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1.
Adv Neurobiol ; 24: 601-614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32006376

RESUMO

Autism is a complex neurodevelopmental disorder that is evident in early childhood and can persist throughout the entire life. The disease is basically characterized by hurdles in social interaction where the individuals demonstrate repetitive and stereotyped interests or patterns of behavior. A wide number of neuroanatomical studies with autistic patients revealed alterations in brain development which lead to diverse cellular and anatomical processes including atypical neurogenesis, neuronal migration, maturation, differentiation, and degeneration. Special education programs, speech and language therapy, have been employed for the amelioration of behavioral deficits in autism. Although commonly prescribed antidepressants, antipsychotics, anticonvulsants, and stimulants have revealed satisfactory responses in autistic individuals, adverse side effects and increased risk of several other complications including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, etc. have compelled the researchers to turn their attention toward herbal remedies. Alternative approaches with natural compounds are on continuous clinical trial to confirm their efficacy and to understand their potential in autism treatment. This chapter aims to cover the major plant-based natural products which hold promising outcomes in the field of reliable therapeutic interventions for autism.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Medicina Herbária , Fitoterapia , Transtorno Autístico/tratamento farmacológico , Humanos
2.
Lancet ; 395(10221): 371-383, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007172

RESUMO

Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. However, inhaled or systemic corticosteroids are ineffective treatments in many patients with asthma and few treatment options exist for patients with steroid resistant asthma. Although mechanisms for corticosteroid refractory asthma are likely to be numerous, the development of a new class of biologic agents that target airway type 2 inflammation has provided a new model for treating some patients with corticosteroid refractory asthma. The objective of this Therapeutic paper is to summarise the new type 2 therapeutics, with an emphasis on the biological rationale and clinical efficacy of this new class of asthma therapeutics.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Biomarcadores/metabolismo , Ensaios Clínicos Fase III como Assunto , Citocinas/antagonistas & inibidores , Citocinas/fisiologia , Eosinófilos/fisiologia , Previsões , Humanos , Ácidos Indolacéticos/uso terapêutico , Interleucina-4/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Omalizumab/uso terapêutico , Piridinas/uso terapêutico , Células Th2/fisiologia , Resultado do Tratamento
3.
Gut ; 69(1): 32-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30979718

RESUMO

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children. METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text. RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text. CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.


Assuntos
Ensaios Clínicos como Assunto/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fatores Etários , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Criança , Ensaios Clínicos como Assunto/normas , Relação Dose-Resposta a Droga , Aprovação de Drogas/métodos , Fármacos Gastrointestinais/administração & dosagem , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Methodist Debakey Cardiovasc J ; 15(3): 192-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687098

RESUMO

The extract of red yeast rice (RYR) is the most effective cholesterol-lowering nutraceutical on the market. In particular, its effectiveness is directly related to the amount of monacolin K within the extract (up to 10 mg/day). Consuming monacolin K on a daily basis reduces low-density lipoprotein (LDL) cholesterol plasma levels between 15% and 25% within 6 to 8 weeks. Certainly, the decrease in LDL-cholesterol is accompanied by a similar reduction in total cholesterol, non-high-density lipoprotein cholesterol, plasma apolipoprotein B, matrix metalloproteinases 2 and 9, and high-sensitivity C-reactive protein. Furthermore, the RYR lipid-lowering effect is associated with significant improvements in pulse wave velocity and endothelial function, which are validated and reliable biomarker tools able to detect vascular aging. Although it has a mechanism of action similar to statins, a daily consumption of between 3 and 10 mg monacolin K has only minimal associated risks, and mild myalgias are seen only in the frailest patients (those who also cannot tolerate minimal dosages of statin). The monacolin K found in RYR is a safe and effective supplement for managing mild to moderate hypercholesterolemia in people with no additional cardiovascular risk factors.


Assuntos
Produtos Biológicos/uso terapêutico , Colesterol/sangue , Suplementos Nutricionais , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lovastatina/uso terapêutico , Animais , Produtos Biológicos/efeitos adversos , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Regulação para Baixo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Lovastatina/efeitos adversos , Resultado do Tratamento
5.
Clin Biochem ; 74: 31-35, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672652

RESUMO

BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/terapia , Produtos Biológicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Rituximab/uso terapêutico , Transferrina/análise , Adulto , Idoso , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Eletroforese Capilar , Feminino , Seguimentos , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/sangue , Índice de Gravidade de Doença , Transferrina/química , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 98(48): e18115, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770237

RESUMO

INTRODUCTION: The aim of this report is to present a case of an apically involved tooth with successful regeneration by only applying enamel matrix derivative. The root of the tooth was planed and the defect area was well debrided using various instruments, including curettes and an ultrasonic scaler, and the root surface of the tooth and the defect area were loaded with enamel matrix derivative. PATIENT CONCERNS: A 32-year-old man visited the clinic due to a referral for the evaluation of his mandibular left first molar. DIAGNOSIS: The clinical and radiographic assessment displayed the loss of the periodontium around the tested tooth with apical involvement of the mesial root. Bleeding upon probing was noted at the mandibular first molar, with the deepest periodontal probing depth of 15 mm. INTERVENTIONS: A nonsurgical approach was firstly performed on the tooth, and the deepest probing depth was reduced to 12 mm. After re-evaluation, elevation of a full-thickness flap was done, the root of the tooth was planed, and the defect area was well debrided using various instruments, including curettes and an ultrasonic scaler. The defect area on the mandibular left first molar was grafted with enamel matrix derivative. OUTCOMES: The 7-month postoperative clinical and radiographic evaluation showed healthy gingiva and an increase in radiopacity. The final 1-year and 9-month postoperative evaluation showed that regeneration of bony defect was well maintained up to the final evaluation with reduction of probing depth. CONCLUSION: In conclusion, a case of apically involved tooth can be treated only with enamel matrix derivative after meticulous debridement with curettes and an ultrasonic scaler.


Assuntos
Produtos Biológicos/uso terapêutico , Matriz Óssea/transplante , Esmalte Dentário/transplante , Ápice Dentário/cirurgia , Odontopatias/cirurgia , Adulto , Raspagem Dentária/métodos , Humanos , Masculino , Mandíbula/cirurgia , Dente Molar/patologia , Dente Molar/cirurgia , Periodonto/patologia , Periodonto/cirurgia , Ápice Dentário/patologia , Odontopatias/patologia
7.
Surg Clin North Am ; 99(6): 1083-1094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676049

RESUMO

Patients with ulcerative colitis and Crohn's disease often present to surgery malnourished and on combination immunosuppression. These factors affect operation selection and postoperative outcomes. Corticosteroids have a well-established detrimental effect on postoperative outcomes, whereas the impact of biologic agents is more controversial. In a patient exposed to these medications, and in the presence of other risk factors, temporary intestinal diversion is likely the best choice. Enteral nutrition may help optimize malnourished patients at high risk of adverse postoperative outcomes.


Assuntos
Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Colectomia/métodos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Tomada de Decisão Clínica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Nutrição Enteral/métodos , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Desnutrição/terapia , Período Pré-Operatório , Prognóstico , Resultado do Tratamento
8.
Dis Colon Rectum ; 62(11): 1344-1351, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31596761

RESUMO

BACKGROUND: Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity. OBJECTIVE: The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis. DESIGN: This is a retrospective case-control study. SETTINGS: This study was conducted at a tertiary-care IBD center. PATIENTS: Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the incidence of pouchitis. RESULTS: Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes. LIMITATIONS: The retrospective design was a limitation of this study. CONCLUSION: In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.


Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Complicações Pós-Operatórias , Pouchite , Proctocolectomia Restauradora , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Estudos de Casos e Controles , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Illinois/epidemiologia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Pouchite/diagnóstico , Pouchite/epidemiologia , Pouchite/etiologia , Período Pré-Operatório , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Medição de Risco , Fatores de Risco
9.
Clin Exp Rheumatol ; 37 Suppl 120(5): 135-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621568

RESUMO

A disease-modifying osteoarthritis drug (DMOAD) is a drug that modifies the underlying OA pathophysiology and potentially inhibits the structural damage to prevent or reduce long-term disability with potential symptomatic relief. The focus of this narrative review is on describing the state of the field for disease-modifying pharmacologic agents that are in late-stage development-specifically phase 2/3.


Assuntos
Osteoartrite , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Osteoartrite/tratamento farmacológico
12.
Anticancer Res ; 39(10): 5231-5259, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570421

RESUMO

BACKGROUND/AIM: Prostate cancer is one of the most common cancers in men which remains a global public health issue. Treatment of prostate cancer is becoming increasingly intensive and aggressive, with a corresponding increase in resistance, toxicity and side effects. This has revived an interest in nontoxic and cost-effective preventive strategies including dietary compounds due to the multiple effects they have been shown to have in various oncogenic signalling pathways, with relatively few significant adverse effects. MATERIALS AND METHODS: To identify such dietary components and micronutrients and define their prostate cancer-specific actions, we systematically reviewed the current literature for the pertinent mechanisms of action and effects on the modulation of prostate carcinogenesis, along with relevant updates from epidemiological and clinical studies. RESULTS: Evidence from various recent experimental, clinical and epidemiological studies indicates that select dietary micronutrients (i.e., lycopene, epigallocatechin gallate, sulforaphane, indole-3-carbinol, resveratrol, quercetin, curcumin & piperine) and zinc play a key role in prostate cancer prevention and progression and therefore hold great promise for the future overall management of prostate cancer. CONCLUSION: A formulation that comprises these micronutrients using the optimal, safest form and dosing should be investigated in future prostate cancer chemoprevention studies and as part of standard prostate cancer therapy.


Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/prevenção & controle , Animais , Quimioprevenção/métodos , Dieta/métodos , Estudos Epidemiológicos , Humanos , Masculino , Micronutrientes/farmacologia , Micronutrientes/uso terapêutico
13.
Anticancer Res ; 39(10): 5261-5284, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570422

RESUMO

Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Humanos
14.
Acta Gastroenterol Belg ; 82(3): 365-372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31566323

RESUMO

BACKGROUND: The natural history of ulcerative colitis (UC) is unpredictable. Factors associated with the need for different types of step-up therapy in UC patients failing on 5-aminosalicylic acid (5-ASA) or corticosteroids are understudied. AIMS: Describe step-up therapy in patients with UC the first year after failing on 5-ASA or corticosteroids. METHODS: A Belgian, multi-center, prospective, non-interventional observational study comprising adult UC patients failing on 5-ASA or corticosteroids and naïve to immunomodulators/ biologicals. During a 12 months follow-up, patient characteristics, demography, medical therapy, biomarkers, therapy adherence and quality of life (QoL) were assessed. RESULTS: After 1 year, 35% of the patients were on biological therapy. Use of anti-TNF differed depending on baseline treatment: corticosteroid-refractory patients (55.8%), 5-ASA refractory (20.0%), and corticosteroid-dependent (16.0%) patients (p<0.001). The decision to start a line of therapy was based on the Mayo combined severity but not on biomarkers like faecal calprotectin, haemoglobin, CRP, albumin, platelets, and number of extraintestinal manifestations. At year 1, 84.2% of the patients had only mild UC or remission and a significant improvement of fatigue (p=0.004) and IBDQ scores (p<0.001) were observed implying an improved QoL. CONCLUSION: Treatment step-up, based on clinical scores in immunomodulatory and anti-TNF naïve patients with UC, provides good clinical outcomes and QoL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Corticosteroides/uso terapêutico , Adulto , Nível de Saúde , Humanos , Estudos Prospectivos , Qualidade de Vida
15.
Dis Colon Rectum ; 62(11): 1352-1362, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567927

RESUMO

BACKGROUND: The evidence regarding the association of preoperative biologic exposure and postoperative outcomes remains controversial for both antitumor necrosis factor agents and vedolizumab and largely unknown for ustekinumab. OBJECTIVE: The purpose of this study was to determine differences in the rates of 30-day postoperative overall infectious complications and intra-abdominal septic complications among the 3 classes of biologic therapies as compared with no biologic therapy. DESIGN: This was a retrospective review. SETTINGS: The study was conducted at an IBD referral center. PATIENTS: Adult patients with Crohn's disease who received an antitumor necrosis factor, vedolizumab, ustekinumab, or no biologic therapy within 12 weeks of a major abdominal operation between May 20, 2014, and December 31, 2017, were included. MAIN OUTCOMES MEASURES: Thirty-day overall postoperative infectious complications and intra-abdominal septic complications were measured. RESULTS: A total of 712 patients with Crohn's disease were included; 272 patients were exposed to an antitumor necrosis factor agents, 127 to vedolizumab, 38 to ustekinumab, and 275 to no biologic therapy within the 12 weeks before an abdominal operation. Patients exposed to a biologic were more likely to be taking a concurrent immunomodulator, but there was no difference in concurrent corticosteroid usage. The particular class of biologic was not independently associated with total overall infectious complications. Vedolizumab was associated with an increased rate of intra-abdominal sepsis on univariate analysis but not on multivariable analysis. Combination immunosuppression was associated with both an increased rate of overall postoperative infectious complications and intra-abdominal sepsis. LIMITATIONS: The study was limited by its retrospective design and single-center data. CONCLUSIONS: The overall rate of total infectious complications or intra-abdominal septic complications was not increased based on preoperative exposure to a particular class of biologic. Rates increased with combination immunosuppression of biologic therapy with corticosteroids and previous abdominal resection. See Video Abstract at http://links.lww.com/DCR/B24. BIOLÓGICOS Y COMPLICACIONES POSTOPERATORIAS DE 30 DÍAS DESPUÉS DE LAS OPERACIONES ABDOMINALES PARA LA ENFERMEDAD DE CROHN: ¿EXISTEN DIFERENCIAS EN LOS PERFILES DE SEGURIDAD?:: La evidencia sobre la asociación de la exposición biológica preoperatoria y los resultados postoperatorios sigue siendo controvertida controversial tanto para los agentes del factor de necrosis tumoral (anti-TNF) como para el vedolizumab, y en gran parte desconocida para el ustekinumab.Determinar las diferencias en las tasas de complicaciones infecciosas generales postoperatorias de 30 días y complicaciones sépticas intraabdominales entre las tres clases de terapias biológicas en comparación con ninguna terapia biológica.Revisión retrospectiva.centro de referencia de la enfermedad inflamatoria intestinal.Pacientes adultos con enfermedad de Crohn que recibieron un factor de necrosis antitumoral, vedolizumab, ustekinumab o ningún tratamiento biológico dentro de las 12 semanas de una operación abdominal mayor entre el 5/20/2014 y el 12/31/2017.Complicaciones infecciosas postoperatorias generales de 30 días, complicaciones sépticas intraabdominales.Se incluyeron setecientos doce pacientes con enfermedad de Crohn; 272 pacientes fueron expuestos a un anti-TNF, 127 a vedolizumab, 38 a ustekinumab y 275 a ninguna terapia biológica dentro de las 12 semanas previas a una operación abdominal. Los pacientes expuestos a un producto biológico tenían más probabilidades de tomar un inmunomodulador concurrente, pero no hubo diferencias en el uso simultáneo de corticosteroides. La clase particular de productos biológicos no se asoció de forma independiente con las complicaciones infecciosas totales. Vedolizumab se asoció con una mayor tasa de sepsis intraabdominal en el análisis univariable, pero no en el análisis multivariable. La inmunosupresión combinada se asoció tanto con una mayor tasa de complicaciones infecciosas postoperatorias generales como con sepsis intraabdominal.Diseño retrospectivo, datos de centro único.La tasa general de complicaciones infecciosas totales o complicaciones sépticas intraabdominales no aumentó en función de la exposición preoperatoria a una clase particular de productos biológicos. Las tasas aumentaron con la combinación de inmunosupresión de la terapia biológica con corticosteroides y resección abdominal previa. Vea el Resumen del Video en http://links.lww.com/DCR/B24.


Assuntos
Anticorpos Monoclonais Humanizados , Colectomia , Doença de Crohn , Infecções Intra-Abdominais , Complicações Pós-Operatórias , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Colectomia/efeitos adversos , Colectomia/métodos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Doença de Crohn/cirurgia , Monitoramento de Medicamentos/métodos , Feminino , Seguimentos , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/epidemiologia , Infecções Intra-Abdominais/etiologia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Estados Unidos , Ustekinumab/efeitos adversos , Ustekinumab/uso terapêutico
16.
Planta Med ; 85(17): 1316-1325, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31618777

RESUMO

Alzheimer's disease is a neurodegenerative disease that leads to irreversible neuronal damage. Senile plaques, composed of amyloid beta peptide, is the principal abnormal characteristic of the disease. Among the factors involved, the secretase enzymes, namely, α secretase, beta-site amyloid precursor protein-cleaving enzyme, ß secretase, and γ secretase, hold consequential importance. Beta-site amyloid precursor protein-cleaving enzyme 1 is considered to be the rate-limiting factor in the production of amyloid beta peptide. Research supporting the concept of inhibition of beta-site amyloid precursor protein-cleaving enzyme activity as one of the effective therapeutic targets in the mitigation of Alzheimer's disease is well accepted. The identification of natural compounds, such as ß-amyloid precursor protein-selective beta-site amyloid precursor protein-cleaving enzyme inhibitors, and the idea of compartmentalisation of the beta-site amyloid precursor protein-cleaving enzyme 1 action have caused a dire need to closely examine the natural compounds and their effectiveness in the disease mitigation. Many natural compounds have been reported to effectively modulate beta-site amyloid precursor protein-cleaving enzyme 1. At lower doses, compounds like 2,2',4'-trihydroxychalcone acid, quercetin, and myricetin have been shown to effectively reduce beta-site amyloid precursor protein-cleaving enzyme 1 activity. The currently used five drugs that are marketed and used for the management of Alzheimer's disease have an increased risk of toxicity and restricted therapeutic efficiency, hence, the search for new anti-Alzheimer's disease drugs is of primary concern. A variety of natural compounds having pure pharmacological moieties showing multitargeting activity and others exhibiting specific beta-site amyloid precursor protein-cleaving enzyme 1 inhibition as discussed below have superior biosafety. Many of these compounds, which are isolated from medicinal herbs and marine flora, have been long used for the treatment of various ailments since ancient times in the Chinese and Ayurvedic medical systems. The aim of this article is to review the available data on the selected natural compounds, giving emphasis to the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 activity as a mode of Alzheimer's disease treatment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Produtos Biológicos/uso terapêutico , Alcaloides/uso terapêutico , Flavonoides/uso terapêutico , Humanos , Fenóis/uso terapêutico , Fitoterapia
17.
Pharmacol Rev ; 71(4): 596-670, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554644

RESUMO

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Produtos Biológicos/farmacologia , Células Espumosas/efeitos dos fármacos , Células Espumosas/patologia , Animais , Produtos Biológicos/uso terapêutico , Humanos
18.
Planta Med ; 85(17): 1351-1362, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559607

RESUMO

Atremorine is a novel bioproduct with neuroprotective effects on dopaminergic neurons and a natural L-DOPA donor in Parkinson's disease (PD). In the present study, we show the effects of a single dose of Atremorine (5 g, p. o.) on plasma dopamine (DA) response and brain function in PD (n = 183) and the influence that pathogenic (LRRK2), metabolic (CYP2D5, CYP2C9, CYP2C19, CYP3A5, NAT2), transporter (ABCB1), pleiotropic (APOE), and detoxifying genes (CYP1B1, GSTT1, GSTP1, GSTM1, SOD2) involved in the pharmacogenetic network exerts on Atremorine-induced DA response. Over 90% of PD patients at diagnosis show plasma DA levels below 20 pg/mL. Atremorine induces DA synthesis causing a significant increase in plasma DA levels 1 h after administration in practically 100% of patients. Females tend to show lower basal DA levels than males and the response of DA to Atremorine is stronger in males than in females. Atremorine-induced DA response is pharmacogenotype-specific and lasts from 6 - 12 h depending upon the pharmacogenetic profile of each patient. Genetic variants in pathogenic genes, metabolic genes, and genes involved in the detoxification processes affect the response of DA to Atremorine in a genotype-specific manner. Atremorine or any of its bioactive components can cross the blood-brain barrier and improve brain function and motor function, as revealed by the reduction in slow wave activity in brain mapping and psychometric assessment, respectively. Atremorine is a selective neuroprotective agent for dopaminergic neurons with prophylactic and therapeutic potential in PD.


Assuntos
Produtos Biológicos/uso terapêutico , Dopamina/sangue , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Transportadores de Cassetes de Ligação de ATP/genética , Sistema Enzimático do Citocromo P-450/genética , Eletroencefalografia , Feminino , Pleiotropia Genética , Variação Genética , Técnicas de Genotipagem , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/genética , Vicia faba/química
20.
Nat Commun ; 10(1): 4015, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488839

RESUMO

The interrogation of complex biological pathways demands diverse small molecule tool compounds, which can often lead to important therapeutics for the treatment of human diseases. Since natural products are the most valuable source for the discovery of therapeutics, the derivatization of natural products has been extensively investigated to generate molecules for biological screenings. However, most previous approaches only modified a limited number of functional groups, which resulted in a limited number of skeleta. Here we show a general strategy for the preparation of a library of complex small molecules by combining state-of-the-art chemistry - the site-selective oxidation of C-H bonds - with reactions that expand rigid, small rings in polycyclic steroids to medium-sized rings. This library occupies a unique chemical space compared to selected diverse reference compounds. The diversification strategy developed herein for steroids can also be expanded to other types of natural products.


Assuntos
Produtos Biológicos/química , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Bibliotecas de Moléculas Pequenas/química , Alquilação , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Engenharia Química/métodos , Humanos , Imidas , Estrutura Molecular , Oxirredução , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico
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