Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.229
Filtrar
1.
PLoS One ; 15(9): e0239072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915894

RESUMO

We aimed to evaluate choroid structural changes using swept-source optical coherence tomography (SS-OCT) following hemodialysis initiation in diabetic and nondiabetic patients with end-stage kidney disease (ESKD). In this multicenter, prospective, cross-sectional study, diabetic (DM group; 30 eyes; 16 patients) and nondiabetic patients (NDM group; 30 eyes; 15 patients) with ESKD were evaluated after hemodialysis initiation. SS-OCT findings were analyzed using a manual delineation technique and binarization method before the first and last hemodialysis sessions, conducted approximately 2 weeks apart. Subfoveal choroidal thickness changes and mean large choroidal vessel layer thickness were significantly greater in the DM group (-13.3% ± 2.5% and -14.5% ± 5.2%, respectively) than the NDM group (-9.5% ± 3.1% and -9.2% ± 3.4%, respectively; p = 0.049 and p = 0.02, respectively). Binarized SS-OCT analysis revealed that the mean subfoveal choroidal area was significantly larger in the DM group (-21.9% ± 6.5%) than the NDM group (-17.2% ± 5.9%; p = 0.032). The change ratio in mean luminal area values was significantly greater in the DM group (-27.7% ± 8.7%) than the NDM group (-17.7% ± 5.8%; p = 0.007). The DM group exhibited substantial changes in the choroidal layer, possibly reflecting choroidal vascular disorders caused by diabetes.


Assuntos
Doenças da Coroide/diagnóstico , Corioide/diagnóstico por imagem , Complicações do Diabetes/diagnóstico , Falência Renal Crônica/complicações , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Corioide/irrigação sanguínea , Corioide/patologia , Doenças da Coroide/etiologia , Doenças da Coroide/patologia , Estudos Transversais , Complicações do Diabetes/patologia , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica
2.
Am J Forensic Med Pathol ; 41(4): e61-e63, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969849

RESUMO

The autopsy findings for 3 cases of SARS-(CoV-2) pneumonia-related deaths are reported with pulmonary histology and immunohistochemistry findings. In 2 cases (cases 1 and 2), the time interval from presentation to death was approximately 1 week, whereas for case 3, the time interval from presentation to death was hours. Case 1 and case 2 presented with shortness of breath, cough, and flu-like symptoms. The decedent from case 3 died shortly after presenting to a local emergency room with high fever, chest and abdominal pain, and shortness of breath. All 3 cases had 1 or more comorbidities. The postmortem interval for cases 1 and 2 was 2 weeks as they died at sea and were stored on board within the respective cruise ships' refrigeration units, whereas case 3 was examined within 24 hours of death. The autopsies were conducted at the Miami-Dade County Medical Examiners Department under routine infectious precautions. Salient clinical history and autopsy findings are summarized. Microscopic examination revealed pneumonia with associated atypical endovascular cells.


Assuntos
Betacoronavirus , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Autopsia , Cardiomegalia/complicações , Cardiomegalia/patologia , Círculo Arterial do Cérebro/patologia , Comorbidade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Infecções por Coronavirus/complicações , Complicações do Diabetes/patologia , Evolução Fatal , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Obesidade/complicações , Obesidade/patologia , Pandemias , Pneumonia Viral/complicações , Edema Pulmonar/complicações , Edema Pulmonar/patologia , Uso de Tabaco/patologia
3.
Medicine (Baltimore) ; 99(36): e22161, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899103

RESUMO

BACKGROUND: Diabetes mellitus with erectile dysfunction (DMED) is one of the most common causes of disability in diabetic population, and its pathogenesis is related to a variety of factors. Because its pathogenesis is complex and the existing treatment methods have limitations, DMED is difficult to treat in clinical. Recently, some studies have shown that α-lipoic acid (ALA) is associated with DMED, but there is no systematic review and meta-analysis on the relationship between ALA and DMED. METHODS: We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieve clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials (RCTs) about ALA for DMED to assess its efficacy. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. Erectile dysfunction (ED) will be diagnosed by the International Index of Erectile Function 5 (IIEF-5) score. Finally, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will synthesize and provide high quality to evaluate the effectiveness of ALA supplementation for the treatment of DMED. CONCLUSION: This systematic review aims to provide new options for ALA supplementation treatment of DMED in terms of its efficacy and safety. PROSPERO REGISTRATION NUMBER: INPLASY202070130.


Assuntos
Complicações do Diabetes/patologia , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Ácido Tióctico/uso terapêutico , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Ácido Tióctico/administração & dosagem , Ácido Tióctico/efeitos adversos
4.
PLoS One ; 15(8): e0237296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760127

RESUMO

BACKGROUND: To avoid a surge of demand on the healthcare system due to the COVID-19 pandemic, we must reduce transmission to individuals with chronic conditions who are at risk of severe illness with COVID-19. We aimed at understanding the perceptions, context and attitudes of individuals with chronic conditions during the COVID-19 pandemic to clarify their potential risk of infection. METHODS: A cross-sectional survey was nested in ComPaRe, an e-cohort of adults with chronic conditions, in France. It assessed participants' perception of their risk of severe illness with COVID-19; their context (i.e., work, household, contacts with external people); and their attitudes in situations involving frequent or occasional contacts with symptomatic or asymptomatic people. Data were collected from March 23 to April 2, 2020, during the lockdown in France. Analyses were weighted to represent the demographic characteristics of French patients with chronic conditions. The subgroup of participants at high risk according to the recommendations of the French High Council for Public Health was examined. RESULTS: Among the 7169 recruited participants, 63% patients felt at risk because of severe illness. About one quarter (23.7%) were at risk of infection because they worked outside home, had a household member working outside home or had regular visits from external contacts. Less than 20% participants refused contact with symptomatic people and <20% used masks when in contact with asymptomatic people. Among patients considered at high risk according to the recommendations of the French High Council for Public Health, 20% did not feel at risk, which led to incautious attitudes. CONCLUSION: Individuals with chronic conditions have distorted perceptions of their risk of severe illness with COVID-19. In addition, they are exposed to COVID-19 due to their context or attitudes.


Assuntos
Infecções por Coronavirus/patologia , Conhecimentos, Atitudes e Prática em Saúde , Pneumonia Viral/patologia , Adulto , Idoso , Asma/complicações , Asma/patologia , Asma/psicologia , Betacoronavirus/isolamento & purificação , Doença Crônica , Infecções por Coronavirus/virologia , Estudos Transversais , Complicações do Diabetes/patologia , Complicações do Diabetes/psicologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Neoplasias/psicologia , Pandemias , Pneumonia Viral/virologia , Risco , Índice de Gravidade de Doença , Inquéritos e Questionários
5.
PLoS One ; 15(8): e0236817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813684

RESUMO

STUDY AIM: To develop and apply a natural language processing algorithm for characterization of patients diagnosed with chronic pancreatitis in a diverse integrated U.S. healthcare system. METHODS: Retrospective cohort study including patients initially diagnosed with chronic pancreatitis (CP) within a regional integrated healthcare system between January 1, 2006 and December 31, 2015. Imaging reports from these patients were extracted from the electronic medical record system and split into training, validation and implementation datasets. A natural language processing (NLP) algorithm was first developed through the training dataset to identify specific features (atrophy, calcification, pseudocyst, cyst and main duct dilatation) from free-text radiology reports. The validation dataset was applied to validate the performance by comparing against the manual chart review. The developed algorithm was then applied to the implementation dataset. We classified patients with calcification(s) or ≥2 radiographic features as advanced CP. We compared etiology, comorbid conditions, treatment parameters as well as survival between advanced CP and others diagnosed during the study period. RESULTS: 6,346 patients were diagnosed with CP during the study period with 58,085 radiology studies performed. For individual features, NLP yielded sensitivity from 88.7% to 95.3%, specificity from 98.2% to 100.0%. A total of 3,672 patients met cohort inclusion criteria: 1,330 (36.2%) had evidence of advanced CP. Patients with advanced CP had increased frequency of smoking (57.8% vs. 43.0%), diabetes (47.6% vs. 35.9%) and underweight body mass index (6.6% vs. 3.6%), all p<0.001. Mortality from pancreatic cancer was higher in advanced CP (15.3/1,000 person-year vs. 2.8/1,000, p<0.001). Underweight BMI (HR 1.6, 95% CL 1.2, 2.1), smoking (HR 1.4, 95% CL 1.1, 1.7) and diabetes (HR 1.4, 95% CL 1.2, 1.6) were independent risk factors for mortality. CONCLUSION: Patients with advanced CP experienced increased disease-related complications and pancreatic cancer-related mortality. Excess all-cause mortality was driven primarily by potentially modifiable risk factors including malnutrition, smoking and diabetes.


Assuntos
Processamento de Linguagem Natural , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Índice de Massa Corporal , Complicações do Diabetes/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fumar , Tomografia Computadorizada por Raios X
6.
PLoS One ; 15(8): e0236819, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817645

RESUMO

AIMS: To examine the relationship between baseline structural characteristics of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) and functional disease progression in patients with open-angle glaucoma (OAG) over 5 years. METHODS: 112 OAG patients were prospectively examined at baseline and every 6 months over a period of five years. Structural glaucomatous changes were examined with optical coherence tomography (OCT) and Heidelberg retinal tomography-III (HRT-III), and functional disease progression with automated perimetry (Humphrey visual fields). Cox proportional hazard models were used to assess the relationship between baseline structural measurements and functional disease progression. RESULTS: From baseline over a 5-year period, statistically significant increases were found in OCT disc (D) area (p<0.001), cup (C) area (p<0.001), C/D area ratio (p<0.001), C/D horizontal ratio (p<0.001), C/D vertical ratio (p = 0.018), and a decrease in superior RNFL thickness (p = 0.008). Statistically significant increases were found in HRT-III C volume (p = 0.021), C/D area ratio (p = 0.046), mean C depth (p = 0.036), C shape (p = 0.008), and height variation contour (p = 0.020). Functional disease progression was detected in 37 of the 112 patients (26 of European descent and 11 of African descent; 33%). A statistically significant shorter time to functional progression was seen in patients with larger baseline OCT D area (p = 0.008), C area (p = 0.003), thicker temporal RNFL (p = 0.003), and in patients with a larger HRT-III C area (p = 0.004), C/D area ratio (p = 0.004), linear C/D ratio (p = 0.007), C shape (p = 0.032), or smaller rim area (p = 0.039), rim volume (p = 0.005), height variation contour (p = 0.041), mean RNFL thickness (p<0.001), or RNFL cross-sectional area (p = 0.002). CONCLUSION: Baseline ONH and RNFL structural characteristics were associated with a significantly shorter time to functional glaucomatous progression and visual field loss through the five-year period in OAG patients.


Assuntos
Cegueira/diagnóstico , Glaucoma de Ângulo Aberto/patologia , Fibras Nervosas/fisiologia , Disco Óptico/fisiopatologia , Idoso , Cegueira/etiologia , Complicações do Diabetes/patologia , Progressão da Doença , Feminino , Glaucoma de Ângulo Aberto/complicações , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , Retina/diagnóstico por imagem , Retina/fisiopatologia , Tomografia de Coerência Óptica , Testes de Campo Visual
7.
Diabetes Res Clin Pract ; 168: 108374, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805345

RESUMO

AIMS: We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. METHODS: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. RESULTS: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. CONCLUSION: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.


Assuntos
Infecções por Coronavirus/diagnóstico , Complicações do Diabetes/diagnóstico , Diabetes Mellitus/diagnóstico , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Admissão do Paciente , Pneumonia Viral/diagnóstico , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/fisiologia , Glicemia/análise , Glicemia/metabolismo , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Feminino , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/terapia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Gene ; 758: 144952, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32683074

RESUMO

Diabetic nephropathy (DN) as one of the most frequent microvascular complications of diabetic patients causes chronic renal failure and end-stage renal disease. Noncoding RNAs including circular RNAs (circRNAs) and micro RNAs (miRNAs) were widely reported to play a critical role in numerous human diseases including DN. This research was designed to investigate the role of circ_0000064 in diabetic nephropathy progression. The results showed that circ_0000064 significantly promoted mesangial cells proliferation and aggravated fibrosis in DN. In the subsequent mechanism investigation, we found that circ_0000064 was involved in this process by targeting micro RNA miR-143. The inhibition of miR-143 significantly reverses the effect of circ_0000064 silencing on DN. In conclusion, we demonstrated the regulatory role of circ_0000064 in DN and clarified that circ_0000064 play a role in DN via targeting miR-143. Circ_0000064 and miR-143 also showed the potential as a biomarker for DN.


Assuntos
Nefropatias Diabéticas/genética , Fibrose/genética , Células Mesangiais/patologia , MicroRNAs/genética , RNA Circular/genética , Animais , Proliferação de Células/genética , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Diabetes Mellitus/patologia , Fibrose/patologia , Humanos , Camundongos
9.
Korean J Radiol ; 21(8): 935-945, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32677378

RESUMO

We retrospectively reviewed the cases in which complications occurred during below-the-knee (BTK) endovascular treatments that were performed at our hospital from 2005 to 2014. Several interesting cases have been described herein. All the patients had diabetes and non-healing wounds on their feet and/or rest pain in their foot or leg, and therefore, endovascular treatment was performed for the BTK arteries of the affected lower extremity. The complications that occurred during the procedure were classified into six categories-vascular spasm, flow limiting dissection, perforation, broken guidewire, distal thromboembolism, and unusual puncture site bleeding. Each complication has its own solutions and management. We discuss these different classes of complications and describe how cases of each type were managed.


Assuntos
Angioplastia/efeitos adversos , Isquemia/cirurgia , Joelho/irrigação sanguínea , Joelho/cirurgia , Idoso , Artérias/fisiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/patologia , Feminino , Pé/irrigação sanguínea , Humanos , Isquemia/etiologia , Articulação do Joelho/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos e Lesões/patologia , Ferimentos e Lesões/cirurgia
10.
PLoS One ; 15(6): e0234812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555738

RESUMO

BACKGROUND: Due to the absence and or costliness of biological measures such as glycated haemoglobin, diabetes case ascertainment and prevalence studies are usually conducted using surveys or routine health service use databases. However, the use of each of these sources is associated with its limitations potentially impacting the quality of the case ascertainment and prevalence estimation. This study aimed at ascertaining diabetes cases and estimating prevalence among mid- and older-age women through simultaneous use of a longitudinal survey and multiple healthcare administrative data sources. METHODS: Data were available for 12,432 and 13,714 women born in 1921-26 and 1946-51 from the Australian Longitudinal Study on Women's Health (ALSWH). Diabetes was ascertained using the ALSWH survey, health service use, and cause of death data. Parsimonious multiple logistic regression analyses tested associations between sociodemographic and health variables and the presence of diabetes. RESULTS: In both cohorts, two or more of the sources captured more than 80% of the women with diabetes. The point prevalence of diabetes increased from 8.4% when the mean age of the women were aged 73, to 22.0% of surviving women at age 90 in the 1921-26 cohort; and from 2.6% at age 48 to 15.8% at age 68 in the 1946-51 cohort. In the 1921-26 cohort, women who were obese (OR: 3.56; 95 CI: 3.04-4.17) and women who were sedentary (OR: 1.18; 95 CI: 1.09-1.40) were more likely to have diabetes compared to those who had a normal weight and engaged in a moderate level of physical activity. In the 1946-51 cohort, the odds of diabetes increased three times (OR: 2.99; 95 CI: 2.54-3.52) for overweight women and nine times (OR: 8.78; 95 CI: 7.46-10.33) for obese women compared to those who had normal weight. CONCLUSIONS: The simultaneous use of multiple data sources improved the validity of diabetes case ascertainment. Application of this methodology in future studies may have important benefits including estimation of disease burden, health service needs, and resource allocation with improved precision. Diabetes prevalence increased with age, was much higher in the 1946-51 cohort than in 1921-26 at similar ages, and was significantly associated with physical inactivity and obesity. Interventions to promote physical activity and a healthy weight are needed to prevent the rising prevalence of diabetes across successive generations.


Assuntos
Diabetes Mellitus/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Estudos de Coortes , Complicações do Diabetes/patologia , Diabetes Mellitus/epidemiologia , Exercício Físico , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/patologia , Prevalência , Saúde da Mulher
12.
Cell Prolif ; 53(6): e12834, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32468637

RESUMO

OBJECTIVES: Advanced glycation end products (AGEs) are considered a cause of diabetic osteoporosis. Although adipose-derived stem cells (ASCs) are widely used in the research of bone regeneration, the mechanisms of the osteogenic differentiation of ASCs from diabetic osteoporosis model remain unclear. This work aimed to investigate the influence and the molecular mechanisms of AGEs on the osteogenic potential of ASCs. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay was used to measure the change of AGEs in diabetic osteoporotic and control C57BL/6 mice. ASCs were obtained from the inguinal fat of C57BL/6 mice. AGEs, 5-aza2'-deoxycytidine (5-aza-dC) and DKK-1 were used to treat ASCs. Real-time cell analysis and cell counting kit-8 were used to monitor the proliferation of ASCs within and without AGEs. Real-time PCR, Western blot and Immunofluorescence were used to analyse the genes and proteins expression of osteogenic factors, DNA methylation factors and Wnt/ß-catenin signalling pathway among the different groups. RESULTS: The AGEs and DNA methylation were increased in the adipose and bone tissue of the diabetic osteoporosis group. Untreated ASCs had higher cell proliferation activity than AGEs-treatment group. The expression levels of osteogenic genes, Opn and Runx2, were lower, and mineralized nodules were less in AGEs-treatment group. Meanwhile, DNA methylation was increased, and the Wnt signalling pathway markers, including ß-Catenin, Lef1 and P-GSK-3ß, were inhibited. After treatment with 5-aza-dC, the osteogenic differentiation capacity of ASCs in the AGEs environment was restored and the Wnt signalling pathway was activated during this process. CONCLUSIONS: Advanced glycation end products inhibit the osteogenic differentiation ability of ASCs by activating DNA methylation and inhibiting Wnt/ß-catenin pathway in vitro. Therefore, DNA methylation may be promising targets for the bone regeneration of ASCs with diabetic osteoporosis.


Assuntos
Tecido Adiposo/citologia , Metilação de DNA , Complicações do Diabetes/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Células-Tronco/metabolismo , Tecido Adiposo/metabolismo , Animais , Osso e Ossos/metabolismo , Proliferação de Células , Células Cultivadas , Decitabina/farmacologia , Complicações do Diabetes/patologia , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Camundongos Endogâmicos C57BL , Osteoporose/patologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Via de Sinalização Wnt
13.
BMC Med Genet ; 21(1): 91, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375679

RESUMO

BACKGROUND: Renal hypouricemia (RHUC) is a hereditary disorder where mutations in SLC22A12 gene and SLC2A9 gene cause RHUC type 1 (RHUC1) and RHUC type 2 (RHUC2), respectively. These genes regulate renal tubular reabsorption of urates while there exist other genes counterbalancing the net excretion of urates including ABCG2 and SLC17A1. Urate metabolism is tightly interconnected with glucose metabolism, and SLC2A9 gene may be involved in insulin secretion from pancreatic ß-cells. On the other hand, a myriad of genes are responsible for the impaired insulin secretion independently of urate metabolism. CASE PRESENTATION: We describe a 67 year-old Japanese man who manifested severe hypouricemia (0.7 mg/dl (3.8-7.0 mg/dl), 41.6 µmol/l (226-416 µmol/l)) and diabetes with impaired insulin secretion. His high urinary fractional excretion of urate (65.5%) and low urinary C-peptide excretion (25.7 µg/day) were compatible with the diagnosis of RHUC and impaired insulin secretion, respectively. Considering the fact that metabolic pathways regulating urates and glucose are closely interconnected, we attempted to delineate the genetic basis of the hypouricemia and the insulin secretion defect observed in this patient using whole exome sequencing. Intriguingly, we found homozygous Trp258* mutations in SLC22A12 gene causing RHUC1 while concurrent mutations reported to be associated with hyperuricemia were also discovered including ABCG2 (Gln141Lys) and SLC17A1 (Thr269Ile). SLC2A9, that also facilitates glucose transport, has been implicated to enhance insulin secretion, however, the non-synonymous mutations found in SLC2A9 gene of this patient were not dysfunctional variants. Therefore, we embarked on a search for causal mutations for his impaired insulin secretion, resulting in identification of multiple mutations in HNF1A gene (MODY3) as well as other genes that play roles in pancreatic ß-cells. Among them, the Leu80fs in the homeobox gene NKX6.1 was an unreported mutation. CONCLUSION: We found a case of RHUC1 carrying mutations in SLC22A12 gene accompanied with compensatory mutations associated with hyperuricemia, representing the first report showing coexistence of the mutations with opposed potential to regulate urate concentrations. On the other hand, independent gene mutations may be responsible for his impaired insulin secretion, which contains novel mutations in key genes in the pancreatic ß-cell functions that deserve further scrutiny.


Assuntos
Complicações do Diabetes/genética , Proteínas Facilitadoras de Transporte de Glucose/genética , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Erros Inatos do Transporte Tubular Renal/genética , Cálculos Urinários/genética , Idoso , Complicações do Diabetes/complicações , Complicações do Diabetes/patologia , Glucose/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Heterozigoto , Proteínas de Homeodomínio/genética , Homozigoto , Humanos , Insulina/biossíntese , Insulina/genética , Secreção de Insulina/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Mutação/genética , Erros Inatos do Transporte Tubular Renal/complicações , Erros Inatos do Transporte Tubular Renal/patologia , Ácido Úrico/metabolismo , Cálculos Urinários/complicações , Cálculos Urinários/patologia , Sequenciamento Completo do Exoma
14.
Sci Rep ; 10(1): 7238, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350374

RESUMO

Acute kidney injury (AKI) predicts poor prognosis in patients with acute myocardial infarction (MI) and diabetes mellitus (DM) is an independent risk factor of AKI. Recent clinical studies have shown the beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular and renal outcomes in patients with DM. We recently reported that canagliflozin normalized susceptibility of diabetic rats to AKI after acute MI via ß-hydroxybutyrate-mediated suppression of NOX expression. Here we examined whether the same renoprotective effect is shared by empagliflozin. Serum creatinine levels were not changed by MI induced by coronary artery occlusion in LETO, non-diabetic control rats, and OLETF, obese type 2 diabetic rats. However, immunohistochemistry revealed that MI increased renal expression of NGAL and KIM-1, early markers of tubular injury, by 3.2-fold and 2.6-fold, respectively, in OLETF. These increases in injury markers were not observed in LETO. Pretreatment with empagliflozin of OLETF for 2 weeks improved hyperglycemia, increased blood ß-hydroxybutyrate level, and suppressed MI-induced expression of NGAL and KIM-1. Empagliflozin suppressed upregulation of NOX2 and NOX4 in the kidney of OLETF. Taken together with the results of our previous study, it was concluded that treatment with the SGLT2 inhibitor protects the diabetic kidney from MI-induced AKI.


Assuntos
Lesão Renal Aguda , Compostos Benzidrílicos/farmacologia , Complicações do Diabetes , Diabetes Mellitus Experimental , Glucosídeos/farmacologia , Rim , Infarto do Miocárdio , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Rim/metabolismo , Rim/patologia , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos
15.
Sci Rep ; 10(1): 7702, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382160

RESUMO

In this retrospective study, we investigated the impact of diabetes mellitus (DM) on patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT). We analyzed the demographic and clinical characteristics, treatment tolerance, and toxicities of patients with HNC undergoing primary or adjuvant CCRT with or without DM between 2007 and 2016. Of the 556 patients undergoing CCRT, 84 (15.1%) had DM. Compared with patients without DM, patients with DM were significantly older (56.2 ± 11.2 vs. 51.9 ± 9.5 years, P < 0.001), received lower doses of cisplatin (adjuvant CCRT: 175.30 ± 84.03 vs. 214.88 ± 68.25, P = 0.014; primary CCRT: 142.84 ± 79.49 vs. 187.83 ± 76.19, P < 0.001), and experienced higher rates of infection (adjuvant CCRT: 52% vs. 30.5%, P = 0.042; primary CCRT: 45.8% vs. 22.9%, P < 0.001). Among patients undergoing primary CCRT, compared with those without DM, the patients with DM experienced significantly higher rates of hematologic toxicity (65.7% vs. 39.3%, P = 0.004) and treatment-related deaths (10.2% vs. 3.5%, P = 0.051); and a greater weight loss (-6.17 ± 9.27% vs. -4.49 ± 6.84, P = 0.078). Patients with HNC and DM undergoing CCRT, compared with patients without DM, experienced higher rates of infection and hematotoxicity, loss of body weight, and higher treatment-related mortality.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Complicações do Diabetes/patologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/patologia , Diabetes Mellitus/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Diabetes Metab Syndr ; 14(4): 319-323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298984

RESUMO

INTRODUCTION: and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. MATERIALS AND METHODS: A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. RESULTS: The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. CONCLUSION: The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.


Assuntos
Betacoronavirus/isolamento & purificação , Simulação por Computador , Infecções por Coronavirus/complicações , Complicações do Diabetes/patologia , Diabetes Mellitus/fisiopatologia , Hemoglobina A Glicada/análise , Modelos Estatísticos , Pneumonia Viral/complicações , Glicemia/metabolismo , Infecções por Coronavirus/virologia , Complicações do Diabetes/etiologia , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/virologia , Humanos , Metanálise como Assunto , Pandemias , Pneumonia Viral/virologia , Análise de Regressão
18.
Medicine (Baltimore) ; 99(12): e19502, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195951

RESUMO

BACKGROUND: Diabetic foot (DF) problems are common throughout the world, about one-fourth of them develop a foot ulcer and serious cases would suffer from amputation, which seriously affects the patient's work and life. Previous studies indicated that acupuncture as adjuvant therapy would be effective in treating DF. However, these studies have no consistent results. Therefore, the aim of our study was to explore the efficacy and safety of acupuncture as adjuvant therapy for DF. METHODS: The randomized controlled trials associated with acupuncture therapy (or as adjuvant therapy) for DF will be included. We will search 6 electronic databases relevant to health sciences, including PubMed, Embase, the Cochrane Library, the Chinese databases Sino-Med, CNKI, and WANFANG database. All searches were from databases inception to March 30, 2019. The primary outcomes are the total curative effective rate, and the hemodynamic parameter and adverse events will be deemed as secondary outcomes. The Stata15.1 software and Review Manager (RevMan 5.3; Cochrane Collaboration, Copenhagen, Denmark) will be used for analysis, to assess the bias risk, subgroup analysis, and data synthesis. RESULTS: In this systematic review and meta-analysis, we will synthesize the studies to assess the safety and efficacy of acupuncture as adjuvant therapy for DF. CONCLUSION: The summary of our study will clarify whether acupuncture as adjuvant therapy could be an efficient method for DF.


Assuntos
Terapia por Acupuntura/métodos , Pé Diabético/complicações , Pé Diabético/terapia , Úlcera do Pé/complicações , Amputação , Complicações do Diabetes/patologia , Diabetes Mellitus/epidemiologia , Pé Diabético/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
Sci Rep ; 10(1): 2854, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071320

RESUMO

The current study aimed to formulate Selenium-Chitosan-Mupirocin (M-SeNPs-CCH) complex. The nanohybrid system was prepared using chitosan-cetyltrimethylammonium bromide (CTAB)-based hydrogel (CCH) that entrapped mupirocin (M) and selenium nanoparticles (SeNPs). The in vitro studies were performed by evaluation of the antibacterial activity and toxicity on L929 mouse fibroblast cell line. The in vivo study was conducted on rat diabetic wound infection model that was infected by mupirocin-methicillin-resistant Staphylococcus aureus (MMRSA). The wounds were treated by M-SeNPs-CCH nanohybrid system with concentrations of M; 20 mg/ml, CCH; 2 mg/ml and SeNPs; 512 µg/ml in two times/day for 21 days. The therapeutic effect of this nanohybrid system was evaluated by monitoring wound contraction and histopathological changes. Evaluation of the average wound healing time showed a significant difference between the treatment and control groups (P≤0.05). The histopathological study indicated that the amount of wound healing was considerable in M-SeNPs-CCH nanohybrid system groups compared to the control and M groups. The M-SeNPs-CCH nanohybrid system formulated in this study was able to reduce 3-fold MIC of mupirocin with synergistic antibacterial activity as well as to play a significant role in wound contraction, angiogenesis, fibroblastosis, collagenesis, proliferation of hair follicle, and epidermis growth compared to the control group (P ≤ 0.05). This research suggests that this nanohybrid system might be a development for the treatment of diabetic wound infection at mild stage.


Assuntos
Antibacterianos/farmacologia , Complicações do Diabetes/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Quitosana/química , Quitosana/farmacologia , Complicações do Diabetes/microbiologia , Complicações do Diabetes/patologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Mupirocina/química , Mupirocina/farmacologia , Nanoestruturas/química , Ratos , Selênio/química , Selênio/farmacologia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA