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1.
Artigo em Inglês | MEDLINE | ID: mdl-36674026

RESUMO

The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary's second-largest city (Debrecen) for the COVID-19 vaccine. To achieve this aim, a discrete choice experiment was conducted with 1011 participants, and the vaccine characteristics included in the design of the experiment were determined by qualitative methods and a pilot survey: (1) country of origin; (2) efficiency; (3) side effect; and (4) duration of protection. During the data collection at three vaccination sites, respondents were asked to choose between three vaccine alternatives and one "no choice" option in eight decision situations. Discrete choice model estimations were performed using a random parameter logit (RPL) specification with the final model extended to include a latent variable measuring pandemic awareness. The results showed that the vaccine with a Chinese country of origin is the least preferred among the respondents, while the Hungarian and the European vaccines are the most preferred. Furthermore, the increase in the vaccine efficiency level increased the respondents' sense of utility for the vaccine; the short-term side effect was preferred to the long-term one; and the increase in the duration of protection provided by the vaccine increased the respondents' sense of utility for the vaccine. Based on the parameter estimated for the latent variable, it can be concluded that as the level of pandemic awareness (which is more positive among people with chronic diseases and less important among health workers) increases, the choice of a vaccine option becomes more preferred among respondents compared to the "no choice". The results of our investigation could contribute towards increasing compliance in the case of the vaccination-rejecting population, not only for COVID-19, but for any kind of vaccination procedure.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19/uso terapêutico , Pandemias/prevenção & controle , Hungria , Comportamento de Escolha , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
3.
Front Pharmacol ; 12: 650207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935754

RESUMO

Retinal complications of diabetes often lead to deterioration or even loss of vision. This hastens discovery of pharmacological agents able to counterbalance diabetic retinopathy. BGP-15, an emerging small molecule agent, was formerly proven by our workgroup to be retinoprotective on nonobese diabetic animals, Goto-Kakizaki rats. In the present study, we aimed to examine its long-term tolerability or incidental side effects on obese-prone Zucker diabetic fatty (ZDF) rats to further increase the rationale for a future human translation. To make terminal visual status comparable with our other investigations, we also carried out electroretinography (ERG) at the end of the experiment. Our study was started on 16-week-old ZDF rats and lasted for 52 weeks, while BGP was administered daily by gavage. During the 12 months of treatment, 100% of BGP-treated animals survived compared to the non-treated ZDF group, where 60% of the animals died, which was a statistically significant difference. Based on ERG results, BGP-15 was able to counterbalance visual deterioration of ZDF rats caused by long-term diabetes. Some moderate but significant changes were seen in OGTT results and some relationship to oxidative stress by the western blot method: BGP-15 was able to increase expression of HSP70 and decrease that of NFkB in eyes of rats. These were in concert with our previous observations of SIRT1 increment and MMP9 decrement in diabetic eyes by BGP. In summary, not only is BGP-15 not harmful in the long run but it is even able to reduce the related mortality and the serious consequences of diabetes. BGP-15 is an excellent candidate for future drug development against diabetic retinopathy.

4.
Int J Mol Sci ; 21(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204537

RESUMO

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements-like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results-electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/prevenção & controle , Hipoglicemiantes/farmacologia , Oximas/farmacologia , Piperidinas/farmacologia , Retina/efeitos dos fármacos , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Eletrorretinografia , Glibureto/farmacologia , Humanos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacologia , Insulina/farmacologia , Masculino , Metformina/farmacologia , Estrutura Molecular , Oximas/química , Pioglitazona/farmacologia , Piperidinas/química , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Retina/fisiopatologia
5.
Arch Pharm Res ; 36(3): 293-305, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23456693

RESUMO

A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.


Assuntos
Átrios do Coração/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Agonistas do Receptor Purinérgico P1/farmacologia , Antagonistas de Receptores Purinérgicos P1/farmacologia , Receptor A1 de Adenosina , Xantinas/farmacologia , Animais , Relação Dose-Resposta a Droga , Cobaias , Masculino , Contração Muscular/fisiologia , Técnicas de Cultura de Órgãos , Agonistas do Receptor Purinérgico P1/química , Antagonistas de Receptores Purinérgicos P1/química , Distribuição Aleatória , Receptor A1 de Adenosina/fisiologia , Resultado do Tratamento , Xantinas/química
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