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Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1ß, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1ß release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.
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With the progressive increase in the use of reproductive biotechnologies in the cattle industry, like artificial insemination and in vitro embryo production, the accurate determination of fertilizing competence of cryopreserved sperm samples is an essential issue. The routine methodology to assess bull sperm quality relies primarily on count, viability and motility of spermatozoa. However, these parameters do not tightly predict the reproductive success of samples. Therefore, identification of complementary markers of sperm functionality to strengthen the predictability of traditional spermogram is desirable to improve livestock reproduction practices. Previous results from our laboratory indicated that α5ß1 integrin plays a key role in bovine sperm function and mediates their interaction with the female reproductive tract. Thus, this study aimed to investigate whether the localization of α5ß1 held a correlation with fertilizing ability of bovine cryopreserved semen samples. Firstly, we assessed the quality of samples from six different bulls (A-F). We determined motility and viability of sperm samples after thawing and selection. Additionally, we measured the capacitation state of the samples by chlortetracycline (CTC) assay in the presence or absence of heparin, as an indicator of their responsiveness to a capacitating stimulus. Based on these assays, samples were classified being A the bull with the lowest quality and F the bull with the highest quality. Then, we studied the presence and localization of α5ß1 integrin. This protein showed a distribution pattern in the acrosomal (A), post-acrosomal (P) and acrosomal + post-acrosomal (A + P) regions with different localization percentages among the studied samples. Next, we determined the fertilizing ability of the samples in in vitro fertilization (IVF) assays and performed correlation analyses between IVF outcome and the routine spermogram parameters or α5ß1 integrin localization patterns. When the percentage of cells showing α5ß1 integrin was compared to fertilization rate, no correlation was observed. However, the presence of α5ß1 integrin in P and A + P regions (PA pattern), positively correlated with IVF rate (p < 0.05). These results suggest that while routine semen analyses failed to predict sperm reproductive competence, integrin localization in post-acrosomal region (PA pattern) showed a positive correlation with IVF outcome, thus posing an attractive marker to predict more accurately the reproductive performance of an individual.
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Integrinas , Motilidad Espermática , Animales , Bovinos , Criopreservación/veterinaria , Femenino , Fertilidad , Masculino , EspermatozoidesRESUMEN
La osteoartritis (OA) es una enfermedad crónica, degenerativa, muy invalidante, que destruye en forma gradual y progresiva el cartílago articular en diversas regiones: rodillas, caderas, hombros, manos, tobillos y columna vertebral. En este sentido, el ejercicio ha sido descrito como la intervención no farmacológica más recomendada para pacientes con OA. La práctica regular de ejercicio es considerada un componente integral del estilo de vida saludable; sin embargo, su efecto en el cartílago se mantiene como objeto de debate y especulaciones, así como la relación del ejercicio con el desarrollo de OA. Algunos estudios de modelos animales sugieren que el ejercicio puede ser beneficioso para la salud del cartílago, mientras otros demuestran su efecto nocivo. Una explicación general a estos resultados inconsistentes es que el correr a intensidad moderada tiene efectos beneficiosos, mientras que correr "vigorosamente" o de manera "extenuante" lleva a un efecto nocivo. El objetivo de este trabajo consistió en realizar una revisión de la literatura acerca de los efectos del ejercicio sobre el cartílago artícular, especialmente enfocado a modelos animales experimentales con ratas.
Osteoarthritis (OA) is a chronic, degenerative, and very disabling disease that gradually and progressively destroys articular cartilage in various regions: knees, hips, shoulders, hands, ankles and spine. In this sense, exercise has been described as the most recommended non-pharmacological intervention for patients with OA. Regular exercise is considered an integral component of the healthy lifestyle. However, its effect on cartilage remains the subject of debate and speculation, as well as the relationship between exercise and the development of OA. Some animal model studies suggest that exercise may be beneficial for cartilage health, while others demonstrate its harmful effect. A general explanation for these inconsistent results is that running at moderate intensity has beneficial effects, while running "vigorously" or "strenuously" leads to a harmful effect. The aim of this work was to make a literature review about the effects of exercise on cartilage, especially focused on experimental animal models with rats.
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Animales , Ratas , Osteoartritis/patología , Ejercicio Físico/fisiología , Cartílago Articular/anatomía & histología , Osteoartritis/fisiopatología , Modelos Animales de EnfermedadRESUMEN
PURPOSE: The effect of combined lifestyle interventions (LSI) including dietary and physical activity on metabolic health, energy metabolism and VO2max in diabetic patients has provided mixed results. We evaluated the impact of 1-year caloric restriction (CR), and 12-week supervised structured exercise training (SSET) on metabolic health, RMR and VO2max in obese adults with type 2 diabetes. METHODS: After 1-month education for LSI, 33 participants had anthropometric, biochemical and metabolic assessments. They then started CR based on RMR, and 3-month SSET during the months 1-3 (Early-SSET) or 4-6 (Late-SSET). Reassessments were planned after 3, 6 and 12 months. Using a per-protocol analysis, we evaluated parameter changes from baseline and their associations for the 23 participants (11 Early-SSET, 12 Late-SSET) who completed the study. RMR was adjusted (adjRMR) for age, sex, fat-free mass (FFM) and fat mass (FM). RESULTS: Compared with baseline, after 6 months we found significant increases in VO2max (+ 14%) and HDL-cholesterol (+ 13%), and reduction in body mass index (- 3%), FM (- 8%) and glycated hemoglobin (HbA1c, - 7%). Training-related caloric expenditure negatively correlated with changes in body weight (p < 0.001), FM (p < 0.001) and HbA1c (p = 0.006). These results were confirmed at the 12-month follow-up. Pooling together all follow-up data, adjRMR changes correlated with changes in glycemia (r = 0.29, p = 0.02), total-cholesterol (r = 0.29, p = 0.02) and VO2max (r = - 0.26,p = 0.02). No significant differences emerged between the Early- and Late-SSET groups. CONCLUSIONS: Combined intervention with SSET and CR improved metabolic control. Changes in metabolic health and fitness correlated with changes of adjRMR, which was reduced improving fitness, glycemia and cholesterolemia. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03785379. URL of registration: http://clinicaltrials.gov .
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Metabolismo Basal/fisiología , Restricción Calórica , Diabetes Mellitus Tipo 2/terapia , Metabolismo Energético/fisiología , Terapia por Ejercicio , Obesidad/terapia , Peso Corporal , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Reductora , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Obesidad/metabolismoRESUMEN
Mechano-electric feedback (MEF) is an established mechanism whereby myocardial deformation causes changes in cardiac electrophysiological parameters. Extensive animal, laboratory and theoretical investigation has demonstrated that abnormal patterns of cardiac strain can induce alteration of electrical excitation and recovery through MEF, which can potentially contribute to the establishment of dangerous arrhythmias. However, the clinical relevance of MEF in patients with heart disease remains to be established. This paper reviews up-to date experimental evidence describing the response to different types of mechanical stimuli in the intact human heart with the support of new data collected during cardiac surgery. It discusses modulatory effects of MEF that may contribute to increase the vulnerability to arrhythmia and describes MEF interaction with clinical conditions where mechanically induced changes in cardiac electrophysiology are likely to be more relevant. Finally, directions for future studies, including the need for in-vivo human data providing simultaneous assessment of the distribution of structural, functional and electrophysiological parameters at the regional level, are identified.
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Fenómenos Electrofisiológicos , Retroalimentación Fisiológica , Fenómenos Mecánicos , Animales , Arritmias Cardíacas/fisiopatología , HumanosRESUMEN
A novel form of alkali low-energy ion scattering is used to probe the deposition of nanoclusters onto a solid surface via buffer layer assisted growth (BLAG) in ultrahigh vacuum. A thin amorphous solid water (ASW) buffer layer is grown on a TiO2(110) single crystal cooled to 100 K. Au atoms deposited onto this layer arrange themselves into nanoclusters. The sample is then annealed to 320 K to desorb the ASW and enable the clusters to soft-land onto the substrate. Time-of-flight low-energy ion scattering, using Li+, Na+, and K+ projectiles, probes the materials during each step of the BLAG process to measure the surface composition and reveal the details of how the clusters form. The neutralization probability of Na+ ions singly scattered from the Au nanoclusters indicates that they increase in size after annealing and that the magnitude of the increase is a function of the buffer layer thickness. The adsorption of a thin, incomplete water layer prior to Au deposition forms nanoclusters that are possibly even smaller than those produced by direct deposition onto the clean substrate.
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Dual screen-printed carbon electrodes modified with 4-carboxyphenyl-functionalized double-walled carbon nanotubes (HOOC-Phe-DWCNTs/SPCEs) have been used as scaffolds for the preparation of electrochemical immunosensors for the simultaneous determination of the cytokines Interleukin-1ß (IL-1ß) and factor necrosis tumor α (TNF-α). IL-1ß. Capture antibodies were immobilized onto HOOC-Phe-DWCNTs/SPCEs in an oriented form making using the commercial polymeric coating Mix&Go™. Sandwich type immunoassays with amperometric signal amplification through the use of poly-HRP-streptavidin conjugates and H2O2 as HRP substrate and hydroquinone as redox mediator were implemented. Upon optimization of the experimental variables affecting the immunosensor performance, the dual immunosensor allows ranges of linearity extending between 0.5 and 100 pg/mL and from 1 to 200 pg/mL for IL-1ß and TNF-α, respectively, these ranges being adequate for the determination of the cytokines in clinical samples. The achieved limits of detection were 0.38 pg/mL (IL-1ß) and 0.85 pg/mL (TNF-α). In addition, the dual immunosensor exhibits excellent reproducibility of the measurements, storage stability of the anti-IL-Phe-DWCNTs/SPCE and anti-TNF-Phe-DWCNTs/SPCE conjugates, and selectivity as well as negligible cross-talking. The dual immunosensor was applied to the simultaneous determination of IL-1ß and TNF-α in human serum spiked at clinically relevant concentration levels and in real saliva samples.
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Electrodos , Interleucina-1beta/análisis , Nanotubos de Carbono , Factor de Necrosis Tumoral alfa/análisis , Técnicas Biosensibles , Técnicas Electroquímicas , Humanos , Peróxido de Hidrógeno , Inmunoensayo , Interleucina-1beta/sangre , Reproducibilidad de los Resultados , Saliva/química , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Conformational constrained ß-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the ß-hairpin peptide. The entity of the stability of the ß-hairpin peptide depends on the length of the bridge.
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Péptidos/química , Triazoles/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación ProteicaRESUMEN
Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor κB (NFκB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation.
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Colitis Ulcerosa/inmunología , Colitis/inmunología , Colon/inmunología , Enfermedad de Crohn/inmunología , Factores de Transcripción de Tipo Kruppel/inmunología , Macrófagos/inmunología , Proteínas Proto-Oncogénicas/inmunología , Animales , Línea Celular , Plasticidad de la Célula/inmunología , Colitis/inducido químicamente , Colitis/genética , Colitis/patología , Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Colon/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Sulfato de Dextran , Regulación de la Expresión Génica , Humanos , Factor 6 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/deficiencia , Factores de Transcripción de Tipo Kruppel/genética , Activación de Macrófagos , Macrófagos/patología , Masculino , Ratones , Ratones Noqueados , Monocitos/inmunología , Monocitos/patología , FN-kappa B/genética , FN-kappa B/inmunología , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/inmunología , Transducción de Señal , Transcripción GenéticaRESUMEN
Classical novae are important contributors to the abundances of key isotopes, such as the radioactive (18)F, whose observation by satellite missions could provide constraints on nucleosynthesis models in novae. The (17)O(p,γ)(18)F reaction plays a critical role in the synthesis of both oxygen and fluorine isotopes, but its reaction rate is not well determined because of the lack of experimental data at energies relevant to novae explosions. In this study, the reaction cross section has been measured directly for the first time in a wide energy range E(c.m.)~/= 200-370 keV appropriate to hydrogen burning in classical novae. In addition, the E(c.m.)=183 keV resonance strength, ωγ=1.67±0.12 µeV, has been measured with the highest precision to date. The uncertainty on the (17)O(p,γ)(18)F reaction rate has been reduced by a factor of 4, thus leading to firmer constraints on accurate models of novae nucleosynthesis.
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BACKGROUND: Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. OBJECTIVE: Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB). STUDY DESIGN AND RESULTS: Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs. CONCLUSIONS: In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.
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Hígado Graso/patología , Gastroplastia , Grasa Intraabdominal/patología , Hígado/patología , Obesidad Mórbida/metabolismo , Obesidad Mórbida/patología , Adulto , Anciano , Análisis de Varianza , Hígado Graso/metabolismo , Femenino , Estudios de Seguimiento , Gastroplastia/métodos , Humanos , Hígado/metabolismo , Estudios Longitudinales , Síndrome Metabólico/etiología , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Tamaño de los Órganos , Periodo Posoperatorio , Periodo Preoperatorio , Pérdida de PesoRESUMEN
Uterine cancer is today the upcoming neoplasia in gynaecological oncology. In Western countries endometrial cancer is mostly diagnosed after menopause and often becomes apparent with atypical uterine bleeding. Because of the great importance of such disease a series of accurate diagnostic analyses which require an adequate expenditure by hospital structures become necessary. Transvaginal sonography (TVS) remains the first choice to diagnose atypical bleeding because it is less invasive and highly bearable by the patients. TVS exam allows the selection of all patients who have an endometrial thickness more than 5 mm and/or with an inhomogeneous endometrial line thickness, who would then undergo further analyses. To achieve the diagnosis, office hysteroscopy carried out in an outpatient departments, is the most useful exam. Such exam allows a complete overview of the uterine cavity with possible detection of smaller lesions and a specific sampling of histological material. Hysteroscopy is today an indispensable aid in last resort diagnosis of endometrial cancer and is highly tolerated by patients.
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Carcinoma/diagnóstico , Neoplasias Endometriales/diagnóstico , Histeroscopía/métodos , Menopausia , Útero/patología , Anciano , Femenino , Humanos , Persona de Mediana Edad , Pacientes Ambulatorios , Hemorragia Uterina/diagnósticoRESUMEN
BACKGROUND: Remote ischaemic preconditioning (RIPC) induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in coronary artery bypass (CABG) surgery patients receiving predominantly cross-clamp fibrillation for myocardial protection. However, cold-blood cardioplegia is the more commonly used method world wide. OBJECTIVE: To assess whether RIPC is cardioprotective in CABG patients receiving cold-blood cardioplegia. DESIGN: Single-centre, single-blinded, randomised controlled trial. SETTING: Tertiary referral hospital in London. PATIENTS: Adults patients (18-80 years) undergoing elective CABG surgery with or without concomitant aortic valve surgery with cold-blood cardioplegia. Patients with diabetes, renal failure (serum creatinine >130 mmol/l), hepatic or pulmonary disease, unstable angina or myocardial infarction within the past 4 weeks were excluded. INTERVENTIONS: Patients were randomised to receive either RIPC (n = 23) or control (n = 22) after anaesthesia. RIPC comprised three 5 min cycles of right forearm ischaemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 min reperfusion. The control group had a deflated cuff placed on the upper arm for 30 min. MAIN OUTCOME MEASURES: Serum troponin T was measured preoperatively and at 6, 12, 24, 48 and 72 h after surgery and the area under the curve (AUC at 72 h) calculated. RESULTS: RIPC reduced absolute serum troponin T release by 42.4% (mean (SD) AUC at 72 h: 31.53 (24.04) microg/l.72 h in controls vs 18.16 (6.67) microg/l.72 h in RIPC; 95% CI 2.4 to 24.3; p = 0.019). CONCLUSIONS: Remote ischaemic preconditioning induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in CABG surgery patients undergoing cold-blood cardioplegia, making this non-invasive cardioprotective technique widely applicable clinically. TRIAL REGISTRATION NUMBER: NCT00397163.
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Puente de Arteria Coronaria/métodos , Paro Cardíaco Inducido/métodos , Precondicionamiento Isquémico Miocárdico/métodos , Daño por Reperfusión Miocárdica/prevención & control , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Método Simple Ciego , Resultado del Tratamiento , Troponina T/sangre , Adulto JovenRESUMEN
BACKGROUND AND PURPOSES: Erythropoietin (EPO) has been shown to protect against myocardial infarction in animal studies by activating phosphatidylinositol-3 kinase (PI3K)/Akt and ERK1/2. However these pro-survival pathways are impaired in the diabetic heart. We investigated the ability of EPO to protect human atrial trabeculae from non-diabetic and diabetic patients undergoing coronary artery bypass surgery, against hypoxia-reoxygenation injury. EXPERIMENTAL APPROACH: Human atrial trabeculae were exposed to 90min hypoxia and 120min reoxygenation. EPO was administered throughout reoxygenation. The developed force of contraction, calculated as a percentage of baseline force of contraction, was continuously monitored. The involvement of PI3K and ERK1/2 and the levels of activated caspase 3(AC3) were assessed. KEY RESULTS: EPO improved the force of contraction in tissue from non-diabetic patients (46.7+/-1.7% vs. 30.2+/-2.2% in control, p<0.001). These beneficial effects were prevented by the PI3K inhibitor, LY294002 and the ERK1/2 inhibitor, U0126. EPO also significantly improved the force of contraction in the diabetic tissue, although to a lesser degree. The levels of activated caspase 3 were significantly reduced in EPO treated trabeculae from both non-diabetic and diabetic patients, relative to their respective untreated controls. CONCLUSIONS AND IMPLICATIONS: EPO administered at reoxygenation protected human myocardial muscle by activating PI3K and ERK1/2 and reducing the level of activated caspase 3. This cardioprotection was also observed in the diabetic group. This data supports the potential of EPO being used as a novel cardioprotective strategy either alone or as an adjunct in the clinical setting alongside existing reperfusion therapies.
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Eritropoyetina/farmacología , Corazón/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteína Quinasa 3 Activada por Mitógenos/fisiología , Daño por Reperfusión Miocárdica/prevención & control , Fosfatidilinositol 3-Quinasas/fisiología , Adulto , Anciano , Caspasa 3/fisiología , Activación Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-akt/fisiología , Proteínas RecombinantesAsunto(s)
Máscaras Laríngeas , Adulto , Cirugía Bariátrica , Diseño de Equipo , Humanos , Intubación Intratraqueal/métodos , Masculino , Obesidad/cirugíaRESUMEN
Ornithine carbamoyltransferase has been purified from the liver of the loggerhead turtle Caretta caretta by a single-step procedure using chromatography on an affinity column to which the transition-state analogue, delta-N-(phosphonoacetyl)-L-ornithine (delta-PALO), was covalently bound. The procedure employed yielded an enzyme which was purified 373-fold and was judged to be homogeneous by nondenaturing and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme showed a specific activity of 224. The molar mass of the C. caretta enzyme was approximately 112 kDa, the single band obtained by SDS-PAGE indicated a subunit molar mass of 39.5 kDa; hence, the enzyme is a trimer of identical subunits. It catalyzes an ordered sequential mechanism in which carbamoyl phosphate binds first, followed by L-ornithine. The Michaelis constants were 0.858 mM for L-ornithine and 0.22 mM for carbamoyl phosphate, the dissociation constant of the enzyme-carbamoyl phosphate complex was 0.50 mM.
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Hígado/enzimología , Ornitina Carbamoiltransferasa/aislamiento & purificación , Ornitina Carbamoiltransferasa/metabolismo , Tortugas/metabolismo , Animales , Cromatografía en Gel , Calor , Concentración de Iones de Hidrógeno , Cinética , Ornitina Carbamoiltransferasa/químicaRESUMEN
In 1990 Sorin Biomedica introduced a new pyrolytic bileaflet heart valve, the Bicarbon, developed using innovative design concepts with new materials, housing, hinge mechanism, leaflet curvature and sewing ring construction. From June 1991 to May 1995, 192 bicarbon valves were implanted in 177 patients by one team. The patient population was 102 males and 75 females with an age range from 16 to 82 years (mean 62.5 years). Ninety-six were AVR, 68 MVR, 12 double valve replacements, 2 patients received another type of bileaflet valve as did the triple valve replacement. Overall hospital mortality was 5.2%. For MVR the mortality was 12.7%; for AVR it was 4.7%. There were no deaths associated with double or triple valve replacement. Five deaths were at reoperation, 2 at emergency operation, 1 aortic dissection, 2 for endocarditis, none of the deaths were valve related. One patient had a haemorrhage due to inadequate control of Warfarin therapy. Four valves were explanted: 3 mitrals for paravalvular leaks and 1 aortic for endocarditis. No patients showed any evidence of thromboembolic complications and there were no late deaths. All the surviving patients have improved their preoperative clinical status. Maximum follow-up is nearly 4 years, mean 32 months (range 1-47). Twenty one patients underwent haemodynamic evaluation by Doppler echocardiography. The mean pressure drop across 12 mitral valves was 8.34 mmHg (mean size 29.7 mm) and for 9 aortic valves it was 15.85 mmHg (mean size 23). Based on these results we are of the opinion that the Bicarbon valve is equivalent to the best of other bileaflet valves currently available.
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Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Válvula Aórtica , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Prótesis Valvulares Cardíacas/estadística & datos numéricos , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral , Complicaciones Posoperatorias/epidemiología , Diseño de Prótesis , Factores de TiempoRESUMEN
The ideal mechanical valve abolishes all potential areas for blood stagnation and hence the potential for micro-emboli and clot formation. This problem has been addressed by the innovative design of the Jyros valve which has evolved from the technology available from Russian space research. The valve comprises two pyrolytic carbon leaflets which can rotate within the solid carbon housing to either align themselves to the optimum haemodynamic configuration, or to respond by rotation either continuous or intermittent, according to the degree of swirl on the inflow profile. This Jyros mechanical heart valve has been assessed in vivo at the London Chest Hospital since August 1992 where the series of unselected patients constitutes the largest single user experience available. 107 valves were implanted in 100 patients of age range 33 to 80 years. 23 patients were re-replacement for failed xenograft and 26 underwent concomitant revascularisation. 92 patients left hospital and 4 died later all from non-valve related causes. Two valves were explanted for endocarditis (one pre-existing) but successfully re-replaced. There have been no late thrombo-embolic events. Two patients with AVR & CABG had strokes at 8 months. There is no excessive haemolysis in excess of that detected for any mechanical valve nor any mechanical valve-related failure. Rotation of the valve is variable and can be visualised by 2D and M mode echo and by X-ray screening as the leaflets are impregnated with Boron carbide. Half of the valves rotate constantly and a quarter intermittently. There appears to be no disadvantage to patients in whom no valve rotation could be demonstrated. We have found that the theoretical potential of performance have been achieved.
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Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Adulto , Anciano , Válvula Aórtica , Velocidad del Flujo Sanguíneo , Prótesis Valvulares Cardíacas/estadística & datos numéricos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral , Complicaciones Posoperatorias/epidemiología , Diseño de PrótesisRESUMEN
An important factor in the production of myocardial damage following cardiopulmonary bypass in the creation of oxygen derived free radicals. Few sources for these radicals have been identified but experimentally activated neutrophils are known to release free radical which contribute to myocyte necrosis. The aim of this pilot study was to identify whether, by depleting patients of leukocytes and particularly neutrophils on bypass, a better degree of myocardial protection could be observed using specific identifiers of myocardial damage. Ten patients undergoing urgent coronary artery bypass for unstable angina with impaired left ventricular function were leuko-depleted using a PALL medical leukocyte filter in the extra corporeal circulation together with leukocyte depletion of all transfused blood. A similar group of matched controls had only an arterial line filter without leukodepletion. All patients were operated by one surgeon using identical techniques of intermittent cross clamping and fibrillation at moderate hypothermia. Full blood count, Glutathione, Troponin T and CPK/MB were measured before, during and at identified intervals up to 72 hour after bypass. Preliminary results show little change in the total leukocyte count but the Troponin T and CPK/MB values were lower in the filtered group than in the control group and an increased level of total Glutathione in the filter group showed that there was less oxidated stress on the myocardium. Currently this filter is an expensive addition to bypass surgery but these preliminary results suggest that activated neutrophil depletion on bypass may be of benefit to patients with unstable angina, impending myocardial necrosis and low ejection fraction.