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1.
J Clin Exp Dent ; 13(5): e433-e439, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33981389

RESUMO

BACKGROUND: To determine the oral colonization capacity of the strains Levilactobacillus brevis KABPTM-052 (CECT 7480) and Lactiplantibacillus plantarum KABPTM-051 (CECT 7481) in healthy subjects. MATERIAL AND METHODS: This randomized, double-blinded, placebo-controlled study included 40 volunteers (22 females, 18 males; age range 18-55 years) with healthy gingiva or mild gingivitis, allocated to receiving probiotic chewing gum (n=20) or placebo (n=20) b.i.d for 6 weeks. At baseline and after 6 weeks of treatment, a periodontics specialist collected saliva samples to assess probiotic colonization by qPCR, and analysed dental plaque, gingival index and dental probing pocket depth in Community Periodontal Index (CPI) teeth subset. Protocol was registered as NCT03540498. RESULTS: Treatment compliance was high (99%). Both L. brevis and L. plantarum were detected in the oral microbiota at baseline. After 6 weeks, volunteers receiving probiotic showed a significant increase of both L. brevis (p = 0.017) and L. plantarum (p = 0.004) versus placebo. This effect remained significant after adjusting for gender and gingival index at baseline. In the probiotic group, reduction in plaque index significantly correlated to higher levels of L. brevis (rho = 0.57, p = 0.022) but not of L. plantarum at study endpoint, and the number of subjects with dental plaque was reduced during intervention (7 of 17, p = 0.016). No such effects were observed in the placebo group. No adverse drug reactions were reported. CONCLUSIONS: Levilactobacillus brevis KABPTM-052 and Lactiplantibacillus plantarum KABPTM-051 colonize the buccal microbiota of healthy volunteers, and higher colonization by L. brevis positively correlated to reduction in dental plaque. Key words:Probiotic, Levilactobacillus brevis, Lactiplantibacillus plantarum, oral colonization, oral microbiota, dental plaque.

2.
Front Cell Infect Microbiol ; 10: 596166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33643929

RESUMO

Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.


Assuntos
Disbiose/virologia , Microbiota/imunologia , Probióticos/uso terapêutico , Viroses/imunologia , Viroses/microbiologia , Animais , COVID-19/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos , Humanos , SARS-CoV-2/isolamento & purificação , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
3.
Pharmaceutics ; 11(9)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480800

RESUMO

Several pharmacogenetic tests to support drug selection in psychiatric patients have recently become available. The current meta-analysis aimed to assess the clinical utility of a commercial pharmacogenetic-based tool for psychiatry (Neuropharmagen®) in the treatment management of depressive patients. Random-effects meta-analysis of clinical studies that had examined the effect of this tool on the improvement of depressive patients was performed. Effects were summarized as standardized differences between treatment groups. A total of 450 eligible subjects from three clinical studies were examined. The random effects model estimated a statistically significant effect size for the pharmacogenetic-guided prescription (d = 0.34, 95% CI = 0.11-0.56, p-value = 0.004), which corresponded to approximately a 1.8-fold increase in the odds of clinical response for pharmacogenetic-guided vs. unguided drug selection. After exclusion of patients with mild depression, the pooled estimated effect size increased to 0.42 (95% CI = 0.19-0.65, p-value = 0.004, n = 287), corresponding to an OR = 2.14 (95% CI = 1.40-3.27). These results support the clinical utility of this pharmacogenetic-based tool in the improvement of health outcomes in patients with depression, especially those with moderate-severe depression. Additional pragmatic RCTs are warranted to consolidate these findings in other patient populations.

4.
Nutrients ; 11(6)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181638

RESUMO

Prebiotic supplements are used to promote gastrointestinal health by stimulating beneficial bacteria. The aim of this study was to compare the potential prebiotic effects of fructans with increasing degrees of polymerization, namely fructooligosaccharides (FOS) and inulins with a low and high polymerization degree (LPDI and HPDI, respectively), using an ex vivo fermentation system to simulate the colonic environment. The system was inoculated with pooled feces from three healthy donors with the same baseline enterotype. Changes in microbiota composition were measured by 16S metagenomic sequencing after 2, 7, and 14 days of fermentation, and acid production was measured throughout the experiment. Alpha-diversity decreased upon inoculation of the ex vivo fermentation under all treatments. Composition changed significantly across both treatments and time (ANOSIM p < 0.005 for both factors). HPDI and LPDI seemed to be similar to each other regarding composition and acidification activity, but different from the control and FOS. FOS differed from the control in terms of composition but not acidification. HDPI restored alpha-diversity on day 14 as compared to the control (Bonferroni p < 0.05). In conclusion, the prebiotic activity of fructans appears to depend on the degree of polymerization, with LPDI and especially HPDI having a greater effect than FOS.


Assuntos
Bactérias/efeitos dos fármacos , Frutanos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Oligossacarídeos/farmacologia , Polimerização , Prebióticos , Adulto , Bactérias/crescimento & desenvolvimento , Técnicas de Tipagem Bacteriana/métodos , Colo/microbiologia , Feminino , Fermentação , Frutanos/química , Humanos , Inulina/química , Inulina/farmacologia , Masculino , Oligossacarídeos/química
5.
Nutrients ; 11(2)2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30704039

RESUMO

Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13⁻2.15, p-value = 0.007, I² = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23⁻2.43, p-value = 0.002, I² = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.


Assuntos
Colite Ulcerativa/terapia , Frutanos/uso terapêutico , Prebióticos , Probióticos/uso terapêutico , Simbióticos , Humanos , Indução de Remissão
6.
Pharmgenomics Pers Med ; 11: 35-42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29588611

RESUMO

BACKGROUND: Bipolar disorder (BD) is a frequent cause of disability, health care costs, and risk of suicide. Pharmacogenetic tests (PGTs) could help clinicians to identify those patients predisposed to the occurrence of adverse events (AEs) improving the understanding of the correlation between genetic variants and drug response. MATERIALS AND METHODS: The study evaluated 30 patients affected by BD type I or II (according to Diagnostic and Statistical Manual of Mental Disorders, version 5) who underwent the PGT Neurofarmagen® (AB-BIOTICS SA, Barcelona, Spain) between March 2016 and March 2017. The primary aim of this study was to identify if the treatment prescribed by the psychiatrists was consistent with the treatment suggested by the PGT at T0 (corresponding to the test report communication). As a secondary aim, we wanted to assess if clinicians had changed the treatment (in case of discordance) at T1 (3-month follow-up visit) according to the results of the PGT. RESULTS: At T0, only 4 patients (13%) had an optimal therapy in line with the PGT suggestions. At 3-month follow-up, 13 patients (40%) had received a change of therapy consistent to the test, showing a significant statistical improvement in the Clinical Global Impression item Severity (CGI-S) score over time compared to those not having changes consistent with the test. Regarding AEs, at baseline 9 out of 10 (90%) of the patients who received a therapy modification according to the test presented AEs, and a significant within-group reduction was observed after 3 months (p = 0.031). CONCLUSION: Despite the small sample size, the study shows promising data about the usefulness of PGT to support clinicians in reaching a more effective and tolerated treatment in the routine approach of BD.

7.
BMC Psychiatry ; 17(1): 250, 2017 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-28705252

RESUMO

BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. METHODS: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. RESULTS: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). CONCLUSIONS: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. TRIAL REGISTRATION: European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.


Assuntos
Antidepressivos/farmacocinética , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Testes Farmacogenômicos , Adulto , Antidepressivos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
CNS Spectr ; 22(4): 315-324, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27098095

RESUMO

OBJECTIVE: We investigated the association between clinical outcome and the recommendations of a pharmacogenetic test (Neuropharmagen) in patients with a variety of psychiatric conditions whose previous treatment regimen had failed. METHODS: This retrospective, naturalistic, multicenter study included adult psychiatric patients (depression, psychosis, anxiety, bipolar, etc.) who had been seen at 3 private clinics. All patients had received pharmacogenetic testing (Neuropharmagen) and were classified depending on whether or not their post-test treatment regimen followed the test recommendations. Clinical severity was assessed with the Clinical Global Impression of Severity (CGI-S) at baseline (pre-test) and 3-month follow-up, and adverse events were recorded. RESULTS: 182 patients were available for analysis. After multivariate adjustment, patients whose treatment followed the test recommendations had odds of improvement about 4 times greater than patients whose treatment did not follow the recommendations (adjusted OR=3.86, 95%CI 1.36-10.95; p=0.011). Importantly, psychiatric diagnosis did not significantly affect the odds of improvement. Also, in the subpopulation with baseline CGI-S score >3 (N=170), the rate of stabilization at follow-up (defined as CGI-S≤3) was significantly higher in patients whose treatment followed the pharmacogenetic recommendations (p=0.033). There was no apparent difference in the incidence of adverse events (6 patients in each group). CONCLUSIONS: Non-drug naïve patients whose treatment followed the recommendations of pharmacogenetic testing were more likely to improve their condition than patients whose treatment did not. These results are consistent with previous clinical research on depressed patients, and this study also suggests that this benefit can be extended to psychiatric conditions other than depression.


Assuntos
Transtornos Mentais/tratamento farmacológico , Testes Farmacogenômicos , Medicina de Precisão , Psicotrópicos/uso terapêutico , Adulto , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transtornos Psicóticos/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha , Resultado do Tratamento
9.
Probiotics Antimicrob Proteins ; 9(1): 71-80, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27832441

RESUMO

Use of probiotic therapy is an active area of investigation to treat intestinal disorders. The clinical benefits of the I3.1 probiotic formula (Lactobacillus plantarum (CECT7484, CECT7485) and P. acidilactici (CECT7483)) were demonstrated in irritable bowel syndrome (IBS) patients in a randomized, double-blind, placebo-controlled clinical trial. The aim of this study was to evaluate the therapeutic effects of I3.1 in two experimental models of colitis, a dextran sulfate sodium (DSS)-induced colitis model and an interleukin (IL)-10-deficient mice model. Colitis was induced in 32 8-week-old Balb/c mice by administering 3% (w/v) DSS in drinking water for 5 days. Probiotics were administered orally (I3.1 or VSL#3, 1 × 109 CFU daily) for 10 days before the administration of DSS. Also, probiotics (I3.1 or VSL#3, 1 × 109 CFU daily) were administered orally to 36 6-week-old C57B6J IL-10(-/-) mice for 10 weeks. Body weight was recorded daily. Colon samples were harvested for histological examination and cytokine measurements. Body weight after DSS administration did not change in the I3.1 group, whereas the VSL#3 group had weight loss. Also, I3.1 normalized IL-6 to levels similar to that of healthy controls and significantly increased the reparative histologic score. In the IL-10-deficient model, both VSL#3 and I3.1 reduced the severity of colitis compared to untreated controls, and I3.1 significantly reduced the levels of IFN-γ compared to the other two groups. In conclusion, I3.1 displays a protective effect on two murine models of experimental colitis. Results suggest that the mechanism of action could be different from VSL#3.


Assuntos
Colite/tratamento farmacológico , Probióticos/administração & dosagem , Animais , Colite/induzido quimicamente , Colite/microbiologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/imunologia , Interleucina-6/imunologia , Lactobacillus plantarum/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
10.
Clin Cancer Res ; 22(10): 2508-19, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26671995

RESUMO

PURPOSE: ABTL0812 is a novel first-in-class, small molecule which showed antiproliferative effect on tumor cells in phenotypic assays. Here we describe the mechanism of action of this antitumor drug, which is currently in clinical development. EXPERIMENTAL DESIGN: We investigated the effect of ABTL0812 on cancer cell death, proliferation, and modulation of intracellular signaling pathways, using human lung (A549) and pancreatic (MiaPaCa-2) cancer cells and tumor xenografts. To identify cellular targets, we performed in silico high-throughput screening comparing ABTL0812 chemical structure against ChEMBL15 database. RESULTS: ABTL0812 inhibited Akt/mTORC1 axis, resulting in impaired cancer cell proliferation and autophagy-mediated cell death. In silico screening led us to identify PPARs, PPARα and PPARγ as the cellular targets of ABTL0812. We showed that ABTL0812 activates both PPAR receptors, resulting in upregulation of Tribbles-3 pseudokinase (TRIB3) gene expression. Upregulated TRIB3 binds cellular Akt, preventing its activation by upstream kinases, resulting in Akt inhibition and suppression of the Akt/mTORC1 axis. Pharmacologic inhibition of PPARα/γ or TRIB3 silencing prevented ABTL0812-induced cell death. ABTL0812 treatment induced Akt inhibition in cancer cells, tumor xenografts, and peripheral blood mononuclear cells from patients enrolled in phase I/Ib first-in-human clinical trial. CONCLUSIONS: ABTL0812 has a unique and novel mechanism of action, that defines a new and drugable cellular route that links PPARs to Akt/mTORC1 axis, where TRIB3 pseudokinase plays a central role. Activation of this route (PPARα/γ-TRIB3-Akt-mTORC1) leads to autophagy-mediated cancer cell death. Given the low toxicity and high tolerability of ABTL0812, our results support further development of ABTL0812 as a promising anticancer therapy. Clin Cancer Res; 22(10); 2508-19. ©2015 AACR.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Nus , Ratos , Transdução de Sinais/efeitos dos fármacos
11.
World J Gastroenterol ; 20(26): 8709-16, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25024629

RESUMO

AIM: To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). METHODS: A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. RESULTS: During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. CONCLUSION: A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea.


Assuntos
Intestinos/microbiologia , Síndrome do Intestino Irritável/terapia , Lactobacillus plantarum/fisiologia , Pediococcus/fisiologia , Probióticos/uso terapêutico , Qualidade de Vida , Adulto , Idoso , Diarreia/microbiologia , Diarreia/psicologia , Diarreia/terapia , Método Duplo-Cego , Feminino , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/psicologia , Masculino , Pessoa de Meia-Idade , Probióticos/efeitos adversos , Espanha , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Eur J Nutr ; 53(2): 567-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23892521

RESUMO

PURPOSE: Our objective was to compare the absorption of microencapsulated ferric saccharate (MFS) and ferrous sulfate (FS) in a fortified milk product, using a crossover design. METHODS: Seventeen non-iron-deficient healthy adults from both sexes participated in the study. On each intervention day (days 1 and 8), after an overnight fast, the volunteers consumed one type of product (test or control) and blood sampling was carried out at different times. The interventions days were separated by 7-day washout periods. This study was double blinded, crossover and randomized for nature of the test meals. The primary outcomes of the study were total serum iron and transferrin saturation. RESULTS: No significant differences could be observed in serum iron concentration during the 6-h postprandial study due to the type of milk product consumed, and there was neither an effect of time nor an interaction between the type of milk product and time. Transferrin saturation significantly increased after the intake of both products (P < 0.005), reaching a peak value between hours 2 and 4. No significant differences were detected between MFS and FS, indicating that iron absorption from MFS is equivalent to absorption from FS. CONCLUSIONS: MFS is a new ingredient that allows the fortification of a wide range of food products, including heat-processed and non-acidic products with similar absorption to FS, designed to produce neither organoleptic changes nor off-color development during storage of fortified food.


Assuntos
Compostos Férricos/farmacocinética , Compostos Ferrosos/farmacocinética , Ácido Glucárico/farmacocinética , Boca/metabolismo , Absorção , Adulto , Animais , Índice de Massa Corporal , Estudos Cross-Over , Método Duplo-Cego , Composição de Medicamentos , Feminino , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado , Ferritinas/sangue , Compostos Ferrosos/administração & dosagem , Alimentos Fortificados , Ácido Glucárico/administração & dosagem , Humanos , Ferro/sangue , Masculino , Leite , Período Pós-Prandial
13.
Food Chem ; 134(2): 940-7, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23107711

RESUMO

Chitosan, a deacetylated form of chitin, is a dietary fibre known for its hypolipidemic properties, which are mainly attributed to its unique cationic characteristics. We studied the selective in vivo effect of chitosan on fat excretion in order to elucidate its hypolipidemic mechanism. A 4-week longitudinal study was conducted in guinea pigs and the effect of chitosan on fat-absorption was compared to that of a soluble fibre: digestion-resistant maltodextrin. Animals were fed with high-fat isocaloric diets containing 12/100g of cellulose, digestion-resistant maltodextrin or chitosan. Subsequently, the excretion of fatty acids, neutral sterols and bile acids was determined. Chitosan selectively reduced fat absorption in comparison to digestion-resistant maltodextrin. The excretion of lauric, myristic and palmitic fatty acids of animals fed with chitosan was more than 10-, 5- and 2-fold higher, respectively, than in the cellulose group, whereas stearic acid excretion was not significantly altered. Oleic, linoleic and α-linolenic acid excretion were also significantly higher (P<0.001). The n-6/n-3 ratio in faeces of the chitosan group was 23.68, compared to 13.95 in the cellulose group. Total neutral sterol excretion was increased by both dietary fibres, whereas bile acid excretion was only increased by chitosan. Nevertheless, chitosan inhibited the intestinal bioconversion of cholesterol and primary bile acids to secondary metabolites. Hence, these results reveal that chitosan and digestion resistant maltodextrin exert their hypolipidemic activity by different mechanisms.


Assuntos
Ácidos e Sais Biliares/metabolismo , Quitosana/metabolismo , Ácidos Graxos/metabolismo , Esteróis/metabolismo , Animais , Colesterol/metabolismo , Feminino , Cobaias , Humanos , Modelos Animais
14.
Lipids ; 47(7): 697-705, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22669591

RESUMO

This study investigated the effect of two partially hydrolyzed guar gums (PHGG) on fatty acid and sterol excretion. PHGG were obtained by chemical hydrolysis of guar gum (GG) with H(2)O:EtOH (1:1) at 100 °C for 1 h (PHGG1) or 2 h (PHGG2). The viscosity of the PHGG in a 1 % (w/v) aqueous solution corresponded to that of a pseudoplastic fluid and was higher for PHGG1 than PHGG2. Guinea pigs (n = 8 per group) were fed high fat diets (17/100 g) that contained 12/100 g of cellulose, PHGG1, or PHGG2 for 4 weeks. Despite the differences in viscosity, the two PHGG exerted similar physiological effects. Compared to the control cellulose group, the body weight gain was lower in animals fed PHGG, although no effect on food consumption was observed. PHGG increased the excretion of fatty acids and neutral sterols, but not bile acids. Consumption of PHGG did not alter the fecal fatty acid profile, while intestinal bioconversion of sterols tended to increase in response to PHGG2. A reduction in the viscosity within the range tested did not correlate with losses in the hypocholesterolemic capacity of PHGG as both were effective in reducing plasma cholesterol. Thus, we conclude that the chemical hydrolysis of guar gum renders the gum suitable for inclusion in food products without significantly altering its beneficial health effects.


Assuntos
Ácidos e Sais Biliares/metabolismo , Galactanos/farmacologia , Mananas/farmacologia , Gomas Vegetais/farmacologia , Esteróis/metabolismo , Animais , Dieta Hiperlipídica , Fibras na Dieta/farmacologia , Ácidos Graxos/metabolismo , Feminino , Galactanos/química , Cobaias , Metabolismo dos Lipídeos/efeitos dos fármacos , Mananas/química , Gomas Vegetais/química , Viscosidade/efeitos dos fármacos
15.
Bioinformatics ; 25(12): 1506-12, 2009 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-19357100

RESUMO

MOTIVATION: Several strategies have been developed to predict the fold of a target protein sequence, most of which are based on aligning the target sequence to other sequences of known structure. Previously, we demonstrated that the consideration of protein-protein interactions significantly increases the accuracy of fold assignment compared with PSI-BLAST sequence comparisons. A drawback of our method was the low number of proteins to which a fold could be assigned. Here, we present an improved version of the method that addresses this limitation. We also compare our method to other state-of-the-art fold assignment methodologies. RESULTS: Our approach (ModLink+) has been tested on 3716 proteins with domain folds classified in the Structural Classification Of Proteins (SCOP) as well as known interacting partners in the Database of Interacting Proteins (DIP). For this test set, the ratio of success [positive predictive value (PPV)] on fold assignment increases from 75% for PSI-BLAST, 83% for HHSearch and 81% for PRC to >90% for ModLink+at the e-value cutoff of 10(-3). Under this e-value, ModLink+can assign a fold to 30-45% of the proteins in the test set, while our previous method could cover <25%. When applied to 6384 proteins with unknown fold in the yeast proteome, ModLink+combined with PSI-BLAST assigns a fold for domains in 3738 proteins, while PSI-BLAST alone covers only 2122 proteins, HHSearch 2969 and PRC 2826 proteins, using a threshold e-value that would represent a PPV >82% for each method in the test set. AVAILABILITY: The ModLink+server is freely accessible in the World Wide Web at http://sbi.imim.es/modlink/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Biologia Computacional/métodos , Domínios e Motivos de Interação entre Proteínas , Bases de Dados de Proteínas , Dobramento de Proteína , Proteínas/química , Proteínas/metabolismo , Análise de Sequência de Proteína
16.
Bioinform Biol Insights ; 1: 77-90, 2009 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-20066127

RESUMO

Loops represent an important part of protein structures. The study of loop is critical for two main reasons: First, loops are often involved in protein function, stability and folding. Second, despite improvements in experimental and computational structure prediction methods, modeling the conformation of loops remains problematic. Here, we present a structural classification of loops, ArchDB, a mine of information with application in both mentioned fields: loop structure prediction and function prediction. ArchDB (http://sbi.imim.es/archdb) is a database of classified protein loop motifs. The current database provides four different classification sets tailored for different purposes. ArchDB-40, a loop classification derived from SCOP40, well suited for modeling common loop motifs. Since features relevant to loop structure or function can be more easily determined on well-populated clusters, we have developed ArchDB-95, a loop classification derived from SCOP95. This new classification set shows a ~40% increase in the number of subclasses, and a large 7-fold increase in the number of putative structure/function-related subclasses. We also present ArchDB-EC, a classification of loop motifs from enzymes, and ArchDB-KI, a manually annotated classification of loop motifs from kinases. Information about ligand contacts and PDB sites has been included in all classification sets. Improvements in our classification scheme are described, as well as several new database features, such as the ability to query by conserved annotations, sequence similarity, or uploading 3D coordinates of a protein. The lengths of classified loops range between 0 and 36 residues long. ArchDB offers an exhaustive sampling of loop structures. Functional information about loops and links with related biological databases are also provided. All this information and the possibility to browse/query the database through a web-server outline an useful tool with application in the comparative study of loops, the analysis of loops involved in protein function and to obtain templates for loop modeling.

17.
BMC Bioinformatics ; 9: 249, 2008 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-18505562

RESUMO

BACKGROUND: A number of studies have used protein interaction data alone for protein function prediction. Here, we introduce a computational approach for annotation of enzymes, based on the observation that similar protein sequences are more likely to perform the same function if they share similar interacting partners. RESULTS: The method has been tested against the PSI-BLAST program using a set of 3,890 protein sequences from which interaction data was available. For protein sequences that align with at least 40% sequence identity to a known enzyme, the specificity of our method in predicting the first three EC digits increased from 80% to 90% at 80% coverage when compared to PSI-BLAST. CONCLUSION: Our method can also be used in proteins for which homologous sequences with known interacting partners can be detected. Thus, our method could increase 10% the specificity of genome-wide enzyme predictions based on sequence matching by PSI-BLAST alone.


Assuntos
Enzimas/metabolismo , Homologia de Sequência de Aminoácidos , Software , Sequência de Aminoácidos/fisiologia , Bases de Dados de Proteínas , Enzimas/análise , Lógica Fuzzy , Reconhecimento Automatizado de Padrão , Valor Preditivo dos Testes , Mapeamento de Interação de Proteínas , Proteínas/análise , Proteínas/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína , Relação Estrutura-Atividade , Especificidade por Substrato/genética
18.
Protein J ; 27(2): 130-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18066655

RESUMO

The functional annotation of the new protein sequences represents a major drawback for genomic science. The best way to suggest the function of a protein from its sequence is by finding a related one for which biological information is available. Current alignment algorithms display a list of protein sequence stretches presenting significant similarity to different protein targets, ordered by their respective mathematical scores. However, statistical and biological significance do not always coincide, therefore, the rearrangement of the program output according to more biological characteristics than the mathematical scoring would help functional annotation. A new method that predicts the putative function for the protein integrating the results from the PSI-BLAST program and a fuzzy logic algorithm is described. Several protein sequence characteristics have been checked in their ability to rearrange a PSI-BLAST profile according more to their biological functions. Four of them: amino acid content, matched segment length and hydropathic and flexibility profiles positively contributed, upon being integrated by a fuzzy logic algorithm into a program, BYPASS, to the accurate prediction of the function of a protein from its sequence.


Assuntos
Algoritmos , Lógica Fuzzy , Alinhamento de Sequência , Análise de Sequência de Proteína/métodos , Proteínas/fisiologia , Curva ROC
19.
Bioinformatics ; 22(18): 2237-43, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16870939

RESUMO

MOTIVATION: The detection of function-related local 3D-motifs in protein structures can provide insights towards protein function in absence of sequence or fold similarity. Protein loops are known to play important roles in protein function and several loop classifications have been described, but the automated identification of putative functional 3D-motifs in such classifications has not yet been addressed. This identification can be used on sequence annotations. RESULTS: We evaluated three different scoring methods for their ability to identify known motifs from the PROSITE database in ArchDB. More than 500 new putative function-related motifs not reported in PROSITE were identified. Sequence patterns derived from these motifs were especially useful at predicting precise annotations. The number of reliable sequence annotations could be increased up to 100% with respect to standard BLAST. CONTACT: boliva@imim.es SUPPLEMENTARY INFORMATION: Supplementary Data are available at Bioinformatics online.


Assuntos
Modelos Químicos , Proteínas/química , Proteínas/metabolismo , Alinhamento de Sequência/métodos , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Simulação por Computador , Modelos Biológicos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Proteínas/classificação , Relação Estrutura-Atividade
20.
Bioinformatics ; 21(16): 3360-8, 2005 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15961445

RESUMO

MOTIVATION: Given that association and dissociation of protein molecules is crucial in most biological processes several in silico methods have been recently developed to predict protein-protein interactions. Structural evidence has shown that usually interacting pairs of close homologs (interologs) physically interact in the same way. Moreover, conservation of an interaction depends on the conservation of the interface between interacting partners. In this article we make use of both, structural similarities among domains of known interacting proteins found in the Database of Interacting Proteins (DIP) and conservation of pairs of sequence patches involved in protein-protein interfaces to predict putative protein interaction pairs. RESULTS: We have obtained a large amount of putative protein-protein interaction (approximately 130,000). The list is independent from other techniques both experimental and theoretical. We separated the list of predictions into three sets according to their relationship with known interacting proteins found in DIP. For each set, only a small fraction of the predicted protein pairs could be independently validated by cross checking with the Human Protein Reference Database (HPRD). The fraction of validated protein pairs was always larger than that expected by using random protein pairs. Furthermore, a correlation map of interacting protein pairs was calculated with respect to molecular function, as defined in the Gene Ontology database. It shows good consistency of the predicted interactions with data in the HPRD database. The intersection between the lists of interactions of other methods and ours produces a network of potentially high-confidence interactions.


Assuntos
Algoritmos , Mapeamento de Interação de Proteínas/métodos , Proteínas/química , Alinhamento de Sequência/métodos , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Sítios de Ligação , Sequência Conservada , Dados de Sequência Molecular , Ligação Proteica , Proteínas/análise , Proteínas/classificação , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade
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