Daniel Bottino

Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome

PURPOSE Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF) and vascular resistance (VR) responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach) and independent (sodium nitroprusside-SNP) vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.

Evaluation of the effects of caffeine in the microcirculation and edema on thighs and buttocks using the orthogonal polarization spectral imaging and clinical parameters.

Gynoid lipodystrophy, also known as cellulite, is a common multifactorial entity that affects millions of women around the world. There have been few scientific articles dealing with its physiology and treatment in the past few years, and vascular changes seem to play an important role in its pathophysiology. Skin microvascular alterations can be observed noninvasively with a new method called orthogonal polarization spectral imaging, which was used to evaluate the effectiveness of an anticellulite drug composed mainly of a 7% caffeine solution. Microcirculatory parameters evaluated were functional capillary density (FCD; number of flowing capillaries per unit area), diameter of the dermic papilla (DPD), and capillary diameter (CD). The clinical parameters analyzed were centimetrical measurements of thighs and hips and the influence of tobacco, alcohol, and physical activities on the efficacy of the treatment. After 1 month of treatment, statistical application of chi‐squared and Z approximation tests showed, in treated patients, statistically significant reduction of thigh circumferences in more than 80% of the cases and reduction of hip circumference in 67.7%. FCD, DPD, and CD did not change significantly after treatment. Smoking as well as alcohol consumption and regular physical activity were not significantly related to the centimetrical reduction observed in treated thighs and hips.

Sidestream dark field imaging: the evolution of real-time visualization of cutaneous microcirculation and its potential application in dermatology

Technological advances during the last years have enhanced the image quality of the microcirculation. Intravital microscopy (IM) has been considered the “gold standard” for many years, but it can be used mostly in anesthetized animals which is a disadvantage. The nailfold videocapillaroscopy, a non-invasive examination that includes a microscope with an epiillumination system, came afterward, but its major disadvantage is the restricted area available for investigation namely the nailfold capillary bed. The orthogonal polarization spectral (OPS) imaging technique, where reflected light allows the visualization of the microcirculation, was the next non-invasive exam, but it still presents some drawbacks such as suboptimal capillary visualization and image blurring due to red blood cell movements. Excessive probe pressure modifies red blood cell velocity. There is suboptimal imaging of capillaries due to motion-induced image blurring by movements of OPS device, tissue and/or flowing red blood cells. Sidestream dark field (SDF) imaging is the newest tool for microcirculatory research. Illumination is provided by concentrically placed light-emitting diodes to avoid image blurring and to enhance image contrast. It represents a simple and non-invasive imaging technique, with low cost, good portability and high sensitivity that provides fine, well-defined images. In addition, the microcirculation can be studied through laser Doppler flowmetry (LDF) or reflectance-mode confocal-laser-scanning microscopy (RCLM). However, LDF cannot show microcirculatory vessels and high cost of RCLM can be an inconvenience. New applications of SDF technique could include skin microcirculatory evaluation and allow dermatological studies on psoriasis, skin tumors and leprosy.

Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome.

Aims  Insulin resistance and a parental history of diabetes mellitus are independently associated with endothelial dysfunction. Oxidative stress has a pivotal role in the pathophysiology of vascular injury. Metformin, in addition to its glucose‐lowering properties, has vasculoprotective effects. We investigated whether metformin has beneficial effects on the nutritive skin capillary circulation and deceases oxidative stress in a group at high risk for Type 2 diabetes mellitus (T2DM) and cardiovascular disease.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm2, p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm2, p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm2, p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1%. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 microm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and renin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

Effects of Cilostazol and Pentoxifylline on Forearm Reactive Hyperemia Response, Lipid Profile, Oxidative Stress, and Inflammatory Markers in Patients With Intermittent Claudication

Peripheral arterial disease may lead to lower limb claudication and increased risk of systemic vascular dysfunction. In this article, the authors have investigated the peripheral vascular dysfunction evaluating forearm blood flow using venous occlusion plethysmography, lipid profile, and C-reactive protein in 60 patients with moderate intermittent claudication treated during 20 weeks with placebo (n = 16), cilostazol (200 mg/d; n = 17), or pentoxifylline (1200 mg/d; n = 15) in a randomized double-blinded clinical trial, taking into account smoking. Forearm blood flow after reactive hyperemia response (FBFh ) or oral nitroglycerine spray to evaluate endothelial-dependent and endothelial-independent vasodilation, respectively, pain-free and maximal walking distance, levels of C-reactive protein, triglycerides, cholesterol, low-density lipoprotein, and high-density lipoprotein—cholesterol in plasma were determined. The results showed that there was an improvement in the high-density lipoprotein—cholesterol, pain-free and maximal walking distance, and FBFh independent of treatment in nonsmoking patients. Cilostazol increased high-density lipoprotein—cholesterol level, maximal walking distance, and FBFh, whereas pentoxifylline reduced C-reactive protein level and increased maximal walking distance in total and nonsmoking groups. No treatment was effective in smokers

Does endothelial dysfunction correlate better with waist-to-hip ratio than with body mass index or waist circumference among obese patients?

PURPOSE Obesity is associated with cardiovascular disease, affecting large arteries and the microcirculation. Waist circumference and body mass index are routinely employed as measures for assessing obesity-related health risk, whereas waist-to-hip ratio is not. We aimed to investigate the association between brachial vascular reactivity and body mass index, waist circumference, and waist-to-hip ratio. METHODS Eighty-five volunteers (21 men/66 women), aged between 20 and 55 years, underwent determination of waist circumference, body mass index, waist-to-hip ratio, and endothelial function by venous occlusion plethysmography. Forearm blood flow was measured in response to intrabrachial artery infusions of 3 different concentrations of endothelium-dependent (acetylcholine 7.5, 15, and 30 mg/min) and endothelium-independent (sodium nitroprusside 2, 4, and 8 mg/min) vasodilators. RESULTS There was an inverse correlation of body mass index and waist circumference with forearm blood flow increments after acetylcholine and sodium nitroprusside infusions, while waist-to-hip ratio showed an inverse correlation with forearm blood flow increments only after acetylcholine. When subjects older than 40 years (n = 25) were excluded from the analysis, the inverse correlation of body mass index with forearm blood flow increments after acetylcholine infusion no longer existed, while waist circumference and waist-to-hip ratio showed the same results observed before. CONCLUSION The waist-to-hip ratio is probably a better estimator of endothelial dysfunction and possibly of cardiovascular risk than body mass index. These findings underscore the importance of routinely collecting hip circumference as an obesity index and risk estimator.

Micronization enhances the protective effect of purified flavonoid fraction against postischaemic microvascular injury in the hamster cheek pouch

1. The present study was designed to evaluate the effect of micronization on the protective effect of the purified flavonoid fraction (MPFF) on increases in macromolecular permeability induced by ischaemia–reperfusion in the hamster cheek pouch microcirculation.

Nailfold videocapillaroscopy in primary Sjögren's syndrome.

Nailfold videocapillaroscopy was performed in 2 groups of subjects: 14 healthy volunteers (C) and 15 patients with primary Sjögren’s syndrome (PSS). This was a controlled clinical trial, matched by age and sex. The aims of this study were to evaluate (1) functional capillary density (number of capillaries with flowing red blood cells per mm2, FCD); (2) capillary red blood cell velocity at rest (RBV), maximum capillary red blood cell velocity (RBVmax) after 1 minute ischemia, and the time to reach it (TRBVmax), taking into account the presence or absence of Raynaud’s phenomenon (RP) in the analysis; (3) nailfold capillary morphology; and (4) afferent (AFD), apical (APD), and efferent (EFD) capillary diameters. The mean values obtained for controls versus patients, respectively, were (mean ± SD): FCD (per mm2) 8.0 ±1.6 and 10.1 ±3.6; RBV (mm/s) 0.9 ±0.4 and 0.7 ±0.2; RBVmax (mm/s) 1.7 ±0.9 and 1.3 ±0.3; TRBVmax (s) 4.5 ±0.8 and 5.8 ±1.6 (p=0.02); and TRBVmax (s) in patients with RP=6.7 ±1.6 and without RP=5.6 ±1.6 (p=0.52). The correlation between RBV and RBVmax for each group, using the Pearson’s coefficient, was significant only for the control group (p=0.007), estimated correlation coefficient = 0.68. Controls and patients showed, in the majority of fields examined, normal morphologic patterns of capillaries. The capillary diameters were AFD (μm) 10.8 ±1.5 and 11.3 ±1.8; APD (μm) 16.3 ±2.4 and 16.8 ±2.9; and EFD (μm) 12.3 ±1.4 and 13.7 ±1.9. These results indicate that these patients have longer time to reach RBVmax, suggesting an impairment of the reactive hyperemia response, which could correlate with clinical features of the disease, ie, abnormal macrovascular and microvascular reactivity.