Biomedical subjects

Sergio Muñoz

Publications and source records attributed to Sergio Muñoz.

At least 19 recordsLinked to original sources

PubMed2006

[Immunohistochemical expression of the E-cadherin-catenin complex in gastric cancer].

BACKGROUND: The E-cadherin/catenin complex plays an essential role in the control of epithelial differentiation. Abnormal expression in tumors correlates with histological grade, advanced stage and poor prognosis. AIM: To evaluate the expression pattern of E-cadherin/catenin complex in gastric carcinoma and analyze their association with tumor clinicopathological features and patient survival. MATERIAL AND METHODS: Inmunohistochemical staining of E-cadherin, alpha and ss-catenin was performed from paraffin specimens of 65 gastric carcinomas. RESULTS: Abnormal expression of E-cadherin, alpha and ss-catenin was demonstrated in 82%, 85% and 88% of gastric carcinomas, respectively. There was a significant correlation between abnormal expression and Lauren pathological classification and depth of infiltration, but not with tumor stage, positive lymph node metastases and survival. CONCLUSION: Abnormal expression of E-cadherin, alpha and ss-catenin occurs frequently in gastric carcinoma and correlates with histological grade.

Cadherins↗

PubMed2006

Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study.

BACKGROUND: Gallstones are considered the most important risk factor for gallbladder cancer. AIM: To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC). METHODS: A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk. RESULTS: Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls. CONCLUSIONS: The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients.

Analysis of Variance↗

PubMed2006

Comparative cytotoxicity of alkyl gallates on mouse tumor cell lines and isolated rat hepatocytes.

Alkyl esters of gallic acid inhibited the respiration rate of mouse sarcoma 786A and mouse mammary adenocarcinoma TA3 cell lines and its multiresistant variant TA3-MTX-R more effectively than gallic acid, both in the absence and in the presence of the uncoupler CCCP. The order of inhibition of the respiration rate by gallates in intact cells was n-octyl- approximately iso-amyl- approximately n-amyl- approximately iso-butyl->n-butyl->iso-propyl->n-propyl-gallate>>gallic acid. Sarcoma 786A was significantly more susceptible to all seven esters than the TA3 cell line. Respiration rates of the TA3-MTX-R cell line showed almost the same sensitivity to these esters as the TA3 cell line. However, hepatocytes were significantly less sensitive than all tumor cells tested. These alkyl gallates blocked mitochondrial electron flow, mainly at the NADH-CoQ segment, preventing ATP synthesis, which would lead to cellular death. These esters also inhibited, in the same order of potencies as respiration, the growth of 786A, TA3 and TA3-MTX-R cells in culture. In mice carrying TA3 or TA3-MTX-R tumor cells, an important decrease of the tumor growth rate and an increase of survival were observed when mice were treated with iso-butyl gallate alone or in combination with doxorubicin. These results indicate that alkyl gallates are selectively cytotoxic to tumor cells, which may be due to the mitochondrial dysfunctions of these cells.

Animals↗

PubMed2006

Promoter methylation profile in gallbladder cancer.

BACKGROUND: Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. METHODS: Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. RESULTS: All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. CONCLUSIONS: The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2006

Prognostic factors of phyllodes tumor of the breast.

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

Adult↗

PubMed2006

Reversal of type 1 diabetes by engineering a glucose sensor in skeletal muscle.

Type 1 diabetic patients develop severe secondary complications because insulin treatment does not guarantee normoglycemia. Thus, efficient regulation of glucose homeostasis is a major challenge in diabetes therapy. Skeletal muscle is the most important tissue for glucose disposal after a meal. However, the lack of insulin during diabetes impairs glucose uptake. To increase glucose removal from blood, skeletal muscle of transgenic mice was engineered both to produce basal levels of insulin and to express the liver enzyme glucokinase. After streptozotozin (STZ) administration of double-transgenic mice, a synergic action in skeletal muscle between the insulin produced and the increased glucose phosphorylation by glucokinase was established, preventing hyperglycemia and metabolic alterations. These findings suggested that insulin and glucokinase might be expressed in skeletal muscle, using adeno-associated viral 1 (AAV1) vectors as a new gene therapy approach for diabetes. AAV1-Ins+GK-treated diabetic mice restored and maintained normoglycemia in fed and fasted conditions for >4 months after STZ administration. Furthermore, these mice showed normalization of metabolic parameters, glucose tolerance, and food and fluid intake. Therefore, the joint action of basal insulin production and glucokinase activity may generate a "glucose sensor" in skeletal muscle that allows proper regulation of glycemia in diabetic animals and thus prevents secondary complications.

Animals↗

PubMed2006

Expression of IGF-I in pancreatic islets prevents lymphocytic infiltration and protects mice from type 1 diabetes.

Type 1 diabetic patients are diagnosed when beta-cell destruction is almost complete. Reversal of type 1 diabetes will require beta-cell regeneration from islet cell precursors and prevention of recurring autoimmunity. IGF-I expression in beta-cells of streptozotocin (STZ)-treated transgenic mice regenerates the endocrine pancreas by increasing beta-cell replication and neogenesis. Here, we examined whether IGF-I also protects islets from autoimmune destruction. Expression of interferon (IFN)-beta in beta-cells of transgenic mice led to islet beta(2)-microglobulin and Fas hyperexpression and increased lymphocytic infiltration. Pancreatic islets showed high insulitis, and these mice developed overt diabetes when treated with very-low doses of STZ, which did not affect control mice. IGF-I expression in IFN-beta-expressing beta-cells of double-transgenic mice reduced beta(2)-microglobulin, blocked Fas expression, and counteracted islet infiltration. This was parallel to a decrease in beta-cell death by apoptosis in islets of STZ-treated IGF-I+IFN-beta-expressing mice. These mice were normoglycemic, normoinsulinemic, and showed normal glucose tolerance. They also presented similar pancreatic insulin content and beta-cell mass to healthy mice. Thus, local expression of IGF-I prevented islet infiltration and beta-cell death in mice with increased susceptibility to diabetes. These results indicate that pancreatic expression of IGF-I may regenerate and protect beta-cell mass in type 1 diabetes.

Animals↗

PubMed2006

Adipose overexpression of phosphoenolpyruvate carboxykinase leads to high susceptibility to diet-induced insulin resistance and obesity.

Obesity and insulin resistance are associated with increased serum free fatty acids (FFAs). Thus, a reduction in circulating FFAs may increase insulin sensitivity. This could be achieved by increasing FFA reesterification in adipose tissue. Transgenic mice with increased adipose tissue glyceroneogenesis, caused by overexpression of phosphoenolpyruvate carboxykinase (PEPCK), show increased FFA reesterification and develop obesity but are insulin sensitive. Here, we examined whether these transgenic mice were protected from diet-induced insulin resistance. Surprisingly, when fed a high-fat diet for a short period (6 weeks), transgenic mice developed severe obesity and were more hyperinsulinemic, glucose intolerant, and insulin resistant than controls. The high triglyceride accumulation prevented white adipose tissue from buffering the flux of lipids in circulation and led to increased serum triglyceride levels and fat deposition in liver. Furthermore, circulating leptin and FFA concentrations increased to similar levels in transgenic and control mice, while adiponectin levels decreased in transgenic mice compared with controls. In addition, transgenic mice showed fat accumulation in brown adipose tissue, which decreased uncoupling protein-1 expression, suggesting that these mice had impaired diet-induced thermogenesis. These results indicate that increased PEPCK expression in the presence of high-fat feeding may have deleterious effects and lead to severe insulin resistance and type 2 diabetes.

Adiponectin↗

PubMed2005

In a diagnostic test study the validity of three serodiagnostic test was compared in patients with liver echinococcosis.

BACKGROUND AND OBJECTIVE: To determine the efficacy of immunoprecipitation (DD5), enzyme immunoanalysis (ELISA-IgG), and immunoelectrotransference or Western blot (WB) in patients with liver echinococcosis (LE) used separately, in parallel and in series. METHODS: Diagnostic test study. DD5, ELISA-IgG, and WB were applied in 75 patients with LE and 75 with cholelithiasis. Surgery was considered a reference standard. The sample size was calculated assuming a 99% confidence interval (99% CI), expected sensitivity (S) of 90% and a worst result of 80%; expected specificity (SP) of 95% and a worst result of 85%. S, SP, and predictive values (PPV and NPV) were calculated. RESULTS: The best S was verified with ELISA-IgG and WB (82.7%) and the best SP with DD5 (94.7%). DD5 presented a better PPV (92.9%) and WB a better NPV (83.5%). When applying the tests in parallel, the best S was obtained from the combination of DD5 and WB (82.7%); and the best SP, PPV and NPV with ELISA-IgG and WB (88.0%, 87.3%, and 83.5%, respectively). CONCLUSIONS: DD5 appears as the most specific test and as having greater PPV; ELISA-IgG and WB are more sensitive. The combined use of these tests does not improve diagnosis validity.

Adolescent↗

PubMed2005

Surgery for morbid obesity: selection of operation based on evidence from literature review.

BACKGROUND: Bariatric surgery is the therapy for morbid obesity. There are a number of surgical procedures, which are performed by open surgery (OS) and more recently also by laparoscopy (LS). The objective of this study was to consider the evidence for the best bariatric surgical options. METHODS: Systematic review of the literature was conducted. Morbid obesity studies published between 1990 and 2002 were analyzed. MEDLINE, LiLACS and COCHRANE databases were used, utilizing MeSH terms and free words. Selected studies were analyzed using a specially designed score of methodological quality, to analyze and compare studies. This validated scale is composed by 3 items, and the final score may range between 6 and 36 points. Means, medians and weighted means were calculated, and a comparative analysis by therapy was performed using median 95% confidence intervals (CI). Number of treated patients, reduction in body mass index (BMI), reduction in co-morbidity, %EWL, morbidity and mortality, hospital stay, follow-up, success and failure of operations, and methodological quality were analyzed. RESULTS: 283 related articles were considered. Only 31 of them had selection criteria (these include 5,216 patients operated by OS and 3,230 by LS). Operative mortality was 0.0% for OS and 0.4% for LS. At 36 months, OS techniques show reduction in BMI, %EWL and reductions in co-morbidity of 30.9%, 61.9% and 74.1% respectively. At 36 months, LS techniques show reduction in BMI, %EWL and reduction in comorbidity of 23.7%, 55.9% and 70.9%. Hospital stay was 3.8 days for LS and 7 for OS. At 2-year follow-up, morbidity was 14.8% for LS and 16.7% for OS, and reoperations were 17.7% for LS and 11.3% for OS. Median score for methodological quality was 13 for OS and 11 for LS. CONCLUSIONS: Methodological quality of primary studies to 2002 has been poor.

Body Mass Index↗

PubMed2004

Abdominal echinococcosis during pregnancy: clinical aspects and management of a series of cases in Chile.

Twelve pregnant women with hydatid disease are presented with median age of 29; 11 (91.7%) had a liver cyst and one (8.3%) had a kidney cyst as the primary disease location. Four (33.3%) had additional cysts located in the pelvis, peritoneal cavity and/or spleen; eight (66.7%) had two or more abdominal cysts. Three patients (25.0%) had surgery at the 3rd month after delivery and nine (75.0%) during their pregnancy. There was no histological evidence of hydatid disease in placentas, and no serological evidence of echinococcosis in the newborns was confirmed. One patient died after surgery. After a mean follow-up time of 39.5 months, we found one recurrent case of pelvic hydatid disease. Management of abdominal echinococcosis during pregnancy is an uncommon and difficult problem owing to the serious potential risks for mother and child.

Adult↗

PubMed2003

Liver abscess of hydatid origin: clinical features and results of aggressive treatment.

BACKGROUND: Cyst infection and subsequent liver abscess formation are complications of liver echinococcosis. Traditionally, this condition has been treated by simple drainage, a procedure associated with unsatisfactory postoperative evolution. METHODS: The present paper examines a series of cases involving infected liver echinococcal cysts. Surgery was performed at the Temuco Regional Hospital after assessment was made of general and liver laboratory parameters, chest X-ray and abdominal ultrasound were performed and antibiotic treatment was administered. The procedure consisted of surgical drainage, parasite material extirpation and pericystic membrane resection with surrounding healthy liver parenchyma. The morbidity and mortality rate, hospital stay and evidence of recurrent hydatid disease were evaluated. RESULTS: Forty-nine patients (21 male and 28 female), with a median age of 45 years (range 16-84 years), with infected cysts measuring 14 cm in ultrasonographical diameter (range 5-30 cm) were operated on. In the majority of cases, liver abscesses were located in the right lobe (37 patients, 75.4%) and the most frequent computed tomography scan pattern was heterogeneous (40 patients, 81.6%). The median hospital stay was 5 days, the median follow-up period was 32 months (range 2-91 months) and perioperative morbidity was 24.4%. Surgical complications were verified in five patients (10.2%) and medical complications occurred in seven cases (14.3%). No recurrence of hydatid disease was observed. Mortality was 2% (one patient). CONCLUSIONS: Good results were obtained when hydatid liver abscesses were treated aggressively.

Adolescent↗

PubMed2003

Uncommon locations of abdominal hydatid disease.

South Chile is an endemic zoonosis area of hydatid disease, where prevalence rates can be 30 to 40/100 000 habitants. Not only is surgery performed on a great number of liver and lung hydatid cysts every year, but also upon cysts found in uncommon abdominal locations such as spleen, peritoneum and kidney. Information on this subject is scarce. We reviewed PubMed index from 1975 to 2001 and found only five related articles, reporting more than 30 cases.

Adult↗

PubMed2002

Initial validation of a questionnaire for detecting gastroesophageal reflux disease in epidemiological settings.

There is a high prevalence of gastroesophageal reflux disease (GERD) in the general population. Prevalence studies are scarce, and there is a lack of valid instruments for measuring them. The aim of this paper is to validate a questionnaire for detecting GERD. A validity study design with pathologic GERD patients and controls was used. A sample of 240 subjects age and sex paired was selected in the ratio of 3:1 (patients to controls). The initial structured questionnaire contained a variety of GERD symptoms. Internal consistency, interobserver reliability, criteria validity using 24-h esophageal pH monitoring, construct validity, and extreme group validation were assessed. Sensitivity, specificity, and predictive values were also obtained in different cutoff points of the definitive scale. A total of 180 confirmed GERD patients and 60 controls were included in the study. Mean age in years was 45 +/- 13, with no statistical difference by gender (67% were female). Internal consistency of 0.75 and interobserver reliability of 0.87 was achieved in building the scale. Extreme group validation was highly significant by assessing the scale score with 24-h esophageal pH monitoring (P <.0001). At cutoff point 3 of the scale and with a correct classification of subjects of 92.4%, sensitivity, specificity, positive, and negative predictive values were 92, 95, 98, and 79%, respectively. The conclusion of this article is that a reliable and valid instrument was built to detect GERD.

Adult↗

PubMed2002

Inhibitory effect of vanillin-like compounds on respiration and growth of adenocarcinoma TA3 and its multiresistant variant TA3-MTX-R.

The effects of some imine and amine derivatives of vanillin on the respiration rate of mouse mammary adenocarcinoma TA3 line, its multiresistant variant TA3-MTX-R line and mouse hepatocytes, together with their respective mitochondrial fractions, are described. These derivatives inhibit respiration in both tumour cell lines more effectively than vanillin in the absence or presence of the uncoupler CCCP. Since both types of derivatives block the electron flow, mainly through the NADH-CoQ span, they behave as oxidative phosphorylation inhibitors. Thus, they prevent ATP synthesis and alter cellular processes requiring energy, which would lead to cellular death. Amine derivatives of vanillin present a similar effect on both tumour cell lines, being amine C the most efficient inhibitor. Moreover, mouse hepatocytes are about 4-fold less sensitive to amine C than tumour cells. These amine derivatives are better inhibitors than the corresponding imines; probably because they should interact better with the respiratory chain reaction site.

Adenocarcinoma↗

PubMed2002

Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance.

Adipose tissue glyceroneogenesis generates glycerol 3-phosphate, which could be used for fatty acid esterification during starvation. To determine whether increased glyceroneogenesis leads to increased fat mass and to explore the role of obesity in the development of insulin resistance, we overexpressed PEPCK, a regulatory enzyme of glyceroneogenesis in adipose tissue. Transgenic mice showed a chronic increase in PEPCK activity, which led to increased glyceroneogenesis, re-esterification of free fatty acids (FFAs), increased adipocyte size and fat mass, and higher body weight. In spite of increased fat mass, transgenic mice showed decreased circulating FFAs and normal leptin levels. Moreover, glucose tolerance and whole-body insulin sensitivity were preserved. Skeletal muscle basal and insulin-stimulated glucose uptake and glycogen content were not affected, suggesting that skeletal muscle insulin sensitivity is normal in transgenic obese mice. Our results indicate the key role of PEPCK in the control of FFA re-esterification in adipose tissue and, thus, the contribution of glyceroneogenesis to fat accumulation. Moreover, they suggest that higher fat mass without increased circulating FFAs does not lead to insulin resistance or type 2 diabetes in these mice.

Adipocytes↗

PubMed2002

[Seroprevalence of antibodies against hantavirus in 10 communities of the IX Region of Chile where hantavirus infection were diagnosed].

BACKGROUND: Thirty six cases of clinical Hantavirus Cardiopulmonary Syndrome occurred in the IX Region of Chile. Most of these patients were young males, farm or timber workers, who lived near the Andes Mountain chain. AIM: To conduct an epidemiological and serosurvey study to determine the seroprevalence of IgG antibodies against Hantavirus in the general adult population living in rural and urban areas of 10 endemic communities of the IX region of Chile. MATERIAL AND METHODS: A total of 400 subjects were included, 40 of each community, 20 rural residents and 20 urban residents, 20 males and 20 females. RESULTS: Seroprevalence was 7.5% in Melipeuco, 5.0% in Lonquimay, 2.5% in Curacautin, 2.5% in Pucón and 0.0% in the remaining communities. Seroprevalence was higher in rural population (2.5%) than in the urban areas (1%). All seropositive subjects worked in farms or forests and observed rodents near their homes or working places. Females were affected the same as males and no differences were observed between Chilean natives and Hispanics. CONCLUSIONS: Prevalence of Hantavirus antibodies correlated with the geographic zone (Andes Mountain chain), overgrowth of wild rodents and exposure to rodent-infested environments.

Adolescent↗

PubMed2002

[Morphological prognostic elements in gallbladder cancer].

BACKGROUND: The exact survival rates and prognostic factors of gallbladder cancer are still incompletely known. AIM: To report the actuarial survival of patients with gallbladder cancer. MATERIAL AND METHODS: Six hundred thirty seven women, aged 59 years old as a mean and 108 men, aged 64 years old as a mean, with gallbladder cancer are reported. Patients were followed for up to 150 months. RESULTS: Two hundred twenty four patients had an early and 521 had an advanced carcinoma. Overall survival was 38% at ten years. Sex or ethnic origin did not influence survival. Early tumors had a 92% survival at 10 years whereas the survival of advanced tumors was 16% at 5 years. Subserous tumors had a 5 years survival of 32% whereas serous tumors had a 5 years survival of 11%. Well-differentiated advanced tumors had a significantly better survival than moderately or poorly differentiated tumors. Vascular or lymphatic infiltration was also associated to a lower survival. All patients with advanced tumors and vascular infiltration died before 5 years. CONCLUSIONS: Tumor infiltration and differentiation degree were the most important prognostic independent factors in gallbladder cancer.

Adenocarcinoma↗