Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency.
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ABSTRACT:
SUBMITTER: Ortega MA
PROVIDER: S-EPMC8358866 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic cerebrospinal venous insufficiency (CCSVI) was implicated in the pathophysiology of multiple sclerosis (MS).We evaluated neurosonography (NS), magnetic resonance venography (MRV), and transluminal venography (TLV) in subsets of MS patients drawn from a single-center, prospective, case-control study of 206 MS and 70 non-MS volunteers.As previously reported, findings on high-resolution B-mode NS imaging with color and spectral Doppler of the extracranial and intracranial venous drainage consistent with CCSVI were similar among MS and non-MS volunteers (3.88% vs 7.14%; p = 0.266). Ninety-nine MS participants consented to intravascular contrast-enhanced 3D MRV to assess their major systemic and intracranial venous circulation, and 40 advanced to TLV that included pressure measurements of the superior vena cava, internal jugular, brachiocephalic, and azygous veins.NS findings and MRV patterns were discrepant for 26/98 evaluable subjects, including four with abnormal findings on NS that had normal venous anatomy by MRV. In no instance were TLV pressure gradients indicative of clinically significant functional stenosis encountered. The three imaging approaches provided generally consistent data with discrepancies referable to inherent technique properties.Our findings lend no support for altered venous outflow dynamics as common among MS patients, nor do they likely contribute to the disease process.
| S-EPMC3783583 | biostudies-literature
Project description:ObjectiveChronic cerebrospinal venous insufficiency (CCSVI) has been implicated in the pathophysiology of multiple sclerosis (MS). We sought to determine whether neurosonography (NS) provides reliable information on cerebral venous outflow patterns specific to MS.MethodsThis was a single-center, prospective case-control study of volunteer MS and non-MS participants. A neurosonologist, blind to the subjects' diagnosis, used high-resolution B-mode imaging with color and spectral Doppler to systematically investigate, capture, and record extracranial and intracranial venous drainage. These neuroimaging results were evaluated and scored by an expert blinded to subjects' information and with no interactions with the participants.ResultsAltogether, 276 subjects were studied: 206 with MS and 70 non-MS. MS patients were older than non-MS subjects (48.3±9.9 vs 44.3±11.8 years, p<0.007), with durations from first symptoms and diagnosis of 13.7±10 and 9.9±7.8 years, and Expanded Disability Status Scale of 2.6±2.0. Overall, 82 subjects (29.7%) fulfilled 1 of 5 NS criteria proposed for CCSVI; 13 (4.7%) fulfilled 2 criteria required for diagnosis, and none fulfilled >2 criteria. The distribution of subjects with 0, 1, or 2 criteria did not differ significantly across all diagnostic groupings, between MS and non-MS subjects, or within MS subgroups. CCSVI was present in 7.14% of non-MS and 3.88% of MS patients (p=0.266). No significant differences emerged between MS and non-MS subjects for extracranial or intracranial venous flow rates.InterpretationNS findings described as CCSVI are much less prevalent than initially reported, and do not distinguish MS from other subjects. Our findings do not support the hypothesis that CCSVI is causally associated with MS.
| S-EPMC3657573 | biostudies-literature
Project description:IntroductionChronic venous insufficiency (CVI) is a common disease affecting mainly lower limbs and significantly influencing the quality of life. This study aims to estimate the prevalence of CVI in the Qassim Region and test the effectiveness of compression stockings as an intervention option.MethodsA cross sectional study was conducted to assess the prevalence of CVI among patients visiting primary health care (PHC) centers in the Qassim Region. CVI patients were diagnosed and classified using the clinical, etiologic, anatomical, and pathophysiological (CEAP) scale. They were randomly divided into two groups, one using compression stockings and the other standard medical therapy. A clinical follow up was done using multiple scale system including CEAP scale. Data analysis was performed using SPSS.ResultsAmong the 226 screened patients, 138 (61.1%) were diagnosed as having CVI (69% female and 45% male, p<0.001). Compared to the baseline, both the clinical and venous scores for CVI at the follow-up were significantly lower among patients using compression stockings, p=0.002 and p=0.003, respectively. Regression analysis suggested that, after controlling for age, sex and body mass index, compliance was the main factor responsible for a significant reduction in the clinical score among CVI patients.ConclusionsChronic venous insufficiency is very common in the Qassim Region. Compression stockings are highly effective in improving clinical symptoms and signs of CVI.Trial registrationThis study is registered at www.clinicaltrials.gov(NCT02050061).
| S-EPMC4257358 | biostudies-literature
Project description: Not available
| S-EPMC8481765 | biostudies-literature
Project description:This article considers the use of autologous stem cell-derived cardiomyocytes as a novel means to aid venous return. The approach consists of creating external cuffs of engineered heart tissue around vein segments with incompetent or poorly competent valves. The engineered heart tissue cuff prevents distention of the impaired vein segments and aids unidirectional flow by its rhythmic contractions. There appear to be no fundamental limitations to this approach as feasibility of all of the individual components has already been shown. Here, we underline the clinical need for novel ways to treat chronic deep venous insufficiency, review previous research that enabled this approach, consider potential designs of engineered heart tissue cuffs, and outline its advantages and future challenges.
| S-EPMC5837029 | biostudies-literature
Project description:This study evaluated the stretching and dilatation of venous segments ex vivo in subjects with primary varicose veins in comparison with comparable segments from subjects that used the supplement Pycnogenol (150 mg/d) for 3 months before surgery. Subjects with varicose veins and chronic venous insufficiency voluntarily used Pycnogenol for a period of at least 3 months. The segments of veins removed with surgery (in 30 subjects that had used Pycnogenol and in 10 comparable control subjects that had not used the supplement) were compared with normal, unused vein segments harvested for bypass grafting. The segments were suspended and a weight was attached to the distal part of the veins for 3 minutes and dilated with pressurized water. Digital images were recorded; the veins were measured before and after stretching to evaluate elongation. The manipulation of the vein segment was minimal. Tests were completed within 20 minutes after harvesting the veins. All segments were 4 cm long. The stretching test indicated a significantly higher level of passive elongation in control, varicose segments (2.29; 0.65 mm) in comparison with 1.39; 0.2 mm in vein segments from Pycnogenol-using patients. The dilation test showed an average higher dilation (2.19; 0.3 mm) in control varicose veins in comparison with varicose veins from Pycnogenol-using patients (1.32; 0.7 mm) (p < 0.05). Stretching and dilatation were lower in veins from Pycnogenol-using subjects (p < 0.05). The measurement of destretching and the recovery after dilatation indicated a better tone and recovery of the original size/shape in varicose segments from patients using Pycnogenol. Varicose segments had a more significant persistent dilatation and elongation in comparison with normal vein segments. Pycnogenol seems to decrease passive dilatation and stretching and gives vein walls a greater tonic recovery and elasticity that allows the vein to recover its original shape after dynamic stresses.
| S-EPMC3933503 | biostudies-other
Project description: Not available
| S-EPMC3216457 | biostudies-literature
Project description:BackgroundChronic venous insufficiency (CVI) is a common disease that causes discomfort and impairs the quality of life of affected persons. Treatments such as physical exercise that aim to increase the movement of the ankle joint and strengthen the muscle pump in the calf of the leg may be useful to reduce the symptoms of CVI.ObjectivesTo assess and summarise the existing clinical evidence on the efficacy and safety of physical exercise programmes for the treatment of individuals with non-ulcerated CVI.Search methodsThe Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (May 2016). In addition, the CIS searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) and trial databases for details of ongoing or unpublished studies.Selection criteriaRandomised controlled trials (RCTs) comparing exercise with no exercise programmes.Data collection and analysisTwo review authors independently assessed the search results and selected eligible studies. We resolved disagreements by discussion. We summarised and double-checked details from included studies. We attempted to contact trial authors for missing data, but obtained no further information.Main resultsWe included two trials involving 54 participants with CVI. Many of our review outcomes were not reported or reported by only one of the two studies. The intensity of disease signs and symptoms was measured in both studies but using different scales; we were therefore unable to pool the data. One study reported no difference between the exercise and control groups whereas the second reported a reduction in symptoms in the exercise group. In one study, increases in change in ejection fraction compared with baseline (mean difference (MD) 4.88%, 95% confidence interval (CI) 3.16 to 6.60; 30 participants; P < 0.00001), half venous refilling time (MD 4.20 seconds, 95% CI 3.28 to 5.12; 23 participants; P < 0.00001) and total venous refilling time (MD 9.40 seconds, 95% CI 7.77 to 11.03; 23 participants; P < 0.00001) were observed in the exercise group compared with the control group. One study reported no difference between the exercise and control groups with regard to quality of life or ankle range of motion. Although muscle strength assessed by dynamometry at slow speed did not differ between the two groups in this study, variable peak torque at fast speed was lower in the control group than in the exercise group (2.8 ± 0.9 compared with -0.3 ± 0.6, P < 0.03). The incidence of venous leg ulcers, incidence of surgical intervention to treat symptoms related to CVI and exercise capacity were not assessed or reported in either of the included trials. We rated both included studies as at high risk of bias; hence, these data should be interpreted carefully. Due to the small number of studies and small sample size, we were not able to verify indirectness and publication bias. Therefore, we judged the overall quality of evidence as very low according to the GRADE approach.Authors' conclusionsThere is currently insufficient evidence available to assess the efficacy of physical exercise in people with CVI. Future research into the effect of physical exercise should consider types of exercise protocols (intensity, frequency and time), sample size, blinding and homogeneity according to the severity of disease.
| S-EPMC6463841 | biostudies-literature
Project description:Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa-/-|Xpa-/- mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes.
| S-EPMC5514997 | biostudies-literature
Project description:Recent advancements in near-infrared fluorescence lymphatic imaging (NIRFLI) technology provide opportunities for non-invasive, real-time assessment of lymphatic contribution in the etiology and treatment of ulcers. The objective of this study was to assess lymphatics in subjects with venous leg ulcers using NIRFLI and to assess lymphatic impact of a single session of sequential pneumatic compression (SPC).Following intradermal microdoses of indocyanine green (ICG) as a lymphatic contrast agent, NIRFLI was used in a pilot study to image the lymphatics of 12 subjects with active venous leg ulcers (Clinical, Etiologic, Anatomic, and Pathophysiologic [CEAP] C6). The lymphatics were imaged before and after a single session of SPC to assess impact on lymphatic function.Baseline imaging showed impaired lymphatic function and bilateral dermal backflow in all subjects with chronic venous insufficiency, even those without ulcer formation in the contralateral limb (C0 and C4 disease). SPC therapy caused proximal movement of ICG away from the active wound in 9 of 12 subjects, as indicated by newly recruited functional lymphatic vessels, emptying of distal lymphatic vessels, or proximal movement of extravascular fluid. Subjects with the longest duration of active ulcers had few visible lymphatic vessels, and proximal movement of ICG was not detected after SPC therapy.This study provides visible confirmation of lymphatic dysfunction at an early stage in the etiology of venous ulcer formation and demonstrates the potential therapeutic mechanism of SPC therapy in removing excess fluid. The ability of SPC therapy to restore fluid balance through proximal movement of lymph and interstitial fluid may explain its value in hastening venous ulcer healing. Anatomical differences between the lymphatics of longstanding and more recent venous ulcers may have important therapeutic implications.
| S-EPMC4782606 | biostudies-literature