Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.603
Filtrar
1.
Ann Hematol ; 99(4): 835-838, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32076826

RESUMO

Despite improvement in survival of newly diagnosed adult precursor B-acute lymphoblastic leukemia/lymphoma (B-ALL), the results of relapsed/refractory disease are poor. Blinatumomab, a bispecific monoclonal antibody directed against CD19/CD3 show clinical activity against relapsed/refractory B-ALL and in minimal residual disease (MRD)-positive patients.We report our "real-world" experience with blinatumomab in patients with relapsed/refractory B-ALL.Twenty-one patients, at a median age 52 years with median disease duration of 10 months, were included. Indications for treatment were hematological relapse (n = 17), MRD positivity (n = 2), inability to continue intensive chemotherapy (n = 1), and bridging to a second alloSCT (n = 1). Blinatumomab was given as first salvage in 11 patients and after at least one prior salvage treatment in eight.Complete response (CR) was newly achieved in 47% and was maintained in 75% of patients with baseline CR. At a median follow-up of 12.4 months, 13 patients were alive, and 11 in CR. Median leukemia-free survival was 8.7 months, and median overall survival was 15.2 months. Median leukemia-free survival and overall survival were not reached in patients proceeding to alloSCT compared to 5.1 and 15.2 months, respectively, for patients who did not receive stem cell transplantation.Treatment was well tolerated with neurological events reported in two patients (10%) and GI events in three patients (14%). Cytokine storm was reported in four patients (19%).In conclusion, treatment with blinatumomab is effective and tolerable in adult patients with relapsed/refractory B-ALL outside of a clinical trial stetting.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígenos CD19/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Complexo CD3/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Biespecíficos/efeitos adversos , Especificidade de Anticorpos , Antineoplásicos Imunológicos/efeitos adversos , Terapia Combinada , Citocinas/metabolismo , Intervalo Livre de Doença , Feminino , Gastroenteropatias/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Doenças do Sistema Nervoso/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
N Engl J Med ; 382(8): 706-716, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32074418

RESUMO

BACKGROUND: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18. RESULTS: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms. CONCLUSIONS: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Prurigo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Gravidade do Paciente , Prurigo/complicações , Prurido/tratamento farmacológico , Prurido/etiologia , Adulto Jovem
3.
PLoS One ; 15(1): e0227781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978146

RESUMO

BACKGROUND: Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). METHODS: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). RESULTS: Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 µV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 µV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 µV^2; p<0.001), lasting till 120 min. (p<0.001). CONCLUSIONS: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.


Assuntos
Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Gastroenteropatias/induzido quimicamente , Motilidade Gastrointestinal/efeitos dos fármacos , Memantina/efeitos adversos , Estômago/efeitos dos fármacos , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Animais , Modelos Animais de Doenças , Eletromiografia , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Humanos , Memantina/administração & dosagem , Estômago/fisiopatologia , Sus scrofa
4.
Immunology ; 159(2): 167-177, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31646612

RESUMO

Immune checkpoint inhibition with monoclonal antibodies is becoming increasingly commonplace in cancer medicine, having contributed to a widening of therapeutic options across oncological indications. Disruption of immune tolerance is the key mechanism of action of checkpoint inhibitors and although immune-related adverse events are a typical class effect of these compounds, the relationship between toxicity and response is not fully understood. Awareness and vigilance are paramount in recognizing potentially life-threatening toxicities and managing them in a timely manner. In this review article, we provide an overview of the clinical features, pathological findings and management principles of common immune-related toxicities, attempting to provide mechanistic insight into an increasingly common complication of cancer therapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doenças do Sistema Endócrino/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Tolerância Imunológica/efeitos dos fármacos , Imunoterapia/efeitos adversos , Pneumopatias/induzido quimicamente , Terapia de Alvo Molecular/efeitos adversos , Neoplasias/tratamento farmacológico , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/terapia , Doenças do Sistema Endócrino/imunologia , Doenças do Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/terapia , Gastroenteropatias/imunologia , Gastroenteropatias/metabolismo , Gastroenteropatias/terapia , Humanos , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Fatores de Risco , Evasão Tumoral/efeitos dos fármacos
5.
Expert Opin Drug Saf ; 19(1): 19-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31739696

RESUMO

Introduction: The 18th Annual Meeting of the Safety Pharmacology Society included a session dedicated to the assessment of drug safety on the gastrointestinal (GI) system.Areas covered: GI anatomy, physiology, adverse effects (AEs) of chemical and biological therapies, and approaches to mitigate them.Expert opinion: GI AEs, albeit common and generally of minor intensity, may prolong clinical development time and reduce patient compliance.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Gastroenteropatias/induzido quimicamente , Trato Gastrointestinal/efeitos dos fármacos , Animais , Desenvolvimento de Medicamentos/métodos , Humanos
6.
Lancet Haematol ; 7(2): e112-e121, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866281

RESUMO

BACKGROUND: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. METHODS: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. FINDINGS: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0-29·7), 13 (93% [95% CI 66-100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86-98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3-4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3-4 atrial fibrillation occurred in one (1%) patient and grade 3-4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). INTERPRETATION: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. FUNDING: Acerta Pharma.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Benzamidas/efeitos adversos , Benzamidas/farmacologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Proteínas de Neoplasias/antagonistas & inibidores , Neutropenia/induzido quimicamente , Dor/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/efeitos adversos , Pirazinas/farmacologia , Qualidade de Vida , Recidiva , Infecções Respiratórias/etiologia , Terapia de Salvação , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/enzimologia , Macroglobulinemia de Waldenstrom/genética
7.
Ann Ist Super Sanita ; 55(4): 338-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850860

RESUMO

INTRODUCTION: Ketamine is an essential medicine used as an anesthetic in low and middle-income countries and in veterinary medicine. Recreational use is widespread throughout the world, especially owing to its lower price compared to other substances. In Western countries its use has been mainly linked to subpopulations of young people who use drugs recreationally. Ketamine misuse is associated with amnesia, dependence, dissociation, lower urinary tract dysfunction and poor impulse control. Regular ketamine use is associated with abdominal pains. AIMS: The aims of this study are to analyze characteristics and main symptoms of ketamine abusers attending emergency departments (EDs) in the metropolitan area of Bologna, Emilia-Romagna Region, northern Italy. METHODS: We identified 74 records of ketamine-related visits: 30% female; 22% non-natives; mean age 25.6 years. Forty-two percent reported ketamine use alone, 46% reported the use of other illegal substance (cocaine 19%, heroin 18%), 26% alcohol misuse. RESULTS: The most common reported symptoms were neurological (soporous state 18%, agitation 14%, confusion 7%, panic attacks 7%, mydriasis 7%, tremors 7%), gastro-intestinal (abdominal pain 15%, vomiting 11%), urological (6.8%) and cardiac (palpitations 5%, chest pain 5%). Complications secondary to falls and cuts (7%) were the most frequent trauma complications. We highlight a significant number of visits regarding suicide attempts (10%) and overdose (4%). CONCLUSIONS: The results highlight a particular population of problematic ketamine users identified using the hospital's ICT system. In particular, poly-drug users who consume ketamine in combination with heroin or cocaine presenting to the ED represent a specific target for targeted prevention projects on non-lethal overdoses and suicide attempts.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Ketamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Adulto , Alcoolismo/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Comorbidade , Estudos Transversais , Overdose de Drogas/epidemiologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Itália/epidemiologia , Masculino , Transtornos Mentais/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Avaliação de Sintomas , Adulto Jovem
8.
N Engl J Med ; 381(12): 1136-1147, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532960

RESUMO

BACKGROUND: Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known. METHODS: In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment. RESULTS: Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir. CONCLUSIONS: Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/fisiologia , Ribonucleosídeos/uso terapêutico , Valganciclovir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Aloenxertos , Antivirais/efeitos adversos , Antivirais/farmacologia , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacologia , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/virologia , Disgeusia/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Transplante de Órgãos/efeitos adversos , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/farmacologia , Valganciclovir/efeitos adversos , Valganciclovir/farmacologia , Ativação Viral/efeitos dos fármacos
9.
BMC Musculoskelet Disord ; 20(1): 399, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472671

RESUMO

BACKGROUND: Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials. METHODS: Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence. RESULTS: Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p = 0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p < 0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p < 0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p < 0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p < 0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p < 0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p < 0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p < 0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p = 0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p = 0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p < 0.0001). CONCLUSION: Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Fraturas por Compressão/prevenção & controle , Osteoporose/complicações , Fraturas por Osteoporose/prevenção & controle , Fraturas da Coluna Vertebral/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Fraturas por Compressão/epidemiologia , Fraturas por Compressão/etiologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Humanos , Oligopeptídeos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Suspensão de Tratamento/estatística & dados numéricos
10.
Am J Health Syst Pharm ; 76(16): 1183-1202, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369120

RESUMO

PURPOSE: The pharmacology, clinical activity, safety, and place in therapy of the cyclin-dependent kinase (CDK) inhibitors palbociclib, ribociclib, and abemaciclib are reviewed. SUMMARY: CDK 4 and CDK 6 are downstream agents in the estrogen signaling pathway that control entry into the cell cycle. CDK4/6 inhibition may prevent tumor cell progression in the cell cycle. Three CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are available for women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. These medications' indications in the treatment of HR+/HER2- advanced breast cancer include use with an aromatase inhibitor (AI) as initial therapy in postmenopausal women and with fulvestrant in women whose disease progressed during endocrine therapy. Ribociclib is also indicated as initial therapy with an AI in premenopausal or perimenopausal women and as initial therapy with fulvestrant in postmenopausal women. Abemaciclib is also indicated as monotherapy in women with disease progression after endocrine therapy and prior chemotherapy. A significant increase in progression-free survival (PFS) was seen with use of all 3 agents as initial therapy with an AI in controlled trials. Each agent also was demonstrated to produce a significant increase in PFS when used with fulvestrant in women whose disease progressed with prior endocrine therapy. Neutropenia is a dose-limiting adverse effect of palbociclib and ribociclib. Fatigue is more common with use of palbociclib and abemaciclib, and gastrointestinal effects are more common with abemaciclib use. CONCLUSION: CDK4/6 inhibitors have significant demonstrated clinical activity in combination with AIs or fulvestrant in women with HR+/HER2- advanced or metastatic breast cancer and are becoming a standard of care in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Humanos , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Purinas/farmacologia , Purinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Int J Clin Pharmacol Ther ; 57(11): 531-541, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397273

RESUMO

OBJECTIVE: Osteoarthritis is highly prevalent in older adults and often treated with nonsteroidal anti-inflammatory drugs (NSAIDs). COX-2-selective NSAIDs have been shown to offer better gastrointestinal (GI) safety benefits than non-selective NSAIDs (ns-NSAIDs). However, most COX-2-selective NSAIDs have not been comprehensively evaluated for use in combination with gastroprotective agents (GPAs). This study compared the risk of adverse GI events in patients treated with COX-2-selective NSAIDs and ns-NSAIDs alone, or in combination with GPAs. MATERIALS AND METHODS: We utilized National Health Insurance Claim Data collected from 2012 to 2015. Newly diagnosed patients with osteoarthritis (60 years or older) were included in this study. The study population was divided into two groups: 1) COX-2-selective NSAID treatment and 2) ns-NSAIDs treatment. Patients were followed-up for up to 6 months to determine whether GI events occurred. The Cox proportional hazards model was used to identify differences in risk. Subgroup analyses were conducted for monotherapies and combination treatments with GPAs. RESULTS: The number of subjects prescribed COX-2-selective NSAID and ns-NSAIDs were 20,868 (5.6%) and 353,494 (94.4%), respectively. After adjustment for confounding factors, COX-2-selective NSAID were safer than ns-NSAIDs (adjusted hazard ratio (aHR) = 0.80, 95% confidence interval (CI): 0.77 - 0.82). Use of GPAs with COX-2-selective NSAID was associated with a lower risk of GI events than use of ns-NSAIDs (aHR = 0.92, 95% CI: 0.87 - 0.97). CONCLUSION: Use of COX-2-selective NSAID was associated with a lower risk of GI adverse events than use of ns-NSAIDs as a monotherapy. Furthermore, COX-2-selective NSAID were safer than ns-NSAIDs in combination with GPAs.
.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Estudos Retrospectivos
12.
Pediatr Blood Cancer ; 66(11): e27953, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31393093

RESUMO

BACKGROUND: Pediatric patients with high-risk, relapsed, or refractory solid tumors have a poor prognosis. We have previously reported a dose-finding experience of high-dose chemotherapy consisting of thiotepa and melphalan ("double-conditioning regimen"). Using doses derived from that study, we have treated patients since 2005. We now report a retrospective review of patients treated by this fixed dose. PROCEDURE: We reviewed 50 patients (median 4 years; range 0-15 years) with high-risk or relapsed/refractory solid tumors treated by this dose-fixed, double-conditioning regimen from April 2005 to May 2014. Doses were thiotepa 800 mg/m2 and melphalan 280 mg/m2 for children ≥2 years of age, and 32 mg/kg and 6 mg/kg, respectively, for children <2 years of age. Further, doses were reduced according to creatinine clearance with poor renal function. RESULTS: Nonhematological toxicity was mainly gastrointestinal-grade 3 mucositis (n = 41) and grade 3-4 diarrhea (n = 10). Neurological, renal, and endothelial cell toxicity and sinusoidal obstruction syndrome were not observed. There were two toxic deaths (interstitial viral pneumonia). This regimen demonstrated antitumor activity against several types of tumors. Although the frequency of gastrointestinal toxicity was high, other severe toxicity was not observed. CONCLUSIONS: Our double-conditioning regimen was very well tolerated and demonstrated antitumor activity. We are moving forward with multi-institutional trials now.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Creatinina/sangue , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Estudos de Viabilidade , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/etiologia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Neoplasias/tratamento farmacológico , Pneumonia Viral/etiologia , Estudos Retrospectivos , Risco , Tiotepa/administração & dosagem , Tiotepa/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo
13.
Farm Hosp ; 43(5): 158-162, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469628

RESUMO

OBJECTIVE: To analyze adverse reactions in patients with nonmetastatic colorectal cancer due to treatment with either innovative  or generic capecitabine and/or to the chemotherapeutic regimen  employed, to the capecitabine alone, or in combination with oxaliplatin  (XELOX). METHOD: Descriptive retrospective study carried out in a secondary level hospital in two study periods (November 2013-April 2014 and  August 2016-May 2017). The collected variables were: exposure  (chemotherapy scheme and/or received medication), control  (demographics, disease and treatment data), and response (adverse  reactions). The statistical analysis of data was performed with the  SPSS® 15.0 program. Results: Fifty patients were included. According to the administered chemotherapeutic scheme, statistically significant  differences were found in the appearance of palmar-plantar  erythrodysesthesia, which is more frequent with monotherapy (p <  0.05), and neurotoxicity, thrombocytopenia and neutropenia, which is  more frequent with XELOX (p < 0.05). Concerning the capecitabine drug  administered, no statistically significant differences were found in  the studied adverse reactions. CONCLUSIONS: The safety profile of two capecitabine formulations - innovative and generic- appears to be associated with the  chemotherapy scheme employed, and not the drug itself. Most palmar- plantar erythrodysesthesia for monotherapy is likely due to the higher  dose of capecitabine used in said scheme. The increase in neurotoxicity,  thrombocytopenia and neutropenia for XELOX is probably due to  cumulative toxicity of two antineoplastic drugs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Relação Dose-Resposta a Droga , Composição de Medicamentos , Medicamentos Genéricos , Feminino , Gastroenteropatias/induzido quimicamente , Síndrome Mão-Pé/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Neutropenia/induzido quimicamente , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
14.
Hematol Oncol ; 37(4): 352-359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385336

RESUMO

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.


Assuntos
Antineoplásicos/efeitos adversos , Benzamidas/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Terapia de Alvo Molecular , Morfolinas/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Subpopulações de Linfócitos B/patologia , Benzamidas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Células-Tronco Neoplásicas/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Rituximab/administração & dosagem , Rituximab/efeitos adversos
15.
Biomed Pharmacother ; 117: 109200, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387194

RESUMO

Bee pollen (BP) is a natural medicine from the hive with various potential health-promoting benefits, but until now there is no study to determine its protective roles in inflammatory bowel disease (IBD). The aim of this study was to reveal the in vitro gastrointestinal protective effects of BP against IBD using molecular and metabolic methods. Dextran sulfate sodium (DSS) challenged Caco-2 cell monolayers were applied to mimic intestinal epithelial cell dysfunctions and metabolic disorders. The pretreatment with BP extract rich in polyphenols ameliorated DSS-induced cell viability losses. It also exerted protective effects against intestinal barrier impairment by strengthening epithelial integrity and tight junction losses induced by DSS. BP up-regulated anti-oxidant (NQO1, Txnrd1, Nrf2) and down-regulated inflammatory (TNF-α and IL-6) mRNA expressions, in accompany with MAPK signaling inhibition. Furthermore, metabolomics analysis based on UPLC-Q-TOF/MS revealed that BP, and DSS treated Caco-2 cells have different metabolomic profiles, with significant changes on key metabolites involved in glycerophospholipid metabolism. Our results showed that BP has great therapeutic potential throughout the early stages of DSS-induced colitis.


Assuntos
Abelhas/química , Produtos Biológicos/farmacologia , Gastroenteropatias/tratamento farmacológico , Intestinos/efeitos dos fármacos , Pólen/química , Substâncias Protetoras/farmacologia , Animais , Células CACO-2 , Linhagem Celular Tumoral , Sulfato de Dextrana/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Polifenóis/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
16.
Int J Sports Med ; 40(11): 711-716, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31434137

RESUMO

The purpose of this study was to evaluate whether NaHCO3, administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO3 -]), has an ergogenic effect on repeated all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at +1-h and +2-h, yielding a total NaHCO3 intake of 0.4 g·kg-1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO3 -], pH and [La-]. Pre-exercise blood [HCO3 -] in PL decreased from 25.6±0.2 mmol·L-1 in bout 1 to 23.6±0.2 mmol·L-1 in bout 4, while increasing from 25.5±0.2 to 31.2±0.4 mmol·L-1 in BIC (P<0.05). Concomitantly, pre-exercise pH values gradually decreased in PL (from 7.41±0.00 to 7.39±0.01) and increased in BIC (from 7.41±0.01 to 7.47±0.01; P<0.05). Mean power output of the four bouts was higher in BIC (428±20 W) than in PL (420±20 W; P<0.05). The ergogenic effect on repeated all-out exercise occurred in the absence of gastrointestinal distress.


Assuntos
Desempenho Atlético/fisiologia , Substâncias para Melhoria do Desempenho/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Teste de Esforço , Gastroenteropatias/induzido quimicamente , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Masculino , Substâncias para Melhoria do Desempenho/efeitos adversos , Substâncias para Melhoria do Desempenho/sangue , Bicarbonato de Sódio/efeitos adversos , Bicarbonato de Sódio/sangue , Adulto Jovem
17.
Curr Gastroenterol Rep ; 21(8): 35, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31289927

RESUMO

PURPOSE OF REVIEW: Short-chain fatty acids (SCFAs), the main bacterial fermentation products in the hindgut of hindgut fermenters, are also present in the foregut lumen. We discuss the impact of SCFAs in the duodenal defense mechanisms and in the gastrointestinal (GI) pathogenesis. RECENT FINDINGS: Luminal SCFAs augment the duodenal mucosal defenses via release of serotonin (5-HT) and glucagon-like peptide-2 (GLP-2) from enteroendocrine cells. Released GLP-2 protects the small intestinal mucosa from nonsteroidal anti-inflammatory drug-induced enteropathy. SCFAs are also rapidly absorbed via SCFA transporters and interact with afferent and myenteric nerves. Excessive SCFA signals with 5-HT3 receptor overactivation may be implicated in the pathogenesis of irritable bowel syndrome symptoms. SCFA production exhibits diurnal rhythms with host physiological responses, suggesting that oral SCFA treatment may adjust the GI clocks. SCFAs are not only a source of energy but also signaling molecules for the local regulation of the GI tract and systemic regulation via release of gut hormones. Targeting SCFA signals may be a novel therapeutic for GI diseases and metabolic syndrome.


Assuntos
Duodeno/metabolismo , Ácidos Graxos Voláteis/fisiologia , Gastroenteropatias/metabolismo , Anti-Inflamatórios não Esteroides/efeitos adversos , Ritmo Circadiano/fisiologia , Duodeno/microbiologia , Gastroenteropatias/induzido quimicamente , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/metabolismo
18.
J Pharm Pract ; 32(3): 339-346, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291840

RESUMO

Such as any field of medicine, it is imperative to stay current with the latest advances and treatment modalities in toxicology. With the absence of rigorous randomized controlled trials, many updated guidelines are created by expert consensus and/or case reports and clinical experience. Over the past 10 years, there have been several changes in the management of drug overdoses in light of new data available. Although this is not a comprehensive review of all available antidotes, this article will focus on several important interventions including the use of gastrointestinal decontamination, hyperinsulinemic-euglycemic therapy, methylene blue, intravenous lipid emulsion, hemodialysis, and extracorporeal membrane oxygenation.


Assuntos
Descontaminação/métodos , Antídotos/farmacologia , Overdose de Drogas/tratamento farmacológico , Oxigenação por Membrana Extracorpórea , Emulsões Gordurosas Intravenosas/uso terapêutico , Gastroenteropatias/induzido quimicamente , Humanos , Azul de Metileno/uso terapêutico , Diálise Renal
19.
J Vet Intern Med ; 33(4): 1619-1626, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31268578

RESUMO

BACKGROUND: Synbiotics decrease antibiotic-associated gastrointestinal signs (AAGS) in cats, but data supporting synbiotic use to ameliorate AAGS in dogs are lacking. OBJECTIVES: To determine if administration of synbiotics mitigates AAGS in dogs. ANIMALS: Twenty-two healthy research dogs. METHODS: Randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with an 8-week washout period. Each period included a 1-week baseline and 3-week treatment phase. Dogs received enrofloxacin (10 mg/kg PO q24h) and metronidazole (12.5 mg/kg PO q12h), followed 1 hour later by a bacterial/yeast synbiotic combination or placebo. Food intake, vomiting, and fecal score were compared using repeated-measures crossover analyses, with P < .05 considered significant. RESULTS: Hyporexia, vomiting, and diarrhea occurred in 41% (95% confidence interval [CI], 21-64), 77% (95% CI, 55-92), and 100% (95% CI, 85-100) of dogs, respectively, during the first treatment period. Derangements in food intake were smaller in both periods for dogs receiving synbiotics (F-value, 5.1; P = .04) with treatment-by-period interactions (F-value, 6.0; P = .02). Days of vomiting differed over time (F-value, 4.7; P = .006). Fecal scores increased over time (F-value, 33.5; P < .001), were lower during period 2 (F-value, 14.5; P = .001), and had treatment-by-period effects (F-value, 4.8; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Enrofloxacin/metronidazole administration is associated with a high frequency of AAGS. Synbiotic administration decreases food intake derangements. The presence of milder AAGS in period 2 suggests that clinical effects of synbiotics persist >9 weeks after discontinuation, mitigating AAGS in dogs being treated with antibiotics followed by placebo.


Assuntos
Antibacterianos/efeitos adversos , Doenças do Cão/induzido quimicamente , Enrofloxacina/efeitos adversos , Gastroenteropatias/veterinária , Metronidazol/efeitos adversos , Simbióticos/administração & dosagem , Vômito/induzido quimicamente , Animais , Estudos Cross-Over , Doenças do Cão/prevenção & controle , Cães , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Masculino , Distribuição Aleatória , Vômito/prevenção & controle , Vômito/veterinária
20.
Nutrients ; 11(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336652

RESUMO

Food intolerances are estimated to affect up to 20% of the population but complete understanding of diagnosis and management is complicated, given presentation and non-immunological mechanisms associated vary greatly. This review aims to provide a scientific update on common food intolerances resulting in gastrointestinal and/or extra-intestinal symptoms. FODMAP sensitivity has strong evidence supporting its mechanisms of increased osmotic activity and fermentation with the resulting distention leading to symptoms in those with visceral hypersensitivity. For many of the other food intolerances reviewed including non-coeliac gluten/wheat sensitivity, food additives and bioactive food chemicals, the findings show that there is a shortage of reproducible well-designed double-blind, placebo-controlled studies, making understanding of the mechanisms, diagnosis and management difficult. Enzyme deficiencies have been proposed to result in other food sensitivities including low amine oxidase activity resulting in histamine intolerance and sucrase-isomaltase deficiency resulting in reduced tolerance to sugars and starch. Lack of reliable diagnostic biomarkers for all food intolerances result in an inability to target specific foods in the individual. As such, a trial-and-error approach is used, whereby suspected food constituents are reduced for a short-period and then re-challenged to assess response. Future studies should aim to identify biomarkers to predict response to dietary therapies.


Assuntos
Hipersensibilidade Alimentar , Intolerância Alimentar , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/dietoterapia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA