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1.
Einstein (Sao Paulo) ; 18: eAO5262, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32130328

RESUMO

OBJECTIVE: To compare the frequency of respiratory tract infections in children treated with OM-85 BV and placebo during the 3-month therapy period, and observation for a further 3 months after treatment. METHODS: A randomized, double-blind, placebo-controlled trial was conducted with 54 children (6 months to 5 years old) with no past history of recurrent respiratory infections attending daycare center. Family members were instructed to administer one capsule per day for 10 consecutive days, for 3 months of OM-85 BV or placebo. Telephone interviews were conducted every 30 days. RESULTS: There was no significant difference in the number of respiratory infections between the groups. The mean number of respiratory tract infection in the OM-85 BV Group in the first 3 months was 0.92±0.87, and in the Placebo Group was 0.74±1.02, and at 6 months it was 1.62±1.47 and 1.03±1.34, respectively. CONCLUSION: OM-85 BV was not effective in the primary prevention of respiratory tract infections. Although most authors recommend the use of this immunostimulant in children with a history of recurrent respiratory infections, more studies are needed to define its usefulness in the primary prevention of respiratory infections in healthy children exposed to few risk factors.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Extratos Celulares/uso terapêutico , Prevenção Primária/métodos , Aleitamento Materno , Creches , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Infecções Respiratórias/tratamento farmacológico , Poluição por Fumaça de Tabaco , Resultado do Tratamento
3.
J Urol ; 203(2): 283-291, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31549936

RESUMO

PURPOSE: The objective of this study was to assess the value of fluorescence in situ hybridization to predict early recurrence in patients with nonmuscle invasive bladder cancer at intermediate and high risk treated with bacillus Calmette-Guérin. MATERIALS AND METHODS: We performed a systematic review using MEDLINE®, Embase® and the Cochrane Library. Individual patient data from prospective observational studies of fluorescence in situ hybridization in patients treated with bacillus Calmette-Guérin were included. A 2-stage individual patient data meta-analysis was done to assess the value of fluorescence in situ hybridization to predict tumor recurrence after bacillus Calmette-Guérin induction therapy. RESULTS: From a total of 4 studies we obtained individual data on 422 patients, of whom 408 with a median followup of 18.8 months were included in the final analysis. When fluorescence in situ hybridization was positive, the recurrence HR was 1.20 (95% CI 0.81-1.79) before bacillus Calmette-Guérin (time 0), 2.23 (95% CI 1.31-3.62) at 6 weeks (time 1), 3.70 (95% CI 2.34-5.83) at 3 months (time 2) and 23.44 (95% CI 5.26-104.49) at 6 months (time 3). CONCLUSIONS: A positive fluorescence in situ hybridization test after bacillus Calmette-Guérin correlated with higher risk of recurrent tumor. Fluorescence in situ hybridization could aid urologists in risk stratifying and counseling patients. Based on the HR and the narrowest CI the preferred timing of fluorescence in situ hybridization is 3 months after transurethral resection of bladder tumor. This is also in time for patients in whom induction therapy fails to enter clinical trials or change the treatment strategy.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Hibridização in Situ Fluorescente , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Quimioterapia Adjuvante , Humanos , Invasividade Neoplásica , Valor Preditivo dos Testes , Medição de Risco
4.
Int J Cancer ; 146(2): 424-438, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31241171

RESUMO

Stem cell chemoresistance remains challenging the efficacy of the front-line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti-O-acetyl-GD2 adjuvant immunotherapy controls glioma stem-like cell-driven chemoresistance. Using patient-derived glioblastoma cells, we found that glioma stem-like cells overexpressed O-acetyl-GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, the combination therapy decreased the expression of the glioma stem-like cell markers CD133 and Nestin and compromised glioma stem-like cell self-renewal capabilities. When tested in vivo, adjuvant 8B6 immunotherapy prevented the extension of the temozolomide-resistant glioma stem-like cell pool within the tumor bulk in vivo and was more effective than the single agent therapies. This is the first report demonstrating that anti-O-acetyl-GD2 monoclonal antibody 8B6 targets glioblastoma in a manner that control temozolomide-resistance driven by glioma stem-like cells. Together our results offer a proof of concept for using anti-O-acetyl GD2 reagents in glioblastoma to develop more efficient combination therapies for malignant gliomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Gangliosídeos/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Autorrenovação Celular/efeitos dos fármacos , Autorrenovação Celular/imunologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Sinergismo Farmacológico , Gangliosídeos/imunologia , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Camundongos , Células-Tronco Neoplásicas/imunologia , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Acta Neurol Scand ; 141(1): 77-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657006

RESUMO

OBJECTIVES: Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti-inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48-week high-dose vitamin D3 supplements were associated with lower circulating NfL levels. MATERIALS & METHODS: Of N = 40 Dutch interferon beta-treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48-week follow-up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty-five hydroxyvitamin D3 (25(OH)D3 ) levels were measured with LC-MS/MS, and NfL levels were measured in duplicate with Simoa. RESULTS: Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205-330] vs 72 [39-88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6-32.2] vs 25.3 [17.9-30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93-6.12] for each 10 pg/mL increase; P = .07). CONCLUSIONS: Supplementation of high-dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro-axonal injury.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Esclerose Múltipla Recidivante-Remitente/sangue , Proteínas de Neurofilamentos/sangue , Vitamina D/sangue , Adjuvantes Imunológicos/uso terapêutico , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
6.
Exp Parasitol ; 207: 107789, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669169

RESUMO

American visceral leishmaniasis is caused by the protozoan Leishmania infantum. The control of the disease depends on the magnitude of the Th1 cell response and IL-10 producing regulatory T cells. Administration of chemokine, such as CXCL10, has shown promising results in the leishmaniasis treatment. Previous studies from our group have shown that CXCL10 induces a reduction in parasite burden in the spleen and a decrease in IL-10 and TGF-ß production in L. infantum-infected BALB/c mice. This work investigated whether CXCL10-treatment reduces IL-10 + Treg cell populations (CD4+CD25+Foxp3+ and Tr1) and induces morphological changes in the spleen. BALB/c mice were infected and treated or not with CXCL10 on the 1st, 3rd and 7th days of infection. CXCL10-treatment was able to reduce the parasite load in the spleen in L. infantum-infected BALB/c mice and this decrease in the number of parasites correlated with the decrease in size of this organ in treated animals compared to untreated animals. 7, 23, and 45 days post-treatment (p.t.), the phenotype and frequency of IL-10 + Treg cells were evaluated by flow cytometry, and the morphological changes of the spleen were analyzed by optical microscopy. After 7 and 23 days p.t., CXCL10-treated animals showed a significant reduction of CD25-Foxp3-IL-10+ (Tr1) cells in the spleen when compared to untreated animals, whereas CD4+CD25+Foxp3+IL-10+ Treg cells reduced later at 23rd and 45th days p.t. Furthermore, while untreated animals showed a significant positive correlation between IL-10 production and Tr1 cells, in CXCL10-treated group this correlation was negative. Thus, these findings show that treatment with CXCL10 chemokine in L. infantum-infected BALB/c mice results in suppression of IL10+ Treg (Foxp3+ and Tr1) cells in the spleen, associated with a reduction in parasite load and splenomegaly.


Assuntos
Quimiocina CXCL10/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Baço/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Adjuvantes Imunológicos/uso terapêutico , Animais , Quimiocina CXCL10/administração & dosagem , Quimiocina CXCL10/farmacologia , Cricetinae , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Humanos , Injeções Intraperitoneais , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/imunologia , Leishmania infantum/patogenicidade , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/imunologia , Carga Parasitária , Baço/parasitologia , Baço/patologia , Linfócitos T Reguladores/imunologia , Virulência
7.
PLoS Negl Trop Dis ; 13(11): e0007789, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31675378

RESUMO

Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (ß-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of ß-glucan against Leptospira infection in hamsters. First, ß-glucan was administered 24 h prior to, during and after infection. The results showed that ß-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of ß-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1ß and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1ß and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, ß-glucan was administered 5 days prior to infection. ß-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that ß-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1ß and IL-6) in vitro, indicating that ß-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of ß-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Leptospirose/imunologia , Leptospirose/prevenção & controle , beta-Glucanas/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Cricetinae , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade Inata/efeitos dos fármacos , Interleucina-1beta/metabolismo , Leptospira/crescimento & desenvolvimento , Leptospira/imunologia , Leptospira/patogenicidade , Leptospira interrogans/crescimento & desenvolvimento , Leptospira interrogans/imunologia , Leptospirose/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor 2 Toll-Like/metabolismo , beta-Glucanas/administração & dosagem
8.
BMC Vet Res ; 15(1): 371, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655595

RESUMO

BACKGROUND: Mycoplasma bovis is a causative agent of disease in cattle causing many clinical conditions. Currently there are no commercial M. bovis vaccines in Europe and treatment is difficult with decreased antimicrobial susceptibility of M. bovis field isolates. Using an M. bovis calf infection model the effectiveness of enrofloxacin given alone; in combination with flunixin meglumine, a nonsteroidal anti-inflammatory drug; and a group with an additional treatment of pegbovigrastim, an immunostimulator, was evaluated. RESULTS: Enrofloxacin given alone stimulated a strong immune response, reduced the clinical manifestation and lung lessions of the M. bovis infection. In contrast the combination therapy appeared ineffective. CONCLUSIONS: In this experiment enrofloxacin given alone appeared to be the most effective treatment of the M. bovis affected calves, whereas co-administration with flunixin meglumine, and pegbovigrastim was not beneficial in this trial.


Assuntos
Doenças dos Bovinos/tratamento farmacológico , Infecções por Mycoplasma/veterinária , Pneumonia/veterinária , Adjuvantes Imunológicos/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bovinos , Doenças dos Bovinos/microbiologia , Clonixina/análogos & derivados , Clonixina/uso terapêutico , Quimioterapia Combinada/veterinária , Enrofloxacina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma bovis/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico
9.
Neurology ; 93(20): e1906-e1916, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31594857

RESUMO

OBJECTIVE: In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS: Eligible patients with RRMS treated with SC interferon-ß-1a (IFN-ß-1a) 44 µg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-ß-1a plus placebo (n = 116) or SC IFN-ß-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS: At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS: SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-ß-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01285401. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS treated with SC IFN-ß-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Colecalciferol/administração & dosagem , Interferon beta-1a/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Encéfalo/diagnóstico por imagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
10.
Nanoscale ; 11(37): 17157-17178, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31531445

RESUMO

Cancer immunotherapy is emerging as a promising treatment modality that suppresses and eliminates tumors by re-activating and maintaining the tumor-immune cycle, and further enhancing the body's anti-tumor immune response. Despite the impressive therapeutic potential of immunotherapy approaches such as immune checkpoint inhibitors and tumor vaccines in pre-clinical and clinical applications, the effective response is limited by insufficient accumulation in tumor tissues and severe side-effects. Recent years have witnessed the rise of nanotechnology as a solution to improve these technical weaknesses due to its inherent biophysical properties and multifunctional modifying potential. In this review, we summarized and discussed the current status of nanoparticle-enhanced cancer immunotherapy strategies, including intensified delivery of tumor vaccines and immune adjuvants, immune checkpoint inhibitor vehicles, targeting capacity to tumor-draining lymph nodes and immune cells, triggered releasing and regulating specific tumor microenvironments, and adoptive cell therapy enhancement effects.


Assuntos
Portadores de Fármacos/uso terapêutico , Imunoterapia , Nanopartículas/uso terapêutico , Nanotecnologia , Neoplasias/terapia , Adjuvantes Imunológicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Nanotecnologia/métodos , Nanotecnologia/tendências
11.
Biochemistry (Mosc) ; 84(7): 720-728, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31509724

RESUMO

Colorectal cancer (CRC) originating from the cells of the colon or rectum has a high mortality rate worldwide. Numerous attempts have been made to raise the overall survival rates of CRC patients. It is well-known that the development of malignant neoplasms is accompanied by suppression of the immune system, which is likely the cause for the failure of standard treatment methods. Immune response has long been an issue of great interest in cancer therapy and anti-tumor immunity that consider the development of immunotherapeutic antitumor methods resulting in the immune system activation as an important issue. This review discusses main immunotherapeutic approaches available for the CRC treatment.


Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Imunoterapia Adotiva , Adjuvantes Imunológicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Engenharia Celular , Citocinas/uso terapêutico , Humanos , Terapia Viral Oncolítica , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
12.
Neurology ; 93(19): e1778-e1786, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484710

RESUMO

OBJECTIVE: To assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS). METHODS: Brain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) ß-1a (30 µg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-ß-1a (44 µg). RESULTS: In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-ß-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-ß-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-ß-1a within the first 8 weeks. CONCLUSION: Epoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Encéfalo/diagnóstico por imagem , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adulto , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Recidiva , Fatores de Tempo , Resultado do Tratamento
13.
Eur J Paediatr Neurol ; 23(6): 783-791, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31540711

RESUMO

BACKGROUND: Cognitive impairment (CI) is a critical feature for patients with childhood or juvenile multiple sclerosis (MS). OBJECTIVE: To promote the understanding of CI and to address the impact of different pharmacological treatment strategies on cognitive performance in this patient group. METHODS: A cohort of 19 patients with therapy-naïve or ß-Interferon-treated juvenile MS completed a comprehensive neuropsychological assessment at initial presentation (baseline) and on average 2.5 years later (follow-up). The assessments were complemented with a neuropaediatric examination and conventional cerebral magnetic resonance imaging (MRI). RESULTS: 9 patients (47%) were impaired in at least one test at baseline (z-score <-1.645 compared with age-adjusted normative data), with the highest impairment frequency in the domains processing speed and attention & executive functions. At follow-up a higher impairment frequency was prominent in those patients whose therapy had not been escalated (N = 13, 69% impaired in at least one test), while cognition was preserved or ameliorated in patients whose treatment had been escalated to highly effective drugs (N = 6, 0% impaired) during the observational period. These group differences at follow-up were not attributable to differences regarding demographics, MRI metrics or cognitive performance at baseline. CONCLUSION: Our findings confirm that paediatric MS is associated with considerable CI already in early disease stages. Early administration of highly effective treatment may protect from cognitive decline or alleviate CI in juvenile MS, but larger controlled trials are warranted to confirm these preliminary results.


Assuntos
Disfunção Cognitiva/etiologia , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Criança , Disfunção Cognitiva/prevenção & controle , Estudos de Coortes , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Masculino , Testes Neuropsicológicos , Resultado do Tratamento
14.
J Ethnopharmacol ; 245: 112047, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394179

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Description of the pharmacological activities of Sanghuang mushrooms (Inonotus Sanghuang) can be traced back to Tang dynasty of China 1300 years ago. This mushroom has been widely accepted in China, Japan, Korea and certain regions of Europe as a nutraceutical medicine for enhancing immunity or an alternative medicine for prevention or inhibition of tumorigenesis. However, this mushroom is rarely available from the mulberry trees in the wild because of the rigorous conditions needed for formation of the Sanghuang mushrooms. AIM OF THE STUDY: This study aims to establish a practical protocol for culture, particularly for a bunch of production of Sanghuang mushrooms possibly to commercialize the cultured Sanghuang based on deep comparison of quality and pharmacological activities between the cultured and the wild Sanghuang. MATERIALS AND METHODS: A phylogenetic tree containing five strains of the wild Sanghuang was constructed using rDNA markers. Different temperatures and medium compositions were surveyed to develop a practical protocol for culture of the Sanghuang mushrooms. 5-fluorouracil was used to induce the immunodeficient mice. Chemotherapeutic components and pharmacological activities were deeply analyzed between a cultured strain (SG) and three strains of the wild Sanghuang. RESULTS: Maintenance of a temperature of 22-28 °C and a high relative humidity of 90-95%, and use of a high ratio (80%) of mulberry tree sticks in the medium were critical to successful culture of Sanghuang. The cultured mushrooms were yellow with a uniform shape, while the wild Sanghuang was dark brown with a smaller and irregular shape. The cultured mushrooms contained significantly higher levels of polysaccharides, amino acids, and water-soluble nutraceuticals, whereas flavones in the wild Sanghuang were significantly higher (P < 0.05). Use of a dose of 8 mg/kg or 16 mg/kg to immunoregenerate the immunodeficient mice was comparable between the cultured and wild Sanghang based on analysis of hematological parameters and histological examination of the thymus and spleen in the treated mice. CONCLUSIONS: This study highlights the potential of the immunoregenerative functions of the cultured Sanghuang for cancer chemotherapy and suggests that the cultured Sanghuang can be an alternative to wild Sanghuang used for nutraceutical medicine.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Agaricales , Síndromes de Imunodeficiência/terapia , Agaricales/genética , Animais , Antineoplásicos , Biônica , Contagem de Células Sanguíneas , Feminino , Fluoruracila , Síndromes de Imunodeficiência/induzido quimicamente , Camundongos Endogâmicos BALB C , Filogenia , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
15.
Medicine (Baltimore) ; 98(33): e16771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415377

RESUMO

The cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 µg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 µg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4 T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.The RD of BCG-CWS was determined to be 100 µg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Esqueleto da Parede Celular/uso terapêutico , Mycobacterium bovis , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacina BCG/administração & dosagem , Contagem de Linfócito CD4 , Esqueleto da Parede Celular/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
16.
Urol Int ; 103(2): 242-244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269502

RESUMO

Due to their immunosuppressed status, solid organ transplant recipients are a special group of patients with an incidence of bladder cancer greater than the rest of the population, especially in the first 6 years after transplantation. Also, treatment with Bacillus Calmette-Guérin, a reference therapy in nonmuscle invasive high-risk bladder cancer, may be less effective in this group of patients and could cause more adverse effects. However, the data published so far and the experience initiated in the Virgen de la Arrixaca Clinical University Hospital do not support these hypotheses.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Humanos , Imunossupressão , Masculino , Gradação de Tumores , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
17.
J Ethnopharmacol ; 242: 112059, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279866

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Rehmannia glutinosa (RR) is a crude drug used in traditional Japanese Kampo medicine and traditional Chinese medicine (TCM). Sometimes, the crude drug is subjected to additional processing before use. AIM OF THE STUDY: To determine the effects of steam processing and pretreatment with liquor of RR through historical investigation, analytical chemistry, and pharmacological experiments. MATERIALS AND METHODS: We inspected TCM literature from the Later Han Dynasty to the present day. Dried RR steamed for 3, 6, 9, or 12 h (steamed RRs, SRRs), dried RR soaked in yellow rice wine (liquor) (liquor-RR), and dried RR steamed for 6 h pretreated with liquor (liquor-SRR) were prepared. These samples were extracted using boiling water, and the inducible effects of the extracts on granulocyte colony-stimulating factor (G-CSF) secretion in cultured enterocytes and the content of their marker compounds were evaluated by using HPLC. RESULTS: The effect of processing using both steaming and the pretreatment using liquor described in TCM literature over different eras was to enhance the warming effect and tonifying qi (energy) of RR. We found that SRR, processed by pretreatment with liquor, became mainstream since the Qing Dynasty. In SRR, stachyose content was decreased and fructose and manninotriose contents were increased with steaming time. However, the content of these compounds was not altered by pretreatment with liquor. RR extract induced G-CSF secretion in cultured enterocytes; moreover, the SRR extract steamed for more than 6 h had significantly stronger effects than that RR. Pretreatment with liquor did not cause any significant differences in the effects of RR or SRR. CONCLUSIONS: The aim of processing for RR by both steaming and pretreatment with liquor in TCM literature over different eras was to enhance the tonifying effect on qi and its immunostimulatory effect. Although the effect of RR on the induction of G-CSF secretion in intestinal epithelial cells was enhanced by steaming, this enhancement was not enhanced by the pretreatment with liquor. These results provide scientific support for steaming, but could not elucidate a reason for pretreatment with liquor in TCM theory.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Medicina Tradicional Chinesa/história , Medicina Kampo/história , Preparações de Plantas/uso terapêutico , Rehmannia , Adjuvantes Imunológicos/farmacologia , Animais , Linhagem Celular , Fator Estimulador de Colônias de Granulócitos/metabolismo , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Medieval , Camundongos , Preparações de Plantas/farmacologia , Raízes de Plantas , Vapor
18.
Biomed Res Int ; 2019: 8980506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341910

RESUMO

Immunomodulatory agents have been proposed as therapeutic candidates to improve outcomes in sepsis. Transferon™, a dialyzable leukocyte extract (DLE), has been supported in Mexico as an immunomodulatory adjuvant in anti-infectious therapy. Here we present a retrospective study describing the experience of a referral pediatric intensive care unit (PICU) with Transferon™ in sepsis. We studied clinical and laboratory data from 123 patients with sepsis (15 in the DLE group and 108 in the control group) that were admitted to PICU during the period between January 2010 and December 2016. Transferon™ DLE use was associated with lower C reactive protein (CRP), increase in total lymphocyte counts (TLC), and decrease in total neutrophil count (TNC) 72 hours after Transferon™ DLE administration. The control group did not present any significant difference in CRP values and had lower TLC after 72 hours of admission. There was no difference in PICU length of stay between control and Transferon™ DLE group. Transferon™ DLE administration was associated with a higher survival rate at the end of PICU stay. This study shows a possible immunomodulatory effect of Transferon™ on pediatric sepsis patients.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Sepse/tratamento farmacológico , Fator de Transferência/uso terapêutico , Proteína C-Reativa/metabolismo , Criança , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Contagem de Linfócitos , Masculino , México , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estudos Retrospectivos , Sepse/metabolismo , Sepse/mortalidade , Taxa de Sobrevida
19.
Int Immunopharmacol ; 75: 105764, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352327

RESUMO

It is becoming apparent that to obtain robust and prolonged antitumor responses in cancer immunotherapy, appropriate adjunct agents promoting both tumor antigen delivery and immune rejection enhancement are critically required. The semisynthetic biopolymer N-dihydrogalactochitosan (GC) is emerging as a promising such candidate. In the present study, the effects of GC were investigated when combined with cancer vaccines generated by photodynamic therapy (PDT) using mouse tumor model SCCVII (squamous cell carcinoma). The adjunct GC treatment was found to enhance therapeutic benefit obtained with PDT vaccine, while reducing the numbers of myeloid-derived suppressor cells. Another important property of GC is promoting directly the death of SCCVII cells sustaining injury from PDT mediated by various photosensitizers. This effect is extended to cells treated by cryoablation therapy (CAT) performed by exposure to -80 °C. A capacity of GC for preferential binding to PDT treated cells was demonstrated using fluorescence microscopy. In vitro testing with specific caspase-1 inhibitor revealed a pro-survival role of this enzyme in membrane lipid repair mechanisms following combined PDT plus GC treatment. In conclusion, GC represents a uniquely promising adjunct for various PDT protocols, photothermal and similar rapid tumor-ablating therapies.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Quitosana/análogos & derivados , Quitosana/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fotoquimioterapia , Animais , Criocirurgia , Imunoterapia , Camundongos Endogâmicos C3H , Fármacos Fotossensibilizantes/uso terapêutico , Células Tumorais Cultivadas
20.
Arch. bronconeumol. (Ed. impr.) ; 55(7): 373-377, jul. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-186077

RESUMO

Tuberculosis still is a major public health problem worldwide, and vaccines may play a major role in its eradication. However, despite 20 years of intensive research, we still do not have a better vaccine than the Bacille Calmette-Guérin vaccine, which has been used since 1921 but exhibits only limited efficacy in the field. This effort has not, however, been entirely in vain as our understanding of TB vaccinology has been substantially expanded and there are currently 17 vaccine candidates in clinical development and several more in preclinical trials. This manuscript reviews the most important recent advances, concerns raised and future prospects in the TB vaccinology field


La tuberculosis (TB) continúa siendo un importante problema de salud pública a nivel mundial, para cuya erradicación las vacunas pueden jugar un papel relevante. Sin embargo, a pesar de 20 años de intensa investigación, todavía no se dispone de una mejor alternativa que la vacuna del bacilo Calmette-Guérin, que se utiliza desde 1921 pero cuya efectividad es limitada en el campo. Sin embargo, este esfuerzo no ha sido en vano, porque nuestro conocimiento sobre la vacunología de la TB ha aumentado sustancialmente, haciendo que actualmente haya 17 vacunas candidatas en estudios clínicos y algunas más en fase preclínica. Este artículo revisa los avances más importantes, problemas y perspectivas de futuro en el campo de la vacunología de la TB


Assuntos
Humanos , Tuberculose/epidemiologia , Tuberculose/imunologia , Vacina BCG/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/imunologia , Vacina contra Brucelose/uso terapêutico
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