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1.
Rev Assoc Med Bras (1992) ; 66(9): 1258-1263, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33027455

RESUMO

INTRODUCTION: This study aims to determine the incidence of de novo nephritic syndrome (NS) in COVID-19 patients and identify its associated factors. METHODS: All ward patients with COVID-19 pneumonia were investigated. After determining the inclusion and exclusion criteria, the study population was identified. The urine dipstick test and urine protein creatinine ratio (UPCR) measurements were performed. Patients with de novo NS findings, nasopharyngeal swab, and urine RT-PCR tests were performed simultaneously. RESULTS: This descriptive cross-sectional study was conducted with 21 patients with COVID-19. The mean age of the patients was 42.2±8.8 years, and 71.4% of them were male. The mean duration of follow-up was 28.4±9.3 days. The urine RT-PCR test was positive in one patient (4.8%). Improvements were observed in hematuria by 71.4%, and proteinuria by 85.7% at the end of the follow-up. A significant decrease in the measured UPCR was found in comparison to the baseline(P=0.000). Also, improvements were recorded in the complete blood counts, inflammatory parameters, ferritin, and coagulation tests, compared to the baseline. There was a positive correlation between baseline UPCR and ferritin, and a negative correlation between baseline UPCR and sodium values. CONCLUSION: COVID-19-induced de novo nephritic syndrome may occur mainly due to tubulointerstitial involvement and often results in spontaneous remission. However, why these findings were not present in all patients who had no comorbidities is not clear.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nefropatias/etiologia , Pandemias , Pneumonia Viral , Adulto , Infecções por Coronavirus/complicações , Creatinina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações
4.
Intensive Care Med ; 46(10): 1863-1872, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816098

RESUMO

PURPOSE: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. METHODS: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. RESULTS: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO2/FiO2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. CONCLUSION: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Estado Terminal , Unidades de Terapia Intensiva , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Feminino , Humanos , Nefropatias/epidemiologia , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Fatores de Risco , Choque/epidemiologia , Choque/etiologia , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
5.
Life Sci ; 258: 118153, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738361

RESUMO

AIMS: Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action. MAIN METHODS: We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2-/-) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting. KEY FINDINGS: Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2-/- mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2-/- mice. SIGNIFICANCE: Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.


Assuntos
Isotiocianatos/uso terapêutico , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/complicações , Substâncias Protetoras/uso terapêutico , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Nefropatias/metabolismo , Glomérulos Renais/citologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Podócitos/citologia , Podócitos/efeitos dos fármacos , Podócitos/metabolismo
7.
Life Sci ; 257: 118138, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712298

RESUMO

AIMS: Hypertension is a relevant sex and sex hormones-dependent risk factor where the cardiovascular and renal health of the population are concerned. Men experience greater losses of renal function (RF) than women, but the mechanisms remain somewhat unclear. Our goal was to evaluate the relationship between oxidative stress (OS), angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activities and RF in male and female SHR. MAIN METHODS: Twelve-week-old spontaneously hypertensive rats (SHR) were submitted to either castration or SHAM surgery and divided into 4 groups, SHAM or Castrated (CAST) males or females. After 51 days we evaluated RF (inulin and sodium para-aminohippurate), ACE and ACE2 activities (fluorimetry), OS (flow cytometry), collagen deposition (picrosirius red) and protein expression (western blot). KEY FINDINGS: Males presented lower RF than females and castration impaired this parameter in both groups. Sexual dimorphism was not observed regarding OS and inflammation; however, castration increased this parameter more severely in males than in females. SHAM males exhibited higher collagen deposition than females, though castration increased it in both sexes, eliminating the difference. We found sexual dimorphism regarding renal ACE and ACE2 activities, which were lower in males than in females. Although castration did not alter ACE activity, it reduced ACE2 activity in females and increased it in males. SIGNIFICANCE: These results indicate that sex hormones affect RF in SHR. As alterations in the oxidative system were capable of promoting podocyte injury, inflammation, and collagen deposition, we put forward that these effects are differently modulated by ACE and ACE2.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Nefropatias/etiologia , Estresse Oxidativo , Peptidil Dipeptidase A/metabolismo , Ratos Endogâmicos SHR/metabolismo , Animais , Western Blotting , Colágeno/metabolismo , Feminino , Rim/enzimologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Orquiectomia , Ovariectomia , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fatores Sexuais
8.
PLoS One ; 15(7): e0234818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663210

RESUMO

BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors used to treat EGFR mutation positive non-small-cell lung cancer (NSCLC). Skin rash and diarrhea are well-known and common adverse events in patients receiving erlotinib, whereas other adverse events, including eye, liver, or renal disorders have not been evaluated adequately. This meta-analysis aimed to evaluate the ocular, hepatobiliary, and renal toxicities of erlotinib in patients with NSCLC cancers. METHODS: In total, sixty studies were assessed, and the results of the included studies were quantitatively integrated using meta-analysis. The incidence of ocular, hepatobiliary (alanine aminotransferase [ALT] and bilirubin elevations; other hepatic adverse events), and renal adverse events were estimated. Additionally, the erlotinib-treated groups and the control groups (placebo or other treatment) were compared with respect to ocular disorders and ALT elevation. The study protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO) CRD42018093758. RESULTS: The overall incidence of ocular disorders was 3.30% (95% confidence interval [CI] 2.20%-5.00%). The incidence of ALT elevation, bilirubin elevation, and other hepatobiliary disorders was 6.40% (95% CI 3.90%-10.4%), 3.80% (95% CI 2.30%-6.10%), and 1.00% (95% 0.60%-1.80%), respectively. The incidence of renal disorder was 3.10% (95% CI 1.90%-5.00%). The risk of ocular toxicity in the erlotinib treatment group was significantly increased (risk ratio = 2.91; 95% CI 1.70-4.98) compared to that in the control group. ALT elevation was not significantly different between the two groups. CONCLUSION: Based on the results, careful monitoring of ocular toxicity in patients receiving erlotinib should be recommended and closer monitoring of hepatic toxicity should be also recommended in patients with liver-related risk factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cloridrato de Erlotinib/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Sistema Digestório/etiologia , Intervalo Livre de Doença , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Exantema/etiologia , Olho/efeitos dos fármacos , Oftalmopatias/etiologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Nefropatias/etiologia , Neoplasias Pulmonares/genética , Masculino , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
9.
Eur J Vasc Endovasc Surg ; 60(3): 395-401, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32665199

RESUMO

OBJECTIVE: The objective of this prospective single centre study was to assess whether branches and fenestrations have different outcomes on renal function in the early phase. METHODS: From March 2018 to June 2019, 67 patients who underwent elective fenestrated and branched endovascular aneurysm repair (F/BEVAR) procedures were enrolled in this study. The patients were divided into two groups according to the renal bridging component configuration (fenestration vs. branch). All of them underwent dynamic renal scintigraphy with 99mTc diethylenetriaminepentaacetic acid (DTPA), two weeks pre-operatively, and three months and one year post-operatively. The primary end points were peri-procedural technical success, 30 day major adverse events, differences in glomerular filtration rate (GFR) between the branch and fenestration configurations, and variations between the pre-operative and the post-operative dynamic renal scintigraphy. RESULTS: Overall, 135 kidneys were analysed: 63 in the 32 patients treated with fenestrations, and 72 in the 35 patients treated with branches; the mean GFR on baseline scintigraphy was 58.4 ± 30.9 mL/min in the fenestration group, and 65.1 ± 29.2 mL/min in the branch group. Only kidneys associated with a patent fenestration/branch were included in the split GFR final analysis. The mean total GFR at three month scintigraphy decreased by 6.0 ± 2.9 mL/min in the fenestration group and by 23.4 ± 6.4 mL/min in the branch group. The split GFR decreased by 3.5 ± 0.6 mL/min in the fenestration group, and by 15.4 ± 5.4 mL/min in the branch group. The GFR decrease remained stable at one year. CONCLUSION: In this study, the use of branches for renal arteries during F/BEVAR resulted in a greater decrease in the GFR than in those patients who were treated with fenestrations alone. The scintigraphic alterations were evident at an early phase.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Nefropatias/diagnóstico por imagem , Cintilografia , Artéria Renal/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Desenho de Prótese , Compostos Radiofarmacêuticos/administração & dosagem , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia , Pentetato de Tecnécio Tc 99m/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
10.
Int J Infect Dis ; 97: 391-395, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32502665

RESUMO

INTRODUCTION: Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital. MATERIALS AND METHODS: This study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis. RESULTS: The adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem. CONCLUSION: There were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Colistina/efeitos adversos , Farmacorresistência Bacteriana , Nefropatias/etiologia , Meropeném/uso terapêutico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Colistina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tailândia
11.
Eur Rev Med Pharmacol Sci ; 24(8): 4607-4615, 2020 04.
Artigo em Inglês | MEDLINE | ID: covidwho-205205

RESUMO

COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms "2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Antígenos HLA/genética , Pneumonia Viral/diagnóstico , Autopsia , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Genoma Viral , Haplótipos , Humanos , Nefropatias/etiologia , Hepatopatias/etiologia , Pandemias , Pneumonia Viral/complicações , RNA Viral/isolamento & purificação , Manejo de Espécimes
12.
Eur Rev Med Pharmacol Sci ; 24(8): 4607-4615, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32374001

RESUMO

COVID-19 pandemic can cause irreparable damage to the involved society. This study aimed to provide a summary of the up-to-dated clinical display, diagnostics, molecular and genetic implications for COVID-19 infected patients. In this review, 73 research articles published before 25 March 2020 were analyzed to better understand the clinical characteristics of patients and to introduce the available serological, hematology and molecular diagnostic methods. Apart from articles extracted from PubMed and Google Scholar, WHO (https://www.who.int/), NHC (National Health Commission of the People's Republic of China (http://www.nhc.gov.cn/), NICE (National Institute for Health and Clinical Excellence, https://www.nice.org.uk/), CDC (Centers for Disease Control and Prevention, https://www.cdc.gov/), and National Administration of Traditional Chinese Medicine (http://www.satcm.gov.cn/) were also accessed to search for eligible studies. Papers published between January 1, 2020, and 25 March 2020 were searched in English and the terms "2019-nCoV, Covid-19, Clinical Characteristics OR manifestation, method of detection, COVID-19 Genome and molecular test" were used. As the pandemic continues to evolve, there have been reports about the possibility of asymptomatic transmission of this newly emerged pneumonia virus. We highlighted the role of HLA haplotype in virus infection as HLA typing will provide susceptibility information for personalized prevention, diagnosis, and treatment in future studies. All the data in this article will assist researchers and clinicians to develop their clinical views regarding infected patients and to emphasize the origin of SARS-CoV-2 for diagnostics.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Antígenos HLA/genética , Pneumonia Viral/diagnóstico , Autopsia , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Genoma Viral , Haplótipos , Humanos , Nefropatias/etiologia , Hepatopatias/etiologia , Pandemias , Pneumonia Viral/complicações , RNA Viral/isolamento & purificação , Manejo de Espécimes
13.
AJR Am J Roentgenol ; 215(2): 406-412, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32374662

RESUMO

OBJECTIVE. IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and fibrosis in various organs. The objective of this study is to investigate CT findings of IgG4-related lesions involving the upper urinary tract and compare them with those of urothelial carcinomas. MATERIALS AND METHODS. This study reviewed pretreatment CT images of 13 consecutive patients with IgG4-related disease with upper urinary tract lesions and 80 consecutive patients with urothelial carcinomas. The findings assessed were laterality, location, growth pattern, margins, internal structure, presence of calcification and lipid component, enhancement pattern, and extraurinary findings. RESULTS. Bilaterality (p < 0.0001), an extramural growth pattern (p < 0.0001), a greater number of affected segments (p = 0.04), and a gradual dynamic enhancement pattern (p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding (p = 0.03), presacral fat stranding (p < 0.001), fat stranding of the pelvic walls (p < 0.001), and aortic involvement (p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant. CONCLUSION. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have a longer urinary tract involvement and exhibit an extramural growth pattern, ill-defined margins, a gradual enhancement pattern, aortic involvement, and fat stranding in the paraaortic, presacral, or pelvic wall areas.


Assuntos
Carcinoma de Células de Transição/diagnóstico por imagem , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Nefropatias/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Doenças Ureterais/diagnóstico por imagem , Neoplasias Ureterais/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/etiologia , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/complicações , Nefropatias/etiologia , Neoplasias Renais/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Doenças Ureterais/etiologia , Neoplasias Ureterais/etiologia
14.
Am J Physiol Renal Physiol ; 318(6): F1489-F1499, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390513

RESUMO

Recently, we reported that obese Dahl salt-sensitive (SS) leptin receptor mutant (SSLepRmutant) rats display progressive renal injury. The present study demonstrated that the early development of renal injury in the SSLepRmutant strain is associated with an increase in the renal infiltration of macrophages compared with lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SSLepRmutant strain. Four-week-old SS and SSLepRmutant rats were treated with either vehicle (PBS) or clodronate (50 mg/kg ip, 2 times/wk) for 4 wk. While the administration of clodronate did not reduce renal macrophage infiltration in SS rats, clodronate decreased macrophages in the kidneys of SSLepRmutant rats by >50%. Interestingly, clodronate significantly reduced plasma glucose, insulin, and triglyceride levels and markedly improved glucose tolerance in SSLepRmutant rats. Treatment with clodronate had no effect on the progression of proteinuria or renal histopathology in SS rats. In the SSLepRmutant strain, proteinuria was markedly reduced during the first 2 wk of treatment (159 ± 32 vs. 303 ± 52 mg/day, respectively). However, after 4 wk of treatment, the effect of clodronate was no longer observed in the SSLepRmutant strain (346 ± 195 vs. 399 ± 50 mg/day, respectively). The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal fibrosis versus SS rats. Treatment with clodronate significantly decreased glomerular injury and renal fibrosis in the SSLepRmutant strain. Overall, these data indicate that the depletion of macrophages improves metabolic disease and slows the early progression of renal injury in SSLepRmutant rats.


Assuntos
Ácido Clodrônico/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Receptores para Leptina/genética , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Feminino , Fibrose , Insulina/sangue , Rim/metabolismo , Rim/patologia , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Mutação , Obesidade/sangue , Obesidade/complicações , Obesidade/genética , Ratos Endogâmicos Dahl , Fatores Sexuais , Fatores de Tempo , Triglicerídeos/sangue
15.
J Biomed Sci ; 27(1): 63, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389123

RESUMO

Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.


Assuntos
Endometriose/fisiopatologia , Cardiopatias/fisiopatologia , Hipóxia/fisiopatologia , Nefropatias/fisiopatologia , Doenças Metabólicas/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Neoplasias/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Doença Crônica , Endometriose/etiologia , Feminino , Cardiopatias/etiologia , Humanos , Hipóxia/complicações , Nefropatias/etiologia , Masculino , Doenças Metabólicas/etiologia , Isquemia Miocárdica/etiologia , Neoplasias/etiologia , Pré-Eclâmpsia/etiologia , Gravidez
16.
Braz J Med Biol Res ; 53(4): e9220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267310

RESUMO

Rab7, an important member of the Rab family, is closely related to autophagy, endocytosis, apoptosis, and tumor suppression but few studies have described its association with renal fibrosis. In the early stage, our group studied the effects of Rab7 on production and degradation of extracellular matrix in hypoxic renal tubular epithelial cells. Because cell culture in vitro is different from the environment in vivo, it is urgent to understand the effects in vivo. In our current study, we established a renal fibrosis model in Rab7-knock-in mice (prepared by CRISPR/Cas9 technology) and wild type (WT) C57BL/6 mice using unilateral ureteral obstruction (UUO). Seven and 14 days after UUO, the expression of the Rab7 protein in WT mice, as well as the autophagic activity, renal function, and the degree of renal fibrosis in WT and Rab7-knock-in mice were examined by blood biochemical assay, hematoxylin-eosin and Masson staining, immunohistochemistry, and western blotting. We found that the Rab7 expression in WT mice increased over time. Furthermore, the autophagic activity constantly increased in both groups, although it was higher in the Rab7-knock-in mice than in the WT mice at the same time point. Seven days after UUO, the degree of renal fibrosis was milder in the Rab7-knock-in mice than in the WT mice, but it became more severe 14 days after surgery. Similar results were found for renal function. Therefore, Rab7 suppressed renal fibrosis in mice initially, but eventually it aggravated fibrosis with the activation of autophagy.


Assuntos
Autofagia/fisiologia , Nefropatias/etiologia , Rim/patologia , Obstrução Ureteral/complicações , Proteínas rab de Ligação ao GTP/genética , Animais , Feminino , Fibrose , Masculino , Camundongos , Camundongos Knockout , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Regulação para Cima , Proteínas rab de Ligação ao GTP/metabolismo
17.
Presse Med ; 49(1): 104017, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234380

RESUMO

IgG4-RD may affect several organs including kidneys. The kidney is involved in approximately 20% of patient with IgG4-RD. The most common intrinsic kidney disease is tubulointerstitial nephritis (IgG4-TIN). Retroperitoneal fibrosis (IgG4-RPF) may induce obstructive acute renal failure. More rarely, IgG4-RKD can manifest as a glomerular disease, in particular as a membranous nephropathy (MN). It mostly affects middle-aged to elderly men and causes acute or chronic renal dysfunction, multiple hypodense lesions on CT-Scan and various extra-renal lesions. Increased serum IgG4 and hypocomplementemia are the most important serological findings for the diagnosis of IgG4-RD and thus should be systematically assessed when IgG4-RKD is suspected. Specific diagnosis criteria for IgG4-TIN including interstitial infiltration of IgG4-positive plasma cells, storiform fibrosis and tubular basement membrane immune complex deposits have been proposed. Corticosteroids are effective and remain the first-line therapy but relapses or severe forms could respond to immunosuppressive therapy.


Assuntos
Doença Relacionada a Imunoglobulina G4/complicações , Nefropatias/etiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Creatinina/sangue , Feminino , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Rim/diagnóstico por imagem , Nefropatias/sangue , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/sangue , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/etiologia , Nefrite Intersticial/patologia , Fibrose Retroperitoneal/complicações , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/patologia , Esteroides/uso terapêutico
18.
Adv Exp Med Biol ; 1238: 1-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32323176

RESUMO

In the past decade, research focusing on the gut microbiota has attracted a growing number of scientists. We increasingly realize that the gut microbiota plays a key role in both maintaining host homeostasis and affecting the progression of multiple diseases, which means that the microorganisms living in the intestines would not only influence the gastrointestinal tract but also impact other important organs such as the liver, brain, kidney, and lung. The underlying modulatory mechanism is complicated; however, we can expand the existing insight on the development of organ damage pathogenesis and discover novel therapeutic targets for organ injury-related diseases by investigating this "hot-topic". In this chapter, we will present a broad overview of the gut microbiota and organ injury, as well as the latest research achievements regarding the linkage between them.


Assuntos
Disbiose , Microbioma Gastrointestinal , Homeostase , Encefalopatias/etiologia , Humanos , Nefropatias/etiologia , Hepatopatias/etiologia , Pneumopatias/etiologia
19.
Inflamm Res ; 69(7): 645-656, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32342116

RESUMO

OBJECTIVE AND DESIGN: Nowadays, sepsis-induced acute kidney injury (AKI) has gradually become a global problem for its high incidence and increasing mortality. Previous study has reported lncRNA ENST00000452391.1 in sepsis patients. However, its potential biological function and downstream molecular mechanism are still mysterious. METHODS AND RESULTS: Our study found that it was upregulated in sepsis-induced AKI patients, so it was identified as "sepsis-induced kidney injury associated transcript 1 (SIKIAT1)". We used lipopolysaccharide (LPS) stimulated HK-2 cells as an in vitro model to demonstrated that SIKIAT1 acts as a ceRNA for miR-96-3p to enhance FOXA1 expression and promote HK-2 cell apoptosis. CONCLUSION: Therefore, it could be a potential biomarker and therapeutic target for sepsis-induced AKI in the development of disease.


Assuntos
Apoptose/fisiologia , Fator 3-alfa Nuclear de Hepatócito/fisiologia , Nefropatias/etiologia , MicroRNAs/fisiologia , Sepse/complicações , Linhagem Celular , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Sepse/genética , Sepse/patologia , Transfecção
20.
West Afr J Med ; 37(2): 107-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150627

RESUMO

BACKGROUND: There are few reports on socioeconomic status (SES) of patients with chronic kidney disease (CKD) in Nigeria and indeed Africa, South of the Sahara. Identifying SES as an important factor for disability in people with CKD would provide a means for early identification of those at risk and, possible intervention. OBJECTIVE: To determine the SES of CKD patients attending renal clinic in the University of Nigeria Teaching Hospital. METHODS: Cross-sectional descriptive design was adopted using pretested questionnaire to elicit data on SES (age, place of residence, household asset ownership, source of drinking water; source of cooking energy; and type of toilet facility) from one hundred and forty-five (145) CKD patients attending renal clinic in the University of Nigeria Teaching Hospital. Principal component analysis was used to classify the SES into five quintiles. RESULTS: Majority of the respondents (patients) in stages 4 and 5 CKD, constituting 17.2% and 39.3% respectively were from the lower SES. There was significant correlation between SES and age of the patients; place of residence; hypertension history; ownership of some household assets; source of drinking water; source of cooking energy; and type of toilet facility. CONCLUSION: This study demonstrated that many of our patients were from the lower SES. It is recommended that both governmental and non-governmental agencies should help these patients with some form of health insurance to alleviate their healthcare cost burden.


Assuntos
Nefropatias/epidemiologia , Insuficiência Renal Crônica , Características de Residência , Classe Social , Estudos Transversais , Hospitais de Ensino , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nigéria/epidemiologia , Pobreza/estatística & dados numéricos , Fatores Socioeconômicos
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