RESUMO
BACKGROUND: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. OBJECTIVES: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. METHODS: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). CONCLUSION: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.
Assuntos
Predisposição Genética para Doença , Lectinas/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Egito , Feminino , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , FicolinasRESUMO
(R)(+) and (S)(-) 4-2H-phenytoin have been used as substrates for the determination of the percentage of deuterium retention (NIH shift) after para-hydroxylation of the substrates in rat. By using GC-MS analyses, the percentages of deuterium retention were found to be 69% and 70% for the (R) and (S) phenyl rings, respectively. The results add additional evidence for the involvement of arene oxide in the oxidation of the pro (R) and pro (S) phenyls of phenytoin. The oxidation process of each ring could be mediated by independent enzyme systems, a rapid oxidative enzyme for the pro (S) phenyl and a slow oxidative enzyme for the pro (R) phenyl.
Assuntos
Anticonvulsivantes/farmacocinética , Fenitoína/farmacocinética , Animais , Deutério , Cromatografia Gasosa-Espectrometria de Massas , Hidroxilação , Ratos , EstereoisomerismoRESUMO
The syntesis of a number of 2-(5-substituted-2-thienylthio)benzoic acid derivatives is described. The synthesized compounds were screened for their muscle relaxant and parasympatholytic activities and the results are reported.
Assuntos
Benzoatos/síntese química , Hidantoínas/síntese química , Relaxantes Musculares Centrais/síntese química , Parassimpatolíticos/síntese química , Bases de Schiff/síntese química , Animais , Benzoatos/farmacologia , Fenômenos Químicos , Química , Relação Dose-Resposta a Droga , Hidantoínas/farmacologia , Técnicas In Vitro , Intestinos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Atividade Motora/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Pilocarpina/farmacologia , Coelhos , Salivação/efeitos dos fármacos , Bases de Schiff/farmacologiaRESUMO
A convenient route is reported for the synthesis of certain series of 2-thiohydantoins carrying various heterocyclic substituents such as 5-bromothienylidene 3a,b, 5-(2-carboxyphenylthio)-2-thienylidene 4a,b and 4H-thieno[2,3-b][1]benzothiopyran-4-one 5a,b. Glycosylation of these thiohydantoins afforded the S-glycosyl derivatives 10a-d. The synthesized compounds were tested for their activity against HIV-1 virus and as antitumor agents.
Assuntos
Fármacos Anti-HIV/síntese química , Hidantoínas/síntese química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Humanos , Hidantoínas/farmacologiaRESUMO
Interaction of ethyl 2-amino-4,5,6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate 1 with 2-thiophene carbonyl chloride 2 afforded ethyl 2-(2-thenoylamino)-4, 5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 3 which upon cyclization yielded 2-(2-thienyl)-5,6,7, 8-tetrahydrobenzo[b]-thieno[2,3-d]-4H-3, 1-oxazin-4-one 4 and 2(2-thienyl)-3-amino-5, 6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]-3,4-dihydropyrimidin-4-one 6. Some of the prepared compounds were screened for their antiinflammatory activity, compound 7c and 9b showed significant activity.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Pirimidinas/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Feminino , Granuloma/tratamento farmacológico , Granuloma/patologia , Dose Letal Mediana , Masculino , Camundongos , Pirimidinas/farmacologia , Pirimidinas/toxicidade , RatosRESUMO
New series of 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 6-alkyl-2-thiouracil-5-carbonitriles 4c,d, 6-alkyl-2-arylmethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 5a-p, 6-alkyl-2-(2-methoxyethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 6a-d, 6-alkyl-2-benzyloxymethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 7a-c, 6-alkyl-2-(5-nitrofuran-2-ylmethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 8a-d, 6-alkyl-4-arylthio-2-(benzylsulfanyl)pyrimidine-5-carbonitriles 10a, b and 2-benzylsulfanyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-6-pentylpyrimidine-5-carbonitrile 11, were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4d, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5 l, 5p, 7a, 7b, 7c, 8a, 8b, 8c, 8d and 11 -displayed marked antibacterial activity particularly against the tested Gram-positive bacteria. Meanwhile, none of these compounds were proved to be active against Candida albicans.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Nitrilas/síntese química , Nitrilas/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Peso Molecular , Solubilidade , Difração de Raios XRESUMO
INTRODUCTION: Patients with diabetic neuropathy have an imbalance, which comes with a higher risk of falls. The aim of this study was to assess posture stability using computerised dynamic posturography in type 2 diabetics mellitus patients with neuropathy as well as its relation to glycaemic control. METHODS: 54 type 2 diabetics mellitus patients with peripheral neuropathy were recruited, together with 18 type 2 diabetics mellitus patients without peripheral neuropathy acting as the control group. The first group was divided into two subgroups according to glycaemic control assessed by HbA1c (A1c), the first subgroup comprising 24 patients had good glycaemic control with A1c less than or equal to seven percent and the second subgroup with 30 patients had poor glycaemic control with A1c more than 7 percent. The postural stability was evaluated using dynamic posturography. RESULTS: The composite equilibrium score, sensory organisation test 1, 2 and 3 conditions were significantly lower in the neuropathic group as compared to the non-neuropathic group (p-value is less than 0.001). A1c was significantly correlated with the composite equilibrium score in the neuropathic group with poor glycaemic control (r-value equal to -0.395) but not correlated in the neuropathic group with good glycaemic control (r-value equal to 0.151). CONCLUSION: Posture instability in type 2 diabetic patients with peripheral neuropathy reflects an impairment of the somatosensory system; also, poor glycaemic control resulted in more posture instability. The early detection of imbalance using dynamic posturography and achieving good glycaemic control may be of great help in the prevention of falls in such patients.
Assuntos
Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/diagnóstico , Equilíbrio Postural , Postura , Idoso , Computadores , Neuropatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-Idade , Software , Testes de Função VestibularRESUMO
The synthesis of a series of 4,5-disubstituted-3-(1-adamantyl)- 1,2,4-triazoles is described. The compounds 3-(1-adamantyl)4-methyl, ethyl and benzyl-5-mercapto-1,2,4-triazoles (3a, 3b and 3f) produced a high dose-dependent anti-inflammatory activity against carrageenin-induced paw oedema in rats. The analgesic activity of these active compounds correlated with their anti-inflammatory activities.
Assuntos
Adamantano/análogos & derivados , Adamantano/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Compostos de Sulfidrila/síntese química , Triazóis/síntese química , Adamantano/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Carragenina , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/patologia , Dose Letal Mediana , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Medição da Dor , Ratos , Compostos de Sulfidrila/farmacologia , Triazóis/farmacologiaRESUMO
The in-vivo metabolic conversion of equal mixture of phenytoin and decadeuteriophenytoin to the para-hydroxy metabolite in rat was investigated in order to verify a possible role of an insertion or abstraction mechanisms in the hydroxylation process. Determination of kH/k2H values of urine samples at 2 h intervals for 24 h indicated that there was no isotope effect during in-vivo para-hydroxylation of phenytoin. This gives evidence of the arene oxide intermediacy possibly being the sole pathway for para-hydroxylation of phenytoin.
Assuntos
Fenitoína/análogos & derivados , Fenitoína/metabolismo , Animais , Deutério , Cromatografia Gasosa-Espectrometria de Massas , Hidroxilação , Masculino , Oxirredução , RatosRESUMO
3'-Azido-2',3'-dideoxyuridines 6 and their corresponding alpha anomers 5 were synthesized by condensation of silylated 6-alkyl and 5,6-dialkyl substituted uracils 2 with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-alpha, beta-D-erythro-pentofuranoside (4). Compounds 5 and 6 were treated with tetrabutylammonium fluoride to obtain the deprotected nucleosides 7 and 8, respectively.