RESUMEN
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.
Asunto(s)
Proteínas Bacterianas/química , Glicoconjugados , Lectinas/química , Pseudomonas aeruginosa/química , Glicoconjugados/síntesis química , Glicoconjugados/química , Humanos , Resonancia Magnética Nuclear BiomolecularRESUMEN
The reperfusion of acute ischaemic myocardium is essential for myocardial salvage, so-called "gold standard" therapy, however it can result in serious damage to the myocardium. Functional alterations occur, including depressed contractile function and decreased coronary flow as well as altered vascular reactivity. Over several decades it has been demonstrated that oxygen radical formation is greatly increased in the post-ischaemic heart and serves as a critical central mechanism of ischaemic-reperfusion injury. However it has been demonstrated that free radicals play an important role in the endogenous adaptation phenomenon of the heart, too. Ischaemic preconditioning is a cellular adaptive response of the heart to stress, which provides the most potent endogenous protection against reperfusion arrhytmias, stunning and infarction. Post-conditioning defined as brief periods of ischaemia and reperfusion during the very early minutes of reperfusion stimulates endogenous adaptation. Post-conditioning may also attenuate the damage to endothelial cells and cardiomyocytes from oxidants, cytokines, proteases and inflammatory cells.
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Radicales Libres/metabolismo , Poscondicionamiento Isquémico , Precondicionamiento Isquémico Miocárdico , Infarto del Miocardio/complicaciones , Isquemia Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Animales , Circulación Coronaria , Humanos , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico Miocárdico/métodos , Daño por Reperfusión Miocárdica/etiologíaRESUMEN
We report on a new anti-influenza virus agent, SA-19, a lipophilic glycopeptide derivative consisting of aglycoristocetin coupled to a phenylbenzyl-substituted cyclobutenedione. In Madin-Darby canine kidney cells infected with influenza A/H1N1, A/H3N2, or B virus, SA-19 displayed a 50% antivirally effective concentration of 0.60 µM and a selectivity index (ratio of cytotoxic versus antiviral concentration) of 112. SA-19 was 11-fold more potent than unsubstituted aglycoristocetin and was active in human and nonhuman cell lines. Virus yield at 72 h p.i. was reduced by 3.6 logs at 0.8 µM SA-19. In contrast to amantadine and oseltamivir, SA-19 did not select for resistance upon prolonged virus exposure. SA-19 was shown to inhibit an early postbinding step in virus replication. The compound had no effect on hemagglutinin (HA)-mediated membrane fusion in an HA-polykaryon assay and did not inhibit the low-pH-induced refolding of the HA in a tryptic digestion assay. However, a marked inhibitory effect on the transduction exerted by retroviral pseudoparticles carrying an HA or vesicular stomatitis virus glycoprotein (VSV-G) fusion protein was noted, suggesting that SA-19 targets a cellular factor with a role in influenza virus and VSV entry. Using confocal microscopy with antinucleoprotein staining, SA-19 was proven to completely prevent the influenza virus nuclear entry. This virus arrest was characterized by the formation of cytoplasmic aggregates. SA-19 appeared to disturb the endocytic uptake and trap the influenza virus in vesicles distinct from early, late, or recycling endosomes. The aglycoristocetin derivative SA-19 represents a new class of potent and broad-acting influenza virus inhibitors with potential clinical relevance.
Asunto(s)
Antivirales/farmacología , Citoplasma/virología , Glicopéptidos/farmacología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Animales , Antivirales/química , Línea Celular , Citoplasma/efectos de los fármacos , Perros , Glicopéptidos/química , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/fisiología , Virus de la Influenza A/fisiología , Virus de la Influenza B/fisiología , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Estructura Molecular , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
The antioxidant glutathione-S-transferase (GST) is a crucial determinant of the development of ischaemic-reperfusion (I/R) injury, and plays a pivotal role in the regulation of the mitogen activated protein kinase (MAPK) pathways involved in stress response and apoptosis. The aim of this study was to investigate whether inhibition of GST can abolish the benefit of ischaemic postconditioning (IPoC). A neonatal rat cardiomyocyte cell culture was prepared and divided into 6 groups: (I) control group without treatment; (II) cells exposed to simulated I/R; (III) simulated I/R (sI/R) with IPoC; (IV) ethacrynic acid (EA) alone; (V) sI/R with EA; and (VI) sI/R and IPoC together with EA. Viability of the cells was measured by MTT assay, the quantity of apoptotic cells was assessed by flow cytometry following annexin V-FITC - propidium-iodide double staining. The activation of JNK, p38, ERK/p42-p44 MAPKs, and GSK-3ß protein kinase was determined by flow-cytometric assay. GST inhibition markedly increased the apoptosis and decreased the cell viability despite IPoC. The protective effect of IPoC was lost in GST-inhibited groups for all MAPKs and GSK-3ß. GST activity is required for the survival of cultured cardiomyocytes under stress conditions. GST inhibition was associated with differential activation of MAP and the protein kinases regulating these pathways in the process of ischaemic postconditioning.
Asunto(s)
Glutatión Transferasa/antagonistas & inhibidores , Glutatión Transferasa/fisiología , Poscondicionamiento Isquémico , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/enzimología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Ácido Etacrínico/farmacología , Citometría de Flujo , Modelos Biológicos , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Proyectos Piloto , Ratas , Ratas WistarRESUMEN
The diagnostic characteristics of electromechanical mapping (EMM) were evaluated in porcine myocardial infarction (MI) models with the parallel application of cardiac magnetic resonance imaging (cMRI) from the aspect of different pathophysiology and localization. Balloon occlusion in the left anterior descending coronary artery (LAD balloon group) or coil deployment in the LAD (LAD coil group) or circumflex artery (Cx coil group) was applied percutaneously in 16 domestic pigs. Regional left ventricular viability data were captured via cMRI and EMM. The unipolar voltage (UV) value was significantly decreased in segments containing transmural and subendocardial late enhancement compared with viable segments in the LAD balloon, LAD coil, and Cx coil groups. Receiver operating characteristic analysis revealed area under the curve values of 0.809 and 0.691 in the LAD infarct territory, and 0.864 and 0.855 in the Cx infarct territory for the UV compared with cMRI viability results as transmural late enhancement or viable tissue and subendocardial late enhancement or viable tissue, respectively. In conclusion, the UV value detected the presence of scar tissue with differential transmural extent and which represented proper diagnostic features both in the reperfused and nonreperfused models. This data could provide additional benefit in the clinical use of EMM for diagnostic purposes.
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Mapeo del Potencial de Superficie Corporal/métodos , Modelos Animales de Enfermedad , Imagen por Resonancia Magnética/métodos , Infarto del Miocardio/diagnóstico , Animales , Angiografía Coronaria , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Curva ROC , Sensibilidad y Especificidad , Sus scrofaRESUMEN
The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range. A few of them showed antiviral activity, in particular against influenza virus.
Asunto(s)
Antibacterianos/síntesis química , Antivirales/síntesis química , Isoindoles/química , Teicoplanina/química , Antibacterianos/química , Antibacterianos/farmacología , Antivirales/farmacología , Antivirales/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Farmacorresistencia Viral/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Isoindoles/síntesis química , Pruebas de Sensibilidad Microbiana , o-Ftalaldehído/químicaRESUMEN
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.
Asunto(s)
Vasos Sanguíneos/patología , Modelos Animales , Stents/efectos adversos , Anciano , Anciano de 80 o más Años , Animales , Perros , Femenino , Humanos , Masculino , Persona de Mediana Edad , Túnica Íntima/patología , Procedimientos Quirúrgicos VascularesRESUMEN
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.
Asunto(s)
Antioxidantes/metabolismo , Intestinos/patología , Isquemia/metabolismo , Poscondicionamiento Isquémico , Estrés Oxidativo , Daño por Reperfusión/prevención & control , Trasplante Autólogo , Isquemia Tibia , Adenosina , Alopurinol , Animales , Modelos Animales de Enfermedad , Glutatión/metabolismo , Insulina , Intestinos/irrigación sanguínea , Laparotomía , Peroxidación de Lípido , Malondialdehído/metabolismo , Soluciones Preservantes de Órganos , Rafinosa , Daño por Reperfusión/metabolismo , Superóxido Dismutasa/metabolismo , Sus scrofa , Factores de TiempoRESUMEN
Pleuromutilin is a fungal diterpene natural product with antimicrobial properties, semisynthetic derivatives of which are used in veterinary and human medicine. The development of bacterial resistance to pleuromutilins is known to be very slow, which makes the tricyclic diterpene skeleton of pleuromutilin a very attractive starting structure for the development of new antibiotic derivatives that are unlikely to induce resistance. Here, we report the very first synthetic modifications of pleuromutilin and lefamulin at alkene position C19-C20, by two different photoinduced addition reactions, the radical thiol-ene coupling reaction, and the atom transfer radical additions (ATRAs) of perfluoroalkyl iodides. Pleuromutilin were modified with the addition of several alkyl- and aryl-thiols, thiol-containing amino acids and nucleoside and carbohydrate thiols, as well as perfluoroalkylated side chains. The antibacterial properties of the novel semisynthetic pleuromutilin derivatives were investigated on a panel of bacterial strains, including susceptible and multiresistant pathogens and normal flora members. We have identified some novel semisynthetic pleuromutilin and lefamulin derivatives with promising antimicrobial properties.
RESUMEN
New sugar derivatives of ristocetin were prepared by copper-catalyzed 1,3-dipolar cycloaddition reaction using azido-ristocetin aglycon and various propargyl glycosides. Some of them were found to be active against gram-positive bacteria and showed favorable antiviral activity against the H1N1 subtype of influenza A virus.
Asunto(s)
Antibacterianos/síntesis química , Antivirales/síntesis química , Doxorrubicina/análogos & derivados , Ristocetina/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacología , Antivirales/química , Antivirales/farmacología , Catálisis , Cobre/química , Doxorrubicina/química , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ristocetina/síntesis química , Ristocetina/farmacologíaAsunto(s)
Educación Médica/historia , Docentes Médicos/historia , Gastroenterología/historia , Medicina Interna/historia , Liderazgo , Sociedades Médicas/historia , Academias e Institutos/historia , Distinciones y Premios , Educación Médica/organización & administración , Gastroenterología/educación , Historia del Siglo XX , Humanos , Hungría , Medicina Interna/educación , Publicaciones Periódicas como Asunto/historiaRESUMEN
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.
Asunto(s)
Pared Abdominal/cirugía , Materiales Biocompatibles , Proliferación Celular , Peritoneo/fisiología , Polipropilenos , Siliconas , Mallas Quirúrgicas , Ingeniería de Tejidos , Animales , Adhesión Celular , Reacción a Cuerpo Extraño/fisiopatología , Hernia Abdominal/cirugía , Inmunohistoquímica , Queratinas/análisis , Antígeno Ki-67/análisis , Microscopía Electrónica de Rastreo , Modelos Animales , Neovascularización Fisiológica , Conejos , Ingeniería de Tejidos/métodos , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
Antibiotic resistance is one of the major challenges in healthcare of our time. To meet this challenge, we designed and prepared guanidine and lipophilic guanidine derivatives of the glycopeptide antibiotic teicoplanin to armed them with activity against the most threatening nosocomial bacteria, multiresistant enterococci. From teicoplanin and its pseudoaglycone, a series of N-terminal guanidine derivatives have been prepared with free and amide C-terminal parts. Six aliphatic and aromatic lipophilic carbodiimides were prepared and used for the synthesis of lipophilic guanidine teicoplanin conjugates. All new N-terminal guanidine antibiotics showed high activity against a standard panel of Gram-positive bacteria. Four selected derivatives displayed excellent antibacterial activity against a series of nosocomial VanA Enterococcus faecium strains.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Microbiana/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Glicopéptidos/farmacología , Guanidinas/farmacología , Teicoplanina/farmacología , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
The limited scope of antiviral drugs and increasing problem of antiviral drug resistance represent a global health threat. Glycopeptide antibiotics and their lipophilic derivatives have emerged as relevant inhibitors of diverse viruses. Herein, we describe a new strategy for the synthesis of dual hydrophobic and lipophobic derivatives of glycopeptides to produce selective antiviral agents without membrane-disrupting activity. Perfluorobutyl and perfluorooctyl moieties were attached through linkers of different length to azido derivatives of vancomycin aglycone and teicoplanin pseudoaglycone, and the new derivatives were evaluated against a diverse panel of viruses. The teicoplanin derivatives displayed strong anti-influenza virus activity at nontoxic concentrations. Some of the perfluoroalkylated glycopeptides were also active against a few other viruses such as herpes simplex virus or coronavirus. These data encourage further exploration of glycopeptide analogues for broad antiviral application.
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Antivirales/síntesis química , Fluorocarburos/química , Teicoplanina/química , Vancomicina/química , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antivirales/química , Antivirales/farmacología , Bacillus subtilis/efectos de los fármacos , Catálisis , Línea Celular , Supervivencia Celular/efectos de los fármacos , Coronavirus/efectos de los fármacos , Perros , Humanos , Pruebas de Sensibilidad Microbiana , Paladio/química , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Virus Zika/efectos de los fármacosRESUMEN
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.
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Supervivencia de Injerto/efectos de los fármacos , Sustancias de Crecimiento/farmacología , Intestino Delgado/metabolismo , Intestino Delgado/trasplante , Estrés Oxidativo/efectos de los fármacos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Animales , Frío , Peroxidación de Lípido/fisiología , Masculino , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Radioinmunoensayo , Ratas , Ratas Wistar , Conservación de Tejido , Trasplante AutólogoRESUMEN
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.
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Antioxidantes/uso terapéutico , Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Sustancias Protectoras/uso terapéutico , Ribavirina/uso terapéutico , Silimarina/uso terapéutico , Adulto , Anciano , Alanina Transaminasa/sangre , Método Doble Ciego , Femenino , Hepacivirus/genética , Hepatitis C Crónica/metabolismo , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/sangre , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Superóxido Dismutasa/sangre , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Amputación Quirúrgica , Miembros Artificiales , Oseointegración , Enfermedades Vasculares Periféricas/rehabilitación , Enfermedades Vasculares Periféricas/cirugía , Muslo/cirugía , Soporte de Peso , Tornillos Óseos , Terapia por Ejercicio/métodos , Femenino , Fémur , Humanos , Hungría , Masculino , Enfermedades Vasculares Periféricas/fisiopatología , Reoperación , TitanioRESUMEN
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.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía , Colon/cirugía , Femenino , Humanos , Hungría , Laparoscopía/métodos , Masculino , Estómago/cirugía , Vagina/cirugíaRESUMEN
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.
Asunto(s)
Acetilcisteína/farmacología , Fármacos Cardiovasculares/farmacología , Hemodinámica/efectos de los fármacos , Precondicionamiento Isquémico , Hígado/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Modelos Animales de Enfermedad , Perros , Hígado/irrigación sanguínea , Hígado/fisiopatología , Daño por Reperfusión/fisiopatologíaRESUMEN
Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conjugation methods. Three series of derivatives bearing two lipophilic groups were synthesized by attaching bis-alkylthio maleimides directly or through linkers of different lengths to the glycopeptide. Access to the fourth and fifth series of compounds was achieved by click chemistry, introducing single alkyl/aryl chains directly or through a tetraethylene glycol linker to the same position. A sixth group of semisynthetic derivatives was obtained by sulfonylation of the N-terminus. Of the 42 lipophilic teicoplanin pseudoaglycon derivatives tested, about half showed broad activity against influenza A and B viruses, with some of them having reasonable or no cytotoxicity. Minor differences in the side chain length as well as lipophilicity appeared to have significant impact on antiviral activity and cytotoxicity. Several lipoglycopeptides were also found to be active against human coronavirus.