RESUMO
The objective of this study was to evaluate effects of butyrate supplementation on plasma concentration of glucagon-like peptide-2 (GLP-2), apparent total-tract digestibility, and responses to a grain challenge of lactating dairy cows fed diets differing in starch content. Eight Holstein cows averaging 58.6 ± 9.96 d in milk (4 primiparous cows fitted with rumen cannula and 4 multiparous intact cows) were blocked by parity and assigned to one of two 4 × 4 Latin squares balanced for carryover effects with a 2 × 2 factorial arrangement of treatments. Treatments were dietary starch content [20.6 vs. 27.5%, respectively, for low starch (LS) and high starch (HS)] and butyrate supplementation (butyrate vs. control) with 21-d periods. Butyrate was provided as Gustor BP70 WS (Norel, S.A., Madrid, Spain), containing 70% sodium butyrate and 30% fatty acid mixture, at 2% of dietary dry matter (providing butyrate at 1.1% of dietary dry matter), and control premix contained 70% wheat bran and 30% fatty acid mixture. Feeds, orts, and fecal samples were collected from d 17 to 19 to determine apparent total-tract nutrient digestibility. Blood and rumen fluid samples were collected on d 19. The baseline of dry matter intake (DMI) was determined as average DMI from d 17 to 19 for each cow, and cows were feed-restricted at 60% of the baseline DMI on d 20, and a grain challenge was conducted by providing steam-flaked corn grain at 0.6% of body weight, on an as-fed basis, in addition to each treatment diet on d 21, and blood and ruminal fluid samples were collected. The interaction of dietary starch content by butyrate supplementation was significant for plasma GLP-2 concentration, being greater for cows fed butyrate with the HS diet than those fed the other 3 diets. Cows fed butyrate increased n-butyrate concentration in the ruminal fluid and tended to increase dry matter and organic matter digestibility compared with the control. During the grain challenge, rumen endotoxin concentration increased over time and was higher for cows fed the HS diets compared with those fed LS diets. However, response variables related to inflammation were not affected by the grain challenge. However, serum haptoglobin, lipopolysaccharide-binding protein, and serum amyloid-A concentrations were greater for cows fed butyrate with the LS diet, but not for those fed the HS diet. These results indicate that butyrate supplementation may increase plasma GLP-2 concentration for cows fed HS diets, and total-tract digestibility regardless of dietary starch content. However, butyrate supplementation did not mitigate inflammation in this study.
Assuntos
Ração Animal , Butiratos/farmacologia , Dieta/veterinária , Trato Gastrointestinal/efeitos dos fármacos , Peptídeo 2 Semelhante ao Glucagon/metabolismo , Amido/metabolismo , Animais , Bovinos , Digestão/efeitos dos fármacos , Ácidos Graxos/metabolismo , Feminino , Fermentação , Lactação , Rúmen/metabolismoRESUMO
MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression post-transcriptionally through complementary base pairing with thousands of messenger RNAs. Although the target genes and precise biological functions of individual miRNAs remain largely unknown, miRNAs are speculated to play important roles in diverse biological processes in both normal and pathological states. The liver is a vital organ that plays major roles in a number of physiological functions. Recent advances in the study of liver miRNAs using gene-modified mice or in vivo nucleic acid delivery to overexpress specific miRNAs or inhibit miRNA functions have revealed the crucial biological roles of individual miRNAs in physiologically essential liver functions in vivo. Because miRNA-based strategies are being applied to clinical therapeutics, the importance of precise knowledge of miRNA functions cannot be underestimated, not only from a scientific point of view, but also from a clinical perspective to make the most of such drugs and avoid unexpected harmful effects. The aims of this review are to describe current knowledge regarding both known and as-yet-undiscovered molecular aspects of the biological roles of miRNAs in the liver, with a special emphasis on lipid, glucose, drug, and iron metabolism as vital functions of the liver as well as important therapeutic targets.
Assuntos
Fígado/metabolismo , MicroRNAs/fisiologia , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/genéticaRESUMO
UNLABELLED: Using solution strontium and pH as independent variables, the metastable equilibrium solubility (MES) behavior of two carbonated apatite (CAP) samples has been examined, a high-crystallinity CAP (properties expected to be similar to dental enamel) and a low-crystallinity CAP (properties expected to be similar to bone mineral). CAP samples were prepared by precipitation/digestion: (CAP A: high-crystallinity, 1.3 wt% CO3, synthesized at 85 degrees C; CAP B: low-crystallinity, 6.4 wt% CO3, synthesized at 50 degrees C). Baseline MES distributions were determined in a series of 0.1 M acetate buffers containing only calcium and phosphate (no strontium) over a broad range of solution conditions. To assess the influence of strontium, MES profiles were determined in a similar fashion with 20, 40, 60, and 80% of the solution calcium being replaced on an equal molar basis by solution strontium. To determine the correct function governing CAP dissolution, ion activity products (IAPs) were calculated from the compositions of buffer solutions based on the hydroxyapatite template (Ca(10-n)Sr(n)(PO4)6(OH)2 (n = 0-10)) and the calcium/hydroxide deficient hydroxyapatite template (Ca(9-n)Sr(n)(HPO4)(PO4)5OH (n = 0-9)). FINDINGS: (a) for CAP A, at high solution strontium/calcium ratios, the MES profiles were essentially superimposable when the solution IAPs were calculated using the stoichiometry of Ca6Sr4(PO4)6(OH)2 and for CAP B by a stoichiometry of Ca7Sr2(HPO4)(PO4)5OH; (b) for CAP A, at low strontium/calcium ratios, the stoichiometry yielding MES data superpositioning was found to be that of hydroxyapatite and for CAP B, that of calcium/hydroxide deficient hydroxyapatite. When other stoichiometries were assumed, good superpositioning of the data was not possible.
Assuntos
Apatitas/química , Carbonatos/química , Estrôncio/química , Cálcio/química , Cristalização , Concentração de Íons de Hidrogênio , Fósforo/química , Sensibilidade e Especificidade , Solubilidade , Soluções/química , Propriedades de SuperfícieRESUMO
Vesicular glutamate transporter is present in neuronal synaptic vesicles and endocrine synaptic-like microvesicles and is responsible for vesicular storage of L-glutamate. A brain-specific Na(+)-dependent inorganic phosphate transporter (BNPI) functions as a vesicular glutamate transporter in synaptic vesicles, and the expression of this BNPI defines the glutamatergic phenotype in the central nervous system (Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI, an additional transporter(s) responsible for vesicular glutamate uptake has been postulated. Here we report that differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., and Takeda, J. (2000) J. Neurochem. 74, 2622-2625), also transports L-glutamate at the expense of an electrochemical gradient of protons established by the vacuolar proton pump when expressed in COS7 cells. Molecular, biological, and immunohistochemical studies have indicated that besides its presence in neuronal cells DNPI is preferentially expressed in mammalian pinealocytes, alphaTC6 cells, clonal pancreatic alpha cells, and alpha cells of Langerhans islets, these cells being proven to secrete L-glutamate through Ca(2+)-dependent regulated exocytosis followed by its vesicular storage. Pancreatic polypeptide-secreting F cells of Langerhans islets also expressed DNPI. These results constitute evidence that DNPI functions as another vesicular transporter in glutamatergic endocrine cells as well as in neurons.
Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/fisiologia , Glutamina/metabolismo , Proteínas de Membrana Transportadoras , Sódio/farmacologia , Proteínas de Transporte Vesicular , Trifosfato de Adenosina/metabolismo , Animais , Ácido Aspártico/metabolismo , Transporte Biológico , Northern Blotting , Células COS , Cálcio/metabolismo , Diferenciação Celular , Células Cultivadas , DNA Complementar/metabolismo , Ácido Glutâmico/metabolismo , Immunoblotting , Imuno-Histoquímica , Ilhotas Pancreáticas/metabolismo , Masculino , Neurônios/metabolismo , Glândula Pineal/citologia , Ligação Proteica , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Vesicular 2 de Transporte de GlutamatoRESUMO
The purpose of this study was to elucidate the effect of amount of ceramic cement powder on drug release from bioactive bone cement. The associated bone-bonding strength was also investigated. The bioactive bone cement under investigation consisted of bisphenol-alpha-glycidyl methacrylate (Bis-GMA), triethylene-glycol dimethacrylate (TEGDMA) resin and a combination of apatite- and wollastonite-containing glass-ceramic (A-W GC) powder. A-W GC powder (50%, 70% and 80% w/w) containing 5% cephalexin (CEX) powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin. The compressive strength of the cement with or without drug increased with increasing the amount of ceramic powder. The compressive strength of the 80% ceramic cement without the incorporation of cephalexin was 194 MPa. This compressive strength was about 3 times higher than that for polymethylmethacrylate cement. After the cement was implanted in the proximal metaphysis of the tibiae of male rabbits, the failure load for the cement was found to increase with increasing of the amount of ceramic powder. This finding suggested that the cement formed a bonding with bone. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. Drug release profile followed the Higuchi equation initially, but not at later stages. The drug release rate increased with increasing amount of ceramic powder in the mixture. Since the pore volume of the cement increased with increasing of amount of ceramic powder, the drug diffused in the pores between the ceramics particle and polymer matrix. As hydroxyapatite precipitated on the cement surface, the drug release rate decreased, as observed at the later release stage. These results suggest that varying the amount of ceramic powder in the cement system could control the drug release rate from bioactive bone cement.
Assuntos
Implantes Absorvíveis , Bis-Fenol A-Glicidil Metacrilato/química , Cimentos Ósseos/química , Cefalexina/química , Cefalexina/farmacocinética , Cefalosporinas/química , Cefalosporinas/farmacocinética , Cerâmica/química , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Animais , Disponibilidade Biológica , Precipitação Química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Força Compressiva , Portadores de Fármacos , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Teste de Materiais , Modelos Animais , Coelhos , Resistência à TraçãoRESUMO
OBJECTIVE: To examine the development of chemical and clinical vitamin B12 deficiency after total gastrectomy, and to evaluate the efficacy of supplemental oral B12 administration. SUMMARY BACKGROUND DATA: Postgastrectomy anemia is due to deficiencies of iron and vitamin B12, and parenteral B12 administration is the only appropriate treatment. However, no guidelines exist for the prophylactic use of B12 in patients who undergo total gastrectomy, the clinical presentation of B12 deficiency in this context has not been defined, and the question of whether oral B12 administration can be used to prevent and treat B12 deficiency has not been examined. METHODS: Serum B12 concentrations were measured in 31 patients who had undergone total gastrectomy. Symptoms related to B12 deficiency were surveyed in detail. Serum B12 concentrations were measured every 6 months after total gastrectomy in 10 patients. Thirty one patients received supplemental B12: 18 patients orally and 13 by intramuscular injection. RESULTS: The B12 concentration dropped below the lower limit of normal (200 pg/mL) for the first time in two patients at 1 year, in four patients at 2 years, in three patients at 3 years, and in one patient at 4 years. Seventy-eight percent of patients reported some symptoms related to B12 deficiency. The serum B12 concentration in patients who received supplemental B12 orally increased rapidly and all symptoms resolved with oral therapy alone. CONCLUSIONS: B12 deficiency can develop as early as 1 year after total gastrectomy and causes symptoms. Because enteral B12 treatment increases the serum B12 concentration and leads to rapid resolution of symptoms, it should be prescribed routinely to patients undergoing total gastrectomy.
Assuntos
Gastrectomia/efeitos adversos , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/administração & dosagem , Administração Oral , Adulto , Idoso , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina B 12/etiologiaRESUMO
To determine dietary factors involved in the pathological process of Alzheimer's disease (AD), we analyzed food consumption and intake of nutrients using Self-administered Diet History Questionnaire (DHQ) developed for Japanese. Sixty four AD patients and 80 age-matched healthy subjects were enrolled in this study. AD was diagnosed according to the criteria of DSM-IV. Dietary behaviors of AD patients was markedly deviated from those of age-matched healthy elderly. AD patients disliked fish and green-yellow vegetables and took more meats than controls. Energy-adjusted analysis of nutrients revealed that AD patients took less vitamin C and carotene. Most conspicuously, AD patients took significantly smaller amount of n-3 polyunsaturated fatty acid (PUFA) reflecting low consumption of fish, and their n-6/n-3 ratio was significantly increased. These habits started from 3 months to 44 years before the onset of dementia, suggesting these dietary abnormalities are not merely the consequence of dementia. Rather, it implies that AD might be a life style-related disease such as coronary heart disease, western style diet-associated cancer and hyperallergy. To see if cognitive function was improved by correcting the n-6/n-3 ratio, we prescribed eicossapentaenoic acid (EPA), one type of n-3 PUFA, for AD patients. Cognitive function was evaluated using MMSE. Administration of EPA (900 mg/day) improved MMSE significantly with maximal effects at 3 months and the effects lasted 6 months. However, the score of MMSE decreased after 6 months. The present study showed that nutritional intervention is useful for the prevention of AD, and also for the therapy of dementia, though it has some limitation.
Assuntos
Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/terapia , Dieta , Fenômenos Fisiológicos da Nutrição , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/dietoterapia , Ingestão de Alimentos , Comportamento Alimentar , Feminino , Humanos , MasculinoRESUMO
Ascorbate is a cofactor of two-enzyme hydroxylation in the pathway of carnitine biosynthesis. The purpose of this study was to investigate the contribution of ascorbate to endogenous carnitine in guinea pigs fed high-fat diets. The contents of carnitine in plasma, urine and tissues of guinea pigs supplemented with L-ascorbic acid were determined and compared with those supplemented with carnitine. Albino-Hartley guinea pigs were fed vitamin C-deficient diets containing lard throughout the experiment. They were administered orally with 5 mg L-ascorbic acid/d/animal for 14 d, and then divided into three groups and administered orally with the following supplements (/d/animal) for 14 d; L (5 mg L-ascorbic acid), LASA (100 mg L-ascorbic acid), and LCAR (10 mg carnitine plus 5 mg L-ascorbic acid). As a control, a normal group was fed vitamin C-deficient diets and administered orally with 5 mg L-ascorbic acid/d/animal for 28 d. The animals fed high-fat diets (L group) had higher free-carnitine contents in the muscle and urine than the normal group. The groups of LCAR and LASA had significantly higher contents of acid-soluble carnitine (p < 0.05) in plasma than the L group. Urinary excretion of carnitine in the LASA group was decreased to the same level as that in the normal group, although no significant difference between the groups of L and LCAR was observed. Moreover, the supplement of ascorbic acid, but not of carnitine, induced a significantly lower content of triacylglycerol in the plasma of the LASA group as compared to the L group (p < 0.05). These data suggest that high doses of ascorbic acid in guinea pigs fed high-fat diets contribute to the enhancement of carnitine synthesis and improvement of the triacylglycerol content in the plasma.
Assuntos
Ácido Ascórbico/metabolismo , Carnitina/biossíntese , Gorduras na Dieta/metabolismo , Animais , Ácido Ascórbico/administração & dosagem , Carnitina/sangue , Carnitina/urina , Cromatografia Líquida de Alta Pressão , Gorduras na Dieta/administração & dosagem , Cobaias , Fígado/química , Masculino , Músculos/química , Triglicerídeos/sangueRESUMO
In order to elucidate the effect of L-ascorbic acid (AsA) on the formation of pyridinoline, a mature crosslink of collagen, its content in cartilage collagen of guinea pigs supplemented with and without AsA in the growing process (4-8 weeks of age) and in the period of maturity (10-14 weeks of age) was examined. The AsA-deficient animals, for four weeks during the growing process, had a significantly higher content of pyridinoline in their collagen than the AsA-supplemented group, indicating that the depletion of AsA induced increasing contents of pyridinoline. On the other hand, in the period of maturity, the pyridinoline content in the collagen decreased with age, whereas no difference between AsA-deficient and -supplemented groups was observed. Based on these results, it is assumed that AsA affects the formation of pyridinoline, especially in the growing period.
Assuntos
Envelhecimento , Aminoácidos/análise , Ácido Ascórbico/farmacologia , Cartilagem/química , Colágeno/química , Glândulas Suprarrenais/química , Aminoácidos/química , Animais , Ácido Ascórbico/análise , Deficiência de Ácido Ascórbico/metabolismo , Cobaias , Fígado/química , Masculino , Aumento de PesoRESUMO
This study showed that the inhibition of cell growth in 3T6, induced by the supplementation of ascorbate at 0.5 mM in cultured medium, was prevented by the addition of catalase in the range of 25-750 units/mL regardless of the degree of activity. However, cytotoxicity induced by concentrations of more than 2 mM ascorbate could not be prevented even when a high level of catalase (5,000 units/mL) was added to the medium. Catalase activity in medium supplemented with ascorbate decreased with incubation time; the higher the concentration of ascorbate, the greater the decrease in catalase activity. These results indicate that even though catalase is present at a high concentration in the medium, it cannot prevent cytotoxicity by a high concentration of ascorbate because the oxygen radical derived from ascorbate inhibits its activity. We therefore investigated whether the inhibition of catalase activity by ascorbate could be observed in animal tissues. The catalase activity in the tissues of guinea pigs 6h after the administration of ascorbate was lower than that in non-administered animals. When guinea pigs were fed diets containing 5 mg or 100 mg ascorbate/animal over a 90 weeks period, a clear affect on catalase activity in the high-dose ascorbate group as compared to that in the low-dose ascorbate group was not observed.
Assuntos
Ácido Ascórbico/farmacologia , Catalase/metabolismo , Animais , Ácido Ascórbico/administração & dosagem , Catalase/antagonistas & inibidores , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Cobaias , Masculino , CamundongosRESUMO
We recently reported that the concentration of supplemental ascorbate which inhibits cell growth is positively related to intracellular catalase activity. It is assumed that the cells with high catalase activity are resistant to high concentrations of ascorbate since catalase can decompose hydrogen peroxide (H2O2) induced by the auto-oxidation of ascorbate in cultured medium. In this study, we investigated whether intracellular catalase activity affects the uptake of ascorbate into animal tissue and cultured cells. Ascorbate concentrations in the tissues of guinea pigs and various cultured cells, with and without supplementation of ascorbate, were determined to evaluate the efficiency of ascorbate uptake. We found a positive correlation between the efficiency of ascorbate uptake and catalase activity in various tissues of guinea pigs (r = 0.767, p < 0.05). Furthermore, a positive correlation between the two was also found in various species of cultured cells. This study indicates that tissues and cells with higher efficiency of ascorbate uptake are required for higher catalase activity, presumably for the decomposition of H2O2 from ascorbate.
Assuntos
Ácido Ascórbico/metabolismo , Catalase/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Cobaias , Humanos , Peróxido de Hidrogênio/metabolismo , Intestino Delgado/metabolismo , Rim/metabolismo , Leucemia Promielocítica Aguda , Fígado/metabolismo , Pulmão/metabolismo , Células PC12 , Ratos , Células Tumorais CultivadasRESUMO
Forty-five mutant male ODS rats, unable to synthesize ascorbic acid, were fed nine diets containing 5, 50 or 250 mg of vitamin E/kg diet and 150, 300 or 900 mg of vitamin C/kg diet for 21 days. The concentrations of vitamins C and E increased in liver and plasma in relation to the level of these vitamins in the diet. Vitamin C dietary supplementation increased the plasma vitamin E content at low levels of vitamin E intake, supporting the concept of an in vivo synergism between both antioxidant vitamins. Vitamin C, at the dietary levels studied, did not affect the lipid peroxidation. Vitamin E decreased liver and plasma endogenous levels of thiobarbituric acid-reactive substances and liver sensitivity to non-enzymatic lipid peroxidation. This was confirmed by a highly specific assay of lipid hydroperoxides using high performance liquid chromatography with chemiluminescence detection. The hepatic concentration of both phosphatidylcholine and phosphatidylethanolamine hydroperoxides decreased as the vitamin E content of the diet increased. The results show for the first time the capacity of vitamin E to protest against peroxidation of major phospholipids in vivo under basal unstressed conditions.
Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Peróxidos Lipídicos/metabolismo , Fígado/metabolismo , Fosfolipídeos/metabolismo , Vitamina E/metabolismo , Animais , L-Gulonolactona Oxidase , Masculino , Fosfolipídeos/sangue , Ratos , Ratos Mutantes , Desidrogenase do Álcool de Açúcar/deficiênciaRESUMO
The effect of ascorbate on cell growth was examined using primary cultured hepatocytes and chondrocytes elicited from guinea pigs and six kinds of cell lines derived from the tissue and blood of mammals. Cells were cultured in medium supplemented with or without ascorbate at various concentrations for 24 and 48 h. There were differences among the cells used here in the effect of ascorbate on growth, and also in the concentrations of ascorbate required to lower cell viabilities. This indicates that different cell species have varying sensitivities to ascorbate in medium. On the other hand, cells such as HL-60, which showed growth inhibition at higher concentrations of ascorbate in medium among observed cells, were damaged by the exposure to higher concentrations of hydrogen peroxide (H2O2). Furthermore, there was a positive correlation between the activity of catalase in cells that decomposed H2O2 and the concentration of ascorbate required to lower cell viability (p < 0.01). These results indicate that the concentration of ascorbate in medium required to inhibit cell growth depends on the activity of catalase in the cells.
Assuntos
Ácido Ascórbico/farmacologia , Catalase/metabolismo , Divisão Celular/efeitos dos fármacos , Animais , Encéfalo/citologia , Cartilagem/citologia , Cartilagem/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura , Cobaias , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Leucemia Promielocítica Aguda , Fígado/citologia , Fígado/efeitos dos fármacos , Camundongos , Ratos , Baço/citologia , Células Tumorais CultivadasRESUMO
Effects of the mixture (SK-204) consisting of dried shiitake mushroom (Lentinus edodes) treated with wet-heating and fructo-oligosaccharides (7:3) on the experimental models of pulmonary thrombosis induced by lactic acidosis in rats were evaluated. Chronic oral administration (10 weeks) of SK-204 significantly prevented the thrombus formation on this thrombosis model. However, decreases in the numbers of platelet and fibrinogen level by lactate were not changed by SK-204. These results suggest that SK-204 have an anti-thrombotic action, which is due to neither the inhibition of platelet aggregation nor coagulation, but probably due to the promotion of fibrinolysis and thrombolysis.
Assuntos
Fibrinolíticos/uso terapêutico , Oligossacarídeos/uso terapêutico , Polyporaceae , Embolia Pulmonar/tratamento farmacológico , Animais , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/farmacologia , Frutose , Masculino , Oligossacarídeos/farmacologia , Contagem de Plaquetas/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
L-Ascorbic acid is required for the synthesis of L-carnitine, which is essential for the oxidation of long-chain fatty acids. The purpose of this study was to investigate the role of ascorbate on the oxidation of long-chain fatty acids in primary cultured guinea pig hepatocytes. The hepatocytes were incubated in medium containing carnitine in the presence or absence of fatty acids. Exogenous fatty acids had no influence on the uptake of total carnitine into cells, but they lowered the free carnitine and consequently raised the concentration of short-chain acyl carnitine. Furthermore, carnitine supplementation of the medium in the presence of fatty acids led to a decrease of triglycerides in cells and an increase in the secretion of beta-hydroxybutyrate. These changes were also induced by the supplementation of the medium with both ascorbate and the precursor of carnitine (gamma-butyrobetaine) in the presence of fatty acids, although either ascorbate of gamma-butyrobetaine alone had no effect. In addition, increasing the concentration of supplemental ascorbate resulted in an enhancement of ketogenesis and a decrease of triglyceride accumulation. These results suggest that ascorbate enhances carnitine synthesis, which in turn stimulates beta-oxidation of fatty acids.
Assuntos
Ácido Ascórbico/farmacologia , Carnitina/biossíntese , Ácidos Graxos Monoinsaturados/metabolismo , Fígado/efeitos dos fármacos , Ácidos Oleicos/metabolismo , Animais , Ácido Ascórbico/fisiologia , Carnitina/metabolismo , Células Cultivadas , Ácidos Graxos Monoinsaturados/farmacologia , Cobaias , Corpos Cetônicos/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Ácidos Oleicos/farmacologia , Oxirredução , Triglicerídeos/metabolismoRESUMO
The distribution of L-ascorbic acid AA and dehydroascorbic acid DHA in wounded and intact skin of guinea pig was investigated to elucidate the utilization of AA during tissue regeneration. Male guinea pigs fed an AA-free diet for 14 days were surgically injured on the dorsal skin, followed by intraperitoneal supplementation of AA (0.5, 5 and 50 mg/day/animal) for 4 days. The wounded skin, its surroundings and intact skin in each animal were removed for the determination of AA, DHA and collagen. The collagen content in wounded and intact skin increased in dose-dependent manner up to 5 mg AA/day, although neither the wounded nor the intact skin of the group supplemented with 50 mg AA had a higher content of collagen than those supplemented with 5 mg. In each group, the wounded skin had only about half the collagen of intact skin. AA content in the wounded skin of the groups supplemented with 5 and 50 mg AA were significantly lower than that in the other parts of their skin, whereas DHA content in wounded skin increased markedly. These results indicate that other factors besides collagen synthesis may enhance the oxidation of AA in the early stage of tissue regeneration.
Assuntos
Ácido Ascórbico/metabolismo , Ácido Desidroascórbico/metabolismo , Regeneração/fisiologia , Fenômenos Fisiológicos da Pele , Cicatrização/fisiologia , Animais , Ácido Ascórbico/administração & dosagem , Cobaias , Masculino , Pele/metabolismoRESUMO
O referido trabalho visa o estudo e a compreensäo global do medicamento Magnesia carbonica, baseando-se no perfil psicodinâmico do experimentador e comparando-o com as características inerentes da substância em questäo
Assuntos
Medicamento Homeopático , Magnesia CarbonicaRESUMO
The levels of phosphatidylcholine hydroperoxide in serially cultured human fetal diploid fibroblasts at various population doubling levels were determined by high-performance liquid chromatography combined with chemiluminescence detection. This methodology utilizes a mixture of cytochrome c and luminol as post-column hydroperoxide group specific luminescent reagents. The cellular hydroperoxide content increased with age from 0.34 to 27.72 pmol/10(6) cells. At the end of the cells' in vitro lifespan (51st population doubling level), the hydroperoxide content per 10(6) cells reached about 80 times the level found in cells of the 20th population doubling level. Supplementation of exogenous alpha-tocopherol to the culture medium prevented hydroperoxide accumulation, but did not extend the lifespan in vitro. The results indicate that substantial intracellular phospholipid hydroperoxide accumulation occurred in the course of aging of human fetal diploid fibroblasts.
Assuntos
Senescência Celular/efeitos dos fármacos , Fosfatidilcolinas/metabolismo , Vitamina E/farmacologia , Linhagem Celular , Senescência Celular/fisiologia , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Medições LuminescentesRESUMO
The endogenous formation of N-nitrosoproline (NPRO) and N-nitrosothioproline (NTPRO, N-nitrosothiazolidine-4-carboxylic acid) was studied by monitoring their excretion in the urine of guinea pigs given oral doses of 10 mg proline or thioproline after supplementation with 34 mg (0.4 mmol) sodium nitrate. In order to estimate the conversion of nitrate to nitrite, the animals were also supplemented with 3.5 mg (0.05 mmol) sodium nitrite instead of sodium nitrate. In animals fed commercial diets, the excretion of NPRO and NTPRO under supplementation with sodium nitrate was 2.0 micrograms and 28.7 micrograms/animal/day, respectively, whereas the excretion under supplementation with sodium nitrite was 0.7 micrograms and 13.3 micrograms/animal/day, respectively. The higher excretion of NTPRO than NPRO in each case shows that thioproline is more effective for nitrite trapping than proline. The animals supplemented with nitrate excreted more than twice the amounts of NPRO or NTPRO than those supplemented with nitrite. It is assumed, therefore, that more than 0.1 mmol nitrate is reduced to nitrite and takes part in the endogenous nitrosation of the guinea pig. When various concentrations of L-ascorbic acid (AsA), known to inhibit the formation of N-nitroso compounds, were also administered orally to animals immediately after supplementation with sodium nitrate, the NPRO excretion decreased with increasing AsA concentration. These data indicate that the guinea pig, which is unable to synthesize AsA as well as humans, may be an appropriate animal model for evaluation of the endogenous nitrosation ability of humans ingesting nitrate.
Assuntos
Nitratos/metabolismo , Nitrosaminas/urina , Compostos Nitrosos/urina , Prolina/metabolismo , Tiazóis/metabolismo , Tiazóis/urina , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/metabolismo , Determinação da Acidez Gástrica , Cobaias , Concentração de Íons de Hidrogênio , Masculino , Nitrosação , TiazolidinasRESUMO
The vitamin C activity of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), which is one of chemically stable derivatives of L-ascorbic acid (AsA), in guinea pigs was investigated. Male guinea pigs were divided into 9 groups and fed AsA-deficient diet for 24 days with the following supplement: AA-2G- or AsA-supplemented groups were orally supplemented with 0.96, 1.92, 9.6 and 192 AA-2G mg/animal/day or equimolar amounts of AsA (0.5, 1, 5 and 100 mg/animal/day, respectively); AsA-deficient group received neither of them. The body weight gain, serum alkaline phosphatase activity, and the concentration of AsA and AA-2G in the liver, adrenals and urine of the guinea pigs were measured at the end of the experimental period. The AA-2G-supplemented guinea pigs showed similar body weight gain to the animals supplemented with equimolar amount of AsA. Serum alkaline phosphatase activity in both AA-2G- and AsA-supplemented groups was significantly higher than that of AsA-deficient group. But there was no significant difference between the groups supplemented with AA-2G and the equimolar amount of AsA. AA-2G-supplemented guinea pigs showed no apparent symptoms of scurvy. In AA-2G-supplemented groups, AA-2G was not detected in the liver, adrenals and urine, but AsA was found and the AsA concentration increased with increasing AA-2G dosage. The AsA concentration in the tissues of each AA-2G-supplemented groups was higher than that of AsA-deficient group, which was similar to that of the groups supplemented with equimolar amount of AsA. These results showed that AA-2G has the same vitamin C activity as AsA on a molar basis for the orally supplemented guinea pigs.