RESUMO
INTRODUCTION: In Pediatrics, adverse drug reactions (ADRs) affect morbidity and mortality. In Mexico, the characteristics of ADRs and suspect drugs have not been described in hospitalized children. OBJECTIVE: To estimate the frequency of ADRs and describe them, as well as suspect drugs, in a tertiary care pediatric hospital in Mexico. METHODS: A total of 1,649 Hospital Infantil de Mexico Federico Gómez ADR reports were analyzed. Completeness of the information was assessed, and ADRs severity and seriousness were assigned based on NOM-220-SSA1-2012, with causality being established according to the Naranjo algorithm. ADRs were classified with WHO Adverse Drug Reaction Terminology (WHO-ART). The drugs involved in ADRs were categorized according to the Anatomical Therapeutic Chemical (ATC) classification. Descriptive analysis was performed using the SPSS 20 statistical package. RESULTS: Of all the reports, 5.8% lacked sufficient information for the analysis (grade 0). ADRs frequency ranged from 2.12% to 8.07%. ADRs occurred most commonly in children (56.9%), in the female gender (52%), in subjects with normal BMI Z-score (46.6%) and malnutrition (35.3%), diagnosed with neoplasms (72.2%) and in the Emergency Department (70.0%). ADRs were severe in 14.4% of cases, in 81.0% they were serious and 2.1% were classified as definite. Most common serious ADR was febrile neutropenia (44.5%). The 0.7% of patients recovering with sequelae; 1.1% died (with the medication being associated) and 70.3% were admitted to the hospital as a result of an ADR. Antineoplastic and immunomodulating agents were more commonly associated with serious ADRs. CONCLUSION: ADRs affected morbidity and mortality, which is why strengthening pharmacovigilance programs in Mexican pediatric hospitals is necessary.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Feminino , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Índice de Gravidade de Doença , Fatores Sexuais , Atenção Terciária à Saúde , Adulto JovemRESUMO
The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change ≥ 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC.
Assuntos
Biomarcadores Tumorais/genética , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/metabolismo , Terapia de Alvo Molecular , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Sequência de Bases , Carcinogênese , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Papillomaviridae/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA) -specific MatAb on the anti- OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti- OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination.
