RESUMO
Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8-12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2-ΔΔCT method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS.
Assuntos
Disfunção Cognitiva/genética , Hipocampo/metabolismo , Lúpus Eritematoso Sistêmico/genética , Transtornos da Memória/genética , Receptores de N-Metil-D-Aspartato/genética , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Expressão Gênica , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Receptores de N-Metil-D-Aspartato/metabolismo , Terpenos/administração & dosagemAssuntos
Imunossupressores , Miosite , Tuberculose do Sistema Nervoso Central , Tuberculose Cutânea , Tuberculose Osteoarticular , Adulto , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Conduta do Tratamento Medicamentoso , México/epidemiologia , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/etiologia , Prevalência , Estudos Retrospectivos , Risco Ajustado , Fatores de Risco , Prevenção Secundária , Tuberculose do Sistema Nervoso Central/complicações , Tuberculose do Sistema Nervoso Central/tratamento farmacológico , Tuberculose do Sistema Nervoso Central/epidemiologia , Tuberculose Cutânea/complicações , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/epidemiologia , Tuberculose Osteoarticular/complicações , Tuberculose Osteoarticular/tratamento farmacológico , Tuberculose Osteoarticular/epidemiologiaRESUMO
BACKGROUND: Pathologic skin scarring reversion remains a big challenge for surgeons, as disfiguring scars have a dramatic influence on patient's quality of life. METHODS: A controlled clinical trial was conducted to evaluate 8% pirfenidone (PFD) gel administered topically 3 times a day during 6 months to 33 pediatric patients with hypertrophic scars caused by burns. A total of 30 patients with hypertrophic scars with identical Vancouver Scar Scale values were treated with pressure therapy and included as controls. Improvements were evaluated by Vancouver Scar Scale and a Visual Analog Scale. Safety parameters were determined by the presence of adverse events and monitoring laboratory and hematology parameters. RESULTS: Patients treated with PFD during 6 months presented a continuous monthly statistically significant scar regression in comparison with the initial Vancouver measurement (P = <0.001). PFD group showed a higher improvement of all scar features as compared with control group treated with pressure therapy (P = <0.001). In the PFD group, 9 of 33 patients (27%) had their scores decreased in Vancouver classification by more than 55%, 22 patients (67%) had a 30% to 45% decrease, whereas 2 patients (6%) had a 30% decrease or less. Control group treated with pressure therapy showed a slight improvement in 16% of cases on an average. Patients did not show serious adverse effects or laboratory alterations throughout the study. CONCLUSIONS: Topical administration of 8% PFD gel 3 times a day is more effective and safe in the treatment of hypertrophic scars caused by burns in children, as compared with standard pressure therapy.
