Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Molecules ; 26(3)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494330

RESUMO

Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-ß-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.


Assuntos
Proteínas de Bactérias/química , Glicoconjugados , Lectinas/química , Pseudomonas aeruginosa/química , Glicoconjugados/síntese química , Glicoconjugados/química , Humanos , Ressonância Magnética Nuclear Biomolecular
2.
Acta Biol Hung ; 63(1): 1-14, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22453796

RESUMO

A comparative analysis of human and experimental animal (canine) tissues was performed to characterize and describe cellular and histological responses during the processes of newly forming intravascular tissues after stent implantation. Routine histological and immunohistochemical evaluation of 20 human samples and 9 samples from animal models were used one day, one week and one month after the stent implantation. After one day of implantation, there was no difference between the human and canine peripheral arteries, suggesting a similar cellular and histological response in the early phase. In contrast, after one week of implantation, during the proliferative phase the repairing human tissue showed less intensive production of inflammatory cells and more intensive increase in number of vascular cells than did the canine model. In addition, cellular changes normally restituted by the end of one month in canine peripheral arteries, but vascular cells persisted in human atherosclerotic arteries. In conclusion, results of this study suggest differences in both phases of vascular repair in the post-stented period, because both proliferative and regressive phases showed histological differences in canine and human samples. In canine, the restitution of vascular wall was completed by the end of first month but persistent vascular cell proliferation was visible in the human peripheral arteries. It can be suggested that delayed cellular response might indicate restenosis but also can be considered considered as a progression of the original arterial disease.


Assuntos
Vasos Sanguíneos/patologia , Modelos Animais , Stents/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Animais , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Túnica Íntima/patologia , Procedimentos Cirúrgicos Vasculares
3.
Magy Seb ; 64(6): 294-300, 2011 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-22169343

RESUMO

INTRODUCTION/AIM: Our study investigated the effect of ischemic postconditioning (IPO) in intestinal warm ischemia/reperfusion (I/R) and autotransplantation models. MATERIALS AND METHODS: Warm ischemia was performed by occlusion of superior mesenteric artery for 1, 3 and 6 hours in white domestic pigs (n = 15). Prior to 3 hours reperfusion the intestine was postconditioned by 3 cycles of 30-seconds ischemia and 30-seconds reperfusion (IPO protocol). In the cold ischemia group (n = 15) the bowel was preserved in University of Wisconsin solution for 1, 3, and 6 hours. Prior to 3 hours reperfusion IPO protocol was applied, too. Tissue samples were collected after laparotomy (control) and at the end of the reperfusion periods. As far as oxidative stress markers, malondialdehyde and reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity were determined. Tissue damage was evaluated by qualitative (Park-classification) and quantitative (Scion Image) methods. RESULTS: As regards oxidative stress parameters, lipidperoxidation decreased and the protective effect of endogenous antioxidants (GSH, SOD) retained significantly by IPO procedure at the end of reperfusion. Tissue injury correlated significantly by the duration of warm ischemia and cold preservation. Quantitative analysis demonstrated that IPO ameliorated tissue injury in each group (p < 0.05). CONCLUSION: IPO significantly attenuated intestinal oxidative stress and morphological damages in warm and cold I/R models.


Assuntos
Antioxidantes/metabolismo , Intestinos/patologia , Isquemia/metabolismo , Pós-Condicionamento Isquêmico , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Transplante Autólogo , Isquemia Quente , Adenosina , Alopurinol , Animais , Modelos Animais de Doenças , Glutationa/metabolismo , Insulina , Intestinos/irrigação sanguínea , Laparotomia , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Soluções para Preservação de Órgãos , Rafinose , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo , Sus scrofa , Fatores de Tempo
4.
Histol Histopathol ; 26(7): 821-30, 2011 07.
Artigo em Inglês | MEDLINE | ID: mdl-21630212

RESUMO

Intraperitoneal surgical mesh implantation is required for laparoscopic ventral hernia repair. Composite meshes are well known in animal models and human practice. The aim of our study is to compare the biological behaviour of two different textured silicone-covered polypropylene meshes. Transmural abdominal wall defect was created in 40 rabbits and treated as follows: In 20 animals a polypropylene mesh with a laminar silicone covering (LSPP) and in the rest a macroporous textured mesh knitted of silicone-impregnated polypropylene filaments (MSPP) was applied. One and three weeks after implantation we evaluated the intraperitoneal adhesion formation of the mesh macroscopically, histologically and immunohistochemically to detect the reactive cells, especially inflammatory, endothelial and mesothelial cells, as well as their proliferative activity, and with Scanning Electron microscopy to visualize the surface of the meshes. The adhesion formation caused by the composites showed no statistical difference after one week although in the three weeks old samples the LSPP adhesion was significantly weaker than that of MSPP. As complications, serome formation in both groups, fistulas, abscesses, and sc. haematoma in the LSPP group were found. Only in MSPP containing tissues was the decrease of Ki-67 positive proliferating cells significant. A significant increase in VEGF expressing cells was observed only in MSPP containing three week old samples, suggesting better regulation of vascular growth in tissues surrounding the implants. In one week old specimens we observed an irregular proliferation of cytokeratin containing mesothelial cells in both group. The intraperitoneal surface of MSPP mesh was covered with neoperitoneum, while it was not regularly seen on LSPP mesh after three week.


Assuntos
Hérnia Ventral/cirurgia , Telas Cirúrgicas , Animais , Materiais Biocompatíveis , Materiais Revestidos Biocompatíveis , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Antígeno Ki-67/metabolismo , Teste de Materiais , Microscopia Eletrônica de Varredura , Modelos Animais , Polipropilenos , Coelhos , Silicones , Fatores de Tempo , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização
5.
Magy Seb ; 63(5): 340-6, 2010 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-20965868

RESUMO

INTRODUCTION/AIM: Laparoscopic ventral hernia repair requires a surgical mesh implanted in intraperitoneal position. The combined, double layer meshes are promising in animal models as well as in human practice. The aim of this study was to compare the biological behaviour of two different textured silicone covered polypropylene mesh. MATERIALS AND METHODS: 3 × 4 cm big full thickness defect of the abdominal wall was created in New Zealand White rabbits. The defect was covered in 20 animals with a polypropylene mesh with laminar silicone layer on the visceral surface (LSPP), while the remaining 20 cases the defects were covered with a macroporous textured silicone impregnated polypropylene mesh (MSPP). Intraperitoneal adhesion formation and tissue ingrowth in the meshes were investigated. Immunohistochemistry was used to detect proliferation activity (Ki-67), neovascularization (VEGF), and to visualize mesothelial layer (CK) over the mesh. Scanning electron microscopy was used to investigate the visceral surface of the meshes. RESULTS: While intraperitoneal adhesion formation showed no difference after 1 week, LSPP mesh induced significantly less adhesions after 21 days. The Ki-67 positivity was significantly lower and the number of the VEGF positive cells increased with time in the MSPP group, this was missing in the LSPP group. The thin neoperitoneum layer was detected over MSPP mesh only with CK antibody. CONCLUSION: The material and texture of the mesh are responsible for tissular incorporation which is in accordance with the generated foreign body reaction.


Assuntos
Parede Abdominal/cirurgia , Materiais Biocompatíveis , Proliferação de Células , Peritônio/fisiologia , Polipropilenos , Silicones , Telas Cirúrgicas , Engenharia Tecidual , Animais , Adesão Celular , Reação a Corpo Estranho/fisiopatologia , Hérnia Abdominal/cirurgia , Imuno-Histoquímica , Queratinas/análise , Antígeno Ki-67/análise , Microscopia Eletrônica de Varredura , Modelos Animais , Neovascularização Fisiológica , Coelhos , Engenharia Tecidual/métodos , Fator A de Crescimento do Endotélio Vascular/análise
6.
J Mol Neurosci ; 42(3): 419-27, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20405239

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed endogenous neuropeptide, also occurring in the cardiovascular system. Among others, PACAP has been suggested as a cardioprotective factor. It has been shown that PACAP inhibits cardiac fibrosis and protects cardiomyocytes against oxidative stress and in vitro ischemia/reperfusion. The aim of the present study was to investigate whether PACAP is protective in doxorubicin-induced cell death of cardiomyocytes. Cardiomyocytes were exposed to 1 µM doxorubicin for 24 h, which resulted in a marked reduction of cell viability and a parallel increase of apoptotic cells assessed by MTT test and annexin V/propidium iodide flow cytometry assay. Co-incubation with 20 nM PACAP increased cell viability and reduced the percentage of apoptotic cells. Furthermore, doxorubicin increased the activation of caspase-3 and decreased the phosphorylation of Bad, while simultaneous PACAP treatment reduced the caspase-3 activation and increased the level of phospho-Bad. In summary, our present results demonstrate that PACAP effectively protects cardiomyocytes against doxorubicin-induced apoptotic cell death.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Animais , Morte Celular/fisiologia , Células Cultivadas , Humanos , Miócitos Cardíacos/citologia , Estresse Oxidativo/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/química , Isoformas de Proteínas/química , Isoformas de Proteínas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar
7.
Magy Seb ; 62(5): 293-7, 2009 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-19828418

RESUMO

INTRODUCTION/AIMS: Prostheses use for lower limb amputees is difficult, while the socket is hard, the prosthesis is heavy. Drawbacks of conventional prosthesis are mainly associated with the socket, therefore osseointegration technique is a promising solution, since it doesn't require a socket. Our aim was to introduce this technique in Hungary and extend indication for vascular patients. METHODS: The method includes two operative and one rehabilitation phases: during first operation a titanium screw is fixed into the femoral bone marrow cavity, this connects to an abutment, which also penetrates the skin, making a direct connection between the femur and the prosthesis during the second intervention. During rehabilitation the patient makes loading exercises and learns to walk with new prosthesis. RESULTS: This method was launched in Hungary in 2005. Two female amputees were operated on initially, their second surgery was performed in 2006 (when titanium screw was applied in the male patients, as well). Incorporation of titanium screw was exquisite, and rehabilitation was successful. One of our male patients died eight months after his first operation due to myocardial infarction. CONCLUSION: Based on our experiences, the osseointegration technique facilitates rehabilitation of vascular patients for prostheses use. Adequate follow-up and stable vascular diseases are not contraindications, although further clinical trials are needed to determine its indication.


Assuntos
Amputação Cirúrgica , Membros Artificiais , Osseointegração , Doenças Vasculares Periféricas/reabilitação , Doenças Vasculares Periféricas/cirurgia , Coxa da Perna/cirurgia , Suporte de Carga , Parafusos Ósseos , Terapia por Exercício/métodos , Feminino , Fêmur , Humanos , Hungria , Masculino , Doenças Vasculares Periféricas/fisiopatologia , Reoperação , Titânio
8.
Orv Hetil ; 150(2): 73-9, 2009 Jan 11.
Artigo em Húngaro | MEDLINE | ID: mdl-19103558

RESUMO

UNLABELLED: Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and sustained virological response to antiviral therapy is limited in HCV1 genotype infection, a double blind study was performed in HCV1 patients treated with pegylated interferon + ribavirin, to assess the efficacy of supplementation with the antioxidant flavonoid silymarin. PATIENTS AND METHODS: Thirty-two naive HCV1 positive patients with biopsy proven chronic hepatitis C, to be treated with pegylated interferon + ribavirin, have been randomized: group A): 16 patients have been given the antiviral therapy for 6-12 months plus placebo for the first 3 months; group B): 16 patients have been treated with pegylated interferon + ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day, was given for 3 months. Serum alanine aminotransferase and HCV-RNA levels as well as parameters of oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained virological response as undetectable serum HCV RNA was evaluated 24 weeks after the end of therapy. RESULTS: In the silymarin group, a more rapid decrease in the malondialdehyde level as well as a marked decrease in superoxide dismutase and an increase in myeloperoxidase activity after month 12 were found, alanine aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained virological response occurred in 3/16 (vs 7/16) patients. DISCUSSION/CONCLUSION: Although silymarin supportation to antiviral therapy improved oxidative stress, it was able to affect favourably neither the alanine aminotransferase nor the sustained virological response. These contradictory findings may be related to randomization bias as patients in study group B had more negative predictors of response: they were older with higher fibrosis score and even with more severe pretreatment baseline oxidative stress. Regarding the recently published in vitro experiments with silybinin on HCV replication as well as the newest convincing clinical observations, we do suggest further studies with more than three times higher doses of silymarin in controlled trials to assess the value of this supplementation in antivirally treated HCV patients.


Assuntos
Antioxidantes/uso terapêutico , Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Substâncias Protetoras/uso terapêutico , Ribavirina/uso terapêutico , Silimarina/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Método Duplo-Cego , Feminino , Hepacivirus/genética , Hepatite C Crônica/metabolismo , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/sangue , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , RNA Viral/isolamento & purificação , Superóxido Dismutase/sangue , Resultado do Tratamento
9.
J Mol Neurosci ; 37(2): 168-76, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18651248

RESUMO

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Substâncias de Crescimento/farmacologia , Intestino Delgado/metabolismo , Intestino Delgado/transplante , Estresse Oxidativo/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Animais , Temperatura Baixa , Peroxidação de Lipídeos/fisiologia , Masculino , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Radioimunoensaio , Ratos , Ratos Wistar , Preservação de Tecido , Transplante Autólogo
10.
Orv Hetil ; 149(47): 2245-9, 2008 Nov 23.
Artigo em Húngaro | MEDLINE | ID: mdl-19004747

RESUMO

UNLABELLED: The aim of the study was to investigate whether repeated ischemic preconditioning or N-acetylcysteine (NAC) prevents ischemic-reperfusion injury as determined by having favourable hemodynamic effects during reperfusion in canine livers. METHODS: The control group ( n = 10) underwent 60 minutes of hepatic ischemia followed by 180 minutes reperfusion. In the NAC group ( n = 5) 150 mg kg -1 of NAC was administered intravenously before inducing ischemia. In the preconditioned group ( n = 5) animals received ischemic preconditioning (10 minutes of ischemia followed by 10 minutes of reperfusion repeated three times) before clamping the portal triad. RESULTS: 18 dogs survived the study period. One dog in the NAC group died due to circulatory failure unresponsive to inotropic drugs. The cardiac index and the intrathoracic blood volume index were significantly higher in the preconditioning group compared to the controls throughout the study period. CONCLUSIONS: Repeated ischemic preconditioning might improve hemodynamic parameters, whereas we were unable to find any significant differences between the groups regarding N-acetylcysteine.


Assuntos
Acetilcisteína/farmacologia , Fármacos Cardiovasculares/farmacologia , Hemodinâmica/efeitos dos fármacos , Precondicionamento Isquêmico , Fígado/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Cães , Fígado/irrigação sanguínea , Fígado/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia
11.
Orv Hetil ; 149(22): 1029-33, 2008 Jun 01.
Artigo em Húngaro | MEDLINE | ID: mdl-18508737

RESUMO

Minimal invasive surgical techniques, namely laparoscopic procedures to the abdominal surgery have been introduced more than 20 years ago. In view of clinical results, the majority of these are considered as routinely performed procedure today. Natural Orifice Transluminal Endoscopic Surgery can be considered as a new generation of abdominal surgery. It means a method directed through natural orifices, and abdominal surgery operated by transluminal endoscopic techniques (transgastric, transcolonic, transvaginal) to reach diagnostic and therapeutic goals. Theoretically, this method allows the possibility to decrease invasiveness and postoperative pain, to prevent postoperative hernias and to improve cosmetic results. At present numerous researchers work worldwide to receive scientifically based answers to arising questions (surgical technique, indication, contraindication, complications, monitoring) and concerns in this area. The present paper gives an overview of the national and international literature on experimental results and clinical approaches in the field of this new surgical technique.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Laparoscopia , Colo/cirurgia , Feminino , Humanos , Hungria , Laparoscopia/métodos , Masculino , Estômago/cirurgia , Vagina/cirurgia
12.
Magy Seb ; 60(6): 301-6, 2007 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-18065369

RESUMO

BACKGROUND: The indication for the surgical treatment of lower limb compartment syndrome mostly depends on the clinical signs, which can be uncertain and often delayed, resulting in a late and insufficient intervention. AIM: In this study, the progression of compartment syndrome was monitored with the measurement of intracompartmental pressure and tissue oxygen saturation. MATERIALS AND METHODS: 16 patients (12 male and 4 female; mean age: 62,7 years) underwent acute lower limb revascularization surgery due to critical (more than 4 hour) limb ischaemia. The indications were the following: 5 iliac artery embolisms and 11 femoral artery occlusions. After revascularization, significant lower limb oedema and swelling were detected. To monitor the elevated intracompartmental pressure (ICP), KODIAG pressure meter was used. Tissue oxygen saturation (StO2) was measured with near-infrared-spectroscopy. RESULTS: In 12 cases the IPC exceeded the critical 40 mmHg. In these patients, StO2 was 50-53%, in spite of the successful re-canalisation. An urgent, semi-open fasciotomy was performed in these cases. In four patients, the clinical picture suggested compartment syndrome. However, the measured parameters did not indicate surgical intervention (ICP: 25-35 mmHg, StO2: normal). SUMMARY: In addition to the empirical guidelines, we describe an evidence based surgical intervention strategy for lower limb compartment syndrome. Our results and advised parameter intervals help the clinicians to decide between conservative and operative treatment of the disease.


Assuntos
Síndrome do Compartimento Anterior/diagnóstico , Síndrome do Compartimento Anterior/cirurgia , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/cirurgia , Embolia/diagnóstico , Artéria Femoral/fisiopatologia , Artéria Ilíaca/fisiopatologia , Doença Aguda , Idoso , Síndrome do Compartimento Anterior/etiologia , Síndrome do Compartimento Anterior/fisiopatologia , Síndrome do Compartimento Anterior/terapia , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/terapia , Pressão Sanguínea , Determinação da Pressão Arterial/instrumentação , Determinação da Pressão Arterial/métodos , Embolia/complicações , Embolia/fisiopatologia , Embolia/terapia , Medicina Baseada em Evidências , Feminino , Artéria Femoral/cirurgia , Humanos , Artéria Ilíaca/cirurgia , Masculino , Pessoa de Meia-Idade , Espectroscopia de Luz Próxima ao Infravermelho , Resultado do Tratamento
13.
Neurotox Res ; 12(2): 95-104, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17967733

RESUMO

The neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) and its receptors are widely expressed in the nervous system including the retina. PACAP has well-known neuroprotective effects in neuronal cultures in vitro and against different insults in vivo. Recently, we have shown that PACAP1-38 is neuroprotective against monosodium glutamate (MSG)-induced retinal degeneration. Studying the molecular mechanisms of this protection has revealed that PACAP1-38 stimulates anti-apoptotic mechanisms such as phosphorylation of ERK1/2 and inhibits pro-apoptotic signaling molecules such as JNK1/2, p38MAPK, caspase-3 and the translocation of mitochondrial cytochrome c and apoptosis inducing factor in glutamate-treated retinas in vivo. In the present study we investigated the effects of PACAP1-38 on a further signal transduction pathway possibly involved in the protective effect of intravitreal PACAP1-38 administration against apoptotic retinal degeneration induced by neonatal MSG treatment. The focus of the present study was the protein kinase A (PKA)-Bad-14-3-3 transduction pathway. In vivo MSG treatment led to a reduction in the levels of anti-apoptotic molecules (phospho-PKA phospho-Bad, Bcl-xL and 14-3-3 proteins) in the retina. Co-treatment with PACAP1-38 counteracted these effects: the level of phospho-PKA, phospho-Bad, Bcl-xL and 14-3-3 were increased. All effects of PACAP1-38 were inhibited by the PACAP antagonist PACAP6-38. In summary, our results show that PACAP1-38 activates the PKA-Bad-14-3-3 pathway which is inhibited by MSG treatment. Our results also provide new insights into the signaling mechanisms possibly involved in the PACAP-mediated anti-apoptotic effects.


Assuntos
Proteínas 14-3-3/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Doenças Retinianas/metabolismo , Transdução de Sinais/fisiologia , Proteína de Morte Celular Associada a bcl/metabolismo , Animais , Animais Recém-Nascidos , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Ácido Glutâmico , Modelos Biológicos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ratos , Ratos Wistar , Doenças Retinianas/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos
14.
Ann N Y Acad Sci ; 1095: 251-61, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17404038

RESUMO

In the study the authors aimed to demonstrate the expression and protective effect of heme oxygenase-1 (HO-1) in the delayed preconditioning (PC) on cultured myocardiac cells. Neonatal rat cardiac myocytes were exposed to ischemic (ischemic medium [IM] for 20 min) and pharmacological (adenosine, epinephrine, opioid) PC. Twenty-four hours later cells were subjected to a simulated ischemia (SI)--culturing for 3 h in IM, followed by 2-h reperfusion in normal medium--and then lactate dehydrogenase (LDH), live/death ratio, and apoptosis were measured. For demonstrating the protective role of HO-1, its enzymatic activity was competitively inhibited by administration of zinc protoporphyrin IX (ZnPPIX), and HO-1 synthesis was blocked with HO-1 siRNA. Cells in control group were cultured under normoxic conditions. In SI group, cells underwent only an SI without PC. HO-1 expression in all of the groups was demonstrated with immunostaining. Our results showed a significant decrease of LDH release, apoptosis, and cell death in PC groups versus SI group, which has been risen in ZnPPIX- and HO-1 siRNA-treated groups. HO-1 immunostaining showed an appreciable HO-1 expression in PC groups, which was abolished with HO-1 siRNA administration, but not in ZnPPIX group. The results therefore suggest that HO-1 expression increases in both ischemic and pharmacological PC, and HO-1 has cellular protective effect against cell death and apoptosis in ischemia-reperfusion-induced oxidative injury.


Assuntos
Heme Oxigenase-1/biossíntese , Precondicionamento Isquêmico Miocárdico , Miocárdio/enzimologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Heme Oxigenase-1/genética , Heme Oxigenase-1/fisiologia , Miocárdio/citologia , Ratos , Ratos Wistar
15.
Regul Pept ; 137(1-2): 20-6, 2006 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-16945433

RESUMO

Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are present in the retina and exert several distinct functions. PACAP has well-known neuroprotective effects in neuronal cultures in vitro and against different insults in vivo. Recently we have shown that PACAP is neuroprotective against monosodium glutamate (MSG)-induced retinal degeneration. In the present study we investigated the possible signal transduction pathways involved in the protective effect of intravitreal PACAP administration against apoptotic retinal degeneration induced by neonatal MSG treatment. MSG induced activation of proapoptotic signaling proteins and reduced the levels of antiapoptotic molecules in neonatal retinas. Co-treatment with PACAP attenuated the MSG-induced activation of caspase-3 and JNK, inhibited the MSG-induced cytosolic translocation of apoptosis inducing factor (AIF) and cytochrome c, and increased the level of phospho-Bad. Furthermore, PACAP treatment alone decreased cytosolic AIF and cytochrome c levels, while PACAP6-38 increased cytochrome c release, caspase-3 and JNK activity and decreased phospho-Bad activity. In summary, our results show that PACAP treatment attenuated the MSG-induced changes in apoptotic signaling molecules in vivo and suggest that also endogenously present PACAP has neuroprotective effects. These results may have further clinical implications in reducing glutamate-induced excitotoxicity in several ophthalmic diseases.


Assuntos
Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Doenças Retinianas/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Glutamato de Sódio/toxicidade , Animais , Ratos , Ratos Wistar
16.
Ann N Y Acad Sci ; 1070: 293-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16891268

RESUMO

The present article investigated the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on oxidative stress-induced apoptosis in neonatal rat cardiomyocytes. Our results show that PACAP decreased the ratio of apoptotic cells following H2O2 treatment. PACAP also diminished the activity of apoptosis signal-regulating kinase. These effects of PACAP were counteracted by the PACAP antagonist PACAP6-38. In summary, our results show that PACAP is able to attenuate oxidative stress-induced cardiomyocyte apoptosis and suggest that its cardioprotective effect is mediated through inhibition of the MAP kinase-dependent apoptotic pathway.


Assuntos
Apoptose/efeitos dos fármacos , MAP Quinase Quinase Quinase 5/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Animais , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Ratos , Ratos Wistar
17.
Ann N Y Acad Sci ; 1070: 507-11, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16891269

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) has well-documented neuroprotective actions, which have also been shown in retinal degeneration induced by monosodium glutamate (MSG) in neonatal rats. The aim of this article was to investigate the activation of extracellular signal-regulated kinase (ERK1/2) and cyclic adenosine 3',5'-phosphate (cAMP)-responsive element binding protein (CREB) signaling pathways by Western blot analysis in retinal degeneration induced by MSG. We found that intravitreal administration of PACAP preceding the MSG treatments induced significant increases in the phosphorylation, that is, the activation of ERK1/2 and its downstream target, CREB, 12 h after the treatment compared to the contralateral untreated eye during the first two treatments, with no further elevations 24 h after treatments. These results demonstrate that the degenerative effect of MSG and the protective effect of PACAP involve complex kinase signaling pathways and are related to cAMP/ERK/CREB activation.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Retina/efeitos dos fármacos , Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glutamato de Sódio/farmacologia , Animais , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar
18.
Magy Seb ; 59(1): 45-9, 2006 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-16637391

RESUMO

OBJECTIVES: In this study we proved the feasibility of a new minimally invasive procedure for the devascularisation of the proximal stomach and the abdominal esophagus to prevent recurrent variceal bleeding in portal hypertension in a new animal model. MATERIALS AND METHODS: Experiments were performed on 12 female pigs, in two animal groups. In the first step (I. group n=6) portal hypertension was created by controlled laparoscopic clip ligation of the portal vein. The increased portal pressure was established by the needle puncture of the portal vein and the spleen. Two weeks later, the dilated veins were sealed along the lesser and greater curvature and the transhiatal esophagus with the 10 mm LigaSure instrument. Successful of the experimental model had encouraged us to perform this method on other animals (II. group, n=6), using the 5 mm instrument. RESULTS: There was no intraoperative bleeding after using both LigaSure instruments. Autopsy (2 weeks later) showed correct placed clips with partial occlusion of the portal vein without portal vein thrombosis. There was no evidence of postoperative bleeding. Histological investigation of the gastric surface confirmed complete sealing of the extended varices. CONCLUSION: The laparoscopic LigaSure instrument was found to be safe and suitable equipment for the ligation of the dilated veins along the gastric surface and the abdominal esophagus, and this method could be an alternate choice for the patients with recurrent variceal bleeding.


Assuntos
Varizes Esofágicas e Gástricas/complicações , Esôfago/cirurgia , Hemorragia Gastrointestinal/prevenção & controle , Laparoscopia , Estômago/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Animais , Modelos Animais de Doenças , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/fisiopatologia , Esôfago/irrigação sanguínea , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/fisiopatologia , Hipertensão Portal/complicações , Hipertensão Portal/fisiopatologia , Pressão na Veia Porta , Estômago/irrigação sanguínea , Suínos
19.
Magy Seb ; 59(1): 50-7, 2006 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-16637392

RESUMO

The authors aimed to study of oxidative stress and thrombocyte function in the perioperative interval following the revascularization surgery of lower limb. The prospective randomised study involved 10 patients whose surgical interventions were indicated by lower limb embolism, thrombosis or abdominal aorta aneurysm, and 10 healthy volunteers were also involved in the study. Peripheral blood samples were collected before, and after the surgery (2, 24 hours and one week). The maximal free radical production and lag time of the free radical production of activated leukocytes were measured, and leukocyte adhesion molecules (CD11a and CD18) signing leucocyte activation were determined as well. Endogenous antioxidant defence status, reduced glutathione (GSH), total thiol-groups (-SH), SOD activity and thrombocyte function were investigated in platelet rich plasma and in whole blood. White blood cell count and free radical production was significantly higher in patients group before surgery than in healthy group (in case of the free radical production the difference proved to be 10 times (p < 0.01)) and elevated continuously during the observation time. The CD11a and CD18 expression of the granulocytes significantly decreased right after the revascularization, but with a gradual elevation, until the 7th day they exceed the ischaemic value. GSH concentration decreased significantly 2 and 24 hours after surgery and total thiol groups (-SH) followed the same kinetics. SOD activity was significantly lower in patients group haemolysates before surgery when it was measured in healthy groups (p < 0.01) and decreased further significantly 24 hours after the surgery (p < 0.01 vs. before surgery). Suppressed thrombocyte aggregation was detected in platelet rich plasma and in whole blood during the observation excepted the one week samples, where a highly significant elevation in ADP and collagen induced aggregation were observed. Our results show a great alteration in the antioxidant-prooxidant balance and the insufficiency of platelet aggregation's inhibition after peripheral vessel closure and revascularization intervention. We suggest the monitoring of the antioxidant status and thrombocyte function of patients going to underwent surgical intervention and if it necessary the therapeutic help.


Assuntos
Antioxidantes/metabolismo , Radicais Livres/metabolismo , Leucócitos/metabolismo , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Estresse Oxidativo , Procedimentos Cirúrgicos Vasculares , Idoso , Antígeno CD11a , Antígenos CD18 , Moléculas de Adesão Celular/sangue , Feminino , Glutationa/sangue , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Estudos Prospectivos , Compostos de Sulfidrila/sangue , Superóxido Dismutase/sangue , Fatores de Tempo
20.
Magy Seb ; 58(4): 245-9, 2005 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-16261872

RESUMO

Ischemic Preconditioning (IPC) can reduce ischemia/reperfusion injury produced during small bowel transplantation. We investigated the effects of classic and delayed preconditioning on oxidative stress prior to autotransplantation. Total orthotopic intestinal autotransplantation was performed on 18 dogs. In group I (G-I, non-preconditioned) 3-hours cold preservation in University of Wisconsin solution followed by 1-hour of reperfusion. In group II (G-II, classic preconditioned) before this procedure the intestine was preconditioned with 4 cycles of 5 minutes ischemia and 10 minutes reperfusion (IPC protocol). In group III (G-III, delayed preconditioned) on day 1 the animals underwent IPC protocol, and on day 2 autotransplantation was performed. We determined the content of malondialdehyde (MDA), reduced glutathione (GSH), and the activity of superoxide dismutase (SOD) in tissue samples. Our results showed increased lipid peroxidation, slightly elevated GSH level and decreased SOD activity in G-I. In G-II MDA slightly elevated, GSH increased markedly and SOD activity preserved by the end of reperfusion. In G-III GSH significantly increased and SOD activity passed the control activity. Our findings confirmed that both forms of preconditioning could moderate the severity of oxidative stress prior to preservation and auto transplantation. Delayed preconditioning is more effective especially to protect bowel tissue against oxidative injury.


Assuntos
Intestino Delgado/metabolismo , Intestino Delgado/transplante , Precondicionamento Isquêmico/métodos , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Animais , Cães , Glutationa/análise , Intestino Delgado/enzimologia , Peroxidação de Lipídeos , Masculino , Malondialdeído/análise , Superóxido Dismutase/metabolismo , Transplante Autólogo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA