Effect of dithiocarbamate thiram on Wistar rat growth plate and articular cartilage

Avaliou-se o efeito do tirame, ditiocarbamato largamente utilizado na agricultura como antifúngico e repelente de roedores, na ossificação endocondral de mamíferos, usando, como modelo, ratos Wistar. Não foram observadas lesões na cartilagem articular, nem nas placas de crescimento, o que pode ser atribuído à dose utilizada e à duração do ensaio. A diminuição da altura da placa de crescimento nos animais aos quais foi administrado o tirame parece traduzir o atraso verificado no crescimento em geral, e não um efeito específico na cartilagem, uma vez que as diferentes zonas da placa epifisária mantiveram as proporções dos animais do grupo-controle. Embora não tenham sido verificados, no presente trabalho, os efeitos registrados para outras espécies nos tecidos cartilaginosos, sugere-se a avaliação dos efeitos crónicos do tirame no crescimento e no desenvolvimento dos ossos longos em mamíferos

Ultrasound-guided aspiration of cystic ovarian lesions

Introduction and Objective: In the last two decades the increased accuracy of ultrasonography has allowed simple ovarian cysts to be reliably identified. As clinical data suggest that simple cystic lesions rarely become malignant, surgical treatment of these cysts may therefore represent overtreatment. Our study aimed to evaluate the results of ultrasound (US) guided aspiration of cystic ovarian lesions performed in our institution in the last ten years

Modelling competing risks in nephrology research: an example in peritoneal dialysis

BACKGROUND: Modelling competing risks is an essential issue in Nephrology Research. In peritoneal dialysis studies, sometimes inappropriate methods (i.e. Kaplan-Meier method) have been used to estimate probabilities for an event of interest in the presence of competing risks. In this situation a competing risk analysis should be preferable. The objectives of this study are to describe the bias resulting from the application of standard survival analysis to estimate peritonitis-free patient survival and to provide alternative statistical approaches taking competing risks into account. METHODS: The sample comprises patients included in a university hospital peritoneal dialysis program between October 1985 and June 2011 (n = 449). Cumulative incidence function and competing risk regression models based on cause-specific and subdistribution hazards were discussed. RESULTS: The probability of occurrence of the first peritonitis is wrongly overestimated using Kaplan-Meier method. The cause-specific hazard model showed that factors associated with shorter time to first peritonitis were age (>=55 years) and previous treatment (haemodialysis). Taking competing risks into account in the subdistribution hazard model, age remained significant while gender (female) but not previous treatment was identified as a factor associated with a higher probability of first peritonitis event. CONCLUSIONS: In the presence of competing risks outcomes, Kaplan-Meier estimates are biased as they overestimated the probability of the occurrence of an event of interest. Methods which take competing risks into account provide unbiased estimates of cumulative incidence for each specific outcome experienced by patients. Multivariable regression models such as those based on cause-specific hazard and on subdistribution hazard should be used in this competing risk setting

The protective effect of endogenous melatonin on gilthead seabream sperm during cryopreservation

Cryopreservation is widely used for artificial reproduction techniques (ART) but requires good gamete quality to succeed. Considering the endogenously produced melatonin by the fish and its protective role in the organism, the objective of this experiment was to search for the best moment of the day to collect gilthead seabream (Sparus aurata) sperm with better quality and, at the same time, to test the potential protective effect of the exogenous melatonin during sperm freezing and thawing processes. Fish were first sampled every 6 h, corresponding to the beginning of the light period (6 h), mid-light (12h), beginning of the dark period (18 h), and mid-dark (24 h) to determine melatonin concentration in blood plasma by radioimmunoassay (RIA). The analysis showed higher values at 24 h (244 pg/mL) compared with 12 h (99 pg/mL), which allowed the selection of those moments for the next experiment. After, fish were sampled for sperm collection at mid-light (ML, 12 h) and mid-dark (MD, 24 h), and fresh sperm was used to assess gamete quality and for the cryopreservation assay. Sperm samples were cryopreserved to test supplementation of different melatonin concentrations (0.001 mM, 0.01 mM and 0.1 mM) together with a control group without added melatonin. Gamete quality was assessed through spermatozoa concentration and motility (CASA system), cell viability (PI/SYBR-green) and DNA fragmentation (Comet assay). Despite cell viability that was higher at ML, most of the fresh sperm motility parameters did not differ between ML and MD, only linearity (LIN) was enhanced at MD. Nevertheless, in cryopreserved samples, total motility (TM) was significantly higher at MD in all melatonin treatments, control, and fresh samples, revealing an endogenous night-effect. Moreover, spermatozoa concentration was also higher at MD (28.9 x 109/mL) than at ML (20.7 x 109/mL). Supplemented melatonin did not confer extra protection to gilthead seabream sperm during cryopreservation since the tested concentrations did not differ between the control in any sperm quality test. It is here suggested that endogenously produced melatonin may contribute to the improvement of some gamete quality parameters at mid-dark, allowing the aquaculture sector to select better sperm quality in a noninvasive way by choosing it as the best moment of the day for sperm collection.LA/P/0101/2020info:eu-repo/semantics/publishedVersio

Monoclonal gammopathy of renal significance: Diagnostic workup

The clinical spectrum of diseases associated with monoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always available, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic difficulties of these entities.info:eu-repo/semantics/publishedVersio

Peritoneal dialysis dropouts in different age and era cohorts: focus on the elderly

Introduction and Aims: Peritoneal dialysis (PD) is an efficient renal replacement therapy (RRT), but still remains underutilized at any age. Clinicians fear the rate of dropouts and lower technique survival, particularly in elderly patients. The authors aimed to explore such outcomes over the past 3 decades, in different age and era cohorts. Methods: Consecutive incident patients starting PD were identified from an ongoing registry-base prospective study of quality assessment. In order to control for an era effect, patients were assigned to 6 cohorts (5 years interval) according to the admission year between 1985 and 2014. Regression models taking competing risks into account were performed to identify potential prognostic factors for death and transfer to haemodialysis (HD) (adjusted for age, gender, diabetes, cohort era, automated peritoneal dialysis (APD) use, and first treatment modality – PD first, PD after HD, PD after renal transplant (RT). Then the patients were studied according to age at enrolment in the programme: A (18 44 years; n = 193); B (45 64 years; n = 176) and C (≥ 65 years old; n = 75). The HD transfer rates using Poisson analysis were evaluated. The incidence of dropout rates was compared at different times and between age groups, focusing particular attention on the elderly. Results: A total of 525 patients were evaluated: 211 male (40.2%), aged 48 ± 15.7 years old, on PD for 23 (IQR 9 – 41.5) months. The major cause of dropout technique was transfer to HD (35.4%), followed by renal transplantation (27.6%) and death (21.7%). The probability of technical failure and renal transplantation at 2 and 5 years was 19.2% and 18.1% and 34.2%; 27.4%, respectively. Probability of death at 2 and 5 years was 12.7%, and 21.8%, respectively. The contemporary cohort was associated with a lower risk of mortality and lower risk of transfer to haemodialysis, with greater access to renal transplantation. The regression model Fine & Gray showed that older age was associated with increased mortality, but was not associated with greater technical failure. Transfer to HD occurred in the elderly at a rate of 11epy/100 patient year (in comparison to 15 and 14 epy/100 patient-year in non-elderly groups A and B, respectively P= 0.33). The proportions of specific causes of technique failure did not change significantly according to age cohort. The dropout rates due to access-related-infection and ultrafiltration failure decreased in the elderly group in the more contemporary cohort, despite the differences were not statistically significant. Conclusions: The dropout by technique failure decreased significantly in the recent decade. Age at admission in peritoneal dialysis did not show to be a compromising factor of the technique survivalIntrodução e Objetivos: A diálise peritoneal (DP) é uma técnica substitutiva da função renal (TSFR) com eficácia semelhante à hemodiálise (HD); no entanto, ainda permanece subutilizada em qualquer idade. Os médicos temem o elevado drop-out da técnica e a sua menor sobrevida, particularmente nos doentes idosos. Os autores pretenderam explorar causas de drop-out e sobrevida da técnica ao longo das últimas três décadas, em diferentes faixas etárias, centrando uma atenção particular no idoso. Métodos: Foram usados dados do registo prospetivo do programa hospitalar de doentes adultos incidentes em DP. Tendo em conta as diferentes épocas, os doentes foram divididos em 6 coortes (5 anos de intervalo) de acordo com o ano de admissão no programa (1985-2014). Usaram-se modelos de regressão tendo em conta a análise de riscos competitivos para identificar potenciais fatores de prognóstico para a morte e transferência para HD (ajustados para a idade, género, diabetes, era, tipo de técnica e primeira modalidade de TSFR). Posteriormente, os doentes foram estudados de acordo com a idade à admissão no programa: A (18 44 anos); B (45 64 anos) e C (≥ 65 anos de idade). Foram avaliadas as taxas de transferência para HD usando a análise de Poisson. As taxas de incidência de drop-out foram comparadas em diferentes épocas e entre os grupos etários, focando particular atenção no doente idoso. Resultados: Foram avaliados 525 pacientes: 211 eram do sexo masculino (40,2%), com idade média de 48 ± 15,7 anos, com follow-up mediano de 23 meses (IQR 9-41,5). A maior causa de drop-out da técnica foi a transferência para HD (35,4%), seguida do transplante renal (27,6%) e de morte (21,7%). A probabilidade de falência técnica e transplantação renal aos 2 e aos 5 anos foi 19,2% e 18,1% e 34,2%; 27,4%, respetivamente. A probabilidade de morte aos 2 e aos 5 anos foi 12,7%, e 21,8%, respetivamente. A coorte mais recente associou-se a menor risco de mortalidade e menor transferência para HD. O modelo de regressão Fine & Gray mostrou que a idade avançada se associou a maior mortalidade, contudo não se associou a maior falência técnica. Nos idosos, a taxa de transferência para HD foi 11,2 episódios/100 doentes-ano (em comparação com 15 e 14 episódios/100 doentes-ano nos grupos A e B, respectivamente, p= 0,33). Não houve diferenças significativas nas causas de transferência para HD entre os diferentes grupos etários. As taxas de drop-out por falência de acessos e por falência de ultrafiltração diminuíram no grupo mais velho e na coorte mais recente, contudo as diferenças não foram estatisticamente significativas entre os grupos. Conclusões: O drop-out por falência técnica diminuiu significativamente na década mais recente. A idade de admissão na diálise peritoneal não mostrou ser um fator de comprometimento da sobrevida da técnic

Kidney histological alterations and metallothionein and heat shock protein expression in Wistar rats after fungicide thiram exposure

The histological alterations and the expression of metallothionein (MTs) and heat shock protein (Hsp70) in the kidney of Wistar rats after thiram fungicide exposure were evaluated. Animals were distributed into three groups: standard diet group, standard diet + corn oil group and thiram group. Significant differences were found (P<0,05) in the evolution of body weight between rats in the thiram group and those in the control and corn oil groups, and no histological lesions were evident in the animals’ kidneys. Differences were found among animals in the group exposed to thiram and the control and oil groups regarding histomorphometric characteristics of the renal corpuscle – except for the proportion in the area of Bowman’s capsule: glomerulus area – and regarding the height of the epitelium in the distal tubules. In rats exposed to thiram, a positive moderate to strong immunoexpression was observed for MTs, in the cortical convulated tubules decreasing the cortex towards the medulla, and a strong immunoexpression for Hsp70 in the cortex and medulla areas, in the glomerulus and convulated tubules. The results suggest that thiram may have chronic toxicity in mammals affecting their growth, and that the expression of MTs and Hsp70, a probable cellular adaptive response to the oxidative stress caused by thiram, may be used as a biomarker of exposure to this chemical. Keywords: rat, kidney, thiram, histology, metallothioneins, heat shock proteins (Hsp70

Different kidney function trajectory patterns before dialysis in elderly patients: clinical implications and outcomes

Background. Identifying trajectories of kidney disease progression in chronic kidney disease (CKD) patients may help to deliver better care. We aimed to identify and characterize trajectories of renal function decline in CKD patients and to investigate their association with mortality after dialysis.Methods. This retrospective cohort study included 378 CKD patients who initiated dialysis (aged 65 years and over) between 2009 and 2016. Were considered mixed models using linear quadratic and cubic models to define the trajectories, and we used probabilistic clustering procedures. Patient characteristics and care practices at and before dialysis were examined by multivariable multinomial logistic regression. The association of these trajectories with mortality after dialysis was examined using Cox models.Results. Four distinct groups of eGFR trajectories decline before dialysis were identified: slower decline (18.3%), gradual decline (18.3%), early rapid decline (41.2%), and rapid decline (22.2%). Patients with rapid eGFR decline were more likely to have diabetes, more cognitive impairment, to have been hospitalized before dialysis, and were less likely to have received pre-dialysis care compared to the patients with a slower decline. They had a higher risk of death within the first and fourth year after dialysis initiation, and after being more than 4 years in dialysis.Conclusions. There are different patterns of eGFR trajectories before dialysis initiation in the elderly, that may help to identify those who are more likely to experience an accelerated decline in kidney function, with impact on pre ESKD care and in the mortality risk after dialysis

Pericardial and pleural effusions associated with sirolimus and discussion of possible mechanisms

Sirolimus, a mammalian target of rapamycin inhibitor, is an increasingly used immunosuppressant in solid-organ transplantation. There are an increasing number of reports of unusual oedematous adverse effects associated with this drug, including lymphoedema, ascites and pleural effusions, and a few reports of pericardial effusions. No pathophysiological explanation for these phenomena has been disclosed. We report a 33-year-old sirolimus-treated kidney transplant recipient with chronic pericardial and pleural effusions identified nine years after transplantation. He was initially treated for a presumed tuberculous pericarditis, even though cultures for Mycobacterium tuberculosis were negative. After 12 months of antitubercular therapy, visceral effusions persisted. Pericardial effusion was drained and stabilised. After exclusion of other causes, sirolimus toxicity was considered the most likely cause. Two months after discontinuation of sirolimus, visceraleffusions disappeared. Interaction of mammalian target of rapamycin inhibitors with mediators of lymphangiogenesis may be a common link in oedematous states associated with sirolimus

Are we building too many arteriovenous fistulas? A single-center experience

Introduction: Arteriovenous fistula has been associated with improved morbimortality in hemodialysis patients. This has resulted in the “fistula First, catheter last” initiative. Nonetheless, the survival benefit of arteriovenous fistula has been questioned. Methods: We conducted a retrospective observational study of all patients with non-end stage renal disease referred for first vascular access building between January 2014 and December 2015 in our hospital center. Our main goal was to evaluate the clinical impact and burden of building fistula in predialysis patients. Results: During this period, of 178 first arteriovenous accesses placed, 87 patients remained in predialysis and 91 patients started a chronic hemodialysis program. Median follow-up time by a nephrologist was 3.9 (2.5, 9.7) years. The mean age was 65.8±14.7 years, with 50.6% (n=90) of male patients. A higher rate of thrombosis in the predialysis group (26% vs 13%, p=0.037) was observed, but vascular access survival did not differ significantly (55% vs 67%, p=0.12). Mean vascular access placing was higher in the predialysis group (1.4±0.7 vs 1.2±0.4, p=0.006) and less interventions were requested (0.2±0.5 vs 0.3±0.6, p=0.10). Median time from vascular access placement to hemodialysis start was 22 (13, 41) months. At hemodialysis initiation, 10 (10.9%) patients used a central venous catheter; 80 (87.9%) patients an arteriovenous fistula, and one patient a graft. A total of 227 vascular accesses were built; 121 (53.3%) in predialysis vs 106 (46.7%) in incident hemodialysis patients. In a multivariate model, the presence of a functional arteriovenous fistula at hemodialysis start was only associated with a trend to survival benefit (HR 0.38, 95% CI 0.14-1.00, p=0.05). Conclusions: Our results stress the need for an individual approach and for future tools to assess the risk of death and progression to end-stage renal disease, therefore helping reduce the number of unutilized vascular accesses and rising cost of interventions.info:eu-repo/semantics/publishedVersio