Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.568
Filtrar
1.
Medicine (Baltimore) ; 100(3): e23887, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545956

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disorder. The global incidence of IBS is as high as 9% to 23%, accounting for about 50% of outpatients in gastroenterology, and the new case detection rate is 0.2% every year. IBS has become a global gastrointestinal functional disease. Although IBS is not a life-threatening disease, it seriously affects the quality of life of patients, causing huge economic and mental burden to individuals, society and families. Lipi Guben decoction (LPGBD) is an important auxiliary treatment for IBS, but lack of robust Evidence-based medicine evidence proving its efficacy. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of LPGBD in the treatment of IBS. METHODS: In this randomized controlled trial, a total of 100 eligible patients will be allocated to the blank control group or LPGBD group in a ratio of 1:1. The treatment period was 12 weeks. The primary outcome measure will be the total clinical effective rate. The Secondary outcomes will include IBS clinical symptom scores, IBS-Severity Scoring System, IBS-Quality of life, Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Bristol Stool Form Scale. The safety outcome will include Echocardiogram, blood examination (including blood routine test, liver function test, and renal function test), urine routine test and stool routine test. The evaluation indicators and all safety results will be performed at baseline, week 4, week 8 and week 12. RESULTS: This study will be helpful to evaluate the efficacy and safety of LPGBD in the treatment of IBS. CONCLUSION: LPGBD may improve the clinical efficacy of patients with IBS, which has important value in practical application. TRIAL REGISTRATION: Chictr20000039617, registration time: November 3, 2020.


Assuntos
Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Adolescente , Adulto , Idoso , Diarreia/patologia , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
2.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348552

RESUMO

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott-Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients.


Assuntos
Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Diarreia/etiologia , Diarreia/patologia , Oftalmopatias Hereditárias/etiologia , Oftalmopatias Hereditárias/patologia , Hipertensão/complicações , Enteropatias/etiologia , Enteropatias/patologia , /mortalidade , Anormalidades da Pele/etiologia , Anormalidades da Pele/patologia , Vasa Vasorum/patologia , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Autopsia , Encéfalo/patologia , Isquemia Encefálica/patologia , Células Cultivadas , Endocitose/genética , Células Endoteliais/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Nexinas de Classificação/genética , Transfecção
3.
Arch Virol ; 165(12): 3011-3015, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33025200

RESUMO

The hemagglutinin-esterase (HE) protein of betacoronavirus lineage A is a secondary receptor in the infection process and is involved in the emergence of new betacoronavirus genotypes with altered host specificity and tissue tropism. We previously reported a novel recombinant bovine coronavirus (BCoV) strain that was circulating in dairy cattle in China, but this virus was not successfully isolated, and the genetic characteristics of BCoV are still largely unknown. In this study, 20 diarrheic faecal samples were collected from a farm in Liaoning province that had an outbreak of calf diarrhea (≤ 3 months of age) in November 2018, and all of the samples tested positive for BCoV by RT-PCR. In addition, a BCoV strain with a recombinant HE (designated as SWUN/A1/2018) and another BCoV strain with a recombinant HE containing an insertion (designated as SWUN/A10/2018) were successfully isolated in cell culture (TCID50: 104.25/mL and 104.73/mL, respectively). Unexpectedly, we identified the emergence of a novel BCoV variant characterized by a 12-nt bovine gene insertion in the receptor-binding domain in a natural recombinant HE gene, suggesting a novel evolutionary pattern in BCoV.


Assuntos
Doenças dos Bovinos/epidemiologia , Infecções por Coronavirus/veterinária , Coronavirus Bovino/genética , Diarreia/veterinária , Hemaglutininas Virais/genética , RNA Viral/genética , Proteínas Virais de Fusão/genética , Animais , Bovinos , Doenças dos Bovinos/patologia , Doenças dos Bovinos/virologia , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Coronavirus Bovino/classificação , Coronavirus Bovino/isolamento & purificação , Diarreia/epidemiologia , Diarreia/patologia , Diarreia/virologia , Evolução Molecular , Fezes/virologia , Expressão Gênica , Genótipo , Modelos Moleculares , Mutagênese Insercional , Filogenia , Estrutura Secundária de Proteína , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
4.
PLoS One ; 15(9): e0238231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881883

RESUMO

BACKGROUND: In Ethiopia, uncomplicated severe acute malnutrition is managed through the outpatient therapeutic program at health posts level. This brings the services for the management of Severe Acute Malnutrition closer to the community by making services available at decentralized treatment points within the primary health care settings. So far, evidence of the treatment outcome of the program is limited. OBJECTIVE: The main aim of this study was to determine the magnitude of treatment outcomes of severe acute malnutrition and associated factors among under-five children at outpatient therapeutic feeding units in Gubalafto Wereda, Ethiopia, 2019. METHODS: This was a retrospective cohort study conducted on 600 children who had been managed for Severe Acute Malnutrition (SAM) under Outpatient Therapeutic Program (OTP) in Gubalafto Wereda from April to May/2019. The children were selected using systematic random sampling from 9 health posts. The structured, pre-tested, and adapted questionnaire was used to collect the data. The data was entered by using EPI-data Version 4.2 and exported to SPSS version 24.0 for analysis. Bivariate and Multivariate regression was also carried out to determine the association between dependent and independent variables. RESULTS: A total of 600 records of children with a diagnosis of severe acute malnutrition were reviewed. Of these cases of malnutrition, the recovery rate was found to be 65%. The death rate, default rate, and medical transfer were 2.0, 16.0, and 17.0 respectively. Immunized children had 6.85 times higher odds of recovery than children who were not immunized (AOR = 6.85 at 95% CI (3.68-12.76)). The likelihood of recovery was 3.78 times higher among children with new admission than those with re-admission (AOR = 3.78at 95% CI ((1.77-8.07))). Likewise, children provided with amoxicillin were 3.38 times recovered than their counterparts (AOR = 3.38 at 95% CI ((1.61-7.08))). SAM treatment in OTP is beneficial because of its local access for most severe cases since children reach early before developing complications as a result fatalities will be reduced. CONCLUSIONS: The recovery rate and medical transfer were lower than the sphere standard. Presence of cough, presence of diarrhea admission category, provision of amoxicillin, and immunization status were factors identified as significantly associated with treatment outcome of severe acute malnutrition. The impact on increasing the recovery rates of children treated using the OTP service indicates the potential benefits of increasing the capacity of such services across a target region on child mortality/recovery. Timely intervention is another benefit of a more local service like OTP. Building capacity of OTP service providers and regular monitoring of service provision based on the management protocol was recommended.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Desnutrição Aguda Grave/terapia , Antibacterianos/uso terapêutico , Pré-Escolar , Diarreia/complicações , Diarreia/tratamento farmacológico , Diarreia/patologia , Etiópia , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Estudos Retrospectivos , Desnutrição Aguda Grave/complicações , Desnutrição Aguda Grave/patologia , Resultado do Tratamento , Vacinação , Vitamina A/uso terapêutico
6.
PLoS One ; 15(7): e0235704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716913

RESUMO

BACKGROUND: Diarrhea in infancy can compromise linear growth and this relationship is likely influenced by diarrhea severity, number of episodes, and the timing of those episodes. HIV exposed, uninfected infants (HEU) have higher risk of growth faltering, infectious morbidity and mortality than HIV-unexposed infants and may be representative of children particularly vulnerable to diarrhea-associated linear growth faltering. METHODOLOGY/PRINCIPAL FINDINGS: We utilized data from a cohort of Kenyan HEU infants followed from birth to 12 months of age. Infant length and morbidity were ascertained at monthly study visits and sick visits. Longitudinal models estimated the association between diarrhea severity and length-for-age Z-score (LAZ) in the following month, at 12 months of age, and in 6-month intervals. The 372 enrolled infants experienced an average of 2.15 episodes (range: 0-8) of diarrhea and 0.54 episodes (0-4) of moderate-to-severe diarrhea (MSD) between birth and 12 months. Surviving infants had a mean LAZ of -0.97 (standard deviation: 1.2) at 12 months. MSD was significantly associated with an average loss of 0.14 (95% Confidence Interval [CI]: -0.24, -0.05, p = 0.003) in LAZ one month after the episode. Linear growth outcomes were not predicted by cumulative episodes of diarrhea, or timing of diarrhea during infancy. CONCLUSIONS/SIGNIFICANCE: Diarrhea severity influenced the relationship between diarrhea and subsequent linear growth. HEU infants with MSD may benefit from nutritional interventions following severe diarrhea to protect against linear growth faltering.


Assuntos
Diarreia/patologia , Infecções por HIV/diagnóstico , Adulto , Diarreia/complicações , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Lactente , Quênia/epidemiologia , Estudos Longitudinais , Masculino , Gravidez , Índice de Gravidade de Doença
7.
PLoS One ; 15(7): e0236502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702014

RESUMO

The transmission of human norovirus excreted from infected persons occasionally causes sporadic infections and outbreaks. Both symptomatic patients and asymptomatic carriers have been reported to contribute to norovirus transmission, but little is known about the magnitude of the contribution of asymptomatic carriers. We carried out a 1-year survey of residents of a district of Bangkok, Thailand to determine the percentage of norovirus transmissions originating from asymptomatic individuals. We screened 38 individuals recruited from 16 families from May 2018 to April 2019 for GI and GII genotypes. Norovirus was detected every month, and 101 of 716 stool samples (14.1%) from individuals with no symptoms of acute gastroenteritis were norovirus-positive. The average infection frequency was 2.4 times per person per year. Fourteen genotypes were identified from the positive samples, with GII.4 being detected most frequently. Notably, 89.1% of the norovirus-positive samples were provided by individuals with no diarrhea episode. Similar to cases of symptomatic infections in Thailand, asymptomatic infections were observed most frequently in December. We detected 4 cases of NV infection caused by household transmission, and 3 of the 4 transmissions originated from asymptomatic individuals. We also identified a case in which norovirus derived from an asymptomatic individual caused diarrhea in a family member. These results suggest that asymptomatic individuals play a substantial role in both the maintenance and spreading of norovirus in a community through household transmission.


Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Caliciviridae/transmissão , Gastroenterite/virologia , Norovirus/patogenicidade , Adolescente , Adulto , Idoso , Infecções por Caliciviridae/patologia , Infecções por Caliciviridae/virologia , Criança , Diarreia/patologia , Diarreia/virologia , Surtos de Doenças , Fezes/virologia , Feminino , Gastroenterite/patologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Adulto Jovem
8.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32554697

RESUMO

Coronaviruses (CoVs) have repeatedly emerged from wildlife hosts and infected humans and livestock animals to cause epidemics with significant morbidity and mortality. CoVs infect various organs, including respiratory and enteric systems, as exemplified by newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The constellation of viral factors that contribute to developing enteric disease remains elusive. Here, we investigated CoV interferon antagonists for their contribution to enteric pathogenesis. Using an infectious clone of an enteric CoV, porcine epidemic diarrhea virus (icPEDV), we generated viruses with inactive versions of interferon antagonist nonstructural protein 1 (nsp1), nsp15, and nsp16 individually or combined into one virus designated icPEDV-mut4. Interferon-responsive PK1 cells were infected with these viruses and produced higher levels of interferon responses than were seen with wild-type icPEDV infection. icPEDV-mut4 elicited robust interferon responses and was severely impaired for replication in PK1 cells. To evaluate viral pathogenesis, piglets were infected with either icPEDV or icPEDV-mut4. While the icPEDV-infected piglets exhibited clinical disease, the icPEDV-mut4-infected piglets showed no clinical symptoms and exhibited normal intestinal pathology at day 2 postinfection. icPEDV-mut4 replicated in the intestinal tract, as revealed by detection of viral RNA in fecal swabs, with sequence analysis documenting genetic stability of the input strain. Importantly, icPEDV-mut4 infection elicited IgG and neutralizing antibody responses to PEDV. These results identify nsp1, nsp15, and nsp16 as virulence factors that contribute to the development of PEDV-induced diarrhea in swine. Inactivation of these CoV interferon antagonists is a rational approach for generating candidate vaccines to prevent disease and spread of enteric CoVs, including SARS-CoV-2.IMPORTANCE Emerging coronaviruses, including SARS-CoV-2 and porcine CoVs, can infect enterocytes, cause diarrhea, and be shed in the feces. New approaches are needed to understand enteric pathogenesis and to develop vaccines and therapeutics to prevent the spread of these viruses. Here, we exploited a reverse genetic system for an enteric CoV, porcine epidemic diarrhea virus (PEDV), and outline an approach of genetically inactivating highly conserved viral factors known to limit the host innate immune response to infection. Our report reveals that generating PEDV with inactive versions of three viral interferon antagonists, nonstructural proteins 1, 15, and 16, results in a highly attenuated virus that does not cause diarrhea in animals and elicits a neutralizing antibody response in virus-infected animals. This strategy may be useful for generating live attenuated vaccine candidates that prevent disease and fecal spread of enteric CoVs, including SARS-CoV-2.


Assuntos
Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Interferons/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Vacinas Atenuadas/imunologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/prevenção & controle , Diarreia/patologia , Diarreia/virologia , Modelos Animais de Doenças , Endorribonucleases/antagonistas & inibidores , Fezes/virologia , Íleo/patologia , Imunidade Inata , Jejuno/patologia , Pandemias , Pneumonia Viral/imunologia , Vírus da Diarreia Epidêmica Suína/genética , RNA Viral , Suínos , Doenças dos Suínos/virologia , Células Vero , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
9.
J Med Microbiol ; 69(7): 932-943, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32530393

RESUMO

Introduction. Diarrhoeagenic Escherichia coli (DEC) are difficult to distinguish from non-pathogenic commensal E. coli using traditional culture methods. The implementation of PCR targeting specific virulence genes characteristic of the five DEC pathotypes, has improved the detection of DEC in faecal specimens from patients with symptoms of gastrointestinal disease.Aim. Antimicrobial resistance (AMR) profiles of 660 strains of DEC isolated between 2015 and 2017 from UK travellers reporting symptoms of gastrointestinal disease were reviewed to look for evidence of emerging AMR associated with travellers' diarrhoea.Methodology. All isolates of DEC were sequenced, and sequence type, serotype, pathotype markers and AMR profiles were derived from the genome data.Results. A travel history was provided for 54.1 % (357/660) of cases, of which 77.0 % (275/357) reported travel outside the UK within 7 days of onset of symptoms, and 23.0 % (82/357) reported no travel in that time frame. Of the 660 strains of DEC in this study, 265 (40.2 %) samples were identified as EAEC, 48 (7.3 %) as EIEC, 61 (9.2 %) were ETEC and 286 (43.3 %) were EPEC. EPEC caused the highest percentage of infections in children (40.6 %) whilst the highest proportion of cases reporting recent travel were infected with ETEC (86.1 %). There were 390/660 (59.0 %) isolates resistant to at least one antimicrobial on the panel tested (EIEC, 81.3 %; ETEC, n=65.6 %; EAEC, n=73.2 %; EPEC, 40.9 %) and 265/660 (40.2 %) were multidrug-resistant (EIEC, 33.3 %; ETEC, 32.8 %; EAEC, 56.2 %; EPEC, 28.0 %). Genes conferring resistance to the beta-lactams and fluroquinolones were highest in the EAEC pathotype, 56.6 and 60.7%, respectively.Conclusions. Increasing MDR, along with resistance to the fluroquinolones and the third-generation cephalosporins, in DEC causing travellers' diarrhoea provides further evidence for the need to restrict the use of antimicrobial agents and continuous monitoring.


Assuntos
Farmacorresistência Bacteriana/genética , Disenteria/genética , Escherichia coli/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Criança , Pré-Escolar , Diarreia/patologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Disenteria/epidemiologia , Disenteria/microbiologia , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Fezes/microbiologia , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/genética , Gastroenteropatias/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Viagem , Reino Unido , Virulência/efeitos dos fármacos
10.
Am J Clin Pathol ; 154(3): 403-413, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32459333

RESUMO

OBJECTIVES: We aimed to describe the clinical and histopathologic features of Castleman disease (CD), particularly emphasizing its associations with paraneoplastic pemphigus (PNP) and prognosis. METHODS: We retrospectively enrolled 123 CD patients at our center. Clinical, pathologic, and laboratory data were reviewed. RESULTS: Fifty percent of the patients had PNP. Compared with those without PNP, patients with PNP-associated CD had more hyaline vascular (HV) variants (83.9% vs 57.4%), fewer mixed cellular variants (16.1% vs 24.6%), and no plasmacytic variants (0% vs 18.0%). Thirty-eight of 87 patients with the HV variant of CD (HV-CD) had stroma-rich (SR) features, and the incidence rate was higher in those with PNP-associated CD than in those without PNP (48.4% vs 13.1%, P < .001). The SR variant was associated with higher PNP-associated IgG titers than SR absence before surgery (median 1:160 vs 1:80, P = .019) or after surgery (median 1:160 vs 1:40, P = .013). The SR variant was also an unfavorable prognostic factor for CD survival in univariate analysis. The 3-year survival rates were 47.5% among those with PNP and 87.7% among those without PNP (P < .001). CONCLUSIONS: PNP is associated with specific subtypes of CD and affects survival. The SR variant of HV-CD positively correlates with the incidence of PNP.


Assuntos
Hiperplasia do Linfonodo Gigante/patologia , Diarreia/patologia , Oftalmopatias Hereditárias/patologia , Enteropatias/patologia , Síndromes Paraneoplásicas/patologia , Pênfigo/patologia , Anormalidades da Pele/patologia , Doenças Vasculares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
PLoS One ; 15(5): e0228824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469907

RESUMO

INTRODUCTION: Routine use of probiotics during antibiotic therapy in children remains a subject of discussion. To facilitate synthesis of individual study results and guideline formulation, it is important to assess predefined, similar, and clinically important outcomes. Core outcome sets are a proposed solution for this issue. The aim of this review was to document choice, design, and heterogeneity of outcomes in studies that assessed the effects of probiotics used for the prevention of antibiotic-associated adverse events in children. METHODS: A scoping literature search covering three major databases was performed. Studies that evaluated oral probiotics' use concomitant with antibiotic therapy in children were included. Data on outcome definitions, measurement instruments, and follow-up were extracted. The outcomes were assigned to predefined core areas and domains. Data were analyzed descriptively. RESULTS: Thirty-seven studies were included in this review. Diarrhea, the most commonly reported outcome, had diagnostic criteria clearly defined only in 21 studies. In total, 16 different definitions of diarrhea were identified. Diarrhea duration, severity, and etiology were reported in 9, 4, and 7 studies, respectively. Twenty studies assessed gastrointestinal symptoms other than diarrhea. Seven studies reported outcomes related to resource use or the economic impact of the intervention. Only 2 studies assessed outcomes related to life impact. None of the studies predefined adverse events of probiotic use. CONCLUSIONS: Identified outcomes were characterized by substantial heterogeneity. The majority of outcomes were not designed to evaluate endpoints of real-life relevance. Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making.


Assuntos
Antibacterianos/efeitos adversos , Diarreia/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Probióticos/uso terapêutico , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Bases de Dados Factuais , Diarreia/induzido quimicamente , Diarreia/patologia , Humanos , Resultado do Tratamento
12.
Clin Gastroenterol Hepatol ; 18(8): 1663-1672, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32278065

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Diarreia/epidemiologia , Diarreia/fisiopatologia , Gerenciamento Clínico , Fezes/virologia , Pneumonia Viral/complicações , Criança , Diarreia/patologia , Diarreia/terapia , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Incidência , Controle de Infecções/métodos , Pandemias , Peptidil Dipeptidase A/metabolismo , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Viral , Internalização do Vírus
13.
Clin Gastroenterol Hepatol ; 18(8): 1753-1759.e2, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311512

RESUMO

BACKGROUND & AIMS: We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. METHODS: We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. RESULTS: Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients' hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039). CONCLUSIONS: At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.


Assuntos
Betacoronavirus/isolamento & purificação , Portador Sadio/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diarreia/epidemiologia , Diarreia/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Adulto , Idoso , Contagem de Células Sanguíneas , Análise Química do Sangue , China , Diarreia/patologia , Fezes/virologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/virologia , Pandemias , Faringe/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Adulto Jovem
14.
Hum Genet ; 139(10): 1247-1259, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32306098

RESUMO

Congenital diarrheal disorders (CDD) comprise > 50 monogenic entities featuring chronic diarrhea of early-onset, including defects in nutrient and electrolyte absorption, enterocyte polarization, enteroendocrine cell differentiation, and epithelial integrity. Diarrhea is also a predominant symptom in many immunodeficiencies, congenital disorders of glycosylation, and in some defects of the vesicular sorting and transporting machinery. We set out to identify the etiology of an intractable diarrhea in 2 consanguineous families by whole-exome sequencing, and identified two novel AP1S1 mutations, c.269T>C (p.Leu90Pro) and c.346G>A (p.Glu116Lys). AP1S1 encodes the small subunit of the adaptor protein 1 complex (AP-1), which plays roles in clathrin coat-assembly and trafficking between trans-Golgi network, endosomes and the plasma membrane. An AP1S1 knock-out (KO) of a CaCo2 intestinal cell line was generated to characterize intestinal AP1S1 deficiency as well as identified mutations by stable expression in KO background. Morphology and prototype transporter protein distribution were comparable between parental and KO cells. We observed altered localization of tight-junction proteins ZO-1 and claudin 3, decreased transepithelial electrical resistance and an increased dextran permeability of the CaCo2-AP1S1-KO monolayer. In addition, lumen formation in 3D cultures of these cells was abnormal. Re-expression of wild-type AP1S1 in CaCo2-AP1S1-KO cells reverted these abnormalities, while expression of AP1S1 containing either missense mutation did not. Our data indicate that loss of AP1S1 function causes an intestinal epithelial barrier defect, and that AP1S1 mutations can cause a non-syndromic form of congenital diarrhea, whereas 2 reported truncating AP1S1 mutations caused MEDNIK syndrome, characterized by mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia.


Assuntos
Complexo 1 de Proteínas Adaptadoras/genética , Subunidades sigma do Complexo de Proteínas Adaptadoras/genética , Surdez/genética , Diarreia/genética , Ictiose/genética , Deficiência Intelectual/genética , Ceratodermia Palmar e Plantar/genética , Mutação de Sentido Incorreto , Complexo 1 de Proteínas Adaptadoras/deficiência , Subunidades sigma do Complexo de Proteínas Adaptadoras/deficiência , Sequência de Bases , Células CACO-2 , Claudina-3/genética , Claudina-3/metabolismo , Consanguinidade , Surdez/diagnóstico , Surdez/metabolismo , Surdez/patologia , Diarreia/diagnóstico , Diarreia/metabolismo , Diarreia/patologia , Feminino , Expressão Gênica , Técnicas de Inativação de Genes , Teste de Complementação Genética , Humanos , Ictiose/diagnóstico , Ictiose/metabolismo , Ictiose/patologia , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Deficiência Intelectual/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Linhagem , Permeabilidade , Sequenciamento Completo do Exoma , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
15.
Adv Exp Med Biol ; 1244: 247-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301019

RESUMO

Immune checkpoint inhibitors (ICIs) have shown significant benefit in cancer patients. Their success, however, is associated with immune-related adverse events (irAEs), which commonly affect the gastrointestinal tract, resulting in diarrhea and colitis. IrAEs range from mild self-limiting to severe life-threatening diseases and potentially limit the use of these medications. Diagnosis of ICI-induced enterocolitis is based on clinical symptoms, physical examination, stool tests, endoscopic and histologic evaluation, and/or imaging. Current management strategy is mainly anti-diarrheal agents for mild symptoms and immunosuppressants (e.g., corticosteroids, and infliximab or vedolizumab) for more severe diseases.


Assuntos
Colite/induzido quimicamente , Diarreia/induzido quimicamente , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Colite/tratamento farmacológico , Colite/imunologia , Colite/patologia , Diarreia/tratamento farmacológico , Diarreia/imunologia , Diarreia/patologia , Humanos , Neoplasias/imunologia
16.
Am J Physiol Cell Physiol ; 318(6): C1136-C1143, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293934

RESUMO

The transport of electrolytes and fluid by the intestinal epithelium is critical in health to maintain appropriate levels of fluidity of the intestinal contents. The transport mechanisms that underlie this physiological process are also subject to derangement in various digestive disease states, such as diarrheal illnesses. This article summarizes the 2019 Hans Ussing Lecture of the Epithelial Transport Group of the American Physiological Society and discusses some pathways by which intestinal transport is dysregulated, particularly in the setting of infection with the diarrheal pathogen, Salmonella, and in patients treated with small-molecule inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFr-TKI). The burdensome diarrhea in patients infected with Salmonella may be attributable to decreased expression of the chloride-bicarbonate exchanger downregulated in adenoma (DRA) that participates in electroneutral NaCl absorption. This outcome is possibly secondary to increased epithelial proliferation and/or decreased epithelial differentiation that occurs following infection. Conversely, the diarrheal side effects of cancer treatment with EGFr-TKI may be related to the known ability of EGFr-associated signaling to reduce calcium-dependent chloride secretion. Overall, the findings described may suggest targets for therapeutic intervention in a variety of diarrheal disease states.


Assuntos
Antiporters/metabolismo , Diarreia/metabolismo , Células Epiteliais/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Transportadores de Sulfato/metabolismo , Animais , Antineoplásicos/toxicidade , Diferenciação Celular , Proliferação de Células , Diarreia/induzido quimicamente , Diarreia/microbiologia , Diarreia/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos , Permeabilidade , Inibidores de Proteínas Quinases/toxicidade , Salmonelose Animal/metabolismo , Salmonelose Animal/microbiologia , Salmonelose Animal/patologia
17.
BMC Med Genet ; 21(1): 79, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295532

RESUMO

BACKGROUND: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder causes severe dehydration and electrolyte disturbances. Homozygous variants in the nearby gene SLC26A4 disrupt anion exchange in the inner ear and the thyroid, causing Pendred syndrome (PDS; OMIM 274600), which is the most frequent form of syndromic deafness. CASE PRESENTATION: We report an unusual co-occurrence of two rare homozygous mutations in both the SLC26A3 and SLC26A4 genes, causing a rare combination of both CLD and PDS in two siblings. Although the clinical pictures were typical, the combined loss of these anion transporters might modulate the risk of renal injury associated with CLD. CONCLUSIONS: Familial presentation of two rare autosomal recessive disorders with loss of function of different SLC26 anion transporters is described. Independent homozygous variants in the SLC26A3 and SLC26A4 genes cause CLD and PDS in siblings, shedding light on co-occurrence of rare recessive traits in the progeny of consanguineous couples.


Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , Diarreia/congênito , Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Erros Inatos do Metabolismo/genética , Transportadores de Sulfato/genética , Diarreia/diagnóstico , Diarreia/genética , Diarreia/patologia , Feminino , Genes Recessivos/genética , Testes Genéticos , Bócio Nodular/diagnóstico , Bócio Nodular/patologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/patologia , Mutação , Linhagem , Gravidez , Doenças Raras/diagnóstico , Doenças Raras/genética , Doenças Raras/patologia , Irmãos
18.
PLoS One ; 15(4): e0230708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271786

RESUMO

Neonatal calf diarrhea (NCD) is a major problem to calf health worldwide, in terms of both morbidity and mortality. A five-point ordinal scale clinical assessment scoring (CAS) chart was utilized to assess calves suffering from NCD-related clinical abnormalities (acidosis and dehydration) on commercial farms. The objective of this research was to determine the predictive capability of this CAS chart against gold standard blood gas parameters, designed to assist farmers in the accurate assessment of the clinical consequences of NCD. A total of 443 diarrheic and non-diarrheic calves were enrolled in the study. The CAS chart rated a calf's health from no clinical signs to varying degrees of clinical severity on a 0 (clinically normal) to 4 (grave) scale, based on clinical indicators including calf demeanour, ear position, mobility, suckle reflex, desire-to-feed, and enophthalmos. Blood gas analysis was conducted for individual calves, consisting of pH, base excess, Na+, K+, Ca2+, Cl-, glucose, total hemoglobin, bicarbonate, anion gap, and strong ion difference. Statistical evaluation was performed by comparison of the CAS score with blood gas profiles using ordinal logistic regression and a non-parametric estimation of the Receiver Operating Characteristics (ROC). The ROC analysis indicated that the CAS chart had acceptable specificity (>95%) with low sensitivity (<60%) in differentiating clinically normal from acidotic/dehydrated cases. Assessment of individual severity classes indicated that the chart can predict and differentiate both clinically normal and advanced cases from the other severity classes (peak estimations >80%) but had reduced accuracy in differentiating mild and moderate cases (peak estimations >50%). The chart, as presented, provides a simple tool to differentiate clinically normal from calves suffering the consequences of diarrhea, but fails to accurately differentiate severity for NCD related acidosis and dehydration. Further efforts are required to enhance the sensitivity and differential diagnostic value of this type of chart.


Assuntos
Animais Recém-Nascidos , Doenças dos Bovinos/diagnóstico , Técnicas e Procedimentos Diagnósticos/veterinária , Diarreia/diagnóstico , Design de Software , Acidose/sangue , Acidose/diagnóstico , Acidose/veterinária , Animais , Gasometria/normas , Gasometria/veterinária , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/patologia , Desidratação/sangue , Desidratação/diagnóstico , Desidratação/veterinária , Técnicas e Procedimentos Diagnósticos/normas , Diarreia/sangue , Diarreia/patologia , Diarreia/veterinária , Feminino , Masculino , Valor Preditivo dos Testes , Prognóstico , Projetos de Pesquisa , Índice de Gravidade de Doença
19.
Clin Sci (Lond) ; 134(8): 941-953, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227118

RESUMO

The sodium-hydrogen exchanger isoform 3 (NHE3, SLC9A3) is abundantly expressed in the gastrointestinal tract and is proposed to play essential roles in Na+ and fluid absorption as well as acid-base homeostasis. Mutations in the SLC9A3 gene can cause congenital sodium diarrhea (CSD). However, understanding the precise role of intestinal NHE3 has been severely hampered due to the lack of a suitable animal model. To navigate this problem and better understand the role of intestinal NHE3, we generated a tamoxifen-inducible intestinal epithelial cell-specific NHE3 knockout mouse model (NHE3IEC-KO). Before tamoxifen administration, the phenotype and blood parameters of NHE3IEC-KO were unremarkable compared with control mice. After tamoxifen administration, NHE3IEC-KO mice have undetectable levels of NHE3 in the intestine. NHE3IEC-KO mice develop watery, alkaline diarrhea in combination with a swollen small intestine, cecum and colon. The persistent diarrhea results in higher fluid intake. After 3 weeks, NHE3IEC-KO mice show a ∼25% mortality rate. The contribution of intestinal NHE3 to acid-base and Na+ homeostasis under normal conditions becomes evident in NHE3IEC-KO mice that have metabolic acidosis, lower blood bicarbonate levels, hyponatremia and hyperkalemia associated with drastically elevated plasma aldosterone levels. These results demonstrate that intestinal NHE3 has a significant contribution to acid-base, Na+ and volume homeostasis, and lack of intestinal NHE3 has consequences on intestinal structural integrity. This mouse model mimics and explains the phenotype of individuals with CSD carrying SLC9A3 mutations.


Assuntos
Anormalidades Múltiplas/genética , Diarreia/congênito , Células Epiteliais/metabolismo , Erros Inatos do Metabolismo/genética , Trocador 3 de Sódio-Hidrogênio/genética , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Animais , Diarreia/genética , Diarreia/metabolismo , Diarreia/mortalidade , Diarreia/patologia , Modelos Animais de Doenças , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Erros Inatos do Metabolismo/metabolismo , Erros Inatos do Metabolismo/mortalidade , Erros Inatos do Metabolismo/patologia , Camundongos , Camundongos Knockout , Mutação , Trocador 3 de Sódio-Hidrogênio/metabolismo
20.
J Zoo Wildl Med ; 51(1): 232-235, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32212569

RESUMO

This study presents the gross and histopathological findings of adenoviral hemorrhagic disease (AHD) in two yearling and one adult mule deer (Odocoileus hemionus). These cases represent the first known outbreak of deer adenovirus (Odocoileus adenovirus 1) in Arizona. Over the span of a month, three female captive mule deer were submitted to Midwestern University's Animal Health Institute for postmortem examination. All of these deer were from the same deer farm and historical findings were similar, consisting of acute presentation of hemorrhagic diarrhea and sudden death. Grossly and histopathologically, all cases had severe pulmonary edema and hemorrhagic enteritis. Additionally, two of the three cases had low numbers of large amphophilic intranuclear inclusions expanding endothelial cells within the small intestine and lungs. Viral PCR of pooled small intestine, lung, and spleen from each of the three cases were positive for deer adenovirus and negative for blue tongue and epizootic hemorrhagic disease.


Assuntos
Infecções por Adenoviridae/veterinária , Atadenovirus/isolamento & purificação , Cervos , Diarreia/veterinária , Hemorragia Gastrointestinal/veterinária , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/patologia , Animais , Animais de Zoológico , Arizona , Diarreia/diagnóstico , Diarreia/patologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...