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1.
J Sci Food Agric ; 100(2): 705-713, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31599967

RESUMO

BACKGROUND: Despite the growing importance of probiotics apparent health benefits, an impediment to the use of new probiotic cultures is their safety. Hence there is a need to strictly examine the biosafety as well as health benefits of probiotics in in vivo model systems. RESULTS: In this study, two lactic acid bacterial (LAB) cultures Lactobacillus fermentum NCMR 2826 and FIX proven for their in vitro probiotic properties were investigated for their in vivo safety in Wistar rats. An acute toxicity study (14 days) with a high dose of biomass (1016 colony-forming units (CFU) mL-1 ) followed by a subchronic test for 13 weeks with oral feeding of the probiotic cultures in three different doses (107 , 108 and 1010 CFU mL-1 ) on a daily basis revealed the safety of the L. fermentum cultures. The probiotic feeding had no toxic effects on survival, body weight and food consumption with any of the dosages used throughout the treatment period. No statistically significant changes in relative organ weights and serum biochemical and hematological indices were found between the control and the probiotic fed animals. In addition to the safety attributes, the L. fermentum culture fed rats showed reduced serum cholesterol levels, macrovesicular steatosis and hepatocyte ballooning compared with control animals. Further, quantification of intestinal microbiota using real-time polymerase chain reaction (PCR) analysis from animal feces indicated a significant increase and stability of Lactobacillus and Bifidobacterium counts but a decrease of Escherichia coli numbers. CONCLUSION: This study of safety and beneficial features highlights the use of the two native L. fermentum isolates as potential probiotic food supplements. © 2019 Society of Chemical Industry.


Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus fermentum/metabolismo , Probióticos/administração & dosagem , Animais , Anticolesterolemiantes/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colesterol/sangue , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Lactobacillus fermentum/crescimento & desenvolvimento , Masculino , Probióticos/metabolismo , Ratos , Ratos Wistar
2.
Vet Parasitol ; 277: 109009, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31862509

RESUMO

The present study investigated the effects of dietary supplementation with several Bacillus strains on growth performance, intestinal inflammatory and anti-inflammatory cytokines, anti-oxidants and tight junction (TJ) protein mRNA expression in broiler chickens challenged with mixed coccidia infection (oocysts of Eimeria tenella, Eimeria maxima and Eimeria acervulina). Ten different Bacillus strains were screened for their beneficial effects on coccidiosis challenge by measuring relative body weight gain (RBWG), lesion score, and total oocyst count. Three out of ten Bacillus strains were evaluated in depth by measuring RBWG, lesion score, total oocyst count, and the gene expression of proinflammatory (IL-6 and IL-8), anti-inflammatory (IL-10 and TGF-ß), anti-oxidant (SOD1 and HMOX1), and TJ (JAM2 and occludin) proteins. Our results showed that out of the ten different Bacillus strains, chickens fed with three strains, one Bacillus licheniformis and two Bacillus amyloliquefaciens, showed significantly higher RBWG, lower lesion scores (ceca, jejunum, and duodenum), and lower total fecal oocyst counts compared to non-Bacillus-fed control chickens. Post-coccidia challenge, the RBWG for the Bacillus-fed groups were 95-100 % as opposed to the control birds (70 %) at 6 days post infection (dpi) and 10 dpi. Similarly, the lesion scores for three organs were around 0.8-0.9 for the Bacillus-fed groups as opposed to control birds (lesion score range ∼1.4-2). The total oocyst counts were much lower in the Bacillus-fed group (10-20 folds lesser) than the control group. Furthermore, the Bacillus-fed groups showed differential gene expression at 3 dpi in different tissues, such as caecum, jejunum, and duodenum. Bacillus-fed chickens showed significant pro- and anti-inflammatory responses and higher expression of anti-oxidants and TJ proteins in the ceca, duodenum, and jejunum. Overall, our results demonstrated that dietary supplementation with Bacillus strains as direct-fed microbials (DFM) significantly improved the body weight gain after mixed coccidia challenge compared to non-Bacillus-fed and coccidia challenged control group. In conclusion, the results of this study are promising and indicate the many beneficial effects of DFM-supplementation in poultry diets to reduce the negative consequences of enteric diseases and to decrease economic losses imposed by coccidia infection in chickens.


Assuntos
Bacillus , Coccidiose/veterinária , Suplementos Nutricionais , Ração Animal , Animais , Bacillus/fisiologia , Galinhas/crescimento & desenvolvimento , Fezes/parasitologia , Intestinos/parasitologia , Intestinos/fisiologia , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/terapia
3.
Adv Clin Exp Med ; 28(10): 1429-1436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31670915

RESUMO

BACKGROUND: Hirschsprung's disease-associated enterocolitis (HE) is a life-threatening septic complication of Hirschsprung's disease (HD), leading to bacterial translocation (BT) and sepsis. Many factors, such as intestinal stasis, HD-related inherited immune disorders and abnormal mucosal secretion have been implicated in its pathogenesis. OBJECTIVES: To investigate the effect of intestinal stasis as an independent factor in the pathogenesis of HE intestinal lesions and its systematic effects. MATERIAL AND METHODS: The rectal ganglion cells of 46 Wistar rats were chemically ablated through local benzalkonium chloride (BAC) injection, in order to create a HD model (megacolon rats) that does not carry the possible genetic burden of HD. The animals were sacrificed either on the 20th or 25th day after ablation and were examined for histopathological changes on the wall of the small intestine, presence of bacterial translocation in body organs, body biometrics, and white blood cell count (WBC) and hemoglobin concentration. The results were compared to control animals. RESULTS: In the megacolon rats, severe damage on the small intestine as well as BT proportional to the extent of the intestinal damage and to the time elapsed after ablation was observed. Significant effects on the WBCs, hemoglobin concentration and biometric parameters were also observed. CONCLUSIONS: In megacolon rats, intestinal stasis can lead by itself to a full-blown HE. The HE lesions that promote BT are present even in regions distant from the aganglionic bowel and are proportional to the time elapsed under the influence of intestinal stasis. Systematic effects such as growth retardation are also produced.


Assuntos
Enterocolite , Doença de Hirschsprung/patologia , Obstrução Intestinal , Megacolo/complicações , Animais , Translocação Bacteriana , Modelos Animais de Doenças , Enterocolite/diagnóstico , Enterocolite/etiologia , Intestinos/microbiologia , Megacolo/patologia , Ratos , Ratos Wistar , Sepse
4.
Adv Exp Med Biol ; 1197: 97-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732937

RESUMO

The colonization of body surfaces, notably of the intestine, by a complex microbiota is generally highly mutualistic, where vital functions are provided by the commensal microbiota to the host, including the synthesis of vitamins, the degradation of complex polysaccharides into small chain fatty acids (which are essential for the maintenance of the intestinal epithelial barrier), and, finally, the outcompetition of pathogens that accidentally gain access to the body ("colonization resistance") (Chow et al. 2011; Backhed 2005). However, under certain conditions, such as changes of environmental factors in a genetically predisposed host, some of these normally symbiotic bacteria may act as pathogens and induce pathologies. Hence, the term "pathobionts" was coined for these bacterial species with ambiguous biological properties (Round et al. 2009).


Assuntos
Colite , Helicobacter , Animais , Colite/microbiologia , Modelos Animais de Doenças , Helicobacter/fisiologia , Humanos , Intestinos/microbiologia
5.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(11): 1021-1026, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31770832

RESUMO

Radiation-induced bowel injury is a common complication of radiation therapy for pelvic malignancy. Given the huge number of patients diagnosed with pelvic malignancy, the number of patients diagnosed with radiation-induced bowel injury increased year by year, which put a great burden on the clinical diagnosis and treatment of radiation-induced bowel injury. In particular, chronic radiation-induced bowel injury, which is manifested in the process of prolonged, repeated and progressive aggravation, seriously affects the physical and mental health of patients and makes clinical diagnosis and treatment difficult. However, due to insufficient attention and understanding from doctors and patients, standardized diagnosis and treatment of radiation-induced bowel injury still have a long way to go. Radiation-induced bowel injury is self-limited but irreversible. During diagnosis, we should pay attention to overall evaluation of the stage of disease based on clinical symptoms, endoscopic examination, imaging examination, pathology and nutritional risk. The treatment methods include health education, drug therapy, enema therapy, formalin local treatment, endoscopic treatment and surgical treatment, etc. The treatment decision-making should be based on clinical symptoms, endoscopic or imaging findings to alleviate the clinical symptoms of patients as the primary goal and to improve the long-term quality of life of patients as the ultimate goal.


Assuntos
Enteropatias/terapia , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/terapia , Radioterapia/efeitos adversos , Doença Crônica , Humanos , Enteropatias/diagnóstico , Enteropatias/etiologia , Intestinos/efeitos da radiação , Qualidade de Vida , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(11): 1034-1040, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31770834

RESUMO

Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients' diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions: Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.


Assuntos
Enteropatias/cirurgia , Lesões por Radiação/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Doença Crônica , Enterostomia , Feminino , Humanos , Enteropatias/etiologia , Intestinos/efeitos da radiação , Intestinos/cirurgia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Lesões por Radiação/complicações , Estudos Retrospectivos , Resultado do Tratamento
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(11): 1095-1100, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31770844

RESUMO

Colonic organoids are three-dimensional organotypic cultures of the colonic stem cells or pluripotent stem cells. Its essence is the culture of colonic stem cells or pluripotent stem cells, and their derived intestinal epithelial cells, intestinal endocrine cells and goblet cells in basement membrane extract with specific growth factors. Colonic organoids are comprised of all major types of colonic epithelial cells and represent the architecture and function remarkably similar to those of the colonic epithelium, faithfully recapitulating the functional colonic epithelium ex vivo. As a superior basic experimental model, colonic organoids are representing advantages over conventional cell models and animal models in many aspects, such as high successful rate, short productive cycle, and high consistency with source tissue. Since first reported in 2011, colonic organoids have soon become an important topic in the field of colonic diseases. It has now been applied in the field of physiology of colonic epithelium, infectious diarrhea, ulcerative colitis, regeneration of intestinal injury, and colon tumors. In this review, we summarize the research advances of establishment and application of colonic organoids.


Assuntos
Colo/fisiologia , Mucosa Intestinal/fisiologia , Organoides/fisiologia , Células-Tronco/fisiologia , Animais , Colo/citologia , Humanos , Intestinos
8.
J Agric Food Chem ; 67(46): 12761-12769, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31675233

RESUMO

There is convincing evidence that consuming whole grains (WGs) may decrease the risk of colorectal cancer (CRC). Wheat bran (WB) is a rich source of dietary fiber and phytochemicals with health-promoting properties. However, the active components especially the interaction between different components in WG wheat have not been fully explored. Here, we investigated whether one of the major WB phytochemicals, alkylresorcinol (AR) C21, and the major active intestinal microbial metabolite of fiber, butyrate, could synergistically suppress human colon cancer cells. Our results demonstrated for the first time that the combination of C21 and butyrate synergistically inhibited the growth of human colon cancer cells and induced apoptosis. Further mechanistic studies demonstrated that the cotreatment of C21 and butyrate induced significant up-regulations in cleaved Poly(ADP-ribose) polymerase (PARP), cleaved caspase 3, p53 upregulated modulator of apoptosis (PUMA), cytochrome C, lipid-conjugated membrane-bound form of microtubule-associated protein 1A/1B-light chain 3 (LC3-II), and C/EBP homologous protein (CHOP) expressions, indicating the synergistic anticancer effects of C21 and butyrate were associated with induction of apoptosis, autophagy, and ER stress pathways. Notably, the C21 concentrations in the large intestinal tract of mice treated with human relevant doses of C21, were from 0.86 to 1.78 µmol/g, suggesting the C21 doses used in vitro may be achievable after daily WG wheat intake. These results provide novel insights into the dietary prevention of CRC regarding the potential interaction of bioactive WG wheat phytochemicals and the microbial metabolites of fiber.


Assuntos
Butiratos/metabolismo , Neoplasias do Colo/tratamento farmacológico , Fibras na Dieta/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Compostos Fitoquímicos/administração & dosagem , Resorcinóis/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/microbiologia , Neoplasias do Colo/fisiopatologia , Humanos , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Compostos Fitoquímicos/química , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Resorcinóis/química
9.
Surg Clin North Am ; 99(6): 1209-1221, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676059

RESUMO

Short bowel syndrome / intestinal failure (SBS/IF) is a rare and debilitating disease process that mandates a multidisciplinary approach in its management. Inflammatory bowel disease (IBD), in particular Crohn's disease (CD), predisposes patients to development of SBS/IF. This review discusses SBS/IF from the perspective of IBD, with an emphasis on prevention and treatment in the setting of CD. The aims of this review are to emphasize the unique treatment goals of the newly diagnosed SBS/IF patient, and highlight the role of both medical and surgical therapies in the management of IBD-related SBS/IF, including intestinal transplantation.


Assuntos
Doenças Inflamatórias Intestinais/cirurgia , Intestinos/transplante , Síndrome do Intestino Curto/etiologia , Síndrome do Intestino Curto/terapia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Tratamento Conservador/métodos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Prognóstico , Recuperação de Função Fisiológica , Reoperação/métodos , Medição de Risco , Síndrome do Intestino Curto/fisiopatologia
10.
Cell Host Microbe ; 26(5): 569-570, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31726023

RESUMO

Intestinal pathogens encounter the microbiota as they seek their host target, potentially impacting the infection. In a recent Cell paper, Shi et al. (2019) show that unique segmented filamentous bacteria prevent rotavirus from infecting the intestinal epithelium. Proposed mechanisms include direct effects on the virus and stimulation of epithelial proliferation.


Assuntos
Microbioma Gastrointestinal , Infecções por Rotavirus , Bactérias , Humanos , Mucosa Intestinal , Intestinos
11.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3170-3177, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602869

RESUMO

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.


Assuntos
Caprifoliaceae/química , Medicamentos de Ervas Chinesas/farmacocinética , Absorção Intestinal , Extratos Vegetais/farmacocinética , Animais , Intestinos , Ratos , Ratos Sprague-Dawley
12.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3645-3652, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602936

RESUMO

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.


Assuntos
Biofarmácia , Absorção Intestinal , Humanos , Intestinos/efeitos dos fármacos , Medicina Tradicional Chinesa , Perfusão , Permeabilidade
13.
Zhonghua Nei Ke Za Zhi ; 58(10): 782-785, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594178

RESUMO

To explore the therapeutic effect of fecal microbiota transplantation (FMT) for severe psoriasis. A patient, male, 36 years old, diagnosed as severe plaque psoriasis for 10 years and irritable bowel syndrome (IBS) for 15 years, was administrated twice FMT via both upper endoscopy and colonoscopy with a 5-week interval. The following items were used to evaluate responses: body surface area (BSA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), histological examination, intestinal symptoms, adverse reactions and serum level of tumor necrosis factor (TNF)-α. After second FMT treatment for 5 weeks, aforementioned items were improved greatly compared with those before treatment. Moreover, IBS was completely relieved and no adverse reactions were observed during the treatment and follow-up. In conclusion, FMT could be a novel therapy for psoriasis. Further clinical trials are needed to provide solid evidences.


Assuntos
Transplante de Microbiota Fecal , Síndrome do Intestino Irritável/terapia , Psoríase/terapia , Fator de Necrose Tumoral alfa/sangue , Adulto , Endoscopia , Transplante de Microbiota Fecal/tendências , Fezes/microbiologia , Microbioma Gastrointestinal , Humanos , Intestinos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/psicologia , Masculino , Psoríase/psicologia , Qualidade de Vida , Resultado do Tratamento
14.
Artigo em Inglês | MEDLINE | ID: mdl-31594645

RESUMO

The number of disorders now linked to increased intestinal mucosal permeability implies that a substantial percent of the population is affected. Drug interventions targeting reduced tight junctional permeability are being pursued. Although hyper-permeability in itself is not a clinically recognized disease entity, its relationship to disease processes has driven interest in measuring, and even monitoring mucosal permeability in vivo. Along with improved knowledge of gut barrier physiology, advances have been made in tests and biomarkers of barrier function. Drawing from our experiences in the past decade, considerations and challenges faced in assessing in vivo intestinal permeability are discussed herein, along with indications of what the future might hold.


Assuntos
Biomarcadores/metabolismo , Mucosa Intestinal/fisiologia , Intestinos/fisiopatologia , Permeabilidade , Humanos
15.
Int J Nanomedicine ; 14: 7095-7106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564867

RESUMO

Background: Norisoboldine (NOR), the main isoquinoline alkaloid constituent in Radix Linderae, was demonstrated to have an outstanding anti-arthritis activity. However, a poor oral bioavailability of NOR creates a barrier for its development and application. Methods: A new self-nanoemulsifying drug delivery system (SNEDDS) loaded with the phospholipid complex (PC) was designed to improve the oral bioavailability of NOR. NOR-PC was prepared by solvent evaporation method with a mixture of phospholipid and NOR at a mass ratio of 3:1. The property of PC is to improve the liposolubility of NOR, and made PC embedded in the drug delivery system. The physicochemical property of NOR-PC was characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). According to the ability to dissolve NOR-PC, the oil and cosurfactant were chosen. The surfactant was selected based on its emulsification efficiency in SNEDDS. Pseudo-ternary phase diagram was created to select the best formulation of NOR-PC-SNEDDS, and the pharmacokinetic parameters were detected in rats. In addition, intestinal lymphatic transport and liver microsome experiment were studied to gain insight into the mechanism for NOR-PC-SNEDDS increasing the oral bioavailability of NOR. Results: Solubility detection showed that the PC significantly improved the liposolubility of NOR. NOR-PC-SNEDDS was prepared using NOR-PC, Ethyl oleate, Labrasol, Cremophor EL and transcutol HP at a weight ratio of 1:2:3.36:2.24:2.4 (w/w/w/w/w). The particle size and zeta potential of NOR-PC-SNEDDS were 36.72±1.47 nm and -4.91±0.49 mV after dilution with distilled water at a ratio of 1:50 (w/w). The absolute bioavailability of NOR in the NOR-PC-SNEDDS group significantly increased and the value was 372% in relative to NOR group. Further studies indicated that NOR-PC-SNEDDS promoted the oral bioavailability of NOR by enhancing intestinal lymphatic absorption and inhibiting Phase II metabolism of NOR. Conclusion: These findings suggested that NOR-PC-SNEDDS was able to promote the oral bioavailability of NOR, which provided a foundation for the further development and application of NOR.


Assuntos
Absorção Fisiológica , Alcaloides/farmacologia , Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Fosfolipídeos/química , Administração Oral , Alcaloides/sangue , Alcaloides/química , Alcaloides/farmacocinética , Animais , Varredura Diferencial de Calorimetria , Intestinos/fisiologia , Sistema Linfático/fisiologia , Masculino , Desintoxicação Metabólica Fase II , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Transição de Fase , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Termodinâmica , Fatores de Tempo
17.
Adv Exp Med Biol ; 1141: 361-405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571170

RESUMO

Oral drug administration is the most favorable route of drug administration in the clinic. Intestinal transporters have been shown to play a significant role in the rate and extent of drug absorption of some, but not all, drug molecules. Due to the heterogeneous expression of multiple transporters along the intestine, the preferential absorption sites for drugs may vary significantly. In this chapter, we aim to summarize the current research on the expression, localization, function, and regulation of human intestinal transporters implicated in altering the absorption of low to medium molecular weight drug molecules. The role played by bile acid transport proteins (e.g., ASBT and OST-α/ß) is included in the discussion. The synergistic action of intestinal drug metabolism and transport is also discussed. Despite the complicated regulatory factors, the biopharmaceutics drug disposition classification system (BDDCS) put forward by Wu and Benet may help us better predict the effect of transporters on drug absorption. The drug-induced toxicity in the intestine, which may result from drug-drug interaction, gut microbiota, and bile salt toxicity, is also discussed.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Absorção Intestinal , Intestinos , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Interações de Medicamentos , Humanos , Intestinos/efeitos dos fármacos , Preparações Farmacêuticas/metabolismo
18.
Medicine (Baltimore) ; 98(39): e17079, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574807

RESUMO

Advancements in diagnostic modalities have improved the diagnosis of meconium peritonitis (MP) both in utero and ex utero. This study aimed to determine the efficacy of prompt prenatal and postnatal diagnoses of MP on the postnatal outcomes of these patients.We conducted a retrospective chart review of neonates with MP admitted to the Mackay Memorial Hospital Systems from 2005 to 2016. The prenatal diagnoses, postnatal presentations, surgical indications, operative methods, types of MP, operative findings, associated anomalies, morbidities, patient outcomes, and survival rates were analyzed. Morbidities included postoperative adhesion ileus, bacteremia, and short bowel syndrome. We also performed subgroup analyses of the morbidity and survival rates of prenatally versus postnatally diagnosed patients, as well as inborn versus outborn neonates.Thirty-seven neonates with MP were enrolled. Of this number, 24 (64.9%) were diagnosed prenatally. Twenty-two (59.5%) were born preterm. The most common prenatal sonographic findings included fetal ascites followed by dilated bowel loops. Abdominal distention was the most frequent postnatal symptom. Thirty-four (91.9%) neonates underwent surgery, whereas 3 were managed conservatively. Volvulus of the gastrointestinal tract was the most frequent anatomic anomaly. The total morbidity and survival rates were 37.8% and 91.9%, respectively. The morbidity and survival rates did not differ significantly between prenatally and postnatally diagnosed patients (37.5% vs 33.3%, P = 1.00; 91.7% vs 92.3%, P = 1.00, respectively). Inborn and outborn patients did not differ in terms of morbidity and survival rates (27.3% vs 53.3%, P = .17; 100% vs 80.0%, P = .06, respectively).Although not statistically significant, inborn MP neonates had higher survival rates when compared with outborn MP neonates. Prompt postnatal management at tertiary centers seemed crucial.


Assuntos
Mecônio , Peritonite/diagnóstico por imagem , Ultrassonografia Pré-Natal , Ascite/etiologia , Dilatação Patológica/etiologia , Diagnóstico Precoce , Feminino , Humanos , Recém-Nascido , Volvo Intestinal/etiologia , Intestinos/patologia , Avaliação de Resultados da Assistência ao Paciente , Peritonite/complicações , Peritonite/mortalidade , Peritonite/terapia , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Tempo para o Tratamento
19.
J Agric Food Chem ; 67(45): 12335-12340, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31617360

RESUMO

The Human Microbiome Project has prompted unprecedented advancement in microbiome science. Personalized microbiome modulation with precision (PMMP) is one of the emerging yet challenging fields in microbiome research. Carbohydrate-based prebiotics (CBPs) have been shown to modulate the gut microbiome to various extents according to different structural characteristics, such as degree of polymerization, branching, glycosidic linkage, monosaccharide profile, and chemical modification. Subsequently, a targeted modulation of the microbiome might be achieved by using CBPs with a specific structure. A multidimensional database can be established based on the structure-microbiome and structure-microbial-marker relationships. Such relationships could facilitate the development of synbiotics and PMMP.


Assuntos
Carboidratos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Carboidratos/química , Humanos , Intestinos/microbiologia
20.
Exp Parasitol ; 207: 107781, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31626796

RESUMO

The paradigm that Toxoplasma gondii infection generates sterilizing protective immunity was broken by case studies in which reinfections were observed in immunocompetent pregnant women in the chronic phase of toxoplasmosis. Since then, several murine models have suggested that immunoprotection against a previous T. gondii infection may be violated after reinfection with strains of different genotypes. This study aimed to evaluate the dissemination of the parasite after reinfection with the virulent TgCTBr9 and EGS strains in BALB/c mice chronically infected with the avirulent TgCTBr5 strain. Three mice were euthanized at 2, 4, 8, 12, 24 and 48 h post challenge (p.c.) and at 7, 14 and 30 days p.c. Intestines, mesenteric lymph nodes, lungs and brains were collected for PCR-RFLP. Blood samples were collected to measure total IgG, IgG1 and IgG2a by ELISA. The reinfected animals survived and presented reduced morbidity after challenge with the virulent strains. Mice challenged with the TgCTBr9 strain showed a slight increase in anti-T. gondii IgG1. The spread of the TgCTBr5 strain was observed to occur earlier than the dissemination of the virulent TgCTBr9 or EGS strains. The TgCTBr9 strain was observed in the mesenteric lymph node at 7 days post challenge (d.p.c.); in the intestine and lungs at 14 d.p.c.; and in the brain at 30 d.p.c. EGS strain was demonstrated in the mesenteric lymph node and lung at 7 d.p.c and in the intestine and brain at a later time point. The immune response promoted by the primary infection with the avirulent strain (TgCTBr5) protected the animals from death after challenge with the virulent strains (TgCTBr9 or EGS).


Assuntos
Anticorpos Antiprotozoários/sangue , Toxoplasma/fisiologia , Toxoplasmose Congênita/parasitologia , Animais , Peso Corporal , Encéfalo/parasitologia , Brasil , Feminino , Genótipo , Humanos , Imunoglobulina G/sangue , Intestinos/parasitologia , Pulmão/parasitologia , Linfonodos/parasitologia , Mesentério , Camundongos , Camundongos Endogâmicos BALB C , Morbidade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Recidiva , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose Congênita/imunologia , Virulência
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