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1.
Ann Palliat Med ; 10(8): 8939-8951, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488381

RESUMO

BACKGROUND: A systematic review and meta-analysis were conducted to explore the clinical efficacy and coagulation function of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) in critically ill patients, to provide an effective treatment options for CRRT in severe patients. METHODS: The English databases Embase, Medline, PubMed, Ovid, Springer, and Web of Science were searched to screen for randomized controlled trials (RCTs) on RCA in the CRRT treatment of critically ill patients published before June 1, 2020. Meta analysis using the RevMan5.3 provided by the Cochrane collaboration network. The search terms included "citrate anticoagulation", "patient in severe condition", "CRRT", "clinical effect", and "coagulation function". RESULTS: ten articles meeting requirements were included, comprising 1,411 subjects. Meta-analysis results showed that after treatment, total calcium/ionized calcium (totCa/ionCa) [mean difference (MD) =0.05; 95% confidence interval (CI): (-0.02 to 0.12); Z=1.31; P=0.19], prothrombin time [MD =4.51; 95% CI: (2.77, 6.24); Z=5.10; P<0.00001], activated partial thromboplastin time [MD =2.56; 95% CI: (1.17, 3.95); Z=3.61; P=0.0003], and thrombin time [MD =4.22; 95% CI: (2.07, 6.36); Z=3.85; P=0.0001] all increased. However, platelet count [MD =-5.75; 95% CI: (-8.85, -2.64); Z=3.63; P=0.0003], cystatin [MD =-0.39; 95% CI: (-0.63, -0.15); Z=3.22; P=0.001], alanine aminotransferase [MD =-17.63; 95% CI: (-20.09, -15.16); Z=14.02; P<0.00001], aspartate aminotransferase [MD =-6.49; 95% CI: (-11.94, -1.04); Z=2.33; P=0.02], creatinine [MD =-3.70; 95% CI: (-5.08, -2.32); Z=5.24; P<0.00001], and total bilirubin [MD =-3.65; 95% CI: (-5.91, -1.40); Z=3.18; P=0.001] all decreased. Except for totCa/ionCa, the differences in other indicators were not statistically significant compared with the control group. DISCUSSION: RCA can significantly improve the clinical efficacy and blood coagulation indicators of CRRT for severely ill patients.


Assuntos
Terapia de Substituição Renal Contínua , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Citratos/farmacologia , Ácido Cítrico/farmacologia , Ácido Cítrico/uso terapêutico , Humanos , Terapia de Substituição Renal , Resultado do Tratamento
2.
Biochim Biophys Acta Gen Subj ; 1865(9): 129941, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090976

RESUMO

BACKGROUND: The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils. METHODS: Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay. RESULTS: Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between ß-sheets stabilizing the amyloid fibrils. CONCLUSION: COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles. GENERAL SIGNIFICANCE: The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.


Assuntos
Amiloide/antagonistas & inibidores , Citratos/farmacologia , Ácido Cítrico/farmacologia , Goma Arábica/farmacologia , Nanopartículas de Magnetita/química , Muramidase/química , Amiloide/metabolismo , Animais , Células Cultivadas , Galinhas , Citratos/química , Ácido Cítrico/química , Goma Arábica/química , Células HEK293 , Humanos , Tamanho da Partícula , Agregados Proteicos/efeitos dos fármacos , Propriedades de Superfície
3.
Biol Pharm Bull ; 44(6): 844-852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34078817

RESUMO

Acidic extracellular pH (pHe) is characteristic of the tumor microenvironment. Several reports suggest that increasing pHe improves the response of immune checkpoint inhibitors in murine models. To increase pHe, either sodium bicarbonate (NaHCO3) or citric acid/potassium-sodium citrate (KNa-cit) was chronically administered to mice. It is hypothesized that bicarbonate ions (HCO3-), produced from these alkalinizing agents in vivo, increased pHe in the tumor, and excess HCO3- eliminated into urine increased urinary pH values. However, there is little published information on the effect of changing serum HCO3- concentrations, urinary HCO3- concentrations and urinary pH values on the therapeutic outcomes of immunotherapy. In this study, we report that oral administration of either NaHCO3 or KNa-cit increased responses to anti-programmed cell death-1 (PD-1) antibody, an immune checkpoint inhibitor, in a murine B16 melanoma model. In addition, we report that daily oral administration of an alkalinizing agent increased blood HCO3- concentrations, corresponding to increasing the tumor pHe. Serum HCO3- concentrations also correlated with urinary HCO3- concentrations and urinary pH values. There was a clear relationship between urinary pH values and the antitumor effects of immunotherapy with anti-PD-1 antibody. Our results imply that blood HCO3- concentrations, corresponding to tumor pHe and urinary pH values, may be important factors that predict the clinical outcomes of an immunotherapeutic agent, when combined with alkalinizing agents such as NaHCO3 and KNa-cit.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bicarbonatos/uso terapêutico , Citratos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Administração Oral , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Bicarbonatos/sangue , Bicarbonatos/farmacologia , Linhagem Celular Tumoral , Citratos/farmacologia , Feminino , Concentração de Íons de Hidrogênio , Inibidores de Checkpoint Imunológico/farmacologia , Linfócitos/imunologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/química , Neoplasias/imunologia , Neoplasias/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Macrófagos Associados a Tumor/imunologia , Urina/química
4.
J Trace Elem Med Biol ; 66: 126763, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33915410

RESUMO

BACKGROUND: The paper presents a study on the influence of different lithium carbonate and lithium citrate concentration on proteolytic enzymes, namely pepsin and trypsin, in vitro. Lithium can directly affect enzyme activity. Its influence on many bodily functions in both ill and healthy people has been proven. METHODS: To assess the influence of Li+ ions concentration and the substrate/enzyme ratio on pepsin and trypsin activity in vitro, 60 factorial experiments were conducted (each repeated 30 times). MAIN FINDINGS: For both enzymes, statistically significant changes in their activity under the influence of lihium carbonate and lithium citrate were observed. The biggest increase in enzyme activity reached even 198.6 % and the largest decrease in enzyme activity reached about 50 %. CONCLUSIONS: The study shows that both organic and inorganic forms of lithium salts cause changes in the activity of digestive enzymes. Different concentrations of lithium carbonate and lithium citrate stimulate or inhibit the activity of trypsin and pepsin.


Assuntos
Citratos/farmacologia , Inibidores Enzimáticos/farmacologia , Carbonato de Lítio/farmacologia , Pepsina A/antagonistas & inibidores , Tripsina/metabolismo , Relação Dose-Resposta a Droga , Humanos , Íons/farmacologia , Pepsina A/metabolismo
5.
J Vet Emerg Crit Care (San Antonio) ; 31(2): 269-273, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33709630

RESUMO

OBJECTIVE: The objective of this study was to evaluate the biochemical and blood gas alterations of whole blood of buffaloes that was stored in citrate-phosphate-dextrose with adenine (CPDA-1) and CPD/SAG-M blood bags for 42 days. DESIGN: Prospective study. INTERVENTIONS: Ten male buffaloes were used in this study. A total volume of 900 mL of blood was collected from each buffalo so that 450 mL was stored in CPDA-1 and 450 mL was stored in CPD/SAG-M bags at 2-6°C for 42 days. The stored blood was evaluated at 7 time points (D): D0 (immediately after blood collection) and 7 (D7), 14 (D14), 21 (D21), 28 (D28), 35 (D35), and 42 (D42) days after collection. Blood gas, biochemical, and microbiological parameters were monitored. MEASUREMENTS AND MAIN RESULTS: The overall blood pH decreased from 6.997 ± 0.05 at D0 to 6.784 ± 0.09 at D42, differing from baseline from D14 onward (P < 0.05). There were increases in partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), lactate, and potassium (K) and decreases in the concentrations of sodium, bicarbonate, glucose, and pH (P < 0.05) during storage in both bags but no alterations in total protein concentration. Most of the variables were consistently similar between the 2 types of blood bags (P > 0.05) evaluated, with the exception of pCO2 , HCO3, cholesterol, and total protein, which had higher values in the CPDA-1 bag (P < 0.05). The K, pO2 , and lactate had the highest alterations during storage, with increases from baseline to D42 of 563%, 317%, and 169%, respectively. CONCLUSION: In general, no significant changes of clinical importance were observed after storage of whole blood samples from buffaloes for 42 days in the 2 types of blood bags that are indicated for use with this species.


Assuntos
Anticoagulantes/farmacologia , Preservação de Sangue/veterinária , Búfalos/sangue , Citratos/farmacologia , Glucose/farmacologia , Adenina , Animais , Anticoagulantes/química , Citratos/química , Eritrócitos , Glucose/química , Masculino , Fosfatos , Potássio/sangue , Estudos Prospectivos
7.
Pak J Biol Sci ; 24(1): 19-24, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33683027

RESUMO

BACKGROUND AND OBJECTIVE: Sessiline ciliates live as eco commensals (low numbers) and parasites (high numbers) on different hosts, like mollusks copepods, mysids and fish. Riboscyphidia ecto-protozoan is moderately pathogenic but high numbers of it on the gills can physically prevent gas exchange. The present study aimed to describe the epizoic ciliates Riboscyphidia found on the Red Sea cultured Asian sea bass and obtain more information on the Epidemiology of the parasite with special references to control and histopathological examination of naturally infected sea bass. MATERIALS AND METHODS: The occurrence of epizoic ciliates on the adult Asian Sea bass. About 100 Asian sea bass were collected by the fishing net at a private marine fish farm at Ismailia governorate and transferred to the hydrobiology laboratory at National Research Centre. A parasitological and histopathological study of epizoic sessile ciliate species was done. ANOVA test was used for Statistical analysis. RESULTS: Riboscyphidia sp. was found and isolated after parasitological examination of investigated adult's Asian sea bass. The prevalence of Riboscyphidiosis was 64%. Sessile ciliates were found on gills, skin and fins. The clinical signs of Riboscyphidiosis were respiratory distress, flashing and off food. Histopathological alterations in naturally infested Asian sea bass were investigated. CONCLUSION: The treatment of choice of Riboscyphidiosis was prolonged immersion by Copper citrate with a dose of 0.56 mg mL-1 for 7 days.


Assuntos
Antiprotozoários/farmacologia , Aquicultura , Bass/parasitologia , Citratos/farmacologia , Doenças dos Peixes/tratamento farmacológico , Infecções Protozoárias em Animais/tratamento farmacológico , Animais , Doenças dos Peixes/parasitologia , Oceano Índico , Infecções Protozoárias em Animais/parasitologia
8.
Nutrients ; 13(2)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499382

RESUMO

The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms.


Assuntos
Garcinia mangostana/química , Síndrome Metabólica/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Xantonas/farmacologia , Animais , Antocianinas/farmacologia , Citratos/farmacologia , Cor , Dieta , Suplementos Nutricionais , Frutas/química , Masculino , Síndrome Metabólica/patologia , Obesidade/complicações , Proantocianidinas/farmacologia , Ratos , Ratos Wistar
9.
J Agric Food Chem ; 68(40): 11229-11241, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32940033

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most complex liver diseases in the world, which is characterized by hepatic steatosis, oxidative stress, inflammation, and apoptosis. (-)-Hydroxycitric acid [(-)-HCA] can regulate obesity in different animals, while whether this beneficial effect of (-)-HCA can alleviate the NAFLD and its mechanism is unclear. Hence, this study aimed to determine the potential actions and mechanisms of (-)-HCA on NAFLD in oleic acid (OA)-induced hepatocytes. We found that (-)-HCA effectively improved OA-induced hepatic steatosis by regulating the expression level of fat metabolism key factors, which was achieved by activating AMP-activated protein kinase (AMPK) signaling in hepatocytes. Importantly, activated AMPK alleviates mitochondrial disorder via the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)-nuclear transcription factor 1 (NRF-1)-mitochondrial transcription factor A (TFAM) pathway, then reduces reactive oxygen species production, and blocks the activation of p38 MAPK-NF-κB pathway in OA-induced hepatocytes. These results not only provide a theoretical basis for the occurrence and development of NAFLD but also offer compelling evidence for prevention of NAFLD supplemental with (-)-HCA.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Citratos/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Galinhas , Hepatócitos/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
10.
AAPS PharmSciTech ; 21(7): 243, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32856144

RESUMO

The objective of this work was to develop taste-masked donut-shaped tablet formulations utilizing fused filament fabrication three-dimensional printing paired with hot-melt extrusion techniques. Caffeine citrate was used as the model drug for its bitter taste, and a 3-point bend test was performed to assess the printability of filaments. The stiffness constant was calculated to represent the printability by fitting the breaking distances and stress data into Hooke's law. The formulations without Eudragit E PO (F6) and with Eudragit E PO (F7) filaments exhibited the desired hardness with a "k" value of 48.30 ± 3.52 and 45.47 ± 3.51 g/mm3 (n = 10), respectively, and were successfully printed. The donut-shaped tablets were 3D printed with 10, 50, and 100% infill densities. In vitro dissolution studies were performed in simulated salivary fluid (pH 6.8, artificial saliva) to evaluate the taste-masking efficiency of the printed donuts. In the first minute, the concentrations of caffeine citrate observed in the dissolution media from all the printed donuts were less than the bitter threshold of caffeine citrate (0.25 mg/mL). Formulation F7, which contained Eudragit E PO copolymer, demonstrated better taste-masking efficiency than formulation F6. Furthermore, both formulations F6 and F7 demonstrated immediate drug release profiles in gastric medium (10% infill, > 80% release within 1 h). Taste-masked caffeine citrate formulations were successfully developed with donut shapes, which will enhance appeal in pediatric populations and increase compliance and patient acceptance of the dosage form.


Assuntos
Composição de Medicamentos/métodos , Tecnologia de Extrusão por Fusão a Quente/métodos , Impressão Tridimensional , Paladar/efeitos dos fármacos , Cafeína/química , Cafeína/farmacologia , Citratos/química , Citratos/farmacologia , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Excipientes/química , Excipientes/farmacologia , Humanos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Comprimidos , Paladar/fisiologia
11.
J Neuroinflammation ; 17(1): 200, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611425

RESUMO

BACKGROUND: Astrocytes are crucial regulators in the central nervous system. Abnormal activation of astrocytes contributes to some behavior deficits. However, mechanisms underlying the effects remain unclear. Here, we studied the activation of A1 astrocytes and their contribution to murine behavior deficits. METHODS: A1 astrocytes were induced by treatment with lipopolysaccharide (LPS) in vitro. The functional phenotype of astrocytes was determined by quantitative RT-PCR, ELISA, and immunohistochemistry. To assess the role of A1 astrocytes in vivo, mice were injected intraperitoneally with LPS. Then, murine behaviors were tested, and the hippocampus and cortex were analyzed by quantitative RT-PCR, ELISA, and immunohistochemistry. The function of IL-10 and fluorocitrate on A1 astrocyte activation was also examined. RESULTS: Our results show that astrocytes isolated from B6.129S6-Il10tm1Flv/J homozygotes (IL-10tm1/tm1) were prone to characteristics of A1 reactive astrocytes. Compared with their wild-type counterparts, IL-10tm1/tm1 astrocytes exhibited higher expression of glial fibrillary acidic protein (GFAP). Whether or not they were stimulated with LPS, IL-10tm1/tm1 astrocytes exhibited enhanced expression of A1-specific transcripts and proinflammatory factors IL-1ß, IL-6, and TNFα. In addition, IL-10tm1/tm1 astrocytes demonstrated hyperphosphorylation of STAT3. Moreover, astrocytes from IL-10tm1/tm1 mice showed attenuated phagocytic ability and were neurotoxic. IL-10tm1/tm1 mice demonstrated increased immobility time in the forced swim test and defective learning and memory behavior in the Morris water maze test. Moreover, enhanced neuroinflammation was found in the hippocampus and cortex of IL-10tm1/tm1 mice, accompanying with more GFAP-positive astrocytes and severe neuron loss in the hippocampus. Pretreatment IL-10tm1/tm1 mice with IL-10 or fluorocitrate decreased the expression of proinflammatory factors and A1-specific transcripts in the hippocampus and cortex, and then alleviated LPS-induced depressive-like behavior. CONCLUSION: These results demonstrate that astrocytes isolated from B6.129S6-Il10tm1Flv/J homozygotes are prone to A1 phenotype and contribute to the depression-like behavior and memory deficits. Inhibiting A1 astrocyte activation may be an attractive therapeutic strategy in some neurodegenerative diseases.


Assuntos
Astrócitos/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Citratos/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Depressão/tratamento farmacológico , Interleucina-10/farmacologia , Animais , Astrócitos/metabolismo , Comportamento Animal/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Citratos/uso terapêutico , Disfunção Cognitiva/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Interleucina-10/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos
12.
Apoptosis ; 25(9-10): 686-696, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666259

RESUMO

Caloric restriction mimetics (CRMs) are promising molecules to prevent age-related diseases as they activate pathways driven by a true caloric restriction. Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy. Importantly, it can reduce inflammation and tumour development. In order to identify phenotypically relevant new HCA targets we have investigated HCA effects in Saccharomyces cerevisiae, where ACLY is lacking. Strikingly, the drug revealed a powerful anti-aging effect, another property proposed to mark bona fide CRMs. Chronological life span (CLS) extension but also resistance to acetic acid of HCA treated cells were associated to repression of cell apoptosis and necrosis. HCA also largely prevented cell deaths caused by a severe oxidative stress. The molecule could act widely by negatively modulating cell metabolism, similarly to citrate. Indeed, it inhibited both growth reactivation and the oxygen consumption rate of yeast cells in stationary phase. Genetic analyses on yeast CLS mutants indicated that part of the HCA effects can be sensed by Sch9 and Ras2, two conserved key regulators of nutritional and stress signal pathways of primary importance. Our data together with published biochemical analyses indicate that HCA may act with multiple mechanisms together with ACLY repression and allowed us to propose an integrated mechanistic model as a basis for future investigations.


Assuntos
ATP Citrato (pro-S)-Liase/genética , Envelhecimento/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Citratos/farmacologia , Envelhecimento/genética , Apoptose/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética
13.
Eur Rev Med Pharmacol Sci ; 24(11): 6434-6445, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32572941

RESUMO

OBJECTIVE: Kidney stone formers have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication for treatment. Hydroxycitric acid (HCA), which is the major component of Garcinia cambogia extract, can dissolve calcium oxalate crystals in vitro, suggesting that Garcinia cambogia could be used to treat calcium oxalate kidney stone. In this study, we used the Drosophila kidney disease model to evaluate the effect of Garcinia cambogia on the prevention and removal of calcium oxalate stones in vivo. MATERIALS AND METHODS: Flies were reared in fly food containing different concentrations of GCE for one week. The effect of GCE on preventing the formation of calcium oxalate stone was examined. WT and v-ATPase gene RNAi knockdown flies were reared in fly food with 0.3% NaOx for one week, then fed different concentrations of GCE for one week. The effect of GCE on the removal of calcium oxalate stone was examined. RESULTS: Garcinia cambogia extract dissolves calcium oxalate crystals from Malpighian tubules in both genetic and non-genetic Drosophila kidney stone models compared to citric acid. Hydroxycitric acid also directly dissolves calcium oxalate crystals in Drosophila Malpighian tubules ex vivo. CONCLUSIONS: Garcinia cambogia extract removes calcium oxalate kidney stones from Drosophila Malpighian tubules via directly dissolving calcium oxalate stones by HCA. Our study strongly suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.


Assuntos
Oxalato de Cálcio/química , Citratos/farmacologia , Garcinia cambogia/química , Cálculos Renais/tratamento farmacológico , Túbulos Renais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Oxalato de Cálcio/isolamento & purificação , Citratos/química , Citratos/isolamento & purificação , Cristalização , Modelos Animais de Doenças , Drosophila , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
14.
Vet Clin Pathol ; 49(2): 198-206, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32542780

RESUMO

BACKGROUND: Canine packed red blood cells (pRBCs) can be stored under refrigeration for several days; however, cellular metabolism remains active inside the units, thus producing substances that affect their quality. OBJECTIVES: We aimed to evaluate hematologic, biochemical, and blood gas variable alterations that occur in canine pRBCs during storage, and their effects on recipient clinicopathologic parameters. METHODS: The study was conducted in two phases. In phase I, 15 pRBC units containing CPDA-1 were stored for 28 days; samples were collected weekly from the units of days 0 to 28 to measure the packed cell volume (PCV), pH, partial pressure carbon dioxide (PCO2 ), partial pressure oxygen (PO2 ), concentrations of lactate and potassium, and the percent hemolysis. In phase II, another 22 canine pRBC units stored for different time periods (maximum of 21 days) were transfused, and the recipients were evaluated before and after transfusion for changes in clinical parameters (heart rate, respiratory rate, systolic arterial pressure, and rectal temperature) and hematologic variables (PCV, lactate and potassium concentrations, pH, PCO2 , the ratio of arterial oxygen partial pressure to fractional inspired oxygen [PO2 /FiO2 ] ratio, oxygen saturation [SaO2 ], base excess, and bicarbonate [HCO3 ]). RESULTS: In the pRBC units, the PCV increased from 70% to 78.33%, the lactate concentration increased 627%, the potassium concentration increased 183%, the percent hemolysis reached 0.69%, and the pH decreased 9% after 28 days. However, the dogs who received transfusions were not negatively affected. There was a significant increase in PCVs, and a significant decrease in heart rates. CONCLUSION: Canine pRBCs undergo hematologic, blood gas, and biochemical alterations during storage; however, the transfusion of pRBCs stored for up to 21 days increased PCVs without causing harm to the dogs.


Assuntos
Adenina/farmacologia , Anticoagulantes/farmacologia , Citratos/farmacologia , Cães/sangue , Glucose/farmacologia , Fosfatos/farmacologia , Manejo de Espécimes/veterinária , Animais , Análise Química do Sangue/veterinária , Gasometria/veterinária , Preservação de Sangue/veterinária , Eritrócitos/metabolismo , Hematócrito/veterinária , Testes Hematológicos/veterinária , Hemólise , Ácido Láctico/sangue , Potássio/sangue , Embalagem de Produtos , Fatores de Tempo
15.
Biomed Pharmacother ; 127: 110187, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361638

RESUMO

Increasing evidence suggests that activation of satellite glia cells (SGCs) in sensory ganglia play important roles in the development of neuropathic pain. The present study aimed to investigate the involvement of SGC activation in a novel model of motor nerve injury induced pain hypersensitivity. The neuropathic pain model was established by cervical 8 ventral root avulsion (C8VA). Glial fibrillary acidic protein (GFAP) was used as a marker of SGC activation. Unilateral C8VA resulted in mechanical allodynia, but not thermal hyperalgesia in bilateral paws. Expectedly, SGCs were robustly activated on as early as 1 day and persisted for at least 7 days in the ipsilateral and contralateral dorsal root ganglia (DRG) of C6, C7 and C8 after C8VA. Double immunofluorescence showed that almost all the activated SGCs enveloped neurofilament 200 (NF200) positive myelinated neurons in DRG. Local application of fluorocitrate (FC), a glial metabolism inhibitor, significantly decreased the number of activated SGCs and alleviated bilateral mechanical allodynia. These results suggest that SGC activation contributed to ipsilateral and mirror-image pain hypersensitivity after C8VA. Inhibition of SGC activation represented a promising therapeutic strategy for the management of neuropathic pain following brachial plexus root avulsion.


Assuntos
Hiperalgesia/fisiopatologia , Neurônios Motores/patologia , Neuralgia/fisiopatologia , Células Satélites Perineuronais/metabolismo , Animais , Citratos/farmacologia , Modelos Animais de Doenças , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/etiologia , Masculino , Proteínas de Neurofilamentos/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Pharmacol Res Perspect ; 8(3): e00596, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32412185

RESUMO

Caffeine is widely used in preterm neonates suffering from apnea of prematurity (AOP), and it has become one of the most frequently prescribed medications in neonatal intensive care units. Goal of this study is to investigate how caffeine citrate treatment affects sleep-wake behavior in preterm neonates. The observational study consists of 64 preterm neonates during their first 5 days of life with gestational age (GA) <32 weeks or very low birthweight of < 1500 g. A total of 52 patients treated with caffeine citrate and 12 patients without caffeine citrate were included. Sleep-wake behavior was scored in three stages: active sleep, quiet sleep, and wakefulness. Individual caffeine concentration of every neonate was simulated with a pharmacokinetic model. In neonates with GA ≥ 28 weeks, wakefulness increased and active sleep decreased with increasing caffeine concentrations, whereas quiet sleep remained unchanged. In neonates with GA < 28 weeks, no clear caffeine effects on sleep-wake behavior could be demonstrated. Caffeine increases fraction of wakefulness, alertness, and most probably also arousability at cost of active but not quiet sleep in preterm neonates. As such, caffeine should therefore not affect time for physical and cerebral regeneration during sleep in preterm neonates.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Citratos/farmacologia , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacocinética , Citratos/administração & dosagem , Citratos/farmacocinética , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Modelos Biológicos
17.
Life Sci ; 254: 117785, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32416167

RESUMO

As the most important bioactive substance in Garcinia cambogia, (-)-hydroxycitric acid (HCA) is widely used in food additives to regulate obesity and diabetes in animals or humans, while the mechanism is poorly understood. The purpose of this study was to elucidate the regulatory effect and mechanism of (-)-HCA in regulating glucose and lipid metabolism in chicken primary hepatocytes. The results showed that (-)-HCA obviously decreased triglyceride content through inhibiting the fatty acid synthase protein level, and enhancing the protein level of phosphorylated acetyl CoA carboxylase, enoyl coenzyme A hydratase short chain 1 and carnitine palmitoyltransferase 1A in hepatocytes. Moreover, (-)-HCA markedly enhanced the protein level of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase A and complex IV, and which led to the enhancing of glucose uptake and catabolism in hepatocytes. Importantly, the regulation of (-)-HCA on these key factors associated with lipid and glucose metabolism in hepatocytes was mainly achieved through activation of AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α-nuclear respiratory factor 1 signaling pathway. These results convincingly demonstrated the mechanism of (-)-HCA's regulating on glucose and lipid metabolism, and provided a strategy in prevention of diseases associated with glycolipid metabolic abnormalities in animals, even in humans.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Citratos/farmacologia , Metabolismo Energético/fisiologia , Hepatócitos/metabolismo , Fator 1 Relacionado a NF-E2/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Galinhas , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Enoil-CoA Hidratase/metabolismo , Glucose/metabolismo , Fosfofrutoquinase-1/metabolismo , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Piruvato Desidrogenase (Lipoamida)/metabolismo , Transdução de Sinais/fisiologia , Succinato Desidrogenase/metabolismo , Triglicerídeos/metabolismo
18.
Cells ; 9(5)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32443525

RESUMO

The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100ß, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1ß (IL-1ß), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1ß, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1ß, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.


Assuntos
Sistema Nervoso Entérico/patologia , Inflamação/patologia , Neuroglia/metabolismo , Obesidade/patologia , Receptor A2B de Adenosina/metabolismo , Taquicininas/metabolismo , Acetamidas/farmacologia , Aminopiridinas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Citratos/farmacologia , Dieta Hiperlipídica , Comportamento Alimentar/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Modelos Biológicos , Fatores de Crescimento Neural/metabolismo , Neuroglia/efeitos dos fármacos , Ácido Palmítico/farmacologia , Purinas/farmacologia , Proteínas S100/metabolismo , Substância P/metabolismo , Receptor 4 Toll-Like/metabolismo
19.
Steroids ; 160: 108656, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32439410

RESUMO

Hydroxycitric acid (HCA), a dietary-derived weight loss supplement, competitively inhibits ATP citrate lyase (ACLY). Tamoxifen (TAM) is the most frequently used therapy for estrogen receptor (ER)-positive breast cancer patients, but its application was restricted due to efficacy related issues. Lipid metabolic reprogramming plays a key role in cancer progression and response to treatment. This study will test the hypothesis that targeting lipid metabolic enzymes could enhance TAM effect against breast cancer cells. MCF-7 ER-positive breast cancer cell line was used, and the cytotoxic effect of TAM treatment, alone and in combination with HCA was evaluated. Flowcytometric analysis of apoptosis following TAM and/or HCA treatment was additionally performed. Besides, the effects of TAM and/or HCA on ACLY, acetyl CoA carboxylase alpha (ACC-α) and fatty acid synthase (FAS) expression were investigated. Likewise, expression of ER-α protein through TAM and/or HCA treatment was examined. Cell contents of cholesterol and triglyceride were quantified. Treatment with TAM or HCA significantly reduced cell viability in a concentration-dependent manner whereas co-treatment synergistically reduced cell viability, promoted apoptosis, and decreased the expression of ACLY, ACC-α, and FAS. Intracellular triglyceride and cholesterol were accumulated in response to treatment with TAM and/or HCA. Moreover, either solitary TAM or TAM/ HCA co-treatment increased ER-α protein levels non significantly. Our results revealed that TAM effects on breast cancer are mediated, in part, through the regulation of key genes involved in lipid metabolism. Accordingly, inhibition of ACLY by HCA might be beneficial to enhance the therapeutic index of TAM against breast cancer.


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Citratos/farmacologia , Inibidores Enzimáticos/farmacologia , Tamoxifeno/farmacologia , ATP Citrato (pro-S)-Liase/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade
20.
Artigo em Inglês | MEDLINE | ID: mdl-32229663

RESUMO

Background The aim of this study was to evaluate the antioxidant activity and to determine the chemical compounds of organic extracts of fruits and leaves of Zizyphus lotus. The litholytic effect was determined on the basis of the in vitro effect of the aqueous extracts on the formation of crystals of stones. Finally, chemical compounds were investigated to identify their target using an in silico approach. Methods The antioxidant activity was determined with the diphenylpicrylhydrazyl radical trapping method. An aliquot of 2 mL of urine and 100 µL of an infusion of fruit and leaf aqueous extract of Z. lotus at different concentrations were used. The induction of calcium oxalate (CaOx) crystals was done by the addition of oxalic acid at 0.1 mol/L. The effect of aqueous extracts was compared with two inhibitors (citrate and magnesium) used as references. In silico modelization was carried out using SwissTargetPrediction. Results The antioxidant activity test showed that the methanol extract was active with an IC50 of 5 mg/mL. The aqueous extracts of fruits and leaves inhibit the formation of crystals of CaOx. Then, the composition of the methanol extracts of the leaves and fruits in high-performance liquid chromatography showed majority compounds such as quercetin-3-galactoside and hyperin. In silico assays showed that the identified molecules exert their effect by targeting enzymes responsible for calcium regulation, urate regulation, and maintenance of acid-base balance, and that had anti-inflammatory properties. Conclusions The present study showed that Z. lotus may be considered as a functional or nutraceutical food. However, further studies should be carried out in order to extract and purify these compounds to test their effect on urinary lithiasis.


Assuntos
Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Quercetina/química , Ziziphus/química , Antioxidantes/química , Oxalato de Cálcio/química , Citratos/farmacologia , Simulação por Computador , Cristalização , Relação Dose-Resposta a Droga , Frutas/química , Magnésio/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/farmacologia , Urina/química
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