Why medical schools are tolerant of unethical behavior.

The exposure to unethical and unprofessional behavior is thought to play a major role in the declining empathy experienced by medical students during their training. We reflect on the reasons why medical schools are tolerant of unethical behavior of faculty. First, there are barriers to reporting unprofessional behavior within medical schools including fear of retaliation and lack of mechanisms to ensure anonymity. Second, deans and directors do not want to look for unethical behavior in their colleagues. Third, most of us have learned to take disrespectful circumstances in health care institutions for granted. Fourth, the accreditation of medical schools around the world does not usually cover the processes or outcomes associated with fostering ethical behavior in students. Several initiatives promise to change that picture.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis.

INTRODUCTION: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. HYPOTHESIS: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. OBJECTIVE: To evaluate the main markers of atherosclerosis in patients with PG. METHOD: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. RESULTS: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. DISCUSSION AND CONCLUSION: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Association between chronic kidney disease stages and changes in ambulatory blood pressure monitoring parameters.

INTRODUCTION: Blood pressure (BP) assessment affects the management of arterial hypertension (AH) in chronic kidney disease (CKD). CKD patients have specific patterns of BP behavior during ambulatory blood pressure monitoring (ABPM). OBJECTIVES: The aim of the current study was to evaluate the associations between progressive stages of CKD and changes in ABPM. METHODOLOGY: This is a cross-sectional study with 851 patients treated in outpatient clinics of a university hospital who underwent ABPM examination from January 2004 to February 2012 in order to assess the presence and control of AH. The outcomes considered were the ABPM parameters. The variable of interest was CKD staging. Confounding factors included age, sex, body mass index, smoking, cause of CKD, and use of antihypertensive drugs. RESULTS: Systolic BP (SBP) was associated with CKD stages 3b and 5, irrespective of confounding variables. Pulse pressure was only associated with stage 5. The SBP coefficient of variation was progressively associated with stages 3a, 4 and 5, while the diastolic blood pressure (DBP) coefficient of variation showed no association. SBP reduction was associated with stages 2, 4 and 5, and the decline in DBP with stages 4 and 5. Other ABPM parameters showed no association with CKD stages after adjustments. CONCLUSION: Advanced stages of CKD were associated with lower nocturnal dipping and greater variability in blood pressure.

Predictors of autosomal dominant polycystic kidney disease progression: a Brazilian single-center cohort.

INTRODUCTION: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. METHODS: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. RESULTS: The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome. CONCLUSIONS: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.

ANCA-associated vasculitis following Oxford-AstraZeneca COVID-19 vaccine in Brazil: Is there a causal relationship? A case report.

This article presents a case of rapidly progressive glomerulonephritis following the Oxford-AstraZeneca COVID-19 vaccine in a female patient 58 years old. After 5 days, she presented fatigue, paleness, arthralgia on hands, knees, ankles, foamy urine, and elevated blood pressure. Exams showed serum creatinine of 2.2 mg/dL (baseline creatinine of 1.0 mg/dL). Urinalysis revealed hematuria, and her 24-h urinary protein excretion was 4.4 g. Additional exams showed hypercholesterolemia, severe anemia, and normal serum albumin. Testing of antineutrophil cytoplasmic antibodies anti-myeloperoxidase was positive at a titer of 1/80. Serum and urine protein electrophoresis and other exams showed no alterations. She was started on steroid pulse therapy after worsening kidney function, reaching serum creatinine of 3.3 mg/dL. A kidney biopsy revealed crescentic glomerulonephritis with glomerular sclerosis, fibrous crescents, interstitial fibrosis, and tubular atrophy. Induction therapy was given with intravenous cyclophosphamide 0.5 g/m2 for 6-monthly pulses, followed by maintenance therapy with oral azathioprine at 2 mg/kg and prednisone tapering. The patient did not develop any complications during the induction therapy, and is currently on maintenance therapy with a serum creatinine of 1.87 mg/dL.

Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have potent self-renewal capacity and differentiate into multiple cell types. For many reasons, these cells are a promising therapeutic alternative to treat patients with severe COVID-19 and pulmonary post-COVID sequelae. These cells are not only essential for tissue regeneration; they can also alter the pulmonary environment through the paracrine secretion of several mediators. They can control or promote inflammation, induce other stem cells differentiation, restrain the virus load, and much more. In this work, we performed single-cell RNA-seq data analysis of MSCs in bronchoalveolar lavage samples from control individuals and COVID-19 patients with mild and severe clinical conditions. When we compared samples from mild cases with control individuals, most genes transcriptionally upregulated in COVID-19 were involved in cell proliferation. However, a new set of genes with distinct biological functions was upregulated when we compared severely affected with mild COVID-19 patients. In this analysis, the cells upregulated genes related to cell dispersion/migration and induced the γ-activated sequence (GAS) genes, probably triggered by IFNGR1 and IFNGR2. Then, IRF-1 was upregulated, one of the GAS target genes, leading to the interferon-stimulated response (ISR) and the overexpression of many signature target genes. The MSCs also upregulated genes involved in the mesenchymal-epithelial transition, virus control, cell chemotaxis, and used the cytoplasmic RNA danger sensors RIG-1, MDA5, and PKR. In a non-comparative analysis, we observed that MSCs from severe cases do not express many NF-κB upstream receptors, such as Toll-like (TLRs) TLR-3, -7, and -8; tumor necrosis factor (TNFR1 or TNFR2), RANK, CD40, and IL-1R1. Indeed, many NF-κB inhibitors were upregulated, including PPP2CB, OPTN, NFKBIA, and FHL2, suggesting that MSCs do not play a role in the "cytokine storm" observed. Therefore, lung MSCs in COVID-19 sense immune danger and act protectively in concert with the pulmonary environment, confirming their therapeutic potential in cell-based therapy for COVID-19. The transcription of MSCs senescence markers is discussed.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis / Avaliação dos fatores de risco de aterosclerose e disfunção endotelial em pacientes com glomerulopatias primárias

Abstract Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

Gamma Oryzanol Treats Obesity-Induced Kidney Injuries by Modulating the Adiponectin Receptor 2/PPAR-α Axis.

The kidney is an important organ in the maintenance of body homeostasis. Dietary compounds, reactive metabolites, obesity, and metabolic syndrome (MetS) can affect renal filtration and whole body homeostasis, increasing the risk of chronic kidney disease (CKD) development. Gamma oryzanol (γOz) is a compound with antioxidant and anti-inflammatory activity that has shown a positive action in the treatment of obesity and metabolic diseases. Aim. To evaluate the effect of γOz to recover renal function in obese animals by high sugar-fat diet by modulation of adiponectin receptor 2/PPAR-α axis Methods. Male Wistar rats were initially randomly divided into 2 experimental groups: control and high sugar-fat diet (HSF) for 20 weeks. When proteinuria was detected, HSF animals were allocated to receive γOz or maintain HSF for more than 10 weeks. The following were analyzed: nutritional and biochemical parameters, systolic blood pressure, and renal function. In the kidney, the following were evaluated: inflammation, oxidative stress, and protein expression by Western blot. Results. After 10 weeks of γOz treatment, γOz was effective to improve inflammation, increase antioxidant enzyme activities, increase the protein expression of adiponectin receptor 2 and PPAR-α, and recover renal function. Conclusion. These results permit us to confirm that γOz is able to modulate PPAR-α expression, inflammation, and oxidative stress pathways improving obesity-induced renal disease.

Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic Syndrome in Animals Submitted to High Sugar-Fat Diet.

BACKGROUND: The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as diabetes, and cardiovascular and kidney diseases. Different strategies have been used to prevent these diseases associated with obesity, such as changes in eating habits and/or the addition of dietary components with anti-inflammatory and anti-oxidant properties, such as gamma-oryzanol (γOz) present mainly in bran layers and rice germ. METHODS: Animals were randomly divided into four experimental groups and fed ad libitum for 20 weeks with control diet (C, n = 8), control diet + γOz (C + γOz, n = 8), high-sugar and high-fat diet (HSF, n = 8), and high-sugar and high-fat diet + γOz (HSF + γOz, n = 8). HSF groups also received water + sucrose (25%). The dose of γOz was added to diets to reach 0.5% of final concentration (w/w). Evaluation in animals included food and caloric intake, body weight, plasma glucose, insulin, triglycerides, uric acid, HOMA-IR, glomerular filtration rate, protein/creatinine ratio, systolic blood pressure, and Doppler echocardiographic. RESULTS: Animals that consumed the HSF diet had weight gain compared to group C, increased insulin, HOMA, glucose and triglycerides, there were also atrial and ventricular structural alterations, deterioration of systolic and diastolic function, decreased glomerular filtration rate, and proteinuria. Gamma-oryzanol is significantly protective against effects on body weight, hypertriglyceridemia, renal damage, and against structural and functional alteration of the heart. CONCLUSION: Gamma-oryzanol shows potential as a therapeutic to prevent Cardiorenal Metabolic Syndrome.

Mentoria durante pandemia: um ambiente de acolhimento, pertencimento e humanização para primeiranistas / Mentoring during the pandemic: a welcoming environment of belonging and humanization for first-year students

Resumo: Introdução: O Programa de Mentoria da FMB foi construído coletivamente durante os anos 2018-2019, com assessoria externa e amplo apoio institucional. O sofrimento psíquico dos alunos de graduação nas áreas da saúde, já descrito na literatura, intensificou-se com a pandemia da Covid-19, fortalecendo a necessidade do programa para os primeiranistas dos cursos de Enfermagem e Medicina. Relato de experiência: Foram realizadas oficinas para formação do grupo gestor do programa e do grupo de mentores. Em agosto de 2020, após divulgação entre representantes e conselhos, a Oficina de Sensibilização com os primeiranistas teve grande adesão. A construção de um ambiente virtual caloroso, leve e lúdico foi prioridade do grupo, assim os mentores foram apresentados aos alunos, e estes receberam o convite para ingresso ao programa. Os alunos declararam suas preferências por seus mentores em questionário que ficou aberto por duas semanas. Formaram-se grupos foram que se encontraram ao menos mensalmente, para que pudessem construir ambientes de acolhimento e afetividade, e discutir temas de interesse e escolha dos alunos. O grupo gestor se reúne com mentores bimestralmente, de modo a priorizar espaços de trocas e compartilhamento das vivências, dos desafios e das superações, e construir um ambiente colaborativo de aprendizado mútuo. Na Enfermagem, a adesão dos alunos foi de 100%, e na Medicina, de 85%. As avaliações dos alunos sobre o programa foram muito positivas. Discussão: O programa propiciou ambiente de diálogo sobre a saúde física e mental, gestão do tempo e atividades acadêmicas, como iniciação científica e extensão universitária. Mentores, mentorados, grupo gestor e instituição vivenciaram momentos de construção de vínculo afetivo e ambiente colaborativo. Conclusão: O programa conseguiu ter visibilidade entre alunos, professores e profissionais, e está conseguindo se firmar como estratégia para resgatar a afetividade e humanizar as relações na instituição, num momento de tantas inseguranças, sofrimentos e desafios.

Abstract: Introduction: The FMB Mentoring Program was built collectively between 2018/19, with external advisory and institutional support. Mental suffering among undergraduate students in the health area is well known, but became more intense with the onset of the Covid-19 pandemic, and programs like mentoring have been especially necessary for first-year students. Experience Report: Workshops were held to create the program steering group and mentoring team. In August 2021, once the program had been presented to representatives and boards, the Awareness Raising Workshop was conducted with high student participation. The group prioritized the construction of a warm, light-hearted and playful virtual environment, and the mentors were introduced to the students in this vein, who in turn received the invitation to join the program. The students named their preferred mentors in a questionnaire that remained available for two weeks. The groups were formed and met at least once a month in a welcoming and affectionate setting to discuss issues of interest to and chosen by the students. The steering group meets with the mentors every two months, focusing on spaces for exchange and sharing of experiences: challenges faced and overcome, and building a collaborative environment of mutual learning. In Nursing, 100% of the students joined the program, and in Medicine, 85%. The student assessments of the program were very positive. Discussion: The program provided an environment of dialogue in mental and physical health, time management, and academic activities such as scientific initiation and university extension. Mentors, mentees, the steering group and institutional coordinators experienced moments of caring, collaboration and affection. Conclusion: The mentoring program attained visibility among students, teachers and professionals and is becoming established as a strategy to retrieve the caring and humanistic aspects of relations in the institution at a time of such uncertainty, suffering and challenges.

Internato na pandemia Covid-19: a experiência de uma escola médica / Medical internship in the Covid-19 pandemic: the experience of a medical school

Resumo: Introdução: A pandemia da Covid-19 provocou milhares de mortes e levou a incontáveis mudanças na forma de organização de serviços de saúde e nas escolas de Medicina mundo afora. Relato de experiência: Este artigo relata a experiência da Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (Unesp), cujas aulas foram suspensas em função da pandemia. Discussão: Descrevem-se as motivações para a suspensão e os procedimentos para a retomada das aulas do internato, depois de 15 semanas da interrupção. Conclusão: Ressalta-se a importância das decisões coletivas, da comunicação empática, do acolhimento e cuidado com a saúde mental e da parceria com o Hospital das Clínicas na realização de rastreamento para a presença do vírus entre os estudantes. Por fim, destaca-se o aprendizado para o professor ao se defrontar, por um lado, com a impotência diante da morte e do desconhecido, e, por outro, com a potência do cuidado que pode ser oferecido em situação tão singular quanto uma pandemia.

Abstract: Introduction: The COVID-19 pandemic has caused thousands of deaths and led to countless changes in the way health services and medical schools are organized around the world. Experience report: This article reports on the experience of the Botucatu Faculty of Medicine, UNESP, located in the interior of the state of São Paulo, where classes were suspended due to the pandemic. Discussion: The reasons for the suspension of internship classes and the procedures for their resumption, after 15 weeks, are described. Conclusions: The study highlights the importance of collective decisions, empathic communication, mental health care and attention and the partnership with the Hospital das Clínicas in performing track and trace for presence of the virus among the students. Finally, particular emphasis is given to the learning gained by teachers who found themselves feeling, on the one hand, powerless in the face of death and the unknown and, on the other, the strength of the care that can be offered in a situation as unique as the pandemic.

Membranous nephropathy PLA2R+ associated with Chagas disease.

Chagas disease (CD) - a tropical parasitic disease caused by the protozoan Trypanosoma cruzi - is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure.

Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.

Proteinuria predicts relapse in adolescent and adult minimal change disease.

OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis) of 34 (23-49) years were studied, including 23 males and 40 females. At diagnosis, eight (12.7%) patients presented with microscopic hematuria, 17 (27%) with hypertension and 17 (27%) with acute kidney injury. After the initial treatment, 55 (87.3%) patients showed complete remission, six (9.5%) showed partial remission and two (3.1%) were nonresponders. Disease relapse was observed in 34 (54%) patients who were initial responders (n = 61). In a comparison between the relapsing patients (n = 34) and the non-relapsing patients (n = 27), only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0) vs. 6.0 (3.6-7.3) g/day, respectively, p = 0.001). Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

Comparative analysis of different doses of coherent light (laser) and non-coherent light (light-emitting diode) on cellular necrosis and apoptosis: a study in vitro

Introduction Threshold doses of electromagnetic radiation can initiate necrosis and apoptosis in cells. The purpose of this study was to evaluate cellular apoptosis and necrosis immediately (t0) and 24 hours (t24) after irradiation with different doses of coherent light (laser) or non-coherent light (LED). Methods CHO-K1 lineage cells were irradiated with laser (810nm) or LED (945±20nm), with 24mW, contact area of 1cm2 and doses of 10, 20, 30, 40 and 50J/cm2 for 300, 660, 960, 1230 and 1620s, respectively, at both wavelengths. Cells were evaluated by fluorescence microscopy, differentiating viable, apoptotic and necrotic cells immediately and 24 hours after irradiation. Results The number of necrotic cells at t0 was higher in the LED 40 and 50J/cm2 groups (86±14 and 84±16% respectively, p <0.05), than in the 10 and 20J/cm2 laser (5±2 and 5±3%, p<0.05) and LED (5±3 and 4±1%, p<0.05) conditions. At t24, the LED 40J/cm2 (80±20%, p<0.05) group also showed more necrosis than the control and lower dose groups (laser 10, 20, and 30J/cm2 percentage of 6±4, 10±3 and 7±3%, p<0.05; LED 10 and 20J/cm2 percentage of 3±1 and 17±10%, p<0.05). A decrease in apoptotic cells was observed in the laser group with doses of 10, 40, and 50J/cm2 (6±4, 3±1 and 1±1% respectively, not significant), as well as in the LED 40J/cm2 (2±2%, not significant) group versus control. The cells had a higher percentage of apoptosis cells in the control group and with laser doses of 10 and 30J/cm2 (percentage of 20±1 and 20±4%, not significant), while only the LED 40J/cm2 (10±10%, not significant) had a lower percentage compared the control group. Conclusion Laser or LED stimulation promoted an increase in cell necrosis in a high energy density condition as characterized in a dose-dependent inhibition therapy. Laser or LED infrared irradiation in low doses (up to 20J/cm2) reduced the percentage of apoptosis in CHO-K1 cells, while high doses (30J/cm2) elevated apoptosis.

[Clinical and laboratorial characteristics associated with biopsy proved hypertensive nephroangiosclerosis]. / Características clínicas e laboratoriais associadas à nefroangioesclerose hipertensiva confi rmada por biópsia renal.

INTRODUCTION: Hypertensive nephroangiosclerosis is a major cause of chronic kidney disease requiring dialysis. Clinical characteristics that distinguish a patient with hypertension that evolves to nephroangiosclerosis from another that keeps stable renal function are not well established because of the difficulty in ensuring that the carriers of that disease are not actually suffering from glomerulonephritis or other kidney diseases. Thus, our objective was to identify clinical or laboratory features that distinguish the patients who developed chronic renal failure from hypertension, confirmed by renal biopsy, of those who, even with arterial hypertension, did not develop nephroangiosclerosis. METHODS: We conducted a retrospective comparison of clinical and laboratory data of 15 patients with hypertensive nephroangiosclerosis confirmed by renal biopsy and 15 hypertensive patients from the outpatient clinic of the Hypertension Center, whose lack of nephroangiosclerosis was defined as absence of proteinuria. The groups were matched for age and gender. RESULTS: Among the evaluated variables, duration of hypertension, pulse pressure, blood glucose, uric acid, creatinine and frequency of use of diuretics and sympatholytic differed statistically between the two groups. All these variables were higher in nephroangiosclerosis patients. CONCLUSION: This study links biopsy proven hypertensive nephroangiosclerosis with metabolic features, hypertension intensity and duration, corroborating the idea that primary prevention of hypertension, postponing its initiation, a more intensive hemodynamic control (when hypertension is well established) and metabolic control of these patients have the potential to prevent hypertensive nephroangiosclerosis.

Estudo conformacional e modulação da proteína NF-κB na via de sinalização de processos inflamatórios produzidos pelo complexo Mycobacterium tuberculosis (MTC) / Conformational study and modulation of NF-κB protein in the signaling pathway of inflammatory processes produced by the Mycobacterium tuberculosis complex (TCM)

A tuberculose é uma das doenças infecciosas que mais mata em todo o mundo e é causada por micobactérias do complexo Mycobacterium tuberculosis (MTC). A infecção desencadeia um processo inflamatório que leva à ativação de diversas vias celulares dependentes do fator nuclear kappa B (NF-κB), sendo este um fator transcricional que desempenha um papel fundamental na transcrição de mediadores inflamatórios. A terapia utilizada para o tratamento da tuberculose apresenta efeitos adversos agressivos ao paciente, levando à descontinuidade do tratamento e consequentemente ao surgimento de cepas resistentes. O estudo de novos compostos que atuem também sobre o sistema imune do paciente, auxiliando na contenção da infecção e resolução da inflamação, é indispensável. Como objetivo geral se propõe a análise do comportamento estrutural, dinâmico e modulador do NF-κB na presença da substância Tiofenoacetamida (TAA)

Essa substância demonstrou atividade inibitória contra o M. tuberculosis e foi revelado que se liga no NF-κB, conforme os estudos in vitro. O estudo foi conduzido por meio de simulações de docagem molecular e simulações de dinâmica molecular. Essas metodologias são fundamentais no planejamento racional de fármacos dado que oferecem informação estrutural sobre o reconhecimento molecular de complexos receptor-ligante. Os resultados obtidos nos permitem inferir que a ligação do TAA na subunidade p65, com e sem DNA, influencia na ligação com o DNA na região de contato. As simulações de dinâmica molecular indicaram que o TAA interfere no comportamento dinâmico do NF-κB, tanto na ausência/presença do DNA. Além disso, foi observado que houve comprometimento dos pares de bases no sistema NF-κB-DNA-TAAp65, sugerindo que a expressão gênica fica prejudicada. O TAA apresenta-se como um potencial inibidor do NF-κB. (AU)

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica / Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.