El fondo de ojo, una ventana a la microvasculatura del paciente hipertenso / The fundus, a window to microvasculature in hypertensive patients

Introducción: La hipertensión arterial constituye una de las enfermedades más frecuentes en la población general. En la actualidad llega a una prevalencia global del 30 al 45 %. La microcirculación retiniana puede considerarse como una representación anatómica de las características fisiológicas y funcionales de la circulación coronaria y cerebral. Objetivos: Profundizar en la relación existente entre los niveles de presión arterial y el daño del órgano diana, específicamente a través del fondo de ojo, así como de las posibles complicaciones oftalmológicas derivadas de la hipertensión arterial, y la comparación de algunas de las clasificaciones existentes sobre los cambios oftalmológicos que esta provoca. Métodos: Se emplearon los métodos de análisis-síntesis y análisis bibliográfico y documental. Los motores de búsqueda utilizados fueron: Google y Google Académico, y las bases de datos Hinari, SciELO Cuba, Pubmed, entre otras. Conclusiones: La retinopatía hipertensiva es una de las complicaciones adversas de la hipertensión arterial aguda o crónica. Por su parte, las oclusiones venosas y la formación de macroaneurismas, constituyen otras de gran envergadura. Mientras más eficaz sea el diagnóstico y seguimiento de los pacientes hipertensos, menos recursos se necesitarán para su tratamiento, y se evitarán así las complicaciones de otros órganos diana como el cerebro y el riñón, lo que provocaría en los pacientes una mayor discapacidad.

Introduction: arterial hypertension is one the most frequent diseases in general population. Nowadays, it reaches a global prevalence of 30 to 45 %. Retinal microcirculation can be considered as an anatomical representation of the physiological and functional characteristics of the coronary and cerebral circulation. Objectives: to delve into the relationship between blood pressure levels and target organ damage, specifically through the fundus, as well as the possible ophthalmological complications derived from arterial hypertension, and the comparison of some of the existing classifications on the ophthalmological changes that it causes. Methods: analysis - synthesis and bibliographic- documentary analyses were the used methods. Google and Google Scholar as well as Hinari, SciELO Cuba, Pubmed and others databases were the search engines. Conclusions: hypertensive retinopathy is one of the adverse complications of acute or chronic arterial hypertension. On the other hand, venous occlusions and the formation of macroaneurysms constitute other serious ones to consider. The more effective the diagnosis and follow-up of hypertensive patients, the fewer resources will be needed for their treatment, thus avoiding complications in other target organs such as the brain and kidney, which would cause greater disability in patients.

Nuclear Medicine Methods for Assessment of Chronic Chagas Heart Disease

Abstract Several different imaging methods can be used to evaluate patients with Chagas heart disease (CHD) for diagnostic and prognostic purposes, including plain chest radiography; echocardiography; myocardial perfusion scintigraphy, for detection of ischemia and fibrosis; radionuclide gated-angiography, for evaluation of biventricular function; 123I-MIBG labeling of sympathetic myocardial innervation; MRI, for detection and quantitation of myocardial fibrosis; and coronary angiography. This study aims to review the contributions of these nuclear medicine methods to understanding of the pathophysiology of chronic Chagas cardiomyopathy (CCC). Careful analysis and integration of findings provided by these imaging methods in patients with CCC at different stages has contributed significantly to improving understanding of several peculiarities of the disease. Clinical and experimental studies in animal models show that perfusion abnormalities detected in association with dysfunctional but viable myocardium are a common finding in CCC patients and correspond to areas of cardiac sympathetic denervation, as assessed by 123I-MIBG imaging. Furthermore, recent reports have demonstrated a close relationship between coronary microvascular disturbances and myocardial inflammation. Thus, ongoing research, mainly focused on refinements of 18F-FDF -PET techniques and further exploration of nuclear methods, such as SPECT, have the potential to contribute to detection and monitoring of early subclinical myocardial damage thereby enabling evaluation of therapeutic strategies targeting inflammation and microvascular ischemia that could result in better prognostic stratification of patients with CHD.

Efeitos da morte cerebral na microvasculatura pulmonar em um modelo experimental de doador de pulmão / Brain death effects on lung microvasculature in an experimental model of lung donor

RESUMO Objetivo A morte cerebral (MC) desencadeia alterações hemodinâmicas e inflamatórias importantes, comprometendo a viabilidade dos órgãos empregados em transplantes. Para compreender melhor as alterações microcirculatórias nos pulmões de doadores com MC, o presente estudo investigou a microcirculação pulmonar em um modelo de roedor com MC via microscopia intravital. Métodos Ratos Wistar machos foram anestesiados e ventilados mecanicamente. Eles foram submetidos a trepanação e a MC induzida por meio do aumento da pressão intracraniana. Os ratos do grupo Sham (SH), utilizado como controle, foram submetidos apenas à trepanação. Em ambos os grupos, foram monitorados o O2 expiratório e o CO2, e, após 3 horas, foi realizada a toracotomia e criada uma janela para observar a superfície pulmonar usando o sistema de microscopia intravital. As expressões pulmonares das moléculas de adesão intercelular (ICAM)-1 e da óxido nítrico-sintase endotelial (eNOS) foram avaliadas por imuno-histoquímica, e as citocinas foram medidas em amostras pulmonares. Resultados Três horas após os procedimentos cirúrgicos, a perfusão pulmonar foi de 73% no grupo SH. Por outro lado, os animais com MC apresentaram uma importante diminuição na perfusão do órgão para 28% (p = 0,036). O comprometimento microcirculatório pulmonar após a indução de MC foi associado a um aumento do número de leucócitos recrutados para o tecido pulmonar, além de uma redução na expressão de eNOS e um aumento na expressão de ICAM-1 nas células endoteliais do pulmão. Os ratos com MC apresentaram valores mais elevados de O2 expiratório e valores mais baixos de CO2 em comparação com os animais SH após 3 horas de monitorização. Conclusões Os dados apresentados demonstraram que a MC desencadeia uma importante hipoperfusão e inflamação nos pulmões, comprometendo a microcirculação pulmonar do doador.

ABSTRACT Objective Brain death (BD) triggers important hemodynamic and inflammatory alterations, compromising the viability of organs suitable for transplantation. To better understand the microcirculatory alterations in donor lungs caused by BD. The present study investigated the pulmonary microcirculation in a rodent model of BD via intravital microscopy. Methods Male Wistar rats were anaesthetized and mechanically ventilated. They were trepanned and BD was induced through the increase in intracranial pressure. As control group, sham-operated (SH) rats were trepanned only. In both groups, expiratory O2 and CO2 were monitored and after three hours, a thoracotomy was performed, and a window was created to observe the lung surface using an epi-fluorescence intravital microscopy. Lung expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) was evaluated by immunohistochemistry, and cytokines were measured in lung samples. Results Three hours after the surgical procedures, pulmonary perfusion was 73% in the SH group. On the other hand, BD animals showed an important decrease in organ perfusion to 28% (p = 0.036). Lung microcirculatory compromise after BD induction was associated with an augmentation of the number of leukocytes recruited to lung tissue, and with a reduction in eNOS expression and an increase in ICAM-1 expression on lung endothelial cells. BD rats showed higher values of expiratory O2 and lower values of CO2 in comparison with SH animals after three hours of monitoring. Conclusion Data presented showed that BD triggers an important hypoperfusion and inflammation in the lungs, compromising the donor pulmonary microcirculation.

The effect of hirudin on antagonisting thrombin induced apoptosis of human microvascular endothelial cells

Abstract Purpose: To investigate whether hirudin exerts its antithrombin action to decrease the ratio of Human Microvascular Endothelial Cells (HMVECs) apoptosis. Methods: Human microvascular endothelial cells (HMVECs) cultured in the third and fifth generations were used. HMVECs were divided into normal group, thrombin group (T group), natrual hirudin group (H group), thrombin + natrual hirudin group (T + H group), AG490 group, thrombin + AG490 group (T + AG490 group), natrual hirudin + AG490 group (H + AG490 group), thrombin + natural hirudin + AG490 (T + H + AG490 group).Apart from the normal group, the other groups were exposed to the relevant drugs for 24 hours.HMVEC apoptosis was assessed by flow cytometric and double Immunofluorescence of phosphorylation of JAK (P-JAK2) and TUNEL assay. Results: Compared with the normal group, in thrombin group the HMVECs apoptosis rate were significantly increased (P<0.05).The results indicated that the index of apoptosis and the apoptosis rate were improved in cultures treated by natural hirudin (T + H group), relative to cultures with thrombin only (T group). We found that the index of apoptosis and the apoptosis rate in the AG490 + thrombin group were higher than that in the hirudin + thrombin group (P<0.05). Double Immunofluorescence of p-JAK2 and TUNEL assays showed that cells were double positive for P-JAK2 uptake and TUNEL detection liquid binding. Conclusion: The natural hirudin and JAK2/STATs signal inhibitor AG490 could block the effects of thrombin. Natural hirudin could attenuate HMVECs apoptosis via antagonizing thrombin and it is suggested that this effect may occur by blocking the JAK2/STATs signaling pathway and this signaling pathways appears to be not the only pathway.

Pharyngo-ileo-colo-anastomosis with micro-vascular blood supply augmentation for esophago-gastric replacement due to esophago-gastric necrosis after caustic ingestion / Faringo-íleo-colo-anastomose com suprimento sanguíneo microvascular para substituição esofagogástrica por necrose esofagogástrica após ingestão cáustica

ABSTRACT Background : Complete esophago-gastric necrosis after caustic ingestion is a challenging surgical scenario for reconstruction of the upper digestive transit. Aim : To present a surgical technique for reconstruction of the upper digestive tract after total esophagectomy and gastrectomy due to esophageal and gastric necrosis Method: The transit was re-established by means of a pharyngo-ileo-colic interposition with microsurgical arterial and venous anastomosis for augmentation of blood supply. Colo-duodeno-anastomosis and ileo-transverse colic anastomosis were performed for complete digestive transit reconstruction. Result: This procedure was applied in a case of 41 years male attempted suicide by ingesting alkali caustic liquid (concentrated sodium hydroxide). Total necrosis of the esophagus and stomach occurred, which required initially total esophago-gastrectomy, closure at the level of the crico-pharyngeal sphincter and jejunostomy for enteral feeding with a highly deteriorated quality of life . The procedure was performed later and there were no major early and late postoperative complications and normal nutritional conditions were re-stablished. Conclusion: The procedure is feasible and must be managed by multidisciplinary team in order to re-establish a normal quality of life.

RESUMO Racional: A necrose esofagogástrica completa após ingestão cáustica é um cenário cirúrgico desafiador para a reconstrução do trânsito digestivo alto. Objetivo: Apresentar uma técnica cirúrgica para reconstrução do trato digestivo superior após esofagectomia total e gastrectomia por necrose esofágica e gástrica. Método: O trânsito foi restabelecido por interposição faringo-íleo-cólica com anastomose arterial e venosa microcirúrgica com aumento do suprimento sanguíneo. Adicionalmente, anastomose colo-duodeno-anastomótica e íleo-transversa foram realizadas para reconstrução completa do trânsito digestivo. Resultado: Este procedimento foi aplicado em um homem de 41 anos com tentativa de suicídio pela ingestão de líquido cáustico alcalino (hidróxido de sódio concentrado). Ocorreu necrose total do esôfago e do estômago, o que exigiu inicialmente esofagogastrectomia total, fechamento ao nível do esfíncter cricofaríngeo e jejunostomia para alimentação enteral produzindo qualidade de vida altamente deteriorada. O procedimento foi realizado mais tardiamente e não houve maiores complicações pós-operatórias precoces e tardias e condições nutricionais normais foram restabelecidas. Conclusão: O procedimento é viável e deve ser manejado por equipe multidisciplinar a fim de restabelecer a qualidade de vida normal.

Effects of vacuum sealing drainage on the treatment of cranial bone-exposed wounds in rabbits

This study was designed to assess the efficacy of vacuum sealing drainage (VSD) on skull exposure wounds in rabbits and to investigate the underlying mechanism of the process. Full-thickness excisional circular wounds 2×2 cm with or without periosteum involvement were created in 88 New Zealand white rabbits (mean body weight: 3.0±0.65 kg). Animals were randomly divided into 4 groups: periosteum-intact wounds treated with traditional dressing (p+control), periosteum-intact wounds treated with VSD (p+VSD), periosteum-lacking wounds treated with traditional dressing (p-control) and periosteum-lacking wounds treated with VSD (p-VSD). The wounds treated with traditional dressing were covered with Vaseline gauze, while VSD treatment was accompanied with continuous -120 mmHg pressure. Finally, wound tissues were harvested for analysis of hydroxyproline content and histologic detection. VSD hastened the wound healing process significantly (P<0.05) compared to the corresponding control groups. VSD alleviated the inflammation reaction, accelerated re-epithelialization and facilitated the organization of collagen fibers into neat rows. During the wound healing process, the hydroxyproline content increased overtime [i.e., postoperative days (POD) 7, POD 10 and POD 15] in all four groups, and it peaked in the p+VSD group. VSD also promoted angiogenesis via increasing number and quality of collagen. We concluded that VSD can promote healing in bone-exposed wounds via increasing hydroxyproline content and vessel density, reducing inflammatory responses and generating ordered collagen arrangement.

Lymphangiogenesis and angiogenesis in oral cavity and lower lip squamous cell carcinoma / Linfangiogênese e angiogênese em carcinomas de células escamosas de lábio inferior e da cavidade oral

ABSTRACT INTRODUCTION: Tumors of the lip and oral cavity differ in various aspects; therefore a clarification of the distinctions among these sites may help to better understand the biologic behavior of neoplasms occurring in these locations. OBJECTIVE: Considering that angiogenesis and lymphangiogenesis are two major elements that can influence various aspects of tumor biology, we aimed to compare these factors between squamous cell carcinoma of the lower lip and oral cavity. METHODS: A total of 84 primary squamous cell carcinomas including 45 oral and 39 lower lip tumors were selected and immunohistochemically stained with monoclonal antibody against D2-40 and CD105. Mean microvessel density was assessed in tumoral tissue, while lymphatic vessel density was calculated in both neoplastic tissue and invasion front. Data were statistically analyzed using t-test and p-values of <0.05 were considered significant. RESULTS: We found a mean microvessel density ± standard deviation of 31.94 ± 18.9 in oral cavity and 27.54 ± 20.8 in lower lip squamous cell carcinomas, with no significant difference (p = 0.32). Mean lymphatic vessel density ± standard deviation was 13.05 ± 8.2 and 16.57 ± 10.79 in of oral cavity and lower lip neoplastic tissue, respectively. The corresponding values were 9.94 ± 5.59 and 12.50 ± 7.8 in the invasive front. Significant differences were not observed in either of the lymphatic vessel density variables between the two sites. CONCLUSION: According to our results, it seems that the search for additional factors other than those related to the vasculature should continue, to help clarify the differences in biologic behavior between lower lip and oral cavity squamous cell carcinomas.

Resumo Introdução: Os tumores de lábio e da cavidade oral diferem em vários aspectos; portanto, o conhecimento das diferenças entre eles pode ajudar na melhor compreensão do comportamento biológico das neoplasias que ocorrem nesses locais. Objetivo: Considerando que a angiogênese e a linfangiogênese são dois elementos importantes que podem influenciar diversos aspectos da biologia dos tumores, objetivamos comparar esses fatores entre o carcinoma de células escamosas (CCE) de lábio inferior e da cavidade oral. Método: No total, foram selecionados 84 CCEs primários (45 tumores da cavidade oral e 39 tumores de lábio). Esses tumores foram corados por processo imunohistoquímico com anticorpo monoclonal anti-D2-40 e CD105. Avaliamos a densidade média de microvasos (DMV) no tecido tumoral, enquanto que a densidade vascular linfática (DVL) foi calculada tanto no tecido neoplásico como no front de invasão. Os dados foram estatisticamente analisados com o uso do teste t e valores de p < 0,05 foram considerados significantes. Resultados: Chegamos a uma média para DMV ± DP de 31,94 ± 18,9 para CCEs na cavidade oral e de 27,54 ± 20,8 no lábio inferior, sem diferença significante (p = 0,32). As médias para DVL ± DP foram de 13,05 ± 8,2 e 16,57 ± 10,79 no tecido neoplásico da cavidade oral e lábio inferior, respectivamente. Os valores correspondentes foram 9,94 ± 5,59 e 12,50 ± 7,8 no front invasivo. Não foram observadas diferenças significantes nas duas variáveis DVL entre os dois locais. Conclusão: De acordo com os nossos resultados, a pesquisa por fatores adicionais, além daqueles relacionados à vasculatura, deve ter continuidade, para auxiliar no esclarecimento das diferenças do comportamento biológico entre CCEs no lábio inferior e na cavidade oral.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging

Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.

Cirurgia bariátrica e metabólica e complicações microvasculares do diabetes mellitus tipo 2 (DM2) / Bariatric and metabolic surgery and microvascular complications of type 2 diabetes mellitus

ResumoIntrodução:O diabetes mellitus tipo 2 (DM2) é caracterizado por uma desregulação metabólica, originando complicações microvasculares, mais especificamente a retinopatia, nefropatia e a neuropatia. A prevenção e tratamento das complicações são alvo da farmacoterapia, porém, evidências demonstram que a cirurgia bariátrica/metabólica é superior ao melhor tratamento farmacológico, pois apresenta melhor controle da glicemia, hipertensão e dislipidemias.Métodos:Por meio de pesquisa no PubMed, são discutidas as recentes publicações que evidenciam o efeito positivo das intervenções cirúrgicas sobre as complicações microvasculares, como melhora da microalbuminúria e mesmo preservação de função renal.Discussão:Existem evidências de benefício das operações bariátricas/metabólicas sobre a nefropatia diabética. Os dados sobre retinopatia são ainda ambivalentes. Na literatura, há uma diferença significativa no benefício da cirurgia em neuropatia.Conclusão:Apesar de resultados surpreendentes e positivos, para que se estabeleça definitivamente o papel da cirurgia bariátrica/metabólica nas complicações micovasculares do DM2, há a necessidade de novos estudos randomizados controlados e prospectivos.

AbstractIntroduction:Metabolic dysregulation is the defining characteristic of type 2 diabetes mellitus (T2DM) and may lead to microvascular complications, specifically retinopathy, nephropathy and neuropathy. Medical treatment and lifestyle interventions targeting risk factors for microvascular complications can yield therapeutic gains, particularly retinopathy and nephropathy. Bariatric/metabolic surgery is superior to the best medical treatment in several randomized controlled trials. Consequently, evidence of the effect of bariatric/metabolic surgery on microvascular complications is now emerging in the literature.Methods:A search of the recent published evidence base on the effects of bariatric/metabolic surgery on microvascular complications reveals further evidence that supports the efficacy of surgery in preventing the incidence and progression of albuminuria and preserving renal functional decline.Discussion:Data on retinopathy are ambivalent representing the potential in some cases for an influence of reactive hypoglycaemia over the retina but the majority of data emphasize that the metabolic control can halt the progression of the eye disease. A significant gap in the literature remains in relation to the effects of surgery on diabetic neuropathy, although some information sheds a light on the benefits secondary to the surgical metabolic control.Conclusion:Overall, although data so far is exciting, there is a pressing need for prospective randomized controlled trials examining long-term microvascular outcomes following bariatric/metabolic surgery in patients with T2DM.

Descompresión microvascular en espasmo hemifacial: reporte de 13 casos y revisión de la literatura / Microvascular decompression in hemifacial spasm: report of 13 cases and review of the literature

Objetivo: el propósito del presente trabajo es presentar los resultados de 13 pacientes con diagnóstico de espasmo hemifacial (EHF), en los cuales se realizó una descompresión microvascular (DMV). Material y Método: Desde Junio de 2005 a Mayo de 2014, 13 pacientes con diagnóstico de EHF fueron intervenidos quirúrgicamente, realizando una DMV. Se evaluó: edad, sexo, tiempo de evolución de la sintomatología, hallazgos intraoperatorios y resultados postoperatorios. Resultados: De los 13 pacientes intervenidos, 7 fueron mujeres y 6 varones. La media de edad fue de 53 años. El tiempo medio entre el inicio de la sintomatología y la intervención quirúrgica osciló entre 3 y 9 años. En todos los casos el EHF era típico, uno de ellos con neuralgia trigeminal concomitante, observándose en todos compresión neurovascular intraoperatoria. Por orden decreciente de frecuencia la causa de la compresión fue arteria cerebelosa anteroinferior, arteria cerebelosa posteroinferior, arteria dolicomega basilar y arteria dolicomega vertebral. El seguimiento postoperatorio fue en promedio de 24 meses. El 62% presentó desaparición postquirúrgica inmediata de la sintomatología preoperatoria, el 30% desaparición tras un período de 3 semanas a 2 meses (8% con mejoría parcial), y en el 8% no hubo mejoría. En cuanto a las complicaciones postoperatorias: 3 pacientes presentaron paresia facial II-III en la escala de House-Brackman (se recuperaron en un período de 6 meses), y 1 paciente presentó fístula de líquido cefalorraquídeo. Ninguno de los pacientes de la serie presentaron hipoacusia transitorio o permanente. Conclusión: La DMV como tratamiento del EHF es un procedimiento efectivo y seguro, que permite la resolución completa de la patología en la mayoría de los casos.

Objective: the aim of this study is to describe the results of 13 patients with facial hemispasm, treated with microvascular decompression.Method: Between June 2005 and May 2014, 13 patients with facial hemispasm were operated, underwent microvascular decompression. The age, sex, duration of symptoms before surgery, and surgical finds, were all evaluated. In addition, postoperative results were also analyzed. Results: 7 patients were women and 6 were men. The average age of the patients was 53 years. The average time between onset of symptoms and surgery ranged from 3 to 9 years. In all cases the facial hemispasm was typical, one with concomitant trigeminal neuralgia, observed in all neurovascular compression intraoperative. In decreasing order of frequency, the cause of compression was anterior inferior cerebellar artery, posterior inferior cerebellar artery, dolicomega basilar artery and dolicomega vertebral artery. The average time of postoperative follow-up after the surgery was 24 months. Complete relief from spasm occurred in 62%; 30% disappearance after 3 weeks-2 months (8% partial) and in 8% had no improvement. Regarding postoperative complications: 3 patients had facial paresis II-III in House-Brackman scale and 1 patient presented CSF leak. None of the patients in the serie had hearing loss or deafness. Conclusion: The microvascular decompression for facial hemispasm is a safe an effective procedure, which allows complete resolution of the disease in most cases.

Dyslipidemia in young patients with type 1 diabetes mellitus

Objective The association between type 1 diabetes mellitus (T1D) and dyslipidemia (DLP) increases the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the presence of dyslipidemia in young T1D patients.Materials and methods The study design was cross-sectional and descriptive. We reviewed medical records of T1D patients followed at an endocrinology service, from 1998-2012. Data collected: gender, actual age and age at diagnosis, duration of T1D since diagnosis, body mass index (BMI), pubertal stage, glycemic control (GC) determined by glycated hemoglobin (HbA1c), total cholesterol (TC), HDL, LDL, triglycerides (TG). To analyze lipid profile and metabolic control, we used the Brazilian Society of Diabetes Guidelines.Results Were included 239 T1D patients, 136 (56.9%) females; mean ± SD: actual age 15.7 ± 5.0 years and at T1D diagnosis 7.3 ± 3.9; T1D duration 10.6 ± 6.4 years, 86.6% puberty, 15.1% overweight. The prevalence of DLP was 72.5%, 63.3% females, 86.6% puberty, mean ± SD: actual age 15.4 ± 4.8 years and at T1D diagnosis 7.2 ± 4.1 years, duration of T1D 10.7 ± 6.1 years. We found high-CT in 56.7%, low-HDL = 21.7%, high LDL = 44.0%, high-TG = 11.8%. Between females with DLP, 83.5% was in puberty. We find correlation between the presence of DLP, a poor GC and BMC.Conclusion We found a high prevalence of DLP in young patients with T1D, particularly in puberty females. Programs targeting the prevention of dyslipidemia should be adopted, especially for this group, in order to prevent/delay chronic complications and cardiovascular disease. Arch Endocrinol Metab. 2015;59(3):215-9.

The relation between dermoscopy and histopathology of basal cell carcinoma

Abstract BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. .

Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model / Timoquinona protege órgãos terminais da isquemia/reperfusão da aorta abdominal em modelo com ratos

Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10), control (n=10) and thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI). Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons). Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model. .

Introdução: Estudos prévios demonstraram que a timoquinona tem efeitos protetores contra a lesão de isquemia/reperfusão em vários órgãos como pulmão, rins e fígado em diferentes modelos experimentais. Objetivo: Determinar se timoquinona tem efeitos positivos em tecidos do pulmão, rim e coração e no estresse oxidativo em lesão de isquemia/perfusão da aorta abdominal. Métodos: Trinta ratos foram divididos em três grupos: sham (n=10), controle (n=10) e tratamento com timoquinona (TQ) (n=10). Os grupos controle e de tratamento com TQ foram submetidos à isquemia da aorta abdominal durante 45 minutos, seguido por um período de 120 minutos de reperfusão. No grupo de tratamento com TQ, a timoquinona foi administrada 5 minutos antes da reperfusão, dose de 20 mg/kg através da via intraperitoneal. A capacidade total antioxidante, estado oxidativo total (TOS) e o índice de estresse oxidativo (OSI) no soro do sangue foram medidos, e a histopatologia dos tecidos do pulmão, rim e coração foram avaliados com microscopia de luz. Resultados: Estado oxidativo e índice de estresse oxidativo total em amostras de sangue foram estatisticamente mais altos no grupo controle em relação aos grupos sham e tratamento com TQ (P<0,001 para TOS e OSI). Escores de lesões no grupo controle foram estatisticamente mais altos em relação aos grupos sham e tratamento com TQ (P<0,001 para todas as comparações). Conclusão: A timoquinona administrada por via intraperitoneal foi eficaz na redução do estresse oxidativo e lesão histopatológica em modelo de rato de isquemia/reperfusão aguda da aorta abdominal. .

Quantificação da angiogênese induzida por tumor em membrana corioalantóica de embrião de galinha / Quantification of tumor-induced angiogenesis on chicken embryo chorioallantoic membrane

Angiogênese é um processo de surgimento de novos microvasos provenientes de vasos sanguíneos já existentes. O desenvolvimento tumoral e o processo de metástase são dependentes de angiogênese, pois o tumor em crescimento necessita de uma rede capilar que forneça nutrientes e oxigênio. A membrana corioalantóica de embrião de galinha (CAM) é um modelo experimental in vivo que oferece muitas vantagens, como a alta vascularização natural e alta taxa de reprodução, além de ser um modelo simples e de baixo custo. A CAM é composta por proteínas de matriz extracelular, que mimetizam o ambiente fisiológico de células cancerosas. A etapa de contagem do número total de vasos permite a determinação dos efeitos dos estímulos pró ou anti angiogênicos, portanto a padronização de um método eficaz é necessário. O presente estudo teve como objetivo geral avaliar o potencial angiogênico de células de uma linhagem de adenocarcinoma de cólon humano (HT29) e propor um método para quantificação da angiogênese induzida por células tumorais na CAM. Os embriões foram mantidos em sistema ex ovo. No oitavo dia, foram adicionados sobre a CAM, implantes de colágeno contendo células tumorais em diferentes concentrações. No décimo primeiro dia foi feito o registro fotográfico utilizando microscópio estereoscópico e foram determinados quatro scores para a quantificação e caracterização dos vasos, considerando-se se seccionavam o implante e também seu grau de ramificação. A contagem dos vasos, feita em uma área específica ao redor do implante, foi realizada após edição das imagens pelo programa Image Pro Plus. Os resultados mostraram aumento significativo do número de vasos que não seccionavam o implante para aqueles contendo 3 x 104 e 6 x 104 células. Pode-se concluir que a metodologia de contagem dos vasos, utilizando registros fotográficos e edições de imagens, é eficaz. Demonstrou-se que as células HT29 induzem a uma alteração no padrão de crescimento de novos vasos quando depositada sobre a CAM em implantes de colágeno e podem ser utilizadas como modelo experimental para se investigar o efeito de diferentes compostos sobre a angiogênese induzida por tumor.

Angiogenesis is a process of sprouting of new microvessels from existing blood vessels. The tumoral development and the metastasis process are angiogenesis dependent, because the growing tumor needs a capillaries network that provides nutrients and oxygen. The chicken chorioallantoic membrane (CAM) is an experimental in vivo model which offer many advantages, such as the high natural vascularization and high reproducibility, besides the simplicity and low cost. The CAM contains extracellular matrix proteins, which mimics the physiological cancer cell environment. The counting of the total number of vessels allows a determination of pro- and anti-angiogenic effects of different stimulus, therefore patterning an effective method is necessary. The general goal of the present study was to evaluate the angiogenic potential of a human colon adenocarcinoma cell line (HT29) and propose a method to quantify angiogenesis induced by cancer cells on the CAM. Embryos were cultivated in an ex ovo system. At the eighth day, collagen implants containing cancer cells in different concentrations were added on the top of CAM. At the eleventh day, the photographic records were made by using stereoscope microscope and were determined four scores for vessels quantification and characterization. Vessels counting were done in a specific area around the implant, and edition of the captured images were done using Image Pro Plus software. Our results showed a significant increase in vessels that do not section the implant. It was demonstrated that HT29 cells induce a change in the pattern of growth of new blood vessels when placed on CAM into collagen implants and can be used as an experimental model for investigating the effect of different compounds on tumor-induced angiogenesis.

Immunolocalization of FGF-2 and VEGF in rat periodontal ligament during experimental tooth movement

OBJECTIVE: This article aimed at identifying the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) in the tension and pressure areas of rat periodontal ligament, in different periods of experimental orthodontic tooth movement. METHODS: An orthodontic force of 0.5 N was applied to the upper right first molar of 18 male Wistar rats for periods of 3 (group I), 7 (group II) and 14 days (group III). The counter-side first molar was used as a control. The animals were euthanized at the aforementioned time periods, and their maxillary bone was removed and fixed. After demineralization, the specimens were histologically processed and embedded in paraffin. FGF-2 and VEGF expressions were studied through immunohistochemistry and morphological analysis. RESULTS: The experimental side showed a higher expression of both FGF-2 and VEGF in all groups, when compared with the control side (P < 0.05). Statistically significant differences were also found between the tension and pressure areas in the experimental side. CONCLUSION: Both FGF-2 and VEGF are expressed in rat periodontal tissue. Additionally, these growth factors are upregulated when orthodontic forces are applied, thereby suggesting that they play an important role in changes that occur in periodontal tissue during orthodontic movement. .

OBJETIVO: o objetivo desse estudo foi identificar a expressão do fator de crescimento de fibroblastos 2 (FGF-2) e do fator de crescimento vascular endotelial (VEGF) nos lados de tensão e pressão do ligamento periodontal de ratos, durante movimento ortodôntico experimental, em diferentes períodos de tempo. MÉTODOS: uma força ortodôntica de 0,5N foi aplicada no primeiro molar superior direito de 18 ratos Wistar machos, por períodos de 3 (grupo I), 7 (grupo II) e 14 dias (grupo III). O primeiro molar do lado oposto foi utilizado como controle. Os animais foram sacrificados nos períodos de tempo mencionados, sendo a arcada superior removida e fixada. Após a desmineralização, os espécimes foram processados histologicamente e embebidos em parafina. A expressão do FGF-2 e do VEGF foram estudadas por meio de análise imuno-histoquímica. RESULTADOS: o ligamento periodontal dos dentes submetidos à movimentação ortodôntica mostraram maior expressão tanto de FGF-2 quanto de VEGF, em todos os grupos experimentais, quando comparados com os dentes do lado controle (p < 0,05). Diferenças estatisticamente significativas entre os lados de tensão e pressão também foram encontradas nos dentes submetidos à movimentação ortodôntica. CONCLUSÕES: tanto o FGF-2 quanto o VEGF são expressos no tecido periodontal de ratos, e esses fatores de crescimento são aumentados quando forças ortodônticas são aplicadas, sugerindo que esses desempenham um papel importante na reorganização do periodonto durante o movimento ortodôntico. .

FASN expression, angiogenesis and lymphangiogenesis in central and peripheral giant cell lesions

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) are non-neoplastic proliferative processes of the jaws. PGCL is a reactive process induced by irritant local factors and CGCL is an intra-osseous lesion of unknown etiology. Both lesions exhibit similar histologic features showing abundant mononuclear cells, admixed with a large number of multinucleated giant cells and a rich vascularized stroma with extravasated erythrocytes, hemosiderin deposition, and blood-filled pools. Recent studies have linked fatty acid synthase (FASN) with angiogenesis. Objective: To evaluate angiogenesis and lymphangiogenesis and their relationship with FASN expression in CGCL and PGCL. Material and Methods: Thirteen CGCL and 14 PGCL of the jaws were selected for immunoexpression of FASN; CD34 and CD105 (to assess blood microvessel density [MVD] and microvessel area [MVA]); and D2-40 (to assess lymphatic MVD and MVA). Results: Within PGCL and CGCL, MVD-CD34 was signifcantly higher than MVD-CD10S, followed by MVD-D2-40. Moreover, a signifcantly higher number of FASN-positive multinucleated giant cells than mononuclear cells were observed. Between PGCL and CGCL, only MVD-CD34 and all MVA were signifcantly higher in PGCL. Positive correlation between MVA-CD10S with FASNpositive mononuclear cells in both lesions was observed. Conclusions: Our results show both lesions exhibiting similar levels of FASN expression and neoangiogenesis, suggesting constitutive processes that regulate tissue maintenance. .

Cancer stem cells - the current status of an old concept: literature review and clinical approaches

As regards their morphology and biology, tumours consist of heterogeneous cell populations. The cancer stem cell (CSC) hypothesis assumes that a tumour is hierarchically organized and not all of the cells are equally capable of generating descendants, similarly to normal tissue. The only cells being able to self-renew and produce a heterogeneous tumour cell population are cancer stem cells. CSCs probably derive from normal stem cells, although progenitor cells may be taken into consideration as the source of cancer stem cells. CSCs reside in the niche defined as the microenvironment formed by stromal cells, vasculature and extracellular matrix. The CSC assays include FACS sorting, xenotransplantation to immunodeficient mice (SCID), incubation with Hoechst 33342 dye, cell culture in non-adherent conditions, cell culture with bromodeoxyuridine. CSCs have certain properties that make them resistant to anticancer therapy, which suggests they may be the target for potential therapeutic strategies.

Entrenamiento microquirúrgico básico para realizar un modelo animal de alotrasplante compuesto vascularizado / Basic microsurgical training for a vascularized composite allotransplantation animal model

Introduction: rat hind limb transplantation is a complex animal model of vascularized composite allo-transplantation (VCA). A basic microsurgical training is required prior to the implementation of this model. Aim: to propose a training program for the acquisition of basic skills to perform a microsurgical VCA model. Animals and Methods: the training program was conducted in two stages. First, at the dry lab, basic suturing skills with 9-0 to 11-0 nylon sutures were practiced, reproduced from surgical videos performed by experts. In a second stage, at the wet lab using 13 Lewis rats, 6 hind limb microsurgical dissections were performed and the important steps for transplantation were identified: 10 end to end femoral artery anastomoses with 10-0 nylon interrupted suture; 10 end to end femoral vein anastomoses with 10-0 nylon suture; 3 femoral vein interposition in the femoral artery; 6 end to end sciatic nerve neurorrhaphy; 4 femur osteosynthesis with 21g needle and wire cerclage. Anastomotic patency rate and anastomotic surgical time were recorded. Results: arterial and venous patency rate was 100 and 90 percent respectively. Surgical time decreased from 49 to 24 minutes on arterial anastomoses and from 55 to 25 minutes on venous anastomoses after completion of the training program. When a vein interposition was performed, an immediate patency rate of 100 percent was obtained. Conclusion: a successful staged training model of basic microsurgical skills was performed, in order to perform a VCA model.

Introducción: el trasplante de extremidad posterior de la rata es un modelo microquirúrgico de alotras-plante compuesto vascularizado (ACV), que requiere para su implementación de un entrenamiento microquirúrgico básico sistematizado. Objetivo: comunicar un modelo de entrenamiento microquirúrgico básico para adquirir las habilidades y destrezas que permitan realizar un modelo microquirúrgico de ACV Animales y Métodos: el entrenamiento se realizó en 2 etapas: la primera, en laboratorio en seco. A partir de vídeos de microcirugía, se practicó las destrezas para maniobrar suturas de nylon de 9-0 a 11-0. En la segunda etapa in vivo con animales, (13 ratas Lewis), se realizaron: 6 disecciones microquirúrgicas de extremidad posterior para reconocimiento de estructuras anatómicas; 10 anastomosis término-terminal (T-T) de arteria femoral con sutura interrumpida 10-0; 10 anastomosis T-T de vena femoral; 3 interposiciones de vena femoral en arteria femoral; 6 neurorrafias T-T de nervio ciático; 4 fijaciones óseas de fémur con aguja 21 g y cerclaje con alambre. Se evaluó la permeabilidad de las anastomosis y los tiempos quirúrgicos. Resultados: anastomosis arteriales: la permeabilidad inmediata fue de un 100 por ciento. Los tiempos de anastomosis disminuyeron de 49 a 24 min con el entrenamiento. Anastomosis venosas: la permeabilidad inmediata fue de un 90 por ciento. Los tiempos de anastomosis disminuyeron paulatinamente de 55 a 25 min. Interposiciones venosas: se logró una permeabilidad de 100 por ciento. Conclusión: una estrategia de entrenamiento por etapas, es una forma factible de entrenamiento en microcirugía. Este entrenamiento permite obtener una aceptable permeabilidad anastomótica, paso crítico para realizar modelos de ACV.

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. .