RESUMO
The aim of the present study was to investigate the impact of intravenous administration of newly fabricated nanocontainers (NCs) on the last third of pregnancy in rats. Fifteen pregnant 3-month-old Wistar rats were separated into 3 groups. On the 15th and 17th day of pregnancy all animals received an intravenous administration of 1â¯ml of 15â¯mg of NCs (Group A), 1â¯ml of 5â¯mgâ¯NCs (Group B) while Control group received 1â¯ml of 0.9% NaCl. On the 14th and 17th of pregnancy ultrasonography was performed and the parameters evaluated were the width of placenta, the length and width of the embryonic sac, the foetus length and the heart rate. On parturition the number of pups per dam was evaluated. Half of the pups were euthanised the day after parturition and their liver and kidney was histologically evaluated and for the rest of the pups the body growth curve was evaluated until the age of 14 week. At the end of the 14th week the remaining pups were euthanised and their liver and kidney was histologically evaluated. At weaning the dams were euthanised and their liver and kidney was histologically evaluated. Ultrasonography: Baseline measurements of the width of placenta, the length and width of embryonic sac, the foetus length and the heart rate on the 14th day of pregnancy, revealed no statistical significant differences between groups. Comparison of the same values on the 17th day of pregnancy after 2 intravenous administrations of NCs showed no statistical significant effect on the respective parameters. The administration of NCs had no impact on the mean number of pups per dam. Additionally, no impact of the NCs on the body weights of the pups was observed on the 1st day after parturition. Moreover, comparisons between groups, for both sexes showed no difference on growth rate. During the histological evaluation no inflammatory, degenerative or neoplastic lesions were observed as far as the newborn, adult offspring and dams were concerned. According to our results no toxic impact of the low and high doses of the NCs was observed on the parameters selected to be evaluated.
Assuntos
Nanoestruturas/toxicidade , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Placenta/efeitos dos fármacos , Gravidez , Ratos WistarRESUMO
The aim of this study was to evaluate the neuroendocrine and inflammation response to laparoscopic total ovariohysterectomy (TOH) in rabbits, by comparing surgical stress markers of laparoscopic group with those of conventional open ovariohysterectomy and open ovariohysterectomy with pre-incisional local anaesthesia groups. Blood was sampled from 18 rabbits, of which six underwent laparoscopic TOH, six conventional open TOH and six conventional open TOH with pre-incisional local anaesthesia, 30 min before induction of anaesthesia (T0), immediately after skin incision (T1), 90 min postoperatively (T2), and 24 h postoperatively (T3). Cortisol and C-reactive protein serum, and adrenocorticothrophic hormone, tumour necrosis factor-a (TNF-a), adrenaline, noradrenaline and IL-6 plasma concentrations were evaluated. Laparoscopic TOH in rabbits has advantages over the open surgical technique because it causes less surgical stress response in terms of serum cortisol concentrations immediately after skin incision (p = .04), as well as plasma adrenaline (p = .035) and TNF-a (p = .047) concentrations 24 h postoperatively. Impact statement What is already known on this subject? Hysterectomy is the second most common surgery performed on women after caesarean section. Research has focussed on methods to modify the stress response associated with surgery. Various studies both in humans and animals, have demonstrated the less systemic, immunological and neurohormonal response of the laparoscopic technique, which is expressed by less elevated serum enzymes' and proteins' concentrations. However, other studies have documented that the systemic stress response after open hysterectomy is similar to that following laparoscopic surgery. What do the results of this study add? Laparoscopic total ovariohysterectomy in rabbits has advantages over the open surgical technique because it causes less surgical stress response in terms of serum cortisol concentrations, as well as plasma adrenaline and TNF-a concentrations during the first 24 h postoperatively. What are the implications are of these findings for clinical practice and/or further research? There were no significant differences between the groups in number of surgical stress markers (p > .05) perioperatively. We cannot exclude the possibility that a later increase of surgical stress response might take place after the first 24 h postoperatively.
Assuntos
Hidrocortisona/sangue , Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Ovariectomia/efeitos adversos , Estresse Fisiológico , Hormônio Adrenocorticotrópico/sangue , Anestesia , Animais , Proteína C-Reativa/metabolismo , Epinefrina/sangue , Feminino , Histerectomia/métodos , Interleucina-6/sangue , Norepinefrina/sangue , Ovariectomia/métodos , Coelhos , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND AND OBJECTIVE: Although collagen membranes have been clinically applied for guided tissue/bone regeneration for more than 30 years, their in vivo degradation pattern has never been fully clarified. A better understanding of the different stages of in vivo degradation of collagen membranes is extremely important, considering that the biology of bone regeneration requires the presence of a stable and cell/tissue-occlusive barrier during the healing stages in order to ensure a predictable result. Therefore, the aim of this study was to investigate the degradation pattern of a porcine non-cross-linked collagen membrane in an in vivo model of guided bone regeneration (GBR). MATERIAL AND METHODS: Decalcified and paraffin-embedded specimens from calvarial defects of 18, 10-month-old Wistar rats were used. The defects were treated with a double layer of collagen membrane and a deproteinized bovine bone mineral particulate graft. At 7, 14 and 30 days of healing, qualitative evaluation with scanning electron microscopy and atomic force microscopy, and histomorphometric measurements were performed. Markers of collagenase activity and bone formation were investigated using an immunofluorescence technique. RESULTS: A significant reduction of membrane thickness was observed from 7 to 30 days of healing, which was associated with progressive loss of collagen alignment, increased collagen remodeling and progressive invasion of woven bone inside the membranes. A limited inflammatory infiltrate was observed at all time points of healing. CONCLUSION: The collagen membrane investigated was biocompatible and able to promote bone regeneration. However, pronounced signs of degradation were observed starting from day 30. Since successful regeneration is obtained only when cell occlusion and space maintenance exist for the healing time needed by the bone progenitor cells to repopulate the defect, the suitability of collagen membranes in cases where long-lasting barriers are needed needs to be further reviewed.
Assuntos
Regeneração Óssea/fisiologia , Colágeno/metabolismo , Regeneração Tecidual Guiada , Membranas Artificiais , Animais , Materiais Biocompatíveis , Regeneração Óssea/efeitos dos fármacos , Transplante Ósseo , Bovinos , Colágeno/farmacologia , Colagenases/metabolismo , Citocinas/metabolismo , Inflamação , Modelos Animais , Osteogênese/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , CicatrizaçãoRESUMO
BACKGROUND AND AIMS: We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE-/-) mice. METHODS: Fifty male, ApoE-/- mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks). After blood sampling and euthanasia, aortic roots were excised and analyzed for gene expression and/or percentage of aortic stenosis, relative content of macrophages, smooth muscle cells (SMCs), connective tissue, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases-2,-3,-9 (MMP-2,-3,-9) and their inhibitor (TIMP-2) and IL-6. SFE doses were determined by a pilot serum pharmacokinetic study in C57BL/6J wild-type mice. RESULTS: SFE did not affect body weight and total cholesterol levels (p > 0.05), while high SFE dose significantly ameliorated glucose and triglycerides profiles compared to other groups (p < 0.05). SFE considerably decreased aortic stenosis in a dose-dependent manner (p < 0.05). Furthermore, increasing SFE doses proportionally reduced macrophages content and increased within plaques content of collagen, elastin, and SMCs, promoting more stable plaque phenotype compared to COG (p < 0.05). Those effects seemed to be associated with a considerable reduction (>30%) in IL-6, TNF-α, MCP-1, MMP-2,-3,-9 (p < 0.05) and MMP-2/TIMP-2 ratio. CONCLUSIONS: SFE exerted dose-dependent anti-atherosclerotic and plaque-stabilizing effects in Apo-E-/- mice, probably mediated by a favorable modification of inflammatory mechanisms, which requires further investigation.
Assuntos
Anti-Inflamatórios/farmacologia , Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lectinas de Ligação a Manose , Extratos Vegetais/farmacologia , Lectinas de Plantas , Placa Aterosclerótica , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacocinética , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacocinética , Mediadores da Inflamação/metabolismo , Masculino , Lectinas de Ligação a Manose/química , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacocinética , Lectinas de Plantas/química , Ruptura Espontânea , Triglicerídeos/sangueRESUMO
BACKGROUND AND AIMS: Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE(-/-) mice and the underlying molecular mechanisms. METHODS AND RESULTS: WT and ApoE(-/-) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 µg/kg bolus 15 min before R; 4) ApoE(-/-) Control Group, receiving WFI; 5) ApoE(-/-) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE(-/-) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 µg/kg bolus, 15 min before R. Ischemic area/area at risk (I/R%) ratio was measured. Blood samples and ischemic myocardial tissue were collected at the 10th min of reperfusion for assessment of troponin I, malondialdehyde (MDA), nitrotyrosine (NT), p-eNOS, eNOS, p-Akt, Akt, p-p42/p-p44, p-GSK3ß, GSK3ß, IL-6, Nrf2, HO-1 and MnSOD expression. The effect of SFE on Nrf2 expression was also evaluated in vitro. SFE reduced infarct size in WT (16.15 ± 3.7% vs 41.57 ± 2.48%, ***p < 0.001) and in ApoE(-/-) mice (16.14 ± 1.47% vs 45.57 ± 1.73%, ***p < 0.001). The administration of wortmannin resulted in partial inhibition of the infarct size limitation efficacy of SFE (in both WT and Apo-E(-/-) mice). Mice receiving SFE showed increased levels of eNOS, p-Akt, p-ERK1/2, p-44/p-42 and p-GSK3ß-Ser9 and reduced expression of IL-6 and iNOS; furthermore, SFE reduced the levels of MDA and NT. SFE induced Nrf2 expression and its downstream targets, HO-1 and MnSOD in the myocardium of the treated animals, and induced Nrf2 expression in vitro in a dose-dependent manner. CONCLUSIONS: SFE limits myocardial infarction in Wild-Type and ApoE(-/-) mice in a multifaceted manner including activation of Akt/eNOS/ERK1/2/GSK3-ß and through Nrf2 pathway, bestowing antioxidant protection against I/R.
Assuntos
Antioxidantes/farmacologia , Crocus , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Animais , Antioxidantes/isolamento & purificação , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Biomarcadores/metabolismo , Linhagem Celular , Crocus/química , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Flores , Predisposição Genética para Doença , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Transdução de Sinais/efeitos dos fármacosRESUMO
In the present study, to evaluate the effects of wireless 1880-1900MHz Digital Enhanced Communication Telephony (DECT) base radiation on fetal and postnatal development, Wistar rats were exposed at an average electric field intensity of 3.7V/m, 12h/day, during pregnancy. After parturition, a group of dams and offspring were similarly exposed for another 22days. Controls were sham-exposed. The data showed that DECT base radiation exposure caused heart rate increase in the embryos on the 17th day of pregnancy. Moreover, significant changes on the newborns' somatometric characteristics were noticed. Pyramidal cell loss and glia fibrilliary acidic protein (GFAP) over-expression were detected in the CA4 region of the hippocampus of the 22-day old pups that were irradiated either during prenatal life or both pre- and postnatally. Changes in the integrity of the brain in the 22-day old pups could potentially be related to developmental behavioral changes during the fetal period.
Assuntos
Encéfalo , Campos Eletromagnéticos , Efeitos Tardios da Exposição Pré-Natal , Telefone , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Desenvolvimento Embrionário , Feminino , Fertilidade , Desenvolvimento Fetal , Proteína Glial Fibrilar Ácida/metabolismo , Frequência Cardíaca , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Ratos WistarRESUMO
One of the commonly used animal models in fertility, developmental and neurobiological studies is the laboratory rat. The early recognition of rat pregnancy and confirmation of the exact embryonic day are vital. The aim of this study was to investigate the correlation of maternal weight at the time of conception to its increase throughout gestation, aiming to develop a mathematical model, which can be used for the determination of the exact day of pregnancy, set the threshold, and monitor pregnancy from the onset. We studied a total of 173 Wistar rats with a mean body weight of 238.22 ± 34.9 g. After 72 h at the male's cages, we considered as Day 0 (D0) the day in which a copulatory plug or sperm was found during the vaginal smear examination. After that period the female animals were transferred into their cages, and weight monitoring started 14 days (D14) after D0, until parturition. Based on the statistical analysis, there is a correlation between maternal body weight at D0 and maternal body weight from D14 to D19. Moreover, the average weight gain from D14 to D19 is positively correlated to initial female body weight, while there is no correlation between each pregnant animal's weight from D14 to D19 and litter size. A mathematical model was developed as a tool for the verification of the day of pregnancy. In conclusion, continuous monitoring of maternal weight after D14 can be a reliable method for the recognition of pregnancy and determination of the exact gestational day.
Assuntos
Criação de Animais Domésticos/métodos , Peso Corporal , Gravidez , Ratos/fisiologia , Bem-Estar do Animal , Animais , Feminino , Manobra Psicológica , Abrigo para Animais , Modelos Teóricos , Ratos WistarRESUMO
Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatory-related pathways in apolipoprotein E knockout (apoE(-/-)) mice with diabetic atherosclerosis. Forty-five male apoE(-/-) mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorized-treadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339 ± 75.613 x10(3)µm(2)) compared to the control (325.485 ± 72.302 x10(3)µm(2)) and sedentary (340.188 ± 159.108 x 10(3)µm(2)) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE-/- mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.
Assuntos
Apolipoproteínas E , Diabetes Mellitus Experimental , Interleucina-6/sangue , Metaloproteinases da Matriz/sangue , Condicionamento Físico Animal , Placa Aterosclerótica , Inibidor Tecidual de Metaloproteinase-2/sangue , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Inflamação/terapia , Masculino , Camundongos , Camundongos Knockout , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapia , Fatores de TempoRESUMO
The aim of this study is to investigate the neuroprotective effects of the anticonvulsant topiramate in a new model of traumatic brain injury in rats. A new model of traumatic brain injury, based on the weight-drop technique, was developed for the purpose of this study. Seventy-five male Wistar rats weighing 320-470 g were studied. All rats were anesthetized, subsequently submitted to a round craniectomy in the left parietal region and a weight of 50 g was used for the production of a cortical contusion. In study I, 44 rats were randomized in three groups to receive either topiramate 40 mg/kg (n=13), topiramate 60 mg/kg (n=14), or water for injection (n=17) i.p. 30 min after the injury and every 12 h thereafter for 3 days. The rats were tested clinically 24 h, 72 h, 10 days and 20 days after the injury. On day 21 the animals were sacrificed and the brains were removed and prepared for histopathological analysis. In study II, 19 rats were randomized to receive either topiramate 60 mg/kg (n=10) or water for injection (n=9) i.p. 30 min after the injury and every 12 h (four doses in total). 48 h after the injury the animals were sacrificed and the brains were rapidly removed and analyzed for water content with the dry-wet weight technique. The animals that received topiramate performed significantly better in neurological tests compared to the animals that received vehicle ten (P<0.05) and 20 (P<0.001) days after the injury. There was no difference between the high and the low dose of the drug. Topiramate had no effect on the anatomic volume of the lesion. The animals that received topiramate had a tendency to present with less cerebral edema formation, but the difference was not statistically significant (P>0.05). These findings suggest that topiramate promotes neurological recovery in rats after traumatic brain injury without affecting the final size of the traumatic lesion and that it might play a role in the reduction of post-traumatic cerebral edema.
Assuntos
Lesões Encefálicas/complicações , Frutose/análogos & derivados , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Fármacos Neuroprotetores/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Modelos Animais de Doenças , Frutose/uso terapêutico , Lateralidade Funcional , Masculino , Análise Multivariada , Doenças do Sistema Nervoso/patologia , Exame Neurológico , Ratos , Ratos Wistar , Fatores de Tempo , TopiramatoRESUMO
OBJECTIVES: To test the hypothesis that vein graft intimal hyperplasia can be significantly suppressed by a single intra-operative transfection of the graft with a decoy oligonucleotide (ODN) binding the transcription factor Egr-1. DESIGN: Experimental study. MATERIALS AND METHODS: Jugular vein to carotid artery interposition grafts in rabbits were treated with Egr-1 decoy, mutant decoy ODN, vehicle alone, using a non-distending pressure of 300 mm Hg for 20 min, or were left untreated. All animals were fed a 2% cholesterol diet. The animals were sacrificed after 48h, 6 weeks and 12 weeks. Paraffin-embedded vein sections were subjected to angiometric analysis. RESULTS: Successful delivery of the ODN was confirmed by DAPI staining. Quantitative real-time PCR revealed a 60% decrease of the Egr-1 gene expression in the animals in which the Egr-1 decoy ODN was delivered. Cellular proliferation was also significantly decreased as indicated by the Ki-67 labelling index. An increase in intimal and medial thickness was found in all vein grafts. However, intimal thickness was significantly reduced in the grafts treated with Egr-1 decoy ODN, whereas luminal area was significantly increased. CONCLUSION: A single intra-operative pressure-mediated transfection of vein grafts with Egr-1 decoy ODN significantly suppresses intimal hyperplasia in a rabbit hypercholesterolaemic model.
Assuntos
Proteína 1 de Resposta de Crescimento Precoce/genética , Terapia Genética/métodos , Oclusão de Enxerto Vascular/prevenção & controle , Túnica Íntima/patologia , Animais , Artérias Carótidas/cirurgia , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Oclusão de Enxerto Vascular/genética , Hiperplasia , Período Intraoperatório , Veias Jugulares/cirurgia , Masculino , Oligonucleotídeos/química , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
The aim of this study was to investigate the patterns of renal function recovery during partial nephrectomy (PN) on an experimental solitary kidney rabbit model and establish the upper tolerable time limits of applied ischemia. Forty-eight New Zealand rabbits underwent an open right nephrectomy and after 30 days, the animals were clustered into five groups (A, B, C, D, E). The first four groups received an open left PN, under different types of ischemia. Groups A (n = 8) and B (n = 10) were subjected to 90 and 60 min of warm ischemia (WI), respectively, while groups C (n = 10) and D (n = 10) received 90 and 120 min of cold ischemia (CI) with ice-slush cooling. Group E (n = 10) served as sham group. Serum determinations of creatinine (SCr) and BUN were recorded preoperatively and on postoperative days (POD) 1, 3, 6 and 15. The animals were euthanized and the remaining kidneys were harvested and evaluated microscopically. The type and duration of ischemia were statistically significant parameters (P < 0.001). Groups B, C and D exhibited a similar pattern of recovery from trial initiation to the 15th POD (P = 0.788 and P = 0.068, respectively). Group A was extremely differentiated, with 100% mortality caused by uremia. The microscopic findings were consistent to the serum biochemistry. In our solitary kidney rabbit model, the upper limits of tolerable WI seem to be set on 60 min. CI can safely preserve the model's renal function--even up to 120 min.
Assuntos
Isquemia Fria/efeitos adversos , Hipóxia/etiologia , Rim/fisiopatologia , Nefrectomia/métodos , Isquemia Quente/efeitos adversos , Animais , Nitrogênio da Ureia Sanguínea , Isquemia Fria/métodos , Creatinina/sangue , Modelos Animais de Doenças , Rim/patologia , Rim/cirurgia , Nefrectomia/efeitos adversos , Coelhos , Estatísticas não ParamétricasRESUMO
ACE-inhibitors prevent the development of left ventricular hypertrophy (LVH). The tumor suppressor gene p53 up-regulates the cellular renin-angiotensin system, resulting in ANG II synthesis, which activates p53 creating a positive feedback loop. One hundred and fourteen rabbits were separated into groups A (control), B (sham-operated), C and D. In groups C and D, an aortic stenosis was performed, and in group D the animals were treated with enalapril. For p53 determination, LV specimens were examined by Western blot analysis and an immunohistochemical study was performed, except for samples from group D. In conclusion, LVH was significantly induced at 7 and 28 days after aortic stenosis with no difference between the two periods, while enalapril prevented hypertrophy in these two groups. p53 was transcriptionally activated and immunoreactively present after acute pressure overload as well as in the sham-operated group. Enalapril decreased the p53 expression at 180 min, 7 and 28 days following aortic stenosis.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Estenose da Valva Aórtica/complicações , Enalapril/farmacologia , Ventrículos do Coração/citologia , Miócitos Cardíacos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/prevenção & controle , Imuno-Histoquímica , Masculino , Coelhos , Fatores de Tempo , Função Ventricular EsquerdaRESUMO
The objective of this study was to evaluate multiple structural characteristics, in addition to vasa vasorum density, in different aortic regions. The aorta of healthy Landrace pigs was divided into four thoracic and three abdominal segments. Transverse sections were reserved for morphometric analysis. Image analysis showed the aortic diameter, the thickness of the media, the number of elastic lamellae and the thickness of elastic membranes being reduced with increased distance from the heart (P < 0.05). The average thickness of lamellar units remained constant in the thoracic, but increased in the abdominal aorta (P < 0.05). The number of lamellar units, contained in the avascular zone of the media, and the density of vasa vasorum decreased peripherally (P < 0.05), still the average thickness of the avascular zone was invariant. In conclusion, the anatomical properties of the vessel wall alter through the aorta, being optimal for the varying stresses to which the aorta is subjected along its length. The distinct aortic parts may exhibit inherent morphological features, responsible for the various pathological processes that affect the aorta.
Assuntos
Aorta/anatomia & histologia , Suínos/anatomia & histologia , Animais , Aorta/patologia , Aorta Abdominal/anatomia & histologia , Aorta Abdominal/patologia , Aorta Torácica/anatomia & histologia , Aorta Torácica/patologia , Feminino , Processamento de Imagem Assistida por Computador , Masculino , Vasa VasorumRESUMO
OBJECTIVE: To investigate the alterations of structure and mechanical properties of the aortic wall, resulting from impairment of vasa vasorum flow. METHODS: Eight healthy Landrace pigs were subjected to interruption of vasa vasorum flow to the upper segment of their descending thoracic aorta. Under sterile conditions, the periaortic tissue was excised and the contiguous intercostal arteries were ligated. Ten sham-operated pigs were used as controls. Fifteen days postoperatively, the animals were sacrificed and their upper descending thoracic aortas were removed. Histology, and collagen and elastin content determination by image analysis technique were performed. Mechanical analysis of aortic strips was carried out with a uniaxial tension device and stress-strain curves were obtained. RESULTS: In contrast to normal aortic walls of the control group, histology of the avascular aortas revealed severe ischemic necrosis of the outer media along with abnormal straightening of the elastin and collagen fibers, without significant collagen and elastin content changes. The borderline between the outer ischemic and inner non-ischemic media was sharp, and an outset of dissection was observed at this point. Mechanical analysis showed that at the same level of strain, the ischemic aorta was significantly stiffer at both low (P=0.03) and high strains (P=0. 003). CONCLUSIONS: Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flow, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection.
Assuntos
Aorta Torácica/patologia , Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/fisiopatologia , Dissecção Aórtica/patologia , Dissecção Aórtica/fisiopatologia , Vasa Vasorum/fisiopatologia , Animais , Aorta Torácica/fisiopatologia , Aorta Torácica/ultraestrutura , Fenômenos Biomecânicos , Técnicas de Cultura , Modelos Animais de Doenças , Elasticidade , Feminino , Masculino , Necrose , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Estresse Mecânico , Suínos , Vasa Vasorum/patologia , Vasa Vasorum/ultraestruturaRESUMO
Circulating testosterone concentrations and seminal vesicles weights, as well as thymus and spleen weights and histology were assessed in male Wistar rats from the infantile to post-pubertal period. The widely used anti-estrogenic agent tamoxifen was then administered in adult intact and castrated male rats and its long-term effects on thymic involution and splenic growth were examined. The results showed that: (1) age-related involution of the male thymus from the juvenile period through puberty to post-puberty depends on the rising testosterone levels and represents mainly a decrease of thymic lymphoid-cell elements; (2) tamoxifen administration reverses thymic involution in intact adult male rats and this effect is related to a dose-dependent, tamoxifen-induced castration and decrease of testosterone levels; (3) the changes of circulating testosterone levels, either resulting from maturity, or induced by tamoxifen or by castration, have a minimal effect on splenic growth and weight; and (4) in contrast to intact animals, administration of tamoxifen at pharmacological doses to adult castrated rats results in thymic regression. Underscoring the critical role of testosterone on thymic involution, these findings show that tamoxifen is able to reverse ageing changes in the thymus by suppressing testosterone production, while conversely, exerts thymolytic effects in the absence of androgens.