Detection of a New Yellow Fever Virus Lineage Within the South American Genotype I in Brazil

Nucleotide sequences of two regions of the genomes of 11 yellow fever virus (YFV) samples isolated from monkeys or humans with symptomatic yellow fever (YF) in Brazil in 2000,2004, and 2008 were determined with the objective of establishing the genotypes and studying the genetic variation. Results of the Bayesian phylogenetic analysis showed that sequences generated from strains from 2004 and 2008 formed a new subclade within the clade 1 of the South American genotype I. The new subgroup is here designated as 1E. Sequences of YFV strains recovered in 2000 belong to the subclade 1D, which comprises previously characterized YFV strains from Brazil. Molecular dating analyses suggested that the new subclade 1E started diversifying from 1D about 1975 and that the most recent 2004-2008 isolates arose about 1985. J. Med. Virol. 82:175-185, 2010. (C) 2009 Wiley-Liss, Inc.

Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity

The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K(D) similar to 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca(2+)) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation.

The small nuclear ribonucleoprotein U1A interacts with NS5 from yellow fever virus

The flavivirus NS5 protein is one of the most important proteins of the replication complex, and cellular proteins can interact with it. This study shows for the first time that the yellow fever virus (YFV) NS5 protein is able to interact with U1A, a protein involved in splicing and polyadenylation. We confirmed this interaction by GST-pulldown assay and by co-immunoprecipitation in YFV-infected cells. A region between amino acids 368 and 448 was identified as the site of interaction of the NS5 protein with U1A. This region was conserved among some flaviviruses of medical importance. The implications of this interaction for flavivirus replication are discussed.

Yellow fever vaccination coverage among children in Brazilian capitals

Brazil recommends universal yellow fever (YF) vaccination for children who reside in or travel to endemic areas. We conducted a household survey to calculate YF vaccine coverage among children 18-30 months of age in 27 capital cities. A total of 9285 children were surveyed in the 15 cities with YF fever universal vaccination; 7290(79%) had documented evidence of YF vaccination by 12 months of age, 7996 (86%) by 18 months of age, and 8479 (91%) prior to the survey. In 12 cities with selective YF vaccination coverage was only 1% by 18 months of age. YF fever vaccination can be improved to reach all children where vaccine is recommended. (C) 2010 Elsevier Ltd. All rights reserved.

Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions

Background: Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions. Methods: Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system. Results: The severity score was lower in the KGF group than in the control group (11.5 vs 17, p = 0.005). The dissection time was lower in the KGF group (9.2 +/- 1.4 min vs 33.9 +/- 9.2 min, p = 0.004) and presented a significant correlation with the severity score (r = 0.83, p = 0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly tower in the KGF group than in the control group. Conclusion: The simulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs

Objective-To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy.Animals-40 healthy bitches.Procedures-After acepromazine premedication, anesthesia was induced. Dogs randomly received 1 of the following 4 epidural treatments 30 minutes before ovariohysterectomy (n = 10/group): saline (0.9% NaCl) solution (control), morphine (0.1 mg/kg), neostigmine (10 pg/kg), or morphine-neostigmine (0.1 mg/kg and 10 pg/kg, respectively). Analgesia was assessed for 24 hours after surgery by use of a visual analogue.scale (VAS; scale of 0 to 10) or numeric descriptive scale (NDS; scale of 0 to 24) and by the need for supplemental analgesia (morphine [0.5 mg/kg, IM] administered when VAS was >= 4 or NDS was >= 8).Results-Significantly more control dogs (n = 8) received supplemental analgesia, compared with the number of neostigmine-treated dogs (1); no dogs in the remaining groups received supplemental analgesia. Compared with values for the control dogs, the NDS scores were lower for morphine-neostigmine-treated dogs (from 2 to 6 hours and at 12 hours) and for morphine-treated dogs (all time points). The NDS scores were lower for morphine-treated dogs at 3, 12, and 24 hours, compared with values for neostigmine-treated dogs. The VAS was less sensitive than the NDS for detecting differences among groups.Conclusions and Clinical Relevance-Epidurally administered neostigmine reduced the use of supplemental analgesia after ovariohysterectorny in dogs. However, analgesic effects were less pronounced than for epidurally administered morphine or morphine-neostigmine. Adding neostigmine to epidurally administered morphine did not potentiate opioid-induced analgesia.

Trends in rheumatic fever: clinical aspects and perspectives in prophylactic treatments

Introduction: Rheumatic fever (RF), a systemic illness that may occur following Group A beta-hemolytic streptococcal (GABHS) pharyngitis in children, is a major problem in countries with limited resources. Because of its long track record and low cost, an injection of benzathine penicillin G (BPG) suspension every 3 or 4 weeks has been used as secondary prophylaxis. Despite its excellent in vitro efficacy, the inability of BPG to eradicate GABHS has been frequently reported.Areas covered: This work reviews the possible causes of failure, as well as the inconvenience of the current prophylactic treatment of acute RF and suggests a new pharmacotherapeutic system that could replace the current one.Expert opinion: RF is a major problem concerning only countries with limited resources and could be considered as a neglected disease. The dose regimen using BPG suspension results in failures, which could be avoided by the use of nanocarrier-based systems. To meet this ultimate goal, the research should be transposed from the laboratory scale to an industrial and clinical application level. This research should be conducted to produce a pharmaceutical dosage form that will be commercially available, consumed by and affordable for patients. However, health, environmental and socioeconomic hazards should be considered.

Does sealing endotracheal tube cuff pressure diminish the frequency of postoperative laryngotracheal complaints after nitrous oxide anesthesia?

Study Objectives: To study endotracheal tube (ETT) cuff pressures during nitrous oxide (N2O) anesthesia when the cuffs are inflated with air to achieve sealing pressure, and to evaluate the frequency of postoperative laryngotracheal complaints.Design: Prospective, randomized, blind study.Setting: Metropolitan teaching hospital.Patients: 50 ASA physical status I and II patients scheduled for elective abdominal surgery.Interventions: Patients received standard general anesthesia with 66% N2O in oxygen. In 25 patients, the ETT cuff was inflated with air to achieve a sealing pressure (P-seal group). In 25 patients, the ETT cuff was inflated with air to achieve a pressure of 25 cm H2O (P-25 group).Measurements and Main Results: ETT intracuff pressures were recorded before (control) and at 30, 60, 90, 120, and 150 minutes during N2O administration. We investigated the frequency and intensity of sore throat, hoarseness, and dysphagia in patients in the Post-Anesthesia Care Unit (PACU) and 24 hours following tracheal extubation. The cuff pressures in the P-seal group were significantly lower than in the P-25 group at all time points studied (p < 0.001), with a significant increase with time in both groups (p < 0.001). The cuff pressures exceeded the critical pressure of 30 cm H2O only after 90 minutes in the P-seal group and already by 30 minutes in the P-25 group. The frequency and intensity of sore throat, hoarseness, and dysphagia were similar in both groups in the PACU and 24 hours after tracheal extubation (p > 0.05).Conclusions: Minimum ETT sealing cuff pressure during N2O anesthesia did not prevent, but instead attenuated, the increase in cuff pressure and did not decrease postoperative laryngotracheal complaints. (C) 2004 by Elsevier B.V.

Postoperative renal function evaluation, through RIFLE criteria, of elderly patients who underwent femur fracture surgery under spinal anesthesia

Introduction. The postoperative acute renal failure (ARF) incidence in different kinds of surgery has rarely been studied. Age, cardiac dysfunction, previous renal dysfunction, intraoperative hypoperfusion, and use of nephrotoxic medications are mentioned as risk factors for ARF at the postoperative period. The postoperative ARF definition was based on the creatinine increase by the RIFLE classification (R = risk, I = injury, F = failure, L = loss, E = end stage), which corresponds to a 1.5 creatinine increase, two to three times, respectively, above the basal value. This study aimed to evaluate the postoperative ARF incidence in elderly patients who underwent femur fracture surgery under subarachnoid anesthesia and stratify it by the RIFLE criteria. Methods. Ninety patients older than 65 years under spinal anesthesia with fixed dosage of 15 mg of 0.5% isobaric bupivacaine associated with morphine 50 g were studied. Immediate postoperative creatinine was considered basal and compared with maximal creatinine evaluated at 24, 48, and 72 postoperative hours. Results. The mean age of the patients was 80.27 years. ARF incidence was 24.44% and stratified this way: R = 21.11% and I = 3.33%. Conclusions. In conclusion, the postoperative ARF incidence after femur fracture surgery in patients over 65 years was 24.44%. By analyzing the stratification based on the RIFLE classification, the incidence was categorized as Risk (R) = 21.11% and Injury (I) = 3.33%.

Intraoperative lactate levels and postoperative complications of pediatric cardiac surgery

Objectives: Correlate arterial lactate levels during the intraoperative period of children undergoing cardiac surgery and the occurrence of complications in the postoperative period. Aim: Arterial lactate levels can indicate hypoperfusion states, serving as prognostic markers of morbidity and mortality in this population. Background: Anesthesia for cardiac pediatric surgery is frequently performed on patients with serious abnormal physiological conditions. During the intraoperative period, there are significant variations of blood volume, body temperature, plasma composition, and tissue blood flow, as well as the activation of inflammation, with important pathophysiological consequences. Methods/Materials: Chart data relating to the procedures and perioperative conditions of the patients were collected on a standardized form. Comparisons of arterial lactate values at the end of the intraoperative period of the patients that presented, or not, with postoperative complications and frequencies related to perioperative conditions were established by odds ratio and nonparametric univariate analysis. Results: After surgeries without cardiopulmonary bypass (CPB), higher levels of arterial lactate upon ICU admission were observed in patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93 vs 1.40 mm). For surgeries with CPB, the same association was observed for cardiovascular (2.90 mm x 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs 2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs 2.40 mm). Conclusion: Elevated intraoperative arterial lactate levels are associated with a higher morbidity and mortality in low- and medium-risk procedures, with or without CPB, in pediatric cardiac surgery.

Surgical risk tests related to cardiopulmonary postoperative complications: comparison between upper abdominal and thoracic surgery

PURPOSE: To investigate if tests used in the preoperative period of upper abdominal or thoracic surgeries are able to differentiate the patients that presented cardiopulmonary postoperative complications. METHODS: Seventy eight patients, 30 submitted to upper abdominal surgery and 48 to thoracic surgery were evaluated. Spirometry, respirometry, manovacuometry, six-minute walk test and stair-climbing test were performed. Complications from immediate postoperative to discharge from hospital were registered. RESULTS: The postoperative complications rate was 17% in upper abdominal surgery and 10% in thoracic surgery. In the univariate regression, the only variable that kept the correlation with postoperative complications in the upper abdominal surgery was maximal expiratory pressure. In thoracic surgery, the maximal voluntary ventilation, six-minute walk test and time in stair-climbing test presented correlation with postoperative complications. After multiple regression only stair-climbing test continued as an important risk predictor in thoracic surgery. CONCLUSION: The respiratory pressure could differentiate patients with complications in upper abdominal surgery, whereas in thoracic surgery, only spirometric values and exercise tests could differentiate them.

Preoperative and Postoperative Nutritional Evaluation in Patients with Non-advanced Megaesophagus

Megaesophagus, an affection characterized by aperistalses of the esophageal body and deficient relaxation of lower esophageal sphincter, has disphagia as main symptom. The aim of this study was to evaluate the nutritional status of patients with non advanced megaesophagus in pre and post-operative periods of cardiomyotomy. Ten patients were evaluated at 5 moments (pre-operative - M 1 and post-operative - 1, 3, 6 ant 12 months after surgery). The anthropometric, hematimetric and biochemical parameters were studied in the 5 moments. Conclusions: 1. Most 017 the patients with non-advanced megaesophagus are eutrophic; 2. Surgical treatment determines an improvement in nutritional status and an increase in HDL cholesterol values.

Higher prevalence of obsessive-compulsive spectrum disorders in rheumatic fever

Objective: This study aims to compare the prevalence of obsessive-compulsive spectrum disorders (OCSD) in psychiatric outpatients with and without a history of rheumatic fever (RF).Methods: An analytical cross-sectional study assessing a large sample of consecutive psychiatric outpatients at a Brazilian private practice was conducted during a 10-year period. Psychiatric diagnoses were made by a senior psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Best-estimate diagnosis procedure was also performed.Results: The total sample comprised 678 subjects, 13 of whom (1.92%) presented with a previous history of RF. This group showed a higher prevalence of subclinical obsessive-compulsive disorder (P=.025) and OCSD (P=.007) when compared to individuals with no such history.Conclusions: A previous history of RF was associated with OCSD. These results suggest that clinicians should be encouraged to actively investigate obsessive-compulsive symptoms and related disorders in patients with a positive history of RF. (C) 2009 Published by Elsevier B.V.

Comparison between actual and predicted postoperative stair-climbing test, walk test and spirometric values in patients undergoing lung resection

OBJETIVO: Verificar se os testes: Volume Expiratório Forçado no 1º segundo (VEF1), Teste de Caminhada de 6 minutos (TC6) e Teste de Escada (TE) se alteram proporcionalmente ao pulmão funcionante ressecado. MÉTODOS: Foram incluídos pacientes candidatos a toracotomia para ressecção pulmonar. No pré-operatório (pré) e no mínimo três meses após a cirurgia (pós), realizaram espirometria, TC6 e TE. O TE foi realizado em escada com 12,16m de altura. O tempo para subir todos os degraus o mais rápido possível foi chamado tempo de escada (tTE). Os cálculos dos valores dos testes preditos para o pós-operatório (ppo) foram realizados conforme o número de segmentos funcionantes perdidos. Os valores pré, ppo e pós foram comparados entre si para cada teste. Estatística: foi utilizada a análise de variância para medidas repetidas (ANOVA), com significância de 5%. RESULTADOS: Foram estudados 40 pacientes. A ressecção pulmonar variou desde o ganho de dois segmentos funcionantes até a perda de 9. Os valores pré, ppo e pós foram respectivamente: VEF1 -pré = 2,6±0,8L, ppo = 2,3±0,8L, pós = 2,3±0,8L (VEF1pré > VEF1ppo = VEF1pós), TC6-pré = 604±63m, ppo = 529±103m, pós = 599±74m (TC6pré = TC6pós > TC6ppo), tTE-pré = 32,9±7,6s, ppo = 37,8±12,1s, pós = 33,7±8,5s (tTEpré = tTEpós < tTEppo). CONCLUSÃO: Nas ressecções pulmonares, este grupo de pacientes perdeu função pulmonar medida através da espirometria, mas não perdeu a capacidade de exercício, medida através dos testes de escada e caminhada.