Dermatoses bolhosas auto-imunes

Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire), pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. ©2009 by Anais Brasileiros de Dermatologia.

Pneumonias

Pneumonia is an infectious disease with great morbidity and mortality worldwide. According to the current guidelines recommendations the authors reviewed the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). In this paper will be presented data about etiology, clinics and diagnostic tools. © Copyright Moreira Jr. Editora.

Experimental infection of commercial layers using a Salmonella enterica sorovar Gallinarum strain: Blood serum components and histopathological changes

The purpose of the study was to evaluate the blood serum components and histopathological findings of commercial layers experimentally infected with Salmonella Gallinarum (SG), the microorganism responsible for the fowl typhoid. 180 commercial layers were distributed into three groups (G): G1 and G2 received 0.2mL of inoculum containing 3.3x10 8 and 3.3x10 5 CFU of resistant SG to the nalidix acid (Nal r)/mL, respectively, directly into their crops; G3 did not receive the inoculum (control group). The birds were inoculated when they were 5 days old and the euthanasia was performed 24 hours before and after infection and 3, 5, 7 and 10 days after the administration of the inoculum. In each day of collection, blood samples were obtained for biochemical tests of the blood serum besides macroscopic and histopathological examination of the birds. Data were submitted to analysis of variance by the SAS statistical program and the means were compared by Tukeýs test (P<0,05). In the serum biochemical profile it was observed that the infection interfered in the values of total protein, albumin, calcium, phosphorus, cholesterol, triglycerides, GGT and ALT in the infected groups. The macroscopic examination showed hepatomegaly, alteration of the hepatic color and hemorrhagic spots in the kidneys of animals from G1. The histopathology showed degeneration of hepatocytes in G1 and G2 although other lesions like multifocal hepatic necrosis and inflammatory infiltrate on the liver and kidneys were restricted to G1. The alterations were more evident on G1 which received a higher concentration of bacteria/mL when compared to G2. The results showed that the correlation between biochemical alterations and macroscopic and histopathological lesions can assist the comprehension of the pathophysiology of fowl typhoid, supplying important information for the diagnosis and prognosis of this disease.

Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

Mare's folliculogenesis: Assessment of ovarian and perifollicular vascular perfusion by doppler ultrasound

Background: Ultrasound Doppler is a new technology that has recently been used in large animal reproduction. As the conventional ultrasound (B-mode) it is a noninvasive technique, but with the advantage of allows the assessment of the hemodynamic of reproductive tract in real time. The observation of important features of the vascularization and changes that occur during physiological processes that were not previously seen on B-mode encourage a reassessment of the concepts already established on the events of the reproductive physiology of animals and their applications. Review: In attempt to re-understand the equine reproductive physiology and finding practical uses to this new technique, authors showed that, during the follicular deviation, features are observed by Doppler before being observed under B-mode ultrasound like changes in the speed of the blood flow two days before deviation of the follicle size and one day before the increase in blood flow area of the follicular wall. According to another study ovulation is characterized by a decreased blood flow of the follicular wall in the last four hours preceding it, as well as the serration of the granulosa layer and formation of a non vascularized apex, but in our ongoing study, the ability to decrease the vascularity was not found. Very vascularized follicles are associated with higher rates of oocyte maturation and pregnant that does less vascularized follicles in the preovulatory phase. Those follicles that have septated evacuation (or prolonged) showed more vascularization and serration of the granulosa one hour before ovulation than follicles that ovulate normally, and this vascularization includes the apex of the follicle, the follicular wall portion that is not vascularized in normal ovulation. Another study reported that hemorrhagic follicles have better vascularization of the follicular wall on the days preceding ovulation than follicles destined to ovulate. Some authors also showed that anovulatory follicles grow in size at the same rate as ovulatory follicles, but the percentage of vascularization of its wall is much smaller at 35 mm. Another study characterized that the vascular wall of the follicle that results in the first ovulation of the year is much smaller on the day before ovulation than the number of vessels present in a follicle that will ovulate in the middle of the breeding season. In these cases, the use of Doppler ultrasound can help to prevent economic losses as insemination of mares in cycles that are not able of resulting in pregnancy. This review aims to gather the information found in the literature about the characteristics of follicular hemodynamic of mares taking into account moments of deviation in follicle size, ovulation, ovulation failure and follicular viability. Conclusion: The Doppler technology has the potential to provide important information about the follicular environment and thus be used in practice in search of the perfect equine reproductive management, achieving better utilization of genetic material and increasing the financial return. The use of this new tool opens a large area for several interesting studies that will contribute to the knowledge of the physiological events of the mare for that this technique can soon be effectively applied.

Fondaparinux em intervenção coronária percutânea no tratamento da síndrome coronária aguda

Background: Fondaparinux is considered an agent with a well-established safety and efficacy profile in the treatment of non-ST segment elevation acute coronary syndromes, but when used alone, is associated to a higher incidence of thrombotic complications during invasive coronary procedures, requiring the supplementation of an anti-IIa agent. This study aimed to evaluate the efficacy and safety of percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndromes previously treated with fondaparinux. Methods: Prospective, controlled registry enrolling 127 consecutive patients submitted to an early invasive stratification during treatment with fondaparinux, with supplementation of intravenous unfractionated heparin at a dose of 85 U/kg at the time of PCI. Results: The rate of the composite primary endpoint including death, acute myocardial infarction, stroke, stent thrombosis or emergency myocardial revascularization was 3.2%. The cumulative incidence of major bleeding and vascular complications was 3.2%. There were no cases of guidecatheter thrombosis or abrupt vessel closure. Conclusions: PCI in patients with acute coronary syndromes receiving fondaparinux is associated with a low rate of major adverse cardiovascular ischemic events and severe hemorrhagic complications. Supplementation of unfractionated heparin during the invasive procedures eliminates the risk of catheter-related thrombosis.

Molar incisor hypomineralisation: Possible aetiological factors in children from urban and rural areas

Aim: To analyse factors potentially associated with molar incisor hypomineralisation (MIH) development. METHODS: A population-based study was carried out with 903 children aged from 6-12 years old, born and residing in rural and urban areas of the town of Botelhos, State of Minas Gerais, Brazil. Their mothers completed a structured medical history questionnaire, from pregnancy to the child's 3rd year of life. Two examiners evaluated children for MIH according to criteria suggested by the European Academy of Paediatric Dentistry. Descriptive analyses of the data and odds ratios (OR) with 95% test-based confidence intervals (CI) were estimated. Chisquare test was used to evaluate the differences between groups. RESULTS: The prevalence of MIH in children from rural area (RA) was significantly higher than those from the urban area (UA) (24.9% versus 17.8%, p= 0.01). In urban children, neither significant associations with MIH nor medical problems were found. In rural children, however, MIH was significantly more common among those whose mothers had experienced medical problems during pregnancy (OR=2.11; 1.01-4.37 CI 95%; p=0.04), who had throat infections (OR=2.93; 1.47-5.87 CI 95%; p=0.01), who had high fever (OR=1.91; 1.07-3.39 CI 95%; p=0.02), and who had used amoxicillin associated with other antibiotics (OR=1.92; 1.02-3.62 CI 95%; p=0.04) during the first 3 years of life. CONCLUSION: This study suggests a link between MIH and health problems during pregnancy, as well as environmental factors.

American visceral leishmaniasis: Factors associated with lethality in the state of São Paulo, Brazil

Objectives. To identify factors associated with death in visceral leishmaniasis (VL) cases. Patients and Methodology. We evaluated prognostic factors for death from VL in São Paulo state, Brazil, from 1999 to 2005. A prognostic study nested in a clinical cohort was carried out by data analysis of 376 medical files. A comparison between VL fatal cases and survivors was performed for clinical, laboratory, and biological features. Association between variables and death was assessed by univariate analysis, and the multiple logistic regression model was used to determine adjusted odds ratio for death, controlling confounding factors. Results. Data analysis identified 53 fatal cases out of 376 patients, between 1999 and 2005 in São Paulo state. Lethality was 14.1 (53/376), being higher in patients older than fifty years. The main causes of death were sepsis, bleeding, liver failure, and cardiotoxicity due to treatment. Variables significantly associated with death were severe anemia, bleeding, heart failure, jaundice, diarrhea, fever for more than sixty days, age older than fifty years, and antibiotic use. Conclusion. Educational health measures are needed for the general population and continuing education programs for health professionals working in the affected areas with the purpose of identifying and treating early cases, thus preventing the disease evolution towards death. © 2012 Geraldine Madalosso et al.

Triacontyl p-coumarate: An inhibitor of snake venom metalloproteinases

Snake venom metalloproteinases (SVMPs) participate in a number of important biological, physiological and pathophysiological processes and are primarily responsible for the local tissue damage characteristic of viperid snake envenomations. The use of medicinal plant extracts as antidotes against animal venoms is an old practice, especially against snake envenomations. Such plants are sources of many pharmacologically active compounds and have been shown to antagonize the effects of some venoms and toxins. The present study explores the activity of triacontyl p-coumarate (PCT), an active compound isolated from root bark of Bombacopsis glabra vegetal extract (Bg), against harmful effects of Bothropoides pauloensis snake venom and isolated toxins (SVMPs or phospholipase A2). Before inhibition assays, Bg or PCT was incubated with venom or toxins at ratios of 1:1 and 1:5 (w/w; venom or isolated toxins/PCT) for 30 min at 37 °C. Treatment conditions were also assayed to simulate snakebite with PCT inoculated at either the same venom or toxin site. PCT neutralized fibrinogenolytic activity and plasmatic fibrinogen depletion induced by B. pauloensis venom or isolated toxin. PCT also efficiently inhibited the hemorrhagic (3MDH-minimum hemorrhagic dose injected i.d into mice) and myotoxic activities induced by Jararhagin, a metalloproteinase from B. jararaca at 1:5 ratio (toxin: inhibitor, w/w) when it was previously incubated with PCT and injected into mice or when PCT was administered after toxin injection. Docking simulations using data on a metalloproteinase (Neuwiedase) structure suggest that the binding between the protein and the inhibitor occurs mainly in the active site region causing blockade of the enzymatic reaction by displacement of catalytic water. Steric hindrance may also play a role in the mechanism since the PCT hydrophobic tail was found to interact with the loop associated with substrate anchorage. Thus, PCT may provide a alternative to complement ophidian envenomation treatments. © 2012 Elsevier Ltd. All rights reserved.

Intensified peginterferon α-2a dosing increases sustained virologic response rates in heavy, high viral load hepatitis c genotype 1 patients with high low-density lipoprotein

BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS, genotype 1 patients with baseline HCV RNA≥400,000 IU/mL and body weight ≥85 kg were randomized to 48 weeks of 180 μg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 μg/wk PegIFN α-2a followed by 36 weeks of 180 μg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86×10 IU/mL) versus patients with low LDL (n=262; 4.02×10 IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS: Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight. Copyright © 2013 by Lippincott Williams & Wilkins.

Case report: Disseminated Mycobacterium tuberculosis infection in a dog

An uncommon disseminated Mycobacterium tuberculosis infection is described in a 12-year-old female dog presenting with fever, dyspnea, cough, weight loss, lymphadenopathy, melena, epistaxis, and emesis. The dog had a history of close contact with its owner, who died of pulmonary tuberculosis. Radiographic examination revealed diffuse radio-opaque images in both lung lobes, diffuse visible masses in abdominal organs, and hilar and mesenteric lymphadenopathy. Bronchial washing samples and feces were negative for acid-fast organisms. Polymerase chain reaction (PCR)-based species identification of bronchial washing samples, feces, and urine revealed M. tuberculosis using PCR-restriction enzyme pattern analysis-PRA. Because of public health concerns, which were worsened by the physical condition of the dog, euthanasia of the animal was recommended. Rough and tough colonies suggestive of M. tuberculosis were observed after microbiological culture of lung, liver, spleen, heart, and lymph node fragments in Löwenstein-Jensen and Stonebrink media. The PRA analysis enabled diagnosis of M. tuberculosis strains isolated from organs. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.

Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998-2000) and BR3 (2003-05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue. © 2013 Drumond et al.

Structural and Phylogenetic Studies with MjTX-I Reveal a Multi-Oligomeric Toxin - a Novel Feature in Lys49-PLA2s Protein Class

The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of tropical and subtropical countries and is recognized as a neglected disease by the World Health Organization. One of the main components of snake venoms is the Lys49-phospholipases A2, which is catalytically inactive but possesses other toxic and pharmacological activities. Preliminary studies with MjTX-I from Bothrops moojeni snake venom revealed intriguing new structural and functional characteristics compared to other bothropic Lys49-PLA2s. We present in this article a comprehensive study with MjTX-I using several techniques, including crystallography, small angle X-ray scattering, analytical size-exclusion chromatography, dynamic light scattering, myographic studies, bioinformatics and molecular phylogenetic analyses.Based in all these experiments we demonstrated that MjTX-I is probably a unique Lys49-PLA2, which may adopt different oligomeric forms depending on the physical-chemical environment. Furthermore, we showed that its myotoxic activity is dramatically low compared to other Lys49-PLA2s, probably due to the novel oligomeric conformations and important mutations in the C-terminal region of the protein. The phylogenetic analysis also showed that this toxin is clearly distinct from other bothropic Lys49-PLA2s, in conformity with the peculiar oligomeric characteristics of MjTX-I and possible emergence of new functionalities inresponse to environmental changes and adaptation to new preys. © 2013 Salvador et al.

Chemical characterization and acaricide potential of essential oil from aerial parts of Tagetes patula L. (Asteraceae) against engorged adult females of Rhipicephalus sanguineus (Latreille, 1806)

Rhipicephalus sanguineus, commonly known as the brown dog tick, is one of the most widely distributed species of tick. In dogs, it can cause anemia and provide the transmission of pathogenic microorganisms such as Babesia canis, Ehrlichia canis, Hepatozoon canis, Anaplasma platys, and Mycoplasma haemocanis. To man, it can transmit the intracellular parasites Rickettsia rickettsii and Rickettsia conorii, the causative agents of the Rocky Mountain spotted fever in the Americas and Mediterranean and spotted fever in Europe and North Africa. Its control is performed by applying synthetic formulations composed of pyrethroids; however, continued use of these products results in environmental damage and acquisition of resistance. Alternatively, studies with botanical insecticides have been increasingly recurrent. Therefore, this study aimed to test the efficacy of essential oil of Tagetes patula, a ruderal species widely described in the literature for its insecticidal properties, in engorged females of R. sanguineus by the adults immersion test (AIT) and impregnated paper disk test (IPDT). The essential oil used, through gas chromatography coupled to mass spectrometry, revealed the presence of 55 compounds, being the 4-vinyl guaiacol and gamma terpinene the majority ones. The AIT compared to the IPDT was more efficient in inhibiting oviposition of tick; however, the eggs laid by the females submitted to saturated atmosphere with essential oil, from IPDT, not hatched, interrupted their development cycle. Besides being a pioneer work, the results presented here contributes to new researches, aiming the incorporation of essential oil in an acaricide for use in the environment. © 2013 Springer-Verlag Berlin Heidelberg.

Systemic CA-MRSA infection following trauma during soccer match in inner Brazil: Clinical and molecular characterization

Even though community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) was described a decade ago, reports from Brazil are scarce and cases occurred in large urban centers. We report MRSA sepsis in a 16-year-old male from a small town and who had no history of exposure to healthcare or recent travel. After trauma during a soccer match, he presented swelling in the right thigh, which evolved in a month to cellulitis complicated by local abscess, orchitis and pneumonia. The patient presented severe sepsis, with fever and respiratory failure. Laboratory findings included blood leukocyte counts above 40,000/mm3 and thrombocytopenia. He was submitted to mechanical ventilation and therapy with vancomycin and imipenem. He had a slow but favorable response to therapy and was discharged after six weeks of hospitalization. MRSA grew from blood cultures and respiratory aspirates obtained before antimicrobial therapy. The isolate belonged to sequence type 5, spa type t311, harbored SCCmec type IV and genes for Panton-Valentine leukocidin and Enterotoxin A. The pulsed-field gel electrophoresis pattern was distinct from North American classic CA-MRSA clones. However, the sequence type and the spa type revealed that the clone belong to the same clonal complex isolated in Argentina. This is the first CA-MRSA infection reported in that region, with significant epidemiologic and clinical implications. © 2013 Elsevier Inc.