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1.
Nephrol Dial Transplant ; 35(10): 1652-1662, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022712

RESUMO

As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid-base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia-reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Taxa de Filtração Glomerular/fisiologia , Rim/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Lesão Renal Aguda/fisiopatologia , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia
2.
Medicine (Baltimore) ; 99(31): e21438, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756155

RESUMO

RATIONALE: Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene result in a very variable presentation, including maturity onset diabetes of the young (MODY), renal cysts, renal dysplasia, and autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by tubular damage, renal fibrosis, and progressive renal dysfunction. PATIENT CONCERNS: A 22-year-old man came to the hospital presenting with hyperglycemia, hyperuricemia and elevated serum creatinine. His urine protein was within the normal range. The ultrasound examination revealed shrunken kidneys with renal cysts. The patient's mother was diagnosed with diabetes mellitus when she was 25 years old. Her laboratory results showed elevated serum creatinine. Her ultrasonography revealed shrunken kidneys with renal cysts and hydronephrosis without kidney stones. The next-generation sequencing revealed that the proband and his mother held the same heterozygous missense mutation (c.530G>A, NM_000458, p.R177Q) in the HNF1B gene. Bioinformatic analyses predicted that the mutation was likely pathogenic. DIAGNOSIS: The patient and his mother were diagnosed as ADTKD and MODY5 due to HNF1B mutation. INTERVENTION: The proband was administered metformin at a dose of 500 mg/day. OUTCOMES: The patient had well-controlled blood glucose levels and a stable renal function at his 12-month follow-up. LESSONS: We should take into account the diagnoses of ADTKD and MODY5 if patients present with early onset diabetes and multiple renal cysts or evidence of renal tubulointerstitial dysplasia, especially those with negative proteinuria results. Genetic testing helps detect the HNF1B gene mutations.


Assuntos
Doenças do Sistema Nervoso Central/genética , Esmalte Dentário/anormalidades , Diabetes Mellitus Tipo 2/genética , Fator 1-beta Nuclear de Hepatócito/genética , Doenças Renais Císticas/genética , Nefrite Intersticial/genética , Assistência ao Convalescente , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hiperglicemia/etiologia , Hiperuricemia/etiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Rim/diagnóstico por imagem , Rim/patologia , Rim/fisiopatologia , Doenças Renais Císticas/complicações , Doenças Renais Císticas/tratamento farmacológico , Doenças Renais Císticas/patologia , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Mutação de Sentido Incorreto , Nefrite Intersticial/complicações , Nefrite Intersticial/patologia , Linhagem , Ultrassonografia/métodos , Adulto Jovem
3.
Internist (Berl) ; 61(9): 969-979, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32785740

RESUMO

Erdheim-Chester disease (ECD) is nowadays classified as belonging to those neoplasms with origins in the myeloid dendritic cell lines. The clonal alterations maintain a chronic inflammatory condition, which dominates the pathogenesis and clinical expression. Characteristic for ECD are many skeletal manifestations; however, the multisystem disease affects many other organs (including the respiratory tract, heart, retroperitoneum, eyes, central nervous system and endocrine system). The diagnosis is usually first made only after a disease duration of many years. This is due to the rarity of the disease and the very diffuse symptoms in addition to the heterogeneous organ manifestations. There are no uniform diagnostic criteria. The constellation of unclear polyserositis and ostealgia, possibly in association with neurological and endocrine deficiencies, should steer the suspicion towards an ECD. The diagnosis can be confirmed by an organ biopsy and the immunohistochemical examination enables the relatively certain differentiation from other forms of histiocytosis. The detection of activating oncological mutations in signal transduction pathways has opened up the possibility of targeted treatment with kinase inhibitors, such as vemurafenib for BRAF V600E mutations. Up to the discovery of activating mutations, interferon-alpha was used as the first line treatment; however, in view of the superiority of kinase inhibitors, the first line treatment with interferon-alpha currently appears to be questionable. The prognosis for untreated ECD is exceptionally poor and interferon-alpha leads to a clear improvement. Further progress is hoped for with the use of targeted treatments.


Assuntos
Doença de Erdheim-Chester/tratamento farmacológico , Interferon-alfa/uso terapêutico , Rim/fisiopatologia , Mutação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/uso terapêutico , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/genética , Humanos , Prognóstico
4.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
6.
Medicine (Baltimore) ; 99(34): e21794, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846812

RESUMO

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ±â€Š29.0 and 61.6 ±â€Š23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ±â€Š3.4 [with fatigue] vs 17.4 ±â€Š4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Fadiga Muscular , Isquemia Miocárdica/fisiopatologia , Músculos Respiratórios/fisiopatologia , Idoso , Exercício Físico/fisiologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pressões Respiratórias Máximas , Pessoa de Meia-Idade
7.
Life Sci ; 258: 118178, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739468

RESUMO

AIMS: Gentamicin (GEN) is one of the most valuable aminoglycoside antibiotics utilized against life-threatening bacterial infections. Unfortunately, GEN-induced nephrotoxicity limited its clinical utility. The pathologic process of nephrotoxicity caused by GEN may involve epithelial to mesenchymal transition (EMT). Resveratrol (RES) is a natural compound was revealed to inhibit EMT in kidney. The present work was conducted to explore the potential renoprotective role of RES on GEN-induced EMT. Moreover, the underlying signaling pathway of this inhibition was investigated. MAIN METHODS: Mice were treated with GEN by intraperitoneal (i.p.) route daily for 15 days to identify EMT onset with regard to GEN-induced nephrotoxicity. To assess the ameliorative role of RES against GEN-induced EMT, RES was i.p. administrated in high and low doses before and concurrently with GEN treatment. KEY FINDINGS: GEN administration significantly deteriorated kidney functions. In addition, reduced glutathione (GSH) content and catalase (CAT) activity were significantly decreased with a concomitant increase in the content of kidney malondialdehyde (MDA) after GEN treatment. Histological changes and deposition of collagen were extensive in renal corpuscles and tubules. Increased expression of alpha smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and phosphorylated (p)-Smad2 were observed after GEN administration, while E-cadherin expression was decreased. On the contrary, pretreatment with both doses of RES reversed the modifications caused by GEN administration. SIGNIFICANCE: We concluded that EMT contributes to pathogenesis of GEN-induced nephrotoxicity. RES has a protective effect on GEN-induced EMT via suppressing oxidative stress and a possible involvement of TGF-ß/Smad signaling pathway.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Gentamicinas/efeitos adversos , Rim/metabolismo , Rim/patologia , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Biomarcadores/sangue , Fibrose , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Resveratrol/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
8.
Transplantation ; 104(8): 1553-1559, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732831

RESUMO

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.


Assuntos
Lesão Renal Aguda/diagnóstico , Função Retardada do Enxerto/epidemiologia , Seleção do Doador/métodos , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Aloenxertos/provisão & distribução , Biomarcadores/análise , Biópsia , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Seleção do Doador/normas , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Humanos , Rim/patologia , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/normas , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
PLoS One ; 15(8): e0237443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813713

RESUMO

BACKGROUND: It is controversial to evaluate the function of hydronephrotic kidneys by renal dynamic imaging (RDI). Our aim was to study the features of renal dynamic imaging (RDI) at different stages after unilateral ureteral obstruction (UUO) and to investigate a method that could be reasonably used to evaluate renal function and predict renal functional recoverability. METHODS: We made UUO models using fifteen adult New Zealand white rabbits and systematically observed the changes in kidney morphology, blood flow, radiotracer distribution and function by RDI. We then compared the differences in terms of imaging features between different periods and analyzed the relationship between blood flow and function in obstructed kidneys. RESULTS: 1) Obstructed kidneys gradually became larger than preoperative kidneys and contralateral kidneys (P<0.05) and reached their peak size between days 42 and 56, after which they gradually got smaller in size. 2)The correlation between the blood perfusion of the obstructed kidney and the obstruction duration (r = 0.125, P = 0.045) was very weak. In the initial period of obstruction, the perfusion of the obstructed kidney significantly decreased, followed by a sharp rebound in later days, and then the perfusion declined again. The peak in blood perfusion was on day 7. 3) The uptake rate of the obstructed kidney drastically decreased in the early stage and became lower than that of the contralateral kidney and the kidney before the operation (P<0.05), after which uptake increased gradually; the peak was on day 28. After that, uptake gradually decreased. 4) The grading of the radiotracer distribution in obstructed kidneys was positively correlated with the obstruction duration (r = 0.975, P = 0.000), and a uniform renal distribution was an early feature of obstruction. 5) The blood perfusion of the obstructed kidney and its functioning frequently increased or decreased simultaneously, but sometimes there was also a mismatch. The peak of renal blood perfusion recovery occurred prior to the peak of renal function recovery. CONCLUSION: In different periods of severe UUO, the imaged features of obstructed kidneys were different. These features are beneficial for determining the degree of hydronephrosis and renal function and predicting renal functional recoverability.


Assuntos
Rim/fisiopatologia , Pentetato de Tecnécio Tc 99m/química , Obstrução Ureteral/patologia , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Rim/diagnóstico por imagem , Masculino , Coelhos , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único
10.
PLoS Comput Biol ; 16(8): e1008074, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804929

RESUMO

Congestive heart failure is characterized by suppressed cardiac output and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload. Mathematical modeling provides a means to investigate the integrated function and dysfunction of heart and kidney in heart failure. This study updates our previously reported integrated model of cardiac and renal functions to account for the fluid exchange between the blood and interstitium across the capillary membrane, allowing the simulation of edema. A state of heart failure with reduced ejection fraction (HF-rEF) was then produced by altering cardiac parameters reflecting cardiac injury and cardiovascular disease, including heart contractility, myocyte hypertrophy, arterial stiffness, and systemic resistance. After matching baseline characteristics of the SOLVD clinical study, parameters governing rates of cardiac remodeling were calibrated to describe the progression of cardiac hemodynamic variables observed over one year in the placebo arm of the SOLVD clinical study. The model was then validated by reproducing improvements in cardiac function in the enalapril arm of SOLVD. The model was then applied to prospectively predict the response to the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, which has been shown to reduce heart failure events in HF-rEF patients in the recent DAPAHF clinical trial by incompletely understood mechanisms. The simulations predict that dapagliflozin slows cardiac remodeling by reducing preload on the heart, and relieves congestion by clearing interstitial fluid without excessively reducing blood volume. This provides a quantitative mechanistic explanation for the observed benefits of SGLT2i in HF-rEF. The model also provides a tool for further investigation of heart failure drug therapies.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Rim/fisiopatologia , Modelos Cardiovasculares , Volume Sistólico/fisiologia , Compostos Benzidrílicos/uso terapêutico , Cardiomegalia/fisiopatologia , Líquido Extracelular/fisiologia , Glucosídeos/uso terapêutico , Coração/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/fisiologia , Humanos , Miócitos Cardíacos/fisiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
11.
Medicine (Baltimore) ; 99(29): e21098, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702857

RESUMO

INTRODUCTION: Ventricular ectopic beats (VEBs) are very common and often occur in hypertensive or obese individuals, as well as in patients presenting with either sleep apnea or structural cardiac disease. Sympathetic overactivity plays a crucial role in the development, continuation, and exacerbation of ventricular arrhythmias. Recent studies have reported the relevance of sympathetic activation in patients with ventricular arrhythmias and suggested a potential role for catheter-based renal denervation (RDN) in reducing the arrhythmic burden. PATIENT CONCERNS: We describe a 38-year-old female symptomatic patient that at the time of presentation was complaining of fatigue in response to minor and medium efforts and not tolerating any physical activity, and episodes of tachycardia associated with dyspnoea, pre-syncope, and syncope. DIAGNOSIS: She had a high incidence of polymorphic VEBs on 24-hour-Holter monitoring who also presented with left ventricular (LV) hypertrophy for which she was treated with bisoprolol 10 mg/d. The 24-hour-Holter on bisoprolol at baseline showed sinus rhythm with an average heart rate of 92 bpm. There were 44,743 isolated VEBs. A total of 2538 nonsustained ventricular tachycardia events were registered. Her cardiac magnetic resonance imaging showed an increase in LV diastolic diameter and impairment of the right ventricle. INTERVENTIONS: The patient underwent endocardial ablation of the right ventricular outflow tract and the LV free lateral wall, and concomitantly underwent bilateral RDN. OUTCOMES: Three months post-procedure, her 24-hour-Holter off medication demonstrated an average heart rate 72 bpm and a substantially reduced number of 2823 isolated monomorphic VEBs. Thus far, 18-months follow-up, she has been asymptomatic and doing physical exercises. CONCLUSION: In our current patient, we used RDN as a synergistic method to attenuate the sympathetic overactivity, which is narrowly linked to VEBs appearance. Our case report highlighted that RDN may become a potential adjuvant treatment for VEBs in the future.


Assuntos
Denervação/normas , Rim/fisiopatologia , Complexos Ventriculares Prematuros/terapia , Adulto , Denervação/métodos , Eletrocardiografia/métodos , Eletrocardiografia Ambulatorial/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos
12.
Medicine (Baltimore) ; 99(29): e21144, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702868

RESUMO

BACKGROUND: Hypertension becomes increasingly an alarming global health concern. There is a growing interest in treatment of traditional Chinese medicine (TCM), and tonifying kidney therapy (bushen, TKT) has been extensively used in the treatment of hypertension according to TCM theory. In this article, we outline the protocol of research projects and methods to examine comprehensively the effectiveness and safety of TKT in treating hypertensive patients. METHODS: We will collect randomized controlled trails (RCTs) that report the application of TKT for patients with hypertension from electronic databases including PubMed, EMBASE, CENTRAL, CNKI, VIP, CBM, and Wanfang database. Time of literature retrieval is set from the beginning of database construction to the end of June, 2020. Two reviewers will independently perform literature screening, data extraction, and quality assessment of included literature, and any divergences will be worked out via discussion. The primary outcomes include total efficacy rate, systolic and diastolic blood pressure change will be assessed. The secondary outcomes include clinical symptoms and adverse events will also be assessed. RevMan5.3 software will be applied to analyzing data included studies. RESULTS: This study will synthesize and analyze all collated data in order to evaluate TKT for the treatment of hypertension involves different aspects in total efficacy rate, systolic and diastolic blood pressure change, clinical symptoms, and adverse events. CONCLUSION: This study will determine the efficacy of TKT in the treatment of hypertension and recommend its clinical value based on the evaluated the effectiveness and security results. REGISTRATION NUMBER: INPLASY202050044.


Assuntos
Protocolos Clínicos , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Resultado do Tratamento , Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/normas , Humanos , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
Medicine (Baltimore) ; 99(29): e21157, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702871

RESUMO

BACKGROUND: Essential hypertension is one of the risk factors of cardiovascular and cerebrovascular diseases, which can cause target organ damage such as heart, brain and kidney, and has extremely high disability rate and death rate. With the development of economy and society, the prevalence rate of hypertension in China has increased rapidly from 9.8% in the 1980s to over 30% in the 21st century. According to the data published in "China Cardiovascular Disease Report 2018," China currently has 245 million hypertension patients. Comprehensive prevention and treatment of hypertension has become one of the major public health problems in China. The clinical practice and theoretical innovation of traditional Chinese medicine in the prevention and treatment of hypertension have been carried out for decades. Relevant literature points out that Tianma Gouteng Decoction combined with Qiju Dihuang Pill has ideal effect in the treatment of primary hypertension. However, most of the literatures are small sample studies, with uneven quality and clinical evidence, and lack of evidence-based medical evidence for clinical efficacy. Therefore, this study makes further meta-analysis of Tianma Gouteng Decoction combined with Qiju Dihuang Pill in the treatment of primary hypertension, with a view to providing evidence-based medical evidence for the treatment of primary hypertension. METHODS: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure, WangFang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. First, the quality of randomized controlled trials documents included in this study was evaluated by using the improved Jadad scoring scale. Then, the 2 researchers conducted the evaluation independently according to Cochrane bias risk tools. The evidence level of the results will be evaluated by using the recommended evaluation, development and evaluation grading of recommendations assessment, development, and evaluation method. Statistical analysis will be conducted using Revman 5.3. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: The conclusion of this study will provide evidence for the efficacy of Tianma Gouteng Decoction combined with Qiju Dihuang Pills in the treatment of primary hypertension due to the efficacy of western medicine alone in treating primary hypertension. REGISTRATION NUMBER PROSPERO: INPLASY202050088.


Assuntos
Protocolos Clínicos , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Adulto , Medicamentos de Ervas Chinesas/administração & dosagem , Hipertensão Essencial/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
14.
Int J Nanomedicine ; 15: 4311-4324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606679

RESUMO

Purpose: By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy. Materials and Methods: In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-DFDFG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model. Results: The self-assembling peptide was constrained into a classical ß-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the ß-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function. Conclusion: This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling ß-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Hidrogéis/química , Fator de Crescimento Insulin-Like I/química , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Peptídeos/química , Lesão Renal Aguda/fisiopatologia , Animais , Materiais Biocompatíveis/química , Sobrevivência Celular , Feminino , Fibrose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hidrogéis/síntese química , Rim/patologia , Rim/fisiopatologia , Camundongos Transgênicos , Neovascularização Fisiológica , Placenta/citologia , Gravidez , Conformação Proteica em Folha beta , Domínios Proteicos
15.
Dtsch Med Wochenschr ; 145(15): 1068-1073, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32731281

RESUMO

Increasing insight into the clinical phenotype and mechanisms of SARS-CoV-2 infections and COVID-19 has identified damage of the kidneys as a key player in the course of the disease. This manuscript summarizes the current knowledge on direct viral infection of kidney tissue, proteinuria and acute kidney injury in COVID-19, and management of patients on chronic dialysis as well as after kidney transplantation. Direct infection of podocytes and proximal tubular cells by SARS-CoV-2 has been confirmed and results in proteinuria and hematuria at an early stage of COVID-19. In this context, any kidney affection is a predictor of worse outcomes among COVID-19 patients irrespective of the initial presentation and increases the risk of acute kidney injury. Specific therapies for kidney damage and acute kidney injury within COVID-19 that could be generally recommended are currently lacking. Patients on chronic hemodialysis in particular are at risk for contracting SARS-CoV-2 infections as indicated by outbreaks and super-spreading events in hemodialysis facilities. Immunosuppressive therapy after kidney transplantation needs to be adapted upon diagnosis of COVID-19 depending on the severity of the initial presentation.


Assuntos
Lesão Renal Aguda , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/virologia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Hematúria , Humanos , Rim/fisiopatologia , Rim/virologia , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Proteinúria , Diálise Renal , Insuficiência Renal Crônica/terapia , Fatores de Risco
16.
Int J Nanomedicine ; 15: 4191-4203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606672

RESUMO

Purpose: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. Material and Methods: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. Results: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. Conclusion: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.


Assuntos
Antrodia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Reprodução , Ubiquinona/análogos & derivados , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Jejum/sangue , Glutationa Peroxidase/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Estreptozocina , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
17.
Rev Cardiovasc Med ; 21(2): 157-162, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706205

RESUMO

Cardiovascular disease, and in particular coronary artery disease (CAD), remains an important contributor of morbidity and mortality among patients with chronic kidney disease (CKD). Classic symptomatology of CAD and effectiveness of established therapeutic measures is less frequent in patients with CKD. This suggests unique characteristics of CAD among patients with CKD. Two important features of CAD in CKD include increased calcific density of atherosclerotic plaques and of the vessels themselves (coronary artery calcification -- CAC), as well as a decrease in microcirculatory function -- or coronary microcirculatory dysfunction. A multitude of pathophysiologic pathways have been identified that contribute to CAC in CKD; less is known about the pathophysiology of microcirculatory dysfunction. It is not well established if these two processes are directly related to each other, but the combination results in a greater severity of effect on overall myocardial function and may in part explain the greater preponderance of silent myocardial infarction. Further investigation is needed to better understand these unique aspects of CAD in CKD as well as the role they play in overall CVD in this group, and ultimately therapeutics that may lessen the burden of disease.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Vasos Coronários/fisiopatologia , Rim/fisiopatologia , Microcirculação , Insuficiência Renal Crônica/fisiopatologia , Calcificação Vascular/fisiopatologia , Animais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Progressão da Doença , Taxa de Filtração Glomerular , Hemodinâmica , Humanos , Placa Aterosclerótica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/terapia
18.
Medicine (Baltimore) ; 99(27): e20737, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629650

RESUMO

We aimed to investigate the relationship between total homocysteine (tHcy) levels in the plasma and renal function severity in patients with type 2 diabetes mellitus (T2DM) aged ≥75 years.We included 221 patients with T2DM aged ≥60 years (59 aged ≥75 years).tHcy levels among the 4 groups of patients aged ≥60 years significantly differed, but not in those aged ≥75 years. tHcy levels in patients aged ≥60 years were negatively correlated with the estimated glomerular filtration rate. The area under the receiver operating characteristic curve of tHcy for predicting diabetic kidney disease (DKD) was 0.636. Fasting c-peptide and creatinine were independently associated with tHcy levels in patients aged ≥60 years, whereas insulin and creatinine were independently associated with tHcy levels in those aged ≥75 years.tHcy concentrations were elevated in T2DM and can potentially serve as a risk factor for DKD, but it is not an ideal biomarker.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Homocisteína/sangue , Fatores Etários , Idoso , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença
19.
Methodist Debakey Cardiovasc J ; 16(2): 170-174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670481

RESUMO

The column in this issue is supplied by Juan Jose Olivero, MD, who recently retired as a nephrologist at Houston Methodist Hospital and member of the hospital's Nephrology Training Program. Dr. Olivero obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.


Assuntos
Nefropatias/diagnóstico por imagem , Rim/diagnóstico por imagem , Urografia , Adulto , Cistografia , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/fisiopatologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Adulto Jovem
20.
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
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