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1.
Crit Rev Food Sci Nutr ; : 1-20, 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37504497

RESUMEN

Partial digestion of milk proteins leads to the formation of numerous bioactive peptides. Previously, our research team thoroughly examined the decades of existing literature on milk bioactive peptides across species to construct the milk bioactive peptide database (MBPDB). Herein, we provide a comprehensive update to the data within the MBPDB and a review of the current state of research for each functional category from in vitro to animal and clinical studies, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, antioxidant, dipeptidyl peptidase (DPP)-IV inhibitory, opioid, anti-inflammatory, immunomodulatory, calcium absorption and bone health and anticancer activity. This information will help drive future research on the bioactivities of milk peptides.

2.
Pancreatology ; 18(5): 477-481, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29884332

RESUMEN

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

3.
Clin Chem Lab Med ; 55(6): 854-864, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-27837595

RESUMEN

BACKGROUND: Glycoprotein 2 (GP2), the pancreatic major zymogen granule membrane glycoprotein, was reported to be elevated in acute pancreatitis in animal models. METHODS: Enzyme-linked immunosorbent assays (ELISAs) were developed to evaluate human glycoprotein 2 isoform alpha (GP2a) and total GP2 (GP2t) as specific markers for acute pancreatitis in sera of 153 patients with acute pancreatitis, 26 with chronic pancreatitis, 125 with pancreatic neoplasms, 324 with non-pancreatic neoplasms, 109 patients with liver/biliary disease, 67 with gastrointestinal disease, and 101 healthy subjects. GP2a and GP2t levels were correlated with procalcitonin and C-reactive protein in 152 and 146 follow-up samples of acute pancreatitis patients, respectively. RESULTS: The GP2a ELISA revealed a significantly higher assay accuracy in contrast to the GP2t assay (sensitivity ≤3 disease days: 91.7%, specificity: 96.7%, positive likelihood ratio [LR+]: 24.6, LR-: 0.09). GP2a and GP2t levels as well as prevalences were significantly elevated in early acute pancreatitis (≤3 disease days) compared to all control cohorts (p<0.05, respectively). GP2a and GP2t levels were significantly higher in patients with severe acute pancreatitis at admission compared with mild cases (p<0.05, respectively). Odds ratio for GP2a regarding mild vs. severe acute pancreatitis with lethal outcome was 7.8 on admission (p=0.0222). GP2a and GP2t levels were significantly correlated with procalcitonin [Spearman's rank coefficient of correlation (ρ)=0.21, 0.26; p=0.0110, 0.0012; respectively] and C-reactive protein (ρ=0.37, 0.40; p<0.0001; respectively). CONCLUSIONS: Serum GP2a is a specific marker of acute pancreatitis and analysis of GP2a can aid in the differential diagnosis of acute upper abdominal pain and prognosis of severe acute pancreatitis.


Asunto(s)
Proteínas Ligadas a GPI/sangre , Pancreatitis/sangre , Pancreatitis/diagnóstico , Pruebas Serológicas , Enfermedad Aguda , Adulto , Anciano , Análisis Químico de la Sangre , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Isoformas de Proteínas/sangre
4.
Ann Surg ; 261(1): 180-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24743610

RESUMEN

OBJECTIVES: We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. BACKGROUND: The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP. METHODS: Five hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality. RESULTS: The angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046). CONCLUSIONS: The association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.


Asunto(s)
Pancreatitis/genética , Sistema Renina-Angiotensina/genética , Vitamina D/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo de Nucleótido Simple , Renina/genética , Adulto Joven
5.
Nat Genet ; 38(6): 668-73, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16699518

RESUMEN

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.


Asunto(s)
Tripsina/genética , Tripsinógeno/genética , Secuencia de Bases , Enfermedad Crónica , Cartilla de ADN , Haplotipos , Humanos , Hidrólisis , Modelos Moleculares , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Tripsina/química , Tripsina/metabolismo , Tripsinógeno/química , Tripsinógeno/metabolismo
6.
Gastroenterology ; 144(1): 192-201, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23041330

RESUMEN

BACKGROUND & AIMS: The transcription factor nuclear factor-κB (NF-κB) (a heterodimer of NF-κB1p50 and RelA) is activated rapidly in acute pancreatitis (AP). However, it is not clear whether NF-κB promotes or protects against AP. We used the NF-κB inhibitor protein, inhibitor of κB (IκB)α, to study the roles of NF-κB in the development of AP in mice. METHODS: IκBα or the combination of IκBα and RelA selectively were deleted from pancreas of mice using the Cre/locus of cross-over P strategy; cerulein or L-arginine were used to induce AP. We performed microarray analyses of the IκBα- and RelA-deficient pancreata. DNA from healthy individuals and patients with acute or chronic pancreatitis were analyzed for variants in coding regions of alpha-1-antichymotrypsin. RESULTS: Mice with pancreas-specific deletion of IκBα had constitutive activation of RelA and a gene expression profile consistent with NF-κB activation; development of AP in these mice was attenuated and trypsin activation was impaired. However, AP was fully induced in mice with pancreas-specific deletion of IκBα and RelA. By using genome-wide expression analysis, we identified a cluster of NF-κB-regulated genes that might protect against the development of AP. The serine protease inhibitor 2A (Spi2a) was highly up-regulated in IκBα-deficient mice. Lentiviral-mediated expression of Spi2A reduced the development of AP in C57BL/6 and RelA-deficient mice. However, we did not correlate any variants of alpha-1-antichymotrypsin, the human homologue of Spi2a, with acute or chronic pancreatitis. CONCLUSIONS: Pancreas-specific deletion of IκBα results in nuclear translocation of RelA and reduces AP induction and trypsin activation in mice after administration of cerulein or L-arginine. Constitutive activation of RelA up-regulates Spi2A, which protects mice against the development of AP.


Asunto(s)
Proteínas I-kappa B/genética , FN-kappa B/metabolismo , Pancreatitis/genética , Pancreatitis/metabolismo , Serpinas/genética , Factor de Transcripción ReIA/genética , alfa 1-Antiquimotripsina/genética , Células Acinares , Animales , Arginina , Ceruletida , Citosol/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Vectores Genéticos , Genotipo , Proteínas I-kappa B/metabolismo , Lentivirus , Ratones , Ratones Endogámicos C57BL , Análisis por Micromatrices , Inhibidor NF-kappaB alfa , Proteínas Nucleares/metabolismo , Páncreas/enzimología , Pancreatitis/inducido químicamente , Pancreatitis/patología , Fosforilación , Serpinas/metabolismo , Transducción de Señal , Factor de Transcripción ReIA/metabolismo , Tripsina/metabolismo , Regulación hacia Arriba
8.
Nat Commun ; 15(1): 4960, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862499

RESUMEN

Organic-inorganic interactions regulate the dynamics of hydrocarbons, water, minerals, CO2, and H2 in thermal rocks, yet their initiation remains debated. To address this, we conducted isotope-tagged and in-situ visual thermal experiments. Isotope-tagged studies revealed extensive H/O transfers in hydrous n-C20H42-H2O-feldspar systems. Visual experiments observed water microdroplets forming at 150-165 °C in oil phases near the water-oil interface without surfactants, persisting until complete miscibility above 350 °C. Electron paramagnetic resonance (EPR) detected hydroxyl free radicals concurrent with microdroplet formation. Here we propose a two-fold mechanism: water-derived and n-C20H42-derived free radicals drive interactions with organic species, while water-derived and mineral-derived ions trigger mineral interactions. These processes, facilitated by microdroplets and bulk water, blur boundaries between organic and inorganic species, enabling extensive interactions and mass transfer. Our findings redefine microscopic interplays between organic and inorganic components, offering insights into diagenetic and hydrous-metamorphic processes, and mass transfer cycles in deep basins and subduction zones.

9.
Crit Care Med ; 41(4): 1027-36, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23399938

RESUMEN

OBJECTIVE: To determine the value of pancreatic stone protein in predicting sepsis-related postoperative complications and death in the ICU. DESIGN: A prospective cohort study of postoperative patients admitted to the ICU. Blood samples for analysis were taken within 3 hours from admission to the ICU including pancreatic stone protein, white blood cell counts, C-reactive protein, interleukin-6, and procalcitonin. The Mannheim Peritonitis Index and Acute Physiology and Chronic Health Evaluation II clinical scores were also determined. Univariate and multivariate analyses were performed to determine the diagnostic accuracy and independent predictors of death in the ICU [Clinicaltrials.gov, NCT01465711]. SETTING: An adult medical-surgical ICU in a teaching hospital in Germany. PATIENTS: Ninety-one consecutive postoperative patients with proven diagnosis of secondary peritonitis admitted to the ICU were included in the study from August 17, 2007, to February 8, 2010. INTERVENTIONS: Peripheral vein blood sampling. MEASUREMENTS AND MAIN RESULTS: Univariate analysis demonstrated that pancreatic stone protein has the highest diagnostic accuracy for complications and is the best predictor for death in the ICU. Pancreatic stone protein had the highest overall efficacy in predicting death with an odds ratio of 4.0 vs. procalcitonin (odds ratio 3.2), interleukin-6 (odds ratio 2.8), C-reactive protein (odds ratio 1.3), and WBCs (odds ratio 1.4). By multivariate analysis, pancreatic stone protein was the only independent predictor of death. CONCLUSIONS: In a population of patients with sepsis-related complications, serum-pancreatic stone protein levels demonstrate a high diagnostic accuracy to discriminate the severity of peritonitis and to predict death in the ICU. This test could be of value in the clinical diagnosis and therapeutic decision making in the ICU.


Asunto(s)
Enfermedad Crítica/mortalidad , Unidades de Cuidados Intensivos , Litostatina/sangre , Peritonitis/diagnóstico , Peritonitis/mortalidad , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Péptido Relacionado con Gen de Calcitonina , Estudios de Cohortes , Femenino , Alemania , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Peritonitis/sangre , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Precursores de Proteínas/sangre , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Análisis de Supervivencia
10.
Wien Med Wochenschr ; 163(11-12): 295-302, 2013 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-23334214

RESUMEN

UNLABELLED: Progredient tumor-growth does not mean necessarily nihilism since (because of the latest multimodal therapeutic options) it might be possible to convert the malignant disease into a chronic stage depending on tumor entity, specific tumor-associated findings and expertise of the interdisciplinary oncological/oncosurgical team to utilize available and potential therapeutic measures. The aim of this report on an unusual case (with its patient-associated, therapeutic and prognostic aspects) of a leiomyosarcoma of the inferior vena cava with advanced tumor growth (characterized initially by pulmonary and hepatic, later on by additional vertebral metastases) is to illustrate its changeful clinical course after and during multimodal treatment episodes comprising surgical (abdomino-/vascular-/cardio- and neurosurgical-locally, R0 resection status), radiological and chemotherapeutic measures. A relatively stable disease over a specific time period of 5 years and 6 months was achieved. The 54-year old female patient with metastasized leiomyosarcoma of the inferior vena cava underwent local tumor resection en bloc with inferior vena cava segmental resection (following vascular surgical interposition of a prosthesis) and hemihepatectomy as well as resection of hepatic segment I. After recovery, a multistep and -modal treatment was initiated comprising of various protocols of systemic chemotherapy, thermoablation of recurrent hepatic metastases, various brachytherapy procedures (for hepatic and pulmonary metastases) and resection of a cerebral metastasis by a neurosurgeon including subsequent radiation. CONCLUSIONS: The patient demonstrates impressively that even in case of advanced tumor stage with initial, novel and recurrent metastases, a relatively stable disease over an intermediate time period (of more than 5 years) with an acceptable quality of life was achieved despite several complications.


Asunto(s)
Conducta Cooperativa , Comunicación Interdisciplinaria , Leiomiosarcoma/terapia , Complicaciones Posoperatorias/etiología , Neoplasias Vasculares/terapia , Vena Cava Inferior , Implantación de Prótesis Vascular , Quimioradioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Alemania , Humanos , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Flebografía , Complicaciones Posoperatorias/diagnóstico , Pronóstico , Calidad de Vida , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patología , Vena Cava Inferior/patología
11.
Artículo en Inglés | MEDLINE | ID: mdl-37204960

RESUMEN

Progressive visual analytics (PVA) allows analysts to maintain their flow during otherwise long-running computations by producing early, incomplete results that refine over time, for example, by running the computation over smaller partitions of the data. These partitions are created using sampling, whose goal it isto draw samples of the dataset such that the progressive visualization becomes as useful as possible as soon as possible. What makes the visualization useful depends on the analysis task and, accordingly, some task-specific sampling methods have been proposed for PVA to address this need. However, as analysts see more and more of their data during the progression, the analysis task at hand often changes, which means that analysts need to restart the computation to switch the sampling method, causing them to lose their analysis flow. This poses a clear limitation to the proposed benefits of PVA. Hence, we propose a pipeline for PVA-sampling that allows tailoring the data partitioning to analysis scenarios by switching out modules in a way that does not require restarting the analysis. To that end, we characterize the problem of PVA-sampling, formalize the pipeline in terms of data structures, discuss on-the-fly tailoring, and present additional examples demonstrating its usefulness.

15.
Pancreas ; 51(9): 1231-1234, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37078950

RESUMEN

OBJECTIVES: Human and animal studies suggest an important role of autophagy in the pathogenesis of pancreatitis. ATG16L1 (autophagy-related 16 like 1) is part of a protein complex that is involved in the formation of autophagosomes. The c.898A > G (p.T300A) variant of ATG16L1 is associated with Crohn disease. In this study, we analyzed ATG16L1 c.898A > G (p.T300A) for an association with pancreatitis. METHODS: We genotyped 777 patients and 551 control subjects of German origin by melting curve analysis using fluorescence resonance energy transfer probes. The patient group included 429 patients with nonalcoholic chronic pancreatitis (CP), 141 patients with alcoholic CP, and 207 patients with acute pancreatitis (AP). We classified AP by severity according to the Atlanta symposium 1992. RESULTS: Allele and genotype frequencies of ATG16L1 c.898A > G (p.T300A) did not differ significantly between patients and controls (G allele frequencies: nonalcoholic CP, 49.9%; alcoholic CP, 48.2%; AP, 49.5%; controls, 52.7%). We found no significant association with the severity of AP either. CONCLUSIONS: Our data do not support a role of ATG16L1 c.898A > G (p.T300A) in the pathogenesis of AP or CP or an influence on the severity of AP.


Asunto(s)
Enfermedad de Crohn , Pancreatitis , Animales , Humanos , Enfermedad Aguda , Proteínas Relacionadas con la Autofagia/genética , Pancreatitis/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Autofagia/genética , Polimorfismo de Nucleótido Simple
16.
Hum Mutat ; 32(8): 912-20, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21520337

RESUMEN

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos , Enfermedades Urogenitales Masculinas/genética , Pancreatitis Crónica/genética , Adolescente , Adulto , Proteínas Portadoras/genética , Niño , Epistasis Genética , Humanos , Infertilidad Masculina/genética , Masculino , Persona de Mediana Edad , Mutación/genética , Inhibidor de Tripsina Pancreática de Kazal , Conducto Deferente/anomalías , Adulto Joven
17.
Gastroenterology ; 138(2): 726-37, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19900452

RESUMEN

BACKGROUND & AIMS: Acute pancreatitis is characterized by an activation cascade of digestive enzymes in the pancreas. The first of these, trypsinogen, can be converted to active trypsin by the peptidase cathepsin B (CTSB). We investigated whether cathepsin L (CTSL) can also process trypsinogen to active trypsin and has a role in pancreatitis. METHODS: In CTSL-deficient (Ctsl(-/-)) mice, pancreatitis was induced by injection of cerulein or infusion of taurocholate into the pancreatic duct. Human tissue, pancreatic juice, mouse pancreatitis specimens, and recombinant enzymes were studied by enzyme assay, immunoblot, N-terminal sequencing, immunocytochemistry, and electron microscopy analyses. Isolated acini from Ctsl(-/-) and Ctsb(-/-) mice were studied. RESULTS: CTSL was expressed in human and mouse pancreas, colocalized with trypsinogen in secretory vesicles and lysosomes, and secreted into pancreatic juice. Severity of pancreatitis was reduced in Ctsl(-/-) mice, whereas apoptosis and intrapancreatic trypsin activity were increased. CTSL-induced cleavage of trypsinogen occurred 3 amino acids toward the C-terminus from the CTSB activation site and resulted in a truncated, inactive form of trypsin and an elongated propeptide (trypsinogen activation peptide [TAP]). This elongated TAP was not detected by enzyme-linked immunosorbent assay (ELISA) but was effectively converted to an immunoreactive form by CTSB. Levels of TAP thus generated by CTSB were not associated with disease severity, although this is what the TAP-ELISA is used to determine in the clinic. CONCLUSIONS: CTSL inactivates trypsinogen and counteracts the ability of CTSB to form active trypsin. In mouse models of pancreatitis, absence of CTSL induces apoptosis and reduces disease severity.


Asunto(s)
Catepsina L/metabolismo , Pancreatitis/metabolismo , Índice de Severidad de la Enfermedad , Tripsinógeno/metabolismo , Amilasas/metabolismo , Animales , Apoptosis , Catepsina B/genética , Catepsina B/metabolismo , Catepsina L/genética , Ceruletida/efectos adversos , Modelos Animales de Enfermedad , Humanos , Concentración de Iones de Hidrógeno , Lipasa/metabolismo , Ratones , Ratones Noqueados , Pancreatitis/inducido químicamente , Pancreatitis/patología , Ácido Taurocólico/efectos adversos , Tripsina/metabolismo
18.
BMC Cancer ; 10: 317, 2010 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-20569442

RESUMEN

BACKGROUND: The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carcinoma (HCC) from other liver tumors. METHODS: Tumor and corresponding non-tumor liver tissue samples were obtained from 85 patients with liver tumors. CDKN2A promoter methylation was studied using MethyLight technique and methylation-specific PCR (MSP). In the MethyLight analysis, samples with > or = 4% of PMR (percentage of methylated reference) were regarded as hypermethylated. p16 expression was evaluated by immunohistochemistry in tissue sections (n = 148) obtained from 81 patients using an immunoreactivity score (IRS) ranging from 0 (no expression) to 6 (strong expression). RESULTS: Hypermethylation of the CDKN2A promoter was found in 23 HCCs (69.7%; mean PMR = 42.34 +/- 27.8%), six (20.7%; mean PMR = 31.85 +/- 18%) liver metastases and in the extralesional tissue of only one patient. Using MSP, 32% of the non-tumor (n = 85), 70% of the HCCs, 40% of the CCCs and 24% of the liver metastases were hypermethylated. Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2). The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively). CONCLUSION: Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Metilación de ADN , Neoplasias Hepáticas/química , Neoplasias Hepáticas/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
19.
Pancreatology ; 10(2-3): 243-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20484962

RESUMEN

BACKGROUND/AIMS: A sustained imbalance of pancreatic proteases and their inhibitors seems to be important for the development of chronic pancreatitis (CP). Mesotrypsin (PRSS3) can degrade intrapancreatic trypsin inhibitors that protect against CP. Genetic variants that cause higher mesotrypsin activity might increase the risk for CP. METHODS: We analyzed all 5 exons and the adjacent non-coding sequences of PRSS3 by direct sequencing of 313 CP patients and 327 controls. Additionally, exon 4 was investigated in 855 patients and 1,294 controls and a c.454+191G>A variant in 855 patients and 1,467 controls. The c.499A>G (p.T167A) variant was analyzed functionally using transiently transfected HEK 293T cells. RESULTS: In the exonic regions, the previously described common c.94_96delGAG (p.E32del) variant and a novel p.T167A non-synonymous alteration were identified. Extended analysis of the p.T167A variant revealed no association to CP and in functional assays p.T167A showed normal secretion and activity. Variants of the intronic regions, including the extensively analyzed c.454+191G>A alteration, were not associated with the disease. Haplotype reconstruction using variants with a minor allele frequency of >1% revealed no CP-associated haplotype. CONCLUSIONS: Although the trypsin inhibitor-degrading activity qualified PRSS3 as a candidate for a novel CP susceptibility gene, we found no association between a specific variant or haplotype and CP in our cohort with a high suspicion of genetically determined disease.


Asunto(s)
Pancreatitis Crónica/genética , Tripsina/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Niño , Preescolar , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mutación
20.
S Afr J Surg ; 48(3): 86-8, 2010 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-21924000

RESUMEN

OBJECTIVES: Chylothorax is an infrequent but serious complication after thoracic surgery. Optimal management is still controversial. Surgical re-interventions are associated with significant morbidity and mortality. DESIGN: During a 2-year period, 3 patients developed chylothorax after oesophagectomy. This was treated conservatively, following our departmental protocol. RESULTS: Conservative management (total parenteral nutrition, bowel rest, pleural drainage and octreotide, followed by a low-fat diet) was successful in all 3 cases within a reasonable period of time (14 - 18 days). CONCLUSION; We recommend conservative measures as the first-line treatment for postoperative chylothorax.


Asunto(s)
Quilotórax/terapia , Esofagectomía/métodos , Algoritmos , Quilotórax/etiología , Femenino , Fármacos Gastrointestinales/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Octreótido/administración & dosificación , Nutrición Parenteral Total
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