Production of the First Effective Hyperimmune Equine Serum Antivenom against Africanized Bees

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Recent advances in the understanding of brown spider venoms: From the biology of spiders to the molecular mechanisms of toxins

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

L-Aminoacid oxidase from bothrops leucurus venom Induces nephrotoxicity via apoptosis and necrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pancreatitis subtypes survey in 852 childhood-onset systemic lupus erythematosus patients: a multicenter cohort

Pancreatitis is a rare and a life-threatening SLE manifestation in childhood-onset systemic lupus erythematosus (c-SLE). The objective of this study was to systematically classify pancreatitis in c-SLE according to the International Study Group of Pediatric Pancreatitis (INSPPIRE) and determine the overall prevalence, clinical features, laboratory and first episode outcomes. A multicenter cohort study in 10 Pediatric Rheumatology centers, including 852 cSLE patients. Pancreatitis was diagnosed in 22/852 (2.6%) cSLE patients. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%) and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration [1(0-10) vs. 4(0-23) years, p < 0.0001] and higher median of SLEDAI-2K [21(0-41) vs. 2(0-45), p < 0.0001]. The frequencies of fever (p < 0.0001), weight loss (p < 0.0001), serositis (p < 0.0001), nephritis (p < 0.0001), arterial hypertension (p < 0.0001), acute renal failure (p < 0.0001), macrophage activation syndrome (p < 0.0001) and death (p = 0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (p < 0.0001) and the median of prednisone dose [55(15-60) vs. 11(1-90)mg/day, p < 0.0001] were significantly higher in patients with pancreatitis. Of note, the two patients with acute recurrent pancreatitis had two episodes, with pain-free interval of 1 and 4 years. This was the first study characterizing pancreatitis using the INSPPIRE standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.

Effluent volume and dialysis dose in CRRT: time for reappraisal

The results of several studies assessing dialysis dose have dampened the enthusiasm of clinicians for considering dialysis dose as a modifiable factor influencing outcomes in patients with acute kidney injury. Powerful evidence from two large, multicenter trials indicates that increasing the dialysis dose, measured as hourly effluent volume, has no benefit in continuous renal replacement therapy (CRRT). However, some important operational characteristics that affect delivered dose were not evaluated. Effluent volume does not correspond to the actual delivered dose, as a decline in filter efficacy reduces solute removal during therapy. We believe that providing accurate parameters of delivered dose could improve the delivery of a prescribed dose and refine the assessment of the effect of dose on outcomes in critically ill patients treated with CRRT.

Role of Heme Oxygenase-1 in Polymyxin B-Induced Nephrotoxicity in Rats

Polymyxin B (PMB) is a cationic polypeptide antibiotic with activity against multidrug-resistant Gram-negative bacteria. PMB-induced nephrotoxicity consists of direct toxicity to the renal tubules and the release of reactive oxygen species (ROS) with oxidative damage. This study evaluated the nephroprotective effect of heme oxygenase-1 (HO-1) against PMB-induced nephrotoxicity in rats. Adult male Wistar rats, weighing 286 +/- 12 g, were treated intraperitoneally once a day for 5 days with saline, hemin (HO-1 inducer; 10 mg/kg), zinc protoporphyrin (ZnPP) (HO-1 inhibitor; 50 mu mol/kg, administered before PMB on day 5), PMB (4 mg/kg), PMB plus hemin, and PMB plus ZnPP. Renal function (creatinine clearance, Jaffe method), urinary peroxides (ferrous oxidation of xylenol orange version 2 [FOX-2]), urinary thiobarbituric acid-reactive substances (TBARS), renal tissue thiols, catalase activity, and renal tissue histology were analyzed. The results showed that PMB reduced creatinine clearance (P < 0.05), with an increase in urinary peroxides and TBARS. The PMB toxicity caused a reduction in catalase activity and thiols (P < 0.05). Hemin attenuated PMB nephrotoxicity by increasing the catalase antioxidant activity (P < 0.05). The combination of PMB and ZnPP incremented the fractional interstitial area of renal tissue (P < 0.05), and acute tubular necrosis in the cortex area was also observed. This is the first study demonstrating the protective effect of HO-1 against PMB-induced nephrotoxicity.

Tailored Therapy: Matching the Method to the Patient

Clinicians frequently have to decide when dialysis should be initiated and which modality should be used to support kidney function in critically ill patients with acute kidney injury. In most instances, these decisions are made based on the consideration of a variety of factors including patient condition, available resources and prevailing local practice experience. There is a wide variation worldwide in how these factors influence the timing of initiation and the utilization of various modalities. In this article, we review the therapeutic goals of renal support and the relative advantages and shortcomings of different dialysis techniques. We describe strategies for matching the timing of initiation to the choice of modality to individualize renal support in intensive care unit patients. Copyright (C) 2012 S. Karger AG, Basel

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents. Arq Bras Endocrinol Metab. 2012;56(5):331-5

Religious/spiritual coping in people with chronic kidney disease undergoing hemodialysis

The objective of the present study is to investigate the use of religious/spiritual coping mechanisms in patients with chronic kidney disease undergoing hemodialysis, by means of interviews using a sociodemographic questionnaire and the religious/spiritual coping scale. Data analysis was performed using descriptive statistics and multiple linear regression. A total of 123 individuals were interviewed, 79.6% of whom presented a high score for religious/spiritual coping and none of whom presented low or irrelevant scores. The variables that affected the religious/spiritual coping behavior were: gender, age group, treatment time, family income, and religious practice. In conclusion, the participants used religious/spiritual coping mechanisms as a strategy to cope with the disease, particularly women with a higher family income who attend church every week.

Haemodynamic effects of aliskiren in decompensated severe heart failure

Aim: The renin-angiotensin-aldosterone system (RAAS) has dual pathways to angiotensin II production; therefore, multiple blockages may be useful in heart failure. In this study, we evaluated the short-term haemodynamic effects of aliskiren, a direct renin inhibitor, in patients with decompensated severe heart failure who were also taking angiotensin-converting enzyme ( ACE) inhibitors. Materials and methods: A total of 16 patients (14 men, two women, mean age: 60.3 years) were enrolled in the study. The inclusion criteria included hospitalisation due to decompensated heart failure, ACE inhibitor use, and an ejection fraction < 40% (mean: 21.9 +/- 6.7%). The exclusion criteria were: creatinine > 2.0 mg/dl, cardiac pacemaker, serum K+ > 5.5 mEq/l, and systolic blood pressure < 70 mmHg. Patients either received 150 mg/d aliskiren for 7 days (aliskiren group, n = 10) or did not receive aliskiren (control group, n = 6). Primary end points were systemic vascular resistance and cardiac index values. Repeated-measures analysis of variance (ANOVA) was used to assess variables before and after intervention. A two-sided p-value < 0.05 was considered statistically significant. Results: Compared to pre-intervention levels, systemic vascular resistance was reduced by 20.4% in aliskiren patients, but it increased by 2.9% in control patients (p = 0.038). The cardiac index was not significantly increased by 19.0% in aliskiren patients, but decreased by 8.4% in control patients (p = 0.127). No differences in the pulmonary capillary or systolic blood pressure values were observed between the groups. Conclusion: Aliskiren use reduced systemic vascular resistance in patients with decompensated heart failure taking ACE inhibitors.

Fatores de risco pré-operatórios para mediastinite após cirurgia cardíaca: análise de 2768 pacientes

INTRODUÇÃO: A esternotomia mediana longitudinal é a via de acesso mais utilizada no tratamento das doenças cardíacas. As infecções profundas da ferida operatória no pós-operatório das cirurgias cardiovasculares são uma complicação séria, com alto custo durante o tratamento. Diferentes estudos têm encontrado fatores de risco para o desenvolvimento de mediastinite e as variáveis pré-operatórias têm tido especial destaque. OBJETIVO: O objetivo deste estudo é identificar fatores de risco pré-operatórios para o desenvolvimento de mediastinite em pacientes submetidos a revascularização do miocárdio e a substituição valvar. MÉTODOS: Este estudo observacional representa uma coorte de 2768 pacientes operados consecutivamente. O período considerado para análise foi de maio de 2007 a maio de 2009 e não houve critérios de exclusão. Foi realizada análise univariada e multivariada pelo modelo de regressão logística das 38 variáveis pré-operatórias eleitas. RESULTADOS: Nesta série, 35 (1,3%) pacientes evoluíram com mediastinite e 19 (0,7%) com osteomielite associada. A idade média dos pacientes foi de 59,9 ± 13,5 anos e o EuroSCORE de 4,5 ± 3,6. A mortalidade hospitalar foi de 42,8%. Na análise multivariada, foram identificadas três variáveis como preditoras independentes de mediastinite: balão intra-aórtico (OR 5,41, 95% IC [1,83 -16,01], P=0,002), hemodiálise (OR 4,87, 95% IC [1,41 - 16,86], P=0,012) e intervenção vascular extracardíaca (OR 4,39, 95% IC [1,64 - 11,76], P=0,003). CONCLUSÃO: O presente estudo demonstrou que necessidade do suporte hemodinâmico pré-operatório com balão intra-aórtico, hemodiálise e intervenção vascular extracardíaca são fatores de risco para o desenvolvimento de mediastinite após cirurgia cardíaca.

Age influences outcomes in 70-year or older patients undergoing isolated coronary artery bypass graft surgery

Objective: To analyze the results of isolated on-pump coronary artery bypass graft surgery (CABG) in patients >= 70 years old in comparison to patients <70 years old. Methods: Patients undergoing isolated CABG were selected for the study. The patients were assigned into two groups: G1 (age >= 70 years old) and G2 (age <70 years old). The endpoints were in-hospital mortality, acute myocardial infarction (AMI), stroke, re-exploration for bleeding, intraaortic balloon pump for circulatory shock, respiratory complications, acute renal failure, mediastinitis, sepsis, atrial fibrillation, and complete atrioventricular block (CAVB). Results: A total of 1,033 were included in the study: G1 comprised 257 (24.8%) patients G2 776 (75.2%). Patients in G1 were more likely to have in-hospital mortality than in G2 (8.9% vs. 3.6%, respectively; P=0.001), while the incidence of AMI was similar (5.8% vs. 5.5%; P=0.87) in G2. More patients in G1 had re-exploration for bleeding (12.1% vs. 6.1%; P=0.003). Compared to G2, G1 had more incidences of respiratory complications (21.4% vs. 9.1%; P<0.001), mediastinitis (5.1% vs. 1.9%; P=0.013), stroke (3.9% vs. 1.3%; P=0.016), acute renal failure (7.8% vs. 1.3%; P<0.001), sepsis (3.9% vs. 1.9%; P=0.003), atrial fibrillation (15.6% vs. 9.8%; P=0.016), and CAVB (3.5% vs. 1.2%; P=0.023). There was no significant difference in the use of the intraaortic balloon pump. In the forward stepwise multivariate logistic regression analysis, age >= 70 years was an independent predictive factor for higher in-hospital mortality (P=0.004), re-exploration for bleeding (P=0.002), sepsis (P=0.002), respiratory complications (P<0.001), mediastinitis (P=0.016), stroke (P=0.029), acute renal failure (P<0.001), atrial fibrillation (P=0.021), and CAVB (P=0.031). Conclusion: This study suggests that patients of age >= 70 years were at increased risk of death and other complications in the CABG's postoperative period in comparison to younger patients.

Production of Human Antibody Fragments Binding to Melittin and Phospholipase A2 in Africanised Bee Venom: Minimising Venom Toxicity

The hybrid created from the crossbreeding of European and African bees, known as the Africanised bee, has provided numerous advantages for current beekeeping. However, this new species exhibits undesirable behaviours, such as colony defence instinct and a propensity to attack en masse, which can result in serious accidents. To date, there is no effective treatment for cases of Africanised bee envenomation. One promising technique for developing an efficient antivenom is the use of phage display technology, which enables the production of human antibodies, thus avoiding the complications of serum therapy, such as anaphylaxis and serum sickness. The aim of this study was to produce human monoclonal single-chain Fv (scFv) antibody fragments capable of inhibiting the toxic effects of Africanised bee venom. We conducted four rounds of selection of antibodies against the venom and three rounds of selection of antibodies against purified melittin. Three clones were selected and tested by enzyme-linked immunosorbent assay to verify their specificity for melittin and phospholipase A2. Two clones (C5 and C12) were specific for melittin, and one (A7) was specific for phospholipase A2. In a kinetic haemolytic assay, these clones were evaluated individually and in pairs. The A7-C12 combination had the best synergistic effect and was chosen to be used in the assays of myotoxicity inhibition and lethality. The A7-C12 combination inhibited the in vivo myotoxic effect of the venom and increased the survival of treated animals.

Current outcome of prioritized patients for kidney transplantation

Purpose: To analyze the outcome of deceased donor recipients given priority in allocation due to lack of access for dialysis and compare this data to the one obtained from non-prioritized deceased donor kidney transplant recipients. Materials and Methods: we reviewed electronic charts of 31 patients submitted to kidney transplantation that were given priority in transplantation program due to lack of access for dialysis from January 2005 to December 2008. Immunological and surgical complications rates, and grafts and patients survival rates were analyzed. These data were compared to those obtained from 100 regular patients who underwent kidney transplantation without allocation priority during the same period. Results: Overall surgical complication rate was 25.8% and 27% in the patients with priority in allocation and in the non-prioritized patients, respectively. There was no statistical significant difference for surgical complications (p = 1.0), immunological complications (p = 0.21) and graft survival (p = 0.19) rates between the groups. However, patient survival rate was statistically significant worse in prioritized patients (p = 0.05). Conclusions: patients given priority in allocation owing to lack of access for dialysis have higher mortality rate when compared to those non-prioritized.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: Analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostate-specific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.