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1.
Animal ; 15(8): 100318, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34311194

RESUMO

Identifying animals that are superior in terms of feed efficiency may improve the profitability and sustainability of the beef cattle sector. However, measuring feed efficiency is costly and time-consuming. Biomarkers should thus be explored and validated to predict between-animal variation of feed efficiency for both genetic selection and precision feeding. In this work, we aimed to assess and validate two previously identified biomarkers of nitrogen (N) use efficiency in ruminants, plasma urea concentrations and the 15N natural abundance in plasma proteins (plasma δ15N), to predict the between-animal variation in feed efficiency when animals were fed two contrasted diets (high-starch vs high-fibre diets). We used an experimental network design with a total of 588 young bulls tested for feed efficiency through two different traits (feed conversion efficiency [FCE] and residual feed intake [RFI]) during at least 6 months in 12 cohorts (farm × period combination). Animals reared in the same cohort, receiving the same diet and housed in the same pen, were considered as a contemporary group (CG). To analyse between-animal variations and explore relationships between biomarkers and feed efficiency, two statistical approaches, based either on mixed-effect models or regressions from residuals, were conducted to remove the between-CG variability. Between-animal variation of plasma δ15N was significantly correlated with feed efficiency measured through the two criteria traits and regardless of the statistical approach. Conversely, plasma urea was not correlated to FCE and showed only a weak, although significant, correlation with RFI. The response of plasma δ15N to FCE variations was higher when animals were fed a high-starch compared to a high-fibre diet. In addition, we identified two dietary factors, the metabolisable protein to net energy ratio and the rumen protein balance that influenced the relation between plasma δ15N and FCE variations. Concerning the genetic evaluation, and despite the moderate heritability of the two biomarkers (0.28), the size of our experimental setup was insufficient to detect significant genetic correlations between feed efficiency and the biomarkers. However, we validated the potential of plasma δ15N to phenotypically discriminate two animals reared in identical conditions in terms of feed efficiency as long as they differ by at least 0.049 g/g for FCE and 1.67 kg/d for RFI. Altogether, the study showed phenotypic, but non-genetic, relationships between plasma proteins δ15N and feed efficiency that varied according to the efficiency index and the diet utilised.


Assuntos
Ração Animal , Proteínas Sanguíneas/análise , Ureia/sangue , Animais , Biomarcadores , Bovinos/genética , Dieta/veterinária , Ingestão de Alimentos , Masculino , Ruminantes
2.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198937

RESUMO

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1ß and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Metformina/administração & dosagem , Própole/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Sinergismo Farmacológico , L-Lactato Desidrogenase/metabolismo , Masculino , Metformina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Própole/farmacologia , Ratos , Estreptozocina , Regulação para Cima , Ureia/sangue , Ácido Úrico/sangue
3.
Biomed Res Int ; 2021: 6632128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258274

RESUMO

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics.


Assuntos
Encéfalo/patologia , Rim/patologia , Fígado/patologia , Nanopartículas/toxicidade , Própole/farmacologia , Titânio/toxicidade , Albuminas/análise , Animais , Glicemia/metabolismo , Encéfalo/efeitos dos fármacos , Cloretos/sangue , Creatinina/sangue , Rim/efeitos dos fármacos , Lipídeos/análise , Fígado/efeitos dos fármacos , Marrocos , Potássio/sangue , Ratos Wistar , Sódio/sangue , Ureia/sangue
4.
Medicine (Baltimore) ; 100(25): e26160, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160382

RESUMO

ABSTRACT: Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67-7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22-2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06-2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76-4.85, P < .001; and low level of urea: HR = 2.69, 95% CI: 1.69-4.29, P < .001). By contrast, melioidosis patients with diabetic had 30.0% lower risk of dying from melioidosis compared to those with non-diabetic (HR = 0.70, 95% CI: 0.52-0.94, P = .016).Identifying the prognostic factors of mortality in patients with melioidosis allows a guideline of early management in these patients, which may improve patient's survival.


Assuntos
Antibacterianos/uso terapêutico , Burkholderia pseudomallei/isolamento & purificação , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Melioidose/mortalidade , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Contagem de Leucócitos , Malásia/epidemiologia , Masculino , Melioidose/sangue , Melioidose/tratamento farmacológico , Melioidose/microbiologia , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Proteção , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Ureia/sangue
5.
Clin Drug Investig ; 41(7): 639-645, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110614

RESUMO

BACKGROUND AND OBJECTIVE: Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets. METHODS: In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods. RESULTS: When OM was administered as 25 1-mg OM slow-release minitablets, AUClast, AUCinf, and Cmax were 0.998-, 1.00-, and 1.29-fold of a single 25-mg OM matrix MR tablet, respectively. When OM was administered as 25 1-mg OM fast-release minitablets, AUClast, AUCinf, and Cmax were 1.26-, 1.25-, and 2.21-fold of a single 25-mg OM matrix MR tablet, respectively. The slow- and fast-release minitablets display approximately dose-proportional pharmacokinetics. There were no serious adverse events or treatment-emergent adverse events leading to discontinuation from the study. CONCLUSIONS: Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.


Assuntos
Preparações de Ação Retardada/química , Comprimidos/química , Ureia/análogos & derivados , Administração Oral , Adolescente , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Composição de Medicamentos , Feminino , Meia-Vida , Voluntários Saudáveis , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Ureia/efeitos adversos , Ureia/sangue , Ureia/farmacocinética , Ureia/uso terapêutico , Adulto Jovem
6.
Biomed Res Int ; 2021: 6684167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34159199

RESUMO

Background: Obesity causes different diseases, eventually. In our study, the results of resistance exercises were examined on selected biochemical markers in Abha City, Saudi Arabia, which is at the height of 2,270 meters above sea level. Methods: A randomized controlled research was conducted with 60 participants equally divided into three groups, 20 subjects in each group: group 1 was composed of obese people who received resistance training exercise, group 2 was composed of the obese control group who did not receive resistance training exercise, and group 3 was composed of normal individuals who received resistance exercise training. The resistance exercises were done in the 6th and 12th weeks. Biochemical blood tests were done. Results: Comparing to the control group, glucose decreased very little with insulin also showing little difference. It has been seen that TC, TG, and LDL reduced to a reasonable extent after resistance exercise, while HDL was increased (p ≤ 0.01). Plasma urea and creatinine showed no differences. Interleukin-6 and leptin decreased significantly (p ≤ 0.01), while there was a significant elevation in adiponectin and testosterone (p ≤ 0.01) once comparing group 1 with group 2 and group 3. Conclusion: We have seen that resistance exercise helps in reducing lipid profile which will result in a decrease of the cardiac and related risk factors when conducted in obese patients in high-altitude regions. Also, alterations of the levels of interleukin-6, leptin, adiponectin, and testosterone showed that resistance exercise is of benefit and favourable in obese persons in high-altitude regions, which can also pave the way for added development of drugs related to the above parameters.


Assuntos
Terapia por Exercício/métodos , Obesidade/terapia , Treinamento de Força/métodos , Adiponectina/sangue , Adulto , Glicemia/análise , Composição Corporal , Creatinina/sangue , Estudos Transversais , Humanos , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Testosterona/sangue , Ureia/sangue
7.
Environ Toxicol Pharmacol ; 86: 103667, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933708

RESUMO

Ingestion of perfluorooctanoic acid (PFOA) elicits toxicities in the hepatorenal system. We investigated the effect of PFOA and N-acetylcysteine (NAC) on the hepatorenal function of rats treated thus: control, PFOA (5 mg/kg), NAC (50 mg/kg), PFOA + NAC (5 and 25 mg/kg), and PFOA + NAC (5 and 50 mg/kg). We observed that NAC significantly (p < 0.05) reduced PFOA-induced increase in hepatic and renal function biomarkers of toxicities relative to PFOA alone and alleviated (p < 0.05) decreases in antioxidant status. Increases in oxidative stress and lipid peroxidation in PFOA-treated rats were reverted to normal by NAC and abated increased pro-inflammatory mediators, and decreased anti-inflammatory cytokine both in the hepatorenal system PFOA treated rats. Histology of the kidney and liver indicated that NAC, abated the severity of PFOA-induced damage significantly. Our findings affirm further that oxido-inflammatory mediators involved in PFOA-mediated toxicity can be effectively blocked by NAC through its antioxidant activity.


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Acetilcisteína/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Creatinina/sangue , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Ratos Wistar , Ureia/sangue , gama-Glutamiltransferase/sangue
8.
World Neurosurg ; 151: e961-e971, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020058

RESUMO

OBJECTIVE: The urea-creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study. METHODS: We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0-2) and critical (day 5-7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months. RESULTS: Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P < 0.001) but decreased back to baseline on day 5-7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5-7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P < 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026). CONCLUSIONS: In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH.


Assuntos
Biomarcadores/sangue , Creatinina/sangue , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicações , Ureia/sangue , Infarto Encefálico/sangue , Infarto Encefálico/epidemiologia , Infarto Encefálico/etiologia , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Int J Lab Hematol ; 43(5): 1243-1251, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33939271

RESUMO

INTRODUCTION: Although factors such as age, sex, diabetes, obesity and changes in certain laboratory investigations are important prognostic factors in COVID-19 infection, these may not apply to all ethnic/racial groups. We hypothesized differences in routine biochemistry and haematology indices in Caucasian and a combined group of Black, Asian and Minority Ethnic (BAME) patients who tested positive for COVID-19 who died, compared to survivors. METHODS: We tested our hypothesis in 445 patients (229 Caucasian, 216 BAME) admitted to secondary care with proven COVID-19 infection, in whom standard routine laboratory indices were collected on admission. RESULTS: After 28 weeks, 190 (42.7%) had died within 28 days of COVID diagnosis (97 Caucasians [42.4%], 93 BAMEs [43.1%], P = .923). A general linear model analysis found the ethnicity interaction with mortality to be significant for fibrinogen, ferritin and HbA1 c (after controlling for age). In a multivariate analysis, a neutrophil/lymphocyte ratio > 7.4 and a urea/albumin ratio > 0.28 increased the odds of death for both the Caucasian and the BAME group. Additional factors increasing the odds ratio in the BAME group included age >60 years and being diabetic. CONCLUSION: Neutrophil/lymphocyte ratio and urea/albumin ratio are simple metrics that predict death to aid clinicians in determining the prognosis of COVID-19 and help provide early intensive intervention to reduce mortality. In the BAME groups, intensive monitoring even at younger age and those with diabetes may also help reduce COVID-19 associated mortality.


Assuntos
COVID-19/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Grupos Étnicos , Feminino , Ferritinas/análise , Fibrinogênio/análise , Hemoglobina A Glicada/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Albumina Sérica Humana/análise , Ureia/sangue
10.
Pharmacology ; 106(5-6): 332-340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33849026

RESUMO

INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.


Assuntos
Nefropatias/prevenção & controle , Intoxicação por Mercúrio/prevenção & controle , Substâncias Protetoras/farmacologia , Trimetazidina/farmacologia , Animais , Creatinina/sangue , Transportadores de Ácidos Dicarboxílicos/urina , Glutationa/metabolismo , Glicosúria/induzido quimicamente , Glicosúria/prevenção & controle , Nefropatias/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Cloreto de Mercúrio/efeitos adversos , Transportadores de Ânions Orgânicos Dependentes de Sódio/urina , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Cloreto de Sódio/urina , Simportadores/urina , Trimetazidina/uso terapêutico , Ureia/sangue , Micção/efeitos dos fármacos
11.
Genes (Basel) ; 12(4)2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805346

RESUMO

Urea is largely derived from the urea cycle reactions through hepatic detoxification of free ammonia and cleared by urination, and the serum urea level is a crucial medical indicator for measuring the kidney function in patients with nephropathy; however, investigative revelations pointing to the serum urea level as a risk factor for cancer are very scarce, and relevant studies are restricted by potential biases. We aimed to explore the causal relationships of the serum urea level with cancer development by focusing on renal cell carcinoma (RCC) using the Mendelian randomization (MR) analyses. Summary estimates were collected from the inverse-variance weighted (IVW) method based on six single nucleotide polymorphisms (SNPs). The selected SNPs related to the serum urea were obtained from a large genome-wide association study (GWAS) of 13,312 European participants. The summary statistics of RCC were also available from public databases (IARC, n = 5219 cases, n = 8011 controls). Sensitivity analyses included the weighted median and MR-Egger methods. Serum urea was inversely associated with RCC in females (effect = 1.93; 95% CI: 1.24 to 3.01; p = 0.004) but exhibited null association with RCC in males, breast cancer (BRCA) in both genders and prostate cancer (PCa) in males. Similar conclusions were also drawn from the weighted median and MR-Egger. These findings reveal an intriguing link between serum urea and cancer risks for the very first time. Without ambiguity, the serum urea is causatively related to RCC specifically in females, although the mechanism(s) by which urea is involved in RCC development remains to be experimentally/clinically investigated. Our studies may well provide novel insights for RCC diagnosis, intervention and/or therapy.


Assuntos
Neoplasias da Mama/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Análise da Randomização Mendeliana/métodos , Neoplasias da Próstata/patologia , Ureia/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/etiologia , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/etiologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/etiologia , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/sangue , Neoplasias da Próstata/etiologia , Fatores de Risco
12.
Molecules ; 26(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917585

RESUMO

Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range of biologically active components that help to neutralize the adverse effects of free radicals. In this study, the effects of GSE prepared form semi-resistant grapevine cultivar Cerason, which is rich in phenolics, on biochemical markers of brown rats exposed to the effects of cadmium were monitored. GSE increased the plasma antioxidant activity and, in the kidneys and the liver, Cd content was significantly lowered by GSE co-administration. Accordingly, the increase in creatinine content and alanine aminotransferase activity and the decrease of catalase and superoxide dismutase activities caused by cadmium were slowed down by GSE co-administration. The results of this work reveal that grape seed extract offers a protective effect against the intake of heavy metals into the organism.


Assuntos
Biomarcadores/metabolismo , Extrato de Sementes de Uva/farmacologia , Saúde , Rim/metabolismo , Fígado/metabolismo , Alanina Transaminase/sangue , Animais , Antioxidantes/análise , Aspartato Aminotransferases/sangue , Cádmio/sangue , Catalase/metabolismo , Creatinina/sangue , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Metalotioneína/metabolismo , Compostos Fitoquímicos/análise , Ratos Wistar , Sementes/química , Superóxido Dismutase/metabolismo , Ureia/sangue
13.
Life Sci ; 275: 119349, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33744325

RESUMO

AIM: Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear. METHODS: Rats received GM (100 mg/kg, i.p.) for 7 days either separately or in combination with oral DS (50 mg/kg). RESULTS: GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-γ) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-γ proteins. SIGNIFICANCE: DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Diosmina/uso terapêutico , Gentamicinas/toxicidade , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína Oncogênica v-akt/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Animais , Western Blotting , Creatinina/sangue , Diosmina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Wistar , Ureia/sangue , Ácido Úrico/sangue
14.
Life Sci ; 275: 119388, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33774028

RESUMO

Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.


Assuntos
Apoptose , Eritropoetina/uso terapêutico , Rim/efeitos da radiação , Transplante de Células-Tronco Mesenquimais , Lesões Experimentais por Radiação/terapia , Animais , Apoptose/efeitos dos fármacos , Terapia Combinada , Creatinina/sangue , Raios gama/efeitos adversos , Masculino , Ratos , Ratos Wistar , Ureia/sangue
15.
Biol Chem ; 402(2): 155-165, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33544471

RESUMO

Fibrillar fibronectin (FFN), an active form of fibronectin (FN), plays important roles in various cellular processes. Our goal is to investigate effect of FFN morphology on cellular behaviors. Plasma FN at two concentrations was cross-linked into FFN by dialysis against 2 M urea followed by morphological analysis under Scanning Electron Microscopy. To evaluate effect of FFN morphology, fibroblasts were cultured on FN or different FFNs. Fibroblast behaviors including adhesion, spreading, and migration were evaluated. Our data showed that FN fibrillogenesis was dependent on FN concentration. At high concentrations (0.75 mg/mL), large FFN approximately 2.167 + 0.875 µm in diameter were formed with attached nodular structures and rough surface. In contrast, smooth surface FFN fibrils with diameter of 1.886 + 0.412 µm were formed from FN at 0.25 mg/mL. Cellular assays revealed morphological dependent biological effects of different FFNs. Fibroblast separately adhered to native FN and remained spherical while on FFN, cells attached with higher quantity and showed spreading morphology. A synergistic ligand interaction of integrin α5ß1 and αvß3 was observed in cell adhering on FFN. Cell migration results showed that large FFN decreased migration rate while small FFN did not. Taken together, our data draws new attention towards controlling biological function of FN by its fibrillar structure.


Assuntos
Fibronectinas/metabolismo , Substâncias Macromoleculares/metabolismo , Animais , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Fibronectinas/sangue , Substâncias Macromoleculares/sangue , Camundongos , Ureia/sangue , Ureia/metabolismo
16.
J Wildl Dis ; 57(1): 178-183, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33635992

RESUMO

Hematology and serum biochemistry reference intervals were estimated for the Iberian hare (Lepus granatensis). Most parameters differed significantly between hunted and livetrapped Iberian hares. Significant differences were found for sex (red blood cell count, mean corpuscular volume, total protein, albumin, uric acid, triglycerides, cholesterol, chloride) and age classes (red blood cell count, hematocrit, mean corpuscular hemoglobin, glucose, calcium, and sodium). Sex- and age-specific reference intervals were estimated for these parameters. Red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin, urea, and potassium show seasonal variations, with the lowest values in summer and the highest in winter. Creatinine, calcium, sodium, and phosphorus achieve their highest values in summer and stable baseline values throughout the rest of the year. These reference intervals can be used as baseline to monitor health, physiology, ecology, and nutrition of Iberian hare populations.


Assuntos
Envelhecimento/sangue , Lebres/fisiologia , Animais , Glicemia , Proteínas Sanguíneas , Cálcio/sangue , Cloretos/sangue , Colesterol/sangue , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Lebres/sangue , Hematócrito/veterinária , Masculino , Potássio/sangue , Valores de Referência , Estações do Ano , Albumina Sérica , Sódio/sangue , Triglicerídeos/sangue , Ureia/sangue , Ácido Úrico/sangue
17.
Anal Bioanal Chem ; 413(6): 1739-1747, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462659

RESUMO

Perovskite materials have attracted attention due to their excellent optical and electrical properties; however, their unsatisfactory stability limits their application in biochemical detection. In this paper, CsPbBr3 perovskite quantum dots were successfully encapsulated in poly(styrene/acrylamide) microspheres, using a swelling-shrinking method. The manufactured perovskite microspheres (PDPS composites) not only maintained strong photoluminescence (PL) stability but also demonstrated great water solubility. Additionally, a real-time pH monitoring platform was constructed based on the prepared PDPS composites and dopamine, and the system showed a good linear relationship in a pH range of 4-12. Furthermore, urea could be hydrolyzed to produce hydroxyl groups, thereby increasing the pH of the solution. Therefore, this system was then extended for urea and urease detection. As a result, the detection limits of urea and urease were recorded as 1.67 µM and 2.1 mU/mL, respectively. This development provides an interesting demonstration of the expanding list of applications of perovskite materials.


Assuntos
Compostos de Cálcio/análise , Óxidos/análise , Titânio/análise , Ureia/sangue , Ureia/urina , Urease/sangue , Urease/urina , Água/química , Técnicas Biossensoriais/métodos , Ácidos Carboxílicos/química , Enzimas Imobilizadas/química , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Hidrólise , Limite de Detecção , Modelos Lineares , Microscopia Eletrônica de Transmissão , Microesferas , Pontos Quânticos , Solubilidade , Temperatura , Difração de Raios X
18.
Life Sci ; 268: 118998, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417953

RESUMO

AIM: Hyperuricemia is defined by the European Rheumatology Society as a uric acid level greater than 6 mg/dl (60 mg/l or 360 µmol/l). Our goal was to evaluate the hypouricemic effect of nettle. For this reason, we have first of all try to create an hyperuricemic animal model which is very suitable because at the level of literature there is not an exact model, there are many models and our objective is to set an adequate model. MATERIALS AND METHODS: An attempt has been made to test acute and chronic hyperuricemia by varying the duration and method of induction of potassium oxonate. Similarly, attempts have been made to induce chronic hyperuricemia through an animal and vegetable diet. The reversibility of hyperuricemia was tested with a maintenance protocol. KEY FINDINGS: For the creation of the hyperuricemia model, it has been shown that acute hyperuricemia cannot be induced by short administration of potassium oxonate and persistent chronic hyperuricemia can be induced only after daily administration of oxonate of potassium by intraperitoneal injection for 15 days. Indeed, hyperuricemia was reversible after stopping the administration of potassium oxonate. The high-purine diet is also capable of inducing chronic hyperuricemia but to a less extent. SIGNIFICANCE: After creating an adequate model of hyperuricemia while setting the dose of potassium oxonate, route of administration and duration. A maintenance protocol was followed which subsequently made it possible to deduce that the daily administration of potassium oxonate must be continued to maintain the hyperuricemia.


Assuntos
Hiperuricemia/etiologia , Hiperuricemia/patologia , Ácido Oxônico/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Doença Crônica , Creatinina/sangue , Modelos Animais de Doenças , Hiperuricemia/induzido quimicamente , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos Wistar , Ureia/sangue , Ácido Úrico/sangue
19.
Trop Anim Health Prod ; 53(1): 73, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400003

RESUMO

In postpartum buffaloes, the process of uterine involution and changes in blood metabolic profile has not been studied in relation to development of subclinical endometritis (SCE). In this study, buffaloes (n = 100) approaching calving were identified. Weekly blood samples were collected on the day of calving up to 6 weeks post-calving. The diameter of uterine horns and onset of ovarian cyclicity (corpus luteum) were recorded through ultrasonography. On the basis of polymorphonuclear cell (PMN) cell count in endometrial cytology at days 45-50 postpartum, buffaloes were divided into two groups, viz., with SCE (> 5% PMN; n = 38) and without SCE (≤ 5% PMN; n = 62). Buffaloes with SCE took longer (P < 0.05) time to complete uterine involution and had larger (P < 0.05) uterine horn diameter between 3rd and 6th weeks postpartum and lower prostaglandin F2α metabolite (PGFM) concentration on the day of calving (P < 0.05) and 1 week (P < 0.001) post-calving than without SCE group. Buffaloes with SCE had lower (P < 0.001) concentration of glucose at weeks 2 and 3, higher (P < 0.001) ß-hydroxybutyric acid (BHBA) at week 3, and lower serum albumin concentration throughout the sampling period (P < 0.05 to 0.001) except at 1 week post-calving as compared to without SCE group. The urea concentration was significantly lower (P < 0.05 to 0.001) in buffaloes with SCE from 4 weeks post-calving onwards than without SCE group. The calcium concentration was lower in buffaloes with SCE at weeks 5 (P < 0.001) and 6 (P < 0.05) postpartum, whereas the concentration of magnesium and phosphorus was uniform between the two groups. No significant (P > 0.05) difference in onset of ovarian cyclicity between the 2 groups was observed, whereas buffaloes with SCE had longer (P = 0.001) median days open (141 days) than their counterpart (117 days). The first service conception rate, cumulative pregnancy rate, and pregnancy rate at 150 days postpartum were lower (P < 0.05) in buffaloes with SCE than without SCE group. In summary, higher BHBA and lower serum concentrations of glucose, albumin, urea, and calcium control onset of subclinical endometritis which in turn has negative impact on fertility of buffaloes.


Assuntos
Búfalos/fisiologia , Endometrite/veterinária , Fertilidade , Período Pós-Parto/sangue , Útero/anatomia & histologia , Ácido 3-Hidroxibutírico/sangue , Animais , Glicemia/metabolismo , Búfalos/sangue , Cálcio/sangue , Endometrite/epidemiologia , Endometrite/fisiopatologia , Endométrio/citologia , Endométrio/metabolismo , Feminino , Magnésio/sangue , Fósforo/sangue , Período Pós-Parto/fisiologia , Gravidez , Prevalência , Albumina Sérica/análise , Ultrassonografia/veterinária , Ureia/sangue , Útero/diagnóstico por imagem , Útero/fisiologia
20.
Am J Physiol Gastrointest Liver Physiol ; 320(4): G474-G483, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404376

RESUMO

Our study provides novel findings of experimental hypokalemia reducing urea cycle functionality and thereby severely increasing plasma ammonia. This is pathophysiologically interesting because plasma ammonia increases during hypokalemia by a hitherto unknown mechanism, which may be particular important in relation to the unexplained link between hypokalemia and hepatic encephalopathy. Potassium deficiency decreases gene expression, protein synthesis, and growth. The urea cycle maintains body nitrogen homeostasis including removal of toxic ammonia. Hyperammonemia is an obligatory trait of liver failure, increasing the risk for hepatic encephalopathy, and hypokalemia is reported to increase ammonia. We aimed to clarify the effects of experimental hypokalemia on the in vivo capacity of the urea cycle, on the genes of the enzymes involved, and on ammonia concentrations. Female Wistar rats were fed a potassium-free diet for 13 days. Half of the rats were then potassium repleted. Both groups were compared with pair- and free-fed controls. The following were measured: in vivo capacity of urea-nitrogen synthesis (CUNS); gene expression (mRNA) of urea cycle enzymes; plasma potassium, sodium, and ammonia; intracellular potassium, sodium, and magnesium in liver, kidney, and muscle tissues; and liver sodium/potassium pumps. Liver histology was assessed. The diet induced hypokalemia of 1.9 ± 0.4 mmol/L. Compared with pair-fed controls, the in vivo CUNS was reduced by 34% (P < 0.01), gene expression of argininosuccinate synthetase 1 (ASS1) was decreased by 33% (P < 0.05), and plasma ammonia concentrations were eightfold elevated (P < 0.001). Kidney and muscle tissue potassium contents were markedly decreased but unchanged in liver tissue. Protein expressions of liver sodium/potassium pumps were unchanged. Repletion of potassium reverted all the changes. Hypokalemia decreased the capacity for urea synthesis via gene effects. The intervention led to marked hyperammonemia, quantitatively explainable by the compromised urea cycle. Our findings motivate clinical studies of patients with liver disease.


Assuntos
Amônia/sangue , Hiperamonemia/etiologia , Hipopotassemia/etiologia , Deficiência de Potássio/complicações , Potássio/sangue , Ureia/sangue , Animais , Modelos Animais de Doenças , Feminino , Regulação Enzimológica da Expressão Gênica , Hiperamonemia/sangue , Hiperamonemia/genética , Hipopotassemia/sangue , Hipopotassemia/genética , Rim/metabolismo , Fígado/metabolismo , Músculo Esquelético/metabolismo , Deficiência de Potássio/sangue , Potássio na Dieta/administração & dosagem , Potássio na Dieta/metabolismo , Ratos Wistar
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