RESUMO
Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.
Assuntos
Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Garcinia cambogia , Obesidade/terapia , Extratos Vegetais/administração & dosagem , Animais , Fármacos Antiobesidade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citratos/administração & dosagem , Citratos/efeitos adversos , Humanos , Mania/induzido quimicamente , Extratos Vegetais/efeitos adversos , Serotonina/metabolismo , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. METHODS: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. RESULTS: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.
Assuntos
Citratos/administração & dosagem , Garcinia cambogia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Degeneração Macular/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Citratos/química , Citratos/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Degeneração Macular/etiologia , Degeneração Macular/genética , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resultado do TratamentoRESUMO
Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.
Assuntos
Citrato de Cálcio/metabolismo , Citratos/administração & dosagem , Suplementos Nutricionais , Cálculos Renais/dietoterapia , Citrato de Cálcio/química , Humanos , Cálculos Renais/química , Cálculos Renais/urina , Eliminação Renal/efeitos dos fármacosRESUMO
This study aimed to evaluate the hepatoprotective effect of whey protein nanoparticles (WP-NPs) coated Zinc citrate (Zn) against oxidative stress complications and disturbances in gene expression in rats treated with CCl4. WP-NPs were used to coat Zn at three levels and amino acids content was determined in WP-NPs and the fabrications. Seven groups of male albino rats included the control group, CCl4-treated group (0.5 ml/100â¯g b.w) and the groups treated with CCl4 plus WP-NPs, Zn and the three Zn-WP-NPs fabrications. Blood and liver samples were collected for different analysis. Particles sizes were 95, 142, 196 and 228â¯nm and zeta potential values were -95, -114, -85 and -79 for WP-NPs and the three Zn-WP-NPs fabrications, respectively. Twelve amino acids were found in WP-NPs and this number was decreased by increasing Zn content. WP-NPs, Zn and the Zn coated WP-NPs counteracted the disturbances in biochemical, parameters, gene expression and histological changes in CCl4-treated rats and Zn-WP-NPs was more effective at the low dose. It could be concluded that WP-NPs enhance the effect of Zn and can be used for coating Zn in the preparation of Zn supplementation to enhance its effect and counteract the side effect of excess Zn.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Proteínas do Soro do Leite/química , Compostos de Zinco/farmacologia , Administração Oral , Animais , Tetracloreto de Carbono/efeitos adversos , Citratos/administração & dosagem , Citratos/farmacologia , Portadores de Fármacos/química , Fibrose , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho da Partícula , Ratos Wistar , Compostos de Zinco/administração & dosagemRESUMO
OBJECTIVE: Evaluate whether saliva could be a useful alternative to serum for routine therapeutic drug monitoring of caffeine in preterm infants using the enzyme multiplied immunoassay technique (EMIT) assay. METHODS: We conducted a prospective study including preterm infants (less than 34 weeks' amenorrhea) admitted to the intensive care and neonatal medicine department. All infants received 5, 10, 15, 20 and 25mg/kg/day of citrate caffeine intravenously from the first to the fifth day of birth, respectively. For each patient, two concomitant blood and saliva samples corresponding to the trough concentrations were collected 24hours after each caffeine dose. The caffeine concentrations were determined using the EMIT®2000 caffeine assay. RESULTS: Thirteen preterm infants were included. The saliva and the serum caffeine concentration increased proportionally to the administered dose. Saliva and serum kinetics were comparable and the saliva caffeine concentrations were correlated to the serum ones (r2=0.76). CONCLUSION: Saliva caffeine monitoring by EMIT is a valid, useful and safe alternative to serum in preterm infants.
Assuntos
Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Citratos/farmacocinética , Monitoramento de Medicamentos/métodos , Técnica de Imunoensaio Enzimático de Multiplicação , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Citratos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Saliva/químicaRESUMO
Numerous food supplements contain phytochemical compounds as active ingredients. Although such supplements are often perceived by consumers as being risk-free, the safety of many of them is currently uncertain. The present review provides two examples for risk assessment for phytochemical ingredients that are used in certain supplements marketed for sportspeople-synephrine (extracted from fruits of Citrus aurantium) and hydroxycitric acid (HCA, isolated from fruits of Garcinia cambogia). Animal and human studies, as well as case reports, provide evidence for cardiovascular effects due to ingestion of high synephrine doses, especially in combination with caffeine and physical exertion. A dose of up to 6.7 mg synephrine/day, however, which is equivalent to the median dietary intake from conventional foods in Germany, is presumed to represent a safe intake from supplements. In subchronic animal studies, administration of high doses of certain HCA-containing preparations led to testicular toxicity (i.e., testicular atrophy and impaired spermatogenesis), yielding a no observed adverse effect level of 389 mg HCA/kg bw/day. In view of lack of adequate human data on the safety of HCA preparations, particularly with respect to the human male reproductive system, substantial uncertainties exist regarding the safety of supplements containing high amounts of HCA.
Assuntos
Citratos/efeitos adversos , Compostos Fitoquímicos/efeitos adversos , Fenômenos Fisiológicos da Nutrição Esportiva , Sinefrina/efeitos adversos , Animais , Citratos/administração & dosagem , Citrus/química , Suplementos Nutricionais , Modelos Animais de Doenças , Frutas , Humanos , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de RiscoRESUMO
AIM: The aim of this review is to provide an overview of the clinical assessment and evidence-based treatment options for managing diabetes-associated chronic constipation. METHODS: A literature search of published medical reports in English language was performed using the OVID Portal, from PUBMED and the Cochrane Database of Systematic Reviews, from inception to October 2015. A total of 145 abstracts were identified; duplicate publications were removed and 95 relevant full-text articles were retrieved for potential inclusion. RESULTS: Chronic constipation is one of the most common gastrointestinal symptoms in patients with diabetes, and occurs more frequently than in healthy individuals. Treatment goals include improving symptoms and restoring bowel function by accelerating colonic transit and facilitating defecation. Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor. Lactulose, polyethylene glycol and lactitol are the most frequently prescribed osmotic agents. Lactulose has a prebiotic effect and a carry-over effect (continued laxative effect for at least 6 to 7 days, post cessation of treatment). Stimulants such as bisacodyl, sodium picosulphate and senna are indicated if osmotic laxatives are not effective. Newer agents such as chloride-channel activators and 5-HT4 agonist can be considered for severe or resistant cases. CONCLUSION: The primary aim of intervention in diabetic patients with chronic constipation is to better manage the diabetes along with management of constipation. The physician should explain the rationale for prescribing laxatives and educate patients about the potential drawbacks of long-term use of laxatives. They should contact their physician if short-term use of prescribed laxative fails to provide relief.
Assuntos
Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Complicações do Diabetes/complicações , Bisacodil/administração & dosagem , Agonistas dos Canais de Cloreto/administração & dosagem , Doença Crônica , Citratos/administração & dosagem , Fibras na Dieta/administração & dosagem , Medicina Baseada em Evidências , Terapia por Exercício , Estilo de Vida Saudável , Humanos , Laxantes/administração & dosagem , Metilcelulose/administração & dosagem , Compostos Organometálicos/administração & dosagem , Picolinas/administração & dosagem , Psyllium/administração & dosagem , Extrato de Senna/administração & dosagem , Agonistas do Receptor 5-HT4 de Serotonina/administração & dosagemRESUMO
Athletes make great efforts to increase their endurance capacity in many ways. Using nutrition supplements for stimulating lipolysis is one such strategy to improve endurance performance. These supplements contain certain ingredients that affect fat metabolism; furthermore, in combination with endurance training, they tend to have additive effects. A large body of scientific evidence shows that nutrition supplements increase fat metabolism; however, the usefulness of lipolytic supplements as ergogenic functional foods remains controversial. The present review will describe the effectiveness of lipolytic supplements in fat metabolism and as an ergogenic aid for increasing endurance exercise capacity. There are a number of lipolytic supplements available on the market, but this review focuses on natural ingredients such as caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptides and octacosanol, all of which have shown scientific evidence of enhancing fat metabolism associated with improving endurance performance. We excluded some other supplements owing to lack of data on fat metabolism or endurance capacity. Based on the data in this review, we suggest that a caffeine and green tea extract improves endurance performance and enhances fat oxidation. Regarding other supplements, the data on their practical implications needs to be gathered, especially for athletes.
Assuntos
Suplementos Nutricionais , Lipólise/fisiologia , Resistência Física/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Cafeína/administração & dosagem , Capsaicina/administração & dosagem , Carnitina/administração & dosagem , Citratos/administração & dosagem , Gorduras na Dieta/metabolismo , Exercício Físico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Oxirredução , Panax , Extratos Vegetais/administração & dosagem , Taurina/administração & dosagem , Chá/químicaRESUMO
BACKGROUND: Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability. OBJECTIVE: We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains. DESIGN: We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios. RESULTS: Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice. CONCLUSIONS: Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759.
Assuntos
Citratos/análise , Ácido Cítrico/análise , Difosfatos/análise , Alimentos Fortificados , Ferro/farmacocinética , Oryza/química , Adolescente , Adulto , Disponibilidade Biológica , Índice de Massa Corporal , Peso Corporal , Proteína C-Reativa/metabolismo , Citratos/administração & dosagem , Ácido Cítrico/administração & dosagem , Culinária , Estudos Cross-Over , Difosfatos/administração & dosagem , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Humanos , Ferro/administração & dosagem , Ferro/análise , Ferro/sangue , Ferro da Dieta/administração & dosagem , Estado Nutricional , Método Simples-Cego , Adulto JovemRESUMO
OBJECTIVE: Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and lowers postprandial glycemia in rodents, but its effect in humans is unknown. The aim of this study was to investigate the effects of small intestinal perfusion with HCA on glucose absorption, as well as the incretin and glycemic responses to a subsequent intraduodenal glucose infusion, in both healthy individuals and patients with type 2 diabetes. METHODS: Twelve healthy participants and 8 patients with type 2 diabetes received an intraduodenal infusion of HCA (2800 mg in water) or control (water) over 60 min, followed by an intraduodenal infusion of 60 g glucose over 120 min, in a double-blind, randomized crossover design. In healthy individuals, 5 g 3-O-methylglucose (3-OMG) was co-infused with glucose as a marker of glucose absorption. Blood was sampled frequently. RESULTS: In healthy individuals, blood glucose was lower with HCA than control, both before and during the intraduodenal glucose infusion (P < 0.05 for each). Plasma glucose-dependent insulinotropic polypeptide (GIP; P = 0.01) and glucagon (P = 0.06) were higher with HCA, but there were no differences in plasma glucagon-like peptide (GLP)-1, insulin, or serum 3-OMG concentrations. In patients with type 2 diabetes, blood glucose, and plasma GIP, GLP-1, and insulin did not differ between HCA and control either before or after intraduodenal glucose, but during glucose infusion, plasma glucagon was higher with HCA (P = 0.04). CONCLUSION: In healthy individuals, small intestinal exposure to HCA resulted in a modest reduction in glycemia and stimulation of plasma GIP and glucagon, but no effect on plasma GLP-1 or insulin, or on glucose absorption. HCA had no effect on glycemia in patients with type 2 diabetes.
Assuntos
Citratos/uso terapêutico , Diabetes Mellitus Tipo 2/dietoterapia , Carboidratos da Dieta/metabolismo , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Incretinas/metabolismo , Absorção Intestinal , 3-O-Metilglucose/sangue , 3-O-Metilglucose/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Citratos/administração & dosagem , Citratos/efeitos adversos , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Duodeno/metabolismo , Feminino , Glucose/administração & dosagem , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Incretinas/sangue , Mucosa Intestinal/metabolismo , Intubação Gastrointestinal , Masculino , Pessoa de Meia-IdadeRESUMO
Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta-alanine (~3-6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing factor to fatigue. Furthermore, sodium bicarbonate, sodium citrate and sodium/calcium lactate supplementation have been employed in an attempt to increase the extracellular buffering capacity. Although all attempts have increased blood bicarbonate concentrations, evidence indicates that sodium bicarbonate (0.3 g/kg body mass) is the most effective in improving high-intensity exercise performance. The evidence supporting the ergogenic effects of sodium citrate and lactate remain weak. These nutritional strategies are not without side effects, as gastrointestinal distress is often associated with the effective doses of sodium bicarbonate, sodium citrate and calcium lactate. Similarly, paresthesia (i.e. tingling sensation of the skin) is currently the only known side effect associated with beta-alanine supplementation, and it is caused by the acute elevation in plasma beta-alanine concentration after a single dose of beta-alanine. Finally, the co-supplementation of beta-alanine and sodium bicarbonate may result in additive ergogenic gains during high-intensity exercise, although studies are required to investigate this combination in a wide range of sports.
Assuntos
Acidose/prevenção & controle , Suplementos Nutricionais , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/efeitos adversos , Compostos de Cálcio/metabolismo , Citratos/administração & dosagem , Citratos/efeitos adversos , Citratos/metabolismo , Suplementos Nutricionais/efeitos adversos , Metabolismo Energético , Líquido Extracelular/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Líquido Intracelular/metabolismo , Lactatos/administração & dosagem , Lactatos/efeitos adversos , Lactatos/metabolismo , Fadiga Muscular , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/efeitos adversos , Bicarbonato de Sódio/sangue , Citrato de Sódio , Lactato de Sódio/administração & dosagem , Lactato de Sódio/efeitos adversos , Lactato de Sódio/metabolismo , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos , beta-Alanina/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume, a traditional Chinese herb, was widely used against convulsant, vertigo, paralysis, epilepsy, tetanus, asthma and immune dysfunctions. Gastrodin is one of the major bioactive components of G. elata and it is known for its anticonvulsive, anti-inflammatory, antiepileptic and neuroprotective effects. MATERIALS AND METHODS: An ultra high performance liquid chromatography-fluorescence detection (UHPLC-FLD) method was developed to determine gastrodin in rat plasma. Gastrodin and Thiamphenicol (internal standard, IS) were extracted from rat plasma by immediately protein precipitation. The pharmacokinetics of gastrodin in rats by following differently administered types was studies: intragastric administration of gastrodin (100mg/kg), parishin (116 mg/kg, with the same mole of gastrodin moiety) and G. elata extract (2.3g/kg, with the same mole of gastrodin moiety). Non-compartmental pharmacokinetic profiles were constructed using the software of WinNonlin (Phoenix, version 6.3), and the pharmacokinetic parameters were compared using unpaired Student's t-test. RESULTS: The results showed that the pharmacokinetic parameters, including Cmax, Tmax, AUC0-∞, t1/2, MRT, Vd, CL, were quite different among the three types of gastrodin administration. The administration of parishin and G. elata extract, which either could convert to gastrodin in vivo or contained free gastrodin and abundant gastrodin conjugates, gave rise to higher elimination half-life (t1/2) and mean residence time (MRT) values for gastrodin compared to free gastrodin administered. CONCLUSION: The comparison of the pharmacokinetics of gastrodin among three different administered types of gastrodin in rats suggested that administration of parishin or G. elata extract in clinic may result in a longer duration time of action than that of the administration of free gastrodin. The results may provide some guidance for the clinical applications of parishin and G. elata.
Assuntos
Álcoois Benzílicos/farmacocinética , Citratos/farmacocinética , Gastrodia , Glucosídeos/farmacocinética , Extratos Vegetais/farmacocinética , Animais , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Citratos/administração & dosagem , Citratos/sangue , Glucosídeos/administração & dosagem , Glucosídeos/sangue , Infusões Parenterais , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Ratos Sprague-Dawley , RizomaRESUMO
The pharmacokinetics of parishin, gastrodin, Gastrodia elata extract and Rhizoma Gastrodiae capsule was investigated by intragastric and/or intravenous administration to rats. Parishin was metabolized into nine metabolites after intravenous administration, and the area under the curve (AUC0-∞) of parishin and its metabolites (except parishin G and parishin E) increased nonlinearly from 72.5 to 220 mg/kg. When combining regression equation with the AUC0-∞ and dose of gastrodin injection, the percent conversion of parishin to gastrodin was obtained as 50 %. Based on multi-active metabolites of parishin in vivo, integrated pharmacokinetic mode was established. It is notable that each metabolite from parishin shares the similar metabolic process at three dosages of parishin and the bioavailability of parishin was approximately 14 %. The integrated pharmacokinetic mode was successfully applied to evaluate the holistic pharmacokinetics of gastrodin injection, G. elata extract and Rhizoma Gastrodiae capsule. The results showed that the holistic pharmacokinetics of gastrodin injection and G. elata extract was closed to that of gastrodin, but for parishin and Rhizoma Gastrodiae capsule, integrated pharmacokinetic parameters were more suitable to evaluate its holistic pharmacokinetics. Graphical abstract Pharmacokinetic study of Gastrodia elata in rats.
Assuntos
Álcoois Benzílicos/sangue , Citratos/sangue , Glucosídeos/sangue , Extratos Vegetais/sangue , Administração Intravenosa , Animais , Área Sob a Curva , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/metabolismo , Citratos/administração & dosagem , Citratos/metabolismo , Feminino , Gastrodia/química , Glucosídeos/administração & dosagem , Glucosídeos/metabolismo , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND/AIMS: Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli that contribute to various diseases, including chronic renal failure (CRF). Sodium citrate plays an important role in antioxidant and cellular immunity, but whether it improves ERS in CRF is unclear. METHODS: The rats were randomly divided into five groups: the control group, the sodium citrate control group, the model group, model rats with low dose sodium citrate (216 mg/kg), and model rats with a high dose of sodium citrate (746 mg/kg). The rats were euthanized at 6, 8, 12, and 16 weeks with their blood and renal tissue in detection. RESULTS: The increased concentrations of blood urea nitrogen and serum creatinine in the model group were significantly decreased by sodium citrate treatment. Hematoxylin-eosin and Masson staining showed that sodium citrate treatment apparently improved renal pathological changes in CRF rats. Western blot analysis showed that sodium citrate treatment decreased the protein levels of transforming growth factor-beta 1 and collagen type IV, which were increased in model rats. Moreover, immunohistochemical staining demonstrated that sodium citrate could effectively reduce the protein expression of glucose-regulated protein 78 kDa and CCAAT/enhancer-binding protein homologous protein in the model rats, which was consistent with western blot results. Additionally, the high dose of sodium citrate had a stronger protective effect in CRF rats than the low dose of sodium citrate. CONCLUSIONS: Sodium citrate has a protective effect on CRF through its effects on ERS.
Assuntos
Citratos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Adenina , Animais , Nitrogênio da Ureia Sanguínea , Soluções Tampão , Citratos/administração & dosagem , Colágeno Tipo IV/metabolismo , Creatinina/sangue , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Falência Renal Crônica/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Citrato de Sódio , Fator de Transcrição CHOP/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , eIF-2 Quinase/metabolismoRESUMO
The objective of this study was to compare the effect of 4 antiseptic compounds on the healing rate and incidence of infection of umbilical cords in newborn calves (n=60). Late gestation Jersey cows were monitored at a commercial farm (Sioux Jersey, Salix, IA) and newborn purebred (n=30) and crossbred (n=30) calves were obtained within 30min after birth. Calves were alternately assigned by birth order to 4 treatment groups: 7% tincture of iodine, 0.1% chlorine created using a novel chlorine disinfectant technology, chlorohexidine gluconate 4.0% wt/vol, and 10% trisodium citrate. Prior to dipping (within 30min of birth), diameter of the umbilical cords (as an indicator of cord drying and healing) were determined using digital calipers. In addition, as an indicator of umbilical infections, surface temperature of the umbilical stump (along with a reference point at the midpoint of the sternum) was determined using a dual-laser infrared thermometer. These measurements were all repeated at 24±1 h of age. All data were analyzed using mixed model methods. All models included fixed effects of breed (Jersey or Jersey cross), sex (bull or heifer), and treatment. Fixed effect interactions were not included in the statistical model due to the relatively small sample size. No treatment differences were noted for healing rate of umbilical cords. Initially, mean umbilical cord diameter was 22.84±3.89mm and cords healed to a mean diameter of 7.64±4.12mm at 24 h of age. No umbilical infections were noted for calves on any treatment during the course of this study. Mean surface temperature of the umbilical stump was 33.1±2.2°C at birth (1.5±1.6°C higher than the sternal reference temperature), and at 24±1 h of age the mean temperature of the umbilical stump was 33.0±4.3°C (0.5±1.8°C lower than the sternal reference temperature). These data suggest that these antiseptic compounds are equally effective for preventing infections and permitting healing of the umbilical cord when used within 30min of birth.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/veterinária , Doenças dos Bovinos/prevenção & controle , Cordão Umbilical/efeitos dos fármacos , Cordão Umbilical/microbiologia , Animais , Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Bovinos , Doenças dos Bovinos/etiologia , Doenças dos Bovinos/microbiologia , Clorexidina/administração & dosagem , Citratos/administração & dosagem , Feminino , Iodo/administração & dosagem , MasculinoRESUMO
Colonoscopy is the method of choice for colorectal cancer screening. To be effective, screening colonoscopy must have high quality standards. The key element is the quality of the preparation. However, up to 20% of patients are inadequately prepared and, at present, anterograde washing is the least tolerated part of the procedure. In the choice of preparation, safety is a prerequisite and efficacy is a priority. Tolerance is a secondary but nevertheless influential factor in the quality of preparation and has consequently been the primary focus of many recent studies. In the last few years, a rapidly increasing number of studies have evaluated new drugs, dosages and adjuvant therapies to improve efficacy and tolerability. These studies have collaterally shown that inadequate preparation and lack of adherence to the prescribed regimen can be partially predicted, making it essential to identify this patient subgroup and invest the necessary effort in their instruction. New individualized and flexible approaches are expected for the different clinical scenarios. The search for the ideal colonoscopy preparation, which would be tolerable, safe and above all effective, remains open.
Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Detecção Precoce de Câncer/métodos , Bisacodil/administração & dosagem , Catárticos/efeitos adversos , Citratos/administração & dosagem , Ácido Cítrico/administração & dosagem , Colonoscopia/tendências , Neoplasias Colorretais/diagnóstico , Fibras na Dieta , Detecção Precoce de Câncer/tendências , Previsões , Humanos , Compostos Organometálicos/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde , Fosfatos/administração & dosagem , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Extrato de Senna/administração & dosagem , Senosídeos , Irrigação TerapêuticaRESUMO
PURPOSE: Similarly to a wrestling match, upper-body intermittent sprint performance (UBISP) test elicits severe acidosis. This study aimed to determine whether sodium citrate (CIT) ingestion would help to better maintain peak power (PP) and mean power (MP) output across four consecutive UBISP tests simulating wrestling matches of a competition-day. METHODS: In a double-blind, counterbalanced, crossover manner, 11 trained wrestlers ingested either placebo (PLC) or CIT (900 mg kg(-1)) within a 17-h supplementation period. Thereafter they completed four (T1-T4) 6-min UBISP tests interspersed with 30-min recovery periods. RESULTS: Compared with PLC, CIT supplementation resulted in a persistent increase (P < 0.05) in blood HCO3 (-) concentration and pH: pre-T1 25.6 % and 0.08 units, post-T4 39.1 % and 0.14 units, respectively. Post-T1 blood lactate concentration in CIT (16.1 ± 3.8 mmol L(-1)) was higher (P = 0.037) than that in PLC (13.7 ± 2.3 mmol L(-1)). Decrease in plasma volume across the supplementation period and UBISP tests was greater (P = 0.03) in PLC (-6.91 ± 4.37 %) than in CIT (-1.51 ± 4.34 %). There was an overall decrease (P = 0.028) in ratings of perceived exertion in CIT compared with PLC, but no between-trial difference (P > 0.05) in PP or MP in any UBISP test occurred. CONCLUSION: In trained wrestlers, CIT ingestion induces alkalosis, counteracts reduction in plasma volume, increases post-test blood lactate concentration and reduces perceived exertion, but does not improve PP or MP attained in consecutive UBISP tests simulating four wrestling matches of a competition-day.
Assuntos
Desempenho Atlético , Citratos/farmacologia , Exercício Físico , Tronco/fisiologia , Luta Romana/fisiologia , Adulto , Citratos/administração & dosagem , Comportamento Competitivo/efeitos dos fármacos , Suplementos Nutricionais , Humanos , Ácido Láctico/sangue , Masculino , Esforço Físico/efeitos dos fármacos , Volume Plasmático/efeitos dos fármacos , Citrato de SódioRESUMO
Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/fisiopatologia , Citratos/administração & dosagem , Suplementos Nutricionais , Falência Renal Crônica/dietoterapia , Falência Renal Crônica/fisiopatologia , Tolerância ao Sal/efeitos dos fármacos , Injúria Renal Aguda/diagnóstico , Administração Oral , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Citrato de Sódio , Resultado do TratamentoRESUMO
A rapid, sensitive and reliable UHPLC-ESI-MS/MS method was developed for simultaneous determination of gastrodin and parishin in rat plasma. The LLOQ of the two analytes were 1.00×10(-1) and 8.30×10(-5)µg/mL, respectively. The intra-day and inter-day precision were all less than 10% of the relative standard deviation (RSD), whilst the accuracy were all within ±15% of the relative error (RE). The proposed method was successfully applied for pharmacokinetics study on the two analytes in rats after oral administration of Gastrodiae rhizoma (GR) extract and powder at low, medium and high dosages. Blood samples were collected from the suborbital vein at predetermined time points and were precipitated using methanol. Chromatographic separations were carried out on a Kinetex XB-C18 column (2.1mm×150mm, 1.7µm) with a gradient mobile phase of acetonitrile-water with 0.1% formic acid as a modifier. The pharmacokinetic parameters of the two analytes in rats were obtained and the relative bioavailability of gastrodin and parishin in two formulations were calculated. The results indicated that higher bioavailability was obtained when low dosage of GR powder was used, whereas, higher bioavailability values were obtained when medium and high dosages of GR extract were used.
Assuntos
Álcoois Benzílicos/farmacocinética , Citratos/farmacocinética , Gastrodia , Glucosídeos/farmacocinética , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/sangue , Disponibilidade Biológica , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Citratos/administração & dosagem , Citratos/sangue , Estabilidade de Medicamentos , Gastrodia/química , Glucosídeos/administração & dosagem , Glucosídeos/sangue , Masculino , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Plantas Medicinais , Pós , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Rizoma , Espectrometria de Massas por Ionização por Electrospray/normas , Espectrometria de Massas em Tandem/normasRESUMO
CONTEXT: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases in phosphate, PTH, and calcium concentrations are associated with increases in circulating fibroblast growth factor 23 (FGF23); however, whether or not acute changes in serum calcium modulate short-term FGF23 release is unknown. OBJECTIVE/DESIGN: To assess the direct effect of acute changes in calcium and PTH on circulating FGF23 levels. SETTING: A university clinical and translational research center. PATIENTS/PARTICIPANTS: Twelve healthy volunteers and 10 dialysis patients. INTERVENTIONS: Calcium gluconate and sodium citrate were infused for 120 minutes on 2 consecutive days. MAIN OUTCOME MEASURES: Serum levels of ionized calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120 minutes during the infusions. RESULTS: During the calcium infusion, serum calcium concentrations increased from 1.33 ± 0.01 to 1.57 ± 0.04 mmol/L (P < .05 from baseline) and from 1.20 ± 0.05 to 1.50 ± 0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis patients, respectively, whereas serum calcium values decreased from 1.33 ± 0.01 to 1.03 ± 0.02 mmol/L (P < .05 from baseline) and from 1.26 ± 0.04 to 1.07 ± 0.03 mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL (healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86) pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169, 928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D levels and plasma FGF23 values remained unchanged during both infusions in both groups. CONCLUSIONS: Short-term changes in calcium and PTH levels do not affect FGF23 concentrations in either healthy volunteers or dialysis patients.