57-0.76); infragenicular Kappa=0.66 (95%-CI: 0.58-0.73)). The minimum training requirement in ultrasound imaging of peripheral arterial disease appears to be less than 50 ultrasound examinations (probably only 15 examinations) for the supragenicular segments and 100 examinations for the infragenicular segments.

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

Science.gov (United States)

Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-07-01

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction : a case study

NARCIS (Netherlands)

van Breda, E.; Keizer, H.A.; Kuipers, H.; Wolffenbuttel, B.H.R.

The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often

Association between Low Serum Bicarbonate Concentrations and Cardiovascular Disease in Patients in the End-Stage of Renal Disease

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Vaia D. Raikou

2016-11-01

Full Text Available Background: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. Methods: We studied 52 on-line-pre-dilution hemodiafiltration (on-l HDF patients, 32 males and 20 females, with a mean age of 58.01 ± 15.4 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22 mmol/L. Residual renal function (RRF was defined by interdialytic urine volume. Kaplan–Meier curves and Cox regression models were performed to predict coronary artery disease (CAD, defined by ejection fraction <50%, or diastolic dysfunction congestive heart failure (CHF and peripheral vascular disease (PVD. Results: Kaplan–Meier analyses showed that a lower or higher than 22 mmol/L serum bicarbonate metabolic acidosis status was significantly associated with both PVD and diastolic dysfunction (log-rank = 5.07, p = 0.02 and log-rank = 5.84, p = 0.01, respectively. A similar prevalence of serum bicarbonate on CAD or CHF by low ejection fraction was not shown. The RRF was associated with PVD event and serum bicarbonate less than 22 mmol/L (log-rank = 5.49, p = 0.01 and log-rank = 3.9, p = 0.04, respectively. Cox regression analysis revealed that serum bicarbonate and RRF were significant risk factors for PVD after adjustment for confounders. Furthermore, RRF adjusted for covariates was shown to be a significant risk factor for diastolic dysfunction. Conclusion: Low serum bicarbonate was associated with peripheral vascular disease and diastolic dysfunction in intermittent dialysis. The residual renal function may impact patients’ outcomes through its relationship with metabolic acidosis status, particularly for peripheral vascular disease manifestation.

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

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Adamski, Mateusz G; Sternak, Magdalena; Mohaissen, Tasnim; Kaczor, Dawid; Wierońska, Joanna M; Malinowska, Monika; Czaban, Iwona; Byk, Katarzyna; Lyngsø, Kristina S; Przyborowski, Kamil; Hansen, Pernille B L; Wilczyński, Grzegorz; Chlopicki, Stefan

2018-03-26

Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β 1-42 accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity. We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation. © 2018 The Authors. Published on behalf of the American Heart

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

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Hernández, Domingo; Triñanes, Javier; Armas, Ana María; Ruiz-Esteban, Pedro; Alonso-Titos, Juana; Duarte, Ana; González-Molina, Miguel; Palma, Eulalia; Salido, Eduardo; Torres, Armando

2017-07-01

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Supply and demand: Will we have enough vascular surgeons by 2030?

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Williams, Katherine; Schneider, Brandon; Lajos, Paul; Marin, Michael; Faries, Peter

2016-08-01

The increase in prevalence of certain cardiovascular risk factors increases susceptibility to vascular disease, which may create demand for surgical intervention. In our study, data collected by the American Association of Medical Colleges Physician Specialty Databook of 2012, the United States Census Bureau, and other nationwide organizations were referenced to calculate future changes in vascular surgeon supply and prevalence of people at risk for vascular disease. In 2010, there were 2853 active vascular surgeons. By 2040, the workforce is expected to linearly rise to 3573. There will be an exponential rise in people with cardiovascular risk factors. Adding to concern, in 2030, an estimated 3333 vascular surgeons will be available for 180,000,000 people with at least one risk factor for peripheral arterial disease. The paucity of properly trained surgeons entering the workforce needs to be addressed before this shortage becomes a larger burden on healthcare providers and governmental spending. © The Author(s) 2015.

Effect of x irradiation on the vascularization of experimental animal tumors

Energy Technology Data Exchange (ETDEWEB)

Saeki, Y; Ogawa, F; Nishiguchi, H; Tanaka, N; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan)

1975-03-01

The authors studied the effect of ionizing radiation on blood vessels and tumor growth in two animal tumor systems: a third generation isoplants of a mammary cancer and a spontaneously arising squamous cell carcinoma. Single cell suspensions were transplanted into a C3H and a C3Hf mouse respectively. They were irradiated once with 2000 rad when the tumors reached about 8 mm in diameter. Microangiography was performed at a constant temperature and pressure, and a contrast medium containing lead-oxide and gelatin was flushed the vena cava for 10 min. at 120 mmHg. Tumor shrinkage was followed by continuous regrowth. The basic vasculature of the mammary carcinoma consisted of abundant large and fine blood vessels corkscrewed or stretched from the periphery of the tumor to its center in complex reticular networks. One day after irradiation there were small scattered avascular areas which, by the third day formed a large central necrosis. Supervascularization was also observed, indicating that some hypoxic tumor cells could be reoxygenized. In 5 days vascularization was similar to that of a nonirradiated tumor. Conversely, The squamous cell carcinoma showed peripheral and central vascularization with abundant vascular and avascular areas and extravasion in the large avascular area. Two days after irradiation the vessels were dilated. At 3 days peripheral fine vessels were damaged but the central vasculature remained intact. Unlike the mammary carcinoma, supervascularization was not the typical finding. At 5 days, vascularization was similar to that of a nonirradiated tumor.

Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

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Stuti L. Misra

2014-01-01

Full Text Available Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P=0.12 and P=0.33, resp.. Tear lipid thickness (P=0.02, stability (P<0.0001, and quantity (P=0.01 were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P<0.001 and tear film stability was inversely associated with total neuropathy score (r=-0.29, P=0.03. Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

Evaluation and management of patients with peripheral artery disease by interventional radiologists: current practices.

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Prince, Ethan A; Murphy, Timothy P; Dhangana, Raj; Soares, Gregory M; Ahn, Sun H; Dubel, Gregory J

2008-05-01

Traditionally, surgeons have served as primary consultants for patients with peripheral vascular disease for whom revascularization is considered. An important component of care for patients with peripheral artery disease (PAD) is risk factor management. The present study was undertaken to determine current management practices of interventional radiologists for patients with PAD and compare them to published data for vascular surgeons. If PAD patient management practices are similar, this would support direct referral of PAD patients who are considered for revascularization from primary care doctors to interventional radiologists. An online survey was administered to full members of the Society of Interventional Radiology with e-mail addresses on file. Filtering was done to examine and compare interactions among several responses. The margin of error for the survey was +/-2%, based on 95% CIs for the entire surveyed population (N=2,371). Seventy-five percent of respondents see PAD patients in ambulatory office settings. Only eight percent see themselves as the physician responsible for risk factor management, similar to reported results of vascular surgeons (10%). Other variables examined, such as frequency of inquiring about Framingham risk factors, indicate similar practices to those previously reported for vascular surgeons. For interventional radiologists who accept direct referrals for medical management of patients with PAD, disease management by interventional radiologists is similar to that previously reported for vascular surgeons. This supports the role of interventional radiologists who accept direct referrals of patients with PAD as primary consultants to primary care doctors.

Quality of provided care in vascular surgery : outcome assessment & improvement strategies

NARCIS (Netherlands)

Flu, Hans Christiaan

2010-01-01

The aim of this thesis was to evaluate the quality of care in vascular surgery in end-stage renal disease (ESRD) and peripheral arterial occlusive disease (PAOD): intermittent claudication (IC) and critical lower limb ischaemia (CLI) patients. Therefore firstly it focused on the improvement of the

Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat.

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Balakumar, Pitchai; Chakkarwar, Vishal Arvind; Singh, Manjeet

2009-01-01

The study has been designed to investigate the effect of benfotiamine and fenofibrate in diabetes-induced experimental vascular endothelial dysfunction (VED) and nephropathy. The single administration of streptozotocin (STZ) (50 mg/kg, i.p.) produced diabetes, which was noted to develop VED and nephropathy in 8 weeks. The diabetes produced VED by attenuating acetylcholine-induced endothelium dependent relaxation, impairing the integrity of vascular endothelium, decreasing serum nitrite/nitrate concentration and increasing serum TBARS and aortic superoxide anion generation. Further, diabetes altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. The nephropathy was noted to be developed in the diabetic rat that was assessed in terms of increase in serum creatinine, blood urea, proteinuria, and glomerular damage. The benfotiamine (70 mg/kg, p.o.) and fenofibrate (32 mg/kg, p.o.) or lisinopril (1 mg/kg, p.o., a standard agent) treatments were started in diabetic rats after 1 week of STZ administration and continued for 7 weeks. The treatment with benfotiamine and fenofibrate either alone or in combination attenuated diabetes-induced VED and nephropathy. In addition, the combination of benfotiamine and fenofibrate was noted to be more effective in attenuating the diabetes-induced VED and nephropathy when compared to treatment with either drug alone or lisinopril. Treatment with fenofibrate normalizes the altered lipid profile in diabetic rats, whereas benfotiamine treatment has no effect on lipid alteration in diabetic rats. It may be concluded that diabetes-induced oxidative stress, lipids alteration, and consequent development of VED may be responsible for the induction of nephropathy in diabetic rats. Concurrent administration of benfotiamine and fenofibrate may provide synergistic benefits in preventing the development of diabetes-induced nephropathy by reducing the oxidative stress and lipid

Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism.

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Rossmeisl, J H

2010-01-01

Hypothyroidism has been implicated in the development of multiple peripheral mono- and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. Eighteen purpose-bred, female dogs. Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic-tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic-tibial and ulnar F-wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (Pmuscle action potentials over time, which were attributed to the concurrent myopathy. No significant differences between control and hypothyroid dogs were detected in electrophysiologic tests of motor (P>or=.1) or sensory nerve conduction velocity (P>or=.24) or nerve roots (P>or=.16) throughout the study period, with values remaining within reference ranges in all dogs. Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.

Peripheral MR Angiography of Klippel-Trenaunay Syndrome

International Nuclear Information System (INIS)

Fontana, Alessandro; Olivetti, Lucio

2004-01-01

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disease of unknown etiology that affects one or more limbs. It is characterized clinically by three physical findings (the so-called triad): port-wine stain hemangioma, hypertrophy of the bony and/or soft tissue, and varicose veins. A review of the medical literature in 1999 revealed about 1,000 case studies. We present here the case of a patient with clinical diagnosis of KTS studied using peripheral magnetic resonance angiography

Further validation of the peripheral artery questionnaire: results from a peripheral vascular surgery survey in the Netherlands.

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Smolderen, K G; Hoeks, S E; Aquarius, A E; Scholte op Reimer, W J; Spertus, J A; van Urk, H; Denollet, J; Poldermans, D

2008-11-01

Peripheral arterial disease (PAD) is associated with adverse cardiovascular events and can significantly impair patients' health status. Recently, marked methodological improvements in the measurement of PAD patients' health status have been made. The Peripheral Artery Questionnaire (PAQ) was specifically developed for this purpose. We validated a Dutch version of the PAQ in a large sample of PAD patients. Cross-sectional study. The Dutch PAQ was completed by 465 PAD patients (70% men, mean age 65+/-10 years) participating in the Euro Heart Survey Programme. Principal components analysis and reliability analyses were performed. Convergent validity was documented by comparing the PAQ with EQ-5D scales. Three factors were discerned; Physical Function, Perceived Disability, and Treatment Satisfaction (factor loadings between 0.50 and 0.90). Cronbach's alpha values were excellent (mean alpha=0.94). Shared variance of the PAQ domains with EQ-5D scales ranged from 3 to 50%. The Dutch PAQ proved to have good measurement qualities; assessment of Physical Function, Perceived Disability, and Treatment Satisfaction facilitates the monitoring of patients' perceived health in clinical research and practice. Measuring disease-specific health status in a reliable way becomes essential in times were a wide array of treatment options are available for PAD patients.

Supplementation of a γ-tocopherol-rich mixture of tocopherols in healthy men protects against vascular endothelial dysfunction induced by postprandial hyperglycemia.

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Mah, Eunice; Noh, Sang K; Ballard, Kevin D; Park, Hea Jin; Volek, Jeff S; Bruno, Richard S

2013-01-01

Postprandial hyperglycemia induces oxidative stress responses, impairs vascular endothelial function (VEF) and increases the risk of cardiovascular disease. We hypothesized that the antioxidant and anti-inflammatory activities of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) would protect against vascular dysfunction that is otherwise caused by postprandial hyperglycemia by decreasing oxidative stress and proinflammatory responses, and improving nitric oxide (NO•) homeostasis. In a randomized, crossover study, healthy men (n=15; 21.8 ± 0.8 years) completed a fasting oral glucose challenge (75 g) with or without prior supplementation of γ-TmT (5 days). Brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine and asymmetric dimethylarginine (ADMA) were measured at regular intervals during a 3-h postprandial period. Supplementation of γ-TmT increased (P.05). Postprandial FMD decreased 30%-44% (P<.05) following glucose ingestion, but was maintained with γ-TmT. Supplementation of γ-TmT also attenuated postprandial increases in MDA that occurred following glucose ingestion. Plasma arginine decreased (P<.05) in both trials to a similar extent regardless of γ-TmT supplementation. However, the ratio of ADMA/arginine increased time-dependently in both trials (P<.05), but to a lesser extent following γ-TmT supplementation (P<.05). Inflammatory proteins were unaffected by glucose ingestion or γ-TmT. Collectively, these findings support that short-term supplementation of γ-TmT maintains VEF during postprandial hyperglycemia possibly by attenuating lipid peroxidation and disruptions in NO• homeostasis, independent of inflammation. Published by Elsevier Inc.

The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

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Annayya R Aroor

2013-10-01

Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

Peripheral venous malformations and pulmonary hypertension: A case report and literature review

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Nambakam Tanuja Subramanyam

2015-01-01

Full Text Available Extensive pure peripheral venous malformations are rare. We report occurrence of peripheral venous malformations associated with pulmonary hypertension in a middle-aged male, who had nodular, irregular, soft, compressible, painless, non-pulsatile swellings over dependant positions such as forearms, hands, axilla, and genitalia, with overgrowth of hands and fingers enlarging slowly since early childhood. He had right ventricular failure signs. Plain films showed soft-tissue mass with diffuse calcifications (phleboliths. Doppler study showed low flow vascular channels, compressible hypoechoic lesions along with occasional hyperechoeic lesion corresponding with phleboliths. Magnetic resonance imaging (MRI, T1-weighted showed polypoidal mass with heterogenous hypo to intermediate signal with no flow voids. T2-weighted MRI showed high-signal intensity mass. Computed tomography (CT pulmonary angiogram showed pulmonary hypertension, no thrombi or vascular malformation. He was treated with angiotensin-converting enzyme inhibitors, diuretics, amiodarone, antiplatelets, and venous stockings. Specific therapy such as sclerosis and surgical resection could not be done as he was discharged against medical advice.

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

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Helena U Westergren

Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

Surveillance of Hemodialysis Vascular Access with Ultrasound Vector Flow Imaging

DEFF Research Database (Denmark)

Brandt, Andreas Hjelm; Olesen, Jacob Bjerring; Lindskov Hansen, Kristoffer

2015-01-01

-functioning vascular access with as few complications as possible and preferred vascular access is an AVF. Dysfunction due to stenosis is a common complication, and regular monitoring of volume flow is recommended to preserve AVF patency. UDT is considered the gold standard for volume flow surveillance, but VFI has...... proven to be more precise, when performing single repeated instantaneous measurements. Three patients with AVF were monitored with UDT and VFI monthly for five months. A commercial ultrasound scanner with a 9 MHz linear array transducer with integrated VFI was used to obtain data. UDT values were...... be used for surveillance of volume flow....

Cerebral blood flow single-photon emission tomography with 123I-IMP in vascular dementia

International Nuclear Information System (INIS)

Kawahata, Nobuya; Gotoh, Chiharu; Yokoyama, Sakura; Daitoh, Nobuyuki

2001-01-01

Cerebral blood flow differences between patients with vascular dementia, patients with multiple lacunar infarction without cognitive dysfunction, and age-matched controls were examined. Thirty four patients with vascular dementia (VD) were selected from consecutive referrals to the Memory Clinic at Narita Memorial Hospital. All the patients had routine assessment including history, physical and neurological examinations, neuropsychological assessment, blood tests, EEG, head MRI, and single photon emission computed tomography (SPECT). All of them fulfilled the NINDS-AIREN diagnostic criteria for vascular dementia. Thirty nine patients with multiple lacunar infarction without cognitive dysfunction and 110 age-matched controls were included in this study. Mean cerebral blood flow (mCBF) and regional cerebral blood flow (rCBF) were measured using N-isopropyl-P- 123 I-iodoamphetamine ( 123 I-IMP) and SPECT imager. The mCBF in VD was 27.6±5.3 ml/100 g/min, while those in the control group and multiple lacunar infarction without cognitive dysfunction were 36.6±6.1 ml/100 g/min and 32.5±5.5 ml/100 g/min, respectively. The patients with VD demonstrated significantly reduced mCBF and rCBF in twenty regions including both cerebellar hemispheres as compared with those of the control group. Although there was no significant rCBF differences in bilateral inferior occipital regions and the right cerebellar hemisphere between patients with VD and multiple lacunar infarction without cognitive dysfunction, we could find significant lower rCBF in the remaining brain areas. In spite of the severity of VD, the diffuse decrease of cerebral blood flow was recognized in all patients with VD. (author)

[Focus on beta-blockers for vascular specialists in 2012].

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Mairesse, S; Blacher, J; Safar, M-E

2011-12-01

Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta-blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Effects of Swimming and Cycling Exercise Intervention on Vascular Function in Patients With Osteoarthritis.

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Alkatan, Mohammed; Machin, Daniel R; Baker, Jeffrey R; Akkari, Amanda S; Park, Wonil; Tanaka, Hirofumi

2016-01-01

Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle-aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

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Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

2016-04-01

Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (Ppreeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (Ppreeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

Vascular channels in metacarpophalangeal joints : a comparative histologic and high-resolution imaging study

NARCIS (Netherlands)

Scharmga, A.; Keller, K.K.; Peters, M.; van Tubergen, A.; van den Bergh, J.P.W.; van Rietbergen, B.; Weijers, R.; Loeffen, D.; Hauge, E.M.; Geusens, P.P.M.M.

2017-01-01

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and

Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis.

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Clark, Christopher E; Taylor, Rod S; Shore, Angela C; Ukoumunne, Obioha C; Campbell, John L

2012-03-10

Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality. We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta-analysis to combine estimates of the association between differences in SBP between arms and each outcome. We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36·9 mm Hg (95% CI 35·4-38·4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8·8, 95% CI 3·6-21·2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2·5, 95% CI 1·6-3·8; sensitivity 15%, 9-23; specificity 96%, 94-98); pre-existing cerebrovascular disease (five cohorts; RR 1·6, 1·1-2·4; sensitivity 8%, 2-26; specificity 93%, 86-97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1·7, 95% CI 1·1-2·5) and all-cause mortality (HR 1·6, 1·1-2·3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2·4, 1·5-3·9; sensitivity 32%, 23-41; specificity 91%, 86-94). A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of

Exploring in vivo models to characterize peripheral microcirculation – a pilot study

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Henrique Silva

2013-06-01

Full Text Available In recent years cutaneous circulation has emerged as an interesting window through which to study microcirculatory function and dysfunction mechanisms. Non-invasive technologies, including Laser Doppler Flowmetry (LDF, transcutaneous gasimetry and Transepidermal Water Loss (TEWL, helped to consider cutaneous circulation as a useful translational model in vascular disease. In this study we attempted to evaluate the response profile from a group of healthy young individuals (n=8, of both genders (24,5 ± 0,8 years old to three perfusion-conditioning maneuvers in the lower limb - A: leg elevation while seated; B: leg elevation during dorsal decubitus; C: supra-systolic occlusion with a tourniquet-cuff. Measurement techniques included LDF, transcutaneous (tc pO2 and pCO2 partial pressures, by gasimetry and TEWL by evaporimetry. Descriptive and nonparametric statistics were applied and a 95% confidence level adopted. tcpO2 and tcpCO2 changed significantly during the maneuvers. A reciprocal evolution profile was registered in LDF and TEWL in A and C which might suggest that under the present experimental conditions local perfusion might influence the epidermal “barrier” function. The proposed models seem to be appropriate to characterize the peripheral microcirculation in vivo, justifying further development studies.

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

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Aparna Areti

2014-01-01

Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and LymphangiogenesisSummary

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Masatake Tanaka

2016-11-01

Full Text Available The lymphatic vascular system has been minimally explored in the liver despite its essential functions including maintenance of tissue fluid homeostasis. The discovery of specific markers for lymphatic endothelial cells has advanced the study of lymphatics by methods including imaging, cell isolation, and transgenic animal models and has resulted in rapid progress in lymphatic vascular research during the last decade. These studies have yielded concrete evidence that lymphatic vessel dysfunction plays an important role in the pathogenesis of many diseases. This article reviews the current knowledge of the structure, function, and markers of the hepatic lymphatic vascular system as well as factors associated with hepatic lymphangiogenesis and compares liver lymphatics with those in other tissues. Keywords: VEGF, Inflammation, Cirrhosis, Portal Hypertension

RENAL INVOLVEMENT IN SUBJECTS WITH PERIPHERAL ATHEROSCLEROSIS

International Nuclear Information System (INIS)

FAWZY, A.; IBRAHIM, S.

2008-01-01

Ischemic nephropathy is an important cause of renal failure.Sub-clinical renal function abnormalities may exist in patients with extra renal atherosclerosis and may precede the onset of overt ischemic nephropathy. To assess the impact of extrarenal atherosclerosis on the kidney, the study evaluated renal function in 50 subjects with differing degrees of peripheral atherosclerosis without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension.All laboratory testing including total LDL and HDL-cholesterol, triglycerides, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance) were determined as well as smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). The results showed no change in plasma creatinine while DTPA clearance was increased from 91.58±26.53 to 93.47±24.82 ml/min/1.73 m. MAG3 clearance was progressively declined with the severity of vascular damage from 244.86 ± 60.60 to 173.59±58.74 ml/min/1.73 m.Stepwise, multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized B coefficient -0.40; P< 0.001), smoking habit (-0.34;P=0.004) and serum LDL-cholesterol (-0.24; P<0.035).It could be concluded that the renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors

A case of William's syndrome associated peripheral pulmonary arterial stenosis

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Jung, Kyung Hwa; Hwang, Mi Soo; Kim, Sun Yong; Chang, Jae Chun; Park, Bok Hwan [College of Medicine, Yeungam University, Daegu (Korea, Republic of)

1988-06-15

William's syndrome, in order to more completely delineate the total spectrum of the disorder, indicates that 'infantile hypercalcemia', 'peculiar facies' and 'supravalvular aortic stenosis.' In has other many vascular anomalies, such as peripheral pulmonary arterial stenosis, coronary arterial stenosis, celiac arterial stenosis, and renal aterial stenosis. Only 32% of the patients have evidence of supravalvular aortic stenosis. And it is very rare disease entity that has been reported rarely in Korea. Recently authors experienced a case that was questioned William's syndrome with peripheral pulmonary arterial stenosis, clinically and preliminary radiologically and this case was confirmed by operation. Here we report a case of William's syndrome with peripheral pulmonary arterial stenosis and reviewed literatures.

ABCD1 dysfunction alters white matter microvascular perfusion

DEFF Research Database (Denmark)

Lauer, Arne; Da, Xiao; Hansen, Mikkel Bo

2017-01-01

Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability...... of the blood–brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic reson- ance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased...... capillary flow heterogeneity in asymptom- atic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow hetero...

Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

Science.gov (United States)

Busch, Albert; Hoffjan, Sabine; Bergmann, Frauke; Hartung, Birgit; Jung, Helena; Hanel, Daniela; Tzschach, Andeas; Kadar, Janos; von Kodolitsch, Yskert; Germer, Christoph-Thomas; Trobisch, Heiner; Strasser, Erwin; Wildenauer, René

2016-08-03

The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

Science.gov (United States)

Masha, A; Martina, V

2014-01-01

Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

Aerobic Exercise and Other Healthy Lifestyle Factors That Influence Vascular Aging

Science.gov (United States)

Santos-Parker, Jessica R.; LaRocca, Thomas J.; Seals, Douglas R

2014-01-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development…

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

Science.gov (United States)

Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

2017-11-01

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function

Vascular access in pediatric patients in the emergency department: types of access, indications, and complications [digest].

Science.gov (United States)

Whitney, Rachel; Langhan, Melissa; Pade, Kathryn H

2017-06-22

Vascular access is a potentially life-saving procedure that is a mainstay of emergency medicine practice. There are a number of challenges associated with obtaining and maintaining vascular access, and the choice of the route of access and equipment used will depend on patient- and provider-specific factors. In this issue, the indications and complications of peripheral intravenous access, intraosseous access, and central venous access are reviewed. Timely and effective assessment and management of difficult-access patients, pain control techniques that can assist vascular access, and contraindications to each type of vascular access are also discussed. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

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Iveta Bernatova

2014-01-01

Full Text Available Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP. The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (prehypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

Subtracted versus non-subtracted digital imaging in peripheral angiography

International Nuclear Information System (INIS)

Fink, U.; Heywang, S.; Mayr, B.; Berger, H.

1989-01-01

Digital subtraction angiography (DSA) plays an important role in the management of vascular diseases of the lower extremities. A disadvantage is the lack of an automatically moving table top. We used a 1,024x1,024 matrix with a large-screen intensifier system and an automated 'stepping' facility. In 161 examinations of the arteries of the lower extremity digital peripheral arteriography was performed with and without the subtraction technique. We compared the influence of different iodine concentrations in DA and DSA. Peripheral DA proved to be equal to peripheral DSA in the region of the pelvis, thigh and knee, with no adequate contrasting being obtained merely in the region of the lower leg arteries in about 45%. It is necessary to use contrast medium at a concentration of 300 mg I/ml. The installation of an automated 'stepping' facility reduces the amount of contrast' medium needed and the exposure time. (orig.)

Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease

NARCIS (Netherlands)

M.M. van den Heuvel (Mieke); O. Sorop (Oana); P. Musters (Paul); R.T. van Domburg (Ron); T.W. Galema (Tjebbe); D.J.G.M. Duncker (Dirk); W.J. van der Giessen (Wim); K. Nieman (Koen)

2015-01-01

textabstractBackground Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. Methods In 93 patients, PAT was performed resulting in reactive

Imaging findings of pulmonary vascular disorders in portal hypertension

International Nuclear Information System (INIS)

Nagasawa, Kenichi; Takahashi, Koji; Furuse, Makoto

2004-01-01

The purpose of this study was to demonstrate and compare the imaging findings of hepatopulmonary syndrome and portopulmonary hypertension. We retrospectively reviewed the imaging findings of five patients with hepatopulmonary syndrome and four patients with portopulmonary hypertension. We evaluated chest radiographs, chest and abdominal computed tomography (CT) scans, 99m Tc-macroaggregated albumin (MAA) lung perfusion scans, and pulmonary angiograms. In patients with hepatopulmonary syndrome, the presence of peripheral pulmonary vascular dilatation was detected by chest radiograph, chest CT scan, and pulmonary angiogram, especially the basilar segment. 99m Tc-MAA lung perfusion scan showed extrapulmonary tracer distribution (brain, thyroid, and kidney), which revealed pulmonary right-left shunting. In patients with portopulmonary hypertension, chest radiographs and chest CT scans showed the classic findings of primary pulmonary hypertension. In patients with both disorders, extrahepatic features of portal hypertension including ascites, splenomegaly, and portosystemic collateral vessels were seen on abdominal CT. In conclusion, chest radiographs and CT in hepatopulmonary syndrome usually showed peripheral pulmonary vascular dilatation, whereas those in portopulmonary hypertension showed central pulmonary artery dilatation. The extrahepatic features of portal hypertension might be helpful for the diagnosis of both disorders. (author)

Bletilla colloid as a vascular embolization agent: experimental studies

International Nuclear Information System (INIS)

Zheng Chuansheng; Feng Gansheng; Zhang Yanfang

1998-01-01

Purpose: To study the efficacy, safety and related characteristics of bletilla colloid as a vascular embolization agent. Materials and methods: The authors prepared bletilla colloid as a vascular embolization agent from the stem tubers of bletilla of Chinese medicinal herb. Related characteristics of bletilla colloid were studied. In four pigs hepatic arterial embolization was performed with the bletilla colloid. Results: The bletilla colloid was a homogenous viscous colloid whose relative viscosity was 2324.6 mm 2 /s. It was easily injected through 4-F catheter and hyperattenuating under fluoroscopy, meanwhile, with good histocompatibility and hemo-compatibility, without pyrogenetic response and toxicity. In vitro, the mixture of bletilla colloid and MMC did not produce separation and suspension phenomena but released 50% of MMC at 1.8h and 100% at 3.4h. The bletilla colloid mainly embolized peripheral arteries, maintaining occlusion for 5 weeks and without formation of collateral circulation. The injuries of normal hepatic tissues were slight, without hepatic cytonecrosis. Conclusions: Bletilla colloid, safe and effective in use with angioembolic function and characteristics of carrier and slow-release, is a potential peripheral embolization agent

Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

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Ulf G. Bronas

2017-01-01

Full Text Available Chronic kidney disease (CKD is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

Cerebral blood flow single-photon emission tomography with {sup 123}I-IMP in vascular dementia

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Kawahata, Nobuya; Gotoh, Chiharu; Yokoyama, Sakura; Daitoh, Nobuyuki [Narita Memorial Hospital, Toyohashi, Aichi (Japan)

2001-06-01

Cerebral blood flow differences between patients with vascular dementia, patients with multiple lacunar infarction without cognitive dysfunction, and age-matched controls were examined. Thirty four patients with vascular dementia (VD) were selected from consecutive referrals to the Memory Clinic at Narita Memorial Hospital. All the patients had routine assessment including history, physical and neurological examinations, neuropsychological assessment, blood tests, EEG, head MRI, and single photon emission computed tomography (SPECT). All of them fulfilled the NINDS-AIREN diagnostic criteria for vascular dementia. Thirty nine patients with multiple lacunar infarction without cognitive dysfunction and 110 age-matched controls were included in this study. Mean cerebral blood flow (mCBF) and regional cerebral blood flow (rCBF) were measured using N-isopropyl-P-{sup 123}I-iodoamphetamine ({sup 123}I-IMP) and SPECT imager. The mCBF in VD was 27.6{+-}5.3 ml/100 g/min, while those in the control group and multiple lacunar infarction without cognitive dysfunction were 36.6{+-}6.1 ml/100 g/min and 32.5{+-}5.5 ml/100 g/min, respectively. The patients with VD demonstrated significantly reduced mCBF and rCBF in twenty regions including both cerebellar hemispheres as compared with those of the control group. Although there was no significant rCBF differences in bilateral inferior occipital regions and the right cerebellar hemisphere between patients with VD and multiple lacunar infarction without cognitive dysfunction, we could find significant lower rCBF in the remaining brain areas. In spite of the severity of VD, the diffuse decrease of cerebral blood flow was recognized in all patients with VD. (author)

Detecting Vascular-Targeting Effects of the Hypoxic Cytotoxin Tirapazamine in Tumor Xenografts Using Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Bains, Lauren J.; Baker, Jennifer; Kyle, Alastair H.; Minchinton, Andrew I.; Reinsberg, Stefan A.

2009-01-01

Purpose: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). Methods and Materials: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K trans ) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. Results: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K trans and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K trans and IAUC values. Conclusions: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.

Newly diagnosed type 1 diabetes complicated by ketoacidosis and peripheral thrombosis leading to transfemoral amputation

DEFF Research Database (Denmark)

Bisgaard Jørgensen, Line; Skov, Ole; Yderstræde, Knud Bonnet

2014-01-01

Peripheral vascular thromboembolism is a rarely described complication of diabetic ketoacidosis. We report a 41-year-old otherwise healthy man admitted with ketoacidosis and ischaemia of the left foot. The patient was unsuccessfully treated with thromboendarterectomy, and the extremity was ultima...... was ultimately amputated. The patient had no family history of cardiovascular disease, and all blood sample analyses for hypercoagulability were negative. We recommend an increased focus on peripheral thromboembolism, when treating patients with severe ketoacidosis....

Effect of statin versus fibrate on postprandial endothelial dysfunction: role of remnant-like particles

NARCIS (Netherlands)

Wilmink, H. W.; Twickler, M. B.; Banga, J. D.; Dallinga-Thie, G. M.; Eeltink, H.; Erkelens, D. W.; Rabelink, T. J.; Stroes, E. S.

2001-01-01

BACKGROUND: Postprandial lipemia is associated with endothelial dysfunction. Remnant-like particles (RLP) have been suggested to contribute to these adverse vascular effects. We investigated the effect of cerivastatin and gemfibrozil upon oral fat load induced changes in endothelial function and

[The magneto-, photo- and laser therapy of headaches in patients with vascular brain lesions].

Science.gov (United States)

Troshin, V D; Miasnikov, I G; Belousova, T E

1994-01-01

To manage vascular cephalalgia, a combined approach is proposed: segmentally oriented magnetic, photo- and photomagnetic therapy plus intravenous laser treatment. The effect was directly correlated with cerebral hemodynamic condition, damage to vegetative innervation segmental-peripheral link and physiotherapeutic factors.

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update

Directory of Open Access Journals (Sweden)

Mohammad Khan

2017-01-01

Full Text Available Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.

Relationship between female pelvic floor dysfunction and sexual dysfunction: an observational study.

Science.gov (United States)

Bortolami, Arianna; Vanti, Carla; Banchelli, Federico; Guccione, Andrew A; Pillastrini, Paolo

2015-05-01

The ability to express one's sexuality and engage in sexual activity requires multisystemic coordination involving many psychological functions as well as the integrity of the nervous, hormonal, vascular, immune, and neuromuscular body structures and functions. The purpose of this study was to investigate the associations among pelvic floor function, sexual function, and demographic and clinical characteristics in a population of women initiating physical therapy evaluation and treatment for pelvic floor-related dysfunctions (urinary incontinence, pelvic organ prolapse, vulvodynia, vaginismus, and constipation). We consented and collected completed demographic data and data related to symptoms and clinical condition on 85 consecutive patients in an outpatient physical therapy clinic. Clinical and anthropometric characteristics were analyzed descriptively. Analysis of variance and linear regression analyses were used to analyze Female Sexual Function Index (FSFI) scale ratings, whereas zero-inflated beta-binomial regression was applied to the pain subscale. Main outcome measure was FSFI score, whereas the secondary outcome measure was the FSFI subscale score related to pain. Women in our sample were 38 years old on average, 33% of whom had given birth and 82% of whom had high tone pelvic floor. Being in the middle-tercile age group and exhibiting low pelvic floor tone (Beta = 6.8; 95% confidence interval [CI] = [1.4; 12.0]) were significantly associated with lower levels of sexual dysfunction. Women with low tone pelvic floor also reported lower pain (odds ratio = 4.0; 95% CI = [1.6; 9.6]), whereas younger aged and physically unsatisfied subjects were more likely not to have sexual activity in the month prior to scale measurement. In female patients with pelvic floor muscle dysfunction undergoing physical therapy and rehabilitation, sexual dysfunction appears to be significantly correlated with age and high pelvic floor muscle tone. © 2015

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

International Nuclear Information System (INIS)

Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

2010-01-01

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Inflammation and peripheral venous disease. The San Diego Population Study.

Science.gov (United States)

Cushman, M; Callas, P W; Allison, M A; Criqui, M H

2014-09-02

The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

Science.gov (United States)

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients

NARCIS (Netherlands)

Lima, Alexandre; van Bommel, Jasper; Sikorska, Karolina; van Genderen, Michel; Klijn, Eva; Lesaffre, Emmanuel; Ince, Can; Bakker, Jan

2011-01-01

We conducted this observational study to investigate tissue oxygen saturation during a vascular occlusion test in relationship with the condition of peripheral circulation and outcome in critically ill patients. Prospective observational study. Multidisciplinary intensive care unit in a university

TREATMENT OF NEUROGENIC ERECTILE DYSFUNCTION IN PATIENTS WITH TYPE I DIABETES

Directory of Open Access Journals (Sweden)

D. G. Kurbatov

2017-01-01

Full Text Available Introduction. The urogenital form of autonomic diabetic polyneuropathy is a specific lesion of the autonomic nervous system in diabetic patients. It is main pathogenetic cause of sexual disorders in this category of patients. The most common violation of sexual function in patients with diabetes is erectile dysfunction (ED.Objective. Diagnosis of peripheral neuropathy with ED caused by type I diabetes and assessment of the effectiveness phosphodiesterase type 5 inhibitor (PDE5-I in its treatment.Materials and methods. The study included 40 patients with ED due to type 1 diabetes at the age of 25.7 ± 6.1. The duration of type 1 diabetes was 18 ± 9.7 years. All 40 patients, initially and after the course of therapy with the PDE5-Is, underwent a neuromyographic study with the determination of the excitation propagation rate for nervus peroneus and nervus pudendus, endothelial function evaluation on the EndoPat ™ device, and the questionnaire on the international index of erectile function (IIEF-5 scale.Results. In 30 (75.0% men, endothelial dysfunction was determined according to EndoPat ™. In the range of the gray zone of reactive hyperemia index (RHI was detected in 7 men (16.6%. Normal function of the endothelium was revealed in 3 cases (8.4%. In the control study, the following data were found: endothelial dysfunction was detected in 6 patients (16.6% according to Endo Pat ™, in 14 patients (33.4% in the range of gray zone of RHI, endothelial function was normalized in 20 patients (50.0%. According to the neuromyographic study, initially all patients had diabetic neuropathy in both the distal and urogenital forms. After therapy, significant positive dynamics were shown. Based on the results of the questionnaire on the scale of IIEF-5, initially all patients showed ED of varying severity. With the control questionnaire after therapy, there was an improvement in erectile function.Conclusions. Given the high incidence of endothelial

A case of late-onset allgrove syndrome presenting with predominant autonomic dysfunction

Directory of Open Access Journals (Sweden)

Debmalya Sanyal

2013-01-01

Full Text Available Allgrove Syndrome or triple A syndrome is a rare familial multisystem disorder characterized by achalasia, alacrima and adrenal insufficiency. The objective was to describe a case of 4A syndrome where autonomic dysfunction was the presenting feature. A 22-year-old male presented with erectile dysfunction and loss of spontaneous morning erections for six months. He was having nocturnal diarrhea and recurrent postural dizziness for three months. He was found to have hyperpigmentation at pressure points, postural hypotension and other features of autonomic dysfunction. Laboratory investigations and imaging studies revealed hypoadrenalism, achalasia, alacrima and peripheral neuropathy. Autonomic neuropathy-related features persisted even after correction of hypoadrenalism. Based on clinical features and investigation he was diagnosed as a case of 4A syndrome presenting with autonomic dysfunction. Allgrove or 4A syndrome should be considered as a rare differential diagnosis of someone presenting with features of autonomic neuropathy.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

Science.gov (United States)

Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.