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1.
J Inherit Metab Dis ; 45(4): 696-709, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35527480

RESUMO

Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (Phe). Currently, the most commonly used treatment for PKU is dietary Phe restriction. Problems associated with Phe restricted diets include lack of universal availability, high treatment costs, and reduced adherence to continued treatment with age and finally the development of psychological and neurological problems in a significant proportion of patients despite early start of treatment. One possible approach to decreasing blood Phe level, is inhibition of GI tract absorption of this amino acid. We had previously shown that a Phe selective molecularly imprinted polymer was able to bind Phe in the GI tract and attenuate its plasma concentration. In this work, we used different orally administered Phe selective molecularly imprinted polymer doses in a PKU mouse model to further study the effects of this treatment on biochemical profile and cognitive function in test animals. Treatments started 21 days postnatally. After 3 weeks, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Behavioral profile was also evaluated. Treatment with 2% and 5% Phe selective molecularly imprinted polymer significantly reduced levels of blood Phe in PKU model animals (46% and 48% respectively) meanwhile levels of other amino acids remained unchanged. Brain dopamine concentrations in hippocampus was effectively restored by supplementation of Phe selective molecularly imprinted polymer. Finally, polymer treatment improved locomotor dysfunction in PKU model animals. Our data suggest that the Phe selective molecularly imprinted polymer can be a new candidate for treatment of PKU patients. Take home message: Orally administered Phenylalanine Selective Molecularly Imprinted Polymer is able to inhibit absorption of phenylalanine from the GI tract and may offer a new treatment, in conjunction with dietary restriction, for PKU patients.


Assuntos
Fenilalanina , Fenilcetonúrias , Administração Oral , Animais , Modelos Animais de Doenças , Camundongos , Polímeros Molecularmente Impressos , Fenilalanina/metabolismo , Fenilcetonúrias/metabolismo
2.
Drug Dev Res ; 81(7): 765-767, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32337769

RESUMO

Successful treatment of viral infections has proven to be huge challenge for modern medicine with the most effective approach being prior vaccination. The problem with vaccination is the time it takes to develop an effective vaccine, validate its safety and manufacture it in large quantities. Facing Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), we simply do not have the time to develop the vaccine before thousands of people die. Therefore, any treatment which can decrease the severe symptoms due to lung damage may help attenuate mortality rates. Inactivation of ACE2 during virus fusion into the host cell may be one of the underlying reasons for intense immunological reaction seen in the lung tissue. This overreaction is probably mediated through the bradykinin receptor activation. Noscapine, a medication used for the treatment of cough, has been shown to inhibit bradykinin enhanced cough response in man. As it is already marketed in a number of countries as a cough medicine, even for children, a suitable formulation with all the required licenses is available that can be rapidly utilized in preliminary trials.


Assuntos
Bradicinina/antagonistas & inibidores , COVID-19/imunologia , Noscapina/farmacologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Bradicinina/metabolismo , Citocinas/metabolismo , Regulação para Baixo , Humanos , Noscapina/uso terapêutico , Receptores da Bradicinina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
3.
Int J Mycobacteriol ; 5 Suppl 1: S214, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28043562

RESUMO

BACKGROUND/OBJECTIVES: The genus Mycobacterium contains over 140 species comprises pathogenic and nonpathogenic strains. Nontuberculous mycobacteria (NTM) causing clinical disease have become increasingly common and more diverse. Widespread features of NTM infection can make the diagnosis difficult. Precise species-level detection can aid in distinguishing environmental contamination from actual infection and, furthermore, can assist in making a choice of antimicrobial therapy. MATERIALS AND METHODS: Mycolic acids extracted from saponified mycobacterial cells were examined by high performance liquid chromatography (HPLC) in addition to phenotypic tests for the identification of 20 clinical isolates of mycobacteria at Masoud Laboratory during 2014-2015. RESULTS: Mycobacterium abscessus (8 isolates), Mycobacterium tuberculosis (6 isolates), Mycobacterium intracellulare (3 isolates) and Mycobacterium fortuitum (3 isolates) were identified in these isolates. The phenotypic tests also confirmed the identity of the clinical isolates. CONCLUSION: Our results showed that HPLC is a more reliable, rapid, simple, easy-to-perform, cost-effective, and specific identification method compared with other identification procedures like phenotypic tests.

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