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1.
Expert Opin Investig Drugs ; 28(10): 871-889, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566013

RESUMO

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.


Assuntos
Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Gastroenteropatias/tratamento farmacológico , Dor Abdominal/etiologia , Desenvolvimento de Medicamentos/métodos , Dispepsia/fisiopatologia , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/fisiopatologia , Gastroparesia/tratamento farmacológico , Gastroparesia/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia
2.
Internist (Berl) ; 60(10): 1043-1058, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31501913

RESUMO

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor­α, interleukin-12 and -23; α4ß7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores ErbB/efeitos dos fármacos , Gastroenterologia , Humanos , Fatores Imunológicos/farmacologia , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
4.
Chem Biol Interact ; 310: 108711, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31207224

RESUMO

Gastrointestinal infections are considered a serious public health problem in view of their high incidence and the increasing antibiotic resistance of the microorganisms involved in their pathogenesis, namely Escherichia coli. Consequently, finding new ways to prevent and/or threat these infections is urgent. In this study we investigated whether a well-characterised polyphenolic red wine extract is able to inhibit the cytotoxic effects induced by a clinical pathogenic Escherichia coli strain (E. coli 270) against HT-29 colon epithelial cells. Firstly, we provide evidences showing that the E. coli strain triggered the death of the intestinal epithelial cells through the production and release of a toxin. Then we support that, in a concentration dependent way, RWE through both, a direct interaction with bacterial exotoxin and the epithelial cells, prevented the action of the toxin on the cells, significantly reducing cell death. This intends to constitute a position paper as detailed mechanisms for the inhibition of E. coli-induced toxicity by polyphenols are yet to be completely unraveled. However, considering that the amount of red wine polyphenols used can be easily achieved in a normal diet, this study suggests that RWE may provide a readily available dietary product with potential benefit for the prevention and/or treatment of intestinal infections induced by intestinal pathogenic bacteria and may open new therapeutic avenues for the development of potential natural antimicrobial agents.


Assuntos
Infecções por Escherichia coli/prevenção & controle , Gastroenteropatias/prevenção & controle , Polifenóis/uso terapêutico , Vinho , Morte Celular/efeitos dos fármacos , Células Epiteliais/patologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Células HT29 , Humanos , Polifenóis/farmacologia
6.
Medicine (Baltimore) ; 98(18): e15479, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045830

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease that affects the quality of life in patients with AD. Since there is limitation of conventional treatment of AD, complementary treatment is required to treat AD symptoms more effectively and safely Soshiho-tang (SSHT) is a traditional herbal medicine that exhibits anti-inflammatory and anti-ulcer effects and improves the immune function. In this clinical trial, we will evaluate the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders in comparison with placebo. METHODS/DESIGN: This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3 to 18 years with AD and gastrointestinal disorders and who received a diagnosis of AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 will be enrolled. Participants will be randomly assigned to the SSHT or placebo group in a ratio of 1:1. Additionally, they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SSHT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcome measures include the following: survey questionnaires for the perception of gastrointestinal disorders, amount and frequency of ointment usage for AD, dermatology quality of life index, itchiness and sleep disability score in visual analog scale, percutaneous water loss, skin surface temperature, Hamilton anxiety rating scale, and children's depression inventory. DISCUSSION: In our knowledge, this will be the first clinical trial to assess the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders. The findings of this study will provide new treatment options for patients with AD and gastrointestinal disorders. TRIAL REGISTRATION: Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0003713) https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=13489<ype=&rtype=.


Assuntos
Dermatite Atópica/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Pomadas/uso terapêutico , Extratos Vegetais/uso terapêutico , Adolescente , Criança , Pré-Escolar , Dermatite Atópica/complicações , Método Duplo-Cego , Feminino , Gastroenteropatias/complicações , Humanos , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Nat Commun ; 10(1): 2012, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043597

RESUMO

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.


Assuntos
Disbiose/microbiologia , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/metabolismo , Intestino Delgado/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , DNA Bacteriano/isolamento & purificação , Fibras na Dieta/administração & dosagem , Açúcares da Dieta/efeitos adversos , Disbiose/dietoterapia , Disbiose/tratamento farmacológico , Disbiose/fisiopatologia , Feminino , Gastroenteropatias/dietoterapia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/fisiopatologia , Voluntários Saudáveis , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Permeabilidade , Projetos Piloto , Adulto Jovem
8.
Nat Biotechnol ; 37(5): 527-530, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936561

RESUMO

Oral antibodies that interfere with gastrointestinal targets and can be manufactured at scale are needed. Here we show that a single-gene-encoded monomeric immunoglobulin A (IgA)-like antibody, composed of camelid variable single domain antibodies (VHH) fused to IgA Fc (mVHH-IgA), prevents infection by enterotoxigenic Escherichia coli (F4-ETEC) in piglets. The mVHH-IgA can be produced in soybean seeds or secreted from the yeast Pichia pastoris, freeze- or spray-dried and orally delivered within food.


Assuntos
Doenças Transmissíveis/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Imunoglobulina A/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico , Administração Oral , Animais , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Escherichia coli/patogenicidade , Alimentos , Gastroenteropatias/imunologia , Gastroenteropatias/prevenção & controle , Gastroenteropatias/veterinária , Humanos , Imunoglobulina A/imunologia , Anticorpos de Domínio Único/imunologia , Suínos
9.
Curr Med Sci ; 39(2): 173-184, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31016507

RESUMO

The therapeutic potentials of probiotics in autism spectrum disorder (ASD) remains controversial, with the only existing systematic review on this topic published in 2015. Results from new trials have become available in recent years. We therefore conducted an updated systematic review, to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities. Our review includes two randomized controlled trials, which showed improvement of ASD behaviors, and three open trials, all which exhibited a trend of improvement. Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy. Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Sintomas Comportamentais/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Trato Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Ensaios Clínicos como Assunto , Humanos
10.
J Vet Intern Med ; 33(3): 1434-1439, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31004383

RESUMO

Gastrointestinal (GI) pythiosis is a severe and often fatal disease in dogs that traditionally has been poorly responsive to medical treatment. Although aggressive surgical resection with wide margins is the most consistently effective treatment, lesion location and extent often preclude complete resection. Recently, it has been suggested that the addition of anti-inflammatory doses of corticosteroids may improve outcome in dogs with nonresectable GI pythiosis. This report describes 3 dogs with colonic pythiosis in which complete resolution of clinical signs, regression of colonic masses, and progressive decreases in serological titers were observed after treatment with itraconazole, terbinafine, and corticosteroids. This treatment protocol represents a promising treatment for dogs with GI pythiosis in which surgical intervention is not feasible.


Assuntos
Doenças do Cão/tratamento farmacológico , Itraconazol/uso terapêutico , Prednisona/uso terapêutico , Pitiose/tratamento farmacológico , Terbinafina/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Colo/patologia , Doenças do Cão/microbiologia , Cães , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Gastroenteropatias/veterinária , Itraconazol/administração & dosagem , Prednisona/administração & dosagem , Pythium/imunologia , Testes Sorológicos/veterinária , Terbinafina/administração & dosagem
11.
Int J Mol Sci ; 20(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995806

RESUMO

The intestinal epithelium constitutes an indispensable single-layered barrier to protect the body from invading pathogens, antigens or toxins. At the same time, beneficial nutrients and water have to be absorbed by the epithelium. To prevent development of intestinal inflammation or tumour formation, intestinal homeostasis has to be tightly controlled and therefore a strict balance between cell death and proliferation has to be maintained. The proinflammatory cytokine tumour necrosis factor alpha (TNFα) was shown to play a striking role for the regulation of this balance in the gut. Depending on the cellular conditions, on the one hand TNFα is able to mediate cell survival by activating NFκB signalling. On the other hand, TNFα might trigger cell death, in particular caspase-dependent apoptosis but also caspase-independent programmed necrosis. By regulating these cell death and survival mechanisms, TNFα exerts a variety of beneficial functions in the intestine. However, TNFα signalling is also supposed to play a critical role for the pathogenesis of inflammatory bowel disease (IBD), infectious diseases, intestinal wound healing and tumour formation. Here we review the literature about the physiological and pathophysiological role of TNFα signalling for the maintenance of intestinal homeostasis and the benefits and difficulties of anti-TNFα treatment during IBD.


Assuntos
Gastroenteropatias/imunologia , Homeostase , Intestinos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anticorpos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Descoberta de Drogas , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/patologia , Homeostase/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/patologia
12.
Nat Commun ; 10(1): 1891, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015401

RESUMO

Genome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10-8/23) for statistical significance are identified. We investigate the implications of these GWAS findings in relation to biological mechanism, potential drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes are 16 known therapeutic-effect target genes for medications from 9 categories. Two of the medication classes studied are for disorders that have not previously been subject to large GWAS (hypothyroidism and gastro-oesophageal reflux disease).


Assuntos
Uso de Medicamentos/estatística & dados numéricos , Genoma Humano , Estudo de Associação Genômica Ampla , Testes Farmacogenômicos/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Idoso , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Bases de Dados Factuais , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/genética , Gastroenteropatias/fisiopatologia , Loci Gênicos , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/fisiopatologia , Autoadministração , Autorrelato , Reino Unido
13.
Complement Ther Med ; 43: 265-270, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935541

RESUMO

OBJECTIVE: Gastrointestinal (GI) disorders are estimated to be frequent among general population. Various types of traditional and complementary therapies, primarily phytotherapy, can be used for prevention and treatment of many diseases and conditions, including GI complaints. Thus, the aim of this study was to investigate the patterns of use of medicinal herbs in treatment and prevention of GI disorders, together with their efficacy and safety. METHODS: A prospective, repeated cross-sectional, descriptive study was conducted in the form of a specifically created questionnaire, filled in by consumers and/or patients in pharmacies on the territory of Autonomous Province of Vojvodina, Republic of Serbia. All data were statistically analyzed in Microsoft Excel 2007. RESULTS: In the total number of 1137 patients, 10.4% declared themselves as consumers of phytopreparations for GI disorders. The most common diseases were constipation (44%) and dyspepsia (23%). The most frequently used preparations contained laxatives (with both anthraquinones and dietary fibers), artichoke and silymarin. Iberogast® was also frequently used. Pharmacists were the main source of recommendation for the most adequate herbal remedies. At the same time, phytopreparations were well tolerated, with no major side effects, and were evidently or presumably effective. CONCLUSIONS: Some mild and moderate GI disorders seem to be treated frequently with phytopreparatons. Various herbal remedies are well accepted by patients, and the phytopreparations seem to have favorable ratio of safety and efficacy. Further integration into conventional medicine will improve the quality of the products used and provide a rational plan of use of medicinal plants.


Assuntos
Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/prevenção & controle , Hepatopatias/tratamento farmacológico , Hepatopatias/prevenção & controle , Plantas Medicinais/química , Adulto , Estudos Transversais , Cynara scolymus/química , Feminino , Humanos , Laxantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Sérvia , Silimarina/uso terapêutico , Inquéritos e Questionários
14.
Biomed Pharmacother ; 111: 1393-1398, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841454

RESUMO

BACKGROUND: Citri Reticulatae Pericarpium (CRP), Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are all important Citrus species used in traditional Chinese medicines (TCMs) for the treatment of gastrointestinal disorders. Although they have been used since ancient times and are still in use today, the mechanistic basis for their regulation of adrenergic receptors (ARs) is still not clear. PURPOSE: In this study, we aimed to determine the active components and mechanisms of action of CRP, AFI and AF in treating gastrointestinal disorders related to ARs. METHODS: First, the phenethylamine alkaloid components of CRP, AFI and AF were identified and compared across 30 samples of three Citrus species by UPLC-Q/TOF-MS in combination with content difference analysis. Second, the effect of the main active alkaloid component on AR-based gastrointestinal disorders was investigated by an in vivo small intestinal propulsive test and an in vitro relaxing small intestinal smooth muscle activity test. The mechanism of AR regulation of the active alkaloid was further studied by evaluating its effect on relaxing small intestinal smooth muscle in the presence of an inhibitor. Lastly, the enzymes, which played an important role in epinephrine synthesis and AR regulation, were detected by immunohistochemistry. RESULTS: Three phenethylamine AR regulators (N-methyltyramine, synephrine and hordenine) in CRP, AFI and AF were characterized. It was found that N-methyltyramine could relax mouse small intestinal smooth muscle and inhibit small intestinal propulsion. The effect of N-methyltyramine on relaxing small intestinal smooth muscle could be inhibited by a-methyl-l-tyrosine. The enzymes related epinephrine synthesis and AR function were found in the mouse small intestine. The biotransformation process that converts N-methyltyramine to epinephrine was determined. CONCLUSION: The treatment of gastrointestinal disorders of CRP, AFI and AF is associated with their alkaloid component N-methyltyramine via the regulation of ARs, and the mechanism is considered to be the biotransformation of N-methyltyramine to epinephrine by serial synthase, which takes place at the nerves cells in small intestine.


Assuntos
Epinefrina/metabolismo , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/metabolismo , Receptores Adrenérgicos/metabolismo , Tiramina/análogos & derivados , Alcaloides/farmacologia , Animais , Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Frutas/química , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Masculino , Camundongos , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Fenetilaminas/metabolismo , Tiramina/farmacologia
15.
World J Gastroenterol ; 25(10): 1185-1196, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30886502

RESUMO

There is overwhelming evidence that functional gastrointestinal disorders (FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms (UGI Sx). Among patients with UGI Sx, approximately equal proportions (25%) of patients have delayed gastric emptying (GE), reduced gastric accommodation (GA), both impaired GE and GA, or neither, presumably due to increased gastric or duodenal sensitivity. Treatments targeted to the underlying pathophysiology utilize prokinetics, gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia (with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome (IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2D6, 2C19 and 3A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here; pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.


Assuntos
Fármacos Gastrointestinais/farmacologia , Gastroenteropatias/tratamento farmacológico , Neurotransmissores/farmacologia , Variantes Farmacogenômicos , Medicina de Precisão/métodos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Dissacaridases/deficiência , Dissacaridases/genética , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/genética , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/genética , Humanos , Neurotransmissores/uso terapêutico , Diafragma da Pelve/fisiopatologia , Resultado do Tratamento
16.
Rev Bras Parasitol Vet ; 28(1): 59-67, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30892462

RESUMO

The purpose of this work was to identify, critically assess, and summarize available data from primary research about the anthelmintic resistance of injectable macrocyclic lactones in cattle. Meta-analysis was performed to estimate the pooled Odds Ratio and 95% Confidence Intervals. Of the 1504 abstracts screened for eligibility, 80 were deemed relevant for full publication review. Thirteen publications were included in the qualitative synthesis and assessed for systematic bias. Only five studies were included in the quantitative analysis because they showed a low risk of producing biased results in all the parameters. The forest plot indicated four studies that discuss anthelmintic resistance (P<0.05), while only one study did not discuss anthelmintic resistance (P<0.05). The pooled estimate showed 0.59 (95% Confidence intervals: 0.08, 0.47) times higher odds for studies that report anthelmintic resistance than for studies reporting efficacious anthelmintic treatment, with significant and substantially low heterogeneity (I2=25%). Anthelmintic resistance to injectable macrocyclic lactones is a reality. There are need to improve methodological reporting in studies, which is a problem for investigations that involves systematic review and meta-analysis (SR-MA).


Assuntos
Anti-Helmínticos/administração & dosagem , Resistência a Medicamentos , Gastroenteropatias/veterinária , Lactamas Macrocíclicas/administração & dosagem , Infecções por Nematoides/veterinária , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/parasitologia , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia
17.
Drug Dev Ind Pharm ; 45(4): 651-663, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30638411

RESUMO

OBJECTIVE: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO3) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO3) as a gas generating agent. RESEARCH DESIGN AND METHODS: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box-Behnken design was used for optimization. RESULTS: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X1 = 275.92 mg, X2 = 28.60 mg, and X3 = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X1 = 253.62 mg, X2 = 24.60 mg, and X3 = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h. CONCLUSION: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.


Assuntos
Carbonato de Cálcio/administração & dosagem , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Antagonistas dos Receptores Histamínicos H2/administração & dosagem , Nizatidina/administração & dosagem , Administração Oral , Alginatos/química , Antiácidos/administração & dosagem , Antiácidos/farmacocinética , Disponibilidade Biológica , Carbonato de Cálcio/farmacocinética , Estudos Cross-Over , Combinação de Medicamentos , Gastroenteropatias/tratamento farmacológico , Voluntários Saudáveis , Antagonistas dos Receptores Histamínicos H2/farmacocinética , Humanos , Nizatidina/farmacocinética , Bicarbonato de Sódio/química , Comprimidos
19.
PLoS One ; 14(1): e0210064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625189

RESUMO

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.


Assuntos
Transtorno Autístico/tratamento farmacológico , Colostro , Gastroenteropatias/tratamento farmacológico , Probióticos/uso terapêutico , Animais , Transtorno Autístico/fisiopatologia , Bovinos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Gastroenteropatias/fisiopatologia , Humanos , Interleucina-13/metabolismo , Masculino , Prebióticos , Fator de Necrose Tumoral alfa/metabolismo
20.
Vet Parasitol ; 265: 7-14, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30638523

RESUMO

The control of parasitic infections is particularly challenging in environments that are conducive to the maintenance of parasite lifecycles, such as the greyhound kennel, where the long-term breeding and rearing of dogs is common. The prevalence of gastrointestinal (GI) parasites within the Australian greyhound population has never previously been assessed, which seriously constrains the implementation of effective control measures. The aims of this study were to determine the prevalence and risk factors for GI parasites in Australian greyhounds, identify parasites which may be detrimental to the health and performance of dogs, and evaluate the likelihood of zoonotic transmission to kennel staff. Faecal samples were collected from 721 individual greyhounds situated in kennels across five states of Australia; Western Australia, Queensland, New South Wales, Victoria and Tasmania. Animal husbandry and current parasite control protocols were obtained from each kennel and analysed in conjunction with the detected level of parasitism. Overall parasite prevalence was approximately 60%, ranging from 50 to 70% between states. Eleven parasite genera were identified, with Sarcocystis, hookworm, Giardia and Toxocara detected most frequently. Generalised linear mixed model analyses found the major risk factors associated with parasitism were: a) the type of substrate which dogs were housed; b) age of dogs; and c) geographic region. Parasitism was associated most frequently with young dogs housed on grass/sand substrates, which allowed parasite lifecycles to continue, with constant reinfection the likely outcome. Routine treatment with broad-spectrum anthelmintics did not provide effective control in these environments and the adoption of alternate parasite control strategies is recommended. A substantial risk from zoonotic parasites was also identified, with six of the eleven parasite genera detected considered to be zoonotic and a poor understanding of zoonotic transmission among kennel managers.


Assuntos
Doenças do Cão/parasitologia , Gastroenteropatias/veterinária , Doenças Parasitárias em Animais/parasitologia , Envelhecimento , Criação de Animais Domésticos , Animais , Anti-Helmínticos/uso terapêutico , Austrália , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologia , Cães , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/epidemiologia , Gastroenteropatias/parasitologia , Doenças Parasitárias em Animais/tratamento farmacológico , Doenças Parasitárias em Animais/epidemiologia , Fatores de Risco
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