ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas.

The metastatic progression of cancer is a multi-step process initiated by the local invasion of the peritumoral stroma. To identify the mechanisms underlying colorectal carcinoma (CRC) invasion, we collected live human primary cancer specimens at the time of surgery and monitored them ex vivo. This revealed that conventional adenocarcinomas undergo collective invasion while retaining their epithelial glandular architecture with an inward apical pole delineating a luminal cavity. To identify the underlying mechanisms, we used microscopy-based assays on 3D organotypic cultures of Caco-2 cysts as a model system. We performed two siRNA screens targeting Rho-GTPases effectors and guanine nucleotide exchange factors. These screens revealed that ROCK2 inhibition triggers the initial leader/follower polarization of the CRC cell cohorts and induces collective invasion. We further identified FARP2 as the Rac1 GEF necessary for CRC collective invasion. However, FARP2 activation is not sufficient to trigger leader cell formation and the concomitant inhibition of Myosin-II is required to induce invasion downstream of ROCK2 inhibition. Our results contrast with ROCK pro-invasive function in other cancers, stressing that the molecular mechanism of metastatic spread likely depends on tumour types and invasion mode.

Family income is associated with quality of life in patients with chronic kidney disease in the pre-dialysis phase: a cross sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a condition of high prevalence in the general population mainly due to hypertension and diabetes mellitus. It is often associated with a high prevalence of complications and worse quality of life. The main objective of this study is to evaluate quality of life (QOL) using the generic instrument SF-36 in patients with CKD in pre-dialysis and identify the possible influence of the degree of renal function, hemoglobin level, age, gender, family income and level of education on QOL. METHODS: A cross-sectional study was conducted and included 170 individuals (83 men) with a mean age of 57 ± 15 years who met the inclusion criteria and answered the SF-36. Laboratory tests and clinical and demographic data were obtained, and the glomerular filtration rate was estimated using the CKD-EPI formula. RESULTS: The degree of renal function did not influence QOL. Women had lower scores in functional capacity, physical aspects, pain, and mental health. Patients younger than 47 years old showed better QOL in the functional capacity; however, their QOL was worse in terms of social aspects. Subjects with an income higher than 5.1 times the minimum wage had better QOL in the functional capacity, pain, social, physical and emotional roles, and mental health. Hemoglobin levels and education did not globally influence QOL. CONCLUSION: Gender and age influenced QOL, but family income was the most important factor affecting QOL (6 out of 8 domains investigated by SF-36) in this sample of 170 individuals with CKD in pre-dialysis. These findings suggest that many efforts should be made to reduce the effect of these factors on quality of life in patients with CKD and reinforce the need for longitudinal studies and intervention.

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. OBJECTIVE: To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. METHODS: Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. RESULTS: Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. CONCLUSION: Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

Characterization of the early stages of thymic NKT cell development.

Upon reaching the mature heat stable antigen (HSA)low thymic developmental stage, CD1d-restricted Valpha14-Jalpha18 thymocytes undergo a well-characterized sequence of expansion and differentiation steps that lead to the peripheral interleukin-4/interferon-gamma-producing NKT phenotype. However, their more immature HSAhigh precursors have remained elusive, and it has been difficult to determine unambiguously whether NKT cells originate from a CD4+ CD8+ double-positive (DP) stage, and when the CD4+ and CD4- CD8- double-negative (DN) NKT subsets are formed. Here, we have used a CD1d tetramer-based enrichment strategy to physically identify HSAhigh precursors in thymuses of newborn mice, including an elusive DPlow stage and a CD4+ stage, which were present at a frequency of approximately 10(-6). These HSAhigh DP and CD4+ stages appeared to be nondividing, and already exhibited the same Vbeta8 bias that characterizes mature NKT cells. This implied that the massive expansion of NKT cells is separated temporally from positive selection, but faithfully amplifies the selected TCR repertoire. Furthermore, we found that, unlike the DN gammadelta T cells, the DN NKT cells did not originate from a pTalpha-independent pathway bypassing the DP stage, but instead were produced during a short window of time from the conversion of a fraction of HSAlow NK1.1neg CD4 cells. These findings identify the HSAhigh CD4+ stage as a potential branchpoint between NKT and conventional T lineages and between the CD4 and DN NKT sublineages.

Depressed mood and poor quality of life in male patients with chronic renal failure undergoing hemodialysis.

OBJECTIVE: To assess mood and quality of life in male hemodialysis patients, and to correlate mood swings with the different domains of the quality of life questionnaire. METHOD: Forty-seven male patients undergoing regular hemodialysis for more than six months were included in the study. The Hamilton Rating Scale for Depression and the Kidney Disease Quality of Life Questionnaire, in a version translated into and adapted to Portuguese, were used. RESULTS: The patients' age was 39.4±8.9 years (median±SD). Depression was observed in 32 (68.1%) patients according to the Hamilton Rating Scale for Depression. A significant negative correlation was found between the results from the Hamilton Rating Scale for Depression and the following parameters of the specific dimensions of the Kidney Disease Quality of Life Questionnaire: list of symptoms and problems (rs=-0.399; p=0.005), quality of social interaction (rs=-0.433; p=0.002), and quality of sleep (rs=-0.585; p<0.001). Among the generic domains, mood showed a significant negative correlation with general health (rs=-0.475; p<0.001), emotional well-being (rs=-0.354; p=0.015), social functioning and energy/fatigue (rs=-0.518; p<0.001). The other parameters of the Kidney Disease Quality of Life Questionnaire did not show significant correlations with the Hamilton Rating Scale for Depression. CONCLUSION: Mood showed a negative correlation with the various scores of quality of life assessed by the Kidney Disease Quality of Life Questionnaire, suggesting a possible influence of mood on the quality of life of chronic renal patients undergoing hemodialysis.

Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride.

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of inflammation and has an important role in human and experimental renal diseases. Pentoxifylline (PTX) has been shown to inhibit cytokine synthesis, including TNF-alpha. The aim of the present study was to examine the effect of PTX on meglumine antimonate (Sb(V)) and antimony pentachloride (SbCl(5))-induced renal toxicity in rats. Sixty Wistar rats were divided into six groups according to the treatment employed over the period of 7 days: group I-saline (NaCl 0.9%); group II-PTX plus saline; group III-meglumine antimonate (Sb(V)) plus saline; group IV-meglumine antimonate (Sb(V)) plus PTX; group V-SbCl(5) plus saline; group VI-SbCl(5) with PTX. The animals' urinary concentration ability was evaluated before and after the end of the treatment. Urine and blood osmolality, sodium and creatinine concentration, and urine volume per minute (V) were determined. Creatinine clearance (CrCl), fractional sodium excretion (FE(Na)), and urine to plasma osmolality ratio (U/P osm) were calculated. TNF-alpha concentration in blood was assessed. On the seventh day, the animals were sacrificed and their kidneys were submitted to histological analysis. The meglumine antimonate (Sb(V))-treated animals showed an impaired renal capacity to concentrate urine, with low values of the ratio U/P osm, reduction in CrCl, and an increment in TNF-alpha serum levels. PTX associated with meglumine antimonate (Sb(V)) reduced TNF-alpha serum levels and was effective in preventing renal functional alterations. Rats treated with SbCl(5) showed functional and histopathologic alterations compatible with acute tubular necrosis, and treatment with PTX did not prevent SbCl(5)-induced nephrotoxicity. PTX was effective in preventing renal functional alterations induced by meglumine antimonate (Sb(V)) in rats.

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease / Impacto das diferentes modalidades de diálise peritoneal automatizada sobre o perfil inflamatório de idosos portadores de doença renal crônica

Abstract Introduction: Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. Objective: To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. Methods: Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. Results: Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. Conclusion: Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

Resumo Introdução: A doença renal crônica, mais prevalente em idosos, é considerada um problema de saúde pública em todo o mundo. Objetivo: Avaliar o impacto das modalidades de diálise peritoneal automatizada, intermitente e contínua, no perfil inflamatório de idosos renais crônicos. Métodos: Estudo prospectivo, transversal e analítico realizado em uma clínica de diálise em Brasília, com 74 idosos com idade igual ou maior que 60 anos. Os pacientes foram submetidos ao Teste de Equilíbrio Peritoneal rápido, avaliação clínica, coleta de sangue para avaliações bioquímicas e de citocinas, interleucina 6 e fator de crescimento transformador beta 1, e questionário de qualidade de vida (KDQOL-SF36). Foram utilizadas para análise dos dados, associações e correlações com nível de significância de 5%. Resultados: Pacientes na modalidade contínua apresentaram valores séricos do fator de crescimento transformador beta 1 maiores do que os em modalidade intermitente. Estes apresentaram fator de crescimento transformador beta 1 no peritônio, idade e função renal residual maiores do que os em modalidade contínua. A dosagem da interleucina 6 no peritônio foi associada à idade, enquanto a IL-6 sérica foi associada à IL-6 no peritônio, ao tempo em diálise e à idade. Não houve associação entre a modalidade e a presença de diabetes, volemia ou estado nutricional. Ambas as modalidades permitem boa adequação à terapia dialítica. Conclusão: A inflamação na diálise peritoneal automatizada está associada principalmente à baixa função renal residual, à idade avançada e ao maior tempo em terapia, e não à modalidade de diálise realizada.

Sleep Parameters in Short Daily versus Conventional Dialysis: An Actigraphic Study.

Previous studies have observed worse sleep quality in patients undergoing conventional dialysis as compared to daily dialysis. Our aim was to compare the sleep parameters of patients undergoing daily or conventional dialysis using an objective measure (actigraphy). This cross-sectional study was performed in three dialysis centers, including a convenience sample (nonprobability sampling) of 73 patients (36 patients on daily hemodialysis and 37 patients on conventional hemodialysis). The following parameters were evaluated: nocturnal total sleep time (NTST), expressed in minutes; wake time after sleep onset (WASO), expressed in minutes; number of nighttime awakenings; daytime total sleep time (DTST), expressed in minutes; number of daytime naps; and nighttime percentage of sleep (% sleep). The Mini-Mental State Examination and the Beck Depression Inventory were also administered. The mean age was 53.4 ± 17.0 years. After adjustment of confounding factors using multiple linear regression analysis, no difference in actigraphy parameters was detected between the groups: NTST (p = 0.468), WASO (p = 0.88), % sleep (p = 0.754), awakenings (p = 0.648), naps (p = 0.414), and DTST (p = 0.805). Different from previous studies employing qualitative analysis, the present assessment did not observe an influence of hemodialysis modality on objective sleep parameters in chronic renal patients.

Acute and chronic influence of hemodialysis according to the membrane used on phagocytic function of neutrophils and monocytes and pro-inflammatory cytokines production in chronic renal failure patients.

This work evaluated the phagocytic capacity of monocytes and neutrophils, and tumor necrosis factor-alpha, interleukin 6, 1 and 8 serum levels in chronic renal failure patients under peritoneal dialysis and hemodialysis treatment, compared with chronic renal failure patients without dialysis treatment and healthy individuals, in order to contribute to a better understanding of the action of these therapies on the evolution of chronic renal failure patients. All patients with chronic renal failure (under dialysis or not) showed decreased phagocytic capacity of neutrophils and monocytes. All those in hemodialysis (cellulose acetate or polysulfone membranes) showed a decreased phagocytic capacity. The phagocytic index for neutrophil was 13 times lower than that of the control group for both membranes, whereas for monocytes, only those using polysulfone membrane showed a significant decrease of 4.9 times in phagocytic capacity. There was an acute stimulation of the phagocytosis by neutrophils after a single session of dialysis with both types of membrane, while only cellulose acetate membrane decreased the phagocytic index of monocytes after the hemodialysis session. Patients using cellulose acetate showed a chronic increase in tumor necrosis factor-alpha serum levels, while those using polysulfone showed a chronic increase in interleukin 6. After a single hemodialysis procedure, no acute effect of the treatment on tumor necrosis factor-alpha and interleukin 6 levels was identified. The decreased phagocytic function of neutrophils and monocytes may account for the high levels of susceptibility of chronic renal failure patients to infections with pyogenic bacteria and tuberculosis. Furthermore, inflammatory activity may occur with both types of membrane studied, suggesting that it will be useful for these patients to evaluate some anti-inflammatory or anti-cytokine therapies against tumor necrosis factor-alpha and interleukin 6, in order to avoid cardiovascular complication.

Phospholipid scramblase, a new effector of FcepsilonRI signaling in mast cells.

The signaling network of the high-affinity receptor for IgE in mast cells involves tyrosine phosphorylation of a number of proteins. Here we report evidence that phospholipid scramblase, a protein involved in the distribution of phospholipids between the two leaflets of the plasma membrane, is a target for tyrosine kinases in this signal. The implication of this observation is briefly discussed.

Effect of systemic inflammation on level of ferritin seminal in chronic renal male patient undergoing hemodialysis.

BACKGROUND: Most hemodialysis patients present with chronic systemic inflammation characterized by the elevation of serum C-reactive protein (CRP) levels and/or the production of proinflammatory interleukins by the immune system in response to the hemodialysis process. Plasma ferritin(PF) is one of the parameters used to correct anemia. An PF level of >500 ng/mL is not recommended for correction of anemia because of the uncertainty of whether these levels are elevated because of anemia or a mere reaction to inflammation. we aimed to study the effects of inflammation on seminal ferritin (SF) levels and hypothesized that SF is not affected because of the testicular immune privilege. METHODS: A prospective prevalence study was conducted at the Department of Hemodialysis of the University Hospital of Brasília (HuB) between June 2010 and July 2011. The sample included 60 chronic renal patients undergoing hemodialysis and 20 control subjects from the health promotion general outpatient clinic. All participants were males aged 18-60 years. Inflammation was assessed through serum CRP levels, and the testicular condition was determined by measuring sex hormone levels. In the patient group, inflammation was considered to be present when CRP was >5 mg/L (n = 27) and absent when CRP was ≤5 mg/L (n = 33). Control group (n = 20) CRP was ≤1 mg/L. Blood and semen were collected via arm venoclysis and after voluntary masturbation, respectively. CRP was measured by turbidimetry; PF, SF, and sex hormone levels by immunochemoluminescence. Statistical significance was set at p < 0.05. RESULTS: There was no significant difference in mean SF levels among patients with inflammation (295.34 ± 145.39 ng/mL), those without inflammation (324.42 ± 145.51 mg/mL), and controls (335.70 ± 075.90 ng/mL; p = 0.49). There was no correlation between mean SF and PF levels in the patients with and without inflammation). All participants were eugonadal with mean serum FSH, LH, and testosterone levels of 3.76 ± 2.17 mUI/mL, 7.00 ± 3.53 mUI/mL, and 454.18 ± 173.08 ng/dL, respectively. CONCLUSION: Systemic inflammation did not significantly alter SF levels in eugonadal hemodialysis patients.

Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension.

BACKGROUND: In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. OBJECTIVE: To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. METHODS: This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. RESULTS: In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). CONCLUSION: CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.

An activin receptor IIA ligand trap corrects ineffective erythropoiesis in ß-thalassemia.

The pathophysiology of ineffective erythropoiesis in ß-thalassemia is poorly understood. We report that RAP-011, an activin receptor IIA (ActRIIA) ligand trap, improved ineffective erythropoiesis, corrected anemia and limited iron overload in a mouse model of ß-thalassemia intermedia. Expression of growth differentiation factor 11 (GDF11), an ActRIIA ligand, was increased in splenic erythroblasts from thalassemic mice and in erythroblasts and sera from subjects with ß-thalassemia. Inactivation of GDF11 decreased oxidative stress and the amount of α-globin membrane precipitates, resulting in increased terminal erythroid differentiation. Abnormal GDF11 expression was dependent on reactive oxygen species, suggesting the existence of an autocrine amplification loop in ß-thalassemia. GDF11 inactivation also corrected the abnormal ratio of immature/mature erythroblasts by inducing apoptosis of immature erythroblasts through the Fas-Fas ligand pathway. Taken together, these observations suggest that ActRIIA ligand traps may have therapeutic relevance in ß-thalassemia by suppressing the deleterious effects of GDF11, a cytokine which blocks terminal erythroid maturation through an autocrine amplification loop involving oxidative stress and α-globin precipitation.

The association of markers of oxidative-inflammatory status with malnutrition in hemodialysis patients with serum ferritin lower than 500 ng/mL.

INTRODUCTION: Enhanced inflammatory-oxidative status is well established in chronic kidney disease. OBJECTIVE: The objective of this study was to evaluate the oxidative- inflammatory status and iron indices in patients undergoing maintenance hemodialysis (HD) with serum ferritin lower than 500 ng/mL, and to correlate them with nutritional status. METHOD: In a cross-sectional survey 35 HD patients (23 with normal nutritional status, 12 with Protein-Energy-Wasting syndrome, PEW), and healthy volunteers (n = 35) were studied. Serum concentration of iron, ferritin, transferrin saturation, malondialdehyde (MDA), protein carbonyl (PC), high-sensitive serum C -reactive protein (hs-CRP) and blood counts were determined. The nutritional status was determined by anthropometric and biochemical criteria. RESULTS: HD patients showed low values of hemoglobin and higher values of ferritin, MDA and PC when compared with healthy volunteers. HD subjects with PEW had higher values of PC and hs-PCR as compared to HD patients with normal nutritional status. A multiple logistic regression analysis showed that the independent variables PC (Wald Statistic 4.25, p = 0.039) and hs-CRP (Wald Statistic 4.83, p = 0.028) where related with the patients' nutritional condition. CONCLUSION: In HD patients with serum ferritin below 500 ng/mL was observed one association of the markers of oxidative stress and inflammation with poor nutritional status independently of serum ferritin, gender and age.

Does acute alcohol intoxication interfere with colonic anastomosis wound healing? A rat model of nondestructive colon trauma.

PURPOSE: To evaluate the effects of acute alcohol intoxication on healing of colonic anastomosis. METHODS: Thirty-six rats were allocated into two groups. Animals in the alcohol (A) were given 2 mL of ethanol diluted in 0.9% saline solution to a concentration of 40% by gavage immediately before anesthesia, whereas control (C) animals received 2 mL of 0.9% saline solution via the same route. A colonic anastomosis was then performed in all animals. On postoperative days 1, 3, and 7, anastomotic breaking strength was assessed and histopathological examination was performed. Change in body weight and mortality were also evaluated. RESULTS: The median of anastomotic tensile strength on the postoperative day 1 was 0.09 Newtons for group A and 0.13 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 3 was 0.13 Newtons for group A and 0.17 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 7 was 0.30 Newtons for group A and 0.35 for group C. (p>0.05). There was no significant difference between the groups A and C, in the first, third or seventh POD (p>0.05), in any of the analyzed parameters. There were no statistical differences between groups in the weight. Three animals died, all from the group A. CONCLUSION: Acute alcohol intoxication did not interfere with wound healing of colonic anastomoses, although it caused early postoperative mortality.

Alcohol acute intoxication before sepsis impairs the wound healing of intestinal anastomosis: rat model of the abdominal trauma patient.

INTRODUCTION: Most trauma patients are drunk at the time of injury. Up to 2% of traumatized patients develop sepsis, which considerably increases their mortality. Inadequate wound healing of the colonic repair can lead to postoperative complications such as leakage and sepsis. OBJECTIVE: To assess the effects of acute alcohol intoxication on colonic anastomosis wound healing in septic rats. METHODS: Thirty six Wistar rats were allocated into two groups: S (induction of sepsis) and AS (alcohol intake before sepsis induction). A colonic anastomosis was performed in all groups. After 1, 3 or 7 days the animals were killed. Weight variations, mortality rate, histopathology and tensile breaking strength of the colonic anastomosis were evaluated. RESULTS: There was an overall mortality of 4 animals (11.1%), three in the group AS (16.6%) and one in the S group (5.5%). Weight loss occurred in all groups. The colon anastomosis of the AS group didn't gain strength from the first to the seventh postoperative day. On the histopathological analysis there were no differences in the deposition of collagen or fibroblasts between the groups AS and S. CONCLUSION: Alcohol intake increased the mortality rate three times in septic animals. Acute alcohol intoxication delays the acquisition of tensile strength of colonic anastomosis in septic rats. Therefore, acute alcohol intoxication before sepsis leads to worse prognosis in animal models of the abdominal trauma patients.

Perfil do sono de pacientes idosos submetidos à hemodiálise / Sleep profile of elderly patients undergoing hemodialysis

Introdução: Distúrbios do sono são frequentemente observados na população idosa. O objetivo deste estudo foi avaliar, por meio de análises qualitativas e paramétricas, o sono de pessoas idosas submetidas à hemodiálise. Métodos: Trata-se de um estudo transversal realizado em três centros de hemodiálise, com amostra de conveniência composta por 28 pacientes que preencheram os critérios de inclusão. Foi analisada a qualidade do sono por meio do índice de Pitsburgh e medidas actimétricas por sete dias com as seguintes variáveis: tempo total de sono noturno (TTSN), tempo acordado após iniciar o sono (TAIS), número de despertares noturnos (despertares), tempo total de sono diurno (TTSD), número de cochilos e percentual de sono noturno (% sono). RESULTADOS: 17 pacientes (58,6%) apresentavam PSQI > 5, caracterizando um sono de má qualidade nos últimos 30 dias. As análises actimétricas demonstraram parâmetros ruins na média: TTSN de 341,2 ± 90,8 minutos por noite; TAIS de 91,1 ± 46,44 minutos por noite; %sono de 79,6 ± 9,8 por noite; 28,5 ± 11,4 despertares por noite; 48,5 ± 14,6 cochilos por dia e TTSD de 222,4 ± 73,9 minutos por dia. Conclusão: Este estudo observou, por meio de análise qualitativa subjetiva (PSQI) e por parâmetros actimétricos (actimetria), que idosos submetidos à hemodiálise apresentam má qualidade do sono.

Introduction: Sleep disturbances are frequently observed in the elderly population. The objective of this study was to evaluate, by means of qualitative and parametric analyses, the sleep pattern of elderly people undergoing dialysis. Methods: This cross-sectional study was performed at three hemodialysis centers, with a convenience sample composed of 28 patients who fulfilled the inclusion criteria. Their sleep quality was analyzed by means of the Pittsburgh index and actimetric measurements for seven days with the following variables: total nocturnal sleep time (TNST), time awake after the onset of sleep (TAOS), number of nocturnal awakenings (awakenings), total daytime sleep time (TDST), number of naps, and percentage of nocturnal sleep (% sleep). RESULTS: Seventeen patients (58.6%) presented PSQI > 5, characterizing poor quality sleep in the last 30 days. The actimetric analyses demonstrated poor parameters on average: TNST of 341. 2 ± 90.8 minutes per night; TAOS of 91.1 ± 46.44 minutes per night, % sleep of 79.6 ± 9.8 per night; 28.5 ± 11.4 times woken up per night; 48.5 ± 14.6 naps per day, and TDST of 222.4 ± 73.9 minutes per day. Conclusion: This study observed, by means of a subjective qualitative analysis (PSQI) and actimetric parameters (actimetry), that elderly people undergoing hemodialysis demonstrate having poor sleep quality.

Cistatina C, PCR, Log TG/HDLc e Sindrome Metabolica estao Relacionados a Microalbuminuria na Hipertensao / Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

Fundamento: Em pacientes com hipertensão arterial sistêmica, a microalbuminúria é um marcador de lesão endotelial e está associada a um risco aumentado de doença cardiovascular. Objetivo: O objetivo do presente estudo foi determinar os fatores que influenciam a ocorrência de microalbumiúria em pacientes hipertensos com creatinina sérica menor que 1,5 mg/dL. Métodos: Foram incluídos no estudo 133 pacientes brasileiros atendidos em um ambulatório multidisciplinar para hipertensos. Pacientes com creatinina sérica maior do que 1,5 mg/dL e aqueles com diabete mellitus foram excluídos do estudo. A pressão arterial sistólica e diastólica foi aferida. O índice de massa corporal (IMC) e a taxa de filtração glomerular estimada pela fórmula CKD-EPI foram calculados. Em um estudo transversal, creatinina, cistatina C, colesterol total, HDL colesterol, LDL colesterol, triglicerídeos, proteína C-reativa (PCR) e glicose foram mensurados em amostra de sangue. A microalbuminúria foi determinada na urina colhida em 24 horas. Os hipertensos foram classificados pela presença de um ou mais critérios para síndrome metabólica. Resultados: Em análise de regressão múltipla, os níveis séricos de cistatina C, PCR, o índice aterogênico log TG/HDLc e a presença de três ou mais critérios para síndrome metabólica foram positivamente correlacionados com a microalbuminuria (r2: 0,277; p < 0,05). Conclusão: Cistatina C, PCR, log TG/HDLc e presença de três ou mais critérios para síndrome metabólica, independentemente da creatinina sérica, foram associados com a microalbuminúria, um marcador precoce de lesão renal e de risco cardiovascular em pacientes com hipertensão arterial essencial. .

Background: In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective: To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods: This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results: In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion: CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension. .

Avaliação do eletrocardiograma de pacientes com leishmaniose tegumentar americana tratados com antimonial pentavalente (glucantime) / Electrocardiographic assessment of patients with american cutaneous leihmaniasis treated with pentavalent antimonial (glucantime)

Os antimoniais pentavalentes (Antimoniato de N-metilglumina – Glucantime®) são fármacosde primeira escolha no tratamento da leishmaniose tegumentar americana (LTA). Apresentama cardiotoxicidade como importante efeito adverso e é evidenciada por alterações noeletrocardiograma de repouso (ECG). O alargamento do intervalo QT corrigido (QTc) é a principale potencialmente mais grave delas. O presente estudo teve como objetivo avaliar as alteraçõesno ECG e sua frequência nos pacientes com LTA tratados com Glucantime® no Serviço deDermatologia de nossa instituição. Para isso, um cardiologista avaliou os ECGs de 15 pacientes entre 18 e 59 anos de idade diagnosticados com LTA. Os exames foram realizados imediatamenteantes, no 7º, 14º e 21º dias do tratamento. Desses pacientes, cinco (33 por cento) desenvolveram algumdistúrbio no eletrocardiograma, cuja frequência foi diretamente proporcional ao tempo de uso dofármaco. Bradicardia sinusal nova foi o mais comum (5/15 pacientes), seguida por alargamento dointervalo QTc (2/15 pacientes, os quais também apresentaram bradicardia). Não houve registro decomplicações graves e nenhum paciente desenvolveu sintomatologia cardiovascular. Em apenasum caso foi necessária a interrupção do tratamento. A frequência de alterações no ECG observada écompatível com a relatada por estudos anteriores sobre o tema. Concluímos que a cardiotoxicidadedos antimoniais pentavalentes se manifestou de forma insidiosa, cumulativa, em proporçãocompatível com os relatos da literatura e sem repercussões clínicas.

The pentavalent antimonial compounds (Meglumine Antimoniate – Glucantime®) are thecornerstone for the treatment of American Cutaneous Leishmaniasis (ACL). Cardiotoxicity is theirprincipal adverse effect, which becomes evident as abnormalities in the resting Electrocardiogram(ECG), the prolongation of the corrected QT interval (QTc) being the most important and potentiallyhazardous of them. The purpose of this study was to evaluate the disturbances on ECG and theirfrequency in patients diagnosed with ACL and treated with Glucantime® at our Institution. Fifteenpatients between 18 and 59 years had their ECGs assessed by a senior cardiologist. The tests wereperformed prior to treatment, as well as on its 7th, 14th and 21st day. Five patients (33 percent) developed anabnormality not previously observed, and frequency correlated with the duration of the treatment.The most common was sinus bradycardia (5 of 15 patients), followed by prolongation of the QTcinterval (2 of 15 patients; both also had sinus bradycardia). No major cardiovascular symptomsor complications were reported. Only one patient had to interrupt the treatment. This proportionof ECG disturbances is consistent with previous studies on the subject. We conclude that thecardiotoxicity of the pentavalent antimonial drugs occurred insidiously in a percentage of patientscompatible with the literature, and was not associated with major clinical complications.

Variability and robustness in T cell activation from regulated heterogeneity in protein levels.

In T cells, the stochasticity of protein expression could contribute to the useful diversification of biological functions within a clonal population or interfere with accurate antigen discrimination. Combining computer modeling and single-cell measurements, we examined how endogenous variation in the expression levels of signaling proteins might affect antigen responsiveness during T cell activation. We found that the CD8 co-receptor fine-tunes activation thresholds, whereas the soluble hematopoietic phosphatase 1 (SHP-1) digitally regulates cell responsiveness. Stochastic variation in the expression of these proteins generates substantial diversity of activation within a clonal population of T cells, but co-regulation of CD8 and SHP-1 levels ultimately limits this very diversity. These findings reveal how eukaryotic cells can draw on regulated variation in gene expression to achieve phenotypic variability in a controlled manner.