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2.
Medicine (Baltimore) ; 99(24): e20401, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541461

RESUMO

Depression may hamper the immune system and nutritional status, which leads to poor outcomes of treatment. It is very common in dialysis patients. There are the numbers of parameters affected by the depression of patients and available studies are not enough to define the association between biological parameters and depression in the dialysis population. The purposes of the study were to find the prevalence of depression and association of it with the biochemical abnormalities in the dialysis patients.The selected battery of tests (clinician-administered questionnaires) were applied to dialysis patients (test cohort, n = 298) and caregivers (control cohort, n = 202) for establishing depression. The demographic and clinical conditions of participants were also collected. Univariate analysis followed by multiple regression analysis was performed for demographical parameters, clinical conditions, and laboratory results for the detection of association of them with depression. The abnormal test considered as more than 2 SD of mean below the normal value. Out of all tests, at least 2 abnormal tests were considered as mild depression. More than half of abnormal parameters among all tests were considered as moderate depression and all abnormal parameters were considered as severe depression.There was a significant difference for all the test between dialysis patients and the caregivers (P < .0001 for all). The half (153 out of 298) of dialysis patients were depressive and clinically asymptomatic. 70 (23%) dialysis patients were mild depressive, 45 (15%) dialysis patients were moderate depressive, and 38 (13%) dialysis patients were severely depressive. Serum phosphate (P = .023), level of parathyroid hormone (P = .021), and urea reduction rate (P = .048) were directly associated with depression.Biochemical abnormalities (serum phosphate level, parathyroid hormone, and urea reduction rate) were independent predictors of depression in the dialysis population.Level of evidence: III.


Assuntos
Depressão/psicologia , Diálise Renal/psicologia , Uremia/terapia , Adulto , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Cuidadores/psicologia , Estudos de Casos e Controles , China/epidemiologia , China/etnologia , Estudos de Coortes , Depressão/sangue , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Prevalência , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Uremia/complicações
3.
G Ital Nefrol ; 37(2)2020 Apr 09.
Artigo em Italiano | MEDLINE | ID: mdl-32281763

RESUMO

In recent years imaging techniques that use radionuclides have become more and more clinically relevant as they can provide functional information for specific anatomical districts. This has also involved nephrology, where radionuclides are used to study patients with different degrees of renal function failure up to terminal uremia. Although chronic kidney disease, and dialysis in particular, may affect the distribution and the elimination of radiopharmaceuticals, to date there are no consistent data on the risks associated with their use in this clinical context. In addition to the lack of data on the safety of radio-exposure in dialysis patients, there is also a shortage of information concerning the risk for healthcare staff involved in conducting the dialysis sessions performed after a nuclear test. This study, performed on 29 uremic patients who underwent hemodialysis immediately after a scintigraphic examination, assessed the extent of radio-contamination of the staff and of hemodialysis devices such as monitor, kits and dialysate. The data collected has been used to quantify the radiological risk in dialysis after the exposure to the most common radionuclides.


Assuntos
Falência Renal Crônica/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , Diálise Renal , Soluções para Diálise/química , Soluções para Diálise/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Cintilografia/efeitos adversos , Cintilografia/métodos , Compostos Radiofarmacêuticos/efeitos adversos , Medição de Risco , Uremia/metabolismo
4.
Am J Physiol Renal Physiol ; 318(5): F1188-F1198, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32249611

RESUMO

Caloric restriction (CR) is known to have multiple beneficial effects on health and longevity. To study the effect of CR on phosphorus metabolism and vascular calcification (VC), rats were fed normal or restricted calories (67% of normal). The phosphorus content of the diets was adjusted to provide equal phosphorus intake independent of the calories ingested. After 50 days of CR, rats had negative phosphorus balance, lower plasma phosphorus, glucose, triglycerides, and leptin, and higher adiponectin than rats fed normal calories. Uremia was induced by 5/6 nephrectomy (Nx). After Nx, rats were treated with calcitriol (80 ng/kg ip every other day) and high-phosphorus diets (1.2% and 1.8%). No differences in aortic calcium content were observed between rats that ate normal or restricted calories before Nx in either rats that received 1.2% phosphorus (11.5 ± 1.7 vs. 10.9 ± 2.1 mg/g tissue) or in rats that received 1.8% phosphorus (12.5 ± 2.3 vs. 12.0 ± 2.9 mg/g of tissue). However, mortality was significantly increased in rats subjected to CR before Nx in both the 1.2% phosphorus groups (75% vs. 25%, P = 0.019) and 1.8% phosphorus groups (100% vs. 45%, P < 0.001). After calcitriol administration was stopped and phosphorus intake was normalized, VC regressed rapidly, but no significant differences in aortic calcium were detected between rats that ate normal or restricted calories during the regression phase (5.7 ± 2.7 and 5.2 ± 1.5 mg/g tissue). In conclusion, CR did not prevent or ameliorate VC and increased mortality in uremic rats.


Assuntos
Aorta/metabolismo , Doenças da Aorta/prevenção & controle , Restrição Calórica , Rim/metabolismo , Fósforo na Dieta/metabolismo , Uremia/dietoterapia , Calcificação Vascular/prevenção & controle , Animais , Aorta/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Calcitriol , Modelos Animais de Doenças , Progressão da Doença , Metabolismo Energético , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/metabolismo , Rim/patologia , Nefrectomia , Ratos Wistar , Fatores de Tempo , Uremia/etiologia , Uremia/metabolismo , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 124-127, 2020 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-32131951

RESUMO

Patients with uremia can suffer from decreased renal function and endocrine and metabolism disorders,which can lead to the accumulation of toxins in the body.Accumulation of uremic toxins is a major cause of cognitive dysfunction in uremic patients.This article summarizes some of the cognitive dysfunction-related uremic toxins and their possible mechanisms.


Assuntos
Disfunção Cognitiva/fisiopatologia , Toxinas Biológicas , Uremia/fisiopatologia , Humanos
6.
Nat Commun ; 11(1): 721, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024848

RESUMO

Myo-inositol hexakisphosphate (IP6) is a natural product known to inhibit vascular calcification (VC), but with limited potency and low plasma exposure following bolus administration. Here we report the design of a series of inositol phosphate analogs as crystallization inhibitors, among which 4,6-di-O-(methoxy-diethyleneglycol)-myo-inositol-1,2,3,5-tetrakis(phosphate), (OEG2)2-IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG2)2-IP4 potently stabilizes calciprotein particle (CPP) growth, consistently demonstrates low micromolar activity in different in vitro models of VC (i.e., human serum, primary cell cultures, and tissue explants), and largely abolishes the development of VC in rodent models, while not causing toxicity related to serum calcium chelation. The data suggest a mechanism of action independent of the etiology of VC, whereby (OEG2)2-IP4 disrupts the nucleation and growth of pathological calcification.


Assuntos
Fosfatos de Inositol/química , Fosfatos de Inositol/farmacologia , Calcificação Vascular/tratamento farmacológico , 6-Fitase/metabolismo , Adenina/efeitos adversos , Animais , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Difusão Dinâmica da Luz , Etilenoglicol/química , Humanos , Injeções Subcutâneas , Fosfatos de Inositol/farmacocinética , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Ratos Sprague-Dawley , Uremia/tratamento farmacológico , Uremia/fisiopatologia , Calcificação Vascular/induzido quimicamente , Difração de Raios X
7.
BMC Infect Dis ; 20(1): 167, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087689

RESUMO

BACKGROUND: Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. CASE PRESENTATION: A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. CONCLUSIONS: Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.


Assuntos
Antibacterianos/uso terapêutico , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Resistência a Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Vancomicina/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Diálise Renal , Resultado do Tratamento , Uremia/terapia , Vancomicina/efeitos adversos
8.
Arch Med Res ; 51(1): 21-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32086105

RESUMO

OBJETIVE: Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia. MATERIAL AND METHODS: Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry. RESULTS: Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment. CONCLUSIONS: These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.


Assuntos
Apoptose/efeitos dos fármacos , Indicã/farmacologia , Mioblastos/efeitos dos fármacos , Sarcopenia/induzido quimicamente , Uremia/induzido quimicamente , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Camundongos , Células Musculares/efeitos dos fármacos , Células Musculares/fisiologia , Mioblastos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sarcopenia/complicações , Toxinas Biológicas/metabolismo , Toxinas Biológicas/farmacologia , Regulação para Cima/efeitos dos fármacos , Uremia/complicações
9.
10.
N Engl J Med ; 382(3): 222-232, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31702883

RESUMO

BACKGROUND: Difelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients undergoing hemodialysis who had moderate-to-severe pruritus to receive either intravenous difelikefalin (at a dose of 0.5 µg per kilogram of body weight) or placebo three times per week for 12 weeks. The primary outcome was the percentage of patients with an improvement (decrease) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS; scores range from 0 to 10, with higher scores indicating greater itch intensity). The secondary outcomes included the change from baseline in itch-related quality-of-life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety. RESULTS: A total of 378 patients underwent randomization. A total of 82 of 158 patients (51.9%) in the difelikefalin group had a decrease of at least 3 points in the WI-NRS score (primary outcome), as compared with 51 of 165 (30.9%) in the placebo group. The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.1% in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001). Difelikefalin also resulted in a significant improvement from baseline to week 12 in itch-related quality of life as measured by the 5-D itch scale and the Skindex-10 scale. The imputed percentage of patients with a decrease of at least 4 points in the WI-NRS score at week 12 was significantly greater in the difelikefalin group than in the placebo group (37.1% [observed data: 64 of 158 patients] vs. 17.9% [observed data: 35 of 165 patients], P<0.001). Diarrhea, dizziness, and vomiting were more common in the difelikefalin group than in the placebo group. CONCLUSIONS: Patients treated with difelikefalin had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo. (Funded by Cara Therapeutics; KALM-1 ClinicalTrials.gov number, NCT03422653.).


Assuntos
Falência Renal Crônica/complicações , Piperidinas/uso terapêutico , Prurido/tratamento farmacológico , Receptores Opioides/agonistas , Diálise Renal , Uremia/complicações , Adulto , Método Duplo-Cego , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Prurido/etiologia , Qualidade de Vida , Resultado do Tratamento
11.
Internist (Berl) ; 61(4): 340-348, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31578597

RESUMO

Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity and mortality. This is mediated by the high prevalence of traditional cardiovascular risk factors in patients with CKD such as arterial hypertension and diabetes mellitus, but also by the presence of CKD-specific so-called nontraditional cardiovascular risk factors such as vascular calcification, uremic toxins, uremic dyslipidemia as well as inflammation and oxidative stress. Therefore, the primary and secondary prevention of cardiovascular disease represents an integral part of nephrology. This entails optimal control of blood pressure and diabetes, therapy of the uremic dyslipidemia as well as lifestyle-modifying factors such as weight reduction and smoking cessation.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/epidemiologia , Insuficiência Renal Crônica/complicações , Toxinas Biológicas/sangue , Uremia/complicações , Pressão Sanguínea/fisiologia , Cálcio/metabolismo , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/etiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertensão/prevenção & controle , Inflamação/complicações , Estresse Oxidativo , Fatores de Risco , Uremia/epidemiologia , Uremia/metabolismo , Calcificação Vascular/complicações , Calcificação Vascular/epidemiologia , Rigidez Vascular
16.
Clin Sci (Lond) ; 134(1): 15-32, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31860056

RESUMO

Fibroblast growth factor 23 (FGF23) increases phosphorus excretion and decreases calcitriol (1,25(OH)2D) levels. FGF23 increases from early stages of renal failure. We evaluated whether strict control of phosphorus intake in renal failure prevents the increase in FGF23 and to what extent inflammation impairs regulation of FGF23. The study was performed in 5/6 nephrectomized (Nx) Wistar rats fed diets containing 0.2-1.2% phosphorus for 3 or 15 days. FGF23 levels significantly increased in all Nx groups in the short-term (3-day) experiment. However, at 15 days, FGF23 increased in all Nx rats except in those fed 0.2% phosphorus. In a second experiment, Nx rats fed low phosphorus diets (0.2 and 0.4%) for 15 days received daily intraperitoneal lipopolysaccharide (LPS) injections to induce inflammation. In these rats, FGF23 increased despite the low phosphorus diets. Thus, higher FGF23 levels were needed to maintain phosphaturia and normal serum phosphorus values. Renal Klotho expression was preserved in Nx rats on a 0.2% phosphorus diet, reduced on a 0.4% phosphorus diet, and markedly reduced in Nx rats receiving LPS. In ex vivo experiments, high phosphorus and LPS increased nuclear ß-catenin and p65-NFκB and decreased Klotho. Inhibition of inflammation and Wnt signaling activation resulted in decreased FGF23 levels and increased renal Klotho. In conclusion, strict control of phosphorus intake prevented the increase in FGF23 in renal failure, whereas inflammation independently increased FGF23 values. Decreased Klotho may explain the renal resistance to FGF23 in inflammation. These effects are likely mediated by the activation of NFkB and Wnt/ß-catenin signaling.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Uremia/metabolismo , Animais , Calcitriol/farmacologia , Cálcio/metabolismo , Rim/efeitos dos fármacos , Masculino , Fósforo/metabolismo , Ratos Wistar , Insuficiência Renal/metabolismo , Insuficiência Renal Crônica/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia
17.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(12): 924-927, 2019 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-31887819

RESUMO

Objective: To investigate the etiology, characteristics and prevention of severe facial deformity in patients with uremia entering the dialysis stage. Methods: Four cases with uremia in the dialysis stage who presented with severe facial deformity between October 2011 and November 2018 were reviewed, including 3 males and 1 female. The ages were 31, 15, 51 and 61, respectively. The general information, clinical symptoms, biochemical indicators, relevant imaging indicators, diagnoses, treatments and efficacies of the 4 patients admitted to the First Affiliated Hospital of Anhui Medical University were collected. Results: All the 4 patients appeared obviously shorter, accompanied by a certain degree of decline in self-care ability, multiple bone and joint pain and severe facial deformity. They presented with significantly increased serum levels of alkaline phosphatase, calcium, phosphorus and parathyroid hormone, and parathyroid hormone level>2 500 pg/ml.Ultrasonography and (99)Tc(m) radionuclide scan showed in situ or ectopic hyperplasia of parathyroid tissue. Bone radiography showed local decrease of bone mineral density and cystic changes.After parathyroidectomy, the serum levels of alkaline phosphatase, parathyroid hormone, calciumand phosphorus decreased significantly, while bone pain symptoms and facial deformities gradually improved. Conclusion: Secondary hyperparathyroidism is a serious complication in patients with dialysis and few of patients may have severe facial deformity (Sagliker syndrome) affecting their normal life and social activities. Parathyroidectomy can improve the facial deformity and the quality of life of patients.


Assuntos
Hiperparatireoidismo Secundário , Uremia , Adolescente , Adulto , Cálcio , Feminino , Humanos , Hiperparatireoidismo Secundário/complicações , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides , Hormônio Paratireóideo , Paratireoidectomia , Qualidade de Vida , Uremia/complicações
18.
Pesqui. vet. bras ; 39(11): 889-899, Nov. 2019. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1056916

RESUMO

Pathological mineralization is the abnormal deposition of minerals in body tissues, previously injured or not. In these lesions, in addition to calcium, other minerals can be found at lower concentrations. Classically, mineralization is divided into two types: dystrophic and metastatic. However, currently, there is no consensus among researchers on the type of mineralization that occurs in uremic dogs. The objective of this study was to elucidate the type of pathological mineralization that occurs in dogs with uremic syndrome through the correlation of biochemical examinations with gross and histopathological changes, given the existence of controversial information on this theme in the specialized literature. The Shapiro-Wilk, D'Agostino and Pearson tests were used to evaluate data normality distribution, and analysis of variance (ANOVA) was applied to compare the data between more than two groups. Additionally, the Dunnett's multiple comparison test was used in the comparison between the Control Group (CG) and the Experimental Groups (G1, G2, and G3). Serum levels of urea, creatinine, total and ionized calcium, phosphorus, calcium-phosphorus product (CPP), parathyroid hormone (PTH), and albumin of 40 azotemic dogs with chronic kidney disease (CKD) were evaluated. Dogs were categorized by degree of azotemia (mild, moderate, and severe). Ionized hypocalcemia was observed in 97.5% (39/40) of the dogs, and no animals presented ionized hypercalcemia. Hyperphosphatemia was frequent (62.5%), especially in dogs with severe azotemia. PTH concentration increased with progression of azotemia, and high PTH levels were verified in 100% of the dogs with severe azotemia. CPP >60mg2/dl2 was observed in 75% (30/40) of the dogs. Of the 29 dogs that died during the study period, 16 were necropsied. Soft tissue mineralization was observed in 93.7% (15/16) of these dogs at gross and histopathological evaluation (HE and Von Kossa), regardless of the degree of azotemia, in nine organs/tissues: kidneys (75%), lungs (50%), stomach (31.2%), heart (25%), larynx (25%), intercostal muscles (25%), aorta (6.2%), intestines (6.2%), and tongue (6.2%). In one animal, the serosa of all segments of the small intestine showed whitish, rough, irregular, multifocal plaques of varying sizes, confirmed by histopathology as dystrophic mineralization of the longitudinal outer muscular layer, which presented necrosis of coagulation and of the intestinal serosa. This intestinal lesion has not been described in dogs with uremic syndrome to date. In conclusion, the laboratory and histopathologic data previously described, especially regarding tissue and vascular mineralization, which occur in association with previous degenerative/necrotic lesions in the absence of hypercalcemia in dogs with CKD, assist with clarifying inconsistencies found in the existing literature. Therefore, conceptually, mineralization that occurs in uremic dogs should be considered dystrophic.(AU)


Mineralização patológica é a deposição anormal de minerais em tecidos previamente lesados ou não. Nessas lesões, além do cálcio, outros minerais podem ser encontrados em concentrações inferiores. Classicamente, as mineralizações são divididas em dois tipos: distrófica e metastática. Contudo, atualmente, ainda não há consenso entre os pesquisadores sobre o tipo de mineralização que ocorre em cães urêmicos. Objetivou-se com esse estudo elucidar o tipo de mineralização patológica que ocorre em cães com síndrome urêmica através da correlação de exames bioquímicos com alterações macroscópicas e histopatológicas, visto a existência de informações controversas na literatura especializada. Os dados obtidos foram submetidos ao teste de Shapiro-Wilk e teste de D'Agostino e Pearson para avaliação da normalidade da distribuição e para comparação de dados em mais de dois grupos foi utilizado o teste ANOVA. Adicionalmente, o teste de comparações múltiplas de Dunnett permitiu a comparação entre o grupo controle (GC) com os demais grupos (G1, G2 e G3). Foram avaliados os níveis séricos de ureia, creatinina, cálcio total e ionizado, fósforo, produto cálcio-fósforo (PCF), PTH e albumina de 40 cães azotêmicos com doença renal crônica (DRC). Os cães foram classificados quanto ao grau de azotemia (leve, moderada e severa). Verificou-se hipocalcemia ionizada em 97,5% (39/40) dos cães e, em nenhum animal houve hipercalcemia ionizada. Hiperfosfatemia foi frequente (62,5%), principalmente em cães com azotemia severa. A concentração do PTH aumentou conforme a progressão da azotemia, encontrando-se elevada em 100% dos cães com azotemia severa. Em 75% (30/40) dos cães o PCF foi superior a 60mg2/dl2. Durante o estudo, 29 cães morreram, sendo 16 desses necropsiados. Em 93,7% (15/16) desses cães observou-se mineralização de tecidos moles, durante a avaliação macroscópica e histopatológica (HE e Von Kossa), independentemente do grau de azotemia, em nove órgãos/tecidos: rins (75%), pulmões (50%), estômago (31,2%), coração (25%), laringe (25%), músculos intercostais (25%), aorta (6,2%), intestino (6,2%) e língua (6,2%). Adicionalmente, em um animal verificou-se na serosa de todos os segmentos do intestino delgado placas multifocais brancacentas, rugosas, irregulares de tamanhos variados, cuja histopatologia confirmou tratar-se de mineralização distrófica da camada longitudinal muscular externa que apresentava necrose de coagulação e da serosa intestinal. Essa lesão intestinal nunca havia sido descrita em cães com síndrome urêmica. Em suma, os dados laboratoriais e histopatológicos aqui descritos, sobretudo, no que se refere à mineralização tecidual e vascular, que ocorrem relacionadas a lesões degenerativo-necróticas prévias, na ausência de hipercalcemia, em cães com DRC, ajudam a esclarecer as incongruências existentes na literatura. Por conseguinte, conceitualmente, as mineralizações que ocorrem em cães urêmicos devem ser consideradas distróficas.(AU)


Assuntos
Animais , Cães , Uremia/veterinária , Calcinose/veterinária , Insuficiência Renal Crônica/veterinária , Azotemia/veterinária
19.
ACS Appl Mater Interfaces ; 11(47): 43843-43856, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31663727

RESUMO

Protein-bound uremic toxins (PBUTs) can cause noxious effects in patients suffering from renal failure as a result of inhibiting the transport of proteins and inducing their structural modification. They are difficult to remove through standard hemodialysis (HD) treatment. Herein, we report an organic bioelectronic HD device system for the effective removal of PBUTs through electrically triggered dissociation of protein-toxin complexes. To prepare this system, we employed electrospinning to fabricate electrically conductive quaternary composite nanofiber mats-comprising multiwalled carbon nanotubes (MWCNTs), poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS)-on conventional polyethersulfone (PES) dialysis membranes. These composite nanofiber platforms exhibited (i) long-term water resistance (due to cross-linking among PSS, PEO, and GOPS), (ii) high adhesion strength on the PES membrane (due to GOPS functioning as an adhesion promoter), (iii) enhanced electrical properties [due to the MWCNTs and PEDOT:PSS promoting effective electrical stimulation (ES) operation in devices containing bioelectronic interfaces (BEI)], and (iv) good anticoagulant ability and negligible hemolysis of red blood cells. We employed this organic BEI electronic system as a novel single-membrane HD device to study the removal efficiency of four kinds of uremic toxins [p-cresol (PC), indoxyl sulfate, and hippuric acid as PBUTs; creatinine as a non-PBUT] as well as the effects of ES on lowering the protein binding ratio. Our organic BEI devices provided a high rate of removal of PC with low protein loss after 4 h of a simulated dialysis process. It also functioned with low complement activation, low contact activation levels, and lower amounts of platelet adsorption, suggesting great suitability for use in developing next-generation bioelectronic medicines for HD.


Assuntos
Nanotubos de Carbono/química , Proteínas/química , Diálise Renal/instrumentação , Toxinas Biológicas/química , Uremia/terapia , Adsorção , Cresóis/sangue , Cresóis/química , Eletrônica/instrumentação , Hipuratos/sangue , Hipuratos/química , Humanos , Indicã/sangue , Indicã/química , Polímeros/química , Toxinas Biológicas/sangue , Uremia/sangue
20.
BMC Neurosci ; 20(1): 52, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585527

RESUMO

BACKGROUND: Neurological complications may occur in patients with acute or chronic renal failure; however, in cases of acute renal failure, the signs and symptoms are usually more pronounced, and progressed rapidly. Oxidative stress and nitric oxide in the hippocampus, following kidney injury may be involved in cognitive impairment in patients with uremia. Although many women continue taking hormone therapy for menopausal symptom relief, but there are also some controversies about the efficacy of exogenous sex hormones, especially estrogen therapy alone, in postmenopausal women with kidney injury. Herein, to the best of our knowledge for the first time, spatial memory and synaptic plasticity at the CA1 synapse of a uremic ovariectomized rat model of menopause was characterized by estradiol replacement alone. RESULTS: While estradiol replacement in ovariectomized rats without uremia, promotes synaptic plasticity, it has an impairing effect on spatial memory through hippocampal oxidative stress under uremic conditions, with no change on synaptic plasticity. It seems that exogenous estradiol potentiated the deleterious effect of acute kidney injury (AKI) with increasing hippocampal oxidative stress. CONCLUSIONS: Although, estrogen may have some positive effects on cognitive function in healthy subjects, but its efficacy in menopause subjects under uremic states such as renal transplantation, needs to be further investigated in terms of dosage and duration.


Assuntos
Lesão Renal Aguda/fisiopatologia , Região CA1 Hipocampal/fisiopatologia , Estradiol/efeitos adversos , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Lesão Renal Aguda/complicações , Animais , Feminino , Menopausa/psicologia , Neurônios/fisiologia , Ovariectomia , Ratos , Memória Espacial/fisiologia , Uremia/complicações , Uremia/fisiopatologia
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