Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration-effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.

Semi-Mechanistic Pharmacokinetic Modeling of Lipid Core Nanocapsules: Understanding Quetiapine Plasma and Brain Disposition in a Neurodevelopmental Animal Model of Schizophrenia.

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naive and schizophrenic (SCZ-like) rats and developed a semimechanistic model to describe changes in both compartments following administration of the drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/ml) presented 166 ± 39 nm, low polydispersity, and high encapsulation (93.0% ± 1.4%). A model was built using experimental data from total and unbound plasma and unbound brain concentrations obtained by microdialysis after administration of single intravenous bolus dose of FQ or QLNC to naive and SCZ-like rats. A two-compartment model was identifiable both in blood and in brain with a bidirectional drug transport across the blood-brain barrier (CLin and CLout). SCZ-like rats' significant decrease in brain exposure with FQ (decrease in CLin) was reverted by QLNC, showing that nanocarriers govern quetiapine tissue distribution. Model simulations allowed exploring the potential of LNC for brain delivery. SIGNIFICANCE STATEMENT: A population approach was used to simultaneously model total and unbound plasma and unbound brain quetiapine concentrations allowing for quantification of the rate and extent of the drug's brain distribution following administration of both free drug in solution or as nanoformulation to naive and SCZ-like rats. The model-based approach is useful to better understand the possibilities and limitations of this nanoformulation for drug delivering to the brain, opening the opportunity to use this approach to improve SCZ-treatment-limited response rates.

Quetiapine lipid core nanocapsules restore prepulse inhibition deficits in a neurodevelopmental model of schizophrenia in male and female rats.

Lipid core nanocapsules (LNC) have been extensively studied as a new treatment strategy to improve therapeutic effects of antipsychotic drugs. We investigated the efficacy of quetiapine LNCs (QLNCs) on the poly(i:c) model of schizophrenia in both male and female rats using the pre-pulse inhibition of startle response (PPI) test paradigm after evaluating the outcomes of three different poly(i:c) doses administered to pregnant damns at GD15 on neurodevelopmental outcomes of maternal immune activation (MIA) in adult offspring. QTP solution was not capable of producing a reversal in the sensorimotor gating-disruptive effect caused by the prenatal poly(i:c) exposure. The same dose of QTP given as QLNCs significantly improved PPI-impairment. This is the first study reporting the restoration of the PPI deficits in a neurodevelopmental model of SCZ using LNCs. This is a promising delivery system strategy to improve antipsychotic effects contributing to the development of better SCZ pharmacological treatments.

Lactobacillus rhamnosusGG reduces hepatic fibrosis in a model of chronic liver disease in rats

BACKGROUND: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. AIM: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. METHODS: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 107 CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. RESULTS: The hepatic gene expression of Tlr4, Tnfα, IL-6, Tgfß, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. CONCLUSION: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats.

Lactobacillus rhamnosus GG reduces hepatic fibrosis in a model of chronic liver disease in rats / El Lactobacillus rhamnosus GG reduce la fibrosis hepática en un modelo de enfermedad hepática crónica en ratas

Background: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. Aim: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. Methods: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 107 CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. Results: The hepatic gene expression of Tlr4, Tnfα, IL-6, Tgfβ, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. Conclusion: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats (AU)

Introducción: la disbiosis intestinal es común en la enfermedad hepática crónica y puede inducir respuestas inflamatorias y mediar la deposición hepática de colágeno. Objetivo: evaluar el efecto del probiótico Lactobacillus rhamnosus GG (LGG) en el tratamiento de la fibrosis hepática en un modelo de enfermedad hepática colestásica en ratas. Métodos: se sometió a ratas Wistar macho adultas (n = 29) a ligadura del conducto biliar común (grupo BDL) o a manipulación del conducto biliar sin ligadura (grupo Ctrl). Dos semanas después, cada grupo se dividió aleatoriamente para recibir 1 ml de PBS (Ctrl y BDL) o PBS con 2,5 x 107 UFC de LGG (Ctrl-P y BDL-P) durante 14 días. Se aplicó la eutanasia 33 días después de la cirugía y se recogieron muestras de sangre y de tejido hepático. Resultados: las expresiones hepáticas de Tlr4, Tnfα, IL-6, Tgfβ, metaloproteinasa-2 y -9 fueron mayores en los grupos BDL. La reacción ductular evaluada por el inmunocontenido de citoqueratina 7 (CK7) y el contenido de colágeno se aumentó en los grupos BDL. Además, hubo un desequilibrio en las defensas antioxidantes (superóxido dismutasa y catalasa) y un aumento en el estrés oxidativo (sulfhidrilo) en los grupos BDL. El tratamiento con LGG redujo la expresión génica de IL-6, la deposición de colágeno y la reacción ductular en el hígado de los animales del grupo BDL-P. Conclusión: el tratamiento con LGG redujo la expresión génica de IL-6 en el hígado, la fibrosis hepática y la reacción ductular en un modelo de enfermedad hepática colestásica en ratas (AU)

Cell therapy in the treatment of bronchiolitis obliterans in a murine model.

OBJECTIVE: To evaluate the importance of stem cells derived from adipose tissue in reducing graft inflammation in a murine model of allogeneic heterotopic tracheal transplant. METHODS: We performed a heterotopic tracheal allografting in dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells derived from adipose tissue. The animals were divided into two groups according to the time of sacrifice: T7 and T21. We also carried out histological analysis and digital morphometry. RESULTS: The T7 animals treated with cell therapy had median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The treated T21 subjects had median obstructed graft area of 0.25 versus 0 in controls (p = 0.041). CONCLUSION: The systemically injected cell therapy in experimental murine model of bronchiolitis obliterans did not reduce the severity of the allograft inflammation in a statistically significant way in seven days; Conversely, in 21 days, it increased the allograft inflammatory process.

Cell therapy in the treatment of bronchiolitis obliterans in a murine model / Terapia celular no tratamento da bronquiolite obliterante em modelo murino

OBJECTIVE: To evaluate the importance of stem cells derived from adipose tissue in reducing graft inflammation in a murine model of allogeneic heterotopic tracheal transplant. METHODS:We performed a heterotopic tracheal allografting in dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells derived from adipose tissue. The animals were divided into two groups according to the time of sacrifice: T7 and T21. We also carried out histological analysis and digital morphometry. RESULTS:The T7 animals treated with cell therapy had median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The treated T21 subjects had median obstructed graft area of 0.25 versus 0 in controls (p = 0.041). CONCLUSION:The systemically injected cell therapy in experimental murine model of bronchiolitis obliterans did not reduce the severity of the allograft inflammation in a statistically significant way in seven days; Conversely, in 21 days, it increased the allograft inflammatory process.

OBJETIVO: Avaliar a importância das células-tronco derivadas de tecido adiposo na redução do processo inflamatório no enxerto em modelo murino de transplante traqueal heterotópico alogênico. MÉTODOS:Foi realizado alotransplante traqueal heterotópico em bolsa dorsal subcutânea e injetado 5x105 células-tronco mesenquimais, derivadas de tecido adiposo, sistemicamente. Os animais foram distribuídos em dois grupos, conforme o tempo de sacrifício: T7 e T21. Procedida a análise em HE e morfometria digital. RESULTADOS:Os T7 tratados com terapia celular apresentaram mediana de área obstruída do enxerto de 0 contra 0,54 dos controles (p=0,635). Os T21 tratados apresentaram mediana de área obstruída da luz do enxerto de 0,25 nos tratados e 0 nos controles (p=0,041). CONCLUSÃO: A terapia celular injetada sistemicamente em modelo experimental murino de bronquiolite obliterante não reduziu a gravidade do processo inflamatório no aloenxerto de forma estatisticamente significativa em sete dias; de modo contrário, em 21 dias, aumentou o processo inflamatório no aloenxerto.

Experimental histopathological study on retinal and renal cellular response to intravitreous antiangiogenic drugs.

AIM: To evaluate histopathological retinal and renal response after one single dose of intravitreous injection of antiangiogenic drugs ranibizumab and bevacizumab in rats. METHODS: Experimental study in 60d of life adults Wistar rats. Ten animals were included. Group 1 included 5 animals that were injected with 1 µL ranibizumab 1.25 mg in the right eye and with 1 µL of balanced salt solution (BSS) in the left eye, as control; Group 2 included 5 animals that were injected with 1 µL of bevacizumab in the right eye and with 1 µL of BSS in the fellow eye. All injections were performed with Hamilton syringes. After 15d of the interventions, all animals were sacrificed in CO2 chamber. Both eyes were enucleated and one kidney was removed, fixed and embedded in paraffin for histopathological analysis by optic microscopy. For statistical purposes the initial expected abnormal histopathological responses were defined as 0%. RESULTS: Atypical histopathological retinal response was detected in 2 eyes injected with ranibizumab (40%) as well as in 2 control eyes in group 1. Same was detected in 1 eye injected with bevacizumab (20%) as well as in 1 control eye, in group 2. The noted atypical findings were lymphocytes and eosinophils in the vitreous posterior cavity and mild retinal inflammatory reaction with ganglion cell layer edema but without clinical significance. No atypical histopathological renal response was detected. CONCLUSION: Unexpected atypical histopathological retinal response without clinical significance was observed in 3 eyes injected with antiangiogenic drugs (2 in group 1 and 1 in group 2) as well as in 3 control eyes (2 in group 1 and 1 in group 2). No atypical renal response was detected suggesting no extra ocular involvement of the intravitreous injected antiangiogenic drugs.

Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis?

AIM: To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis. METHODS: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 × 10(6) MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling assay. RESULTS: Intravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with intraperitoneal transplantation (P = 0.006). An increase in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC infusion, suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation (P = 0.027). CONCLUSION: Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.

Oxidative stress evaluation of ischemia and reperfusion in kidneys under various degrees of hypothermia in rats

PURPOSE:To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS:Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.

Oxidative stress evaluation of ischemia and reperfusion in kidneys under various degrees of hypothermia in rats.

PURPOSE: To design an animal model of ischemia-reperfusion (I/R) in kidneys and evaluate the role that predetermined ranges of local hypothermia plays on markers of stress-oxydative as well as on histologic sections. METHODS: Twenty eight male rats Wistar, under general anesthesia, undergone right nephrectomy (G0, control group) followed by left kidney ischemia during 40 min. Four temperatures groups were designed, with seven animals randomized for each group: normothermic (G1, ±37ºC), mild hypothermia (G2, 26ºC), moderate hypothermia (G3, 15ºC) and deep hypothermia (G4, 4ºC). Left kidney temperature was assessed with an intraparenchymal probe. Left nephrectomy was performed after 240 min of reperfusion. After I/R a blood sample was obtained for f2-IP. Half of each kidney was sent to pathological evaluation and half to analyze CAT, SOD, TBARS, NO3, NO2. RESULTS: Histopathology showed that all kidneys under I/R were significantly more injured than the G0 (p<0.001). TBARS had increased levels in all I/R groups compared with the G0 (p<0.001). CAT had a significant difference (p<0.03) between G1 and G4. Finally, no difference was found on SOD, NO3, NO2 nor on f2-IP. CONCLUSION: This model of I/R was efficient to produce oxidative-stress in the kidney, showing that 4ºC offered significant decrease in free radicals production, although tissue protection was not observed.

Intraperitoneal implant of recombinant encapsulated cells overexpressing alpha-L-iduronidase partially corrects visceral pathology in mucopolysaccharidosis type I mice.

BACKGROUND AIMS: Mucopolysaccharidosis type I (MPS I) is characterized by deficiency of the enzyme alpha-L-iduronidase (IDUA) and storage of glycosaminoglycans (GAG) in several tissues. Current available treatments present limitations, thus the search for new therapies. Encapsulation of recombinant cells within polymeric structures combines gene and cell therapy and is a promising approach for treating MPS I. METHODS: We produced alginate microcapsules containing baby hamster kidney (BHK) cells overexpressing IDUA and implanted these capsules in the peritoneum of MPS I mice. RESULTS: An increase in serum and tissue IDUA activity was observed at early time-points, as well as a reduction in GAG storage; however, correction in the long term was only partially achieved, with a drop in the IDUA activity being observed a few weeks after the implant. Analysis of the capsules obtained from the peritoneum revealed inflammation and a pericapsular fibrotic process, which could be responsible for the reduction in IDUA levels observed in the long term. In addition, treated mice developed antibodies against the enzyme. CONCLUSIONS: The results suggest that the encapsulation process is effective in the short term but improvements must be achieved in order to reduce the immune response and reach a stable correction.

Histological analysis of cobalt-chromium stents with and without Camouflage® polymer coating: experimental porcine carotid artery model.

This study evaluated the arterial response to cobalt-chromium stents with and without polymer coating (Camouflage®, Hemoteq AG, Wuerselen, Germany) implanted in pigs. Cobalt-chromium balloon-expandable stents (4 × 16 mm) were implanted in the common carotid arteries of nine pigs. Histological analysis of endothelialization, inflammation and injury was performed one month later. All stents were successfully deployed, and all but one animal survived the 30 study days. All arteries were patent. Endothelialization was nearly complete in most sections of all carotid stents in both groups. There were mild inflammatory infiltrate and mild-to-moderate injury, which were associated with the stent shafts and not significantly different between groups. Our findings suggest that, in porcine carotid arteries, the histological response to balloon-expandable cobalt-chromium stents coated with polymer (Camouflage®, Hemoteq AG) is similar to the response to non-coated cobalt-chromium stents.

O modelo experimental de carcinogênese gástrica induzido por n-methyl-n-nitrosourea em ratos F344 e camundongos C3H é válido para os ratos Wistar? / Experimental model of gastric carcinogenesis with N-methyl-N-nitrosourea for F344 rats and C3H mices is valid for Wistar rats?

INTRODUÇÃO: O N-metil-N-nitrosourea (MNU) tem ação cancerígena direta, induzindo tumores em várias espécies em uma variedade de órgãos, incluindo o estômago de ratos. Tratamento do MNU na água de beber por 25-42 semanas, seletivamente, induz carcinoma gástrico glandular de ratos F344 e camundongos C3H. OBJETIVO: Estabelecer um modelo experimental para indução seletiva de câncer no estômago glandular de ratos Wistar com MNU. MÉTODOS: Um total de 48 ratos Wistar machos com oito semanas, foram utilizados no presente estudo. MNU (Sigma-Aldrich) foi dissolvido em DMSO e liberada água potável ad libitum por um período variando de 16 a 70 semanas. Após 16 semanas, quatro ratos foram selecionados aleatoriamente e mortos. Depois, de seis em seis semanas, quatro animais também foram mortos até 70 semanas. RESULTADOS: A taxa de sobrevivência foi superior a 90 por cento. Ocorreu a indução de dois adenocarcinomas, um carcinoma espinocelular e um sarcoma. A incidência de adenocarcinoma gástrico foi de 4,5 por cento (0,5 a 15). CONCLUSÕES: O modelo experimental de carcinogênese gástrica em ratos Wistar, utilizando MNU dissolvido na água, não mostrou viabilidade prática neste estudo, devido à baixa taxa de adenocarcinoma gástrico que ocorreu.

BACKGROUND: The N-methyl-N-nitrosourea (MNU) is a direct acting carcinogen, inducing tumors in several species in a variety of organs, including stomach of rats. Treatment of MNU in the drinking water for 25-42 weeks selectively induced glandular gastric carcinoma in F344 rats and C3H mice. AIM: To establish an experimental model for selective MNU induction of glandular stomach cancer in Wistar rats. METHODS: A total of 48 males eight-week-old Wistar rats were used in the present study. MNU (Sigma-Aldrich) was dissolved in DMSO and provided as the drinking water ad libitum for a period ranging from 16 to 70 weeks. After 16 weeks, four rats were randomly selected and killed. After every six weeks four animals were killed until 70 weeks. RESULTS: Survival rate was higher than 90 percent. It had the induction of two adenocarcinomas, one squamous cell carcinoma and one sarcoma. The incidence of gastric adenocarcinoma was 4.5 percent (0.5 to 15). CONCLUSIONS: The experimental model of gastric carcinogenesis in Wistar rats, using MNU dissolved in water, showed not practice viability in this study due to the low rate of gastric adenocarcinoma.

Experimental model of the formation of pelvic adhesions by videolaparoscopic in female rabbits.

PURPOSE: To verify the frequency of postsurgical pelvic adhesion formation in an experimental animal model using videolaparoscopy. METHODS: Experimental study in a sample of 11 non-pregnant female rabbits, aged 5 to 7 months. After general anesthesia, access to the abdominal cavity was performed by an open puncture technique, with 10mm optics, placing two other 5 mm trochars under direct visualization, in the iliac fossae. Then a fragment of peritoneum was resected, followed by electrocauterization. In 21 days, the videolaparoscopy was repeated, and adhesion formation and score was looked at, with biopsies at the surgical site. RESULTS: 54 % of adhesion formation was observed, and the median score of adhesions was 6 (minimum of 3 and maximum of 10), all of them found in the bladder and the anterior abdominal wall. CONCLUSION: The method used presents a high frequency of intra-abdominal adhesion formation.

Anesthetic protocol for videolaparoscopic surgery in rabbits.

PURPOSE: To describe the anesthetic protocol and the intubation technique without visualizing the trachea in rabbits, in order to enable the videolaparoscopic surgical procedure. METHODS: The experiment was performed on 33 female rabbits (Oryctolagus cuniculus), aged from 5 to 7 months. It consisted of general anesthesia and endotracheal intubation by manual palpation of the trachea of the rabbits, without using the laryngoscope, orally, for later videolaparoscopic surgical access to the abdominal cavity. RESULTS: The mean values and standard deviation of vital parameters of the animals were 223.8 + or - 15.61 beats per minute for heart rate; 35 + or - 9 movements per minute for respiratory rate; 96.94 + or - 0.99% of oxymetry and 42.82 + or - 4.02 mmHg for capnometry; 16.7 + or - 4.3 minutes for pneumoperitoneum (duration of surgery) and 1 hour and 14 + or - 8.52 minutes for time of observation (from induction to recovery from anesthesia). All animals were intubated in at most three attempts. No animals were lost after the introduction of this anesthetic technique. CONCLUSION: This protocol proved adequate, safe and easy to perform, on rabbits submitted to videolaparoscopic surgery.

Experimental model of the formation of pelvic adhesions by videolaparoscopic in female rabbits / Modelo experimental de formação de aderências pélvicas por videolaparoscopia em coelhas

PURPOSE: To verify the frequency of postsurgical pelvic adhesion formation in an experimental animal model using videolaparoscopy. METHODS: Experimental study in a sample of 11 non-pregnant female rabbits, aged 5 to 7 months. After general anesthesia, access to the abdominal cavity was performed by an open puncture technique, with 10mm optics, placing two other 5 mm trochars under direct visualization, in the iliac fossae. Then a fragment of peritoneum was resected, followed by electrocauterization. In 21 days, the videolaparoscopy was repeated, and adhesion formation and score was looked at, with biopsies at the surgical site. RESULTS: 54 percent of adhesion formation was observed, and the median score of adhesions was 6 (minimum of 3 and maximum of 10), all of them found in the bladder and the anterior abdominal wall. CONCLUSION: The method used presents a high frequency of intra-abdominal adhesion formation.

OBJETIVO: Verificar a freqüência da formação de aderências pélvicas pós-cirúrgicas, em um modelo experimental animal, por videolaparoscopia. MÉTODOS: Estudo experimental, em uma amostra de 11 coelhas, não prenhas, com idade entre cinco e sete meses. Após anestesia geral, o acesso da cavidade abdominal foi efetuado por técnica de punção aberta, com óptica de 10 mm, colocando-se outros dois trocateres de 5 mm, sob visão direta, nas fossas ilíacas. Realizou-se, então, ressecção de fragmento de peritônio, seguida de cauterização com eletrocautério. Em 21 dias, foi repetida a videolaparoscopia, verificando-se a formação e escore de aderências e realizando-se biópsias do local da cirurgia. RESULTADOS: Observou-se 54,5 por cento de formação de aderências, sendo o escore total mediano de aderências seis (mínimo de três e máximo de 10), todas encontradas na bexiga e na parede abdominal anterior. CONCLUSÃO: O procedimento utilizado apresentou alta freqüência de formação de aderências intra-abdominais.

Anesthetic protocol for videolaparoscopic surgery in rabbits / Protocolo anestésico para cirurgia videolaparoscópica em coelhos

PURPOSE: To describe the anesthetic protocol and the intubation technique without visualizing the trachea in rabbits, in order to enable the videolaparoscopic surgical procedure. METHODS: The experiment was performed on 33 female rabbits (Oryctolagus cuniculus), aged from 5 to 7 months. It consisted of general anesthesia and endotracheal intubation by manual palpation of the trachea of the rabbits, without using the laryngoscope, orally, for later videolaparoscopic surgical access to the abdominal cavity. RESULTS: The mean values and standard deviation of vital parameters of the animals were 223.8±15.61 beats per minute for heart rate; 35±9 movements per minute for respiratory rate; 96.94±0.99 percent of oxymetry and 42.82±4.02 mmHg for capnometry; 16.7±4.3 minutes for pneumoperitoneum (duration of surgery) and 1 hour and 14±8.52 minutes for time of observation (from induction to recovery from anesthesia). All animals were intubated in at most three attempts. No animals were lost after the introduction of this anesthetic technique. CONCLUSION: This protocol proved adequate, safe and easy to perform, on rabbits submitted to videolaparoscopic surgery.

OBJETIVO: Descrever o protocolo anestésico e a técnica de intubação sem visualização da traqueia em coelhos, para viabilização de procedimento cirúrgico videolaparoscópico. MÉTODOS: O experimento foi realizado em 33 coelhas (Oryctolagus cuniculus), com idade entre 5 e 7 meses. Consistiu de anestesia geral e intubação endotraqueal por meio de palpação manual da traquéia das coelhas, sem o uso de laringoscópio, pela via oral, para posterior acesso cirúrgico videolaparoscópico da cavidade abdominal. RESULTADOS: Os valores médios e desvio padrão dos parâmetros vitais dos animais foram de 223,8±15,61 batimentos por minuto para freqüência cardíaca; 35±9 movimentos por minuto para frequência respiratória; 96,94±0,99 por cento de oximetria e 42,82±4,02 mmHg para capnometria; 16,7±4,3 minutos para o pneumoperitônio (tempo de cirurgia) e 1 hora e 14±8,52 minutos para o tempo de observação (desde a indução até a recuperação anestésica). Todos os animais foram intubados em, no máximo, três tentativas. Não houve perda de animais após a introdução dessa técnica anestésica. CONCLUSÃO: Este protocolo mostrou-se adequado, seguro e de fácil realização, para a aplicação em coelhos submetidos à cirurgia videolaparoscópica.

Considerações técnicas no treinamento de anastomoses microvasculares em laboratório de microcirurgia: [revisão] / Microvascular anastomosis in the laboratory - technical considerations: [review]

Anastomoses microvasculares são um procedimento cirúrgico complexo e um armamento essencial utilizado em diversas sub especialidades. A primeira etapa de treinamento em anastomose microcirúrgica deve ser sempre no laboratório. Este artigo é uma revisão sobre os fatores envolvidos no para a realização de anastomoses microvasculares. Instrumental cirúrgico, microscópio, estrutura do laboratório, procedimentos cirúrgicos, questões éticas e parâmetros radiológicos e histológicos são discutidos.