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1.
BMC Surg ; 19(1): 85, 2019 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31286905

RESUMEN

BACKGROUND: Enterovesical fistula (EVF) is a abnormal connection between the intestine and the bladder. The aim of the study was to analyze whether closure of the defect in the bladder wall during surgery is always necessary. METHODS: Fifty-nine patients with benign EVF undergoing surgical treatment were enrolled. A one-stage surgical procedure was performed in all patients. After the separation of the diseased bowel segment, methylene blue was introduced. Through a catheter into the bladder. Only patients with urinary bladder leakage were sutured. RESULTS: The most common intestinal fistula involving the urinary bladder was colovesical fistula, observed in 53% of cases. Two-thirds of patients had diverticular disease as the underlying pathology. There was no relationship between suturing of the bladder and perioperative complications. Recurrent EVF was observed in one patient with bladder suturing and in two patients without suture. CONCLUSIONS: These findings suggest that closure of the bladder defect is not necessary in cases where a leak is not demonstrated from the bladder intraoperatively. This study is limited by its retrospective design and small numbers and a randomized controlled trial is recommended to answer this question definitively.


Asunto(s)
Fístula Intestinal/etiología , Fístula de la Vejiga Urinaria/cirugía , Vejiga Urinaria/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Técnicas de Sutura , Fístula de la Vejiga Urinaria/etiología
2.
Colorectal Dis ; 20(4): 321-330, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28963746

RESUMEN

AIM: The aim of this study was to assess the expression of vascular endothelial growth factor (VEGF) as a key proangiogenic factor and determine whether there is any correlation between its expression and clinical symptoms or endoscopic changes in patients with chronic radiation proctitis (ChRP). METHOD: Fifty patients who had all undergone radiotherapy for prostate, cervical or uterine cancer were included in the study (37 women, 13 men). There was a control group of 20 patients (9 women, 11 men). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system was used for grading the severity of the proctitis. Endoscopic scoring of late rectal mucosal damage was performed using Gilinsky's classification. Serum levels of VEGF were analysed by the enzyme-linked immunosorbent assay method. RESULTS: Most patients presented with Grade 1 symptoms. Endoscopic assessment showed that most patients had Grade 1 late rectal mucosal damage. The predominant endoscopic finding was the presence of telangiectasia. Assessment of VEGF correlation between the control group and the degrees of endoscopic changes showed statistically significant differences for all three degrees (P < 0.0001, P = 0.0251 and P = 0.0005, respectively). Due to the small numbers of patients with Grades 2 and 3 symptoms using the RTOG/EORTC scoring system, they were grouped with Grades 1 and 4 respectively forming two groups for statistical purposes. VEGF expression differed significantly between controls and group I and between controls and group II (P = 0.0001, P = 0.0009, respectively). CONCLUSION: A significant increase in VEGF expression was found to correlate with clinical symptoms and endoscopic rectal mucosa changes in patients with ChRP, suggesting that it may play an important role in pathological angiogenesis.


Asunto(s)
Mucosa Intestinal/efectos de la radiación , Proctitis/sangre , Traumatismos por Radiación/sangre , Recto/efectos de la radiación , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Endoscopía del Sistema Digestivo , Femenino , Humanos , Mucosa Intestinal/irrigación sanguínea , Masculino , Persona de Mediana Edad , Proctitis/etiología , Proctitis/patología , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/patología , Recto/irrigación sanguínea , Índice de Severidad de la Enfermedad , Telangiectasia/etiología , Neoplasias del Cuello Uterino/radioterapia , Neoplasias Uterinas/radioterapia
3.
Colorectal Dis ; 18(7): O252-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27187635

RESUMEN

AIM: This study aimed to assess the influence of the C-reactive protein (CRP) level on the early outcome after elective colorectal resection. METHOD: Patients with colorectal cancer operated on between 2006 and 2013 were identified retrospectively. They were divided into a study group operated on between 2010 and 2013 when CRP was measured routinely on the fourth postoperative day and a control group operated on between 2006 and 2009 when the CRP level was not measured routinely. Mortality, intra-abdominal septic complications (IASC), abscesses and anastomotic leakage (AL), the need for reoperation, the interval from index surgery to relaparotomy, length of hospital stay and imaging studies were compared by multivariate analysis. RESULTS: A total of 1189 patients were assessed, including 598 (50.3%) in the study group (mean age 61.3 ± 13 years; 282 female) and 591 (49.7%) in the control group (mean age 61.8 ± 11 years; 267 female). There were seven (1.2%) postoperative deaths in the study group and nine (1.5%) in the control group (P = 0.598). Abdominal ultrasound (US) was performed more often in the study group [97 (16.2%) vs 71 (12.0%); P = 0.037]. In the study group the interval to diagnosis of IASC was shorter than in the control group (5.7 ± 1.5 days vs 7.3 ± 1.3 days; P = 0.029). The decision to reoperate was also made earlier in the study group (6.2 ± 1.7 days vs 7.4 ± 2.8 days; P = 0.043). CONCLUSION: Routine measurement of CRP can help to make an earlier diagnosis of IASC and earlier decision for relaparotomy, without any influence on mortality or length of hospital stay.


Asunto(s)
Proteína C-Reactiva/análisis , Colectomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Sepsis/diagnóstico , Cavidad Abdominal/patología , Anciano , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/sangre , Fuga Anastomótica/etiología , Neoplasias Colorrectales/cirugía , Diagnóstico Precoz , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Reoperación , Estudios Retrospectivos , Sepsis/sangre , Sepsis/etiología
4.
Langenbecks Arch Surg ; 399(4): 473-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24577938

RESUMEN

PURPOSE: Several European countries are undertaking quality control projects in colorectal cancer. These efforts have led to improvements in survival, but a comparison between different projects reveals questionable results. The aim of this study is the presentation of results from hospitals in three different European countries participating in the International Quality Assurance in Colorectal Cancer (IQACC) project. METHODS: For this publication, patients with cancer of the colon or rectum treated in 2009 and 2010 and recorded in the IQACC (Germany, Poland and Italy) were analysed. The comparison included number of patients, age, preoperative diagnostics (CT of the abdomen and thorax, MRI, colonoscopy, ultrasound, tumour markers), surgical approach, metastasis, height of rectal cancer and histopathological examination of a specimen (T stage, N stage and MERCURY classification for rectum resection). For short-term outcomes, general complications, wound dehiscence, tumour-free status at discharge, anastomotic leakage and in-hospital mortality were analysed. RESULTS: A total of 12,691 patients (6,756 with colon cancer, 5,935 with rectal cancer) were included in the analysis. Preoperative diagnostics differed significantly between countries. For pT and pN stages, several quality differences could be demonstrated, including missing stages (colon cancer: pT 5.7-12.5 %, pN 2.5-11.0 %; rectal cancer: pT 1.1-5.6 %, pN 1.1-15.5 %). The most relevant differences for short-term outcomes in colon cancer were found in general complications (4.2-22.8 %) and tumour-free status at discharge (74.5-91.7 %). In-hospital deaths ranged between 2.5 and 4.3 % and did not show significant differences. For rectal cancer, the country with the highest percentage of tumours localised less than 4 cm from the anal verge (16.0 %) showed the lowest frequency of amputation (8.5 %). Outcome differences were found for general complications (3.2-18.8 %), anastomotic leakage (0-4.3 %) and tumour-free status at discharge (72.9-87.6 %). In-hospital deaths ranged between 1.1 and 3.2 %. CONCLUSION: This study demonstrates the feasibility of an international quality assurance project in colorectal cancer. This concept ensures data analysis based on a comparable data input. Differences in preoperative diagnostics, completeness of histopathological evaluation and short-term outcomes for Germany, Poland and Italy might result from disparities in socioeconomic factors and implementation of existing guidelines. Further activities are necessary to warrant the use of common standards in outcome control.


Asunto(s)
Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/normas , Cooperación Internacional , Evaluación de Procesos y Resultados en Atención de Salud , Pautas de la Práctica en Medicina/normas , Garantía de la Calidad de Atención de Salud , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Europa (Continente)/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Pautas de la Práctica en Medicina/estadística & datos numéricos
5.
Dig Dis Sci ; 56(7): 2073-80, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21321790

RESUMEN

BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD), which are complex genetic disorders resulting from the interplay between several genetic and environmental risk factors. The arylamine N-acetyltransferase 2 (NAT2) enzyme detoxifies a wide spectrum of naturally occurring xenobiotics including carcinogens and drugs. Acetylation catalyzed by NAT2 is an important process in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. The aim of our study was to determine whether there is any association between the susceptibility to inflammatory bowel disease among the variations of NAT2 genotypes. METHODS: This study was carried out in 80 patients with IBD. The control group consisted of 100 healthy volunteers. The most common mutations found in the Caucasian population are at the positions 481T, 803G, 590A and 857A on the NAT2 gene. This was determined using the polymerase chain reaction-restriction fragment length polymorphism method with DNA extracted from peripheral blood. RESULTS: Risk of IBD development was 3.86 for the carriers of the NAT2*5/NAT2*7 genotype and 2.53 for the carriers with NAT2*6/NAT2*7, but it was not statistically significant. A statistically significant correlation between the NAT2*7 allele prevalence and the risk for developing IBD was found (OR = 5.8; P = 0.005). CONCLUSIONS: Higher prevalence of the NAT2*7 allele in patients with IBD and the obtained OR values could suggest that this mutation has the effect of increasing IBD development. Future studies are needed to confirm our assumptions on larger group of patients.


Asunto(s)
Arilamina N-Acetiltransferasa/genética , Enfermedades Inflamatorias del Intestino/enzimología , Enfermedades Inflamatorias del Intestino/genética , Polimorfismo Genético , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Riesgo
6.
Colorectal Dis ; 12(7 Online): e61-7, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19486103

RESUMEN

OBJECTIVE: The aims of the study were to analyse the early and late results of surgical treatment in patients with stage IV colorectal cancer (CRC) and to evaluate the effect of primary tumour resection and other clinical factors on survival. METHOD: A group of 134 patients with stage IV CRC was electively operated on between 1996 and 2000. The first group underwent resection of the primary tumour (52 patients; mean age 63.4 +/- 10.3) and the second group of patients underwent procedures without resection (82 patients; mean age 62.6 +/- 10.6). RESULTS: Postoperative morbidity occurred significantly more often (P = 0.041) in the first group--in 26 patients (50%) than in the second group - 19 patients (23.1%). The resection of the primary tumour increased the survival probability; hazard ratio (HR): 1.78; 95% confidence interval (CI): 1.21-2.78%; P = 0.004. Bi-lobar metastases increased mortality risk compared with uni-lobar; HR 2.32; 95% CI: 1.47-3.68; P = 0.0003. The 2-year survival rate in patients with uni-lobar metastases in the first group was 44.2%, in the second group: 30.7%; P = 0.023. CONCLUSION: Primary tumour resection in stage IV CRC increases the risk of postoperative complications. In the given setting, however, it results in an increased 2-year survival rate but it may not influence the 5-year survival rate. In patients with bi-lobar liver metastases resection of the primary tumour does not prolong survival time.


Asunto(s)
Colectomía/métodos , Neoplasias Colorrectales/cirugía , Estadificación de Neoplasias , Cuidados Paliativos/métodos , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Periodo Posoperatorio , Estudios Retrospectivos , Tasa de Supervivencia/tendencias
7.
Dig Dis Sci ; 55(4): 1037-43, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19437119

RESUMEN

Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn's disease, both of which are associated with increased colorectal cancer risk. The relationship between genetically determined polymorphic metabolism of exogenous substances by oxidation catalyzed by CYP2D6 isoenzyme and susceptibility to cancer has aroused great interest. We determined whether there was an association between susceptibility to inflammatory bowel disease and particularly to CYP2D6 genotypes. The study was carried out in 39 patients with IBD. The control group consisted of 129 healthy volunteers. The CYP2D6 genotypes were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method with DNA extracted from peripheral blood. Among 39 patients with inflammatory bowel disease, extensive metabolizer (EM) genotype constituted 97.4%. One patient (2.6%) was poor metabolizer with CYP2D6*4/CYP2D6*4 genotype. Results obtained in the inflammatory bowel disease group did not differ significantly from those of the control group. Although the odds ratio for EM metabolizers was about 3.8-fold greater in the group of patients with inflammatory bowel disease, this association was not statistically significant. This data also showed no overall statistically significant association between alleles and incidence risk of inflammatory bowel disease [odds ratio (OR) of 1.36 for CYP2D6*1 allele, 0.83 for CYP2D6*3 allele, and 0.74 for CYP2D6*4 allele]. The present results suggest that EM genotype may be the risk factor of inflammatory bowel disease. Future studies are needed to confirm our assumptions on larger group of patients.


Asunto(s)
Alelos , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Citocromo P-450 CYP2D6/genética , Genotipo , Polimorfismo Genético/genética , Adulto , Anciano , Neoplasias Colorrectales/genética , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes/genética , Tamización de Portadores Genéticos , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción/genética , Factores de Riesgo , Adulto Joven
8.
Gastroenterol Res Pract ; 2017: 3840243, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28386271

RESUMEN

Polymorphisms in DNA repair genes may affect the activity of the BER (base excision repair) and NER (nucleotide excision repair) systems. Using DNA isolated from blood taken from patients (n = 312) and a control group (n = 320) with CRC, we have analyzed the polymorphisms of selected DNA repair genes and we have demonstrated that genotypes 51Gln/His and 148Asp/Glu of APEX gene and 23Gly/Ala of XPA gene may increase the risk of colorectal cancer. At the same time analyzing the gene-gene interactions, we suggest the thesis that the main factor to be considered when analyzing the impact of polymorphisms on the risk of malignant transformation should be intergenic interactions. Moreover, we are suggesting that some polymorphisms may have impact not only on the malignant transformation but also on the stage of the tumor.

9.
Oxid Med Cell Longev ; 2016: 3125989, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26649135

RESUMEN

DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation.


Asunto(s)
Neoplasias Colorrectales/genética , Daño del ADN , Reparación del ADN , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia
10.
Cancer Lett ; 181(1): 23-30, 2002 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-12430175

RESUMEN

We analysed the distribution of genotypes of two polymorphisms in the urokinase-type plasminogen activator (uPA) gene: C-->T substitution in exon 6 and T-->C substitution in intron 7 in 52 subjects with colorectal cancer. Genotypes were determined in tumour tissue and distant mucosa samples by allele-specific polymerase chain reaction. The antigen levels of uPA in cancer tissue were higher than in distant mucosa as measured by enzyme-linked immunosorbent assay. The level of uPA antigens in cancer samples with the C/C genotype of C-->T polymorphism in exon 6 was higher than in samples with C/T and T/T genotypes. No differences in the level of uPA antigens between the alleles of the intron 7 T-->C polymorphism were found. As uPA can be involved in cancer invasion and metastasis, C/C genotype in exon 6 of uPA gene can be further considered as being related to colorectal cancer progression.


Asunto(s)
Neoplasias Colorrectales/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/inmunología , Anciano , Antígenos/análisis , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético
11.
Shock ; 7(3): 217-24, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9068089

RESUMEN

Endogenous opioids are known to mediate some of the cardiovascular sequelae of sepsis. Inhibition of adrenergic action has been implicated as a physiological path by which endogenous opioids cause deleterious changes in cardiovascular function during endotoxin shock, but where and to what extent this accounts for changes in regional vascular resistance remains unclear. In this study, we addressed this question by examining the role of alpha-adrenergic actions in cardiovascular performance and the regional perfusion changes caused by naloxone during endotoxin shock. Rats had catheters inserted into the tail artery, left cardiac ventricle, and jugular vein. Twenty-four hours later, rats received saline or endotoxin (2 mg/kg) challenge intravenously over 30 min, followed at 40 min by intravenous naloxone (or saline) treatment (4 mg/kg + 2 mg/kg x h) in the presence or absence of phentolamine (100 micrograms/kg + 600 micrograms/kg x h) or yohimbine (40 micrograms/kg + 4 micrograms/kg x h). Radiolabeled microspheres were used to determine cardiac outputs and blood flows at 0, 30, 60, and 120 min after beginning endotoxin infusion. Naloxone attenuated the endotoxin-induced decline in mean arterial pressure (MAP) and cardiac output (CO), but had no effect on increased systemic vascular resistance (SVR). Phentolamine blocked naloxone's ability to increase MAP and CO, but permitted an increase in SVR by naloxone. In the presence of yohimbine, naloxone still increased MAP, but not CO nor SVR. Regional vascular responses varied, with naloxone demonstrating a vasoconstrictive effect despite alpha-adrenergic receptor blockade in some beds, and no effect in others. The response of individual organs in the hepatosplanchnic circulation was heterogenous as well. These data suggest that some effects of endogenous opioids during endotoxin shock are mediated via inhibition of alpha-adrenergic effects, but that some cardiovascular effects of endogenous opioids are independent of adrenergic control during endotoxin shock.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Fentolamina/farmacología , Choque Séptico/fisiopatología , Yohimbina/farmacología , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Endotoxinas/farmacología , Hemodinámica/efectos de los fármacos , Hipotensión/inducido químicamente , Masculino , Ratas , Ratas Sprague-Dawley , Resistencia Vascular/efectos de los fármacos , Vasoconstricción/efectos de los fármacos
12.
Shock ; 1(3): 201-12, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7735952

RESUMEN

The characteristics of two types of intraperitoneal (i.p.) soilage sepsis models, autologous fecal inoculum (FEC) and a pure culture of Escherichia coli (EC), were studied in 26 male Yucatan minipigs (20-30 kg). Early (1-4 h) and late (24-72 h) changes were different between the two groups. The EC group was characterized early by hypotension, low cardiac output, and increased systemic and pulmonary vascular resistances, along with leukopenia, hypoglycemia, lactacidemia, and elevated blood urea nitrogen. Of the pigs in the EC group that survived the early effects, there were few significant differences in physiological parameters, compared to control pigs, that would indicate ongoing pathological processes. In contrast, the FEC group pigs demonstrated early hypotension, but with increased cardiac output and reduced systemic vascular resistance. Other parameter changes were similar to those seen in the EC pigs, but to a lesser degree, with the exception of elevations in serum lactate dehydrogenase. Also in contrast to the EC group, most of the changes in the FEC group persisted in later days, and FEC pigs demonstrated leukocytosis. There were also greater elevations in circulating lipopolysaccharide (LPS) concentrations in the EC group that returned later to baseline levels. In the FEC group, there were persistently elevated LPS concentrations over 72 h. These observations suggest that pigs challenged with intraperitoneal E. coli demonstrated an initial acute peritonitis and damaging physiologic effects of high levels of circulating LPS. Survivors in this group improved and were physiologically stable after 24 h. Pigs that received i.p. autologous feces developed an early acute peritonitis phase with lower levels of circulating LPS, and later developed pronounced peritoneal reaction as demonstrated by multiple abdominal abscesses, pyogenic granuloma formation, and adhesions with physiological evidence of developing sepsis over 72 h. These observations indicate that i.p. EC models evoke a systemic response not unlike intravenous administration of LPS or EC, however, the FEC model produced a systemic response akin to a slower developing septic process.


Asunto(s)
Enfermedades Peritoneales/microbiología , Sepsis/etiología , Animales , Modelos Animales de Enfermedad , Escherichia coli/aislamiento & purificación , Heces/microbiología , Masculino , Enfermedades Peritoneales/patología , Sepsis/patología , Tasa de Supervivencia , Porcinos , Factores de Tiempo
13.
Surgery ; 119(1): 89-97, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8560392

RESUMEN

BACKGROUND: Bile acid exposure produces cellular hypercalcemia in gastric and hepatic cells. It is not known, however, whether this event contributes to cell injury or if it results from passive equilibration of calcium ion concentrations across the membranes of irreversibly damaged cells. This study was performed to determine whether the cellular hypercalcemia produced by bile acid exposure in gastric cells is reversible and to determine whether the source of this hypercalcemia is from intracellular stores of calcium, extracellular sources, or both. METHODS: Cytosolic free calcium concentrations ([Ca]i) were measured in rabbit gastric mucosal cells that had been loaded with the intracellular probe FURA-2. Measurements were performed in suspensions of dispersed cells by using standard spectrofluorometry and in primarily cultured cells by using fluorescence videomicroscopy. Measurements were made before and after exposure to 0.2, 0.5, and 1.0 mmol/L deoxycholic acid (DC). These measurements were made in the presence of 1 mmol/L extracellular calcium and in the absence of any extracellular calcium (0.5 mmol/L EGTA). RESULTS: In experiments with dispersed cells and spectrofluorometry, [Ca]i increased from a pretreatment level of 194 +/- 8 nmol/L to 396 +/- 21 nmol/L within 3 minutes of exposure to 0.2 mmol/L DC. When these cells were washed and resuspended in DC-free medium, [Ca]i] decreased to 180 +/- 5 nmol/L. In experiments with cultured cells and fluorescence videomicroscopy, rapid, reversible hypercalcemia was observed after exposure to 0.5 and 1.0 mmol/L DC. Removal of extracellular calcium from the incubating medium reduced both the magnitude and duration of the observed hypercalcemia. CONCLUSIONS: These data show that the cellular hypercalcemia that accompanies DC-induced injury in gastric cells is a reversible event. The initial increase in [Ca]i appears to come from both intracellular and extracellular sources, although sustained hypercalcemia requires a source of extracellular calcium. As a reversible event, cellular hypercalcemia may be an important pathophysiologic feature of bile acid induced injury of the upper gastrointestinal tract.


Asunto(s)
Colagogos y Coleréticos/farmacología , Ácido Desoxicólico/farmacología , Mucosa Gástrica/citología , Hipercalcemia/inducido químicamente , Animales , Calcio , Células Cultivadas , Espacio Extracelular , Hipercalcemia/patología , Conejos , Espectrometría de Fluorescencia
14.
J Exp Clin Cancer Res ; 20(4): 569-72, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11876553

RESUMEN

Urokinase plasminogen activation system can play an important role in the appearance and progression of many cancers. Urokinase-type plasminogen activator (uPA) is implicated in the control of cell adhesion and invasion, and is regarded as a strong prognostic marker in colorectal cancer. A C-->T substitution (the C/T polymorphism) in the nucleotide sequence encoding the kringle structure of uPA results in an alteration from proline to leucine at position 121. This substitution may be directly or indirectly involved in the decreased affinity for uPA substrates. In the present work the distribution of genotypes and frequencies of alleles of the C/T polymorphism were investigated. Tumour tissues and distal mucosa samples were obtained from 40 patients with colorectal cancer. Blood samples from sex and age matched healthy individuals served as control. The C/T polymorphism was determined by PCR amplification using the allele specific primers. No differences between genotypes of the C/T polymorphism in cancer tissue and distant mucosa of each patient were found. The distributions of the genotypes in both patients and control differed significantly (p < 0.05) from that predicted by the Hardy-Weinberg distribution. A distinct preference of heterozygotes (70% - patients, 65% - controls) was observed in both patients and controls. Additionally, there were no differences in the frequencies of the C and T alleles in both groups. The C/T polymorphism of the uPA gene may not be linked with colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/genética , Polimorfismo de Nucleótido Simple , Activador de Plasminógeno de Tipo Uroquinasa/genética , Adulto , Anciano , Citosina , Cartilla de ADN/química , ADN de Neoplasias/análisis , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Timidina/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
15.
J Exp Clin Cancer Res ; 20(2): 247-52, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11484982

RESUMEN

The high level of plasminogen activator inhibitor 1 (PAI-1) in colorectal cancer predicts poor prognosis for patients. The insertion (5G)/deletion (4G) polymorphism (the 4G/5G polymorphism) and G-->A single base substitution (the G/A polymorphism) located at promoter of PAI-1 gene may have functional significance in regulation of its expression. In the present work the level of PAI-1, distribution of genotypes and frequency of alleles of the 4G/5G and G/A polymorphisms in samples of cancer tissue and normal mucosa as well as in blood were investigated. Blood, tumor and normal tissues were obtained from 40 patients with colorectal cancer. The 4G/5G and G/A polymorphism were determined by PCR amplification using the allele specific primers. The PAI-1 level was measured by enzyme linked immunosorbent assay (ELISA). The distribution of the genotypes of both polymorphisms did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distributions and allele frequencies between blood, normal mucosa samples and cancer tissue. The 4G/5G and G/A polymorphisms were in linkage disequilibrium. The average level of PAI-1 in tumor samples was significantly (p < 0.05) higher than in normal tissue. The results obtained indicate that a higher level of PAI-1 can be associated with colorectal cancer. On the other hand, in colon cancer, the 4G/5G and G/A polymorphisms are not linked with elevated levels of PAI-1 and therefore may not be used to predict colon cancer prognosis.


Asunto(s)
Neoplasias Colorrectales/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético , Adulto , Anciano , Secuencia de Bases , Neoplasias Colorrectales/mortalidad , Cartilla de ADN/química , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Inhibidor 1 de Activador Plasminogénico/metabolismo , Reacción en Cadena de la Polimerasa , Pronóstico , Regiones Promotoras Genéticas
16.
Gen Physiol Biophys ; 19(4): 373-9, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11409840

RESUMEN

Salts of divalent cadmium are well-known human mutagens and carcinogens. In the present work, the ability of vitamin C to modulate genotoxic effects of cadmium chloride on human lymphocytes was assessed using single cell gel electrophoresis (comet assay). Vitamin C at 20 and 100 micromol/l and cadmium at 5, 30 and 150 micromol/l significantly increased the tail moment of lymphocytes. Vitamin C also increased the tail moment of cells exposed to cadmium. This effect was concentration-dependent: the higher the vitamin C concentration the greater the tail moment. The combined effects of cadmium and vitamin C were more pronounced at all concentrations tested than the sum of the effects of the compounds applied separately (p < 0.05), so cadmium and vitamin C can be considered to have synergistic effects. The results obtained can be partly explained by the participation of cadmium in the Fenton reaction and reduction of its oxidized form by vitamin C.


Asunto(s)
Ácido Ascórbico/toxicidad , Cloruro de Cadmio/toxicidad , Daño del ADN , ADN/efectos de los fármacos , Linfocitos/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , ADN/sangre , Sinergismo Farmacológico , Humanos , Técnicas In Vitro , Linfocitos/citología , Linfocitos/fisiología
17.
Pol J Pathol ; 45(1): 45-53, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8177618

RESUMEN

Lack of decrease in the level of calcium ions in the cytoplasm after incubation of cell suspension with deoxycholic acid (DC) may be an early sign of cellular damage. The purpose of the study was to find out whether an increase in free calcium level in the cytoplasm preceded other signs of damage and whether calcium channel blockade may inhibit calcium increase in the cytoplasm. The cell suspension from the gastric mucosa in rabbits was incubated with DC in various concentrations. The calcium level was measured by means of spectrofluorimetry after prior incubation with FURA 2/AM. The viability of cells was determined by measuring oxygen consumption and using trypan blue test. Deoxycholic acid in the concentration of 0.2 mM produced an increase in [Ca2+]i from 177 +/- 5 to 285 +/- 24 nM. Incubation of the cell suspension with 0,5 mM DC also produced an abrupt increase in [Ca2+]i from 177 +/- 5 nM to 639 +/- 49 nM. In addition, the studies showed that 0,2 mM DC despite increasing free calcium level in the cytoplasm did not reduce the cell viability. It was revealed on the basis of oxygen consumption and trypan blue test. The studies showed that an increased intracellular [Ca2+]i may be a very early sign of their damage.


Asunto(s)
Calcio/metabolismo , Citoplasma/efectos de los fármacos , Ácido Desoxicólico/farmacología , Mucosa Gástrica/efectos de los fármacos , Animales , Citoplasma/metabolismo , Mucosa Gástrica/metabolismo , Homeostasis/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Conejos , Verapamilo/farmacología
18.
Curr Med Chem ; 19(29): 4896-902, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22963639

RESUMEN

Current trends in research dealing with methods of developing effective chemotherapy for the two most dangerous killers - breast and colon cancers have been discussed. The input brought by nanotechnology is presented with particular stress on the use of dendrimers. These unique "polymeric compounds" after modification can form intelligent species, transporting drugs into specific areas and at the same time can be used for monitoring the state of organs attacked by cancer cells, as well as the progress of the curing process. They can help to limit the anticancer drugs delivery to designed goals only, eliminating many side effects of chemotherapy. Breast and colon cancer are major problem for public health care in many countries all over the world. During last twenty years a dramatic increase in incidence of both of them has been observed, especially in industrialized countries. Probably, both of them are caused, apart from the hereditary syndromes, by specific point mutation, some hormonal factors in breast cancer and by the strong co-influence of environmental factors and dietary exposure of a patient.


Asunto(s)
Neoplasias de la Mama/terapia , Neoplasias Colorrectales/terapia , Dendrímeros/administración & dosificación , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Portadores de Fármacos/administración & dosificación , Femenino , Técnicas de Transferencia de Gen , Humanos , Nanopartículas/administración & dosificación
19.
Eur J Surg Oncol ; 38(6): 467-71, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22285051

RESUMEN

AIMS: The EURECCA (European Registration of Cancer Care) consortium is currently formed by nine independently founded national colorectal audit registrations, of which most already run for many years. The cumulative experience of EURECCA's participants could be used to identify a 'core dataset' that covers all important aspects needed for high quality auditing and at the same time lacking needless data items that only consumes administrative effort. The aim of this study is to compare the data items used by the nine registries participating in EURECCA to identify a core dataset and explore options for future research. METHODS: All colorectal outcome registrations participating in the EURECCA project were asked to supply a list with all the data items they score. Items were scored 'present' if they appeared literally in a registration or in case they could be calculated using other items in the same registration. The definition of a 'shared data item' was that at least eight of the nine participating registries scored the item. RESULTS: The number of registered data items varied between 254 (Belgium) and 83 (Norway). Among the 45 variables were patient data, data about preoperative staging, surgical treatment, pre- or postoperative radio- and/or chemotherapy, and follow-up. Items about tumour recurrence or quality of life were scored too little to become shared data items. CONCLUSIONS: A total of 45 items were collected by 8 or more of the participating registries and subsequently met the criteria for a shared data item.


Asunto(s)
Neoplasias Colorrectales , Auditoría Médica , Garantía de la Calidad de Atención de Salud , Sistema de Registros , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Unión Europea , Humanos , Sistema de Registros/normas , Sistema de Registros/estadística & datos numéricos , Resultado del Tratamiento
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