This study investigated the use of Novo Pro-D® (NPD) and Ficin (FC) as alternative proteases for the production of bioactive peptides with reduced allergenicity from whey protein concentrate (WPC). In addition, the use of high hydrostatic pressure processing as pre-treatment of WPC and its impact on the final characteristics of hydrolysates were also evaluated. NPD treatments generated hydrolysates with a 98% reduction of soluble proteins, greater in vitro antioxidant capacity, and less immunoreactivity when compared to FC ones. However, pre-treatment was an essential tool to improve WPC hydrolysis when FC was used, resulting in hydrolysates with less soluble proteins, enhanced antioxidant capacity, and less allergenicity compared with conventional hydrolysis. As for NPD, the pre-treatment of WPC improved the in vitro antioxidant capacity and resulted in a 100% reduction in immunoreactivity to β-lactoglobulin in a shorter processing time. Importantly, bioactive peptides generated by FC displayed an improved ability to induce in vitro arterial relaxation, compared with those obtained from NPD process. Therefore, this study provides innovative evidence regarding how the proteases used for production of whey hydrolysates can improve its biological effects, and discloses the use of high hydrostatic pressure combined with enzymatic hydrolysis as a promising alternative to produce hydrolysates with improved properties.

The administration of the α₂-adrenergic receptor agonist clonidine via intracerebroventricular route produces hypotension in pentobarbital-anesthetized rats and pressor responses in conscious normotensive rats. We explored the impact of different anesthetics on the central nervous system-dependent cardiovascular effects of clonidine. Normotensive male Wistar rats with guide cannulas previously implanted in the cerebroventricular system were anesthetized with pentobarbital or ketamine/xylazine and prepared for blood pressure measurement. The animals received intracerebroventricular injections of 10 μg clonidine or 0.6 μg dexmedetomidine, and the effects on the systolic, diastolic, mean arterial pressure, and heart rate were evaluated. The influence of 5 μg yohimbine, a selective α₂-adrenergic receptor antagonist, was also assessed. The i.c.v. microinjection of clonidine decreased all three components of systemic arterial pressure and the heart rate of pentobarbital-anesthetized rats. On the other hand, clonidine increased the blood pressure and generated a less intense reduction in the heart rate of ketamine/xylazine-anesthetized rats. The pressor and bradycardic effects of clonidine in ketamine/xylazine-anesthetized animals were reproduced by dexmedetomidine, a more selective α₂-adrenergic receptor agonist. Notably, the previous intracerebroventricular injection of yohimbine significantly inhibited the hypertensive effect of clonidine and dexmedetomidine. This study discloses that while normotensive rats anesthetized with pentobarbital show hypotensive responses, the stimulation of α₂-adrenergic receptors increases the blood pressure in rats under ketamine/xylazine-induced anesthesia, reproducing the effects seen in conscious normotensive animals. Recognizing the mechanisms involved in these differences may allow us to understand better the final effects of clonidine and other α₂-adrenergic receptor agonists in the central nervous system, contributing to the repurposing of these drugs.

INTRODUÇÃO: a crescente prevalência da infertilidade, associada às dificuldades da concepção natural que afeta um número significativo de casais em idade reprodutiva, tem reforçado a busca por técnicas de reprodução humana assistida na prática clínica. Assim, este estudo teve como objetivo analisar, por meio de uma revisão de literatura, o papel dos métodos de reprodução assistida diante das variáveis clínicas que causam a problemática da infertilidade. METODOLOGIA: as buscas foram realizadas nas bases de dados do PubMed, SciELO e na biblioteca digital da Universidade Positivo entre março e novembro de 2025, selecionando artigos publicados nos últimos 20 anos. Foram incluídos estudos que abordassem a fisiologia da fecundação, fatores femininos e masculinos da infertilidade e desempenho das técnicas de reprodução assistida. RESULTADOS E DISCUSSÃO: os resultados mostraram que a qualidade dos gametas, condições hormonais, idade avançada dos pacientes e as condições laboratoriais influenciam significativamente na escolha adequada da técnica e nas taxas de fertilização, implantação e gestação. Também foi possível identificar os fatores clínicos mais frequentes associados à infertilidade, como anovulação, alterações tubárias, endometriose e distúrbios espermáticos. Além disso, técnicas como inseminação intrauterina, fertilização in vitro e injeção intracitoplasmática de espermatozoide demonstram eficácia variável conforme o perfil clínico do casal e a qualidade embrionária. CONCLUSÃO: apesar das dificuldades que os casos de infertilidade trazem aos indivíduos, a reprodução assistida desempenha um papel essencial e eficaz no seu tratamento gestacional.