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1.
Minerva Pediatr ; 62(5): 459-73, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20940680

RESUMO

Polycystic ovary syndrome (PCOS) is a complex disorder, involving primarily ovarian hyperandrogenism in females and linked with insulin resistance in the majority of cases. Clinical features are widely variable and include a combination of menstrual irregularities, acne, hirsutism, and alopecia. Although it typically presents around puberty, several risk factors during childhood may help raise a high index of suspicion for the development of PCOS in adolescents. The pathophysiology of PCOS still remains unknown and likely includes a combination of genetic factors, insulin resistance, and environmental factors. A thorough diagnostic work up is required in suspected cases and several management modalities have been suggested. Since various long term complications and comorbidities are associated with PCOS, early diagnosis and therapeutic intervention is warranted in these cases.


Assuntos
Síndrome do Ovário Policístico , Adolescente , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/terapia
2.
J Pept Sci ; 14(10): 1084-95, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18523964

RESUMO

Synthesis, structural and biological studies of pentapeptides containing two DeltaPhe residues (Z and E isomers) in position 2 and 4 in peptide chain were performed. All the investigated peptides adopted bent conformation and majority of them could exist as two different conformers in solution. Only pentapeptides, containing free N-termini appeared to act as weak inhibitors of cathepsin C with the slow-binding, competitive mechanism of inhibition, free acids being bound slightly better than their methyl esters. Results of molecular modeling suggested significant difference between peptides, depending of the type of amino acid residue in position 5 in peptide chain. Dehydropeptides containing Gly residue in this position may act as competitive slow-reacting substrates and therefore exhibit inhibitory-like properties.


Assuntos
Catepsina C/antagonistas & inibidores , Catepsina C/metabolismo , Oligopeptídeos/química , Oligopeptídeos/síntese química , Fenilalanina/análogos & derivados , Ligação Competitiva/fisiologia , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Oligopeptídeos/fisiologia , Fenilalanina/química , Fenilalanina/metabolismo , Fenilalanina/fisiologia , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Estrutura Secundária de Proteína , Especificidade por Substrato/fisiologia
3.
Eur J Med Chem ; 41(6): 768-72, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16690170

RESUMO

Fully deprotected phosphonamidate dipeptides, predicted as effective inhibitors of cytosolic leucine aminopeptidase, showed unexpected instability in water solution at pH below 12. Their hydrolysis rate was strictly correlated with basicity of the N-terminal amino group. To improve this feature a phosphonamidate analogue containing less basic, aromatic 2-aminophenylphosphonate residue in P1 position of the inhibitor was designed. The target compound was synthesised starting from diethyl 2-nitrophosphonate in several step procedure. The decrease in basicity of the terminal amino moiety of the modified analogue in fact resulted in satisfactory improvement of hydrolytic stability of the P-N bond. The developed phosphonamidate was proved to be fully resistant to hydrolysis above pH 7. Surprisingly, tested in enzymatic assays towards leucine aminopeptidase (optimum pH 8.5), it did not exhibit inhibition activity up to milimolar concentration. The explanation could be that diminishing the basic character of the terminal amino group may result in a change of its affinity towards the zinc ions.


Assuntos
Leucil Aminopeptidase/antagonistas & inibidores , Compostos Organofosforados/farmacologia , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Desenho de Fármacos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Inibidores de Proteases/química
4.
J Pept Sci ; 7(3): 141-5, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11297349

RESUMO

Three dehydrotetrapeptides of rationally varying structure were prepared and tested as affectors of cathepsin C. These compounds appeared to be substrates of the enzyme, being equipotent with their classical counterparts. Thus, replacement of amino acid in a short peptide by corresponding dehydroamino acid does not prevent cathepsin C in recognizing dehydropeptide as its substrate.


Assuntos
Alanina/análogos & derivados , Alanina/química , Anilidas/síntese química , Catepsina C/metabolismo , Oligopeptídeos/síntese química , Fenilalanina/análogos & derivados , Fenilalanina/química , Aminoácidos/química , Anilidas/química , Animais , Catepsina C/química , Bovinos , Espectroscopia de Ressonância Magnética , Modelos Químicos , Oligopeptídeos/química , Baço/metabolismo
5.
Mycotoxin Res ; 4(2): 89-96, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23605162

RESUMO

Totally 39% out of 8371 feed and their component samples were contaminated by aflatoxin B1. Mean contamination was 36µg/kg with maximum yield 10100 µg/kg. Contamination of samples by total count of organisms, mean contamination and maximum yield, respectively was: 1) bacteria 99%, 2.2×10(6), 2.4×10(8); 2) proteolytic bacteria 94%, 1.2×10(5), 3.0×10(6);3) moulds 98%, 1.3×10(5), 9.0×10(6); 4) yeasts 44 %, 3.3×10(4), 3.6×10(6). The samples were contaminated in 92 % byAspergillus spp, in 71% byAspergillus flavus, in 83% byPenicillium spp, and in 20% byFusarium spp with mean contamination 8.3×104, 1.1×10(3), 4.2×10(4), 5.0×10(3) , and maximum yield 6.8×10(6), 1.0×10(5), 5.0×10(6), 1.5×10(6), respectively. Totally 8.5% of strains were aflatoxinogenic and 4.4% of the strains were isolated from feed and 21 % of the strains from grain/nut.

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