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Objective: To analyze the clinicopathological features of pseudotumor-like tissue around aseptic joint arthroplasty and aseptic lymphocytic vasculitis-associated lesions (ALVAL) scores. The characters of wear granules were observed. Methods: Total 122 cases were retrieved from the surgical pathology files between May 2015 and August 2018 in the department of pathology in Beijing Jishuitan Hospital, which included the knee joint arthroplasty (10 cases) and hip arthroplasty (112 cases). There were 62 females and 60 males. Patients' age ranged from 29 to 86 years (mean 56 years). The pseudotumor-like tissue around aseptic joint arthroplasty were stained with HE and analyzed by two ALVAL score systems. The characters of wear granules were observed by light microscope and polarized light. Results: The cohort included 62 females and 60 males. Patients' age ranged from 29 to 86 years (mean 56 years). Compbell-ALVAL system includes synovial lining,inflammatory infiltrate and tissue organization. The scores were: low (0-4): 18cases; moderate (5-8): 101 cases; high (9-10): 3 cases. Oxford-ALVAL system only evaluated the inflammatory infiltrate,and the scores were:0 grade:56 cases; 1 grade:51 cases; 2 grade: 12 cases; 3 grade:3 cases. Cases with high score in the Compbell-ALVAL system were concordant with the 3 grade of the Oxford-ALVAL system. Under light microscope,the metal particles were small black granules; the polyethylene fibers were needle-like and easily visible in polarized light. The polymethylmethacrylate showed clear spaces because of particle melting. Conclusions: The Compbell-ALVAL scoring system is based on the histologic analysis of pseudotumor-like tissue around aseptic joint arthroplasty, and the Oxford-ALVAL scoring systems is based on lymphocytic response. The wear particles could be differentiated by the features in the light microscope.
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Artroplastia de Reemplazo , Artropatías/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Metales , Persona de Mediana Edad , Diseño de Prótesis , Falla de PrótesisRESUMEN
Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.
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Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Ácido Mevalónico/metabolismo , Polimorfismo de Nucleótido Simple/genética , Posmenopausia/efectos de los fármacos , Posmenopausia/genética , Anciano , Alelos , Pueblo Asiatico/genética , Densidad Ósea/genética , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/genética , Femenino , Haplotipos , Humanos , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genéticaRESUMEN
UNLABELLED: The bone mineral density (BMD) of a total of 1,379 healthy postmenopausal Chinese women was measured. Ten tagging SNPs of the sclerostin (SOST) gene were genotyped. Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in postmenopausal Chinese women. INTRODUCTION: The purpose of the study was to determine the associations between polymorphisms of SOST gene and BMD in postmenopausal Chinese women. METHODS: A total of 1,379 independent healthy postmenopausal Chinese women including 703 in our previous study were recruited. The BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. RESULTS: The rs2023794 and rs74252774 and the haplotype ACCATTCT of SOST gene were associated with age and body mass index (BMI) adjusted L1-4 BMD (P values were 0.010, 0.007, and 0.007, respectively) even after performing the Bonferroni multiple-significance-test correction. There was a clear trend in these regions that the CC genotype of the rs2023794 and the TT genotype of the rs74252774 have higher BMD values than other genotypes. The contributions of the rs2023794 and rs74252774 to the phenotypic variation of L1-4 BMD were 0.6 and 0.7 %, respectively. We failed to find any association between the 10 SNPs and 6 haplotypes of the SOST gene and BMD at the hip site in this study. CONCLUSIONS: Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in a large sample of postmenopausal Chinese women.
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Pueblo Asiatico/genética , Densidad Ósea/genética , Proteínas Morfogenéticas Óseas/genética , Marcadores Genéticos/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales , Anciano , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Vértebras Lumbares/fisiología , Persona de Mediana Edad , Posmenopausia/genética , Posmenopausia/fisiologíaRESUMEN
Patients with haemophilia (PWH) are usually monitored by the one-stage activated partial thromboplastin time (aPTT) factor VIII (FVIII) assay. Different aPTT activators may affect clotting time (CT) and FVIII:C levels in patients treated with PEGylated FVIII. To evaluate the characteristics of PEGylated FVIII (BAY 94-9027) in various aPTT clotting assays, and to identify suitable aPTT reagents for monitoring BAY 94-9027 during the treatment of PWH, BAY 94-9027 and World Health Organization (WHO) 8th FVIII standards (WHO-8) were spiked into pooled and individual severe haemophilia A plasma at 1.0, 0.25 and 0.05 IU mL(-1) . Five commercial aPTT reagents widely used in clinical laboratories were compared and evaluated for BAY 94-9027 activity in plasma from PWH. BAY 94-9027 and WHO-8 bestowed similar CT and excellent precision when ellagic acid (SynthAFax, Dade Actin, and Cephascreen) aPTT reagents were used. In contrast, BAY 94-9027 showed significantly prolonged CT and poor precision compared with WHO-8 using silica aPTT reagents (APTT-SP and STA PTT 5). Furthermore, free 60-kDa polyethylene glycol (PEG), used for the conjugation of FVIII, showed a dose-dependent prolongation of CT in the APTT-SP assay. There was no effect on the SynthAFax-APTT, prothrombin time, or FXIa-initiated thrombin generation assay, demonstrating that the PEG moiety on FVIII has no general effect on the coagulation cascade. In summary, ellagic aPTT reagents (SynthAFax, Dade Actin, and Cephascreen) are most suitable for evaluating potency of BAY 94-9027 and should be the preferred aPTT reagents used in clinical laboratories for monitoring FVIII activity after infusion of BAY 94-9027 to PWH.
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Factor VIII/química , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Tiempo de Tromboplastina Parcial/métodos , Polietilenglicoles/química , Coagulación Sanguínea/efectos de los fármacos , Factor VIII/farmacología , Humanos , Tiempo de Tromboplastina Parcial/instrumentación , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Dióxido de Silicio/química , Resultado del TratamientoRESUMEN
PEGylation of B-domain deleted factor VIII (PEG-FVIII-BDD) prolongs the half-life of the molecule by approximately twofold in animals (Mei et al., Blood 2010; 116: 270). To investigate the role of von Willebrand factor (vWF) in the catabolism of PEG-FVIII-BDD in vivo, a FVIII-BDD mutant (F8V), which is incapable of binding vWF, was generated by deleting the vWF-binding region in the a3 domain of FVIIII-BDD. F8V was expressed, purified and PEGylated by site-specific conjugation. The biochemical and biological properties of F8V and PEGylated F8V (PEG-F8V) were evaluated in vitro and in vivo. The specific activity of purified F8V by a chromogenic assay was similar to FVIII-BDD and PEGylation had minimal impact on the specific activity of F8V in this assay. Analysis by Biacore indicated that both F8V and PEG-F8V display greatly reduced vWF binding in vitro. Pharmacokinetic studies in FVIII knockout (HaemA) mice showed that the terminal half-life (T1/2 ) of F8V was dramatically reduced relative to FVIII-BDD (0.6 h vs. 6.03 h). PEGylation of F8V promoted a significant increase in T1/2 , although PEGylation did not fully compensate for the loss in vWF binding. PEG-F8V showed a shorter T1/2 than PEG-FVIII-BDD both in HaemA mice (7.7 h vs. 14.3 h) and in Sprague-Dawley male rats (2.0 ± 0.3 h vs. 6.0 ± 0.5 h). These data demonstrated that vWF contributes to the longer T1/2 of PEG-FVIII-BDD. Furthermore, this suggests that the clearance of the FVIII:vWF complex, through vWF receptors, is not the sole factor which places an upper limit on the duration of PEG-FVIII circulation in plasma.
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Factor VIII/metabolismo , Polietilenglicoles/metabolismo , Factor de von Willebrand/metabolismo , Animales , Electroforesis en Gel de Poliacrilamida , Factor VIII/aislamiento & purificación , Factor VIII/farmacocinética , Semivida , Humanos , Ratones , Polietilenglicoles/farmacocinética , Unión Proteica , Estructura Terciaria de Proteína , Ratas , Ratas Sprague-Dawley , Eliminación de Secuencia , Especificidad por SustratoRESUMEN
Surgery is the primary treatment for esophageal cancer, but the postoperative complication rate remains high. Therefore, it is important to prevent and manage postoperative complications to improve prognosis. Common perioperative complications of esophageal cancer include anastomotic leakage, gastrointestinal tracheal fistula, chylothorax, and recurrent laryngeal nerve injury. Respiratory and circulatory system complications, such as pulmonary infection, are also quite common. These surgery-related complications are independent risk factors for cardiopulmonary complications. Complications, such as long-term anastomotic stenosis, gastroesophageal reflux, and malnutrition are also common after esophageal cancer surgery. By effectively reducing postoperative complications, the morbidity and mortality of patients can be reduced, and their quality of life can be improved.
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Fístula del Sistema Digestivo , Neoplasias Esofágicas , Humanos , Calidad de Vida , Complicaciones Posoperatorias/prevención & control , Fuga Anastomótica/etiología , Neoplasias Esofágicas/cirugía , Pronóstico , Esofagectomía/efectos adversos , Fístula del Sistema Digestivo/cirugía , Estudios RetrospectivosRESUMEN
The Sunong black pig is a new composite breed under development generated from Chinese indigenous pig breeds (i.e., Taihu and Huai) and intensive pig breeds (i.e., Landrace and Berkshire), which is an important genetic material for studying breeding mechanisms. However, there is currently limited knowledge about the genetic structure and germplasm characteristics of Sunong black pigs. To comprehensively understand their genetic composition and ancestry proportions, we performed population structure and local ancestry inference analysis based on whole-genome sequencing information. The results showed that Sunong black pigs could be clustered independently into a group, whose pedigree was intermediate between indigenous and commercial pig breeds, but closer to commercial pigs. Furthermore, local ancestry inference analysis revealed that Sunong black pigs inherited immune and reproductive traits from indigenous pig breeds, including CC and CXC chemokine family, Toll-like receptor family, IFN gene family, ESR1, AREG and EREG gene, while growth and development-related traits were inherited from commercial pig breeds, including IGF1 and GSY2 gene. Overall, Sunong black pigs have formed a relatively stable genome structure with some advantageous traits inherited from their ancestral breeds. This study deepened the understanding of the breeding mechanism of Sunong black pigs and provided a reference for cross-breeding programmes in livestock.
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Polimorfismo de Nucleótido Simple , Sus scrofa , Porcinos/genética , Animales , Sus scrofa/genética , Linaje , Genoma , Análisis de Secuencia de ADN/veterinaria , Variación GenéticaRESUMEN
SUMMARY: Association between ten single-nucleotide polymorphisms (SNPs) in the human ALOX12 and ALOX15 genes and variations in peak bone mineral density (BMD) in a large sample of Chinese nuclear families with female offspring using the quantitative transmission disequilibrium test (QTDT). Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women. INTRODUCTION: The aim of this study was to investigate whether polymorphisms in the human ALOX12 and ALOX15 genes are associated with variations in peak BMD in Chinese nuclear families with female offspring. METHODS: Each five SNPs in the ALOX12 and ALOX15 genes were genotyped in a total of 1,260 individuals from 401 Chinese nuclear families. The BMD of the lumbar spine, femoral neck and total hip was measured by dual-energy X-ray absorptiometry. We tested whether a single SNP or a haplotype was associated with peak BMD variations using the QTDT. RESULTS: Using QTDT to measure within-family associations in ALOX15, we observed a significant association between rs916055 and BMD in the lumbar spine (p = 0.027 in the permutation 1,000 test). However, in ALOX12, rs312470 was significantly associated with BMD in the femoral neck (p = 0.029 and p = 0.036 in the permutation 1,000 test). The results of a haplotype analysis supported the findings of the single locus test for ALOX15. CONCLUSIONS: Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women.
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Araquidonato 12-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/genética , Pueblo Asiatico/genética , Densidad Ósea/genética , Polimorfismo de Nucleótido Simple , Absorciometría de Fotón , Adulto , Anciano , Femenino , Cuello Femoral/fisiología , Frecuencia de los Genes/genética , Genotipo , Haplotipos , Articulación de la Cadera/fisiología , Humanos , Desequilibrio de Ligamiento/genética , Vértebras Lumbares/fisiología , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase superfamily, which catalyzes the incorporation of molecular oxygen into polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARG). The activation of the PPARG pathway in marrow-derived mesenchymal progenitors stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to determine whether polymorphisms in the ALOX12 gene were associated with variations in peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. METHODS: All six tagging single-nucleotide polymorphisms (SNPs) in the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese nuclear families by allele-specific polymerase chain reaction. The BMD at the lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were measured using dual-energy X-ray absorptiometry. The pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both the individual SNP markers and the haplotypes were tested for an association with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using the quantitative transmission disequilibrium test (QTDT). RESULTS: Using the QTDT, significant within-family association was found between the rs2073438 polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012, respectively). Haplotype analyses were combined with our individual SNP results and remained significant even after correction for multiple testing. However, we failed to find significant within-family associations between ALOX12 SNPs and the BMD at any bone site in young Chinese men. CONCLUSIONS: Our present results suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of obesity phenotypes in young Chinese men, although we failed to replicate the association with the peak BMD variation in this sample. Further independent studies are needed to confirm our findings.
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Araquidonato 12-Lipooxigenasa/genética , Densidad Ósea/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Absorciometría de Fotón , Adulto , Pueblo Asiatico , Distribución de la Grasa Corporal , Índice de Masa Corporal , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Núcleo Familiar , Obesidad/etnologíaRESUMEN
Vessel wall inflammation and matrix destruction are critical to abdominal aortic aneurysm (AAA) formation and rupture. We have previously shown that urokinase plasminogen activator (uPA) is highly expressed in experimental AAA and is essential for AAA formation and expansion. In this study, we examined the effects of overexpression of a natural inhibitor of uPA, plasminogen activator inhibitor-1 (PAI-1), on the development of angiotensin (Ang) II-induced AAA in ApoE-deficient (ApoE(-/-)) mice. Mice were treated with recombinant adenovirus containing either the human PAI-1 gene (Ad5.CMV.PAI-1) or the luciferase gene (Ad5.CMV.Luc) delivered either locally by intra-adventitial injection or systemically by tail vein injection. Our results show that local delivery of the PAI-1 gene completely prevented AAA formation (0 vs 55.6% in Ad5.CMV.Luc controls, P<0.05). In contrast, systemic delivery of the PAI-1 gene did not affect AAA incidence (78 vs 90% in Ad5.CMV.Luc controls, P=0.125). Local delivery of the PAI-1 gene 2 weeks after Ang II infusion prevented further expansion of small aneurysms, but had no significant effect on the progression of larger aneurysms. These data suggest that local PAI-1 gene transfer could be used to stabilize small AAA and reduce the rate of expansion and risk of rupture.
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Aneurisma de la Aorta Abdominal/prevención & control , Terapia Genética/métodos , Inhibidor 1 de Activador Plasminogénico/genética , Transducción Genética/métodos , Angiotensina II , Animales , Aorta Abdominal/enzimología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Apolipoproteínas E/genética , Aterosclerosis/enzimología , Aterosclerosis/patología , Citomegalovirus/genética , Fibrosis , Expresión Génica , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Luciferasas/genética , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Noqueados , Inhibidor 1 de Activador Plasminogénico/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismoRESUMEN
OBJECTIVE: To investigate whether SENP3 protects H9C2 cells from apoptosis triggered by H/R through the signal transducer and activator of transcription 3 (STAT3) pathway. MATERIALS AND METHODS: Male C57BL mice were cultured and mouse models of myocardial I/RI were established. At the same time, cardiomyoblast H9C2 cell line of rat embryo was cultured. Reactive oxygen species (ROS) level was detected during H/R using 2',7'-dichlorofluorescein diacetate (DCFH) kit. Apoptotic cells were checked by flow cytometry. The expressions of p-JAK2, JAK2, STAT3, p-STAT3, cleaved-caspase3 (c-caspase3), and Bcl/Bax were detected using Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: We revealed that SENP3 rose in mice of I/R group and in H9C2 cells following H/R with an increase in p-STAT3. Furthermore, increased expression of SENP3 was found to be dependent on the generation of ROS, as the SENP3 accumulation was inhibited by antioxidant (NAC). Inhibition of SENP3 suppressed the p-STAT3 expression, but promoted cell apoptosis, c-caspase3 expression, and Bcl/Bax ratio. Besides, SENP3 overexpression alleviated the cell apoptosis, which was abrogated by AG490. CONCLUSIONS: SENP3 could protect H9C2 against H/R through enhancing JAK2/STAT3 pathway.
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Apoptosis/fisiología , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Péptido Hidrolasas/biosíntesis , Factor de Transcripción STAT3/biosíntesis , Transducción de Señal/fisiología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Cisteína Endopeptidasas , Inhibidores Enzimáticos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacos , Tirfostinos/farmacologíaRESUMEN
UNLABELLED: ESSENTIALS: Antithrombin III (AT)ß binds heparin with higher affinity than ATα. A conformation-specific antibody against ATß, TPP2009, was made to investigate ATß in hemostasis. TPP2009 bound specifically to heparin-ATß and greatly reduced the anticoagulant effect of AT. This antibody was effective in elucidating the importance of ATß in hemostasis. BACKGROUND: Antithrombin III (AT)ß is an isoform of AT that lacks the post-translational carbohydrate modification at Asn135. This isoform binds heparin with greater affinity than ATα, and has been shown to target antithrombotic function to the extracellular vascular endothelial injury site. OBJECTIVES: To characterize a conformation-specific antibody against ATß and begin to investigate the role of ATß in maintaining hemostasis. METHODS: Surface plasmon resonance (SPR), antigen binding and functional assays were conducted to characterize the mode of action of antibodies generated against heparin-bound ATß (ATß*H) by the use of phage display. RESULTS: SPR and binding studies showed that one of the antibodies, TPP2009, bound specifically to ATß*H and glycosaminoglycan-associated ATß on endothelial cells. In diluted prothrombin and activated factor X (FXa)-induced clotting assays, TPP2009 dose-dependently reduced the anticoagulant effect of heparin in non-hemophilic and FVIII-deficient human plasma, with half-maximal effective concentrations (EC50 ) of 10.5 nm and 4.7 nm, respectively. In AT-deficient human plasma, TPP2009 dose-dependently inhibited the effects of exogenously added ATß and heparin. In purified systems with ATß and pentasaccharide, TPP2009 restored > 91% of FXa activity. TPP2009 dose-dependently reversed the effects of heparin in rabbit (EC50 , 25.7 nm) and cynomolgus monkey (EC50 , 21.5 nm) plasma, but not in mouse plasma. TPP2009 was also effective in partially restoring FXa activity in rabbit and cynomolgus monkey plasma treated with FVIII function-neutralizing antibodies. CONCLUSIONS: TPP2009 specifically targets a unique conformational epitope on ATß*H and blocks ATß-mediated anticoagulation. It effectively promotes coagulation in plasma, indicating the importance of ATß in hemostasis.
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Anticuerpos/farmacología , Antitrombina III/metabolismo , Coagulación Sanguínea/efectos de los fármacos , Coagulantes/farmacología , Animales , Anticuerpos/inmunología , Anticuerpos/metabolismo , Especificidad de Anticuerpos , Antitrombina III/química , Antitrombina III/inmunología , Sitios de Unión de Anticuerpos , Pruebas de Coagulación Sanguínea , Línea Celular , Técnicas de Visualización de Superficie Celular , Coagulantes/inmunología , Coagulantes/metabolismo , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Mapeo Epitopo , Humanos , Unión Proteica , Estructura Secundaria de Proteína , Conejos , Relación Estructura-Actividad , Resonancia por Plasmón de Superficie , Factores de TiempoRESUMEN
EPCR is a type I transmembrane protein, highly expressed on the endothelium of large vessels, that binds protein C and augments its activation. In this study, a 23bp insertion in the EPCR gene was found in 4/198 survivors of myocardial infarction and 3/194 patients with deep vein thrombosis. The EPCR gene with the insertion predicts a protein that lacks part of the extracellular domain, the transmembrane domain and the cytoplasmic tail. Expression studies showed that the truncated protein is not localized on the cell surface, cannot be secreted in the culture medium, and does not bind activated protein C. Since protein C activation depends on the concentration of EPCR, patients with the EPCR insertion could have a diminished protein C activation capacity. Further clinical studies of adequate samples size are necessary to establish whether or not the EPCR insertion predisposes to the development of thrombotic events.
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Factores de Coagulación Sanguínea , Endotelio Vascular/metabolismo , Infarto del Miocardio/genética , Receptores de Superficie Celular/genética , Trombofilia/genética , Trombosis de la Vena/genética , Adulto , Edad de Inicio , Animales , Membrana Celular/metabolismo , Células Cultivadas , Análisis Mutacional de ADN , Activación Enzimática , Exones/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Glicosilación , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Peso Molecular , Mutagénesis Insercional , Infarto del Miocardio/epidemiología , Proyectos Piloto , Unión Proteica/genética , Proteína C/metabolismo , Conformación Proteica , Procesamiento Proteico-Postraduccional , Estructura Terciaria de Proteína , Transporte de Proteínas/genética , Receptores de Superficie Celular/química , Receptores de Superficie Celular/fisiología , Factores de Riesgo , Relación Estructura-Actividad , Trombofilia/epidemiología , Trombosis de la Vena/epidemiologíaRESUMEN
Bioadhesion, and more specifically mucoadhesion, is becoming an important strategy for drug delivery. As a result, it is important to understand the various mechanisms that govern attachment of polymeric substances to the glycoproteins on epithelial surfaces, along with the associated structure-activity relationships of the polymer. This article reviews fundamentals of mucoadhesion, with special emphasis on structural features of the polymer as they contribute to the process of mucoadhesion. There are four possible general interactions between mucoadhesive polymers and glycoproteins: (1) covalent attachment; (2) electrostatic interaction, which requires matching of charge groups between the polymer and mucus; (3) hydrogen bonding; and (4) hydrophobic interactions. Aside from covalent attachment, which is not presently a prominent mechanism for mucoadhesion, the remaining mechanisms require maximum contact between the polymer and mucin for optimum adhesion. With polyelectrolyte polymers, the charged groups are important in controlling the degree of hydration of both the polymer and the mucous network. The expanded nature of the swollen polymer and mucus enhances the interdiffusion process and permits both a mechanical entanglement and an increase in surface contact for hydrogen bonding and/or electrostatic interaction between the polymer and the mucous network. A number of techniques are available to study mucoadhesion. Some of these are better suited to study the kinetics of the mucoadhesion process whereas others are more useful for equilibrium studies. To date, the major deficiency in basic studies of mucoadhesion is the lack of suitable information on the organization and physicochemical properties of the mucin layer.
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Acrilatos/metabolismo , Portadores de Fármacos , Moco/metabolismo , Adhesivos Tisulares/metabolismo , Animales , Epitelio/metabolismo , Humanos , Polímeros/metabolismo , Relación Estructura-ActividadRESUMEN
Reconstruction of long-segment tracheal defects is a problem for the reconstructive surgeon. Difficulties arise with the use of prosthetic materials because of their propensity for infection and extrusion. Autologous tissue is limited by poor structural characteristics and technical complexity. We propose a simple composite bioprosthesis that, through a process of prefabrication and subsequent neovascularization, may provide a functional tracheal analogue superior to existing forms of reconstruction. Ten rats had composite flaps constructed by combining an isolated, perfused, mucosectomized segment with an outer covering of a ring-reinforced woven Dacron vascular graft. This unit remained in the intraabdominal milieu for 20 days and was then inspected for viability, incorporation of jejunum and graft, flexibility, and tolerance to negative pressure. Seven experimental animals survived the initial phase. The jejunal bioprostheses in all cases tolerated negative pressures to -200 mmHg, rotation of 180 degrees, and flexion to 90 degrees without collapse of the graft segments. Vascular casts and standard histologic examination showed neovascularization of the Dacron graft and dense fibrovascular ingrowth into the interstices of the graft. We conclude that prefabrication utilizing autologous and prosthetic components to create a single axial flap for transfer is a feasible solution to long-segment tracheal reconstruction. Neovascularization permeates the full thickness of the prosthetic component and is accompanied by dense fibrous ingrowth during the delay period. This neotracheal analogue also possesses structural characteristics similar to those of the native trachea and a durable submucosal layer that can support ingrowth of epithelium.
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Yeyuno/trasplante , Prótesis e Implantes , Tráquea/cirugía , Animales , Tereftalatos Polietilenos , Ratas , Ratas Sprague-Dawley , Tráquea/citologíaRESUMEN
In recent studies we demonstrated that platelet emboli induced by arterial injury impair the microcirculation. The present study was performed to determine if heparin or dietary cod liver oil reduces the incidence of emboli following the same arterial injury and, in turn, whether these agents prevent the associated decrease in microcirculatory blood flow. The cremaster muscle of 29 male Sprague-Dawley rats was isolated on a single neurovascular bundle consisting of the iliac artery and vein and the genitofemoral nerve. Emboli were generated by a thrombogenic injury of the iliac artery, and their number and their subsequent effect on capillary perfusion in the downstream microcirculation were measured. Nine animals received heparin (10-unit IV bolus plus 10 units/hour IV infusion), 10 were fed cod liver oil (10 percent by weight of food) for 3 weeks prior to the experiment, and 9 animals receiving no treatment served as controls. The number of emboli was significantly reduced in the heparin group, but there was no accompanying improvement in capillary perfusion. In contrast, in the cod liver oil group, the number of emboli was not reduced, but there was significant improvement in capillary perfusion. These findings suggest that the harmful effect that platelet emboli have on the microcirculation is probably biochemical in nature (vasoconstriction) rather than related to simple mechanical obstruction to flow.
Asunto(s)
Arterias/cirugía , Aceite de Hígado de Bacalao/farmacología , Embolia/prevención & control , Heparina/farmacología , Músculos/irrigación sanguínea , Complicaciones Posoperatorias/prevención & control , Anastomosis Quirúrgica , Animales , Embolia/etiología , Ingle , Masculino , Microcirculación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , ReperfusiónRESUMEN
Glycoprotein IIb-IIIa (GPIIb-IIIa) concentration was studied in 11 patients with Glanzmann's thrombasthenia (GT) with sensitive Western blotting technique. 7 patients with severe GPIIb-IIIa deficiency (less than 10% of the normal) were designated as type I (64% of patients), 2 patients with moderate GPIIb-IIIa deficiency (10-25% of the normal) as type II (18%) and 2 patients with GPIIb-IIIa 40-100% of the normal as variants (18%). Southern Blotting was used to analyze the GPIIb and GPIIIa genes in the 11 patients. The results showed that there were no major deletions or insertions in either the GPIIb or GPIIIa genes. However, a small change in GPIIb gene was demonstrated in two sibling patients and the abnormality of GPIIIa gene was found in another two patients. These observations combined with those from literature provide a basis for discussing the molecular pathology of Glanzmann's thrombasthenia.