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1.
Urol Int ; 107(4): 422-428, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35220315

RESUMO

INTRODUCTION: The sheep was evaluated as a potential model for preclinical evaluation of urethral slings in vivo based on: (1) anatomical measurements of the sheep vagina and (2) histological tissue integration and host response to polypropylene (PP) slings. METHODS: Eight female, multiparous sheep were utilized. Three of 8 animals underwent surgery mimicking human tension-free vaginal tape protocols for midurethral slings and were euthanized at 6 months. The following measurements were obtained: vaginal length, maximum vaginal width with retraction, symphysis pubis length, and distance from the pubic bone to incision. Explanted sling samples from sheep and human were stained with hematoxylin and eosin for host reaction assessment. RESULTS: Geometric measurements were similar between humans and sheep. Sheep vaginal anatomy allowed sling placement similar to procedures in human surgeries, and all sheep recovered without problems. Comparative histology between the sheep and human indicated similar host reaction and collagen deposition around implants, confirming suitability of the sheep model for biomaterial response assessment. CONCLUSION: Sheep vaginal length is comparable to humans. Tissue integration and host response to PP slings showed chronic inflammation with rich collagen deposition around the material in both sheep and human specimens, highlighting the sheep as a potential animal model for preclinical testing of midurethral slings.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Humanos , Feminino , Animais , Ovinos , Incontinência Urinária por Estresse/cirurgia , Vagina/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Polipropilenos
2.
J Orthop Res ; 31(12): 1986-91, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24038610

RESUMO

As a potential means of comparing hypothyroidism in humans, this work intended to establish a defined hypothyroid state in immature miniature swine and evaluate specific molecular, cellular, and extracellular responses of their growth plates. Two male, 11-week-old Sinclair miniature swine were given 6-propyl-2-thiouracil (PTU) in their water and two other like animals (controls) were provided water without PTU. Blood levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxin (T4) were monitored weekly. At 25 weeks of age, the hind limb proximal femoral physes were harvested and divided into portions for histology and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Compared to controls, swine administered PTU exhibited increased TSH and decreased T3 and T4 serum levels during the study period, features consistent with a hypothyroid state. Compared to controls, hypothyroid swine exhibited structurally altered physes and demonstrated significantly decreased gene expression of aggrecan (p < 0.05) and type X collagen (p ≤ 0.1). This is the first hypothyroid model established in miniature swine and represents a potentially important advance for understanding the condition in humans, in which, like this swine model, there are changes critical to growth plate molecular biology, biochemistry and structure.


Assuntos
Fêmur/fisiopatologia , Lâmina de Crescimento/fisiopatologia , Hipotireoidismo/fisiopatologia , Agrecanas/genética , Animais , Colágeno Tipo X/genética , Expressão Gênica , Lâmina de Crescimento/metabolismo , Masculino , Propiltiouracila/farmacologia , Suínos , Porco Miniatura
3.
J Mech Behav Biomed Mater ; 21: 47-56, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23466517

RESUMO

One in eight American women develops breast cancer. Of the many patients requiring mastectomy yearly as a consequence, most elect some form of breast reconstruction. Since 2006, only silicone breast implants have been approved by the FDA for the public use. Unfortunately, over one-third of women with these implants experience complications as a result of tissue-material biocompatibility issues, which may include capsular contracture, calcification, hematoma, necrosis and implant rupture. Our group has been working on developing alternatives to silicone. Linear triblock poly(styrene-b-isobutylene-b-styrene) (SIBS) polymers are self-assembling nanostructured thermoplastic rubbers, already in clinical practice as drug eluting stent coatings. New generations with a branched (arborescent or dendritic) polyisobutylene core show promising potential as a biomaterial alternative to silicone rubber. The purpose of this pre-clinical research was to evaluate the material-tissue interactions of a new arborescent block copolymer (TPE1) in a rabbit implantation model compared to a linear SIBS (SIBSTAR 103T) and silicone rubber. This study is the first to compare the molecular weight and molecular weight distribution, tensile properties and histological evaluation of arborescent SIBS-type materials with silicone rubber before implantation and after explantation.


Assuntos
Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Implantes de Mama/efeitos adversos , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Animais/cirurgia , Estirenos/química , Estirenos/toxicidade , Animais , Análise de Falha de Equipamento , Feminino , Teste de Materiais , Peso Molecular , Desenho de Prótese , Coelhos , Elastômeros de Silicone/química , Resistência à Tração
5.
J Vasc Surg Venous Lymphat Disord ; 1(1): 68-74, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26993897

RESUMO

BACKGROUND: Patients with acutely treated femoral shaft fractures with reamed intramedullary nailing are at risk for acute respiratory distress syndrome due to liberation of bone marrow fat particles that travel to the lung and cause damage to the parenchyma. The purpose of this study was to demonstrate: (1) the ability of clinically applicable embolic protection devices to capture such particles; (2) how such a device affects cardiopulmonary function after reamed intramedullary nailing; and (3) evaluation of lung pathology to determine whether filtration affects pulmonary embolic load. METHODS: A total of 12 canines were anesthetized, and hemodynamic monitoring was established. Carotid embolic protection devices were introduced into the iliac vein, and ipsilateral intramedullary reaming and nailing was performed. Cardiopulmonary parameters were recorded at timed intervals up to 60 minutes after the procedure. The control group (n = 4) was compared with groups treated with Accunet (n = 4) and Spider (n = 4) filters. A blinded histopathological review was performed on lung specimens to determine the average number of emboli per section and to measure the area (mm(2)) of embolic load by digital image analysis. RESULTS: Gross inspection of the embolic protection devices showed the presence of bone marrow debris. A significant change was observed in pH levels (control = -0.052, filters = +0.005; P < .05) within the 60 minutes after intramedullary nailing. Serum bicarbonate (meq/dL) values were noted to have similar changes of -2.7 and -1.8 at 10 and 60 minutes, whereas the experimental group was +0.6 and +0.8 at the same time intervals (P =.01 and .0004, respectively). Pulmonary measurements for pO2 and oxygen saturation were analogous to the serum parameters with decreases in the control group in comparison with the filter groups. The mean numbers of emboli and area measurements of embolic load were significantly reduced in the filter group (all P < .01). CONCLUSIONS: Embolic protection devices were effective in capturing embolic debris from reamed intramedullary nailing of lower extremity long bones and demonstrated a protective effect on pulmonary function and significantly decreased the number and size of emboli in the lung. Based on these findings, patients with long bone fractures at risk for pulmonary complications and acute respiratory distress syndrome could benefit from the placement of embolic protection devices prior to intramedullary fixation. While this study utilized filtration devices designed for carotid embolic protection, further study is warranted to determine optimal filter design in this setting.

6.
Anticancer Res ; 32(10): 4307-12, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23060551

RESUMO

BACKGROUND/AIM: Cobalamin and folate are interdependent co-factors of the methionine synthase pathway. This study evaluated the effect of intravenously-administered nitrosylcobalamin (NO-Cbl), a vitamin B12 analog, on serum folate concentrations in healthy dogs. MATERIALS AND METHODS: Four dogs received a 10-mg/kg, 20-mg/kg and 40-mg/kg intravenous bolus dose of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and serum cobalamin and folate concentrations were measured. RESULTS: For each dose, serum cobalamin concentrations were inversely correlated with serum folate concentrations. Spearman rank correlation co-efficient values were -0.976 (10 mg/kg, p<0.0096), and -1.0 (20 mg/kg, p<0.008; 40 mg/kg, p<0.0046). CONCLUSION: Cellular uptake of NO-Cbl, following intravenous administration exerted a biological effect on folate, similar to that previously described for other vitamin B12 analogs. Serum folate concentration may serve as a pharmacodynamic biomarker of intracellular nitrosylcobalamin activity following intravenous administration.


Assuntos
Biomarcadores Farmacológicos/sangue , Ácido Fólico/sangue , Compostos Nitrosos/administração & dosagem , Vitamina B 12/análogos & derivados , Administração Intravenosa , Animais , Cães , Masculino , Compostos Nitrosos/sangue , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue
7.
Anticancer Res ; 32(9): 3749-52, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22993315

RESUMO

BACKGROUND/AIM: Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent. This study evaluated the pharmacokinetic parameters of NO-Cbl following intravenous administration in dogs. MATERIALS AND METHODS: Four dogs received 10 mg/kg, 20 mg/kg and 40 mg/kg intravenous bolus doses of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and noncompartmental pharmacokinetic parameters were determined. RESULTS: Average peak serum concentrations of 2265, 5523 and 13,866 pg/mL were achieved following single-dose bolus intravenous administration of 10 mg/kg, 20 mg/kg and 40 mg/kg of NO-Cbl respectively. The average area under the curve was 12,697 h × pg/mL, 24,497 h × pg/mL and 44,976 h × pg/mL respectively, with an average elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively. CONCLUSION: These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.


Assuntos
Antineoplásicos/farmacocinética , Compostos Nitrosos/farmacocinética , Vitamina B 12/análogos & derivados , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Cães , Injeções Intravenosas , Masculino , Compostos Nitrosos/administração & dosagem , Compostos Nitrosos/sangue , Projetos Piloto , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 12/farmacocinética
8.
J Bone Joint Surg Am ; 94(15): e1111-10, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22855000

RESUMO

BACKGROUND: The effect of compression on the physis is generally defined by the Hueter-Volkmann principle, in which decreased linear growth of the physis results from increased compression. This investigation examined whether mechanically induced compression of rabbit physes causes changes in gene expression, cells, and extracellular components that promote physeal resilience and strength (type-II collagen and aggrecan) and cartilage hypertrophy (type-X collagen and matrix metalloprotease-13). METHODS: Static compressive loads (10 N or 30 N) were applied for two or six weeks across one hind limb proximal tibial physis of thirteen-week-old female New Zealand White rabbits (n = 18). The contralateral hind limb in all rabbits underwent sham surgery with no load to serve as an internal control. Harvested physes were divided into portions for histological, immunohistochemical, and quantitative reverse transcription-polymerase chain reaction analysis. Gene expression was statistically analyzed by means of comparisons between loaded samples and unloaded shams with use of analysis of variance and a Tukey post hoc test. RESULTS: Compared with unloaded shams, physes loaded at 10 N or 30 N for two weeks and at 10 N for six weeks showed histological changes in cells and matrices. Physes loaded at 30 N for six weeks were decreased in thickness and had structurally disorganized chondrocyte columns, a decreased extracellular matrix, and less intense type-II and X collagen immunohistochemical staining. Quantitative reverse transcription-polymerase chain reaction analysis of loaded samples compared with unloaded shams yielded a significantly (p ≤ 0.05) decreased gene expression of aggrecan and type-II and X collagen and no significant (p > 0.05) changes in the matrix metalloprotease-13 gene expression with increasing load. CONCLUSIONS: Compressed rabbit physes generate biochemical changes in collagens, proteoglycan, and cellular and tissue matrix architecture. Changes potentially weaken overall physeal strength, consistent with the Hueter-Volkmann principle, and lend understanding of the causes of pathological conditions of the physis.


Assuntos
Lâmina de Crescimento/crescimento & desenvolvimento , Estresse Mecânico , Tíbia/crescimento & desenvolvimento , Actinas/genética , Actinas/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Análise de Variância , Animais , Colágeno/genética , Colágeno/metabolismo , Feminino , Perfilação da Expressão Gênica , Lâmina de Crescimento/metabolismo , Membro Posterior , Imuno-Histoquímica , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tíbia/metabolismo
10.
Am J Physiol Lung Cell Mol Physiol ; 297(3): L487-95, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19592457

RESUMO

The alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure.


Assuntos
Líquidos Corporais/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Alvéolos Pulmonares/patologia , Receptores Adrenérgicos beta/metabolismo , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Hormônios/sangue , Hiperplasia , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Alvéolos Pulmonares/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Terbutalina/farmacologia , Ultrassonografia
11.
JSLS ; 12(1): 37-45, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18402737

RESUMO

BACKGROUND AND OBJECTIVES: Natural orifice translumenal endoscopic surgery (NOTES) is a development of recent origin. In 2004, Kalloo et al first described NOTES investigation in an animal model. Since then, several investigators have pursued NOTES study in animal survival and nonsurvival models. Our objectives for this project included studying NOTES intervention in a laboratory environment using large animal (swine) models and learning to do so in a safe, controlled manner. Ultimately, we intend to introduce NOTES methodology into our surgical residency training program. The expertise of an experienced laparoscopic surgeon, fellowship-trained laparoendoscopic surgeon, and veterinarian along with a senior surgical resident was utilized to bring the input of several disciplines to this study. The Institutional Animal Care and Use Committee (IACUC) of Northeastern Ohio Universities College of Medicine and Pharmacy (NEOUCOM/COP) approved this study. METHODS: A series of 5 laboratory sessions using mixed breed farm swine varying in weight from 37 kg to 43.1 kg was planned for the initial phase of NOTES introduction into our residency program. Animals were not kept alive in this investigation. All animals were anesthetized using a standard swine protocol and euthanized following guidelines issued by the American Veterinary Medical Association Panel on Euthanasia. Equipment included a Fujinon EVE endoscope 0.8 cm in diameter with a suction/irrigation channel and one working channel. Initially, a US Endoscopy gastric overtube, 19.5 mm OD and 50 cm in length, was used to facilitate passage of the endoscope. However, this device was found to have insufficient length. Subsequently, commercially available 5/8" diameter clear plastic tubing, 70 cm to 80 cm in length, was adapted for use as an overtube. Standard endoscopic instruments included Boston Scientific biopsy forceps, needle-knife, papillotome, endoscopic clip applier, and Valley Lab electrosurgical unit. A Karl Storz laparoscope and tower were used for laparoscopic observation of NOTES maneuvers. Necropsy was performed to determine specific details of surgical intervention. RESULTS: NOTES intervention is feasible in an animal model. Insight into the potential of NOTES was obtained in this investigation. CONCLUSIONS: NOTES investigation in a controlled, laboratory setting using an animal model proved to have value for our program. A steep learning curve was encountered despite the availability of an investigator familiar with elementary NOTES procedures. The authors strongly suggest investigators adopt the ASGE/SAGES working group recommendations for a multidisciplinary team possessing advanced therapeutic endoscopic and advanced laparoscopic skills to study NOTES before human investigation. Animal laboratory facilities to perform research and training should be available to the multidisciplinary team for exploration of NOTES techniques and procedures. Institutional Review Board (IRB) approval must be obtained before introduction of NOTES procedures in human patients.


Assuntos
Endoscopia Gastrointestinal/métodos , Cirurgia Geral/educação , Internato e Residência , Laparoscopia , Anastomose Cirúrgica/métodos , Cateterismo , Competência Clínica , Estudos de Viabilidade , Humanos
12.
Am J Physiol Heart Circ Physiol ; 290(1): H323-30, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16143656

RESUMO

Cardiac fibroblast (CF) proliferation and differentiation into hypersecretory myofibroblasts can lead to excessive extracellular matrix (ECM) production and cardiac fibrosis. In turn, the ECM produced can potentially activate CFs via distinct feedback mechanisms. To assess how specific ECM components influence CF activation, isolated CFs were plated on specific collagen substrates (type I, III, and VI collagens) before functional assays were carried out. The type VI collagen substrate potently induced myofibroblast differentiation but had little effect on CF proliferation. Conversely, the type I and III collagen substrates did not affect differentiation but caused significant induction of proliferation (type I, 240.7 +/- 10.3%, and type III, 271.7 +/- 21.8% of basal). Type I collagen activated ERK1/2, whereas type III collagen did not. Treatment of CFs with angiotensin II, a potent mitogen of CFs, enhanced the growth observed on types I and III collagen but not on the type VI collagen substrate. Using an in vivo model of myocardial infarction (MI), we measured changes in type VI collagen expression and myofibroblast differentiation after post-MI remodeling. Concurrent elevations in type VI collagen and myofibroblast content were evident in the infarcted myocardium 20-wk post-MI. Overall, types I and III collagen stimulate CF proliferation, whereas type VI collagen plays a potentially novel role in cardiac remodeling through facilitation of myofibroblast differentiation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Colágeno Tipo VI/fisiologia , Matriz Extracelular/fisiologia , Fibroblastos/citologia , Remodelação Ventricular/fisiologia , Angiotensina II/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/fisiologia , Colágeno Tipo III/fisiologia , Vasos Coronários/patologia , Fibrose/etiologia , Ligadura , Masculino , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Sprague-Dawley
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