During surgery, both anesthesia and tissue damage cause physiological stress responses in the body. The hypothalamic-pituitary-adrenal (HPA) axis is activated with increased levels of glucocorticoids. After surgical procedures the stress response may be a cause of postoperative morbidity and pre-emptive analgesic treatment can attenuate the stress response during the postoperative period. In laboratory animals, buprenorphine is a commonly used analgesic. Subcutaneous (s.c.) administration of buprenorphine is most common, but oral administration would be preferable in many cases, enabling administration without any handling of the rat. In this thesis we studied the surgical stress response in laboratory rats during surgery and in the postoperative period, and its modulation by s.c. injection and oral voluntary ingestion (VI) of buprenorphine. Corticosterone levels and the clinical parameters body weight, water intake and behavior were observed. The concentration of buprenorphine in plasma was measured as well as stock-related differences in postoperative recovery. During surgery and anesthesia there was a higher corticosterone release during a more severe surgery and corticosterone levels were reduced more effectively after buprenorphine treatment than after lidocaine treatment. Buprenorphine treatment, independent of the route of administration, led to better postoperative recovery in body weight and water intake compared to local anesthetics. VI of buprenorphine resulted in a suppression of plasma corticosterone levels compared to s.c. buprenorphine treatment and treatment with local anesthetics during the first day after surgical catheterization. The corticosterone levels of all buprenorphine treated groups had, by the second postoperative day, reverted to the normal diurnal rhythm of corticosterone secretion. Buprenorphine treatment increased locomotor activity in non-operated rats only. The effect of buprenorphine in operated rats could not be detected via the monitoring of locomotor activity or the time spent resting in the present study. Treatment with buprenorphine by VI has similar effects on postoperative plasma corticosterone levels in both Wistar and Sprague-Dawley rats. VI of buprenorphine resulted in a buprenorphine concentration in plasma at least as high as by s.c. treatment. Thus, administration by VI of buprenorphine appears to be an effective stress-reducing method for administrating postoperative analgesia to laboratory rats.

Orientador: Gilson Helio Toniollo / Banca: André Lacerda de Oliveira Abreu / Banca: Juan Carlos Duque Moreno / Banca: Bruno Watanabe Minto / Banca: Andrigo Barboza de Nardi / Resumo: Os procedimentos cirúrgicos contraceptivos possuem como finalidades evitar ou tratar enfermidades do trato reprodutor e promover controle populacional de animais de companhia. Contudo, são traumáticos e implicam em dor pós-operatória, fazendo-se necessário o desenvolvimento de técnicas menos invasivas. O presente estudo objetivou desenvolver e descrever a técnica de ovário-histerectomia (OHE) laparoscópica total transvaginal (total-NOTES) em cadelas e compará-la quanto à dor e o estresse pós-operatórios, parâmetros intra-operatórios e complicações às abordagens vídeo-assistida com único portal (grupo SPVA) e convencional (grupo OPEN). A técnica de OHE por total-NOTES demonstrou-se factível em cadelas. Os grupos NOTES e SPVA apresentaram menores tempo cirúrgico total (25,7 ± 6,8 e 23,1 ± 4,0 minutos, respectivamente) em comparação ao grupo OPEN (34,0 ± 6,4 minutos e 5,3 ± 1,3, respectivamente). As cadelas submetidas a OHE pelas técnicas de total- NOTES e vídeo-assistida com único portal apresentaram menores, dor pós-operatória pela técnica de escala numérica visual (NRS) em todos os momentos de avaliação e cortisol sérico em dois momentos de avaliação em relação aos animais operados pela técnica convencional. Concluiu-se que OHE por total-NOTES é factível em cadelas, tendo apresentado resultados semelhantes à técnica vídeo-assistida com único portal e melhor tempo cirúrgico e menores, dor e estresse pós-operatório em comparação com a abordagem convencional. A técnica de total-NOTES apresentou a vantagem de não requerer cuidados especiais com a ferida cirúrgica / Abstract: The contraceptive surgical procedures aim to avoid or treat reproductive tract disorders and to control the populations of companion animals. However, surgery may lead to surgical trauma and postoperative pain. Thus, the development of new less invasive techniques of surgical contraception is desired. The current study aimed to develop and compare the technique of total transvaginal laparoscopic (total-NOTES) ovariohysterectomy (OHE) to the single-port video-assisted (SPVA group) and conventional (OPEN group) techniques in bitches for postsurgical pain and stress, intra-surgical parameters and complications of ovariohysterectomy performed by the pure-NOTES (NOTES group). The pure-NOTES OHE technique was feasible in bitches. The groups NOTES and SPVA presented shorter overall surgical time (25,7 ± 6,8 and 23,1 ± 4,0 minutes, respectively) and less intra-operative hemorrhage score (1,9 ± 1,8 and 1,1 ± 0,9, respectively) in comparison to the OPEN group (34,0 ± 6,4 minutes and 5,3 ± 1,3, respectively). Bitches submitted to pure- NOTES and single-port video-assisted techniques of OHE presented less pain numerical rating score (NRS) in all time points and less surgical stress by serum cortisol measurement in two moments of evaluation than the animals spayed using the conventional technique. In conclusion, the total-NOTES OHE is feasible in bitches. Both total-NOTEs and single-port video-assisted techniques required lower surgical time and resulted in less postoperative pain and stress in comparison to the conventional approach. The total-NOTES technique required no special care of the surgical wound / Doutor

Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.

Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.

Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.

Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-05-28Bitstream added on 2014-06-13T20:41:20Z : No. of bitstreams: 1 silva_mam_dr_jabo.pdf: 6505610 bytes, checksum: 2358ddbd0b8b030262dc564ebf47e914 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os procedimentos cirúrgicos contraceptivos possuem como finalidades evitar ou tratar enfermidades do trato reprodutor e promover controle populacional de animais de companhia. Contudo, são traumáticos e implicam em dor pós-operatória, fazendo-se necessário o desenvolvimento de técnicas menos invasivas. O presente estudo objetivou desenvolver e descrever a técnica de ovário-histerectomia (OHE) laparoscópica total transvaginal (total-NOTES) em cadelas e compará-la quanto à dor e o estresse pós-operatórios, parâmetros intra-operatórios e complicações às abordagens vídeo-assistida com único portal (grupo SPVA) e convencional (grupo OPEN). A técnica de OHE por total-NOTES demonstrou-se factível em cadelas. Os grupos NOTES e SPVA apresentaram menores tempo cirúrgico total (25,7 ± 6,8 e 23,1 ± 4,0 minutos, respectivamente) em comparação ao grupo OPEN (34,0 ± 6,4 minutos e 5,3 ± 1,3, respectivamente). As cadelas submetidas a OHE pelas técnicas de total- NOTES e vídeo-assistida com único portal apresentaram menores, dor pós-operatória pela técnica de escala numérica visual (NRS) em todos os momentos de avaliação e cortisol sérico em dois momentos de avaliação em relação aos animais operados pela técnica convencional. Concluiu-se que OHE por total-NOTES é factível em cadelas, tendo apresentado resultados semelhantes à técnica vídeo-assistida com único portal e melhor tempo cirúrgico e menores, dor e estresse pós-operatório em comparação com a abordagem convencional. A técnica de total-NOTES apresentou a vantagem de não requerer cuidados especiais com a ferida cirúrgica / The contraceptive surgical procedures aim to avoid or treat reproductive tract disorders and to control the populations of companion animals. However, surgery may lead to surgical trauma and postoperative pain. Thus, the development of new less invasive techniques of surgical contraception is desired. The current study aimed to develop and compare the technique of total transvaginal laparoscopic (total-NOTES) ovariohysterectomy (OHE) to the single-port video-assisted (SPVA group) and conventional (OPEN group) techniques in bitches for postsurgical pain and stress, intra-surgical parameters and complications of ovariohysterectomy performed by the pure-NOTES (NOTES group). The pure-NOTES OHE technique was feasible in bitches. The groups NOTES and SPVA presented shorter overall surgical time (25,7 ± 6,8 and 23,1 ± 4,0 minutes, respectively) and less intra-operative hemorrhage score (1,9 ± 1,8 and 1,1 ± 0,9, respectively) in comparison to the OPEN group (34,0 ± 6,4 minutes and 5,3 ± 1,3, respectively). Bitches submitted to pure- NOTES and single-port video-assisted techniques of OHE presented less pain numerical rating score (NRS) in all time points and less surgical stress by serum cortisol measurement in two moments of evaluation than the animals spayed using the conventional technique. In conclusion, the total-NOTES OHE is feasible in bitches. Both total-NOTEs and single-port video-assisted techniques required lower surgical time and resulted in less postoperative pain and stress in comparison to the conventional approach. The total-NOTES technique required no special care of the surgical wound

Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.

Solid malignancies in cancer patients require surgical intervention; however, surgery has been shown to promote the metastatic potential of tumour cells. Surgery-induced impairment of adaptive immunity is poorly understood, thus, our aim is to characterize the impact of surgery on tumour antigen-specific cytotoxic T lymphocyte function. To generate anti-tumour immunity, we adopted a C57/B6 model of B16 melanoma immunized with intramuscular (IM) AdhDCT, an adenovirus expressing the melanoma-associated antigen human dopachrome tautomerase (hDCT). Surgical stress was induced by left abdominal nephrectomy. We found that surgery reduces overall survival in AdhDCT-immunized mice, whereas those that did not undergo surgery were cured of their tumours. Surgical stress also decreases both the proportion and absolute spleen numbers of DCT-specific IFN-gamma+ CD8+ T-cells by over 2-fold. We have shown that perioperative suppression of antigen-specific T-cells can lead to increased tumour burden in a murine melanoma model.

Background: Surgical stress during resection surgery for colon cancer has previously been shown to be associated with adverse postoperative outcomes. Statin and beta-blocker treatment have been shown to lower postoperative complications and mortality, and been hypothesized to reduce the surgical stress response, although this correlation has not been studied clinically. Aim: To investigate whether perioperative beta-blocker and/or statin treatment reduce the postoperative C-reactive protein (CRP) response. Material and methods: All patients who underwent right sided hemicolectomy or sigmoid resection for cancer at Örebro University Hospital during 2012-2017 were included in this study. Initially, any treatment with statins, beta-blockers or both were compared to those with no treatment. After initial analyses, four treatment groups were compared regarding postoperative CRP response, namely no treatment, statin, beta-blocker, and combination treatment. Comparisons regarding complications were also performed for the four groups. Results: A total of 260 patients were included in this study. The no treatment group had a lower peak postoperative CRP than the treatment group, when comparing any treatment versus no treatment. There were no significant differences in postoperative CRP within the four treatment groups. There was no significant difference in complication rate between any of the treatment groups when compared to no treatment. Conclusion: Treatment with statin or beta-blocker therapy does not reduce the postoperative CRP response. A combination of both treatments demonstrated a trend towards a reduction regarding postoperative CRP response compared with the two treatments individually assessed. Larger studies are needed to verify the results of this study.