AT1-receptor mediated vascular damage in myocardium, kidneys and liver in rats

The systemic aspect of vascular damage induced by angiotensin II (ANG II) has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment), treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.

Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II) appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS). ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.

Evaluation of the use of tomography in penetrating neck trauma

ABSTRACTObjective:the study has the intention of evaluate the accuracy of computed tomography for the diagnosis of cervical lesions on penetrating neck trauma and also identify the most frequent mechanisms of trauma. Most injured structures, determine the age range and the most prevalent sex.Methods: observational descriptive retrospective study executed by the systematic retrospective review of medical records of all patients victims of penetrating neck trauma that went through surgery and CT scans, admitted into Hospital do Trabalhador, between January 2009 and December 2013.Results:the final sample was of 30 patients, 96.7% of the male sex, the median age was of 28 years old. Most patients suffered injuries by gun (56.7%) and 33,3% suffered stab wounds. The most stricken area of the neck was Zone II (77.8%) and the left side (55.2%). Regarding the structures injured, the CT showed 6.7% lesions on airways but the surgery showed 40% of damaged, with a value of p=0.002. As to damages of the esophagus and pharynx the CT detected 10% of lesions, while surgery found 30% of lesions, therefore with a significant value of p=0.013. As for the analysis the CT showed reliable. As for the analysis of vascular damage, the CT showed to be, in most cases, reliable to the findings during the surgical act.Conclusion:besides the great use of CT for the diagnosis of penetrating neck injuries we can say that this is an exam with low accuracy for the diagnosis of lesions of aerodigestive tract, therefore it is important a clinical correlation for a good diagnosis.as for the vascular lesions and of other structures, the CT had high sensibility and specificity, thus a good exam to be used in overall.

Myocyte necrosis is the basis for fibrosis in renovascular hypertensive rats

The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 ± 19 mmHg and RHT8: 194 ± 24 mmHg, P<0.05 vs control: 123 ± 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 ± 0.38 µg/mg; RHT4: 3.02 ± 0.40 µg/mg; RHT8: 3.44 ± 0.45 µg/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local, conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed by scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

Damage control surgery: it's evolution over the last 20 years

In less than twenty years, what began as a concept for the treatment of exsanguinating truncal trauma patients has become the primary treatment model for numerous emergent, life threatening surgical conditions incapable of tolerating traditional methods. Its core concepts are relative straightforward and simple in nature: first, proper identification of the patient who is in need of following this paradigm; second, truncation of the initial surgical procedure to the minimal necessary operation; third, aggressive, focused resuscitation in the intensive care unit; fourth, definitive care only once the patient is optimized to tolerate the procedure. These simple underlying principles can be molded to a variety of emergencies, from its original application in combined major vascular and visceral trauma to the septic abdomen and orthopedics. A host of new resuscitation strategies and technologies have been developed over the past two decades, from permissive hypotension and damage control resuscitation to advanced ventilators and hemostatic agents, which have allowed for a more focused resuscitation, allowing some of the morbidity of this model to be reduced. The combination of the simple, malleable paradigm along with better understanding of resuscitation has proven to be a potent blend. As such, what was once an almost lethal injury (combined vascular and visceral injury) has become a survivable one.

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 µM EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 µg, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 µg/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity

Gadolinium increases the vascular reactivity of rat aortic rings

Gadolinium (Gd) blocks intra- and extracellular ATP hydrolysis. We determined whether Gd affects vascular reactivity to contractile responses to phenylephrine (PHE) by blocking aortic ectonucleoside triphosphate diphosphohydrolase (E-NTPDase). Wistar rats of both sexes (260-300 g, 23 females, 7 males) were used. Experiments were performed before and after incubation of aortic rings with 3 µM Gd. Concentration-response curves to PHE (0.1 nM to 0.1 mM) were obtained in the presence and absence of endothelium, after incubation with 100 µM L-NAME, 10 µM losartan, or 10 µM enalaprilat. Gd significantly increased the maximum response (control: 72.3 ± 3.5; Gd: 101.3 ± 6.4%) and sensitivity (control: 6.6 ± 0.1; Gd: 10.5 ± 2.8%) to PHE. To investigate the blockade of E-NTDase activity by Gd, we added 1 mM ATP to the bath. ATP reduced smooth muscle tension and Gd increased its relaxing effect (control: -33.5 ± 4.1; Gd: -47.4 ± 4.1%). Endothelial damage abolished the effect of Gd on the contractile responses to PHE (control: 132.6 ± 8.6; Gd: 122.4 ± 7.1%). L-NAME + Gd in the presence of endothelium reduced PHE contractile responses (control/L-NAME: 151.1 ± 28.8; L-NAME + Gd: 67.9 ± 19% AUC). ATP hydrolysis was reduced after Gd administration, which led to ATP accumulation in the nutrient solution and reduced ADP concentration, while adenosine levels remained the same. Incubation with Gd plus losartan and enalaprilat eliminated the pressor effects of Gd. Gd increased vascular reactivity to PHE regardless of the reduction of E-NTPDase activity and adenosine production. Moreover, the increased reactivity to PHE promoted by Gd was endothelium-dependent, reducing NO bioavailability and involving an increased stimulation of angiotensin-converting enzyme and angiotensin II AT1 receptors.

Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD.

O "hum" venoso como causa de zumbido pulsátil de origem vascular

Zumbido é uma das queixas otológicas mais comuns com que o otorrinolaringologista se depara. O "hum" venoso é descrito como uma causa pouco comum de zumbido vascular, pouco lembrado ou reconhecido como entidade clínica. OBJETIVO: O objetivo do estudo é identificar os casos de "hum" venoso dentre os pacientes com zumbido pulsátil atendidos no Ambulatório de Zumbido da Disciplina de Otorrinolaringologia da UNIFESP-EPM e compará-los com a literatura. MATERIAL E MÉTODO: Estudo retrospectivo dos pacientes com "hum" venoso realizado na UNIFESP-EPM de abril de 1997 a abril de 2003, analisando-se os parâmetros: idade de aparecimento, freqüência, lado acometido, presença de perda auditiva e tontura associadas, fatores de piora e melhora, resultados de audiometria, exame vestibular e tomografia computadorizada de ossos temporais, evolução e tratamento realizados. Foi utilizado um protocolo de exames e tratamento e os resultados foram comparados com os da literatura. RESULTADOS: O zumbido pulsátil ocorreu em 7,5% e o "hum" venoso em 3% do total de pacientes com zumbido, todos no sexo feminino, sem prevalência por época de aparecimento, acometendo mais a orelha esquerda. Em todos os pacientes houve melhora com tratamento clínico, não sendo necessária intervenção cirúrgica em nenhum caso. CONCLUSÃO: O "hum" venoso não é uma causa incomum de zumbido (39% dos zumbidos pulsáteis) como citado na literatura. O tratamento deve ser realizado atuando-se sobre os fatores responsáveis pelo zumbido e decorrentes do mesmo. Em grande número de casos o mesmo desaparece espontaneamente, não necessitando de tratamento. O tratamento cirúrgico raramente é necessário, devendo ser reservado apenas aos casos em que não haja melhora com o tratamento clínico.

Damage level of the two-spotted spider mite Tetranychus urticae Koch (acari: tetranychidae) in soybeans

Among phytophagous spider mites, the two-spotted spider mite Tetranychus urticae Koch, 1836 is one of the most important agricultural pests, not only because of the damage it causes, but also because it has a wide host range, infesting many commercial crops such as leafy greens, cotton, beans, and soybeans, among others. This study was carried out in a greenhouse of the Faculdade de Ciências Agrárias (FCA) of the Universidade Federal da Grande Dourados (UFGD), located in the city of Dourados, state of Mato Grosso do Sul. The experiment was arranged in a randomized block design with 5 treatments and 4 replicates. The treatments consisted of 5 levels in percentage of chlorotic symptoms (indicating mite damage): 0%, 25%, 50%, 75%, and 100%. All of the characteristics evaluated, except for number of pods per plant, the number of seeds per plant, the total weight (productivity), and the weight of 1000 seeds, were significantly influenced by the different levels of chlorotic symptoms. The economic damage level for the two-spotted spider mite Tetranychus urticae, according to the equation y = 66.63-0.51 x, based on the price of US$ 11.00 per bag of soybeans and a control cost of US$ 16.00, would be 15.80% chlorotic symptoms. At a price of US$ 29.00 per bag with the same control cost, the economic damage level would be 13% of chlorotic symptoms.

Infarto do miocárdio e acidente vascular cerebral associados à alta temperatura e monóxido de carbono em área metropolitana do sudeste do Brasil

Muito se tem publicado e discutido acerca de fatores de risco ligados a estilo de vida e a fatores hereditários em Acidente Vascular Cerebral (AVC) e Infarto do Miocárdio (IM). Porém o estudo da influência de fatores ambientais como poluição por monóxido de carbono e temperatura na determinação nas ocorrências dessas patologias ainda é pouco discutido em nosso meio. Visando preencher esta lacuna, foi verificada a associação existente entre os valores de temperaturas máximas diárias e valores médio e máximo diários de monóxido de carbono e AVC e IM no Município de São Paulo, SP (Brasil). Foi coletada uma série histórica do número de casos novos de AVC e IM atendidos em Pronto Socorro de um hospital de clínicas e valores de temperatura e monóxido de carbono. Conclui-se que das internações anuais por IM, 2,1% são devidos à poluição atmosférica e 4,9% a altas temperaturas. Das internações anuais por AVC, 2,8% são devidas a altas temperaturas. Não foi identificado associação entre monóxido de carbono e AVC.

Permanent vascular access in patients with end-stage renal disease, Brazil

OBJECTIVE: To assess factors associated with the establishment of permanent vascular access for patients with end-stage renal disease. METHODS: Cross-sectional study conducted in a nationally representative sample of Brazilian end-stage renal disease patients in dialysis and transplant centers during 2007. The sample comprised only patients who received hemodialysis as a primary therapy modality and reported the type of vascular access for their primary hemodialysis treatment (N=2,276). Data were from the TRS Project - "Economic and Epidemiologic Evaluation of Modalities of Renal Replacement Therapy in Brazil". Multiple logistic regression analysis was used to assess factors associated with the establishment of permanent vascular access in these patients. RESULTS: About 30% of the patients studied had an arteriovenous vascular access. The following factors were associated with a lower likelihood of having an arteriovenous vascular access as a primary type of access: time of hemodialysis start since the diagnosis of chronic renal failure < 1 year; shorter dialysis therapy; having no private health insurance; living in the central-western, northeastern and southeastern regions of Brazil; and living in the northern region plus having no private health insurance. In the final model there was found a positive association between the outcome and pre-dialysis care and no were association with socioeconomic and comorbidity variables. CONCLUSIONS: The study results showed that the focus should on pre-dialysis care to increase the establishment of an arteriovenous vascular access before starting hemodialysis in Brazil.

Chronic myocardial damage in experimental T. cruzi infection of a new world primate, Cebus sp. monkey

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n=4 and Tulahuen, n=4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been peviously published15 and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.