Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Vaccination with Trypanosoma rangeli modulates the profiles of immunoglobulins and IL-6 at local and systemic levels in the early phase of Trypanosoma cruzi experimental infection

In America, there are two species of Trypanosoma that can infect humans: Trypanosoma cruzi, which is responsible for Chagas disease and Trypanosoma rangeli, which is not pathogenic. We have developed a model of vaccination in mice with T. rangeli epimastigotes that protects against T. cruzi infection. The goal of this work was to study the pattern of specific immunoglobulins in the peritoneum (the site of infection) and in the sera of mice immunized with T. rangeli before and after challenge with T. cruzi. Additionally, we studied the effects triggered by antigen-antibodies binding and the levels of key cytokines involved in the humoral response, such as IL-4, IL-5 and IL-6. The immunization triggered the production of antibodies reactive with T. cruzi in peritoneal fluid (PF) and in serum, mainly IgG1 and, to a lesser magnitude, IgG2. Only immunized mice developed specific IgG3 antibodies in their peritoneal cavities. Antibodies were able to bind to the surface of the parasites and agglutinate them. Among the cytokines studied, IL-6 was elevated in PF during early infection, with higher levels in non-immunized-infected mice. The results indicate that T. rangeli vaccination against T. cruzi infection triggers a high production of specific IgG isotypes in PF and sera before infection and modulates the levels of IL-6 in PF in the early periods of infection.

Analysis of multi-scale systemic risk in Brazil's financial market

This work analyzes whether the relationship between risk and returns predicted by the Capital Asset Pricing Model (CAPM) is valid in the Brazilian stock market. The analysis is based on discrete wavelet decomposition on different time scales. This technique allows to analyze the relationship between different time horizons, since the short-term ones (2 to 4 days) up to the long-term ones (64 to 128 days). The results indicate that there is a negative or null relationship between systemic risk and returns for Brazil from 2004 to 2007. As the average excess return of a market portfolio in relation to a risk-free asset during that period was positive, it would be expected this relationship to be positive. That is, higher systematic risk should result in higher excess returns, which did not occur. Therefore, during that period, appropriate compensation for systemic risk was not observed in the Brazilian market. The scales that proved to be most significant to the risk-return relation were the first three, which corresponded to short-term time horizons. When treating differently, year-by-year, and consequently separating positive and negative premiums, some relevance is found, during some years, in the risk/return relation predicted by the CAPM. However, this pattern did not persist throughout the years. Therefore, there is not any evidence strong enough confirming that the asset pricing follows the model.

SPATIAL VARIABILITY OF SOIL PROPERTIES IN AN AGRARIAN REFORM SETTLEMENT

ABSTRACT The study of soil chemical and physical properties variability is important for suitable management practices. The aim of this study was to evaluate the spatial variability of soil properties in the Malhada do Meio settlement to subsidize soil use planning. The settlement is located in Chapadinha, MA, Brazil, and has an area of 630.86 ha. The vegetation is seasonal submontane deciduous forest and steppe savanna. The geology is formed of sandstones and siltstones of theItapecuru Formation and by colluvial and alluvial deposits. The relief consists of hills with rounded and flat tops with an average altitude of 67 m, and frequently covered over by ferruginous duricrusts. A total of 183 georeferenced soil samples were collected at the depth of 0.00-0.20 m inPlintossolos, Neossolo andGleissolo. The following chemical variables were analyzed: pH(CaCl2), H+Al, Al, SB, V, CEC, P, K, OM, Ca, Mg, SiO2, Al2O3, and Fe2O3; along with particle size variables: clay, silt, and sand. Descriptive statistical and geostatistical analyses were carried out. The coefficient of variation (CV) was high for most of the variables, with the exception of pH with a low CV, and of sand with a medium CV. The models fitted to the experimental semivariograms of these variables were the exponential and the spherical. The range values were from 999 m to 3,690 m. For the variables pH(CaCl2), SB, and clay, there are three specific areas for land use planning. The central part of the area (zone III), where thePlintossolos Pétricos and Neossolos Flúvicos occur, is the most suitable for crops due to higher macronutrient content, organic matter and pH. Zones I and II are indicated for environmental preservation.

Induction of systemic resistance in tomato by the autochthonous phylloplane resident Bacillus cereus

The objective of this work was to verify if the induced resistance mechanism is responsible for the capacity of a phylloplane resident bacteria (Bacillus cereus), isolated from healthy tomato plants, to control several diseases of this crop. A strain of Pseudomonas syringae pv. tomato was used as the challenging pathogen. The absence of direct antibiosis of the antagonist against the pathogen, the significant increase in peroxidases activity in tomato plants exposed to the antagonist and then inoculated with the challenging pathogen, as well as the character of the protection, are evidences wich suggest that biocontrol efficiency presented by the antagonist in previous works might be due to induced systemic resistance (ISR).

Night admission is an independent risk factor for mortality in trauma patients - a systemic error approach

ABSTRACTObjective:to assess the impact of the shift inlet trauma patients, who underwent surgery, in-hospital mortality.Methods:a retrospective observational cohort study from November 2011 to March 2012, with data collected through electronic medical records. The following variables were statistically analyzed: age, gender, city of origin, marital status, admission to the risk classification (based on the Manchester Protocol), degree of contamination, time / admission round, admission day and hospital outcome.Results:during the study period, 563 patients injured victims underwent surgery, with a mean age of 35.5 years (± 20.7), 422 (75%) were male, with 276 (49.9%) received in the night shift and 205 (36.4%) on weekends. Patients admitted at night and on weekends had higher mortality [19 (6.9%) vs. 6 (2.2%), p=0.014, and 11 (5.4%) vs. 14 (3.9%), p=0.014, respectively]. In the multivariate analysis, independent predictors of mortality were the night admission (OR 3.15), the red risk classification (OR 4.87), and age (OR 1.17).Conclusion:the admission of night shift and weekend patients was associated with more severe and presented higher mortality rate. Admission to the night shift was an independent factor of surgical mortality in trauma patients, along with the red risk classification and age.

Volume of breast tissue excised during breast-conserving surgery in patients undergoing preoperative systemic therapy

PURPOSE: We aimed to determine whether clinical examination could adequately ascertain the volume of tissue to be resected during breast-conserving surgery after neoadjuvant therapy. METHODS: We reviewed the clinical reports of 279 patients with histologically diagnosed invasive breast carcinomas treated with neoadjuvant therapy followed by surgery or with primary surgery alone. We estimated volumes of excised tissues, the volume of the tumor mass and the optimal volume required for excision based on 1 cm of clear margins. The actual excess of resected volume was estimated by calculating the resection ratio measured as the volume of the resected specimen divided by the optimal specimen volume. The study endpoints were to analyze the extent of tissue resection and to ascertain the effect of excess resected tissue on surgical margins in both groups of patients. RESULTS: The median tumor diameter was 2.0 and 1.5 cm in the surgery and neoadjuvant therapy groups, respectively. The median volume of resected mammary tissue was 64.3 cm³ in the primary surgery group and 90.7 cm³ in the neoadjuvant therapy group. The median resection ratios in the primary surgery and neoadjuvant therapy groups were 2.0 and 3.3, respectively (p<0.0001). Surgical margin data were similar in both groups. Comparison of the volume of resected mammary tissues with the tumor diameters showed a positive correlation in the primary surgery group and no correlation in the neoadjuvant therapy group. CONCLUSION: Surgeons tend to excise large volumes of tissue during breast-conserving surgery after neoadjuvant therapy, thereby resulting in a loss of the correlation between tumor diameter and volume of the excised specimen.

Systemic acanthamoebiasis associated with canine distemper in dogs in the semiarid region of Paraíba, Brazil

Infections by free-living amoebae can cause systemic disease in animals and humans. We describe the epidemiological, clinical and pathological aspects of disseminated acanthamoebiasis associated with canine distemper in three dogs of the semiarid region of Paraíba, Northeastern Brazil. Affected dogs developed progressive neurological and respiratory signs that progressed to death within in two to 20 days. Gross lesions were irregular and with yellow-reddish nodules randomly distributed in the lungs, heart, kidneys, spleen, lymph nodes, adrenals, and intestine. One dog had foci of malacia in the parietal cortex and another one in nucleus of brain basis. Histologically, pyogranulomas with areas of necrosis and hemorrhage in all organs affected were observed, associated with myriads of intralesional amoebic trophozoites. All three cases were concomitant canine distemper, that possibly triggered immunosuppression in the dogs. The diagnosis was performed through microscopic findings of infection by free-living amoebae and confirmed Acanthamoeba sp. by immunohistochemistry

Effect of ventilation on systemic blood flow evaluated by echodopplercardiography

Systemic blood flow (Q) was measured by echodopplercardiography in 5 normal young adult males during apnea, eupnea and tachypnea. Measurements were made in a recumbent posture at 3-min intervals. Tachypnea was attained by doubling the respiratory frequency at eupnea at a constant tidal volume. An open glottis was maintained during apnea at the resting respiratory level. The Q values were positively correlated with the respiratory frequency, decreasing from eupnea to apnea and increasing from eupnea to tachypnea (P<0.05). These data demonstrate that echodopplercardiography, a better qualified tool for this purpose, confirms the positive and progressive effects of ventilation on systemic blood flow, as suggested by previous studies based on diverse technical approaches

Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) ³115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10, 20, 30, 60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18%, P = NS), DBP (14 vs 8%, P = NS) and HR (22 vs 28%, P = NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 ± 72 vs 41 ± 12 ng/ml, P<0.05; time to reach CMAX (TMAX): 34 ± 18 vs 52 ± 11 min, P<0.05; biological half-life (t1/2b): 0.91 ± 0.54 vs 2.41 ± 1.16 h, P<0.05; area under the curve (AUCT): 245 ± 134 vs 79 ± 54 ng h-1 ml-1, P<0.05; total body clearance (CLT/F): 44 ± 23 vs 26 ± 12 ml min-1 kg-1, P = NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.

Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia

This review describes the ways in which the primary bradycardia and peripheral vasoconstriction evoked by selective stimulation of peripheral chemoreceptors can be modified by the secondary effects of a chemoreceptor-induced increase in ventilation. The evidence that strong stimulation of peripheral chemoreceptors can evoke the behavioural and cardiovascular components of the alerting or defence response which is characteristically evoked by novel or noxious stimuli is considered. The functional significance of all these influences in systemic hypoxia is then discussed with emphasis on the fact that these reflex changes can be overcome by the local effects of hypoxia: central neural hypoxia depresses ventilation, hypoxia acting on the heart causes bradycardia and local hypoxia of skeletal muscle and brain induces vasodilatation. Further, it is proposed that these local influences can become interdependent, so generating a positive feedback loop that may explain sudden infant death syndrome (SIDS). It is also argued that a major contributor to these local influences is adenosine. The role of adenosine in determining the distribution of O2 in skeletal muscle microcirculation in hypoxia is discussed, together with its possible cellular mechanisms of action. Finally, evidence is presented that in chronic systemic hypoxia, the reflex vasoconstrictor influences of the sympathetic nervous system are reduced and/or the local dilator influences of hypoxia are enhanced. In vitro and in vivo findings suggest this is partly explained by upregulation of nitric oxide (NO) synthesis by the vascular endothelium which facilitates vasodilatation induced by adenosine and other NO-dependent dilators and attenuates noradrenaline-evoked vasoconstriction.

New vaccine strategies against enterotoxigenic Escherichia coli: II: Enhanced systemic and secreted antibody responses against the CFA/I fimbriae by priming with DNA and boosting with a live recombinant Salmonella vaccine

The induction of systemic (IgG) and mucosal (IgA) antibody responses against the colonization factor I antigen (CFA/I) of enterotoxigenic Escherichia coli (ETEC) was evaluated in mice primed with an intramuscularly delivered CFA/I-encoding DNA vaccine followed by two oral immunizations with a live recombinant Salmonella typhimurium vaccine strain expressing the ETEC antigen. The booster effect induced by the oral immunization was detected two weeks and one year after the administration of the DNA vaccine. The DNA-primed/Salmonella-boosted vaccination regime showed a synergistic effect on the induced CFA/I-specific systemic and secreted antibody levels which could not be attained by either immunization strategy alone. These results suggest that the combined use of DNA vaccines and recombinant Salmonella vaccine strains can be a useful immunization strategy against enteric pathogens.

Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05), systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05) and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05) from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05). Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05) after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05) after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05) after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock and, particularly, if it has an effect on pulmonary function.

Characterization of the mucosal and systemic immune response induced by Cry1Ac protein from Bacillus thuringiensis HD 73 in mice

The present paper describes important features of the immune response induced by the Cry1Ac protein from Bacillus thuringiensis in mice. The kinetics of induction of serum and mucosal antibodies showed an immediate production of anti-Cry1Ac IgM and IgG antibodies in serum after the first immunization with the protoxin by either the intraperitoneal or intragastric route. The antibody fraction in serum and intestinal fluids consisted mainly of IgG1. In addition, plasma cells producing anti-Cry1Ac IgG antibodies in Peyer's patches were observed using the solid-phase enzyme-linked immunospot (ELISPOT). Cry1Ac toxin administration induced a strong immune response in serum but in the small intestinal fluids only anti-Cry1Ac IgA antibodies were detected. The data obtained in the present study confirm that the Cry1Ac protoxin is a potent immunogen able to induce a specific immune response in the mucosal tissue, which has not been observed in response to most other proteins.

Fever induction pathways: evidence from responses to systemic or local cytokine formation

The immune and central nervous systems are functionally connected and interacting. The concept that the immune signaling to the brain which induces fever during infection and inflammation is mediated by circulating cytokines has been traditionally accepted. Administration of bacterial lipopolysaccharide (LPS) induces the appearance of a so-termed "cytokine cascade" in the circulation more or less concomitantly to the developing febrile response. Also, LPS-like fever can be induced by systemic administration of key cytokines (IL-1ß, TNF-alpha, and others). However, anti-cytokine strategies against IL-1ß or TNF-alpha along with systemic injections of LPS frequently lead to attenuation of the later stages of the febrile response but not of the initial phase of fever, indicating that cytokines are rather involved in the maintenance than in the early induction of fever. Within the last years experimental evidence has accumulated indicating the existence of neural transport pathways of immune signals to the brain. Because subdiaphragmatic vagotomy prevents or attenuates fever in response to intraperitoneal or intravenous injections of LPS, a role for vagal afferent nerve fibers in fever induction has been proposed. Also other sensory nerves may participate in the manifestation of febrile responses under certain experimental conditions. Thus, injection of a small dose of LPS into an artificial subcutaneous chamber results in fever and formation of cytokines within the inflamed tissue around the site of injection. This febrile response can be blocked in part by injection of a local anesthetic into the subcutaneous chamber, indicating a participation of cutaneous afferent nerve signals in the manifestation of fever in this model. In conclusion, humoral signals and an inflammatory stimulation of afferent sensory nerves can participate in the generation and maintenance of a febrile response.