Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011

Background:Circulatory system diseases are the first cause of death in Brazil.Objective:To analyze the evolution of mortality caused by heart failure, by ischemic heart diseases and by ill-defined causes, as well as their possible relations, in Brazil and in the geoeconomic regions of the country (North, Northeast, Center-West, South and Southeast), from 1996 to 2011.Methods:Data were obtained from DATASUS and death declaration records with codes I20 and I24 for acute ischemic diseases, I25 for chronic ischemic diseases, and I50 for heart failure, and codes in chapter XIII for ill-defined causes, according to geoeconomic regions of Brazil, from 1996 to 2011.Results:Mortality rates due to heart failure declined in Brazil and its regions, except for the North and the Northeast. Mortality rates due to acute ischemic heart diseases increased in the North and Northeast regions, especially from 2005 on; they remained stable in the Center-West region; and decreased in the South and in the Southeast. Mortality due to chronic ischemic heart diseases decreased in Brazil and in the Center-West, South and Southeast regions, and had little variation in the North and in the Northeast. The highest mortality rates due to ill-defined causes occurred in the Northeast until 2005.Conclusions:Mortality due to heart failure is decreasing in Brazil and in all of its geoeconomic regions. The temporal evolution of mortality caused by ischemic heart diseases was similar to that of heart failure. The decreasing number of deaths due to ill-defined causes may represent the improvement in the quality of information about mortality in Brazil. The evolution of acute ischemic heart diseases ranged according to regions, being possibly confused with the differential evolution of ill-defined causes.

Atrial Fibrillation and Non-cardiovascular Diseases: A Systematic Review

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an unfavorable prognosis, increasing the risk of stroke and death. Although traditionally associated with cardiovascular diseases, there is increasing evidence of high incidence of AF in patients with highly prevalent noncardiovascular diseases, such as cancer, sepsis, chronic obstructive pulmonary disease, obstructive sleep apnea and chronic kidney disease. Therefore, considerable number of patients has been affected by these comorbidities, leading to an increased risk of adverse outcomes.The authors performed a systematic review of the literature aiming to better elucidate the interaction between these conditions.Several mechanisms seem to contribute to the concomitant presence of AF and noncardiovascular diseases. Comorbidities, advanced age, autonomic dysfunction, electrolyte disturbance and inflammation are common to these conditions and may predispose to AF.The treatment of AF in these patients represents a clinical challenge, especially in terms of antithrombotic therapy, since the scores for stratification of thromboembolic risk, such as the CHADS2 and CHA2DS2VASc scores, and the scores for hemorrhagic risk, like the HAS-BLED score have limitations when applied in these conditions.The evidence in this area is still scarce and further investigations to elucidate aspects like epidemiology, pathogenesis, prevention and treatment of AF in noncardiovascular diseases are still needed.

Clinical presentation and survival of smear-positive pulmonary tuberculosis patients of a University General Hospital in a developing country

From January 1995 to August 1997 we evaluated prospectively the clinical presentation, laboratory findings and short-term survival of smear-positive pulmonary tuberculosis (TB) patients who sought care at our hospital. After providing informed, written consent, the patients were interviewed and laboratory tests were performed. Information about survivorship and death was collected through September 1998. Eighty-six smear-positive pulmonary TB patients were enrolled; 26.7% were HIV-seropositive. Seventeen HIV-seronegative pulmonary TB patients (19.8%) presented chronic diseases in addition to TB. In the multiple logistic regression analysis a CD4+ cell count <= 200 cell/mm³ was independently associated with HIV seropositivity. In the Cox regression model, fitted to all patients, HIV seropositivity and age > or = 50 years were independently associated with decreased survival. Among HIV-seronegative persons, the presence of an additional disease increased the risk of death of almost six-fold. Use of antiretroviral drugs was associated with a lower risk of death among HIV-seropositive smear-positive pulmonary TB patients (RH = 0.32, 95% CI 0.10-0.92). In our study smear-positive pulmonary TB patients had a low short-term survival rate that was strongly associated with HIV infection, age and co-morbidities. Therapy with antiretroviral drugs reduced the short-term risk of death among HIV-seropositive patients after TB diagnosis.

Dengue-2 infection and the induction of apoptosis in human primary monocytes

Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-α and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.

Chromatin regulation in schistosomes and histone modifying enzymes as drug targets

Only one drug is currently available for the treatment and control of schistosomiasis and the increasing risk of selecting strains of schistosome that are resistant to praziquantel means that the development of new drugs is urgent. With this objective we have chosen to target the enzymes modifying histones and in particular the histone acetyltransferases and histone deacetylases (HDAC). Inhibitors of HDACs (HDACi) are under intense study as potential anti-cancer drugs and act via the induction of cell cycle arrest and/or apoptosis. Schistosomes like other parasites can be considered as similar to tumours in that they maintain an intense metabolic activity and rate of cell division that is outside the control of the host. We have shown that HDACi can induce apoptosis and death of schistosomes maintained in culture and have set up a consortium (Schistosome Epigenetics: Targets, Regulation, New Drugs) funded by the European Commission with the aim of developing inhibitors specific for schistosome histone modifying enzymes as novel lead compounds for drug development.

The impact of highly active antiretroviral therapy on the survival of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil

The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < -2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60-7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001).

Triage at the Emergency Department: association between triage levels and patient outcome

AbstractOBJECTIVEIdentify association between sociodemographic, clinical and triage categories with protocol outcomes developed at Hospital São Paulo (HSP).METHODSRetrospective cohort study conducted with patients older than 18 years submitted to the triage protocol in August 2012. Logistic regression was used to associate the risk categories to outcomes (p-value ≤0,05).RESULTSMen with older age and those treated in clinical specialties had higher rates of hospitalization and death. Patients in the high-priority group had hospitalization and mortality rates five and 10.6 times, respectively (p < 0.0001).CONCLUSIONThe high-priority group experienced higher hospitalization and mortality rates. The protocol was able to detect patients with more urgent conditions and to identify risk factors for hospitalization and death.

Behavior of Eucalyptus grandis and E. cloeziana seedlings grown in arsenic-contaminated soil

Arsenic has been considered the most poisonous inorganic soil pollutant to living creatures. For this reason, the interest in phytoremediation species has been increasing in the last years. Particularly for the State of Minas Gerais, where areas of former mining activities are prone to the occurrence of acid drainage, the demand is great for suitable species to be used in the revegetation and "cleaning" of As-polluted areas. This study was carried out to evaluate the potential of seedlings of Eucalyptus grandis (Hill) Maiden and E. cloeziana F. Muell, for phytoremediation of As-polluted soils. Soil samples were incubated for a period of 15 days with different As (Na2HAsO4) doses (0, 50, 100, 200, and 400 mg dm-3). After 30 days of exposure the basal leaves of E. cloeziana plants exhibited purple spots with interveinal chlorosis, followed by necrosis and death of the apical bud at the 400 mg dm-3 dose. Increasing As doses in the soil reduced root and shoot dry matter, plant height and diameter in both species, although the reduction was more pronounced in E. cloeziana plants. In both species, As concentrations were highest in the root system; the highest root concentration was found in E. cloeziana plants (305.7 mg kg-1) resulting from a dose of 400 mg dm-3. The highest As accumulation was observed in E. grandis plants, which was confirmed as a species with potential for As phytoextraction, tending to accumulate As in the root system and stem.

Immunohistochemical evaluation of e-cadherin, Ki-67 and PCNA in canine mammary neoplasias: correlation of prognostic factors and clinical outcome

E-cadherin is a cell-cell adhesion molecule and low e-cadherin expression is related to invasiveness and may indicate a bad prognosis in mammary neoplasms. The expression of cell proliferation markers PCNA and especially Ki-67, has also proved to have a strong prognostic value in this tumor class. The expression of these markers was related to the clinical-pathological characteristics of 73 surgically removed mammary tumors in female dogs by immunohistochemistry. There was no statistical correlation between these markers and death by neoplasm, survival time and disease-free interval. However, the loss of e-cadherin expression and marked Ki-67 expression (p=0.016) were considered statistically significant for the diagnosis (p=0.032). When evaluated as independent factors, there was evidence of the relationship between the loss of e-cadherin expression and high PCNA expression with changes in the body status (divided into obese, normal and cachectic) of female dogs (p=0.030); there was also evidence of the relationship between pseudopregnancy and e-cadherin alone (p=0.021) and for ulceration and PCNA alone (p=0.035). The significant correlation between the markers expression and these well known prognostic factors used individually or in combination suggests their prognostic value in canine mammary tumors.

Experimental infection of rabbits with a recombinant bovine herpesvirus type 5 (BoHV-5) gI, gE and US9-negative

Bovine herpesvirus type 5 (BoHV-5) is a major cause of viral meningoencephalitis in cattle. The expression of different viral proteins has been associated with BoHV-5 neuropathogenesis. Among these, gI, gE and US9 have been considered essential for the production of neurological disease in infected animals. To evaluate the role of gI, gE and US9 in neurovirulence, a recombinant from which the respective genes were deleted (BoHV-5 gI-/gE-/US9-) was constructed and inoculated in rabbits of two age groups (four and eight weeks-old). When the recombinant virus was inoculated through the paranasal sinuses of four weeks-old rabbits, neurological disease was observed and death was the outcome in 4 out of 13 (30.7 %) animals, whereas clinical signs and death were observed in 11/13 (84.6%) of rabbits infected with the parental virus. In eight weeks-old rabbits, the BoHV-5 gI-/gE-/US9- did not induce clinically apparent disease and could not be reactivated after dexamethasone administration, whereas wild type BoHV-5 caused disease in 55.5% of the animals and was reactivated. These findings reveal that the simultaneous deletion of gI, gE and US9 genes did reduce but did not completely abolish the neurovirulence of BoHV-5 in rabbits, indicating that other viral genes may also play a role in the induction of neurological disease.

Sawfly larval poisoning in cattle: Report on new outbreaks and brief review of the literature

Sawfly larval poisoning (SLP) is an acute hepatotoxicosis documented in livestock in Australia, Denmark and in countries of South America. It is caused by the ingestion of the larval stage of insects of the suborder Symphyta, order Hymenoptera, commonly known as "sawfly". Three species of sawfly are reportedly involved in the toxicosis. The insect involved in Australian SLP is Lophyrotoma interrupta (Pergidae), in Denmark the cause of SLP is the ingestion of the larvae Arge pullata (Argidae), and in South American countries documented outbreaks of SLP were caused by the ingestion of yet another sawfly, Perreyia flavipes (Pergidae). In all geographical areas where it occurred, SLP causes important livestock losses. In cattle, as well as in other affected species, the disease has a short clinical course and in many outbreaks affected cattle can be found dead. When observed, clinical signs include apathy, recumbence, tremors, paddling movements and death in 24-48 hours. Neurological signs such aggressiveness attributable to hepatic encephalopathy are also observed. In cases with a more protracted course icterus and photodermatitis may develop. Gross findings included ascites, petechiae and ecchymosis over serosal surfaces of thoracic and abdominal cavities, and an enlarged liver that displays accentuation of the lobular pattern and edema of the gall bladder wall. Sawfly larval body fragments and heads are consistently found in the fore stomachs and occasionally abomasum of affected cattle. Main microscopic lesions are restricted to the liver and consist of centrolobular (periacinar) to massive hepatocellular necrosis. In most lobules necrotic areas extended up to the portal triads where only a few viable hepatocytes remain. Mild to moderate lymphocyte necrosis is seen in lymphatic tissues. Cases occur in the winter months when the larval stages of the sawfly are developing. D-amino acid-containing peptides have been found to be the toxic principle in each sawfly involved in SLP. The octapeptide lophyrotomin is the major toxin in the in the larvae of Australian and Danish sawflies and is present in small amounts in the larvae of South American sawfly. The heptadecapeptide pergidin is the main toxin in the South American sawfly while small amounts of pergidin have been found in the other two species of toxic sawfly. During the winter of 2011 (July-August) four outbreaks of SLP were diagnosed in the State of Rio Grande do Sul, Brazil. The findings in those outbreaks are reported here and a brief review of the literature regarding SLP around the world is provided.

Pathological and parasitological aspects of the peacock (Pavo cristatus) infection by Tanaisia(Paratanaisia)bragai

Abstract:Trematodes belonging to the family Eucotylidae, including Tanaisia(Paratanaisia)bragaiSantos, 1934are parasites of the kidney and ureter that affect several species of domestic and wild birds. Tanaisia bragaiis considered a low pathogenic parasite, but high worm burdens may determine clinical complications, including signs of apathy, weight loss, diarrhea and death. This paper describes the first report of infection by T. bragai in peacocks (Pavo cristatus), which constitutes a new host record and offers data on the lesions associated to this parasitism, although the degree of pathogenicity and parasite load may be considered mild. These birds did not exhibit clinical signs of parasitism. The macroscopic exam revealed discreet yellow spots on the liver. In the histological sections of the kidney, specimens of T. bragai were found in the collecting ducts, which were markedly dilated, with a thickened wall. Other findings included a mild inflammatory reaction in the wall of the ducts (but sometimes absent), flattening of lining epithelial cells and small, multifocal points of calcification around the collecting ducts. The microscopic examination of the parasites revealed trematodes with an elongated body, well-developed sub terminal oral sucker, pharynx present, short esophagus, cecum somewhat undulating or not, with blind end, testes symmetrical, equatorial, irregular in shape or slightly lobed, vitelline fields extending in both pre-ovarian and post ovarian fields, uterus very long, intercecal or sometimes overlapping the cecum and containing large quantities of eggs. The present findings suggest the need for further diagnostic studies on the prevalence of this trematode in peacocks as well as pathologic studies for the determination of the potential pathogenicity of this parasite in this species of bird. Moreover, infected peacocks could serve as carriers of T. bragai to be transferred to other bird species, thereby contributing to the dispersion of the parasite.

Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

Abstract: Amorimia exotropica is an important plant associated with sudden death in cattle in Southern Brazil. In order to understand the mechanisms by which A. exotropica causes acute lesions in the heart and kidney of intoxicated animals, an experiment was conducted to determine the histopathology and ultrastructure of myocardial and renal lesions of intoxicated rabbits. After receiving 18g/kg of dried plant, six rabbits died suddenly. At necropsy, the liver was swollen and no other macroscopic lesions were observed. Histologically, centrolobular and midzonal hepatocytes were vacuolated. These vacuoles were strong PAS stained positive, suggesting that they corresponded to glycogen accumulations. In some regions of the ventricular septum and ventricles were found vacuoles of different sizes and the kidneys of two rabbits showed vacuolar degeneration on distal convoluted tubules. Ultrastructurally, the myocardium had cardiomyocytes swelling with separation of myofibrils bundles and rupture and disorganization of the sarcomeres. The mitochondria displayed swelling, disorganization, disruption of the mitochondrial cristae, and electron-dense matrix. Some mitochondria exhibited eccentric projections of their membranes with disruption of both outer and inner membranes. The sarcoplasmic reticulum had no alterations, whereas the T-tubule system was occasionally dilated and ruptured. The kidneys had mitochondrial swelling with disorganization and disruption of the mitochondrial cristae. The vacuoles result from the swelling of the endoplasmatic reticulum and usually were located between two basolateral infoldings and mitochondria, occurring preferentially around the nucleus. The myocytes and T system damages induced by A. exotropica result in acute heart failure and death. Furthermore, this mechanism of cardiotoxicity may be common to all plant containing monofluoroacetate.

Partial sequence and toxic effects of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

A neurotoxic peptide, granulitoxin (GRX), was isolated from the sea anemone Bunodosoma granulifera. The N-terminal amino acid sequence of GRX is AKTGILDSDGPTVAGNSLSGT and its molecular mass is 4958 Da by electrospray mass spectrometry. This sequence presents a partial degree of homology with other toxins from sea anemones such as Bunodosoma caissarum, Anthopleura fuscoviridis and Anemonia sulcata. However, important differences were found: the first six amino acids of the sequence are different, Arg-14 was replaced by Ala and no cysteine residues were present in the partial sequence, while two cysteine residues were present in the first 21 amino acids of other toxins described above. Purified GRX injected ip (800 µg/kg) into mice produced severe neurotoxic effects such as circular movements, aggressive behavior, dyspnea, tonic-clonic convulsion and death. The 2-h LD50 of GRX was 400 ± 83 µg/kg.

Genetic alterations in head and neck squamous cell carcinomas

The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations) and tumor suppressor gene inactivation (loss of function mutations), leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC) development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.