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1.
Expert Opin Drug Metab Toxicol ; 15(9): 697-703, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382802

RESUMO

Background: D-chiro-inositol (DCI) and glucose transporter inhibitors may inhibit myo-inositol (MI) transporters, and the aim is to clinically evaluate their effect on MI absorption. Research design and methods: Fasting 18 healthy volunteers received orally 6000 mg MI, 6000 mg MI with 1000 mg DCI, and 6000 mg MI with SelectSIEVE® Apple PCQ and Sorbitol, Maltodextrin and Sucralose (PCQ-SMS), in three different phases with a washout period of 7 days. At each phase, blood samples were collected before administration, and every 60 minutes until 540 minutes after administration. MI plasma levels (µmol/L) were quantified by gas chromatography-mass spectrometry; maximum plasma concentration (Cmax), time to reach it (Tmax), and the area under the time-concentration curve of MI (AUC 0-540) were evaluated. Results: The Cmax of MI alone (Tmax = 180min) was 1.29-fold higher than those of MI with DCI (Tmax = 180min) (p < 0.001) and 1.69-fold higher than those of MI with PCQ-SMS (Tmax = 240min) (p < 0.001). The AUC 0-540 was reduced by 19.09% in MI plus DCI (p = 0.0118) and by 31.8% in MI plus PCQ-SMS (p < 0.001) as compared to MI alone. Conclusions: DCI, glucose transporter inhibitors and sugars, such as sorbitol and maltodextrin, seem to inhibit MI absorption, decreasing MI plasma concentration as compared to MI alone.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/antagonistas & inibidores , Inositol/administração & dosagem , Absorção Intestinal , Adulto , Área Sob a Curva , Transporte Biológico , Interações Medicamentosas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Inositol/farmacocinética , Masculino , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Sorbitol/administração & dosagem , Sorbitol/farmacologia , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Sacarose/farmacologia , Fatores de Tempo , Adulto Jovem
2.
J Anim Sci ; 97(9): 3898-3906, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31284292

RESUMO

Two experiments were conducted to determine the effects of myo-inositol and phytase on growth performance, plasma metabolites, and nutrient digestibility of growing pigs. In experiment 1, 96 growing pigs with average initial body weight (BW) of 26.2 kg were used in a 25-d growth performance study. Pigs were assigned to four dietary treatments with three pigs per pen and eight replicate pens per treatment in a randomized complete block design. The four treatments were control diet (CD); CD + 2 g/kg inositol; CD + 1,000 FYT/kg phytase and CD + 3,000 FYT/kg phytase. Pigs were weighed individually every week. On day 25, blood sample was collected from one pig per pen to measure plasma metabolites concentrations. In experiment 2, 16 barrows (initial BW 34.8 ± 8.2 kg) were surgically fitted with T-cannulas. Pigs were allotted to four blocks based on BW and assigned to a quadruplicate 4 × 2 incomplete Latin square design with same four dietary treatments and two periods. Ileal digesta samples were collected from each pig on days 6 and 7 of each period to determine apparent ileal digestibility (AID) of nutrients. Phytase supplementation increased final BW and average daily gain (ADG) compared with CD (P < 0.05) with no effects on average daily feed intake (ADFI) and gain to feed (G:F) was higher in 3,000 FYT/kg phytase (P < 0.05). Inositol supplementation had no effects on growth performance. Plasma myo-inositol concentration was increased by inositol supplementation, and 3,000 FYT/kg phytase increased myo-inositol in the plasma by 97.2% (P < 0.05). Plasma P concentration was increased by 1,000 or 3,000 FYT/kg phytase with no effects on alkaline phosphatase (ALP), glucose, triglycerides (TAG), calcium (Ca), and urea concentrations. Phytase supplementation reduced (P < 0.05) the phytate-P concentration in the ileal digesta and increased the digestibility of phytate-P and total P with no effects on the AID of dry matter (DM), gross energy (GE), nitrogen (N), and Ca. In conclusion, the beneficial effects of 3,000 FYT/kg phytase on feed efficiency may due to the increased release of both myo-inositol and phosphorus (P), and may not be solely due to myo-inositol release by this level of phytase.


Assuntos
6-Fitase/administração & dosagem , Suplementos Nutricionais/análise , Inositol/administração & dosagem , Fósforo na Dieta/metabolismo , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Dieta/veterinária , Digestão/efeitos dos fármacos , Íleo/metabolismo , Masculino , Ácido Fítico/metabolismo , Suínos/sangue
3.
J Anim Sci ; 97(7): 3007-3015, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31069380

RESUMO

A total of 2,156 weaned pigs (6.75 ± 0.11 kg BW) were used in a 42-d study to evaluate whether improvements in growth performance associated with super-dosing phytase can be explained by the complete dephosphorylation of phytate and liberation of inositol. Two phytase doses (0 and 2,500 FTU/kg) and 3 inositol concentrations (0%, 0.15%, and 0.30%) were combined to create 6 dietary treatments in a 2 × 3 factorial arrangement. Pigs were fed a 3-phase feeding program, with periods being 10, 10, and 22 d, respectively. Blood samples were collected on days 0, 21, and 42 from a subset of 48 pigs to analyze mineral and myo-inositol concentrations. During Phase 1, super-dosing phytase tended to improve ADG compared with pigs fed diets without phytase (P = 0.09). Increasing concentrations of inositol improved the efficiency of gain in pigs fed diets without phytase (1,022.1, 1,040.9, and 1,089.2 g/kg), but not diets with phytase (1,102.2, 1,087.2, and 1,076.2 g/kg), and this improvement was equivalent to that observed with super-dosing phytase in the absence of inositol (interaction, P = 0.015). During Phase 2, super-dosing phytase improved ADG (P = 0.001), resulting in heavier BW (P = 0.007). During Phase 3 and overall, inositol supplementation increased ADG and ADFI in a quadratic manner (P < 0.10), with the highest ADG and ADFI observed for pigs fed 0.15% of inositol. Super-dosing phytase increased serum Zn on day 21, but not on day 42 (interaction, P = 0.008), increased serum Cu (P = 0.01), but decreased serum Fe (P = 0.02). Plasma myo-inositol increased linearly from 66.9 to 97.1 and 113.2 nmol/mL with increasing inositol (P < 0.001). When plasma myo-inositol was analyzed within the subgroup of pigs fed diets without added inositol, super-dosing phytase increased plasma myo-inositol from 57.81 to 76.05 nmol/mL (0 and 2,500 FTU/kg, respectively; P = 0.05). Results demonstrate that exogenous inositol improved efficiency of gain in weaned pigs to the same level as that observed with super-dosing phytase, but this occurred only during the first 10 d of the nursery period. This suggests that the improvement in efficiency of growth when applying super-dosing phytase could be linked, in part, to complete dephosphorylation of phytate and liberation of myo-inositol, and that myo-inositol had a greater metabolic impact in piglets immediately after weaning. Consequently, myo-inositol may be a conditionally essential nutrient for young pigs during weaning stress, but further research is needed to prove this hypothesis.


Assuntos
6-Fitase/administração & dosagem , Suplementos Nutricionais/análise , Inositol/administração & dosagem , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Masculino , Minerais/metabolismo , Nutrientes/metabolismo , Fosforilação , Ácido Fítico/metabolismo , Suínos/sangue , Desmame
4.
J Agric Food Chem ; 67(21): 5957-5967, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31066268

RESUMO

d- chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.


Assuntos
Fígado Gorduroso/tratamento farmacológico , Inositol/administração & dosagem , Resistência à Insulina , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C-épsilon/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Proteína Quinase C-épsilon/genética , Proteínas Proto-Oncogênicas c-akt/genética
5.
Fish Shellfish Immunol ; 89: 248-256, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30951852

RESUMO

The effect of acute ammonia challenge on survival, immune response and antioxidant status of Litopenaeus vannamei pretreated with diets containing different inositol levels was investigated. Shrimp (initial mean weight 0.40 ±â€¯0.00 g) were randomly allocated in 18 tanks (30 shrimp per tank) and triplicate tanks were fed with a control diet without myo-inositol (MI) supplementation (242.6 mg inositol kg-1 diet) or diets containing diverse levels of inositol (368.8, 459.7, 673.1, 993.8 and 1674.4  mg kg-1 diet) as treatment groups for 8-week. Randomly selected 10 shrimp per tank (final mean weight approximately 11.1-13.8g) were exposed to ammonia stress (total ammonia-nitrogen, 60.21  mg L-1) for 24 h after feeding trial. The results showed that after exposed to ammonia stress, survival rates of MI-supplemented groups were enhanced by 31-77% when compared with the control group. MI supplementation increased activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in plasma, and reduced its activities in hepatopancreas. It also enhanced activities of total antioxidant capacity (T-AOC), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and content of reduced glutathione (GSH), and lowered malondialdehyde (MDA) and protein carbonyl (PC) content in plasma or hepatopancreas. In addition, mRNA expression levels of ferritin (FT), arginine kinase (AK), thioredoxin (Trx), heat shock protein 70 (Hsp70), catalase (CAT) and peroxiredoxin (Prx) were significantly differentially regulated in hepatopancreas owing to MI supplementation. Therefore, it suggested that L. vannamei pretreated with higher dietary inositol content may have better ammonia stress tolerance and antioxidant status after ammonia stress, and the optimum levels ranged from 459.7 to 993.8 mg inositol kg-1 when total ammonia-nitrogen concentration was 60.21  mg L-1.


Assuntos
Amônia/efeitos adversos , Antioxidantes/metabolismo , Imunidade Inata/efeitos dos fármacos , Inositol/farmacologia , Penaeidae/imunologia , Substâncias Protetoras/farmacologia , Animais , Relação Dose-Resposta a Droga , Inositol/administração & dosagem , Longevidade/efeitos dos fármacos , Penaeidae/efeitos dos fármacos , Penaeidae/fisiologia , Substâncias Protetoras/administração & dosagem , Estresse Fisiológico
6.
Diabetes Metab Res Rev ; 35(5): e3154, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30889626

RESUMO

Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin-sensitizing, anti-inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol- and antioxidant-based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Diabetes Gestacional/prevenção & controle , Inositol/administração & dosagem , Inositol/efeitos adversos , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Resistência à Insulina , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Resultado do Tratamento
7.
J Ovarian Res ; 12(1): 25, 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30904021

RESUMO

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a highly variable syndrome and one of the most common female endocrine disorders. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet. RESULTS: Fifteen PCOS-patients and 15 controls were enrolled. Patients were treated with myo-inositol (1.75 g/day), D-chiro-inositol (0.25 g/day) and glucomannan (4 g/day) for 3 months. Blood concentrations of glucose, insulin, triglycerides and cholesterol, and ovary volumes and antral follicles count, as well as metabolomic profiles, were evaluated for control subjects and for cases before and after treatment. PCOS-patients had higher BMI compared with Controls, BMI decreased significantly after 3 months of treatment although it remained significantly higher compared to controls. 3-methyl-1-hydroxybutyl-thiamine-diphosphate, valine, phenylalanine, ketoisocapric, linoleic, lactic, glyceric, citric and palmitic acid, glucose, glutamine, creatinine, arginine, choline and tocopherol emerged as the most relevant metabolites for distinguishing cases from controls. CONCLUSION: Our pilot study has identified a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan. TRIAL REGISTRATION: ClinicalTial.gov, NCT03608813 . Registered 1st August 2018 - Retrospectively registered, .


Assuntos
Inositol/administração & dosagem , Mananas/administração & dosagem , Metaboloma/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Inositol/farmacologia , Mananas/farmacologia , Ovário/efeitos dos fármacos , Ovário/patologia , Projetos Piloto , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Adulto Jovem
8.
Poult Sci ; 98(9): 3870-3883, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877748

RESUMO

This study was conducted to evaluate the effect of microbial phytase and myo-inositol supplementation in low non-phytate phosphorus (nPP) diets on pH and the solubility of minerals in an in vitro digestion procedure (IVDP) and to compare this with digesta from birds fed different diets (grower diets) compared to the in vitro test (starter diets). A total of 660 1-day-old broilers were randomly allotted into 11 dietary treatments and fed a corn-soybean-meal-based diet with recommended nPP (positive control; PC), an nPP-deficient diet (negative control; NC), NC diets supplemented with phytase (500; 1,000; 2,000; 3,000; 4,000; 5,000; and 6,000 FTU/kg), an NC diet plus 0.15% myo-inositol, and an NC diet with reduced Ca level (Ca: nPP ratio same as PC) from 1 to 23 D of age. The pH and Ca solubility of the NC diet was increased compared with the PC when subjected to IVDP (P < 0.05). P solubility in the gizzard and jejunal digesta was reduced in the NC compared with the PC diet and this was also reflected in the IVDP. Phytase addition to the NC diets linearly increased (P < 0.05) the pH value and Ca and P solubilities in both digesta and diets subjected to IVDP. Higher doses of microbial phytase increased (P < 0.05) Zn and Fe solubilities in both digesta and IVDP. Myo-inositol supplementation of the NC diet had no effect on mineral solubility, but decreased (P < 0.05) the pH of the IVDP. Lowering the Ca content of the NC diet decreased (P < 0.05) the pH of the in vitro digested diets and Ca solubility in both broiler digesta and IVDP and also increased (P < 0.05) P solubility in both the jejunal digesta and IVDP. Correlations were noted between the solubility of P in the in vitro assay and that in the gizzard and jejunal digesta, and also with bird performance, confirms the usefulness of in vitro assay.


Assuntos
6-Fitase/metabolismo , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Inositol/metabolismo , Minerais/metabolismo , Fósforo na Dieta/metabolismo , 6-Fitase/administração & dosagem , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Inositol/administração & dosagem , Distribuição Aleatória , Solubilidade
9.
Gynecol Endocrinol ; 35(8): 695-700, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30880505

RESUMO

The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.


Assuntos
Fertilização In Vitro/métodos , Infertilidade Feminina/terapia , Inositol/administração & dosagem , Síndrome do Ovário Policístico/terapia , Injeções de Esperma Intracitoplásmicas , Adolescente , Adulto , Coeficiente de Natalidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Composição de Medicamentos , Feminino , Humanos , Recém-Nascido , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Adulto Jovem
10.
Poult Sci ; 98(1): 260-268, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165681

RESUMO

This study investigated the effects of graded levels of myo-inositol (INS) in diets containing 2 levels of available P on growth performance, nutrient retention, liver N, fat and vitamin E contents, INS and alkaline phosphatase (ALP) concentrations in blood plasma. A total of 120 male Ross 308 broilers were allocated to 60 small floor pens each holding 2 birds. Two basal mash diets were formulated to be nutritionally adequate for chicks at that age, with one diet designed to have the recommended available P content (RP) (4.8 g/kg non-phytate P) and the other diet containing low available P (LP) (2.5 g/kg non-phytate P). The 2 basal diets were split in 3 batches each and 2 of the batches were supplemented with INS at 3.0 and 30 g/kg diet, with the remaining batch of each basal diet not supplemented, giving a total of 6 experimental diets. Diets were fed ad libitum to 10 pens from 7 to 21 d age following randomization. Feeding RP diets improved (P < 0.001) the birds' growth performance, mineral availability, and blood plasma ALP. Feeding RP diets reduced (P < 0.001) apparent metabolizable energy (AME), dry matter and fat availability, blood plasma INS, and hepatic vitamin E. Dietary INS did not (P > 0.05) influence bird growth, dietary AME, or nutrient retention coefficients. Feeding INS linearly increased (P < 0.05) liver weight and hepatic N content, but linearly reduced (P < 0.05) hepatic fat concentration. It also linearly increased (P < 0.001) the INS concentration in blood plasma, but did not influence (P > 0.05) the endogenous losses (measured as sialic acid concentration) in excreta. Dietary INS did not influence (P > 0.05) the hepatic vitamin E concentration but increased (P < 0.001) the ALP in the blood of birds fed 30 g/kg INS. In conclusion, high-level dietary INS supplementation did not affect bird growth performance, mineral availability, and endogenous losses, and there were no interactions between INS and P.


Assuntos
Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Inositol/administração & dosagem , Fosfatase Alcalina/sangue , Animais , Galinhas/metabolismo , Dieta/veterinária , Inositol/sangue , Fígado/metabolismo , Masculino , Nitrogênio/análise , Fósforo/deficiência , Vitamina E/análise
11.
Nutr Neurosci ; 22(11): 760-767, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29495953

RESUMO

The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut-brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO. Vehicle or VO was administered for 12 weeks. The results showed that there were alterations in levels of metabolites across several metabolic pathways in the hypothalamus. VO treatment increased levels of many amino acids including arginine, glutamine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in the hypothalamus. In addition, levels of 2-hydroxy-2-methyl-butyric acid in the hypothalamus were significantly increased after VO administration in HF diet-fed mice. Among lipid metabolites, levels of fatty acids were higher in the hypothalamus of VO-treated mice than in that of HF diet-fed mice. In terms of the energy status, the ATP/ADP ratio was higher in the hypothalamus of VO-treated mice (P < 0.001), thereby indicating an energy surplus. In conclusion, VO supplementation altered metabolite profiles in the hypothalamus to enhance catabolism, which is possibly responsible for the hypophagic effect of VO in HF diet-fed mice.


Assuntos
Inibidores de Glicosídeo Hidrolases/administração & dosagem , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Inositol/análogos & derivados , Metaboloma/efeitos dos fármacos , Aminoácidos/análise , Animais , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Inositol/administração & dosagem , Masculino , Metabolômica , Camundongos Endogâmicos C57BL
12.
Arch Gynecol Obstet ; 299(1): 55-68, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30564926

RESUMO

PURPOSE: Inositol (ISL) embraces a family of simple carbohydrates with insulin-sensitizing properties, whose most common isoforms are Myo-inositol (MYO) and D-chiro inositol (DCI). The aim of the present study was to assess the efficacy and safety of ISL supplementation during pregnancy for the prevention of gestational diabetes (GDM). METHODS: We conducted a systematic literature search in electronic databases until October 2017. We included all randomized controlled trials (RCTs) comparing pregnant women with GDM who were randomized to either ISL (i.e., intervention group) or either placebo or no treatment (i.e., control group). The primary outcome was the preventive effect on GDM, defined as the rate of GDM in women without a prior diagnosis of GDM. Pooled results were expressed as odds ratio (OR) with a 95% confidence interval (95% CI). RESULTS: Five RCTs were included (including 965 participants). ISL supplementation was associated with lower rate of GDM (OR 0.49, 95% CI 0.24-1.03, p = 0.01) and lower preterm delivery rate (OR 0.35, 95% CI 0.17-0.74, p = 0.006). No adverse effects were reported. Adjusting for the type of intervention (MYO 2 g twice daily vs MYO 1100 mg plus DCI 27.6 mg daily), a significant effect was found only in patients receiving 2 g MYO twice daily. CONCLUSIONS: ISLs administration during pregnancy appears to be safe and may represent a novel strategy for GDM prevention. In particular, the double administration of MYO 2 g per day may improve the glycemic homeostasis and may reduce GDM rate and preterm delivery rate.


Assuntos
Diabetes Gestacional/prevenção & controle , Inositol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Complexo Vitamínico B/administração & dosagem , Adulto , Glicemia , Feminino , Humanos , Recém-Nascido , Inositol/uso terapêutico , Insulina/uso terapêutico , Razão de Chances , Gravidez , Nascimento Prematuro/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Adulto Jovem
13.
J Diet Suppl ; 16(4): 454-462, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29958040

RESUMO

Cycloferin is an extract of the chemicals from the Cyclopia species, which grows only in small areas in the southwest and southeast of South Africa and has been consumed traditionally as a nourishing tea to treat numerous health issues and illnesses. Previous studies report that some of the active compounds in Cycloferin, such as pinitol (a modified sugar) and mangiferin (a glucoside), may reduce blood sugar levels and therefore may be used as a treatment for diabetes. Mangiferin, in particular, has been shown to stimulate carbohydrate oxidation and alleviate some effects of insulin resistance and hyperglycemia. Other active components of Cycloferin include flavones, isoflavones, coumestans, luteolin, 4-hydroxycinnamic acid, polyphenols, and xanthones. These active compounds are antioxidants, which can enhance glucose breakdown, lower blood lipids, and reduce the number of highly reactive compounds known as free radicals, which can alter cellular structure and function when present in large amounts. In this study, we explored the ameliorative effects of Cycloferin by treating streptozotocin- (STZ) injected rats with Cycloferin and evaluating its long-term and short-term effect on blood glucose levels and kidney and liver conditions of the diabetic-rendered rats. Our results demonstrated the ability of Cycloferin to both lower the blood glucose levels and reduce evidence of damage in kidney and liver in diabetic rats with and without exogenous insulin treatment for partial control of diabetic state.


Assuntos
Cyclopia (Planta)/química , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/uso terapêutico , Extratos Vegetais/administração & dosagem , Animais , Glicemia/análise , Diabetes Mellitus Experimental/complicações , Suplementos Nutricionais , Inositol/administração & dosagem , Inositol/análogos & derivados , Inositol/análise , Inositol/farmacologia , Nefropatias/patologia , Nefropatias/prevenção & controle , Hepatopatias/patologia , Hepatopatias/prevenção & controle , Masculino , Fitoterapia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Xantonas/administração & dosagem , Xantonas/análise , Xantonas/farmacologia
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(11): 1378-1383, 2018 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-30514689

RESUMO

OBJECTIVE: To study the effects of myo-inositol and luteolin on human lung cancer A549 cells and explore the possible mechanisms. METHODS: A549 cells were treated with different concentrations of myo-inositol and luteolin, either alone or in combination, and the cell viability was examined using MTT assay. A549 cells and human bronchial epithelial Beas-2B cells were treated for 48 h with 10 mmol/L myo-inositol and 20 µmol/L luteolin, alone or in combination, and the cell proliferation was detected using MTT assay; the colony formation and migration of the cells were examined with colony formation assay and wound healing assay, respectively. The protein expression levels in A549 cells were detected using Western blotting. RESULTS: Both myo-inositol and luteolin could dose-dependently inhibit the viability of A549 cells. Treatments with 10 mmol/L myo-inositol, 20 µmol/L luteolin, and both for 48 h caused significant reduction in the cell viability (92%, 83% and 70% of the control level, respectively) and colony number (79%, 73% and 43%, respectively), and significantly lowered the wound closure rate (24.61%, 13.08% and 8.65%, respectively, as compared with 29.99% in the control group). Similar treatments with myoinositol and luteolin alone or in combination produced no significant inhibitory effect on the growth, colony formation or migration of Beas-2B cells. The expressions of p-PDK1 and p-Akt in myo-inositol-treated A549 cells and the expression of pPDK1 in luteolin-treated cells were significantly decreased (P < 0.05), and the decrements were more obvious in the combined treatment group (P < 0.05). CONCLUSIONS: Luteolin combined with myo-inositol can selectively inhibit the proliferation and migration of A549 cells, and these effects are probably mediated, at least in part, by suppressing the activation of PDK1 and Akt.


Assuntos
Inositol/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Luteolina/uso terapêutico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células A549 , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Inositol/administração & dosagem , Luteolina/administração & dosagem , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Complexo Vitamínico B
15.
Trials ; 19(1): 632, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445999

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) affects between 8 and 18% of women and is the leading cause of female anovulatory infertility. Unfortunately, common treatments for women trying to conceive can be ineffective as well as disruptive or harmful to patients' quality of life. Despite evidence that women with PCOS have expressed the need for alternative fertility treatments, lifestyle interventions incorporating a nutritional plan with supplementation, increased physical activity, and techniques for stress management have not been combined as a program and studied in this population. Literature suggests that each of these individual components can positively influence reproductive hormones and metabolic health. METHODS/DESIGN: This is a randomized controlled trial which will include 240 women diagnosed with PCOS, according to the Rotterdam criteria, who are trying to conceive. Participants will be randomized to either a comprehensive lifestyle intervention program or prescribed an oral fertility medication, letrozole. These two groups will be further randomized to consume either myo-inositol or a placebo. Participants will be between the ages of 18 and 37 years. Exclusion criteria include women who have already begun fertility treatment, who are currently using myo-inositol or have taken it within the past 3 months, or who are being treated for, or have a history of, an eating disorder. The primary outcome will be the ovulation rate, the secondary outcome will be conception. Other outcomes include miscarriage rates, validated rating measures of overall quality of life (including social, relational, mind/body and emotional sub-categories) and mental health scores (depression, anxiety, and stress). DISCUSSION: This trial will determine the effectiveness of a structured lifestyle-based comprehensive intervention program for women with PCOS experiencing infertility. In addition, it will determine whether supplementing with myo-inositol provides any further benefit. The objective of this study is to assess a possible non-pharmacological solution to ovulatory dysfunction in these patients and perhaps improve other associated features of PCOS. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02630485 . Registered on 15 December 2015.


Assuntos
Fármacos para a Fertilidade Feminina/administração & dosagem , Estilo de Vida Saudável , Infertilidade Feminina/terapia , Inositol/administração & dosagem , Letrozol/administração & dosagem , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/terapia , Administração Oral , Adolescente , Adulto , Exercício Físico , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Inositol/efeitos adversos , Letrozol/efeitos adversos , Atenção Plena , Países Baixos , Educação de Pacientes como Assunto , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Relaxamento , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Eur Rev Med Pharmacol Sci ; 22(20): 7078-7085, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30402876

RESUMO

OBJECTIVE: Reduction in motility and number of spermatozoa and change in their morphology are some of the most relevant causes of male infertility. Production of reactive oxygen species may affect motility, morphology and DNA stability of spermatozoa. This study aimed at evaluating the effect of combined treatment with myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins (namely, Sinopol®) on semen parameters of sub-fertile men. PATIENTS AND METHODS: We recruited 143 sub-fertile men, 26-53 years aged, no-smokers, without any testicular pathologies, with a normal endocrinological/metabolic profile, and no concomitant consumption of drugs. Out of them, 25 patients did not meet study inclusion criteria mainly due to the history of genital diseases that came to light after Sinopol® prescription. Among the 118 men that fulfilled inclusion criteria, 10 (8.4%) patients were lost at follow-up and in 8 (6.8%) cases the partner got pregnant spontaneously. Thus, 100 patients completed the study and semen analysis was performed before and after 90 days of treatment. RESULTS: Semen quality improved after 90 days of treatments, with a statistically significant increase of sperm concentration (p=0.0009), of number of spermatozoa (p=0.0017), of progressive motility (p=0.0047), of total motile sperm count (p=0.0010), and of normal sperm morphology (p<0.0001). CONCLUSIONS: For the first time we reported that a combination of nutraceuticals composed of myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins improves sperm parameters in sub-fertile men. We are aware that to clarify the clinical relevance of the data studies with larger sample sizes and longer durations are needed, as well as evaluation of myo-inositol and alpha-lipoic acid co-treatment effectiveness in improving the chances to obtain a pregnancy spontaneously or following assisted reproduction.


Assuntos
Infertilidade Masculina/tratamento farmacológico , Análise do Sêmen , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Adulto , Feminino , Ácido Fólico/administração & dosagem , Humanos , Inositol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Sêmen/efeitos dos fármacos , Contagem de Espermatozoides , Ácido Tióctico/administração & dosagem , Vitaminas/administração & dosagem
17.
BMJ Open ; 8(9): e022831, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30249632

RESUMO

INTRODUCTION: Gestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplement myo-inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial on myo-inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial. METHODS AND ANALYSIS: EMmY is a multicentre, placebo-controlled, double-blind, pilot, randomised trial, with qualitative evaluation. We will recruit pregnant women at 12-15+6 weeks' gestation, with gestational diabetes risk factors, from five maternity units in England between 2018 and 2019. We will randomise 200 women to take either 2 g of myo-inositol powder (intervention) or placebo, twice daily until delivery. We will assess rates of recruitment, randomisation, adherence to intervention and follow-up. Gestational diabetes will be diagnosed at 24-28 weeks as per the National Institute for Health and Care Excellence (NICE) criteria (fasting plasma glucose: ≥5.6 mmol/L and 2-hour plasma glucose: ≥7.8 mmol/L). We will assess the effects of myo-inositol on glycaemic indices at 28 weeks and on other maternal, fetal and neonatal outcomes at postnatal discharge. Qualitative evaluation will explore the acceptability of the trial and the intervention among women and healthcare professionals. Cost data and health-related quality of life measures will be captured. We will summarise feasibility outcomes using standard methods for proportions and other descriptive statistics, and where appropriate, report point estimates of effect sizes (eg, mean differences and relative risks) and associated 95% CIs. ETHICS AND DISSEMINATION: Ethical approval was obtained through the London Queen Square Research Ethics Committee (17/LO/1741). Study findings will be submitted for publication in peer-reviewed journals. Newsletters will be made available to participants, healthcare professionals and members of Katie's Team (a patient and public advisory group) to disseminate. TRIAL REGISTRATION NUMBER: ISRCTN48872100. PROTOCOL VERSION AND DATE: Version 4.0, 15 January 2018.


Assuntos
Diabetes Gestacional , Inositol , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Inglaterra , Feminino , Idade Gestacional , Índice Glicêmico , Humanos , Inositol/administração & dosagem , Inositol/efeitos adversos , Projetos Piloto , Gravidez , Resultado da Gravidez , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/efeitos adversos
18.
Int J Clin Pharmacol Ther ; 56(11): 544-550, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30178742

RESUMO

OBJECTIVE: This study aimed at exploring the effects of metformin on the pharmacodynamics of voglibose, while investigating the pharmacodynamics between a fixed-dose combination (FDC) of voglibose/metformin and coadministered doses of voglibose and metformin tablets in healthy Korean subjects. MATERIALS AND METHODS: A randomized, open-label, 2×3×3 crossover study with a 9-day washout period was conducted in 30 healthy subjects. All subjects received orally administered voglibose alone, individual voglibose and metformin tablets, or FDC 3 times daily for 5 days. Oral sucrose was administered on day -1 (pretreatment) and at 10 minutes after the morning dose of the study drug on day 5 of each period. Plasma glucose and serum insulin were measured over the course of 2 hours following sucrose loading. RESULTS: 21 subjects completed the study. The geometric mean ratios (GMR) of ΔCmax and the AUC of glucose for voglibose plus metformin vs. voglibose alone were 0.995 (90% CI, 0.800 - 1.237) and 0.969 (90% CI, 0.949 - 0.990), respectively; the GMRs for individual tablets vs. FDC were 1.118 (90% CI, 0.930 - 1.344) and 1.010 (90% CI, 0.974 - 1.048), respectively. A relatively smaller number of subjects experienced adverse events when receiving voglibose alone compared to those administered FDC or metformin and voglibose. There were no significant differences in adverse events between individual voglibose and metformin tablets and FDC. CONCLUSION: Coadministered metformin did not have statistically or clinically significant effects on the pharmacodynamics of voglibose in healthy subjects. Glucose levels following sucrose loading seem not to be clinically different between FDC and individual tablets of voglibose and metformin.
.


Assuntos
Inibidores Enzimáticos/farmacocinética , Hipoglicemiantes/farmacocinética , Inositol/análogos & derivados , Metformina/farmacocinética , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Glicemia/análise , Estudos Cross-Over , Combinação de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Voluntários Saudáveis , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Inositol/administração & dosagem , Inositol/efeitos adversos , Inositol/farmacocinética , Insulina/sangue , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Comprimidos , Adulto Jovem
19.
FEMS Microbiol Lett ; 365(20)2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184134

RESUMO

Florfenicol, a synthetic drug with chemical structure and spectrum of antibacterial activity similar to chloramphenicol, has been shown to be effective against a number of bacterial pathogens. However, there are increasing signs of florfenicol-resistant bacteria due to the misuse and overuse of florfenicol in aquaculture. In the present study, florfenicol had a higher bactericidal efficacy in the presence of myo-inositol, which may be due to the ability of myo-inositol to increase susceptibility of Aeromonas hydrophila to florfenicol. Furthermore, in two different infected models, co-administration of myo-inositol and florfenicol significantly reduced the bacterial load in the liver, kidney and spleen tissues of A. hydrophila-infected Cyprinus carpio, and greatly increased the survival rate of infected fish. Finally, it was also found that myo-inositol exhibited synergistic action with other antibiotic drugs including neomycin sulfate, ceftriaxone and enrofloxacin. The results obtained in this study suggest that myo-inositol as an efficient adjuvant to antibiotic drugs could be useful in increasing the antimicrobial activity of antibiotic drugs against A. hydrophila infection, and could also be useful to help decrease the occurrence of antibiotic overuse in aquaculture.


Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Antibacterianos/administração & dosagem , Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/veterinária , Inositol/administração & dosagem , Tianfenicol/análogos & derivados , Estruturas Animais/microbiologia , Animais , Antibacterianos/farmacologia , Carga Bacteriana , Carpas , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Inositol/farmacologia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tianfenicol/administração & dosagem , Tianfenicol/farmacologia , Resultado do Tratamento
20.
Arch Gynecol Obstet ; 298(4): 675-684, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30078122

RESUMO

PURPOSE: To evaluate whether oral myo-inositol supplementation (MI) is able to reduce the amount of gonadotropins (GA) and the length of controlled ovarian hyperstimulation (SL) in both Polycystic Ovarian Syndrome (PCOS) and non-PCOS women undergoing in vitro fertilization (IVF). METHODS: We performed a systematic review (PROSPERO ID: CRD42017069439) of randomized controlled trials (RCTs). We searched articles published in English between January 1985 to August 2017, using the combination of the Medical Subject Headings "Inositol" with "Ovulation Induction", "follicle-stimulating hormone, human, with HCG C-terminal peptide", "Reproductive Techniques, Assisted", and "Fertilization in Vitro". We collected data about GA and SL comparing MI to no treatment or D-Chiro-Inositol (DCI) supplementation (controls). A subgroup analysis was performed to evaluate selected outcomes in PCOS and non-PCOS women. RESULTS: We included 8 studies embedding 812 participants. We found a reduction in GA (p < 0.00001) and SL (p = 0.0007) in patients receiving MI with respect to controls. MI was effective in both PCOS (p < 0.00001) and non-PCOS women (p = 0.02) in reducing GA; conversely, MI supplementation decreased the SL only in PCOS women (p < 0.00001). CONCLUSION: During IVF, MI is effective in both PCOS and non-PCOS women in saving gonadotropins, but reduces efficiently SL only in PCOS women.


Assuntos
Fertilização In Vitro/métodos , Gonadotropinas/administração & dosagem , Inositol/administração & dosagem , Indução da Ovulação , Síndrome do Ovário Policístico/fisiopatologia , Suplementos Nutricionais , Feminino , Humanos , Indução da Ovulação/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
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