Depth of invasion of oral squamous cell carcinoma in Nos2-knockout mice correlated to alterations in systemic inflammatory markers following 4NQO treatment.

BACKGROUND: Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. METHODS: A 50 µg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. RESULTS: Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. CONCLUSION: Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

Alloxan as a better option than streptozotocin for studies involving painful diabetic neuropathy.

Previous data indicate that the diabetogenic substance streptozotocin might act in nociceptive neurons changing the sensory signal, regardless of hyperglycemia. In the present article the effects of streptozotocin were compared with another diabetogenic drug, alloxan, for diabetes induction in rats. A possible direct effect of these drugs was tested by means of in vivo experiments and in vitro assays using cultured primary nociceptive neurons. Streptozotocin (17.5 and 35 mg/kg), alloxan (15 and 30 mg/kg) or vehicle were injected in adult male rats and the animal groups were separated according to glycemic levels. Body mass, glycemia and paw mechanical sensitivity were evaluated for 5 weeks. Streptozotocin caused an increase in mechanical sensitivity in both hyperglycemic and normoglycemic rats, while alloxan induced mechanical sensitization only in hyperglycemic animals. Injection of both substances induced local inflammation at rat paws; however, only streptozotocin caused significant mechanical sensitization when injected near to sensory neurons at the dorsal root ganglia. Also, streptozotocin treatment induced a reduction in intracellular calcium levels and inhibited capsaicin induced calcium transients and membrane depolarization. Alloxan did not affect calcium levels or membrane potential in primary nociceptive neurons. These findings suggest that alloxan might be a better option for animal studies regarding painful diabetic neuropathy as streptozotocin directly affects nociceptive neurons, probably by modulating TRPV1 channel activation.

Hyperglycemia induces mechanical hyperalgesia and depolarization of the resting membrane potential of primary nociceptive neurons: Role of ATP-sensitive potassium channels.

Cumulating data suggests that ion channel alterations in nociceptive neurons might be involved in the development of diabetic painful neuropathy. In the present study we investigated the involvement of ATP-sensitive potassium (K+ATP) channels in the acute effect of high glucose solution in vitro and in vivo. High glucose concentrations depolarized cultured nociceptive neurons and depolarization was blocked by the K+ATP opener, diazoxide or by insulin. Glucose injection at the rat dorsal root ganglia (L5) resulted in acute mechanical hyperalgesia that was blocked by diazoxide. Mannitol injection indicates that osmolarity changes are not responsible for glucose effect. Therefore, this study suggests that K+ATP channels expressed in peripheral sensory neurons might be involved in the development of diabetic painful neuropathy. Since sulfonylureas, that act by blocking K+ATP are used for diabetes treatment, it is important to evaluate the possible side effects of such drugs at primary sensory neurons.

Vulnerabilidade de adolescentes em pesquisa e prática clínica / Vulnerability of adolescents in clinical research and practice / La vulnerabilidad de los adolescentes en la investigación y en la práctica clínica

Resumo Os adolescentes são considerados grupo vulnerável e exposto a diferentes ameaças à saúde, tornando-se necessária a discussão sobre aspectos éticos relacionados a sua participação em pesquisa e prática clínica. Por meio de revisão integrativa de literatura foram selecionados estudos que abordaram aspectos bioéticos relacionados à vulnerabilidade de adolescentes nos últimos quinze anos. Nove artigos atenderam aos critérios pré-estabelecidos para o estudo e foram agrupados em três categorias: 1) trabalhos que pontuaram a compreensão psicológica e cognitiva do adolescente ao participar de pesquisa científica; 2) estudos que enfatizaram aspectos relacionados a decisões médicas; e 3) estudos que abordaram a temática da sexualidade na adolescência. Após análise dos estudos selecionados, verificou-se que não é possível chegar a consenso válido para todas as situações que envolvem adolescentes em pesquisa e prática clínica.

Abstract Adolescents are considered vulnerable and exposed to different threats to health group, making it necessary discussion about ethical aspects related to their participation in research and clinical practice. The employed methodology was an integrative literature review and it was selected studies that approached the subject "bioethical matters related to vulnerability of adolescents" within the last fifteen years. Nine articles included the pre-established criteria to the study, grouped into three categories: 1) works that mentioned the psychological-cognitive comprehension of adolescent to participate in scientific research; 2) works emphasizing aspects related to medical decisions; and 3) studies approaching the issue of sexuality in adolescence. The analysis of selected studies found out it is not possible to reach a valid consensus to all situations involving adolescents in research and clinical practice.

Resumen Los adolescentes son considerados como grupo vulnerable y expuesto a diferentes amenazas en el ámbito de la salud, por lo cual es necesario que exista un debate sobre los aspectos éticos relacionados con su participación en la investigación y en la práctica clínica. Por medio de una revisión integradora de la literatura, se seleccionaron estudios que abordaban aspectos bioéticos relacionados con la vulnerabilidad de los adolescentes en los últimos quince años. Nueve artículos contemplaban los criterios preestablecidos para el estudio y se agruparon en tres categorías: 1) trabajos que contemplaban la comprensión psicológica y cognitiva del adolescente al participar en la investigación científica; 2) estudios que enfatizaban los aspectos relacionados con las decisiones médicas; y 3) estudios que abordaban la sexualidad en la adolescencia. Después del análisis de los estudios seleccionados, se verificó que no es posible llegar a un consenso válido para todas las situaciones que involucran adolescentes en la investigación y en la práctica clínica.