Effect of sildenafil citrate on the cardiovascular system

Sildenafil citrate is a drug commonly used to manage erectile dysfunction. It is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H -pyrazolo[4,3-d]pyrimidin-5-yl)-4 ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate (C22H30N6O4 S). It is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type 5. In late March through mid-November 1998, the US Food and Drug Administration (FDA) published a report on 130 confirmed deaths among men (mean age, 64 years) who received prescriptions for sildenafil citrate, a period during which >6 million outpatient prescriptions (representing about 50 million tablets) were dispensed. The US FDA recently reported that significant cardiovascular events, including sudden cardiac death, have occurred in men with erectile dysfunction who were taking sildenafil citrate. These reports have raised concerns that sildenafil citrate may increase the risk of cardiovascular events, particularly fatal arrhythmias, in patients with cardiovascular disease. In the past few years, the cardiac electrophysiological effects of sildenafil citrate have been investigated extensively in both animal and clinical studies. According to extensive data available to date, sildenafil citrate has been shown to pose minimal cardiovascular risks to healthy people taking this drug. Some precautions are needed for patients with cardiovascular diseases. However, the only absolute contraindication for sildenafil citrate is the concurrent use of nitrates. This article is intended to review sildenafil citrate's cardiovascular effects, as well as current debates about its arrhythmogenic effects.

Alternative pathways for angiotensin II generation in the cardiovascular system

The classical renin-angiotensin system (RAS) consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II) is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

Studies on mosquitoes (Diptera: Culicidae) and anthropic environment: 3- Survey of adult stages at the rice irrigation system and the emergence of Anopheles albitarsis in South-Eastern, Brazil

A study of adult Culicidae ecology was carried out from January 1992 through January 1993 at the rice irrigation system of the Ribeira Valley Experimental Station. The adaptation of Anopheles albitarsis to the anthropic environment became evident through the adult collections made at its various habitats represented by the irrigation system and the edge of the residual pond, as well as at those made within the local patchy residual woods. Other potential disease vectors were prevalent in the irrigated system too. There were Aedes scapularis, Culex nigripalpus and Cx. ribeirensis that were collected at various habitats. Remarkable differences among their prevalences were obtained such as between the natural forest and anthropic environments. In the former An. albitarsis was practically non-existent, thus suggesting that it might be considered as eusynathropic. As the populations of other species seemed to increase in the anthropic environment, they may be regarded as hemisynanthropes. Observations suggest the hypothesis that the development of irrigated land may be a factor in the emergence of An. albitarsis, and some other species, as well as the possibility of an increase in the transmission of mosquito-borne diseases such as malaria.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

Incidence and Predictors of Cardiovascular Complications and Death after Vascular Surgery

AbstractBackground:Patients undergoing arterial vascular surgery are considered at increased risk for post-operative complications.Objective:To assess the incidence and predictors of complications and death, as well as the performance of two models of risk stratification, in vascular surgery.Methods:This study determined the incidence of cardiovascular complications and deaths within 30 days from surgery in adults. Univariate comparison and logistic regression assessed the risk factors associated with the outcomes, and the receiver operating characteristic (ROC) curve assessed the discriminatory capacity of the revised cardiac risk index (RCRI) and vascular study group of New England cardiac risk index (VSG-CRI).Results:141 patients (mean age, 66 years; 65% men) underwent the following surgeries: carotid (15); lower limbs (65); abdominal aorta (56); and others (5). Cardiovascular complications and death occurred within 30 days in 28 (19.9%) and 20 (14.2%) patients, respectively. The risk predictors were: age, obesity, stroke, poor functional capacity, altered scintigraphy, surgery of the aorta, and troponin change. The scores RCRI and VSG-CRI had area under the curve of 0.635 and 0.639 for early cardiovascular complications, and 0.562 and 0.610 for death in 30 days.Conclusion:In this small and selected group of patients undergoing arterial vascular surgery, the incidence of adverse events was elevated. The risk assessment indices RCRI and VSG-CRI did not perform well for complications within 30 days.

Role of sympathetic nervous system and neuropeptides in obesity hypertension

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R). However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this remains a fruitful area for further investigation, especially in view of the current "epidemic" of obesity in most industrialized countries.

Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats

Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

Morphology and stability of aggregates of an Oxisol according to tillage system and gypsum application

Morphological characterization and aggregate stability is an important factor in evaluating management systems. The aim of this paper is to evaluate the stability and morphology of the aggregates of a dystrophic Oxisol managed with no-tillage and conventional tillage with and without the residual action of gypsum. The experimental design was randomized blocks arranged in split-split plot, where the treatments were two soil management systems (plots) with 0 and 2000 kg ha-1 of gypsum (subplots) and five depths (0-0.05, 0.05-0.10, 0.10-0.15, 0.15-0.20 and 0.20-0.30 m) as the subsubplots, with four replications. The aggregate morphology was determined through images and later evaluated by the Quantporo software. Stability was determined by the wet method. The results showed that the no-tillage system, with or without gypsum residual effect, provided the aggregates with the largest geometric diameters. The combination of no-tillage system and the gypsum residual effect provided rougher aggregates.

COMPARISON BETWEEN AUTOMATED SYSTEM AND PCR-BASED METHOD FOR IDENTIFICATION AND ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF CLINICAL Enterococcus spp

Enterococci are increasingly responsible for nosocomial infections worldwide. This study was undertaken to compare the identification and susceptibility profile using an automated MicrosScan system, PCR-based assay and disk diffusion assay of Enterococcus spp. We evaluated 30 clinical isolates of Enterococcus spp. Isolates were identified by MicrosScan system and PCR-based assay. The detection of antibiotic resistance genes (vancomycin, gentamicin, tetracycline and erythromycin) was also determined by PCR. Antimicrobial susceptibilities to vancomycin (30 µg), gentamicin (120 µg), tetracycline (30 µg) and erythromycin (15 µg) were tested by the automated system and disk diffusion method, and were interpreted according to the criteria recommended in CLSI guidelines. Concerning Enterococcus identification the general agreement between data obtained by the PCR method and by the automatic system was 90.0% (27/30). For all isolates of E. faecium and E. faecalis we observed 100% agreement. Resistance frequencies were higher in E. faecium than E. faecalis. The resistance rates obtained were higher for erythromycin (86.7%), vancomycin (80.0%), tetracycline (43.35) and gentamicin (33.3%). The correlation between disk diffusion and automation revealed an agreement for the majority of the antibiotics with category agreement rates of > 80%. The PCR-based assay, the van(A) gene was detected in 100% of vancomycin resistant enterococci. This assay is simple to conduct and reliable in the identification of clinically relevant enterococci. The data obtained reinforced the need for an improvement of the automated system to identify some enterococci.

DISCORDANCE BETWEEN BODY MASS INDEX AND ANTHROPOMETRIC MEASUREMENTS AMONG HIV-1-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY AND WITH LIPOATROPHY/LIPOHYPERTROPHY SYNDROME

Introduction: Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks. Objective: This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS. Methods: An observational study of 227 adult patients in the Secondary Immunodeficiencies Outpatient Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo (3002 ADEE-HCFMUSP). The sample was divided into three groups; Group 1 = 92 patients on HAART and with self-reported lipodystrophy, Group 2 = 70 patients on HAART without self-reported lipodystrophy and Group 3 = 65 patients not taking HAART. The nutritional status of individuals in the study sample was determined by body mass index (BMI) and percentage of body fat (% BF). The cardiovascular risk and diseases associated with abdominal obesity were determined by waist/hip ratio (WHR) and waist circumference (WC). Results: The prevalence of self-reported lipoatrophy/lipohypertrophy syndrome was 33% among women and 59% among men. Anthropometry showed depletion of fat mass in the evaluation of the triceps (TSF) in the treatment groups with HAART and was statistically independent of gender; for men p = 0.001, and for women p = 0.007. Similar results were found in the measurement of skin folds of the upper and lower body (p = 0.001 and p = 0.003 respectively). In assessing the nutritional status of groups by BMI and % BF, excess weight and body fat were more prevalent among women compared to men (p = 0.726). The WHR and WC revealed risks for cardiovascular and other diseases associated with abdominal obesity for women on HAART and with self-reported LLS (p = 0.005) and (p = 0.011). Conclusions: Anthropometric measurements were useful in the confirmation of the prevalence of LLS. BMI alone does not appear to be a good parameter for assessing the nutritional status of HIV-infected patients on HAART and with LLS. Other anthropometric measurements are needed to evaluate patients with the lipoatrophy/lipohypertrophy syndrome.

Relationship between obsessive-compulsive disorders and diseases affecting primarily the basal ganglia

Obsessive-compulsive disorder (OCD) has been reported in association with some neurological diseases that affect the basal ganglia such as Tourette's syndrome, Sydenham's chorea, Parkinson's disease, and Huntington's disease. Furthermore, studies such as neuroimaging, suggest a role of the basal ganglia in the pathophysiology of OCD. The aim of this paper is to describe the association of OCD and several neurologic disorders affecting the basal ganglia, report the existing evidences of the role of the basal ganglia in the pathophysiology of OCD, and analyze the mechanisms probably involved in this pathophysiology.

Effects of bariatric surgery on the central nervous system and eating behavior in humans: a systematic review on the neuroimaging studies

INTRODUCTION: Neuroimaging studies suggest that obese people might show hyperactivity of brain areas regarding reward processing, and hypoactivity of brain areas concerning cognitive control, when exposed to food cues. Although the effects of bariatric surgery on the central nervous system and eating behavior are well known, few studies have used neuroimage techniques with the aim of investigating the central effects of bariatric surgery in humans. OBJECTIVES: This paper systematically and critically reviews studies using functional neuroimaging to investigate changes on the patterns of activation of central areas related to the regulation of eating behavior after bariatric surgery. METHOD: A search on the databases Medline, Web of Science, Lilacs and Science Direct on Line, was conducted in February 2013, using the keywords "Neuroimaging", "Positron-Emission Tomography", "Magnetic Resonance Imaging", "Gastric Bypass", "Gastroplasty", "Jejunoileal Bypass", "Bariatric Surgery". RESULTS: Seven manuscripts were included; the great majority studied the central effects of Roux en Y gastric bypass, using positron emission tomography or functional magnetic resonance. CONCLUSIONS: Bariatric surgery might normalize the activity of central areas concerned with reward and incentive salience processing, as the nucleus accumbens and mesencephalic tegmental ventral area, as well as circuitries processing behavioral inhibition, as the dorsolateral prefrontal cortex.