Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is one of the most important causes of end-stage renal failure. The bradykinin B1 receptor has been associated with tissue inflammation and renal fibrosis. To test for a role of the bradykinin B1 receptor in podocyte injury, we pharmacologically modulated its activity at different time points in an adriamycin-induced mouse model of FSGS. Estimated albuminuria and urinary protein to creatinine ratios correlated with podocytopathy. Adriamycin injection led to loss of body weight, proteinuria, and upregulation of B1 receptor mRNA. Early treatment with a B1 antagonist reduced albuminuria and glomerulosclerosis, and inhibited the adriamycin-induced downregulation of podocin, nephrin, and alpha-actinin-4 expression. Moreover, delayed treatment with antagonist also induced podocyte protection. Conversely, a B1 agonist aggravated renal dysfunction and even further suppressed the levels of podocyte-related molecules. Thus, we propose that kinin has a crucial role in the pathogenesis of FSGS operating through bradykinin B1 receptor signaling. Kidney International (2011) 79, 1217-1227; doi:10.1038/ki.2011.14; published online 16 March 2011

Essential role of nuclear factor-kappa B for NADPH oxidase activity in normal and anhildrotic ectodermal dysplasia leukocytes

This work investigated the functional role of nuclear factor-kappa B (NF-kappa B) in respiratory burst activity and in expression of the human phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase genes CYBB, CYBA, NCF1, and NCF2. U937 cells with a stably transfected repressor of NF-kappa B (IKB alpha-S32A/S36A) demonstrated significantly lower superoxide release and lower CYBB and NCF1 gene expression compared with control U937 cells. We further tested Epstein-Barr virus (EBV)-transformed B cells from patients with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), an inherited disorderof NF-kappa B function. Superoxide release and CYBB gene expression by EDA-ID cells were significantly decreased compared with healthy cells and similar to cells from patients with X-linked chronic granulomatous disease (X91 degrees CGD). NCF1 gene expression in EDA-ID S321 cells was decreased compared with healthy control cells and similar to that in autosomal recessive (A47 degrees) CGD cells. Gel shift assays demonstrated loss of recombinant human p50 binding to a NF-kappa B site 5` to the CYBB gene in U937 cells treated with NF-kappa B inhibitors, repressor-transfected U937 cells, and EDA-ID patients cells. Zymosan phagocytosis was not affected by transfection of U937 cells with the NF-kappa B repressor. These studies show that NF-kappa B is necessary for CYBB and NCF1 gene expression and activation of the phagocyte NADPH oxidase in this model system.

The kidney in different stages of the cardiovascular continuum

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum. The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death. This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress. In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease. Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Prevalência da asma brônquica e seus fatores de risco na população adulta de Pelotas, Rio Grande do Sul, 2001

A asma brônquica é uma doença crônica inflamatória das vias aéreas que vem despertando preocupação crescente, em função do aumento na sua incidência e mortalidade observados nos últimos anos. Com o objetivo principal de avaliar a sua prevalência e seus fatores de risco, conduziu-se um estudo epidemiológico de base populacional, delineamento transversal, em uma amostra representativa de adultos de 20 a 69 anos de idade, residentes na zona urbana de Pelotas, RS. Foram entrevistadas 1.968 pessoas. Desse total, 446 pessoas foram aleatoriamente selecionadas para realizarem espirometria e, quando esta mostrava-se normal, teste de broncoprovocação com metacolina. Ainda foram realizados testes para atopia. Houve 9,6% de recusas para as entrevistas e 20,2% de perdas para os exames complementares. Mais de metade da amostra era constituída por pessoas com idade inferior a 50 anos, sendo 57% do sexo feminino e a maioria da raça branca. A renda familiar, na maioria da amostra, era de até três salários mínimos. A prevalência de “sintomas atuais de asma” foi de 6,0%. Observou-se variação na prevalência de asma com a utilização de diferentes critérios diagnósticos: asma cumulativa: 14,3%; diagnóstico médico de asma: 12,9%; asma atual: 4,7%; e sintomas atuais ou reversibilidade (obstrução com resposta ao broncodilatador ou broncoprovocação positiva): 9,3%. Gravidade da asma foi avaliada conforme história de hospitalização por asma, mais de seis visitas ao pronto-socorro por ano e internação em Unidade de Tratamento Intensivo. Cerca de 30% dos asmáticos preencheram algum critério de gravidade para asma. Apenas 20% dos pacientes com asma haviam consultado no último ano pela doença e somente 30% utilizava alguma medicação antiasmática. Em relação aos fatores de risco, na análise bruta, as variáveis associadas à prevalência de “sintomas atuais de asma” foram: sexo feminino, faixa etária dos 60 aos 69 anos, cor da pele não branca, baixas escolaridade e renda familiar, história familiar de asma e atopia, história pessoal de atopia, tabagismo, índice de massa corporal baixo e a presença de distúrbios psiquiátricos menores. Na análise multivariada, construiu-se um modelo teórico-hierarquizado cujas variáveis de um determinado nível foram controladas pelas variáveis de níveis precedentes e do mesmo nível. Permaneceram relacionados à presença de “sintomas atuais de asma” os seguintes fatores de risco, em ordem decrescente de razão de prevalência: história paterna e materna de asma (RP=5,4), presença de distúrbios psiquiátricos menores (RP=2,8); idade de 60 a 69 anos (RP=2,1); renda familiar inferior a 1,01 SM (RP=2,1); história pessoal de atopia (RP=1,9); e sexo feminino (RP=1,4). Os resultados do presente estudo salientam a variação na prevalência de asma com a utilização de diferentes critérios diagnósticos, e confirmam a importância dos fatores genéticos, sociais e relacionados ao estilo de vida na ocorrência da doença.

Prevalência da deleção 4977pb do DNA mitocondrial em pacientes com doença renal crônica em tratamento conservador ou submetidos a hemodiálise no sul do Brasil

Introdução. Danos no DNA mitocondrial (DNAmt) têm sido descritos em pacientes com doença renal crônica (DRC). Estes danos podem ser avaliados através da deleção 4977pb do DNAmt em diversos tecidos. Métodos. Identificamos a prevalência da deleção 4977pb do DNAmt através da técnica da reação em cadeia da polimerase (PCR) no sangue de pacientes com DRC em tratamento conservador (creatinina >2mg/dl) ou submetidos a hemodiálise. Resultados. A freqüência da ocorrência da deleção do DNAmt foi de 73.1% (38/52) nos pacientes com DRC submetidos a hemodiálise, 57.1% (27/42) nos pacientes com DRC em tratamento conservador e 27.8% (15/54) nos controles (P< 0.001). Não encontramos aumento da freqüência desta deleção em relação a idade dos pacientes com DRC (P= 0.54) ou ao tempo de diálise (P= 0.70). Conclusão. Danos no DNAmt podem ser induzidos pela DRC em especial nos pacientes submetidos a hemodiálise. Desta forma, a deleção 4977pb do DNAmt pode servir como um marcador de danos moleculares em pacientes com DRC.

Dois ensaios em economia da saúde

We test for asymmetric information in health insurance by means of a special survey conducted in 1998 in Brazil. The distinct features of the database are twofold. First, it displays information on individual morbidity-an issue still unexplored in the empiricalliterature on insurance. Second, unlike other countries studied in the literature, the coverage leveI offered by the Brazilian free public health service is much lower than its private counterpart-making informational problems more likely. We find evidence of information asymmetries associated with some diseases (e.g., hypertension and heart disease) but not with others (e.g., cancer and chronic renal disease).

Knowledge of the patients regarding leprosy and adherence to treatment

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is known for its great disfiguring capacity and is considered an extremely serious disease to public health worldwide. The state of Ceará ranks 13th in number of cases of leprosy in Brazil, and fourth in Northeastern region, with an average of 2,149 new cases diagnosed every year. This study aimed to evaluate the knowledge of leprosy patients regarding treatment, and to assess the level of treatment adherence and its possible barriers. The study was conducted in the reference center for dermatology, from September 2010 to October 2010, in Fortaleza, Ceará. The study data were collected by means of a structured interview, along with the Morisky-Green test, in order to assess treatment adherence and barriers to adherence. A total of 70 patients were interviewed, out of whom 66 were new cases. The majority of patients were between 42 and 50 years old, and 37 (52.9%) were male. Most patients were clinically classified as presentingmultibacillary leprosy (80%), and 78.6% of them were from Fortaleza, Brazil. The Morisky-Green test indicated that 62.9% of patients presented a low level of adherence (p < 0.005), despite claiming to aware of the disease risks. However, it was observed that 57.1% of the patients had no difficulty adhering to treatment, while 38.6% reported little difficulty. This study shows that despite the patients claiming to be familiar with leprosy and its treatment, the Morisky-Green test clearly demonstrated that they actually were not aware of the principles of therapy, which is evidenced by the low degree of treatment adherence

Redução da morbi-mortalidade na síndrome de hellp completa com o uso de altas doses de dexametasona

Objective: To determine the clinical maternal and neonatal outcomes in HELLP syndrome patients treated with dexamethasone who either developed renal injury or renal insufficiency and to identify predictive values of urea and creatinine for the identification of subjects with HELLP syndrome at risk of developing renal insufficiency. Methods: Non-radomized intervention study of dexamethasone use in HELLP syndrome. A total of 62 patients were enrolled at Maternidade Escola Januário Cicco (MEJC). Patients received a total of 30 mg of dexamethasone IV, in three doses of 10 mg every 12 hours. A clinical and laboratory follow up were performed at 24, 48 and 72 hours. Patients were followed up to 6 months after delivery. Patients were grouped in accordance to renal function, i.e, normal and some type of renal lesion. Renal lesion was considered when creatinine was equal or greater than 1.3 mg/dl and diuresis less than 100 ml in 4 hours period and renal insufficiency was defined when dialysis was needed. Results: A total of 1230 patients with preeclampsia were admitted at MEJC. Of those 62 (5%) developed HELLP syndrome. There was no statistical difference in the groups with renal involvement or normal renal function with respect to the demographics, type of anesthesia used and delivery, and weight of the newborn. An improvement in the AST, ALT, LDH, haptoglobine, antithrombine, fibrinogenen and platelets was observed within 72 hours after dexamethosone use. There was a significant increase in the diuresis within the interval of 6 hours before the delivery and 24 hours after it. Of the 62 patients, 46 (74. 2%) had normal renal function and 16 (25.8%) evolved with renal lesion, with 5 (8.1%) needing dialysis. These 5 patients who received dialysis recovered the xi renal function. The delay in administering dexamethasone increased in 4.6% the risk of development of renal insufficiency. Patients with renal insufficiency had received significantly more blood products than subjects without renal lesion (p=0.03). Diuresis, leukocytes, uric acid, urea, creatinine were significantly different between the groups with normal renal function, renal lesion and renal insufficiency. The levels of creatinine 1.2mg/dl and uric acid 51mg/dl, at admission are predictive of subjects who will evolve with renal lesion (p<0.001). Maternal mortality was 3.2%. None of the subjects with renal insufficiency evolved with chronic renal disease. Conclusions: Dexamethasone in patients with HELLP syndrome seems to reduce significantly the hepatic microthrombosis and normalize hemostasis as seen by improvement of liver function. Renal injury can be considered, in HELLP syndrome, when creatinine levels are greater than 1.3 mg/dl and diuresis less than 100 ml/h in interval of 4 hours. The level of creatinine greater than 1.2 mg/dl and urea greater than 51mg/dl are predictive of subjects with HELLP syndrome who will develop renal injury. Patients who receive more red cell packs develop renal insufficiency. Finally, the delay in administering dexamethasone increases the risk of developing renal insufficiency

Efetividade da terapia fisica descongestiva na cicatrização de úlceras venosas

A venous ulcer is the most serious clinical manifestation of chronic venous failure, and the most frequent in lower limbs, accounting for 70% of all ulcers. Patients may suffer from this infirmity for several years without healing of the lesion if treatment is inadequate. The aim of this investigation was to verify the effectiveness of decongestive physical therapy in the healing of venous ulcers. This is a quasi-experimental, interventionist study, with paired, non-probabilistic sampling, composed of 50 patients divided into two groups: control and intervention, each composed of 25 patients. Both groups were identically treated for six months with daily dressings and the latter also underwent complex physical therapy consisting of a combination of the following techniques: manual lymphatic drainage, compression bandaging, lower limb elevation, myolymphokinetic exercises and skin care. The study was approved (Protocol no. 59/2007) by the Ethics Committee of the State University of Southeast Bahia. The Mann-Whitney and Chi-square tests were applied for data analysis. After statistical analysis the patients who underwent therapy showed a statistically significant difference with respect to wound contraction starting in the second month of treatment. Compared to the control, the intervention group showed a greater reduction in both pain and edema starting in the third and fourth month of therapy, respectively. To reinforce these findings, the mean percentage of tissue present at the base of the ulcer (granulation/fibrin ratio) was calculated. The intervention group showed greater granulation at the base of the ulcer compared to the control, significant from the second month of treatment on. It was observed in this study that lymphotherapy, when compared between the intervention and control groups, accelerated the healing process, and reduced pain and edema in the affected limbs. It is expected, therefore, that these results widen scientific knowledge and we suggest that this therapy be used 78 not only to reduce lymphedema, but also as a treatment option for venous ulcers, given its easy application and low cost. The data, therefore, demonstrated the importance of basic care on the part of a multiprofessional and transdisciplinary health team involved in the healing process of these infirmities, thereby contributing to better quality of life in these individuals

Avaliação dos efeitos da reeducação postural global (rpg) em pacientes com espondilite anquilosante

The Ankylosing Spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton, leading to limitation of spine mobility and functional disability. Physical therapy, especially exercise, is an important part in your treatment. The Global Postural Reeducation(GPR),a method that uses stretching based on evaluation of muscular chains, with significant interference in postural changes may be a complementary alternative for the treatment of this disease. The aim was to evaluate the effects of Global Postural Reeducation (GPR) in patients with Ankylosing Spondylitis (AS) and compare GPR with group conventional segmental self-stretching and breathing exercises. This is a controlled interventional study of 38 patients divided into 2 groups: a GPR group (n = 22) and a control group (n = 16). Both groups were treated over four months. With the GPR group patients, positions that stretched the shortened muscle chains were used. With the control group patients, conventional segmental self-stretching and breathing exercises were performed. The variables analyzed were: pain intensity, morning stiffness, spine mobility, chest expansion, functional capacity (Health Assessment Questionnaire - Spondyloarthropathies - HAQ-S), quality of life (Medical Outcome Study Short Form 36 Healthy Survey-SF-36), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI). Statistical analysis was used with a significance level of p < 0.05. There was a statistically significant difference for all the parameters analyzed between pre and post-treatment in both groups. In the inter-group comparison the GPR group showed a statistically significant improvement in morning stiffness (p = 0.01), spine mobility parameters, except finger-floor distance (p = 0.11), in chest expansion (p = 0.02), and in the physical aspect component of the SF-36 (p = 0.00).Finally, we observed that this sample of patients with AS ,treatment with RPG 60 seems to have a better response in some clinical measures, than the conventional self stretching performed in groups. Further studies are needed to further evaluate this therapeutic alternative in the EA

Ovine leptospirosis in Brazil

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

Participação da excreção renal de cálcio, fósforo, sódio e potássio na homeostase em cães sadios e cães com doença renal crônica

Na doença renal crônica (DRC) a manutenção da homeostase de água e sódio é o primeiro problema a ser contornado pelo organismo e com o agravamento das lesões renais surgem outros problemas graves relacionados à homeostase de cálcio e fósforo. O presente estudo tem por escopo avaliar a excreção renal de cálcio, fósforo, sódio e potássio, e o perfil sérico destes eletrólitos em cães normais e em cães com DRC naturalmente adquirida. Foram avaliados três grupos de cães adultos, machos ou fêmeas, de raças variadas. Animais normais compuseram o grupo controle (G1) e os cães com DRC foram distribuídos em dois grupos de acordo com os estágios de comprometimento da função renal (G2 e G3, respectivamente, estágios 1-2 e estágios 3-4, descritos pela IRIS 2006 staging CKD). Os cães do G3 apresentaram aumento das concentrações séricas de cálcio ionizado e fósforo, além de diminuição da concentração sérica de sódio. Quanto à excreção renal dos eletrólitos analisados, os animais dos grupos G1 e G2 apresentaram diminuição de carga filtrada e aumento de excreção fracionada, mas as excreções urinárias não variaram significativamente. Os resultados são indicativos de que os rins de cães com DRC podem manter a excreção urinária dos eletrólitos em valores se melhantes aos dos normais. O mecanismo envolve aumento da excreção fracionada na medida em que haja diminuição da filtração glomerular. Esse processo de compensação, entretanto, pode perder a eficiência nos estágios mais avançados da enfermidade no que se refere à manutenção das concentrações séricas de fósforo e sódio.

Qualidade de vida de pessoas com úlceras venosas atendidos no ambulatório de um hospital universitário

Descriptive study aimed to analyze the quality of life (QOL) of patients with venous ulcers (UV) outpatient clinic of a university hospital in Natal / RN. The aim of the study population was composed of 50 patients with UV treated at the cardiology clinic of a university teaching hospital at the tertiary level. The study was approved by the Ethics Committee of the Federal University of Rio Grande do Norte (Protocol 279/09). Data collection was performed over a period of two months by the very a masters degree and an academic nursing through the application of a form concerning the socio-demographic, clinical, and health care, and the instruments WHOQOL and WHOQOL - old. The data were analyzed with SPSS 15.0, using descriptive and inferential statistics presented in the form of tables, charts and graphs. Of the surveyed, female predominance, age range 59 years, Catholic, low education, married, with up to 03 children, not working, retired, or with occupations requiring long periods in one position, wage income of up to 02 minimum wages, inadequate sleep, patients with chronic venous insufficiency and other chronic diseases such as diabetes and hypertension, were taking medications for treatment, being a minority to IVC. In patients with predominant only one injury, time of injury up to five years, inadequate rest, pain, edema and lesions colonized. The assistance the UV patients began treatment of the injury until four months after the onset of the ulcer, and services primary health care most wanted, access to angiologist by reference form, commuted by public transportation, received support regarding the treatment of injuries. The topical product most used in the lesion was healing, and few were using compression therapy. respondents suffer discrimination in society, showed changes in quality of life after the occurrence of ulcer in relation to leisure, pain, restriction of social / school / transportation; barring employment / financial / social ladder; Physical appearance / discrimination and restriction of domestic activity. These changes were related to the time of injury and found that the more chronic injury is the most negative changes occur in their QV (ρ = 0.000). Analyzing the characteristics of QV measured by the WHOQOL-bref, we found for the two general questions they are dissatisfied with their health (ρ = 0.023) and all areas have significant difference compared with the worst QV have the injury of more than 5 years (ρ = 0.000). The QV measured by the WHOQOL-old, we found that these patients had no changes from the time of injury. We conclude that the QV of patients with UV was considered unsatisfactory when compared to the time of injury on more than 5 years which shows that the quality of life worsens with time the chronic UV.

Assistência aos portadores de úlceras venosas: proposta de protocolo

Venous ulcers (VU), recurrent chronic wounds resulting from Chronic Venous Insufficiency (CVI), affect different age groups and would severely affect ambulation of patients. The lesions require treatment lasting and complex and are responsible for significant morbidity and mortality. Thus, this study aims to identify the important aspects covered in the scientific literature protocol for assisting patients with venous ulcers, identifying the issues to be proposed by the judges of the study (nurses, doctors and physiotherapists) to the protocol of care provided to patients venous ulcers and present the structure of protocol proposed by the judges of the study to assist patients with venous ulcers treated at a referral hospital of Rio Grande do Norte. This is a descriptive study using a quantitative approach, carried out at the dressings, located in the outpatient surgical clinic of the Hospital University Onofre Lopes (HUOL), located in East Sanitary District, Natal-RN. The sample consisted of 39 professionals, 30 nurses, seven doctors and two physical therapists, team members HUOL surgical clinic and other public and private institutions of Rio Grande do Norte and Jequié/Bahia. These professionals were the judges responsible for selecting the guidelines already proposed in the literature on VU protocols. Approved by the Ethics in Research HUOL (Report n.o 081/07), began the first stage of the study which consisted of reviewing the scientific literature about the relevant aspects to be included in a protocol for assisting patients with VU. These aspects were organized into a proposed questionnaire to the judges of the study. Following examination, held on the content validation with application of the Kappa (K), accepting a score higher than 0.80 and the Likert Scale, whereas rates from 4.0 to 5.0. The data collected were organized in Microsoft Excel and exported into Statistical Package for Social Sciences (SPSS) 15.0. The literature review included national and international scientific articles, thesis, dissertation and institutional protocols. Regarding the characterization of professional nurses predominated (76.1%), between 34 and 45 years (41.0%), female (79.5%), married/consensual union (46.2%), with specialization in VU care (61.5%), working in the hospital network (46.1%), with up to 5 years experience in VU (69.2%) and claiming to feel prepared to care for these injuries (92.3 %). With regard to aspects that had very good agreement (K ≥ 0.81), remained the items found in the literature with some modifications. In the analysis of the proposed evaluation items had very important, ranging from 4.1 (drug treatment) to 4.9 (patient assessment and care of the injury and the injured and perilesional skin). The proposition of the protocol is arranged in eleven items: A) Evaluation of patient and lesion, B) Registration and documentation, C) the wound and perilesional skin, D) an indication of coverage, E) Use of antibiotic and pain treatment, F) Surgical treatment of CVI, G) Drug treatment, H) Improving venous return and prevetion of recurrence, I) Referral of patients, J) Training and K) Reference and counter reference