Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.435
Filtrar
2.
Transplant Proc ; 51(8): 2693-2696, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351772

RESUMO

Parvovirus B19 (PVB19) has tropism to red blood cell progenitors and can be reactivated after organ transplantation. The aim of study was to describe clinical manifestations, laboratory findings, treatments used, and effectiveness in kidney recipients at Viet Duc hospital. A retrospective descriptive study was performed on 663 kidney recipients who were on regular follow-up from 2000 to 2018. PVB19 was detected by polymerase chain reaction PVB19-DNA. Effectiveness of therapy was assessed by Hemoglobin level. Nine out of 663 kidney recipients (1.4%) were diagnosed with PVB19-associated anemia. Eight of these 9 (89%) were diagnosed within the first 3 months following transplantation. All patients had normoscopic anemia; the average reticulocyte proportion and count were 0.15 ± 0.04% and 0.0039 ± 0.0011T/L, respectively. Graft dysfunction was observed in 4/9 (45%) patients. Treatment included reduction of immunosuppression, intravenous immunoglobulin (IVIG), and blood transfusion. All patients responded well to treatment except 1 (11%), who experienced relapse after using low dose of IVIG. PVB19-associated anemia usually occurred early after transplantation and was associated with very low reticulocyte proportion and count. Actual treatment was effective, but the risk of relapse was present.


Assuntos
Anemia/virologia , Transplante de Rim , Infecções por Parvoviridae , Adulto , Feminino , Humanos , Hospedeiro Imunocomprometido/imunologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano , Estudos Retrospectivos
3.
Med Mycol ; 57(Supplement_3): S294-S306, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292656

RESUMO

Invasive fungal infections (IFIs) occur predominantly in immunocompromised individuals but can also be seen in previously well persons. The human innate immune system recognizes key components of the fungal cell wall as foreign resulting in a myriad of signaling cascades. This triggers release of antifungal molecules as well as adaptive immune responses, which kill or at least contain the invading fungi. However, these defences may fail in hosts with primary or secondary immunodeficiencies resulting in IFIs. Knowledge of a patient's immune status enables the clinician to predict the fungal infections most likely to occur. Moreover, the occurrence of an opportunistic mycosis in a patient without known immunocompromise usually should prompt a search for an occult immune defect. A rapidly expanding number of primary and secondary immunodeficiencies associated with mycoses has been identified. An investigative approach to determining the nature of these immunodeficiencies is suggested to help guide clinicians encountering patients with IFI. Finally, promising adjunctive immunotherapy measures are currently being investigated in IFI.


Assuntos
Imunidade Inata/imunologia , Infecções Fúngicas Invasivas/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções Oportunistas/imunologia
4.
Med Mycol ; 57(Supplement_3): S307-S317, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292657

RESUMO

The use of cytotoxic chemotherapy in the treatment of malignant and inflammatory disorders is beset by considerable adverse effects related to nonspecific cytotoxicity. Accordingly, a mechanistic approach to therapeutics has evolved in recent times with small molecular inhibitors of intracellular signaling pathways involved in disease pathogenesis being developed for clinical use, some with unparalleled efficacy and tolerability. Nevertheless, there are emerging concerns regarding an association with certain small molecular inhibitors and opportunistic infections, including invasive fungal diseases. This is perhaps unsurprising, given that the molecular targets of such agents play fundamental and multifaceted roles in orchestrating innate and adaptive immune responses. Nevertheless, some small molecular inhibitors appear to possess intrinsic antifungal activity and may therefore represent novel therapeutic options in future. This is particularly important given that antifungal resistance is a significant, emerging concern. This paper is a comprehensive review of the state-of-the-art in the molecular immunology to fungal pathogens as applied to existing and emerging small molecular inhibitors.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Imunoterapia , Infecções Fúngicas Invasivas/imunologia , Infecções Fúngicas Invasivas/terapia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico
5.
World Neurosurg ; 130: 206-210, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279104

RESUMO

BACKGROUND: Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases. CASE DESCRIPTION: We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature. CONCLUSIONS: Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.


Assuntos
Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Ventrículos Laterais/diagnóstico por imagem , Mucormicose/diagnóstico , Encéfalo/diagnóstico por imagem , Doença Crônica , Humanos , Lactente , Masculino , Mucormicose/líquido cefalorraquidiano , Mucormicose/tratamento farmacológico , Rhizopus/patogenicidade
6.
Mayo Clin Proc ; 94(8): 1567-1581, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31160063

RESUMO

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/epidemiologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Imunocompetência/imunologia , Hospedeiro Imunocomprometido/imunologia , Incidência , Comunicação Interdisciplinar , Masculino , Dose Máxima Tolerável , Testes de Sensibilidade Microbiana , Infecções por Micobactéria não Tuberculosa/diagnóstico , Infecções por Micobactéria não Tuberculosa/imunologia , Micobactérias não Tuberculosas/isolamento & purificação , Segurança do Paciente , Medição de Risco
7.
Diagn Microbiol Infect Dis ; 95(1): 67-70, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31196687

RESUMO

Hepatitis E virus (HEV) causes worldwide more than 20 million new hepatitis cases yearly. These infections can take on fulminant forms or cause severe extrahepatic manifestations, and integration into hepatitis differential diagnosis is recommended. In developed countries, genotypes 3 and 4 are most common, mainly through zoonotic transmission. HEV diagnosis is usually first approached with serological methods, sometimes completed with PCR. In this study, we tested the VIDAS anti-HEV immunoglobulin M assay for its specificity on 181 serum samples from patients infected with selected pathogens possibly causing comparable symptoms or false-positive hepatitis E IgM, such as cytomegalovirus, enterovirus, or other hepatitis viruses. Additionally, serum samples were included from 29 patients who tested positive for autoantibodies in immune-mediated liver disease. We report 8 false-positives (specificity 96%), predominantly for hepatitis A, Epstein-Barr virus, and cytomegalovirus, with numbers that are generally lower than reported for comparable assays. A small sensitivity study showed that its use is limited in immunocompromised patients, for whom molecular detection is recommended as first-line test.


Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/isolamento & purificação , Hepatite E/diagnóstico , Imunoglobulina M/sangue , Kit de Reagentes para Diagnóstico , Bélgica/epidemiologia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Hepatite E/epidemiologia , Vírus da Hepatite E/imunologia , Hepatite Autoimune/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Sensibilidade e Especificidade
9.
Crit Care ; 23(1): 152, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046842

RESUMO

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.


Assuntos
Coinfecção/mortalidade , Hospedeiro Imunocomprometido/imunologia , Influenza Humana/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Coinfecção/epidemiologia , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Influenza Humana/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Fatores de Risco
10.
Integr Cancer Ther ; 18: 1534735419848047, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31056957

RESUMO

BACKGROUND: The tumor cells responsible for metastasis are highly resistant to chemotherapy and have characteristics of stem cells, with a high capacity for self-regeneration and the use of detoxifying mechanisms that participate in drug resistance. In vivo models of highly resistant cells allow us to evaluate the real impact of the immune response in the control of cancer. MATERIALS AND METHODS: A tumor population derived from the 4T1 breast cancer cell line that was stable in vitro and highly aggressive in vivo was obtained, characterized, and determined to exhibit cancer stem cell (CSC) phenotypes (CD44+, CD24+, ALDH+, Oct4+, Nanog+, Sox2+, and high self-renewal capacity). Orthotopic transplantation of these cells allowed us to evaluate their in vivo susceptibility to chemo and immune responses induced after vaccination. RESULTS: The immune response induced after vaccination with tumor cells treated with doxorubicin decreased the formation of tumors and macrometastasis in this model, which allowed us to confirm the immune response relevance in the control of highly chemotherapy-resistant ALDH+ CSCs in an aggressive tumor model in immunocompetent animals. CONCLUSIONS: The antitumor immune response was the main element capable of controlling tumor progression as well as metastasis in a highly chemotherapy-resistant aggressive breast cancer model.


Assuntos
Neoplasias da Mama/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Hospedeiro Imunocomprometido/imunologia , Animais , Antineoplásicos/farmacologia , Mama/efeitos dos fármacos , Mama/imunologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco Neoplásicas/imunologia
11.
Internist (Berl) ; 60(7): 678-683, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31089769

RESUMO

Infections in immunosuppressed patients represent a particular challenge in the diagnostics and treatment. They often present with atypical and particularly severe courses, for which rapid diagnostics and treatment are decisive for treatment success. Opportunistic infections with human herpes viruses occur not only more frequently in immunocompromised patients compared to healthy people but also represent a special challenge. In the treatment of immunosuppressed patients, e.g. with human immunodeficiency virus infections and patients with solid organ transplantations, infections with herpes simplex virus, varicella zoster virus, Epstein-Barr virus and cytomegalovirus are particularly important. The symtoms are very variable, ranging from asymptomatic detection of viremia to vital life-threatening organ manifestations. This review article describes the most important clinical presentations of these opportunistic infections. Furthermore, the diagnostic, therapeutic and prophylactic strategies for human herpes viruses are summarized.


Assuntos
Herpes Zoster/diagnóstico , Infecções por Herpesviridae/diagnóstico , Hospedeiro Imunocomprometido/imunologia , Infecções Oportunistas/diagnóstico , Transplante de Órgãos , Transplante/efeitos adversos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Infecções por Herpesviridae/tratamento farmacológico , Herpesvirus Humano 3 , Herpesvirus Humano 4 , Humanos , Imunossupressão , Infecções Oportunistas/tratamento farmacológico
12.
Medicina (Kaunas) ; 55(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126152

RESUMO

Varicella-zoster virus (VZV) is a human neurotropic herpes virus that causes chickenpox in children. After becoming latent in dorsal root ganglia, it can reactivate to cause dermatological manifestations, the most common one being shingles or herpes zoster. Severe neurologic dysfunctions can occur in immunocompromised patients such as encephalitis, meningitis, myelitis and neuropathy. Longitudinal extensive transverse myelitis (LETM) is an unusual neurological complication mainly described in immunocompromised patients, with very few cases described in immunocompetent ones. We hereby report a case of VZV-induced LETM in an immunocompetent older adult-a situation rarely described in the literature. LETM is a rare complication of VZV and its pathogenesis; therapeutic interventions and prognosis are far from being fully clarified. However, a prompt diagnosis is needed to allow a rapid initialization of treatment and ensure a better outcome. Although the therapeutic lines are not clear, immunosuppressive agents may have their place in cases of unsuccessful results and/or relapses following acyclovir coupled with a well conducted methylprednisolone therapy. Further studies are highly needed to improve the current understanding of the disease course and mechanisms, and to optimize therapeutic strategies.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Mielite Transversa/complicações , Idoso , Herpesvirus Humano 3 , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Mielite Transversa/diagnóstico por imagem , Mielite Transversa/virologia , Recidiva , Medula Espinal/diagnóstico por imagem , Medula Espinal/virologia
13.
Lett Appl Microbiol ; 69(1): 30-34, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30980551

RESUMO

Low proliferation rate of bacterial populations was recently assumed to be a reason for higher resistance to antibiotics and appearance of many chronic infections. Slowly growing populations, called 'small colony variants' (SCVs) have been described in many bacterial species to make from as low as 0·02% up to 46% of population. Thirty enterococcal strains from urine and faeces of renal transplant recipients with asymptomatic, insignificant bacteriuria were studied. Growth characteristics were estimated by microculture and OD reading after 1, 3 and 5 h of culture. At the same time, penicillin binding and changes of aggregation of the cells were analysed by flow cytometry. The results of our study showed high diversity of the proliferation rates among studied isolates. Based on proliferation rates and aggregation, six of studied strains (20%) could be considered as SCVs-like. Significantly lower binding of penicillin was also observed for these SCV-like strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides relevant information about prevalence of enterococcal strains with low proliferation rate (likely small colony variant (SCV)) among kidney transplant recipients. Percentage of such strains in this cohort was relatively high (20%). Additionally, penicillin binding of these strains measured even at the beginning of proliferation (after 1 and 3 h of incubation), was significantly lower than among other strains. Finally, all of them were determined as penicillin resistant, with minimal inhibitory concentration value above 256 µg ml-1 . As the risk of systemic infections caused by such strains is probably higher than in case of other strains, screening for the SCVs in this group of patients should be recommended.


Assuntos
Antibacterianos/metabolismo , Enterococcus/crescimento & desenvolvimento , Enterococcus/isolamento & purificação , Hospedeiro Imunocomprometido/imunologia , Penicilinas/metabolismo , Aderência Bacteriana/fisiologia , Bacteriúria/microbiologia , Proliferação de Células/efeitos dos fármacos , Enterococcus/classificação , Humanos , Transplante de Rim , Testes de Sensibilidade Microbiana , Transplantados
14.
Transplant Proc ; 51(2): 512-516, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879579

RESUMO

BACKGROUND: A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS: We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS: A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS: In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.


Assuntos
Sistema do Grupo Sanguíneo ABO , Incompatibilidade de Grupos Sanguíneos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Transplante de Rim/métodos , Adulto , Feminino , Rejeição de Enxerto , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade
15.
Burns ; 45(3): 627-640, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30833100

RESUMO

OBJECTIVE: Burn injury induces an acute hyperactive immune response followed by a chronic immune dysregulation that leaves those afflicted susceptible to multiple secondary infections. Many murine models are able to recapitulate the acute immune response to burn injury, yet few models are able to recapitulate long-term immune suppression and thus chronic susceptibility to bacterial infections seen in burn patients. This has hindered the field, making evaluation of the mechanisms responsible for these susceptibilities difficult to study. Herein we describe a novel mouse model of burn injury that promotes chronic immune suppression allowing for susceptibility to primary and secondary infections and thus allows for the evaluation of associated mechanisms. METHODS: C57Bl/6 mice receiving a full-thickness contact burn were infected with Pseudomonas aeruginosa 14 days (primary infection) and/or 17 days (secondary infection) after burn or sham injury. The survival, pulmonary and systemic bacterial load as well as frequency and function of innate immune cells (neutrophils and macrophages) were evaluated. RESULTS: Following secondary infection, burn mice were less effective in clearance of bacteria compared to sham injured or burn mice following a primary infection. Following secondary infection both neutrophils and macrophages recruited to the airways exhibited reduced production of anti-bacterial reactive oxygen and nitrogen species and the pro-inflammatory cytokineIL-12 while macrophages demonstrated increased expression of the anti-inflammatory cytokine interleukin-10 compared to those from sham burned mice and/or burn mice receiving a primary infection. In addition the BALF from these mice contained significantly higher level so of the anti-inflammatory cytokine IL-4 compared to those from sham burned mice and/or burn mice receiving a primary infection. CONCLUSIONS: Burn-mediated protection from infection is transient, with a secondary infection inducing immune protection to collapse. Repeated infection leads to increased neutrophil and macrophage numbers in the lungs late after burn injury, with diminished innate immune cell function and an increased anti-inflammatory cytokine environment.


Assuntos
Queimaduras/imunologia , Tolerância Imunológica/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Animais , Infecções Bacterianas/imunologia , Carga Bacteriana , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Hospedeiro Imunocomprometido/imunologia , Interleucina-10/imunologia , Interleucina-12/imunologia , Interleucina-4/imunologia , Pulmão/microbiologia , Camundongos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Recidiva , Fatores de Tempo
16.
J Immunol ; 202(7): 2017-2026, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30745461

RESUMO

The cytokines TNF-α and IL-17A are elevated in a variety of autoimmune diseases, including rheumatoid arthritis. Both cytokines are targets of several biologic drugs used in the clinic, but unfortunately many patients are refractory to these therapies. IL-17A and TNF-α are known to mediate signaling synergistically to drive expression of inflammatory genes. Hence, combined blockade of TNF-α and IL-17A represents an attractive treatment strategy in autoimmune settings where monotherapy is not fully effective. However, a major concern with this approach is the potential predisposition to opportunistic infections that might outweigh any clinical benefits. Accordingly, we examined the impact of individual versus combined neutralization of TNF-α and IL-17A in a mouse model of rheumatoid arthritis (collagen-induced arthritis) and the concomitant susceptibility to infections that are likely to manifest as side effects of blocking these cytokines (oral candidiasis or tuberculosis). Our findings indicate that combined neutralization of TNF-α and IL-17A was considerably more effective than monotherapy in improving collagen-induced arthritis disease even when administered at a minimally efficacious dose. Encouragingly, however, dual cytokine blockade did not cooperatively impair antimicrobial host defenses, as mice given combined IL-17A and TNF-α neutralization displayed infectious profiles and humoral responses comparable to mice given high doses of individual anti-TNF-α or anti-IL-17A mAbs. These data support the idea that combined neutralization of TNF-α and IL-17A for refractory autoimmunity is likely to be associated with acceptable and manageable risks of opportunistic infections associated with these cytokines.


Assuntos
Artrite Reumatoide/imunologia , Fatores Imunológicos/efeitos adversos , Interleucina-17/antagonistas & inibidores , Infecções Oportunistas/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Artrite Experimental/imunologia , Progressão da Doença , Hospedeiro Imunocomprometido/imunologia , Camundongos , Infecções Oportunistas/etiologia
17.
BMJ Case Rep ; 12(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739086

RESUMO

A 42-year-old woman with a history of cholangiocarcinoma on adjuvant chemotherapy with capecitabine presented with painless haematochezia. She was found to have an isolated twenty-five mm ulcer in the ascending colon. Biopsies of the ulceration demonstrated typical cytomegalovirus (CMV) inclusions and her peripheral blood CMV PCR was significantly elevated. This is an unusual case of a solitary proximal colon ulcer. Non-steroidal anti-inflammatory drugs, inflammatory bowel disease and malignancy, are the most frequent causes of isolated ulcers in the proximal colon. Gastrointestinal (GI) CMV disease most commonly causes CMV colitis and is considered rare outside of the transplant population and other severely immunosuppressed patient groups. Patients who have received chemotherapy may also be at risk for GI CMV disease. The diagnosis should be suspected in patients who present with haematochezia or watery diarrhoea within a broad window of time after receiving chemotherapy.


Assuntos
Colite/diagnóstico , Colo Ascendente/patologia , Infecções por Citomegalovirus/diagnóstico , Úlcera/diagnóstico , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Antivirais/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Colangiocarcinoma/tratamento farmacológico , Colite/complicações , Colite/patologia , Colite/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Pancreaticoduodenectomia , Fatores de Risco , Úlcera/complicações , Úlcera/patologia , Úlcera/virologia , Valaciclovir/uso terapêutico
18.
Biomed Res Int ; 2019: 9461960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723745

RESUMO

In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.


Assuntos
Crassulaceae/química , Imunidade Inata/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Baço/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Ciclofosfamida/administração & dosagem , Citocinas/imunologia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/química , Extratos Vegetais/química , Ratos , Baço/citologia , Baço/imunologia
19.
Indian J Tuberc ; 66(1): 26-29, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30797277

RESUMO

Many western societies have eliminated tuberculosis years before the advent of potent anti-tuberculous drugs, as a result of the improved standards of living and good nutrition. But even with the availability of powerful anti-tuberculous drugs, India still has a long road ahead to reach the "End TB by 2025" goal. One of the major reason is that tuberculosis control program in India till now have focused primarily on case detection and medical treatment of active tuberculosis. Drug treatment alone does not completely prevent the occurrence of new infections in the community and also contributes to development of drug resistant strains if used improperly or incompletely. Although the treatment of active cases can reduce the period of transmission of disease, a significant amount of transmission to contacts occurs even before they have been diagnosed and treated. Additionally, this approach cannot prevent re-activation to active TB in the vast pool of persons with latent TB infection. Tuberculosis occurs in those with suppressed cell mediated immunity mainly due to poor nutritional status. Improving the nutritional status of the society by several social interventions hand-in-hand with utilizing the available anti-tuberculous drugs is possibly the only effective strategy. Promising programmatic guidance for nutritional support in TB patients have been formulated by the Central TB division of India but it needs a refocusing of TB control strategies towards nutrition at all levels and strong public health actions for effective implementation.


Assuntos
Imunidade Celular/imunologia , Hospedeiro Imunocomprometido/imunologia , Desnutrição/imunologia , Estado Nutricional/imunologia , Tuberculose/prevenção & controle , Antituberculosos/uso terapêutico , Controle de Doenças Transmissíveis , Humanos , Índia , Tuberculose Latente/terapia , Desnutrição/dietoterapia , Tuberculose/imunologia , Tuberculose/terapia , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/terapia
20.
Indian J Tuberc ; 66(1): 30-33, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30797279

RESUMO

The elimination of Tuberculosis (TB) in settings with a high dual burden of active and latent TB is one of the most important public health challenges of the 21st century. India has the highest TB burden in the world and nearly 40% of the population being infected with TB. There also exist large often overlapping socially and medically vulnerable populations like the PLHIV, pediatric TB contacts, children with protein-energy malnutrition, homeless people, workers in silica industry and adults with low BMI. A significantly higher risk of progression into active tubercular disease exists in those with compromised immune or nutritional status. It is uncertain if global TB elimination targets can be achieved in the absence of aggressive LTBI treatment strategies for interrupting the chain of transmission of the disease. India hence needs to accelerate and prioritize capacity building in latent TB research. A research agenda is outlined for generating evidence towards the evolution of critical evidence-based policy for LTBI management under Indian health settings.


Assuntos
Erradicação de Doenças , Política de Saúde , Tuberculose Latente/tratamento farmacológico , Desnutrição/terapia , Tuberculose/prevenção & controle , Progressão da Doença , Prática Clínica Baseada em Evidências , Humanos , Hospedeiro Imunocomprometido/imunologia , Índia , Tuberculose Latente/imunologia , Tuberculose Latente/transmissão , Desnutrição/imunologia , Populações Vulneráveis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA