Acetate Causes Alcohol Hangover Headache in Rats

Background: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion: Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction

Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach

Persistent infection with high-risk human papillomavirus (HPV) types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs)-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c.) prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease

Endoprótese revestida de jugular preservada de bovino: estudo comparativo da resposta tecidual em aorta torácica descendente e veia cava inferior de suínos

OBJETIVO: Avaliar e comparar a resposta tecidual de uma endoprótese biosintetica implantada na aorta torácica descendente e veia cava inferior de suínos. MÉTODO: Foi implantada uma endoprótese auto-expansível composta de aço inoxidável, revestida por veia jugular de bovino, processada pelo método L-hydro, com auxilio de uma bainha de liberação Taheri-Leonhardt (Flórida, EUA) na aorta torácica descendente, e a veia cava infra-renal de 10 suínos. Sessenta dias após, as endopróteses foram retiradas e analisadas sob o ponto de vista macro e microscópicos. Foram observados: perviedade, grau de incorporação a parede do vaso, tipo de reação inflamatória, e local de maior resposta, tanto em relação a camada do vaso quanto ao local de contato com o anel de aço RESULTADOS: Todas as endopróteses encontravam-se pérvias, e incorporadas à parede. No setor venoso, seis apresentaram traves fibrosas em sua luz, e quatro apresentaram fibrose perivascular. No setor arterial somente uma prótese apresentou discreta estenose, sem fibrose perivascular. A reação inflamatória crônica tipo corpo estranho ocorreu em 100% das peças, a camada média foi a mais acometida no setor venoso, enquanto a íntima foi mais constante na artéria, o grau de incorporação foi mais firme na veia em comparação a artéria. A reação tecidual mostrou maior tendência nas áreas em intimo contato com o anel de aço (intra-anelar), mais intensa na artéria do que na veia. CONCLUSÃO: A prótese apresentou baixa trombogenicidade em ambos os sistemas, houve maior reação tecidual e baixa biocompatibilidade no setor venoso