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1.
Neurosci Lett ; 764: 136205, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478818

RESUMO

Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund's adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC). Inhibition of glycogenolysis and lactate release in the ACC disrupted the persistent, but not acute, inflammation pain induced by CFA, and this effect was reversed by exogenous L-lactate administration. Knocking down the expression of lactate transporters (MCT1, MCT4, or MCT2) also disrupted the long lasting inflammation pain induced by CFA. Moreover, glycogenolysis in the ACC is critical for the induction of molecular changes related to neuronal plasticity, including the induction of phospho- (p-) ERK, p-CREB, and Fos. Taken together, our findings indicate that astrocyte-neuron lactate transport in the ACC is critical for the occurrence of persistent inflammation pain, suggesting a novel mechanism underlying chronic pain.


Assuntos
Arabinose/farmacologia , Comunicação Celular/imunologia , Dor Crônica/imunologia , Giro do Cíngulo/patologia , Imino Furanoses/farmacologia , Ácido Láctico/metabolismo , Álcoois Açúcares/farmacologia , Animais , Arabinose/uso terapêutico , Astrócitos/metabolismo , Comunicação Celular/efeitos dos fármacos , Dor Crônica/tratamento farmacológico , Dor Crônica/patologia , Modelos Animais de Doenças , Adjuvante de Freund/administração & dosagem , Adjuvante de Freund/imunologia , Glicogenólise/efeitos dos fármacos , Glicogenólise/imunologia , Giro do Cíngulo/citologia , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/imunologia , Humanos , Imino Furanoses/uso terapêutico , Masculino , Camundongos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/imunologia , Neurônios/metabolismo , Álcoois Açúcares/uso terapêutico
2.
Chin Med J (Engl) ; 132(15): 1833-1842, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31268903

RESUMO

BACKGROUND: Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. METHODS: C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. RESULTS: After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315). CONCLUSIONS: Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.


Assuntos
Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos , Probióticos/farmacologia , Probióticos/uso terapêutico , Análise de Variância , Animais , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Microbioma Gastrointestinal/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Distribuição Aleatória , Álcoois Açúcares/farmacologia , Álcoois Açúcares/uso terapêutico
3.
Acta Biomater ; 97: 105-115, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31326667

RESUMO

Advances in the field of nanomedicine have led to the development of various gene carriers with desirable cellular responses. However, unfavorable stability and physicochemical properties have hindered their applications in vivo. Therefore, multifunctional, smart nanocarriers with unique properties to overcome such drawbacks are needed. Among them, sugar alcohol-based nanoparticle with abundant surface chemistry, numerous hydroxyl groups, acceptable biocompatibility and biodegradable property are considered as the recent additions to the growing list of non-viral vectors. In this review, we present some of the major advances in our laboratory in developing sugar-based polymers as non-viral gene delivery vectors to treat various diseases. We also discuss some of the open questions in this field. STATEMENT OF SIGNIFICANCE: Recently, the development of sugar alcohol-based polymers conjugated with polyethylenimine (PEI) has attracted tremendous interest as gene delivery vectors. First, the natural backbone of polymers with their numerous hydroxyl groups display a wide range of hyperosmotic properties and can thereby enhance the cellular uptake of genetic materials via receptor-mediated endocytosis. Second, conjugation of a PEI backbone with sugar alcohols via Michael addition contributes to buffering capacity and thereby the proton sponge effect. Last, sugar alcohol based gene delivery systems improves therapeutic efficacy both in vitro and in vivo.


Assuntos
Portadores de Fármacos , Técnicas de Transferência de Genes , Terapia Genética , Nanopartículas , Álcoois Açúcares , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Álcoois Açúcares/química , Álcoois Açúcares/uso terapêutico
4.
Nutrients ; 11(5)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117218

RESUMO

Psyllium and lactitol have been reported to increase fecal volume, moisture content and bowel movement frequency (BMF). However, the benefits of their combined use on constipation has not been examined. The aim of this study was to evaluate the effects of a 4-week intervention with lactitol and/or psyllium on bowel function in constipated volunteers. Adults (N = 172) who were diagnosed with functional constipation per Rome III criteria were randomized to four treatment groups: 10 g lactitol, 3.5 g psyllium, a combination of 10 g lactitol and 3.5 g psyllium, or placebo. The primary endpoint was change in BMF from Day 0 to 28 as compared to placebo. Secondary endpoints were assessed by inventories, including stool consistency, patient assessment of constipation symptoms and quality of life, relief of constipation, 24-h food recall, physical activity, product satisfaction and adverse events (AE). BMF increased by 3.0 BMs with lactitol, by 2.9 with psyllium, and by 3.1 with the combination, but was not different from placebo (3.7 BMs). Other clinical endpoints were similar between treatments. No serious AEs were reported. In conclusion, this study showed a similar effect on relief of constipation in all treatment groups. The treatments that were administered to the volunteers were well tolerated.


Assuntos
Constipação Intestinal/tratamento farmacológico , Psyllium/uso terapêutico , Álcoois Açúcares/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Psyllium/administração & dosagem , Álcoois Açúcares/administração & dosagem
5.
Molecules ; 23(10)2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30340368

RESUMO

Some point mutations in ß-glucocerebrosidase cause either improper folding or instability of this protein, resulting in Gaucher disease. Pharmacological chaperones bind to the mutant enzyme and stabilize this enzyme; thus, pharmacological chaperone therapy was proposed as a potential treatment for Gaucher disease. The binding affinities of α-1-C-alkyl 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives, which act as pharmacological chaperones for ß-glucocerebrosidase, abruptly increased upon elongation of their alkyl chain. In this study, the primary causes of such an increase in binding affinity were analyzed using protein⁻ligand docking and molecular dynamics simulations. We found that the activity cliff between α-1-C-heptyl-DAB and α-1-C-octyl-DAB was due to the shape and size of the hydrophobic binding site accommodating the alkyl chains, and that the interaction with this hydrophobic site controlled the binding affinity of the ligands well. Furthermore, based on the aromatic/hydrophobic properties of the binding site, a 7-(tetralin-2-yl)-heptyl-DAB compound was designed and synthesized. This compound had significantly enhanced activity. The design strategy in consideration of aromatic interactions in the hydrophobic pocket was useful for generating effective pharmacological chaperones for the treatment of Gaucher disease.


Assuntos
Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/antagonistas & inibidores , Imino Açúcares/química , Álcoois Açúcares/química , Sítios de Ligação , Estabilidade Enzimática/efeitos dos fármacos , Glucosilceramidase/química , Humanos , Imino Açúcares/uso terapêutico , Ligantes , Chaperonas Moleculares/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Mutação Puntual , Ligação Proteica , Álcoois Açúcares/antagonistas & inibidores , Álcoois Açúcares/uso terapêutico
6.
Medicina (Kaunas) ; 54(2)2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30344249

RESUMO

Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as 'safe' by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler's diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists.


Assuntos
Gastroenteropatias/prevenção & controle , Trato Gastrointestinal , Lactose/química , Prebióticos , Probióticos/uso terapêutico , Catárticos/uso terapêutico , Neoplasias do Colo/prevenção & controle , Constipação Intestinal/prevenção & controle , Diarreia/microbiologia , Diarreia/terapia , Galactosídeos/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Encefalopatia Hepática/prevenção & controle , Humanos , Doenças Inflamatórias Intestinais/prevenção & controle , Lactulose/uso terapêutico , Oligossacarídeos/uso terapêutico , Probióticos/farmacologia , Álcoois Açúcares/uso terapêutico , Trissacarídeos/uso terapêutico
7.
Clin Oral Investig ; 21(9): 2733-2740, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28303470

RESUMO

OBJECTIVES: The caries preventive effect of long-term use (1 year) of low-dosage (2.5 g/die) of xylitol chewing gum in a high-caries-risk adult population was evaluated. MATERIALS AND METHODS: In this randomized clinical trial, 179 high-caries-risk adults were assigned to two experimental groups, xylitol and polyols. Caries status, salivary mutans streptococci (MS), and plaque pH were re-evaluated after 2 years from baseline in 66 xylitol and 64 polyol subjects. Outcomes (the net caries increment for initial, moderate, and extensive caries lesions and for the caries experience) were evaluated using the nonparametric Mann-Whitney U test. RESULTS: The total caries experience increment was 1.25 ± 1.26 in the xylitol group and 1.80 ± 2.33 in the polyol group (p = 0.01). Subjects treated with xylitol chewing gums had a reduction of risk rate at tooth level of 23% with respect to those treated with polyols with a number needed to treat of 55 teeth. The area under the curve at pH 5.7 was statistically significantly lower (p = 0.02) during the experimental period in the xylitol group. A decrease of the concentration of salivary MS was noted in the xylitol group (p < 0.01). CONCLUSIONS: Subjects using the low-dose xylitol chewing gum showed a significantly lower increment of initial and extensive caries lesions and overall a lower increment of caries experience. CLINICAL RELEVANCE: One-year use of chewing gums provides an effective means for the prevention of caries disease. TRIAL REGISTRATION NUMBER: NCT02310308.


Assuntos
Goma de Mascar , Cárie Dentária/prevenção & controle , Edulcorantes/uso terapêutico , Xilitol/uso terapêutico , Adulto , Cárie Dentária/epidemiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Saliva/microbiologia , Álcoois Açúcares/administração & dosagem , Álcoois Açúcares/uso terapêutico , Edulcorantes/administração & dosagem , Xilitol/administração & dosagem
8.
Int J Food Sci Nutr ; 68(1): 73-81, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27687609

RESUMO

This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Modelos Animais de Doenças , Hipoglicemiantes/uso terapêutico , Mucosa Intestinal/metabolismo , Maltose/análogos & derivados , Músculo Esquelético/metabolismo , Álcoois Açúcares/uso terapêutico , Absorção Fisiológica , Animais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Esvaziamento Gástrico , Fármacos Gastrointestinais/metabolismo , Fármacos Gastrointestinais/uso terapêutico , Trânsito Gastrointestinal , Glucose/metabolismo , Hiperglicemia/prevenção & controle , Técnicas In Vitro , Insulina/metabolismo , Absorção Intestinal , Jejuno/metabolismo , Masculino , Maltose/metabolismo , Maltose/uso terapêutico , Músculos Psoas , Distribuição Aleatória , Ratos Sprague-Dawley , Álcoois Açúcares/metabolismo
9.
Metab Brain Dis ; 31(6): 1361-1364, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27638474

RESUMO

Nonabsorbable disaccharides have been the mainstay of treatment for hepatic encephalopathy since introduced into clinical practice in 1966. Their beneficial effects reflect their ability to reduce the intestinal production/absorption of ammonia. A recent Cochrane review confirmed the efficacy and safety of nonabsorbable disaccharides for the treatment and prevention of hepatic encephalopathy in patients with cirrhosis. The findings were robust and support the use of nonabsorbable disaccharides as a first line treatment for hepatic encephalopathy, in this patient population, and for its prevention.


Assuntos
Dissacarídeos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/metabolismo , Absorção Intestinal/fisiologia , Amônia/antagonistas & inibidores , Amônia/metabolismo , Animais , Dissacarídeos/farmacologia , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Absorção Intestinal/efeitos dos fármacos , Lactulose/farmacologia , Lactulose/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Álcoois Açúcares/farmacologia , Álcoois Açúcares/uso terapêutico
10.
Cochrane Database Syst Rev ; (5): CD003044, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-27153247

RESUMO

BACKGROUND: Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. OBJECTIVES: To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. SEARCH METHODS: We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. SELECTION CRITERIA: We included RCTs, irrespective of publication status, language, or blinding. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. MAIN RESULTS: We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I(2) = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I(2) = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I(2) = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). AUTHORS' CONCLUSIONS: This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention.


Assuntos
Dissacarídeos/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/prevenção & controle , Lactulose/uso terapêutico , Cirrose Hepática/complicações , Álcoois Açúcares/uso terapêutico , Dissacarídeos/efeitos adversos , Encefalopatia Hepática/mortalidade , Humanos , Neomicina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Conduta Expectante
11.
Cochrane Database Syst Rev ; 4: CD003044, 2016 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-27089005

RESUMO

BACKGROUND: Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. OBJECTIVES: To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. SEARCH METHODS: We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. SELECTION CRITERIA: We included RCTs, irrespective of publication status, language, or blinding. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. MAIN RESULTS: We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I(2) = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I(2) = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I(2) = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). AUTHORS' CONCLUSIONS: This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention.


Assuntos
Antibacterianos/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Lactulose/uso terapêutico , Álcoois Açúcares/uso terapêutico , Encefalopatia Hepática/mortalidade , Encefalopatia Hepática/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Arch Pediatr ; 23(6): 664-7, 2016 Jun.
Artigo em Francês | MEDLINE | ID: mdl-27117998

RESUMO

Functional constipation is a common pediatric problem in general practice and even more so in pediatric gastroenterology clinics. Treatment is often delayed with psychosocial and digestive consequences. However, treatment is well codified and effective. Hyperosmotic mineral water, diet, and endoanal medications are not treatments for established constipation, whatever the age. The lactulose/lactitol-based medications are authorized and effective before 6 months of age and polyethylene-glycol for infants over 6 months. Mineral oil is less prescribed. The rule for treatment is a sufficient dose for a long time. In case of fecal impaction with or without fecal incontinence, the first stage is fecal disimpaction, using a high dose of PEG the first few days, or repeated phosphate enemas. Education regarding the adaptation of toilets and a daily bowel movement should restore colic motility and avoid relapses when the treatment is discontinued. Psychological concerns should be evaluated and treated.


Assuntos
Constipação Intestinal/terapia , Criança , Constipação Intestinal/psicologia , Impacção Fecal/terapia , Humanos , Lactente , Lactulose/uso terapêutico , Laxantes/uso terapêutico , Polietilenoglicóis/uso terapêutico , Álcoois Açúcares/uso terapêutico
13.
J Med Food ; 18(10): 1081-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26061453

RESUMO

Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis, ultimately leading to cirrhosis and liver cancer. It is important to prevent this progression during the initial stages of hepatic fatty degeneration. Maltitol is a polyol produced by the hydrogenation of maltose. We investigated the efficacy of maltitol for treating hepatic fatty degeneration in C57BL/6 male mice using a high-fat diet model. Intake of 5.0% maltitol for 8 weeks significantly suppressed weight gain, hepatic fatty degeneration, hyperglycemia, and hypercholesterolemia. With maltitol intake, sterol regulatory element-binding protein 1c (SREBP1c) mRNA expression was significantly decreased, and farnesoid X receptor (FXR), peroxisome proliferator-activated receptor α (PPARα), and hydroxymethylglutaryl-Co reductase expressions were significantly higher in the liver. The increase in SREBP1c and suppression of FXR and PPARα expressions are correlated with NAFLD. Our results suggest that maltitol may prevent steatosis of NAFLD with a high-fat diet.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Maltose/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Álcoois Açúcares/administração & dosagem , Animais , Suplementos Nutricionais , Expressão Gênica/efeitos dos fármacos , Hidroximetilglutaril-CoA Redutases/genética , Hipercolesterolemia/prevenção & controle , Hiperglicemia/prevenção & controle , Fígado/química , Masculino , Maltose/administração & dosagem , Maltose/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/genética , RNA Mensageiro/análise , Receptores Citoplasmáticos e Nucleares/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Álcoois Açúcares/uso terapêutico , Aumento de Peso/efeitos dos fármacos
14.
Nutrients ; 7(3): 1480-93, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25734563

RESUMO

The antidiabetic effect of a hot water extract of stems of Salacia chinensis (SCE) was evaluated in vivo in KK-Ay mice, a typical type 2 diabetes mellitus mice model. Administration of CE-2 dietary feed containing 0.25 and/or 0.50% of SCE for three weeks to KK-Ay mice significantly suppressed the elevation of both blood glucose and HbA1c levels without significant changes in body weight or food intake. Glucose tolerance was improved by administration to KK-Ay mice for 27 days of AIN93M purified dietary feed containing 0.12% of SCE. No suppressive effect with respect to HbA1c level was observed when AIN93M/Glc dietary feed in which all digestible glucides were replaced with glucose was administered with SCE. Thus, α-glucosidase inhibitory activity approved as the mechanism of action of the antidiabetic effect of SCE by in vitro investigation was reconfirmed also in in vivo studies. Evaluation of the α-glucosidase inhibitory activity of the active constituents, salacinol (1), kotalanol (3), and neokotalanol (4), by employing human α-glucosidases revealed that these compounds inhibited them as potently (IC50 = 3.9-4.9 µM for maltase) as they inhibited rat small intestinal α-glucosidase. The principal sulfonium constituents (1-4) were highly stable in an artificial gastric juice. In addition, 1-4 were hardly absorbed from the intestine in an experiment using the in situ rat ligated intestinal loop model. The results indicate that these sulfoniums are promising leads for a new type of anti-diabetic agents.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Monossacarídeos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Salacia/química , Álcoois Açúcares/uso terapêutico , Sulfatos/uso terapêutico , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Hemoglobinas Glicadas/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Intestino Delgado/metabolismo , Masculino , Camundongos , Monossacarídeos/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Álcoois Açúcares/farmacologia , Sulfatos/farmacologia , Compostos de Sulfônio/farmacologia , Compostos de Sulfônio/uso terapêutico , alfa-Glucosidases/metabolismo
15.
Nutr Clin Pract ; 30(5): 665-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25694210

RESUMO

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fructose, lactose, fructans, galactans, polyols (sorbitol, mannitol, maltitol, xylitol, erythritol, polydextrose, and isomalt), irritable bowel syndrome, and functional gastrointestinal symptoms. FODMAP-restricted diets have been used for a long time to manage patients with IBS. The innovation in the so-called FODMAP concept is that a global restriction should have a more consistent effect than a limited one in preventing abdominal distension. Even though all the potential low FODMAP diets provide good relief of symptoms in many patients, there is just a little relief in others. Several studies highlight the role of low FODMAP diets to improve symptoms in patients with IBS. The evidence on this dietary approach supports the hypothesis that a low FODMAP diet should be the first dietary approach. However, many points remain to be clarified, including the evaluation of possibly significant nutrition concerns.


Assuntos
Dieta , Carboidratos da Dieta/uso terapêutico , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/uso terapêutico , Oligossacarídeos/uso terapêutico , Álcoois Açúcares/uso terapêutico , Fermentação , Humanos
16.
Int J Dent Hyg ; 12(4): 238-44, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24650323

RESUMO

OBJECTIVE: The objective of this study was to test the effect of sugar-free chewing gum sweetened with xylitol or maltitol compared to the use of a gum base or no gum on gingivitis and plaque scores under both brushing and non-brushing circumstances. METHODS: The design of the study was a four-group, double-blinded, randomized controlled study with a 3-week duration. In each group, the participants did not brush the teeth in the lower jaw designated to develop experimental gingivitis, while maintaining normal oral hygiene procedures in the upper jaw. After professional dental prophylaxis, the participants were allocated into one of four groups (xylitol, maltitol, gum base or no gum). Chewing gum was used five times a day for 10 min. RESULTS: 220 participants completed the study and provided evaluable data. The increase in bleeding on marginal probing (BOMP) and plaque scores (PS) in the non-brushed (lower) jaw with experimental gingivitis was significant in all groups (P < 0.001). As compared to the gum base, the increase in BOMP in the xylitol and maltitol group was significantly lower. In the brushed upper jaw, no significant changes for BOMP were observed from the baseline to the end point of the study, and there were no significant differences in BOMP and PS between the groups. CONCLUSION: In circumstances where regular brushing is performed, no effect of chewing gum was observed on bleeding and plaque scores. In the absence of brushing, chewing xylitol or maltitol gum provided a significant inhibitory effect on gingivitis scores compared to chewing gum base. The difference when compared to the group not using gum was not significant.


Assuntos
Goma de Mascar , Placa Dentária/etiologia , Gengivite/etiologia , Maltose/análogos & derivados , Álcoois Açúcares/uso terapêutico , Edulcorantes/uso terapêutico , Xilitol/uso terapêutico , Adolescente , Adulto , Placa Dentária/prevenção & controle , Índice de Placa Dentária , Método Duplo-Cego , Feminino , Gengivite/prevenção & controle , Humanos , Masculino , Maltose/uso terapêutico , Higiene Bucal , Índice Periodontal , Escovação Dentária/métodos , Adulto Jovem
17.
Med Clin (Barc) ; 142(11): 512-4, 2014 Jun 06.
Artigo em Espanhol | MEDLINE | ID: mdl-24480288

RESUMO

Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis.


Assuntos
Encefalopatia Hepática/prevenção & controle , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Depressores do Sistema Nervoso Central/efeitos adversos , Contraindicações , Diuréticos/efeitos adversos , Hemorragia Gastrointestinal/etiologia , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/etiologia , Hiperamonemia/prevenção & controle , Absorção Intestinal , Lactulose/administração & dosagem , Lactulose/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado , Metanálise como Assunto , Peritonite/complicações , Derivação Portossistêmica Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Recidiva , Rifamicinas/administração & dosagem , Rifamicinas/farmacocinética , Rifamicinas/uso terapêutico , Rifaximina , Fatores de Risco , Álcoois Açúcares/administração & dosagem , Álcoois Açúcares/uso terapêutico
18.
Eur J Paediatr Dent ; 14(4): 303-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24313583

RESUMO

AIM: The effects on plaque parameters of sugar free chewing-gums (CG) sweetened with either maltitol or xylitol were assessed to better understand the role polyols can play in dental caries prevention. MATERIALS AND METHODS: A double-blind, parallel, randomised, controlled study was conducted in China. Subjects (N = 258, age = 13 to 15 years-old) were divided into 4 groups: 2 receiving polyols CG, containing respectively maltitol or xylitol, a group receiving gum base (placebo) and a negative control group not receiving any gum. CG were chewed for 30 days. This corresponds to a 10 g consumption of polyol per day. Plaque parameters (growth, pH, bacteria and insoluble glucans) were evaluated throughout the experimental period. RESULTS: All parameters studied were significantly modified with gum base compared to no-gum: plaque pH increased; plaque growth, bacteria (S. mutans, S. sobrinus, A. viscosus and Lactobacillus) and insoluble glucans decreased. Maltitol and xylitol CG led similarly to a higher plaque pH (AUC, p⋜0.05) on short (at baseline after the first CG consumption) and long term (after 4 weeks of daily CG consumption), with or without saliva stimulation compared to both control and placebo groups. They led to a decrease in plaque growth (p=0.02) over the experimental period compared to controls. Moreover, they significantly reduced the concentration of 4 cariogenic bacteria species (p⋜0.05) in dental plaque compared to gum base. CONCLUSION: Sugar free CG sweetened with either maltitol or xylitol can similarly reduce plaque acidogenicity compared to gum base through a decrease in oral bacteria presence. The use of a gum base placebo allowed to isolate effects on parameters involved in dental caries development specific to maltitol and xylitol, and to show these effects were similar.


Assuntos
Cariostáticos/uso terapêutico , Goma de Mascar , Cárie Dentária/prevenção & controle , Maltose/análogos & derivados , Álcoois Açúcares/uso terapêutico , Xilitol/uso terapêutico , Actinomyces viscosus/isolamento & purificação , Adolescente , Análise de Variância , Área Sob a Curva , Placa Dentária/química , Placa Dentária/microbiologia , Índice de Placa Dentária , Método Duplo-Cego , Glucanos/análise , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus/isolamento & purificação , Maltose/uso terapêutico , Estatísticas não Paramétricas , Streptococcus mutans/isolamento & purificação , Streptococcus sobrinus/isolamento & purificação
19.
Metab Brain Dis ; 28(2): 313-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23456517

RESUMO

Management of hepatic encephalopathy (HE) primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treatment of HE needs further validation in large studies.


Assuntos
Dissacarídeos/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Animais , Anti-Infecciosos/uso terapêutico , Dissacarídeos/metabolismo , Fármacos Gastrointestinais/uso terapêutico , Encefalopatia Hepática/prevenção & controle , Humanos , Absorção Intestinal , Lactulose/uso terapêutico , Álcoois Açúcares/uso terapêutico
20.
Mol Med Rep ; 7(2): 401-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23165913

RESUMO

Although antiviral drugs are widely used in the clinic, progression to liver cirrhosis and hepatocellular carcinoma cannot yet be entirely prevented. The aim of this study was to determine the effects of lactitol in chronic viral hepatitis patients with endotoxemia. Ninety-four patients with chronic viral hepatitis were separated into two groups based on plasma endotoxin levels: one group with endotoxemia (≥ 45 ng/l, n=60) and one group without endotoxemia (<45 ng/l, n=34). Sixty patients with gut-derived endotoxemia were randomly and evenly divided into a lactitol treatment group and a control group. Plasma endotoxin levels in patients with chronic viral hepatitis exhibited a negative correlation with superoxide dismutase (SOD) activity (P<0.001) and a positive correlation with levels of malondialdehyde (MDA) (P<0.001). The levels of SOD in the lactitol-treated group increased (P<0.01), while the levels of MDA decreased (P<0.01). Plasma endotoxin levels decreased (P<0.01) and the number of lactobacilli and bifidobacteria in the intestinal tract increased (P<0.01 for all). These results suggest that lactitol administration is capable of reducing injury caused by oxidants through regulating intestinal flora and decreasing gut-derived endotoxemia in patients with chronic viral hepatitis.


Assuntos
Antioxidantes/uso terapêutico , Endotoxemia/tratamento farmacológico , Hepatite Crônica/diagnóstico , Álcoois Açúcares/uso terapêutico , Adulto , Antioxidantes/farmacologia , Bifidobacterium/efeitos dos fármacos , Endotoxemia/complicações , Endotoxinas/sangue , Feminino , Hepatite Crônica/complicações , Humanos , Intestinos/microbiologia , Lactobacillus/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Álcoois Açúcares/farmacologia , Superóxido Dismutase/sangue
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