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1.
Medicine (Baltimore) ; 98(42): e17597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626136

RESUMO

Hyperuricemia has received increasing attention as a major public health problem. This study aims to investigate the risk factors for hyperuricemia and to explore the relationship between changes in biochemical variables and incident hyperuricemia.A cross-sectional and subsequently prospective study was performed among adults who took their health checkups at Zhejiang University Hospital. The participants who were free of hyperuricemia at baseline received annual follow-up examinations during a 6-year period. Cox proportional hazards regression analyses were conducted to calculate the risks for incident hyperuricemia.Of the 9238 participants enrolled, 1704 (18.4%) were diagnosed as hyperuricemia. During 21,757 person-years of follow-up, 1492 incident hyperuricemia cases were identified. The incidence of hyperuricemia was 68.58 cases per 1000 person-year of follow-up in the overall participants. The prevalence and the incidence of hyperuricemia increased greatly in female older than 50 years. High levels of BMI, SBP, FPG, TG, LDL-C, ALT, BUN, and creatinine increased the risk of hyperuricemia. Suffering fatty liver also increased the risk of hyperuricemia. Subjects with increasing DBP, TG, BUN, creatinine, or decreasing HDL-C were more likely to incident hyperuricemia.This study revealed that the change of diastolic blood pressure (DBP), serum triglycerides (TG), blood urea nitrogen (BUN), creatinine, and high-density lipoprotein cholesterol (HDL-C) level were independently associated with incident hyperuricemia.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Creatinina/sangue , Hiperuricemia/etiologia , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
2.
Acta Gastroenterol Belg ; 82(3): 397-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31566327

RESUMO

BACKGROUND AND AIMS: Early prediction of severe acute pancreatitis (SAP)would be helpful for triaging patients to the appropriate level of care and intervention. The aim of this study is to compare the performance of the Change in Amylase And Body mass index (CAB) score and BISAP score for predicting SAP. PATIENTS AND METHODS: A total of 406 with AP were enrolled. The age, gender, body mass index(BMI), blood urea nitrogen determined at the time of admission and serum amylase determined on day 1 and day 2 after hospitalization were collected and analyzed statistically. RESULTS: Multivariable analysis confirmed that blood urea nitrogen (OR 1.06; 95%CI 1.03-1.09) and percentage change in amylase day 2 (OR 0.75; 95%CI 0.65-0.87) were independently associated with development of SAP. No statistically significant association was observed between BMI (OR 1.04; 95%CI 0.951.13) and severity of acute pancreatitis. The area under the receiver operating characteristic curve for Body mass index (BMI), percentage change in amylase day 2, BISAP score and CAB score were 0.57±0.05, 0.68±0.04, 0.84±0.03 and0.53±0.05, respectively. CONCLUSION: BISAP is more accurate for predicting the severity of acute pancreatitis than the CAB score.


Assuntos
Amilases/sangue , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Doença Aguda , Biomarcadores/sangue , Humanos , Pancreatite/classificação , Pancreatite/patologia , Admissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos
3.
Chem Biol Interact ; 311: 108777, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31376360

RESUMO

Nicorandil ameliorated doxorubicin-induced nephrotoxicity; this study aimed to show and explain the mechanism of this protection. A precise method was elucidated to study the effect of nicorandil on doxorubicin-induced nephrotoxicity in rats depending on the critical inflammation pathway TLR4/MAPK P38/NFκ-B. Adult male rats were subdivided into four groups. The 1st group was normal control, the 2nd group received nicorandil (3 mg/kg; p.o., for 4 weeks), the 3rd group received doxorubicin (2.6 mg/kg, i.p., twice per week for 4 weeks), and the fourth group was combination of doxorubicin and nicorandil for 4 weeks. Nephrotoxicity was assessed by biochemical tests through measuring Kidney function biomarkers such as [serum levels of urea, creatinine, albumin and total protein] besides renal kidney injury molecule-1 (KIM-1) and cystatin C], oxidative stress parameters such as [renal tissue malondialdehyde (MDA), reduced glutathione (GSH), SOD, catalase and nrf-2], mediators of inflammation such as [Toll like receptor 4 (TLR-4), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), p38 MAPK, Interleukin 1 beta (IL-1 ß), and Tumor necrosis factor alpha (TNF-α)] and markers of apoptosis [BAX and Bcl-2 in renal tissue]. Finally, our data were supported by histopathology examination. Nicorandil pretreatment resulted in a significant decrease in nephrotoxicity biomarkers, oxidative stress markers, inflammatory mediators and prevented apoptosis through decreasing BAX and increasing Bcl-2 in renal tissues. Nicorandil prevented all the histological alterations caused by doxorubicin. Nicorandil is a promising antidote against doxorubicin-induced nephrotoxicity by neutralizing all toxicity mechanisms caused by doxorubicin through normalizing inflammatory cascade of TLR4/MAPK P38/NFκ-B.


Assuntos
Doxorrubicina/toxicidade , Rim/efeitos dos fármacos , Nicorandil/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Nitrogênio da Ureia Sanguínea , Moléculas de Adesão Celular/sangue , Creatinina/sangue , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Stud Health Technol Inform ; 264: 1867-1869, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438383

RESUMO

The aim of this work is to study the influence of contamination with infusion in clinical chemistry tests and to design an algorithm for detection of inadequate blood specimen. We show that panic value of postassium (K+)/ glucose (GLU) or decrease of total protein (TP), albumin (ALB), urea nitrogen (BUN), uric acid (UA), high-density lipoprotein cholesterol (HDL-C), total cholesterol (T-CHO), and calcium (Ca) is an index of contamination of drip infusion solution. Through a clinical study, we show that our algorithm is useful for preventing adverse medical errors.


Assuntos
Química Clínica , Algoritmos , Nitrogênio da Ureia Sanguínea , HDL-Colesterol , Ácido Úrico
5.
DNA Cell Biol ; 38(10): 1134-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433203

RESUMO

Diabetes mellitus is a complicated metabolic disease characterized by hyperglycemia. Diabetic nephropathy (DN) is a progressive kidney disease, which results in mortality in diabetic patients. The present study was designed to investigate the effect of applying spironolactone (S), captopril (C), and their combination (S+C) on some renal performance indices and microRNAs' (miRNAs) expression. A total of 35 two-month-old male Wistar rats were provided for the study. Intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in cold citrate buffer was used to induce diabetes. Blood samples were examined through calorimetry to assess serum concentrations of glucose, blood urea nitrogen (BUN), and creatinine. To measure the microalbuminuria and transforming growth factor-ß (TGF-ß) levels and to evaluate the miRNAs expression levels of the kidney tissue, the ELISA method and the real-time PCR were used. The obtained results serve as in vivo evidence for the positive relationship between miR-192 and TGF-ß levels in the DN rats. A significant increase and decrease were found for miR-29a/b/c and the miR-192 expression of DN after treatment with S, C, and S+C. TGF-ß levels and microalbuminuria of diabetic rats also increased. The results obtained from this research study suggest that S, C, and S + C can improve DN by targeting miR-192 and miR-29 family and changing their expression. These findings suggest that miR-192 and miRs-29a/b/c can be potential targets for DN remediation.


Assuntos
Captopril/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Espironolactona/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Diuréticos/farmacologia , Combinação de Medicamentos , Reposicionamento de Medicamentos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar , Estreptozocina/administração & dosagem , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento
6.
Int J Nanomedicine ; 14: 4723-4739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308655

RESUMO

Background: Much consideration has been paid to the toxicological assessment of nanoparticles prior to clinical and biological applications. While in vitro studies have been expanding continually, in vivo investigations of nanoparticles have not developed a cohesive structure. This study aimed to assess the acute toxicity of different concentrations of chitosan-coated silver nanoparticles (Ch-AgNPs) in main organs, including liver, kidneys, and spleen. Materials and methods: Twenty-eight male albino rats were used and divided into 4 groups (n=7). Group 1 was kept as a negative control group. Groups 2, 3, and 4 were treated intraperitoneally with Ch-AgNPs each day for 14 days at doses of 50, 25, and 10 mg/kg body weight (bwt) respectively. Histopathological, morphometric and immunohistochemical studies were performed as well as oxidative stress evaluations, and specific functional examinations for each organ were elucidated. Results: It was revealed that Ch-AgNPs induced dose-dependent toxicity, and the repeated dosing of rats with 50 mg/kg Ch-AgNPs induced severe toxicities. Histopathological examination showed congestion, hemorrhage, cellular degeneration, apoptosis and necrosis in hepatic and renal tissue as well as lymphocytic depletion with increasing tangible macrophages in the spleen. The highest levels of malondialdehyde, alanine aminotransferase, aspartate aminotransferase (MDA, ALT, AST) and the lowest levels of reduced glutathione, immunoglobulin G, M and total protein (GSH, IgG, IgM, TP) were observed in this group. On the other hand, repeated dosing with 25 mg/kg induced mild to moderate disturbance in the previous parameters, while there was no significant difference in results of pathological examination and biochemical tests between the control group and those treated with 10 mg/kg bwt Ch-AgNPs. Conclusion: Chitosan-coated silver nanoparticles induce dose-dependent adverse effects on rats.


Assuntos
Quitosana/química , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia
7.
Scand J Immunol ; 90(5): e12810, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31325389

RESUMO

MicroRNAs (miRNAs) play a vital role in the occurrence and development of many human diseases, including systemic lupus erythematosus (SLE). SLE is an autoimmune disease characterized by the production of autoantibodies against nuclear antigens and multiorgan involvement. Study of miRNAs involved in SLE provides new insights into the pathogenesis of SLE and might lead to the identification of new therapeutic interventions. The aim of this study was to investigate the effect of miR-183 injection on the progression of SLE by using MRL/lpr mouse model. The expression levels of miR-183 and mTOR mRNA were detected by quantitative real-time PCR assay. The effect of miR-183 on the course of spontaneous disease progression in the MRL/lpr mice was examined by intraperitoneal injection of miR-183 into mice and followed by monitoring lifespan, anti-dsDNA antibody levels, urinary albumin levels, blood urea nitrogen (BUN) levels, and Tregs and Th17 cell population. We found that miR-183 injection resulted in reduction of anti-DNA antibody and immune complex component levels, restoration of Tregs and Th17 cell population and prolongation of survival. Our findings suggest that miR-183 injection may serve as an effective therapeutic treatment for delaying or easing pathologic features of SLE.


Assuntos
Nefrite Lúpica/terapia , MicroRNAs/genética , MicroRNAs/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Adulto , Albuminúria/urina , Animais , Anticorpos Antinucleares/sangue , Nitrogênio da Ureia Sanguínea , Modelos Animais de Doenças , Feminino , Humanos , Nefrite Lúpica/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , Linfócitos T Reguladores/imunologia , Serina-Treonina Quinases TOR/metabolismo , Células Th17/imunologia
8.
Environ Sci Pollut Res Int ; 26(22): 22562-22574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165450

RESUMO

Zingerone (ZO), one of the active components of ginger (Zingiber officinale), is a phenolic alkanone with antioxidant, antiapoptotic, and anti-inflammatory properties. Cisplatin (CP) is a widely used chemotherapeutic drug for solid tumors, but its therapeutic use is limited due to dose-dependent nephrotoxicity. In the present study, we investigated the ameliorative effect of ZO against CP-induced nephrotoxicity. Intraperitoneal administration of single-dose CP (7 mg/kg body weight) on the first day enhanced kidney lipid peroxidation and reduced antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). CP increased serum urea and creatinine levels and disrupted histological integrity while causing a decrease aquaporin 1 (AQP1) level in the kidney tissues. CP induced inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-33 (IL-33) and nuclear factor kappa B (NF-κB), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it also caused oxidative DNA damage and activation of apoptotic pathway by increasing of 8-hydroxy-2'-deoxyguanosine (8-OHdG), p53, cysteine aspartate-specific protease-3 (caspase-3), and Bcl-2-associated x protein (bax) while decreasing B cell lymphoma-2 (Bcl-2). However, treatment with ZO at a dose of 25 and 50 mg/kg b.wt. for 7 days significantly decreased oxidative stress, apoptosis, inflammation, and histopathological alterations while increased AQP1 levels in the kidney tissue. The results of the current study suggested that ZO as an effective natural product attenuates CP-induced nephrotoxicity.


Assuntos
Antioxidantes/metabolismo , Cisplatino/toxicidade , Guaiacol/análogos & derivados , Rim/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Autofagia , Nitrogênio da Ureia Sanguínea , Catalase/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Guaiacol/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos , Masculino , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismo
9.
Arch Anim Nutr ; 73(4): 287-305, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163993

RESUMO

This study investigated the effects of low-protein diet supplemented with Lysine (Lys), Methionine (Met), Threonine (Thr), and Tryptophan (Trp) on small intestine morphology, enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned piglets. Eighteen weaned pigs weighing an average of 9.57 kg received one of three treatments: a normal protein diet with 20% crude protein (CP, diet [NP]), a moderately reduced protein diet with 17% CP (MP), or a low-protein diet with 14% CP (LP). All three diets were supplemented with Lys, Met, Thr and Trp to meet essential amino acid requirements for post-weaned piglets according to the NRC (2012). Following a 45 d study period, piglets on the LP and MP diets demonstrated atrophic small intestinal morphology, with decreased villus heights and lower ratios of villus height to crypt depth (p < 0.05); pepsin activity in the stomach was also reduced in these two groups (p < 0.05). Increased plasma cholesterol and decreased blood urea nitrogen presented in the MP and LP groups compared with the NP group (p < 0.05). Overall, gastrointestinal hormones were not affected by dietary protein levels with the exception of reduced somatostatin levels in the MP and LP groups. Jejunum and colon microbiota were not affected at either the phyla or genera level in any of the diets. Colonic ammonia nitrogen concentration was reduced in MP and LP groups. Dietary protein level had no effect on short chain fatty acids or biogenic amines. Our data suggest that reducing dietary protein levels by 3% (MP) or 6% (LP) in weaned pigs has the potential to decrease nitrogen emissions and impaired digestive capacity. Therefore, dietary protein level cannot be reduced by more than 3% in consideration of maladaptive changes to small intestinal morphology and pepsin activity in weaned piglets.


Assuntos
Bactérias/metabolismo , Dieta com Restrição de Proteínas/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Sus scrofa/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Nitrogênio da Ureia Sanguínea , Microbioma Gastrointestinal/fisiologia , Intestinos/anatomia & histologia , Intestinos/enzimologia , Distribuição Aleatória , Sus scrofa/anatomia & histologia , Sus scrofa/sangue , Sus scrofa/microbiologia , Desmame
10.
J Vet Emerg Crit Care (San Antonio) ; 29(4): 399-406, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31225690

RESUMO

OBJECTIVE: To compare intravenous and intraosseous blood aspirates using point-of-care diagnostic equipment available in veterinary hospitals. DESIGN: Prospective study. SETTING: Private referral hospital. ANIMALS: Dogs undergoing a tibial plateau leveling osteotomy or extracapsular anterior cruciate ligament stabilization procedure were enrolled. METHODS: Under general anesthesia, simultaneous 0.5 mL intravenous and intraosseous blood samples were collected from the jugular vein and proximal tibia, respectively. Samples were evaluated in duplicate within 10 minutes of collection and averaged for each of the following parameters: blood urea nitrogen (BUN), glucose, packed cell volume, total plasma protein (TPP), plasma lactate, sodium, potassium, chloride, urea, glucose, pH, anion gap, pO2, and pCO2 . Normalcy was tested with Kolmogorov-Smirnov test. A Student's t-test and Bland-Altman plot were used to compare intravenous and intraosseous samples. RESULTS: Twelve dogs were recruited into the study. There were statistically significant differences between intravenous and intraosseous samples for sodium (P = 0.0216), chloride (P = 0.0225), BUN (P = 0.014), and potassium (P < 0.0001), respectively. No significant differences were detected for the other parameters evaluated. DISCUSSION: The intraosseous space provides an easily accessible, noncollapsible alternative for assessing blood parameters. Omitting potassium, the statistically significant differences noted between sites was not felt to be clinically significant. Although statistically insignificant, the large difference in hematocrit values indicates that the samples should not be used interchangeably. CONCLUSION: Intraosseous aspirates, excluding potassium and hematocrit, appear to be a reliable alternative for assessing most point-of-care analytes in healthy dogs, although a larger sample size should be investigated. The application of these data in shock patients is unknown.


Assuntos
Medula Óssea/fisiologia , Cães/sangue , Emergências/veterinária , Testes Imediatos , Equilíbrio Ácido-Base , Animais , Gasometria , Nitrogênio da Ureia Sanguínea , Cloretos/sangue , Hematócrito/veterinária , Infusões Intraósseas/métodos , Veias Jugulares , Ácido Láctico/sangue , Projetos Piloto , Potássio/sangue , Estudos Prospectivos
11.
Chem Biol Interact ; 308: 269-278, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153982

RESUMO

Although cisplatin is an effective anticancer drug, its clinical application is limited due to various side effects, especially nephrotoxicity. In this study, we investigated the protective effects and possible mechanisms of hesperetin on cisplatin-induced kidney damage. In vitro, hesperetin significantly attenuated oxidative stress-induced apoptosis by reducing ROS levels in cisplatin-treated HK-2 cells. Simultaneously, hesperetin activated the Nrf2 signaling pathway and regulated its downstream genes, including NQO1 and HO-1. In vivo, hesperetin could significantly attenuate cisplatin-induced nephrotoxicity, blood urea nitrogen (BUN) and serum creatinine (SCr). Furthermore, hesperetin clarifies cisplatin-induced oxidative stress by reducing MDA/MPO levels and increasing SOD/GSH levels. In addition, from the histopathological analysis of the kidney, hesperetin significantly reduced the nephrotoxicity caused by cisplatin compared with the cisplatin group. Moreover, western blotting of renal tissue revealed that hesperetin activates Nrf2 in a dose-dependent manner, attenuates the MAPK signaling pathway against inflammation, and inhibits the expression of apoptotic proteins to protect kidneys from AKI caused by cisplatin. Altogether, these findings suggest that hesperetin may be a potential protectant against cisplatin-induced nephrotoxicity.


Assuntos
Lesão Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Hesperidina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Animais , Antioxidantes/metabolismo , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/uso terapêutico , Creatinina/sangue , Hesperidina/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Niger J Clin Pract ; 22(6): 750-753, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187757

RESUMO

Objective: To study the role of hypoxia inducible factor-1α (HIF-1α) in patients with diabetic nephropathy (DN). Methods: In total, 133 participants were selected to conduct the investigation, parameters such as fasting blood sugar (FBS), blood urea nitrogen (BUN), and urine albumin-creatinine ratio (UACR) were tested and recorded. The biopsy assessment was conducted when renal function or urinary abnormalities. Western blotting was used to test the expression of serum HIF-1α in all patients and control group. Results: The values of FBS, BUN, and UACR were higher in DN and diabetes groups than in the healthy control. The values of FBG, BUN, and UACR were higher in DN patients than in the diabetes patients with no nephropathy. eGFR in DN patients was lower than the other two groups. The expression of HIF-1α was higher than both diabetes patients with no nephropathy and healthy control, P < 0.05. Patients with lots of albuminuria showed the highest expression of HIF-1α than the other groups. HIF-1α in normoalbuminuria and microalbuminuria groups showed no significant difference. Conclusions: HIF-1α was up-regulated in DN patients, which might give clinical basis to the role of HIF-1α in the development of DN.


Assuntos
Albuminúria/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Adulto , Idoso , Albuminúria/urina , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
13.
J Anim Sci ; 97(7): 2914-2926, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31155652

RESUMO

The objective of this study was to determine the effects of increased AA and energy intake during late gestation on reproductive performance, milk composition, and metabolic and redox status of sows. A total of 118 Yorkshire sows (third through sixth parity) were randomly assigned to dietary treatments from day 90 of gestation until farrowing. Dietary treatments consisted of combinations of 2 standardized ileal digestible (SID) AA levels [14.7 or 20.6 g/d SID Lys, SID Lys and other AA met or exceeded the NRC (2012) recommendations] and 2 energy levels (28.24 or 33.78 MJ/d intake of NE) in a 2 × 2 factorial design. After parturition, all sows were fed a standard lactation diet. Blood samples were collected and analyzed for parameters on metabolism, redox status, and amino acid profile. The data were analyzed using the generalized linear mixed models to reveal the impact of dietary levels of energy, AA, and their interaction. Sows with increased intake of AA had greater BW gain (P < 0.01) during late gestation. Furthermore, the BW loss during lactation was increased in sows with increasing intake of energy (P < 0.05) or AA (P < 0.05). Sows fed high energy had higher total litter birth weights (20.2 kg vs. 18.4 kg, P < 0.05) and shorter duration of farrowing (261 min vs. 215 min, P < 0.05), compared with those fed low energy, which likely was due to higher (P < 0.05) plasma glucose and lower (P < 0.05) plasma lactate prior to parturition. High AA intake in late gestation increased the ADG of piglets during the following lactation (P < 0.05), and increased the concentrations of plasma urea, and the following AA: Lys, Met, Thr, Val, Ile, Leu, Phe, Asp, Ser, and Arg at farrowing (P < 0.05). In conclusion, the increased intake of energy increased total litter weight of newborns and shortened the farrowing duration, which likely was due to improved energy status at farrowing. Furthermore, sows with increased intake of AA led to higher growth rate of piglets during the following lactation, accompanying with the increasing levels of plasma urea and amino acids. Therefore, the higher energy intake in late gestation appeared to improve litter weight and farrowing duration, while higher AA intake may have positive effect on piglets performance in lactation.


Assuntos
Aminoácidos/metabolismo , Ração Animal/análise , Ingestão de Energia , Leite/química , Reprodução/efeitos dos fármacos , Suínos/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Dieta/veterinária , Feminino , Íleo/metabolismo , Lactação/efeitos dos fármacos , Estado Nutricional , Oxirredução , Paridade , Parto , Gravidez , Distribuição Aleatória , Suínos/microbiologia
14.
BMC Vet Res ; 15(1): 180, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146764

RESUMO

BACKGROUND: Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that renal proximal tubular epithelial cells participate in uric acid excretion in chickens, the roles of BCRP and MRP4 therein remain unclear. This study evaluated the relationship between BCRP and MRP4 expression and renal function in chickens. RESULTS: Sixty laying hens were randomly divided into four treatment groups: a control group (NC) fed a basal diet; a sulfonamide-treated group (SD) fed the basal diet and supplemented with sulfamonomethoxine sodium via drinking water (8 mg/L); a fish meal group (FM) fed the basal diet supplemented with 16% fishmeal; and a uric acid injection group (IU) fed the basal diet and intraperitoneally injected with uric acid (250 mg/kg body weight). The results showed that serum uric acid, creatinine, and blood urea nitrogen levels were significantly higher in the SD and IU, but not FM, than in the NC groups. Renal tubular epithelial cells in the SD and IU groups were damaged. Liver BCRP and MRP4 mRNA and protein levels were significantly decreased in the SD and IU groups, but slightly increased in the FM group. In the SD group, BCRP and MRP4 were significantly increased in the ileum and slightly increased in the kidney. In the FM group, BCRP and MRP4 were significantly increased in the kidney and slightly increased in the ileum. In the IU group, BCRP and MRP4 were significantly increased in the kidney and ileum. BCRP and MRP4 expression in the jejunum was not affected by the treatments. CONCLUSION: Together, these results demonstrate that BCRP and MRP4 are involved in renal and intestinal uric acid excretion in chickens and that BCRP is positively related to MRP4 expression. Further, impairment of renal function results in an increase in serum uric acid as well as a compensatory increase in BCRP and MRP4 in the ileum; however, under normal renal function, renal BCRP and MRP4 are the main regulators of uric acid excretion.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Galinhas/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Ácido Úrico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Nitrogênio da Ureia Sanguínea , Galinhas/sangue , Células Epiteliais/ultraestrutura , Feminino , Mucosa Intestinal/metabolismo , Rim/metabolismo , Rim/ultraestrutura , Túbulos Renais/ultraestrutura , Fígado/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , RNA Mensageiro/metabolismo , Ácido Úrico/sangue
15.
Cell Prolif ; 52(4): e12627, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31094028

RESUMO

OBJECTIVES: Based on previous reports that ginsenosides have been shown to exert better preventive effects on cisplatin-induced kidney injury, the present work aims to evaluate the protective effects of ginsenoside Rb3 (G-Rb3) on cisplatin-induced renal damage and underlying mechanisms in vivo and in vitro. MATERIALS AND METHODS: The protective effect of G-Rb3 on cisplatin-induced acute renal failure in ICR mouse model and HEK293 cell model was investigated, and the underlying possible mechanisms were also explored. For animal experiment, renal function, kidney histology, inflammation, oxidative stress, relative protein molecules involved in apoptosis and autophagy signalling pathways were assessed. In addition, rapamycin (a specific inhibitor of mTOR), compound C (a specific inhibitor of AMPK) and acetylcysteine (NAC, a specific ROS scavenger) were employed to testify the effects of AMPK/mTOR signal pathway on the protective effects of G-Rb3 in HEK293 cells. RESULTS: Pre-treatment with G-Rb3 at doses of 10 and 20 mg/kg for ten days significantly reversed the increases in serum creatinine (CRE), blood urea nitrogen (BUN) and malondialdehyde (MDA), and decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Histopathological examination further revealed that G-Rb3 inhibited cisplatin-induced nephrotoxicity. G-Rb3 diminished cisplatin-induced increase in protein expression levels of p62, Atg3, Atg5 and Atg7, and decrease in protein expression level of p-mTOR and the ratio of LC3-I/LC3-II, indicating that G-Rb3 suppressed cisplatin-induced activation of autophagy. Inhibition of autophagy induced inactivation of apoptosis, which suggested that autophagy played an adverse effect on cisplatin-evoked renal damage. Further, we found that G-Rb3 might potentially modulate the expressions of AMPK-related signal pathways. CONCLUSIONS: These findings clearly suggested that G-Rb3-mediated alleviation of cisplatin-induced nephrotoxicity was in part due to regulation of AMPK-/mTOR-mediated autophagy and inhibition of apoptosis in vitro and in vivo.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/farmacologia , Ginsenosídeos/farmacologia , Substâncias Protetoras/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Creatinina/metabolismo , Glutationa/metabolismo , Células HEK293 , Humanos , Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
16.
Ultrasonics ; 98: 1-6, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31121515

RESUMO

The purpose of this work is to investigate whether imaging sequences of flash-replenishment contrast enhanced ultrasound (CEUS) of the kidney result in chronic or acute bioeffects. Kidneys of female Fischer 344 rats were imaged using the flash-replenishment technique. Animals were separated into four groups (N = 31). Imaging was conducted with a 4C1 probe, driven by an Acuson Sequoia system with Definity microbubbles as the ultrasound contrast agent. During the flash phase of the imaging sequence, one kidney in each animal was exposed to either a mechanical index (MI) of 1.0 or 1.9. For each MI, half of the animals were sacrificed shortly after imaging (4 h) or after 2 weeks. A blinded veterinary nephropathologist reviewed the histopathology of both the imaged and control (non-imaged) kidney. Blood urea nitrogen (BUN) was measured for each animal prior to imaging and at the time of necropsy. Histopathology assessments in both the 1.0 and 1.9 MI groups revealed no signs of hemorrhage at either the 4-h or 2-week time point. BUN showed minor but statistically significant elevations in both the 1.0 and 1.9 MI groups, but no significant difference was present at the 2-week time point in the 1.0 MI group. All BUN levels (at both time points) remained in the normal range. In conclusion, CEUS with flash-replenishment imaging sequences did not result in kidney bioeffects observable with histology at early or late time points. Increases in BUN levels were observed after imaging, but were minimized when using a moderate MI (1.0).


Assuntos
Análise Química do Sangue , Meios de Contraste/farmacologia , Fluorcarbonetos/farmacologia , Rim/efeitos dos fármacos , Rim/diagnóstico por imagem , Ultrassonografia , Animais , Nitrogênio da Ureia Sanguínea , Feminino , Microbolhas , Ratos , Ratos Endogâmicos F344
17.
Int J Occup Environ Med ; 10(2): 80-88, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31041925

RESUMO

BACKGROUND: Many workers, particularly those working in manufacture of fertilizers, explosives, rubber, pesticides, textiles, and employees of petrochemical industries are exposed to ammonia in their workplaces. Toxic responses of hematopoietic system and kidney following occupational exposure to this chemical have not been thoroughly investigated. OBJECTIVE: To determine the relationship between long-term occupational exposure to low levels of ammonia and hematological parameters and kidney function. METHODS: In this cross-sectional study, 119 randomly selected, male petrochemical workers and 131 office employees (comparison group) were examined. Urine and blood samples were taken from all participants for urinalysis, complete blood count (CBC), serum calcium level, and blood urea nitrogen (BUN) and plasma creatinine. Personal, environmental, and peak ammonia exposure were also measured. RESULTS: The median personal, environmental, and peak occupational exposure to ammonia were 0.23, 0.16, and 65.50 mg/m3, respectively, among the exposed group. No significant difference was observed between the exposed and unexposed participants in terms of hematological parameters and urinalysis. Conversely, calcium and BUN, while within the normal range, were significantly higher in the exposed than in the comparison group. CONCLUSION: Occupational exposure to low atmospheric concentrations of ammonia was associated with subtle, sub-clinical, pre-pathologic changes in kidney function. Possible longterm consequences and ramifications of these effects require further investigation.


Assuntos
Amônia/toxicidade , Rim/efeitos dos fármacos , Exposição Ocupacional/análise , Adulto , Contagem de Células Sanguíneas , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Creatinina/sangue , Estudos Transversais , Humanos , Testes de Função Renal , Masculino
18.
J Dairy Sci ; 102(7): 6088-6108, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31056327

RESUMO

The objective of this study was to determine whether the partial replacement of barley starch with lactose (fed as dried whey permeate; DWP) affects N utilization, whole-body urea kinetics, and production in dairy cows. Eight lactating Holstein cows were used in a replicated 4 × 4 Latin square design with 28-d periods. Four cows in one Latin square were ruminally cannulated and used to determine dietary effects on whole-body urea kinetics and N utilization. Cows were fed a barley-based diet that contained 3.6% (dry matter basis) total sugar (TSG; designated control), or diets that contained 6.6, 9.6, or 12.6% TSG. Dietary TSG content was increased by the replacement of barley grain with DWP (83% lactose). Diets were isonitrogenous (∼17.3% crude protein), and starch contents of the control, 6.6, 9.6, and 12.6% TSG diets were 24.3, 22.2, 21.2, and 19.1%, respectively. Whole-body urea kinetics were measured using 4-d infusions of [15N15N]-urea with concurrent total collections of feces and urine. Dry matter intake (mean = 26.7 kg/d), milk yield (mean = 34.9 kg/d), and milk protein and fat contents were unaffected by diet. Ruminal ammonia-N concentration decreased linearly as TSG content increased, whereas ruminal butyrate concentration increased linearly as TSG content increased. Urinary excretion of total N and urea-N changed quadratically, whereas urinary excretion of total N (% of N intake) tended to change quadratically as TSG content increased. Fecal N excretion linearly increased as TSG content increased. A quadratic response was observed for total N excretion as TSG content increased. Milk N and retained N were not affected by diet. As TSG content increased, we observed quadratic responses in the omasal flow of fluid-associated and total bacterial nonammonia N, endogenous production of urea-N, urea-N recycled to the gastrointestinal tract, and urea-N returned to the ornithine cycle. Dietary TSG content did not affect the anabolic utilization of recycled urea-N or the proportion of recycled urea-N that was used for bacterial growth. Our results indicate that feeding DWP did not influence dry matter intake, milk yield, or milk composition. Feeding DWP decreased ruminal ammonia-N concentration, but this did not result in positive responses in milk protein secretion or N balance. The quadratic response in omasal flow of total bacterial nonammonia N indicated that including TSG beyond 9.6% of diet dry matter might depress ruminal microbial protein synthesis.


Assuntos
Ração Animal , Bovinos/metabolismo , Hordeum , Lactose/administração & dosagem , Nitrogênio/metabolismo , Omaso/metabolismo , Ureia/metabolismo , Amônia/metabolismo , Ração Animal/análise , Animais , Nitrogênio da Ureia Sanguínea , Indústria de Laticínios , Dieta/veterinária , Feminino , Lactação , Lactose/metabolismo , Leite , Proteínas do Leite/metabolismo , Nutrientes/metabolismo , Amido/administração & dosagem , Amido/metabolismo
19.
Mol Med Rep ; 19(6): 5115-5122, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059037

RESUMO

3,3'­Diindolylmethane (DIM) is a naturally derived indole compound found in the Brassica family of vegetables. DIM has several beneficial effects, including anti­cancer, anti­inflammatory and anti­angiogenic functions. However, the effects of DIM on acute kidney injury (AKI) stimulated by lipopolysaccharide (LPS) are poorly studied. In this present study, male BALB/c mouse models of AKI were established using intraperitoneal injections of 10 mg/kg LPS. DIM (40 mg/kg) was administered intraperitoneally 24 and 2 h before LPS exposure. The results indicated that DIM significantly mitigated histopathological changes in the kidneys and improved the levels of blood urea nitrogen and serum creatinine. DIM also suppressed the LPS­induced production of reactive oxygen species and cell apoptosis. Furthermore, DIM treatment significantly decreased the expression of NADPH oxidase 2 (NOX2) and NOX4 in LPS­treated mice. Therefore, DIM may exert its renoprotective actions by inhibiting NOX­mediated oxidative stress and the apoptosis of renal tubular epithelial cells.


Assuntos
Lesão Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Indóis/farmacologia , Lipopolissacarídeos/toxicidade , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glutationa/metabolismo , Rim/patologia , Túbulos Renais/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NADPH Oxidases/genética , Espécies Reativas de Oxigênio/metabolismo
20.
Kaohsiung J Med Sci ; 35(4): 222-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30958641

RESUMO

Research on anticervical cancer is urgently required to enhance clinical outcomes. As a main anticancer drug for cervical carcinoma, cisplatin (CIS) has been used for a lot of years in clinical therapy. However, serious adverse effects including nephrotoxicity and neurotoxicity limit its long-term treatment. Our main goal of this study is to investigate the improvement of Ganoderma lucidum polysaccharides (GPS) on CIS-induced antitumor effect of in U14 cervical carcinoma-bearing mice. The results showed that GPS + CIS could not only inhibit the growth of the tumor but also improve the spleen and thymus indexes. Moreover, little toxicological effects were observed on hepatic function and renal function in GPS + CIS treated mice bearing U14 tumor cells. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl-2 decreased dramatically in cervical cancer sections after oral administration of GPS + CIS for 14 days. This GPS/CIS combined therapy represents intriguing therapeutic strategy for U14 cervical carcinoma providing not only superior efficacy but also a higher safety level.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Polissacarídeos/uso terapêutico , Reishi/química , Neoplasias do Colo do Útero/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Creatinina/sangue , Feminino , Contagem de Leucócitos , Camundongos , Polissacarídeos/farmacologia , Análise de Sobrevida , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Proteína X Associada a bcl-2/metabolismo
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