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1.
BMC Gastroenterol ; 20(1): 9, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931725

RESUMO

BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. CASE PRESENTATION: A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed-Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. CONCLUSIONS: This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Obstrução Intestinal/virologia , Úlcera/complicações , Idoso de 80 Anos ou mais , Colo Transverso/cirurgia , Colo Transverso/virologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Mucosa Intestinal/cirurgia , Mucosa Intestinal/virologia , Obstrução Intestinal/cirurgia , Masculino , Úlcera/virologia
2.
Antivir Ther ; 23(6): 495-504, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29714167

RESUMO

BACKGROUND: Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC). METHODS: GALT specimens from the terminal ileum, splenic flexure and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/ml. Flow cytometry, drug concentrations, and HIV RNA and DNA were analysed in tissue. CD4/8+ T-cells were tested for γδ TCR, and markers of T-cell activation and exhaustion. Data are reported as median (Q1-Q3). RESULTS: A total of 15 men and 5 women were enrolled. There was no difference in time since HIV diagnosis for those on RTG (9.5 [4-22] years) and DTG (17 [1-24] years; P=0.6), although time on RTG (5.4 [2.3-6.7] years) was greater than DTG (1.0 [0.1-1.5] years; P<0.001). Concentrations of RTG and DTG in rectal tissue were similar to previous reports: median tissue:plasma ratio was 11.25 for RTG and 0.44 for DTG. RNA:DNA ratios were 1.14 (0.18-5.10) for the RTG group and 0.90 (0.30-18.87) for the DTG group (P=0.95). No differences (P≥0.1) between CD4+ and CD8+ T-cell markers were found. CONCLUSIONS: RTG produced higher tissue exposures than DTG, but no significant differences in GALT HIV RNA, DNA or most immunological markers were observed. ClinicalTrials.gov NCT02218320.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Tecido Linfoide/efeitos dos fármacos , Raltegravir Potássico/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Colo Transverso/efeitos dos fármacos , Colo Transverso/patologia , Colo Transverso/virologia , DNA Viral/antagonistas & inibidores , DNA Viral/genética , DNA Viral/metabolismo , Emtricitabina/uso terapêutico , Feminino , Expressão Gênica , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Humanos , Íleo/efeitos dos fármacos , Íleo/patologia , Íleo/virologia , Imunidade Inata/efeitos dos fármacos , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , RNA Viral/antagonistas & inibidores , RNA Viral/genética , RNA Viral/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/virologia , Tenofovir/uso terapêutico , Resultado do Tratamento
3.
PLoS Pathog ; 10(6): e1004198, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24968145

RESUMO

Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques. To assess and characterize the extent of epithelial cell damage in virally-suppressed HIV-infected patients, we analyzed intestinal biopsy tissues for changes in the epithelium at the cellular and molecular level. The intestinal epithelium in the HIV gut is grossly intact, exhibiting no decreases in the relative abundance and packing of intestinal epithelial cells. We found no evidence for structural and subcellular localization changes in intestinal epithelial tight junctions (TJ), but observed significant decreases in the colonic, but not terminal ileal, transcript levels of TJ components in the HIV+ cohort. This result is confirmed by a reduction in TJ proteins in the descending colon of HIV+ patients. In the HIV+ cohort, colonic TJ transcript levels progressively decreased along the proximal-to-distal axis. In contrast, expression levels of the same TJ transcripts stayed unchanged, or progressively increased, from the proximal-to-distal gut in the healthy controls. Non-TJ intestinal epithelial cell-specific mRNAs reveal differing patterns of HIV-associated transcriptional alteration, arguing for an overall change in intestinal epithelial transcriptional regulation in the HIV colon. These findings suggest that persistent intestinal epithelial dysregulation involving a reduction in TJ expression is a mechanism driving increases in colonic permeability and microbial translocation in the ART-treated HIV-infected patient, and a possible immunopathogenic factor for non-AIDS related complications.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Colo/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Proteínas de Junções Íntimas/antagonistas & inibidores , Junções Íntimas/efeitos dos fármacos , Centros Médicos Acadêmicos , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Colo/metabolismo , Colo/patologia , Colo/virologia , Colo Ascendente/efeitos dos fármacos , Colo Ascendente/metabolismo , Colo Ascendente/patologia , Colo Ascendente/virologia , Colo Descendente/efeitos dos fármacos , Colo Descendente/metabolismo , Colo Descendente/patologia , Colo Descendente/virologia , Colo Transverso/efeitos dos fármacos , Colo Transverso/metabolismo , Colo Transverso/patologia , Colo Transverso/virologia , Feminino , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/patologia , Íleo/virologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Masculino , Pessoa de Meia-Idade , Ohio , Especificidade de Órgãos , Permeabilidade/efeitos dos fármacos , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Junções Íntimas/virologia
4.
Acta Paediatr ; 98(11): 1850-2, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19650837

RESUMO

UNLABELLED: Rotavirus is a leading cause of gastroenteritis in young children, which may indicate hospitalization due to dehydration and electrolyte imbalance. Most cases are self-limited with good prognosis. The association between rotavirus and toxic megacolon has never been mentioned in the literature. We report a case of toxic megacolon secondary to rotavirus gastroenteritis. CONCLUSION: Toxic megacolon can occur in patients with rotavirus gastroenteritis. An abdominal radiograph should be taken for patients with rotavirus gastroenteritis who have systemic toxicity and persistent abdominal fullness.


Assuntos
Gastroenterite/virologia , Megacolo Tóxico/etiologia , Infecções por Rotavirus/complicações , Doença Aguda , Pré-Escolar , Colo Transverso/diagnóstico por imagem , Colo Transverso/virologia , Desidratação/diagnóstico , Feminino , Gastroenterite/diagnóstico , Humanos , Megacolo Tóxico/diagnóstico por imagem , Radiografia , Rotavirus/isolamento & purificação
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