Ghrelin and glucagon-like peptide-1 according to body adiposity and glucose homeostasis

ABSTRACT Objective: We investigated the biological behavior of ghrelin and glucagon-like peptide-1 (GLP-1) after a standard liquid meal according to body adiposity and glucose homeostasis. Subjects and methods: This cross-sectional study included 41 individuals (92.7% women; aged 38.3 ± 7.8 years; BMI 32.2 ± 5.5 kg/m²) allocated into three groups according to body adiposity and glucose homeostasis, as follows: normoglycemic eutrophic controls (CON, n = 11), normoglycemic with obesity (NOB, n = 15), and dysglycemic with obesity (DOB, n = 15). They were tested at fasting and 30 and 60 min after the ingestion of a standard liquid meal in which we measured active ghrelin, active GLP-1, insulin, and plasma glucose levels. Results: As expected, DOB exhibited the worst metabolic status (glucose, insulin, HOMA-IR, HbA1c) and an inflammatory status (TNF-α) at fasting, besides a more significant increase in glucose than postprandial NOB (p ≤ 0.05). At fasting, no differences between groups were detected in lipid profile, ghrelin, and GLP-1 (p ≥ 0.06). After the standard meal, all groups exhibited a reduction in ghrelin levels between fasting vs. 60 min (p ≤ 0.02). Additionally, we noticed that GLP-1 and insulin increased equally in all groups after the standard meal (fasting vs. 30 and 60 min). Although glucose levels increased in all groups after meal intake, these changes were significantly more significant in DOB vs. CON and NOB at 30 and 60 min post-meal (p ≤ 0.05). Conclusions: Time course of ghrelin and GLP-1 levels during the postprandial period was not influenced by body adiposity or glucose homeostasis. Similar behaviors occurred in controls and patients with obesity, independently of glucose homeostasis.

Acute effects of exercise with blood flow restriction on endothelial function in healthy young and older populations: a systematic review / Efeitos agudos do exercício com restrição do fluxo sanguíneo na função endotelial de jovens e idosos saudáveis: uma revisão sistemática

The objective of this review is to identify the acute effects of blood flow restriction (BFR) with vs without exercise on endothelial function in healthy individuals and the changes in endothelial function in young and older adults following different levels of exclusive BFR vs free flow. Systematic searches were performed in the following databases: PubMed, Web of Science, Scopus, and Cochrane Library, from inception to July 17, 2021. The studies included healthy individuals who underwent assessments of endothelial function before and after experimental protocols through endothelium-dependent flow-mediated dilatation. In total, 4890 studies were screened, and 6 studies of moderate-to-high methodological quality (Physiotherapy Evidence Database scores 6 ­ 10) including 82 subjects (aged 24 ­ 68 years) were eligible. Overall, flow-mediated dilatation increased in the non-cuffed arm immediately and 15 minutes after exercise, with no change in the cuffed arm (BFR of 60 ­ 80 mmHg). In protocols without exercise, cuff pressures of 25 ­ 30 mmHg applied for 30 minutes did not promote changes in the endothelial function, while those > 50 mmHg induced a dose-dependent attenuation of flow-mediated dilatation only in young individuals. A moderate level of BFR appears to have no effect on endothelial function after acute exercise. In non-exercise conditions, reductions in flow-mediated dilatation seem to result from increased retrograde shear provoked by cuff pressures ≥ 50 mmHg in young but not in older adults. An exercise-related increase in antegrade shear rate leads to a greater nitric oxide-mediated vasodilator response. However, BFR appears to attenuate this effect in young but not in older individuals. (AU)

O objetivo desta revisão foi identificar os efeitos agudos da restrição do fluxo sanguíneo (RFS) com vs. sem exercício na função endotelial de indivíduos saudáveis, bem como as alterações na função endotelial em jovens e idosos após diferentes níveis de RFS vs. fluxo livre. Pesquisas sistemáticas foram realizadas nas bases United States National Library of Medicine (PubMed), Web of Science, Scopus e Cochrane Library até 17 de julho de 2021. Os estudos incluíram indivíduos saudáveis que avaliaram a função endotelial antes e após protocolos experimentais, por meio da dilatação mediada por fluxo. Foi selecionado o total de 4.890 estudos, e foram elegíveis seis de moderada a alta qualidade metodológica (Physioterapy Evidence Database 6 ­ 10 pontos), incluindo 82 indivíduos (24 ­ 68 anos). No geral, a dilatação mediada por fluxo aumentou no braço sem manguito, imediatamente e 15 minutos após o exercício, sem alteração no braço com manguito (RFS de 60 ­ 80 mmHg). Em protocolos sem exercício, pressões do manguito de 25 ­ 30 mmHg aplicadas por 30 minutos não promoveram alterações na função endotelial, enquanto aquelas > 50 mmHg induziram uma atenuação dose-dependente da dilatação mediada por fluxo em indivíduos jovens. Um nível moderado de RFS parece não ter efeito na função endotelial após uma sessão de exercício. Em condições sem exercício, as reduções na dilatação mediada por fluxo parecem resultar do aumento do cisalhamento retrógrado provocado por pressões do manguito ≥ 50 mmHg em jovens, mas não em idosos. O aumento da taxa de cisalhamento anterógrado relacionada ao exercício leva a maior resposta vasodilatadora mediada pelo óxido nítrico. No entanto, a RFS parece atenuar esse efeito em jovens, mas não em . (AU)

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children / Aptidão e atividade física, perfil metabólico, adipocinas e função endotelial em crianças

Abstract Objectives: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Method: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). Results: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p < 0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p < 0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p < 0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho = −0.41; p = 0.01), and this association remained after adjusting for body mass index z-score (rho = 0.28; p = 0.03). Conclusion: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Resumo: Objetivos: A prevalência da obesidade está aumentando. O objetivo deste estudo foi investigar se há disfunção endotelial nas crianças com peso normal ou excesso de peso e se o perfil metabólico, as adipocinas e a disfunção endotelial seriam mais fortemente associados à aptidão física ou aos níveis de atividade física. Método: Estudo transversal que envolve crianças de 5-12 anos. A avaliação incluiu pletismografia de oclusão venosa, níveis séricos de adiponectina, leptina, insulina e lipidograma, escore de atividade física (questionário PAQ-C) e avaliação da aptidão física (teste Yo-yo). Resultados: Um total de 62 crianças participou deste estudo. Com base no índice de massa corporal, 27 eram eutróficos, 10 estavam acima do peso e 25 estavam obesos. Os níveis de triglicerídeos, colesterol LDL, HOMA-RI e leptina estavam mais elevados nas crianças obesas e com excesso de peso que o grupo de eutróficos (p < 0,01). Os níveis de colesterol HDL e adiponectina estavam mais elevados no grupo de eutróficos em comparação ao grupo de obesos e com excesso de peso (p < 0,01). A vasodilatação mediada pelo fluxo após hiperemia foi maior no grupo de eutróficos em comparação aos indivíduos obesos e com excesso de peso (p < 0,05). Não houve nenhuma diferença nos níveis de atividade física entre os grupos medidos pelo PAQ-C. O teste de ida e volta foi significativamente associado ao colesterol HDL (ró = −0,41; p = 0,01) e essa associação continuou após ajustar o escore z do índice de massa corporal (ró = 0,28; p = 0,03). Conclusão: Este estudo mostrou que a disfunção endotelial já está presente nas crianças obesas, sugeriu uma predisposição à doença aterosclerótica. Além disso, os níveis de colesterol HDL foram correlacionados à aptidão física, independentemente do índice de massa corporal.

Obesity and gut microbiota - what do we know so far? / Obesidade e microbiota intestinal - o que sabemos até agora?

In the history of medicine, only recently has obesity been recognized as a disease. We know now that it is a pandemic condition, partly explained by the so-called Western lifestyle and related to multiple other comorbidities in various systems. This lyfestyle includes eating large portions, rich in saturated fats and refined sugar, all coupled with sedentary habits. In recent years, the gut microbiota has been indited as a new culprit in pathophysiological aspects involved in obesity. From studies with animals free of bacteria in the digestive tract, known as "germ-free animals", the relevance of intestinal microbiota in the regulation of body fat became evident and its importance has also been extended to the pathophysiology of diseases such as diabetes mellitus and coronary heart disease. Characterization of Toll-like receptors led to the discovery of mechanisms that link the immune system with some metabolic pathways and opened new avenues of a previously unknown world to biological sciences. Increased knowledge about interactions between gut microbiota and the host can certainly reveal, in a not too distant future, new therapeutic perspectives for obesity and its related diseases.

Na história da medicina apenas recentemente a obesidade foi reconhecida como uma doença. Sabemos agora que é uma doença pandêmica, explicada em parte pelo chamado estilo de vida ocidental e relacionado a múltiplas outras comorbidades em vários sistemas. O referido estilo de vida inclui comer grandes porções, ricas em gorduras saturadas e açúcares refinados, e hábitos sedentários. Nos últimos anos, a microbiota intestinal foi associada aos aspectos fisiopatológicos envolvidos na obesidade. De estudos com animais livres de bactérias no trato digestivo, conhecidos como "animais sem germes", a relevância da microbiota intestinal na regulação da gordura corporal tornou-se evidente e sua importância também se estendeu à fisiopatologia de doenças como diabetes mellitus e doença cardíaca coronária. A caracterização dos receptores "Toll-like" levou à descoberta de mecanismos que ligam o sistema imunológico a algumas vias metabólicas e abriram novas avenidas de um mundo anteriormente desconhecido para as ciências biológicas. O aumento do conhecimento sobre as interações entre a microbiota intestinal e o hospedeiro certamente pode revelar, em um futuro não muito distante, novas perspectivas terapêuticas para a obesidade e suas doenças relacionadas.

Vascular and Inflammatory Acute Responses after a Resistance Exercise Session in Young Women with Excessive Adiposity / Respostas vasculares e inflamatórias agudas depois de uma sessão de exercício resistido em mulheres jovens com excesso de adiposidade

BACKGROUND: Endothelial dysfunction and low-grade inflammation are both positively associated to states of excessive adiposity but reports on the acute effects of resistance exercise on these variables are still lacking. We evaluated these acute effects of resistance exercise on vascular reactivity and on the inflammatory profile in young women. METHODS: Participants were divided into two groups: lean Controls (n=16) and Overweight (n=16). The resistance exercise session consisted of unilateral elbow flexions for five sets of 10 repetitions at 70% of one repetition maximum. Blood pressure, heart rate, forearm blood flow, vascular conductance, cytokines, adipopeptides and endothelin-1 were evaluated at rest and during the acute post-exercise period. RESULTS: The overweight group had higher forearm blood flow at rest (p=0.03) and during post-exercise (p<0.001) while forearm vascular conductance was higher only during post-exercise, at 20 (p=0.02) and 40 min (p<0.001). Endothelial-dependent vasodilation was higher during the post-exercise period in the Overweight group compared to controls (p=0.01). In the Overweight group, the resistance exercise session reduced interleukin-6 (p=0.02) and leptin (p<0.001) but increased endothelin-1 levels (p=0.02). CONCLUSIONS: We conclude that the single resistance exercise session elicited an acute increment of baseline vascular reactivity and an increased endothelial-dependent vasodilation with concomitant changes in inflammatory profile and endothelin-1 in our tested women with excessive adiposity.

ANTECEDENTES: A disfunção endotelial e a inflamação de baixo grau estão positivamente associadas a estados de adiposidade excessiva; entretanto os efeitos agudos do exercício resistido sobre estas variáveis ainda não estão esclarecidos. Avaliamos os efeitos agudos do exercício resistido sobre a reatividade vascular e sobre o perfil inflamatório em mulheres jovens. MÉTODOS: As participantes foram divididas em dois grupos: controles magras (n = 16) e aquelas com sobrepeso (n = 16). A sessão de exercício resistido consistiu de flexões unilaterais de cotovelo em cinco séries de 10 repetições (com 70% de uma repetição máxima). Avaliamos tanto no repouso quanto durante o período pós-exercício agudo a pressão arterial, a frequência cardíaca, o fluxo sanguíneo do antebraço (FBF) e a condutância vascular (CVF), as citocinas, os adipopeptídeos e a endotelina-1. RESULTADOS: O grupo com sobrepeso apresentou maior FBF em repouso (p = 0,03) e pós-exercício (p <0,001), enquanto a CVF foi maior somente após o exercício, aos 20 min (p = 0,02) e aos 40 min (p <0,001) . A vasodilatação endotélio-dependente durante o período pós-exercício foi maior no grupo Overweight em relação aos controles (p = 0,01). No grupo Overweight, a sessão de exercício resistido reduziu a interleucina-6 (p = 0,02) e a leptina (p <0,001) e o aumentou os níveis de endotelina-1 (p = 0,02). CONCLUSÃO: Concluímos que a sessão de exercício resistido provocou um incremento agudo da reatividade vascular basal e um aumento da vasodilatação endotélio-dependente com alterações concomitantes no perfil inflamatório e da endotelina-1 em mulheres com adiposidade excessiva.

Dislipidemia e risco cardiovascular em afrodescendentes: um estudo em comunidades quilombolas do Maranhão, Brasil / Dyslipidemia and cardiovascular risk in Afro-descendants: a study of the Quilombola communities in Maranhão, Brazil / La dislipidemia y el riesgo cardiovascular en los afrodescendientes: un estudio sobre comunidades quilombolas de Maranhão, Brasil

Objetivos: avaliar os fatores de risco cardiovascular associados à dislipidemia em comunidades quilombolas do Maranhão, Brasil. Métodos: um estudo transversal foi realizado no período de fevereiro de 2010 a novembro de 2011 em 202 indivíduos pertencentes às comunidades quilombolas de Codó-MA. Avaliaram-se os fatores de risco associados à dislipidemia e síndrome metabólica (SM). Resultados: o estudo mostrou alta prevalência de dislipidemia (72,28%) e de hipertensão arterial (43,07%). Houve predomínio de hipertrigliceridemia isolada (38,61%) com valores de lipoproteína de alta densidade e lipoproteína de baixa densidade normais na maioria dos indivíduos. A prevalência de síndrome metabólica e o risco cardiovascular estimado foram baixos nesta população. Conclusão: houve grande prevalência de dislipidemia, à custa de triglicerídeos, e hipertensão; entretanto, a frequência de outros fatores de risco para eventos cardiovasculares foi baixa. Uma baixa prevalência de SM e de risco cardiovascular, segundo o escore de Framingham para doenças cardiovasculares, também foi identificada.

Objective: to evaluate the prevalence of cardiovascular risk factors associated with dyslipidemia in Quilombola communities in Maranhão, Brazil. Methods: a cross-sectional study was performed from February 2010 to November 2011. A total of 202 individuals belonging to the Quilombola communities in Codó, Maranhão were assessed. Risk factors associated with dyslipidemia and metabolic syndrome (MS) were evaluated. Results: the results showed a high prevalence of dyslipidemia (72.28%) and hypertension (43.07%). Isolated hypertriglyceridemia (38.61%) with normal levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol was present in most individuals. Furthermore, the prevalence of MS and the estimated cardiovascular risks were low in this population. Conclusion: dyslipidemia, at the expense of triglycerides, and hypertension was highly prevalent. However, the frequency of other risk factors for cardiovascular events was low. A low prevalence of MS and cardiovascular risk according to the Framingham score for cardiovascular diseases was also identified.

Objetivos: evaluar los factores de riesgo cardiovascular asociados con dislipidemia en comunidades quilombolas de Maranhão, Brasil. Métodos: un estudio transversal se realizó entre febrero del 2010 hasta el noviembre del 2011 en 202 individuos pertenecientes a comunidades quilombolas de Codó-MA. Se evaluaron los factores de riesgo asociados con la dislipidemia y el síndrome metabólico (SM). Resultados: el estudio mostró una alta prevalencia de la dislipidemia (72,28%) y de la hipertensión (43,07%). Hipertrigliceridemia aislada (38,61%) con valores de lipoproteínas de alta densidad y lipoproteínas de baja densidad normales estuvieron presentes en la mayoría. La prevalencia del síndrome metabólico y riesgo cardiovascular estimado fue bajo en esta población. Conclusión: hubo una alta prevalencia de dislipidemia, a expensas de los triglicéridos e hipertensión, no obstante, la frecuencia de otros factores de riesgo de eventos cardiovasculares fue baja. Una baja prevalencia de SM y el riesgo cardiovascular según la puntuación de riesgo de Framingham para la enfermedad cardiovascular también se ha identificado.

Gender differences in microcirculation: Observation using the hamster cheek pouch

OBJECTIVES: Estrogen has been shown to play an important protective role in non-reproductive systems, such as the cardiovascular system. Our aim was to observe gender differences in vivo with regard to the increase in macromolecular permeability and leukocyte-endothelium interaction induced by ischemia/reperfusion as well as in microvascular reactivity to vasoactive substances using the hamster cheek pouch preparation. METHODS: Thirty-six male and 36 female hamsters, 21 weeks old, were selected for this study, and their cheek pouches were prepared for intravital microscopy. An increase in the macromolecular permeability of post-capillary venules was quantified as a leakage of intravenously injected fluorescein-labeled dextran, and the leukocyte-endothelium interaction was measured as the number of fluorescent rolling leukocytes or leukocytes adherent to the venular wall, labeled with rhodamin G, during reperfusion after 30 min of local ischemia. For microvascular reactivity, the mean internal diameter of arterioles was evaluated after the topical application of different concentrations of two vasoconstrictors, phenylephrine (α1-agonist) and endothelin-1, and two vasodilators, acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). RESULTS: The increase in macromolecular permeability induced by ischemia/reperfusion was significantly lower in females compared with males [19 (17-22) leaks/cm2 vs. 124 (123-128) leaks/cm2, respectively, p<0.001), but the number of rolling or adherent leukocytes was not different between the groups. Phenylephrine-induced arteriolar constriction was significantly lower in females compared with males [77 (73-102)% vs. 64 (55-69)%, p<0.04], but there were no detectable differences in endothelin-1-dependent vasoreactivity. Additionally, arteriolar vasodilatation elicited by acetylcholine or sodium nitroprusside did not differ between the groups. CONCLUSION: The ...

Evaluation of sublingual microcirculation in children with dengue shock

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target. .

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability.

Avaliação da microcirculação: uma nova arma no manejo da sepse? / Microcirculatory assessment: a new weapon in the treatment of sepsis?

A evolução para disfunção de múltiplos órgãos ainda é comum na sepse e está relacionada diretamente com a disfunção microcirculatória. Através de pesquisa nas bases de dados PubMed, empregando-se os unitermos microcirculação e sepse, vinte e seis artigos foram selecionados para esta revisão, bem como citações consideradas relevantes extraídas de artigos de revisão. Com o advento da técnica de imagem obtida através de polarização ortogonal, que permite a observação à beira do leito da microcirculação em pacientes críticos, é possível estabelecer uma relação entre disfunção microvascular e prognóstico, além de observar diretamente o efeito de diferentes intervenções terapêuticas. No entanto, a relação causal entre disfunção microcirculatória e prognóstico adverso na sepse, bem como os efeitos de terapias dirigidas para correção destas anormalidades microcirculatórias ainda precisam ser melhor definidos.

The progression into multi-organ failure continues to be a common feature of sepsis and is directly related to microcirculatory dysfunction. Based on a PubMed database search using the key words microcirculation and sepsis, twenty-six articles were selected for this review. The relevant references from these articles were also selected and included in this analysis. Orthogonal polarization spectral imaging allows for the bedside assessment of the microcirculation of critically ill patients. Such imaging has established a correlation between microvascular dysfunction and patient outcomes, which allows practitioners to directly assess the effects of therapeutic interventions. However, the causal relationships between microcirculatory dysfunction, adverse outcomes, and the effects of therapies aimed at these microcirculatory changes in sepsis, are not clear.

Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin-induced diabetic hamsters

OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g) were injected with streptozotocin (50 mg/kg, i.p.) or vehicle either 6 (the diabetes mellitus 6 group) or 15 (the diabetes mellitus 15 group) days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, α-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes.

Organic grape juice intake improves functional capillary density and postocclusive reactive hyperemia in triathletes

OBJECTIVE: The aim of this study was to evaluate the effect of organic grape juice intake on biochemical variables and microcirculatory parameters in triathlon athletes. INTRODUCTION: The physiological stress that is imposed by a strenuous sport, such as a triathlon, together with an insufficient amount of antioxidants in the diet may cause oxidative imbalance and endothelial dysfunction. METHODS: Ten adult male triathletes participated in this study. A venous blood sample was drawn before (baseline) and after 20 days of organic grape juice intake (300 ml/day). Serum insulin, plasma glucose and uric acid levels, the total content of polyphenols, and the erythrocyte superoxide dismutase activity were determined. The functional microcirculatory parameters (the functional capillary density, red blood cell velocity at baseline and peak levels, and time required to reach the peak red blood cell velocity during postocclusive reactive hyperemia after a one-min arterial occlusion) were evaluated using nailfold videocapillaroscopy. RESULTS: Compared with baseline levels, the peak levels of serum insulin ( p = 0.02), plasma uric acid ( p = 0.04), the functional capillary density ( p = 0.003), and the red blood cell velocity (p < 0.001) increased, whereas the plasma glucose level (p,0.001), erythrocyte superoxide dismutase activity ( p = 0.04), and time required to reach red blood cell velocity during postocclusive reactive hyperemia ( p = 0.04) decreased after organic grape juice intake. CONCLUSION: Our data showed that organic grape juice intake improved glucose homeostasis, antioxidant capacity, and microvascular function, which may be due to its high concentration of polyphenols. These results indicate that organic grape juice has a positive effect in endurance athletes.

Parâmetros microcirculatórios e clínicos em pacientes com lipodistrofia ginoide tratadas topicamente com alho (15 ppM) / Microcirculatory and clinical parameters in patients with gynoid lipodystrophy treated with topical garlic (15PPM)

Introdução: Lipodistrofi a ginoide, popularmente conhecida como celulite, é considerada por milhões de mulheres como problema estético preocupante. Estudos recentemente publicados demonstraram que o extrato de alho pode ter utilidade para melhorar a lipólise e diminuir a lipogênese. Objetivo: O objetivo primário foi determinar se a aplicação tópica de uma loção contendo alho (15 ppm) melhoraria os parâmetros de celulite. Material e Métodos: 50 mulheres foram tratadas topicamente com uma loção contendo 15 ppm de alho. Todas as pacientes trataram uma perna, não trataram a outra e foram avaliadas (mensuração do diâmetro da coxa) antes do início do tratamento e depois em intervalos quinzenais, até oito semanas depois do início do tratamento. Em oito das participantes, os parâmetros microcirculatórios [velocidade dos eritrócitos nas arteríolas e vênulas (mm/s), densidade capilar funcional (DCF), diâmetro da papila dérmica (µm) e diâmetro do capilar (µm)] foram medidos por Cytoscan®. O exato local na coxa para essas mensurações foi marcado numa folha transparente como garantia de que todas as medidas seriam tomadas no mesmo lugar. Seis mulheres participantes do grupo de exame por Cytoscan® também foram avaliadas por ultrassom, para determinar a espessura do tecido subcutâneo. Resultados: Depois do tratamento com alho, ocorreu redução de 1,62 cm no diâmetro da coxa tratada (p < 0,001) sem mudanças signifi cativas nos diâmetros da papila e dos capilares, mas a DCF melhorou signifi cativamente (p < 0,03), tendo ocorrido redução na espessura da epiderme e da derme depois do tratamento tópico com alho. Conclusões: O uso de extrato de alho na concentração de 0,0015% resultou em melhora clínica, microcirculatória e ultrassonográfi ca signifi cativa da celulite.

Introdução: Gynoid lipodystrophy, popularly known as cellulite, is regarded as an issue of cosmetic concern to millions of women. Recent studies have shown that garlic extract can be useful to enhance lipolysis and decrease lipogenesis. Objective: The primary objective was to determine if topical application of a lotion containing garlic (15 ppm) would improve cellulite parameters. Material and Methods: 50 women were treated topically with a lotion containing 15 ppm of garlic. All patients treated one leg, did not treat the other one and were evaluated (measurement of thigh diameter) before and in biweekly intervals up to 8 weeks after the onset of treatment. On eight of these subjects, microcirculatory parameters [red blood cell velocity in arterioles and venules (mm/s), functional capillary density (FCD), diameter of the dermal papilla (µm) and capillary diameter (µm)] were measured using the Cytoscan®. The exact thigh local for these measurements was marked in a transparent sheet, to assure that all of them were performed on the same place. Six women that performed the Cytoscan® exam group were also evaluated by ultrasound to determine the thickness of subcutaneous tissue. Results: after garlic treatment, there was a reduction of 1.62 cm on the diameter of the treated thigh (p < 0.001) without signifi cant changes on papilla and capillary diameters, but FCD improved signifi cantly (p < 0.03) and epidermis and dermis thickness decreased after topical garlic treatment. Conclusions: Garlic extract at a concentration of 0.0015% showed signifi cant clinical, microcirculatory and ultrasonographic improvement of cellulite.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion / Alterações metabólicas associadas à obesidade: o papel da disfunção da microcirculação tecidual

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 µm), 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 rennin-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.

Associada ao aumento do risco de eventos cardiovasculares e ao câncer, a obesidade é um problema mundial, que atinge tanto países desenvolvidos quanto em desenvolvimento. A microcirculação é composta por arteríolas, capilares e vênulas (diâmetro interno médio < 100 µm) e é o local onde ocorrem a oferta de nutrientes e as trocas entre o tecido e o sangue. A disfunção microcirculatória é um evento precoce na obesidade e este pode ser secundário à disfunção endotelial ou à redução no número de capilares (rarefação capilar). Novas técnicas em pesquisa permitem a avaliação da microcirculação em diferentes leitos vasculares em humanos. Estudos sugerem uma correlação entre disfunção endotelial e obesidade visceral. Acredita-se que o estresse oxidativo, a inflamação e a atividade aumentada do sistema renina-angiotensina estão entre os fatores envolvidos nessa associação. O comprometimento microcirculatório presente na obesidade sugere que esse pode ser um fator causal importante nas desordens relacionadas com a obesidade, como resistência insulínica e hipertensão.

Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9 percent saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm²), distance from the skin flap base to blood flow cessation (Dist with flow, in cm), percentage of viable skin (VA, in percent), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50 percent. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery.

Short-term treatment with metformin improves the cardiovascular risk profile in first-degree relatives of subjects with type 2 diabetes mellitus who have a metabolic syndrome and normal glucose tolerance without changes in C-reactive protein or fibrinogen

OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen. INTRODUCTION: Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation. METHODS: Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5-50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32-42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels. RESULTS: Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4-323.7] mg/L vs. 286.7 [249.6-295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3-1.2] vs. 0.64 [0.3-1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6-347.6] mg/L vs. 290.9 [251.5-301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3-1.1] vs. 0.80 [0.4-0.9] mg/L; NS) in the metformin group. CONCLUSIONS: Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.

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 percent. 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.

Microcirculation in obesity: an unexplored domain

Obesity is traditionally linked to diabetes and cardiovascular diseases. Very recent experimental, clinical and epidemiological, sometimes provocative, data challenge this automaticity by showing that not the amount but the distribution of fat is the important determinant. Moderate abdominal fat accumulation may thus be more harmful than even consequent overweight. In view of the worldwide burden of obesity, factors leading to it in children and young adults must urgently be identified. Since obesity is a very complex cardiometabolic situation, this will require to focus investigations on uncomplicated obese subjects and adequate animal models. The recent discovery of intergenerational transmissions of obesity risk factors and also the key role played by gestational and perinatal events (epigenetic factors) give rise to completely new concepts and research avenues. Considering the potential close relationship between microcirculation and tissue metabolism, demonstrations of structural and/or functional abnormalities in microvascular physiology very early in life of subjects at risk for obesity might provide a solid basis for further investigations of such links. Microcirculation(arterioles, capillaries and venules) is conceivably a key compartment determining over one or several decades the translation of genetic and epigenetic factors into fat accumulation. Available animal models should serve to answer this cardinal question.

A obesidade é tradicionalmente associada ao diabetes e adoenças cardiovasculares. Dados muito recentes, algumasvezes provocativos, experimentais, clínicos e epidemiológicos questionam essa associação automática mostrando que não é a quantidade, mas a distribuição de gordura que é o determinante importante. O acúmulo moderado de gordura abdominal pode ser mais danoso que o conseqüente sobrepeso. Tendo em vista o aumento mundial da obesidade, fatores que levam a isso em crianças e adultos jovens devem ser urgentemente identificados. Como a obesidade é uma situação cardiometabólica muito complexa, essa identificação deve ser feita em obesos não-complicados e em modelos animais adequados. A recente descoberta da transmissão inter-geração de fatores de risco da obesidade e também do papel fundamental da gestação e de eventos perinatais (fatores epi-genéticos) dão origem a conceitos e linhas de pesquisa completamente novos. Considerando a estreita relação potencial entre a microcirculação e o metabolismo tecidual, demonstrações de anormalidades estruturais e/ou funcionais na fisiologia microvascular muito cedo na vida de pessoas com risco para obesidade podem fornecer uma base sólida para investigações futuras dessas ligações. A microcirculação (arteríolas, capilares e vênulas) é conceitualmente um compartimento chave na determinação em uma ou várias décadas dos fatores genéticos e epi-genéticos em acúmulo de gordura. Os modelos experimentais disponíveis devem servir para responder essa questão extremamente relevante.

A reologia microvascular das microesferas de perfluoropropano na presença da isquemia-reperfusão, diabetes e sepsis / The microvascular reology of ultrasound contrast in ischemia-reperfusion injury, diabetes and sepsis

Fundamentos: A adesão das microesferas aos leucócitos no tecido inflamado tem sido discutida, porém, pouco se sabe sobre seu comportamento nos capilares. A avaliação dos efeitos circulatórios desse agente pode trazer informações sobre sua ação no miocárdio. Objetivo: Avaliar o comportamento microvascular e hemodinâmico das microesferas nos seguintes grupos: controle, isquemia-reperfusão, diabetes tipo 2, diabetes com isquemia e sepsis. Métodos: Experimentalmente estudou-se a microcirculação da bolsa da bochecha de 65 hamsters machos, sendo separados por grupos conforme a indução da doença de base G-1 igual isquemia/reperfusão. GD igual diabetes, GDI igual diabetes com isquemia GS igual sepsis em relação ao GC (grupo controle). Dentro de cada grupo avaliou-se a pressão arterial...