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1.
Life Sci ; 259: 118254, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800833

RESUMO

The biological and renal effects made by simultaneous and non-simultaneous exposure to toluene and noise were investigated. Twenty-four New Zealand white rabbits were exposed to 100 dB of white noise and 1000 ppm of toluene vapor for two weeks. The examined biochemical factors were urea, uric acid, creatinine, glucose, triglyceride, cholesterol, and albumin serum levels, measured on different days after the end of the exposure. Moreover, glutathione peroxidase activity (GPX), malondialdehyde dismutase activity (MDA), and superoxide dismutase (SOD) parameters were measured in the kidney tissue. The hematoxylin and eosin staining method was used for histopathological experiments. Overall, the noise increased albumin, uric acid, creatinine, and glucose levels, but it decreased urea, cholesterol, and triglyceride levels. Toluene decreased albumin, uric acid, and urea levels, while it increased creatinine, triglyceride, cholesterol, and glucose levels. Simultaneous exposure to noise and toluene decreased albumin, uric acid, cholesterol, and urea levels, whereas it increased creatinine, glucose, and triglyceride levels. GPX, MDA, and SOD levels increased by simultaneous and non-simultaneous exposure to noise and toluene. Furthermore, massive tubular degeneration, tubular cell vacuolization, glomerular disorganization, congestion, glomerular cell shrinkage, and unclear brush border were detected in the kidney tissue.


Assuntos
Rim/efeitos dos fármacos , Ruído/efeitos adversos , Tolueno/toxicidade , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Colesterol/metabolismo , Creatinina/metabolismo , Feminino , Glucose/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Nefropatias/patologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Superóxido Dismutase/metabolismo , Tolueno/metabolismo , Tolueno/farmacologia , Ureia/metabolismo , Ácido Úrico/metabolismo
2.
Nat Biomed Eng ; 4(9): 853-862, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32632226

RESUMO

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.


Assuntos
Enteroadsorção/métodos , Microbiota , Compostos de Nitrogênio/isolamento & purificação , Insuficiência Renal/terapia , Administração Oral , Alginatos/química , Amônia/metabolismo , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Cápsulas/administração & dosagem , Cápsulas/química , Creatinina/metabolismo , Modelos Animais de Doenças , Fezes/microbiologia , Indóis/química , Camundongos , Microfluídica , Microesferas , Compostos de Nitrogênio/metabolismo , Polímeros/química , Suínos , Resultado do Tratamento , Ureia/metabolismo
3.
Am J Physiol Gastrointest Liver Physiol ; 319(2): G151-G156, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32597708

RESUMO

Laursen TL, Sandahl TD, Kazankov K, Eriksen PL, Kristensen LH, Holmboe CH, Laursen AL, Vilstrup H, Grønbæk H. Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis. Am J Physiol Gastrointest Liver Physiol 319: G151-G156, 2020. First published June 29, 2020; doi:10.1152/ajpgi.00128.2020.-Effects of direct-acting antiviral (DAA) treatment of chronic hepatitis C (CHC) cirrhosis on metabolic liver function are unknown but important for prognosis. Ureagenesis is an essential metabolic liver function involved in whole body nitrogen homeostasis. We aimed to investigate the ureagenesis capacity before and immediately after DAA therapy and relate the findings to hepatic inflammation and structural changes. In an observational before-and-after intervention study, the ureagenesis capacity was quantified by functional hepatic nitrogen clearance (FHNC) in 9 CHC patients with cirrhosis and 10 healthy volunteers. Hepatic inflammation was evaluated by alanine aminotransferase (ALT) and the macrophage activation markers sCD163 and sMR. Structural changes were estimated as liver stiffness and by portal hypertension as the hepatic venous pressure gradient (HVPG). Before treatment, the FHNC in the patients was half of the controls [16.4 L/h (8.2-24.5) vs. 33.4 (29.2-37.6), P = 0.0004]; after successful DAA treatment, it normalized [28.4 (15.9-40.9), P = 0.008 vs. baseline]. DAA treatment normalized ALT (P < 0.0001) and decreased the elevated sCD163 from 5.6 mg/L (3.5-7.7) to 3.4 (2-0-4.8) (P < 0.001) and sMR from 0.35 mg/L (0.21-0.49) to 0.31 (0.17-0.45) (P < 0.01). Liver stiffness fell by 30% (P < 0.05) but remained over the cirrhosis threshold. HVPG was not affected (P = 0.59). DAA treatment restored the severely reduced ureagenesis capacity, along with amelioration of hepatic inflammation but without normalization of other cirrhosis characteristics. Our findings indicate that the anti-inflammatory effect of virus eradication independent of hepatic structural effects rapidly improves metabolic dysfunction. We suggest this effect to be an important early onset part of the expected clinical DAA treatment benefit.NEW & NOTEWORTHY Antiviral treatment of chronic hepatitis C restores the liver's reduced capacity to produce urea along with an improvement in liver inflammation without immediate effects on structural liver changes. The effect is suggested to be an important early onset part of the expected clinical treatment benefit.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/metabolismo , Ureia/metabolismo , Adulto , Estudos de Coortes , Feminino , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade
4.
Chemosphere ; 258: 127228, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32535438

RESUMO

Urea hydrolysis in partial nitritation process forming nitrite and ammonia is advantageous to subsequent treatment with ANAMMOX for total nitrogen removal. In this study, stable partial nitritation for urea wastewater with urea increasing from 250 to 2000 mg L-1 were achieved in an aerobic SBR. Urea removal efficiency and nitrite accumulation percentage both kept above 98%, with nitrite production rate about 0.985 kg N·m-3·d-1. Urea hydrolysis mechanism in this aerobic system was described as, (1) massive urea in the bulk was absorbed into cell, (2) urea was hydrolyzed by intracellular urease inside cell, (3) produced ammonia then slowly diffused into the bulk through membrane, which is later converted by ammonia-oxidizing bacteria (AOB) into nitrite. Due to this mechanism, the activity of AOB could not be inhibited by high FA (free ammonia) value under high urea concentration condition while nitrite-oxidizing bacteria (NOB) remained to be inhibited. An uncultured genus belonging to poorly characterized phylum Gemmatimonadetes was found enriched in this process and became dominant genus. This genus was speculated to have same energy pathway like ureaplasma, by absorbing excessive urea from environment and utilize urea hydrolysis to generate energy. So it was believed to be responsible for urea hydrolysis mechanism mentioned above. This SBR showed stable partial nitritation and high urea removal efficiency for treating urea wastewater, which was obviously feasible as the pretreatment process for subsequent ANAMMOX.


Assuntos
Amônia/análise , Reatores Biológicos/microbiologia , Nitritos/análise , Ureia/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Aerobiose , Amônia/metabolismo , Bactérias/metabolismo , Hidrólise , Nitritos/metabolismo , Nitrogênio/análise , Nitrogênio/metabolismo , Oxirredução , Ureia/metabolismo , Águas Residuárias/química , Poluentes Químicos da Água/metabolismo
5.
Life Sci ; 254: 117782, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407847

RESUMO

AIMS: This study assessed the prophylactic or therapeutic effects of taurine (TR) and/or hesperidin (HES) on carbon tetrachloride (CCl4) induced acute kidney and testicular injury in rats. MAIN METHODS: Rats were randomly divided into nine experimental groups including control; corn oil; CCl4; HES/CCl4; TR/CCl4; HES + TR/CCl4; CCl4/HES; CCl4/TR; and CCl4/HES + TR groups. CCl4 was intraperitoneally injected with a single dose of 2 ml /kg b.w. HES and TR were orally gavaged twice weekly 100 mg/kg b.w. for four weeks. Kidney function, inflammatory response, sexual hormones, and oxidative stress indicators were assessed. Histomorphological and immune-histochemical studies of the inflammatory marker nuclear factor kappa (NF-κB) in renal and testicular tissues were performed. KEY FINDINGS: The results showed that the TR and/or HES treatment significantly suppressed CCl4 induced rise of urea, uric acid, potassium, and follicle-stimulating hormone levels. However, significant restoration of sodium, testosterone, and luteinizing hormone was apparent in CCl4 exposed rats received HES and/or TR. Also, the HES and/or TR treatment significantly rescues CCl4 induced oxidative stress and inflammation. Moreover, the HES and/or TR dosing significantly repaired the CCl4 evoked altered renal and testicular architecture and suppressed NF-κB immunoexpression. Notably, alleviating CCl4 induced renal and testicular damage was more effective in the prophylactic groups than the therapeutic groups. Also, most of the estimated parameters of the HES + TR group did not significantly vary from those of single TR or HES. SIGNIFICANCE: In conclusion, HES or TR could efficiently guard against CCl4 nephro-and reprotoxic effects, but both bioactive combinations afford only a limited synergistic outcome.


Assuntos
Hesperidina/farmacologia , Inflamação/prevenção & controle , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Taurina/farmacologia , Testículo/metabolismo , Animais , Tetracloreto de Carbono , Sinergismo Farmacológico , Hormônio Foliculoestimulante/metabolismo , Rim/patologia , Hormônio Luteinizante/metabolismo , Masculino , NF-kappa B/metabolismo , Potássio/metabolismo , Ratos , Sódio/metabolismo , Testículo/patologia , Testosterona/metabolismo , Ureia/metabolismo , Ácido Úrico/metabolismo
6.
J Dairy Sci ; 103(7): 6209-6217, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32331886

RESUMO

Current feeding systems are based on the assumption that the AA profile of rumen undegraded protein is similar to that of the original feed. The objective of this experiment was to determine rumen bacterial degradation of individual essential AA in fish meal (FM) and blood meal (BM). Eight dual-flow continuous-culture fermentors were used in a completely randomized block design with a factorial arrangement of treatments and 3 replicated periods. Fermentors were supplied with 95 g of dry matter/d of isonitrogenous diets. Treatments contained a nonprotein N source (urea and tryptone) that was substituted with increasing proportions of FM or BM (0, 33, 67, or 100%). Diets consisted of 22.0% crude protein, 35.2% neutral detergent fiber, 34.6% nonfiber carbohydrates, 2.0% ether extract, and 9.2% ash. We hypothesized that the increase in the flow of individual AA would be attributed to the increase in the supply of the AA from each protein supplement. True organic matter degradation was decreased by increasing levels of FM or BM, but did not affect degradation of neutral detergent fiber and acid detergent fiber, total volatile fatty acids (VFA) concentration, or the molar proportion of propionate. There was a substrate by level of inclusion interaction in acetate molar proportion and branched-chain VFA. Butyrate concentration decreased linearly with increasing levels of FM and BM in treatment. Changes in branched-chain VFA reflected differences in content of branched-chain AA between supplements and the level of inclusion, although the quadratic effect suggests that other factors were involved. Ammonia-N concentration showed a substrate by level of inclusion interaction. Total dietary N and AA flows increased with increasing levels of FM or BM in treatment. The efficiency of bacterial crude protein synthesis was not affected by treatment, but the flow of bacterial N decreased in FM diets as the level of FM increased. Flows of AA increased linearly with increasing levels of the respective AA from supplements. Arginine, Ile, Met and Phe were more degradable, while His was more resistant to bacterial degradation. Results suggest that the resistance to rumen bacterial degradation of individual AA varies within FM and BM protein and may affect the estimates of dietary supply of individual AA to the small intestine.


Assuntos
Aminoácidos Essenciais/metabolismo , Reatores Biológicos , Sangue , Produtos Pesqueiros/análise , Rúmen/metabolismo , Amônia/metabolismo , Animais , Bactérias/metabolismo , Butiratos/metabolismo , Digestão , Ácidos Graxos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Ureia/metabolismo
7.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32227169

RESUMO

The objectives were to determine the effects of forage level and grain processing on whole-body urea kinetics, N balance, serosal-to-mucosal urea flux (Jsm-urea), and messenger ribonucleic acid (mRNA) abundance of urea transporter-B (UT-B; SLC14a1) and aquaporins (AQP) in ovine ruminal, duodenal, and cecal epithelia. Thirty-two wether lambs were blocked by body weight into groups of four and assigned to one of four diets (n = 8) in a 2 × 2 factorial design. Dietary factors were forage level (30% [LF] vs. 70% [HF]) and corn grain processing (whole-shelled [WS] vs. steam-flaked [SF]). Four blocks of lambs (n = 4) were used to determine urea kinetics and N balance using 4-d [15N15N]-urea infusions with concurrent fecal and urine collections. Lambs were killed after 23 d of dietary adaptation. Ruminal, duodenal, and cecal epithelia were collected to determine Jsm-urea and mRNA abundance of UT-B and AQP. Lambs fed LF had greater intakes of dry matter (DMI; 1.20 vs. 0.86 kg/d) and N (NI; 20.1 vs. 15.0 g/d) than those fed HF (P < 0.01). Lambs fed SF had greater DMI (1.20 vs. 0.86 kg/d) and NI (20.6 vs. 14.5 g/d) than those fed WS (P < 0.01). As a percentage of NI, total N excretion was greater in lambs fed HF compared with those fed LF (103% vs. 63.0%; P < 0.01) and was also greater in lambs fed WS compared with those fed SF (93.6% vs. 72.1%; P = 0.02). Retained N (% of NI) was greater in lambs fed LF compared with those fed HF (37.0% vs. -2.55%; P < 0.01). Lambs fed SF had a greater (P = 0.02) retained N (% of NI; 28.0% vs. 6.50%) compared with those fed WS. Endogenous urea production (UER) tended (P = 0.09) to be greater in lambs fed HF compared with those fed LF. As a proportion of UER, lambs fed HF had a greater urinary urea-N loss (0.38 vs. 0.22) and lower urea-N transferred to the gastrointestinal tract (GIT; 0.62 vs. 0.78) or urea-N used for anabolism (as a proportion of urea-N transferred to the GIT; 0.12 vs. 0.26) compared with lambs fed LF (P < 0.01). Ruminal Jsm-urea was unaffected by diet. Duodenal Jsm-urea was greater (P < 0.01) in lambs fed HF compared with LF (77.5 vs. 57.2 nmol/[cm2 × h]). Lambs fed LF had greater (P = 0.03) mRNA expression of AQP3 in ruminal epithelia and tended (P = 0.06) to have greater mRNA expression of AQP3 in duodenal epithelia compared with lambs fed HF. Expression of UT-B mRNA was unaffected by diet. Our results showed that feeding more ruminally available energy improved N utilization, partly through a greater proportion of UER being transferred to the GIT and being used for anabolic purposes.


Assuntos
Ingestão de Energia , Nitrogênio/metabolismo , Ovinos/fisiologia , Ureia/metabolismo , Ração Animal/análise , Animais , Aquaporinas/genética , Dieta/veterinária , Grão Comestível , Epitélio/metabolismo , Fezes/química , Fermentação , Trato Gastrointestinal/metabolismo , Cinética , Masculino , Proteínas de Membrana Transportadoras/genética , Distribuição Aleatória , Ovinos/genética , Zea mays
8.
Food Chem ; 319: 126554, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32169766

RESUMO

Bamboo leaves extract (BLE) contains various effective ingredients, including phenolic compounds. In this study, the effect of BLE on ethyl carbamate (EC) formation was investigated in Chinese yellow rice wine brewing with three different fermentation starters (Saccharomyces cerevisiae, Saccharomyces cerevisiae and Lactobacillus brevis, and Chinese yeast). As a result, BLE showed significant inhibition effect on EC in multi-microbial fermented rice wine, by preventing the reactions between urea/citrulline and ethanol. We found that BLE had influence on arginine transport (GAP1, CAN1, ALP1, and VBA2 gene) in Saccharomyces cerevisiae (S. cerevisiae), which significantly up-regulated arginine uptake gene expression in vacuole (VBA2 gene) so that inhibited arginine metabolism. Besides, the presence of BLE could improve the overall quality of Chinese yellow rice wine. Consequently, it was worthwhile applying BLE to Chinese rice wine fermentation, especially the wine brewing with S. cerevisiae and Lactobacillus brevis starter.


Assuntos
Bebidas Alcoólicas , Oryza/metabolismo , Extratos Vegetais/química , Sasa/química , Uretana/metabolismo , Citrulina/metabolismo , Etanol/metabolismo , Fermentação , Oryza/química , Folhas de Planta/química , Ureia/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-32174544

RESUMO

Pimavanserin is a new drug approved by the FDA for Parkinson's disease psychosis and other neurological disorders such as Alzheimer's disease. In this study, we developed a UPLC-MS/MS method to quantify pimavanserin disposition in the brain and its pharmacokinetics in mice. Vilazodone was used as the internal standard. Pimavanserin and IS were extracted by liquid-liquid extraction using tert-butyl methyl ether and separated using an Acquity UPLC BEH™ C18 column. The mobile phase consisted of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in 20 mM ammonium acetate buffer) (A: B, 70:30 v/v) at a flow rate of 0.25 ml/min. The multiple reaction monitoring transitions were performed at m/z 428.23 â†’ 98.15 for pimavanserin and m/z 441.70 > 155.03 for the IS. The developed method was found to be sensitive, fast, and reproducible. The linearity of the method was ˃0.99 over the range of 0.1-300 ng/mL in plasma and 0.25-300 ng/g in the brain homogenate. Precision and accuracy were within the acceptance range. The method was applied to pharmacokinetics and brain uptake studies, which showed that pimavanserin penetrates the blood-brain barrier and reaches a Cmax of 21.9 ± 6.66 ng/g in 2.0 h. We also found that pimavanserin brain to plasma ratio (Kbrain/plasma) is 0.16 ± 0.05 and it is rapidly eliminated.


Assuntos
Piperidinas/metabolismo , Piperidinas/farmacocinética , Ureia/análogos & derivados , Animais , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Extração Líquido-Líquido , Camundongos , Plasma/metabolismo , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Ureia/metabolismo , Ureia/farmacocinética
10.
Dig Dis Sci ; 65(7): 1917-1931, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32170476

RESUMO

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.


Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Amoxicilina/uso terapêutico , Antígenos de Bactérias/análise , Biópsia , Bismuto/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Técnicas de Cultura , Doxiciclina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/etiologia , Fezes/química , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Levofloxacino/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/etiologia , Metronidazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Úlcera Péptica/etiologia , Reação em Cadeia da Polimerase , Rifabutina/uso terapêutico , Salicilatos/uso terapêutico , Terapia de Salvação , Testes Sorológicos , Neoplasias Gástricas/etiologia , Tetraciclina/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Ureia/metabolismo
11.
J Med Chem ; 63(7): 3563-3576, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32207938

RESUMO

In an effort to seek novel agents targeting prostate-specific membrane antigen (PSMA), 16 ligands (L1-L16) with structural modifications in S1' binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with Ki values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based ligands. Computational docking was performed to study the binding mode of the two most potent ligands discovered. FITC-conjugated L14 could selectively stain PSMA+ LNCaP cells over PSMA- PC3 cells. IRDye800CW conjugated L16 can effectively image tumors in a murine xenograft model of prostate cancer.


Assuntos
Corantes Fluorescentes/farmacologia , Neoplasias da Próstata/diagnóstico por imagem , Ureia/análogos & derivados , Ureia/farmacologia , Animais , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Imagem Óptica/métodos , Estudo de Prova de Conceito , Ligação Proteica , Ureia/metabolismo
12.
Carbohydr Polym ; 235: 115952, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122487

RESUMO

Chitin is the second most abundant and renewable polysaccharide, next to cellulose. Hydrolysis of abundant and highly crystalline α-chitin, pretreated with KOH and KOH-urea aqueous solutions, by a single modular endo-chitinase from Enterobacter cloacae subsp. cloacae (EcChi1) was investigated. The hydrolysis of untreated α-chitin and colloidal chitin by EcChi1 produced N-acetylglucosamine and N, N'-diacetylchitobiose, whereas, hydrolysis of treated substrates generated N, N', N''-triacetylchitotriose, in addition to N-acetylglucosamine and N, N'-diacetylchitobiose. The total amount of chitooligosaccharides (COS) generated by EcChi1 from pretreated substrates was 10 to 25-fold higher compared to untreated α-chitin at 24 h (depending on the solvent type and state of substrate). EcChi1 released higher amount of DP1 and DP2 products on treated α-chitin, with a fold change of 45 and 18, respectively. Treatment of α-chitin with KOH/KOH-urea is, therefore, a promising approach for an efficient conversion of rich source of chitin to soluble COS by chitinases like EcChi1.


Assuntos
Quitina/química , Quitinases/química , Enterobacter cloacae/enzimologia , Hidróxidos/química , Compostos de Potássio/química , Ureia/química , Quitina/metabolismo , Quitinases/metabolismo , Hidrólise , Hidróxidos/metabolismo , Compostos de Potássio/metabolismo , Ureia/metabolismo
13.
Eur J Cancer ; 129: 32-40, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32120273

RESUMO

BACKGROUND: 5-Fluorouracil (5-FU)-induced hyperammonaemic encephalopathy is a rare but serious 5-FU adverse drug reaction (ADR). Given the growing number of cancers treated with 5-FU and the paucity of data regarding this ADR, we performed a retrospective national survey to better characterise 5-FU-induced hyperammonaemic encephalopathy. PATIENTS AND METHODS: Since inception of the French pharmacovigilance database, we identified all patients who experienced 5-FU-induced hyperammonaemic encephalopathy. Variables regarding demographics, characteristics, management and outcome of patients were collected. RESULTS: From 1986 to 2018, 30 patients were included. 5-FU-induced hyperammonaemic encephalopathy started 2 [1-4] days after 5-FU infusion onset. Most common neurological disorders were consciousness impairment, seizures and confusion. hyperammonaemia tended to be higher in patients with the lowest Glasgow score and admitted in intensive care unit (ICU) compared to non-ICU patients (250 [133-522] versus 139 [68-220] µmol/L respectively, p = NS). Dihydropyrimidine dehydrogenase deficiency was found in 27% of tested patients (n = 3/11). Encephalopathy-induced mortality was 17%, 57% of patients were admitted in ICU and 70% had a complete neurological recovery within 5 [2-10] days. A 5-FU rechallenge was considered in 14 (67%) patients with neurological recovery and a relapse was observed in 57% of them. No 5-FU-induced hyperammonaemic encephalopathy relapse was observed as long as 5-FU rechallenge was performed with decreased 5-FU dosage. CONCLUSION: We report the largest cohort of 5-FU-induced hyperammonaemic encephalopathy cases so far. This ADR should be suspected and ammonaemia measured in all patients experiencing neurological disorders after 5-FU administration. In patients with complete neurological recovery, a 5-FU rechallenge could be cautiously considered.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Encefalopatias/epidemiologia , Fluoruracila/efeitos adversos , Hiperamonemia/epidemiologia , Neoplasias/tratamento farmacológico , Idoso , Amônia/sangue , Antimetabólitos Antineoplásicos/administração & dosagem , Encefalopatias/sangue , Encefalopatias/induzido quimicamente , Encefalopatias/terapia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , França/epidemiologia , Humanos , Hiperamonemia/sangue , Hiperamonemia/induzido quimicamente , Hiperamonemia/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Resultado do Tratamento , Ureia/metabolismo
14.
J Fish Biol ; 96(4): 986-1003, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32060920

RESUMO

The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air-breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5-fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N-waste excretion (ammonia-N + urea-N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid-base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3 - (up to 33 mM) in the intestinal chyme of all four of these air-breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3 - was upregulated by feeding but not net Cl- uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3 - suggests that the high chyme (HCO3 - ) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid-base balance in these air-breathing fish is discussed.


Assuntos
Comportamento Alimentar/fisiologia , Peixes/fisiologia , Trato Gastrointestinal/fisiologia , Amônia/metabolismo , Animais , Água Doce , Mucosa Intestinal/metabolismo , Íons/metabolismo , Período Pós-Prandial , Sódio/metabolismo , Ureia/metabolismo , Vietnã
15.
Can J Microbiol ; 66(3): 214-227, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32011910

RESUMO

Increasing the use of nitrogen fertilizers in tea orchards has led to intense nitrous oxide (N2O) emissions. Foliar application of Paenibacillus polymyxa biofertilizer has been proven to be beneficial for organic tea production. In this study, tea yield and quality were significantly improved after application of P. polymyxa biofertilizer compared with the control but were not significantly different from chemical fertilizer treatments. However, the average N2O fluxes in tea fields treated with chemical fertilizers and biofertilizers (225 kg N·ha-1·year-1 for both) were 50.6-973.7 and 0.6-29.1 times higher than those in the control treatment, respectively. Pot experiments conducted to explore the mechanism of N2O reduction induced by P. polymyxa biofertilizer showed that applying P. polymyxa in addition to urea could reduce N2O fluxes by 36.5%-73.1%. Quantitative PCR analysis suggested that a significant increase in the quantity of nirK and nosZ genes was linked to the reduction of N2O, and high-throughput sequencing of nosZ revealed active and potentially efficient denitrifiers in different treatments. Our findings suggest that P. polymyxa biofertilizer is in line with the requirements of modern agriculture, which aims to increase product yield and quality while reducing negative environmental impacts.


Assuntos
Inoculantes Agrícolas/metabolismo , Camellia sinensis/microbiologia , Fertilizantes/análise , Óxido Nitroso/metabolismo , Paenibacillus polymyxa/metabolismo , Microbiologia do Solo , Agricultura , Camellia sinensis/crescimento & desenvolvimento , Desnitrificação , Óxido Nitroso/análise , Solo/química , Ureia/metabolismo
16.
J Med Chem ; 63(6): 3261-3273, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32097010

RESUMO

Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine the effect of ß- and γ-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the ß- and γ-amino acid analogues with (S)- or (R)-configuration with keeping α-(l)-Glu as the S1'-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a ß-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors.


Assuntos
Aminoácidos/química , Glutamato Carboxipeptidase II/antagonistas & inibidores , Ureia/análogos & derivados , Aminoácidos/síntese química , Aminoácidos/metabolismo , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Glutamato Carboxipeptidase II/metabolismo , Humanos , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Ureia/síntese química , Ureia/metabolismo
17.
PLoS One ; 15(2): e0229654, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106262

RESUMO

Human hepatocytes are essential materials in pharmaceutical researches. Not only primary human hepatocytes (PHH) but also human iPS cell-derived hepatocyte-like cells (human iPS-HLCs) are expected to be applied as materials for pharmaceutical researches. To date, several culture media have been developed for culturing human hepatocytes. However, there have been no reports comparing these media to determine which is most suitable for culturing human hepatocytes. In this study, we compared five commercial media (Hepatocyte Culture Medium (HCM), HepatoZYME-SFM, Cellartis Power Primary HEP Medium, DMEM/F12, and William's E Medium (WEM)) to determine which is most suitable for culturing PHH and human iPS-HLCs. In hepatic differentiation of human iPS cells (day 14-25 of differentiation), albumin (ALB) and urea secretion abilities and CYP2C9, CYP2C19, and CYP3A4 activities were the highest when using HCM or WEM. During maintenance of human iPS-HLCs, ALB and urea producing abilities and CYP2C9, CYP2C19, and CYP3A4 activities were the highest when using HCM. Importantly, we found that human iPS-HLCs cultured in HCM were maintained for 3 weeks or more without impairment of their hepatic functions. These results suggest that it is necessary to select an optimal medium for hepatic differentiation and maintenance of human iPS-HLCs. In the case of PHH culture, there was little difference in hepatic functions among the five media. However, the CYP2C9, CYP2C19, and CYP3A4 activities were the highest when using HCM and WEM. In conclusion, it is important to select the optimal medium for specific application when carrying out pharmaceutical researches using human hepatocytes.


Assuntos
Técnicas de Cultura de Células/métodos , Meios de Cultura , Hepatócitos/citologia , Hepatócitos/metabolismo , Albuminas/metabolismo , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Ureia/metabolismo
18.
Am J Physiol Renal Physiol ; 318(4): F936-F955, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088967

RESUMO

Kidney water conservation requires a hypertonic medullary interstitium, NaCl in the outer medulla and NaCl and urea in the inner medulla, plus a vascular configuration that protects against washout. In this work, a multisolute model of the rat kidney is revisited to examine its capacity to simulate antidiuresis. The first step was to streamline model computation by parallelizing its Jacobian calculation, thus allowing finer medullary spatial resolution and more extensive examination of model parameters. It is found that outer medullary NaCl is modestly increased when transporter density in ascending Henle limbs from juxtamedullary nephrons is scaled to match the greater juxtamedullary solute flow. However, higher NaCl transport produces greater CO2 generation and, by virtue of countercurrent vascular flows, establishment of high medullary Pco2. This CO2 gradient can be mitigated by assuming that a fraction of medullary transport is powered anaerobically. Reducing vascular flows or increasing vessel permeabilities does little to further increase outer medullary solute gradients. In contrast to medullary models of others, vessels in this model have solute reflection coefficients close to zero; increasing these coefficients provides little enhancement of solute profiles but does generate high interstitial pressures, which distort tubule architecture. Increasing medullary urea delivery via entering vasa recta increases inner medullary urea, although not nearly to levels found in rats. In summary, 1) medullary Na+ and urea gradients are not captured by the model and 2) the countercurrent architecture that provides antidiuresis also produces exaggerated Pco2 profiles and is an unappreciated constraint on models of medullary function.


Assuntos
Simulação por Computador , Rim/irrigação sanguínea , Rim/metabolismo , Modelos Biológicos , Natriurese , Circulação Renal , Reabsorção Renal , Sódio/urina , Animais , Dióxido de Carbono/metabolismo , Pressão Hidrostática , Oxigênio/metabolismo , Permeabilidade , Potássio/urina , Ratos , Ureia/metabolismo
19.
Trop Anim Health Prod ; 52(4): 2135-2143, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32086699

RESUMO

This study evaluated the castor bean meal detoxified with calcium hydroxide [Ca(OH)2] added urea replacing soybean meal in the diet of lactating goats from milk production and composition, intake, digestibility, and ingestive behavior. Eight Alpine multiparous goats weighting 44.3 ± 5.3 kg and at approximately 60 days of lactation were confined and randomly distributed in 4 × 4 double Latin squares, with four inclusion levels of detoxified castor meal: control (0), 25, 50, and 75 g/kg dry matter (DM) total. Detoxified castor bean meal replacing soybean meal (P > 0.05) in goats diet did not affect intake and digestibility of DM, crude protein, ether extract, neutral detergent fiber (NDF), total carbohydrates, non-fibrous carbohydrates and total digestible nutrients, times spent for eating, and efficiency ratios of rumination and eating. However, the times spent for rumination and idling showed a quadratic trend decrease (P < 0.01) from the level of 50.0-g/kg DM. The milk production, and the milk production correction showed a quadratic trend increase and feeding efficiency a quadratic decrease (P = 0.03) due inclusion of detoxified castor bean meal replacing soybean meal up to the level of 25.0 g/kg. The fat, protein, lactose, total solids, nonfat solids, and milk urea nitrogen content (g/day) presented a quadratic increase (P < 0.05) by detoxified castor meal inclusion. Detoxified castor bean meal added urea in the Alpine goats diet could be included up to the 25.0 g/kg level replacing soybean meal in the diet because improve milk production and composition and feeding efficiency of goats without negatively effect on intake, digestibility and ingestive behavior.


Assuntos
Semente de Rícino , Dieta/veterinária , Comportamento Alimentar , Leite/metabolismo , Soja , Ureia/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Indústria de Laticínios , Digestão , Feminino , Cabras , Lactação
20.
ACS Appl Mater Interfaces ; 12(5): 6471-6478, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31960674

RESUMO

Dynamic stability and self-healing ability are two inherently compatible properties for living organisms. By contrast, kinetic stability and intrinsic healability are two desired but mostly incompatible properties for synthetic materials. This is because the healing of these materials heavily relies on the kinetic lability of the chemical bonds or physical interactions in materials. Inspired by the hierarchically and temporally controlled wound healing in biological systems, here, we report the intrinsic healing of kinetically stable hydrogels, regulated by the consumption of chemical nutrients. The acylhydrazone-based polymer hydrogels with preinstalled urease and urea were formed at a low initial pH, followed by in situ enzymatic generation of a base to deactivate the dynamic bonds, allowing efficient fabrication of kinetically stable hydrogels. The healing of damaged hydrogels was effective when fed with proper chemical nutrients (i.e., acidic urea solutions), in which case a transient acidic pH state was temporally programmed by combining a fast acidic activator (for structural healing) with the slow, biocatalytic generation of a base (for property recovery). The ability to regulate both hydrogel fabrication and healing via a single enzymatic reaction could provide a new approach to create kinetically stable materials capable of healing damages on demand.


Assuntos
Hidrogéis/química , Concentração de Íons de Hidrogênio , Polímeros/química , Ureia/metabolismo , Urease/metabolismo
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