Circulating level of 25(OH)D3 with risk factors of asymptomatic adenoma and proximal non-adenoma colorectal polyps / Níveis circulantes de 25(OH)D3 com fatores de risco de adenoma assintomático e pólipos colorretais proximais sem adenoma

ABSTRACT Background: An inverse association between circulating vitamin D and adenoma risk hasbeen reported, but less is known about proximal inflammatory-hyperplastic polyps.Purpose: To investigate circulating 25(OH)D3and risk factors of proximal inflammatory-hyperplastic and adenoma colorectal polyps.Methods: From January 2017 to June 2019, consecutive asymptomatic average-risk partic-ipants undergoing initial screening colonoscopy. Questionnaires provided information oncolorectal polyp risk factors, and plasma samples were assayed for 25-Hydroxyvitamin-D ­25(OH)D3. The colorectal polyps were assessed, and medical history and demographic datawere obtained from each patient.Results: Of the 220 asymptomatic subjects, the prevalence of proximal inflammatory-hyperplastic polyps and adenoma polyps were 16.8%; 18.1% and 22.2%, respectively.Multivariate analysis revealed that low vitamin D (25(OH)D3< 18 ng/mL, OR = 3.94; 95%CI: 1.81­9.51) and current/former smoking (OR = 6.85; 95% CI: 2.98­15.70), high bodymass index (BMI > 24, OR = 5.32, 95% CI: 2.62­4.71) were independent predictors forproximal inflammatory-hyperplastic colorectal polyps (non-adenoma). Low vitamin D(25(OH)D3< 18 ng/mL, OR = 7.75; 95% CI: 3.19­18.80) and current/former smoking (OR = 3.75;95% CI: 1.30­10.81), age over 60 years old (OR = 2.38, 95% CI: 1.02­5.57), were independentpredictors for adenoma colorectal polyps.Conclusion: Low vitamin D and smoking are common risk factors for both adenomatous andproximal inflammatory hyperplastic polyps. Old age and BMI are additional risk factors forthe development of adenomatous and non-adenomatous colorectal polyps.

RESUMO Background: An inverse association between circulating vitamin D and adenoma risk hasbeen reported, but less is known about proximal inflammatory-hyperplastic polyps.Purpose: To investigate circulating 25(OH)D3and risk factors of proximal inflammatory-hyperplastic and adenoma colorectal polyps.Methods: From January 2017 to June 2019, consecutive asymptomatic average-risk partic-ipants undergoing initial screening colonoscopy. Questionnaires provided information oncolorectal polyp risk factors, and plasma samples were assayed for 25-Hydroxyvitamin-D ­25(OH)D3. The colorectal polyps were assessed, and medical history and demographic datawere obtained from each patient.Results: Of the 220 asymptomatic subjects, the prevalence of proximal inflammatory-hyperplastic polyps and adenoma polyps were 16.8%; 18.1% and 22.2%, respectively.Multivariate analysis revealed that low vitamin D (25(OH)D3< 18 ng/mL, OR = 3.94; 95%CI: 1.81­9.51) and current/former smoking (OR = 6.85; 95% CI: 2.98­15.70), high bodymass index (BMI > 24, OR = 5.32, 95% CI: 2.62­4.71) were independent predictors forproximal inflammatory-hyperplastic colorectal polyps (non-adenoma). Low vitamin D(25(OH)D3< 18 ng/mL, OR = 7.75; 95% CI: 3.19­18.80) and current/former smoking (OR = 3.75;95% CI: 1.30­10.81), age over 60 years old (OR = 2.38, 95% CI: 1.02­5.57), were independentpredictors for adenoma colorectal polyps.Conclusion: Low vitamin D and smoking are common risk factors for both adenomatous andproximal inflammatory hyperplastic polyps. Old age and BMI are additional risk factors forthe development of adenomatous and non-adenomatous colorectal polyps.

Calcium Intake and Health.

There are striking inequities in calcium intake between rich and poor populations. Appropriate calcium intake has shown many health benefits, such as reduction of hypertensive disorders of pregnancy, lower blood pressure particularly among young people, prevention of osteoporosis and colorectal adenomas, lower cholesterol values, and lower blood pressure in the progeny of mothers taking sufficient calcium during pregnancy. Studies have refuted some calcium supplementation side effects like damage to the iron status, formation of renal stones and myocardial infarction in older people. Attention should be given to bone resorption in post-partum women after calcium supplementation withdrawal. Mechanisms linking low calcium intake and blood pressure are mediated by parathyroid hormone raise that increases intracellular calcium in vascular smooth muscle cells leading to vasoconstriction. At the population level, an increase of around 400-500 mg/day could reduce the differences in calcium intake between high- and middle-low-income countries. The fortification of food and water seems a possible strategy to reach this goal.

Physical activity during adolescence and risk of colorectal adenoma later in life: results from the Nurses' Health Study II.

BACKGROUND: Physical activity during adulthood has been consistently associated with lower risk of colorectal cancers, but whether physical activity during adolescence may also play a role in colorectal carcinogenesis is unclear. METHODS: We included 28,250 women in the Nurses' Health Study II who provided data on physical activity during adolescence (ages 12-22 years) in 1997 and underwent lower bowel endoscopy (1998-2011). We used logistic regression models for clustered data to examine the association between physical activity during adolescence and risk of adenoma later in life. RESULTS: Physical activity during adolescence was inversely associated with risk of colorectal adenoma (2373 cases), independent of physical activity during adulthood. The multivariable-adjusted odds ratio (OR) of adenoma was 0.89 (95% CI 0.77-1.02; Ptrend = 0.03) comparing women with ≥ 72 metabolic equivalent of tasks-hours/week (MET-h/week) to < 21 MET-h/week. Women with high physical activity during both adolescence (≥53.3 MET-h/week) and adulthood (≥23.1 MET-h/week) had significantly lower risk of adenoma (all adenomas: OR 0.76; 95% CI 0.66-0.88; advanced adenoma: OR 0.61; 95% CI 0.45-0.82) compared to women with low physical activity during both stages of life. CONCLUSIONS: Our findings suggest that physical activity during adolescence may lower the risk of colorectal adenoma later in life.

Incidencia de adenomas hipofisiarios en pacientes ingresados al servicio de neurocirugía del Hospital Roosevelt. Guatemala, enero 2010 a diciembre 2011 / Incidence of pituitary adenomas in patients admitted to the neurosurgery department of Roosevelt Hospital. Guatemala, January 2010 to December 2011

Introducción: Los adenomas de hipófisis sonneoplasias benignas que afectan más a adultosde sexo femenino. No se cuenta con tasa deincidencia anual de adenomas hipofisarios anivel nacional. Se realizó un estudio descriptivocon el fin de determinar la incidencia local deadenomas hipofisarios. Metodología: Se realizóun estudio descriptivo transversal en pacientesque ingresaron al Departamento de Neurocirugíadel Hospital Roosevelt para intervención quirúrgicadurante enero 2010 a diciembre 2011. Lasvariables estudiadas fueron edad, sexo, tipo deadenoma hipofisario, síntomas y signos clínicos,complicaciones postoperatorias tempranas,estancia en cuidados críticos y mortalidad. El plande análisis estadístico incluyó la recolección de lainformación, el ordenamiento de datos y uso delprograma Epi Info 3.5.6 para el análisis estadísticode medidas de frecuencia y proporciones. Se utilizóMicrosoft Excell para la elaboración de tablas ygráficas. Resultados: La tasa de incidencia deadenomas hipofisarios fue de 15 casos por cada 100tumores. El predominio del tumor fue en pacientesfemeninas y en edades comprendidas entre los 31-65 años. La disminución de la agudeza visual y lacefalea fueron los signos y síntomas más frecuentes(81% y 77% respectivamente). La complicaciónpostoperatoria inmediata más frecuente fue ladiabetes insípida (4/10 casos). El 54% de los casospermaneció en cuidados intensivos por un periodoentre uno y tres días. Para este estudio la tasa demortalidad fue cero...

Introduction: Pituitary adenomas are benignneoplasms affecting more female adults. Thereis no annual incidence of pituitary adenomasnationwide. A descriptive study was conducted todetermine the local incidence of pituitary adenomas.Methodology: A descriptive cross-sectional studyin patients admitted to the Department of Neurosurgeryat Roosevelt Hospital for surgery injanuary 2010 to december 2011. The variablesstudied were age, sex, type of pituitary adenoma,clinical signs and symptoms, early postoperativecomplications, hospital stay and mortality in criticalcare. The statistical analysis plan included collectinginformation , the ordering of data and use of Epi Info3.5.6 program for statistical analysis of frequencymeasurements and proportions. Microsoft Excelwas used to produce tables and graphs. Results:The incidence of pituitary adenomas was 15 casesper 100 tumors. The prevalence of the tumor was infemale patients and aged 31-65 years. Decreasedvisual acuity and headache were the most commonsigns and symptoms (81% and 77% respectively).The most common immediate postoperative complicationwas diabetes insipidus (4 /10 cases) 54%of the cases remained in intensive care for a periodof one to three days. For this study, the mortality ratewas zero...

Effects of selenium on Pteridium aquilinum and urethane-induced lung carcinogenesis.

The results of our previous study demonstrated that ptaquiloside, the main toxic agent found in Pteridium aquilinum, suppresses natural killer (NK) cell-mediated cytotoxicity. However, the ability of ptaquiloside to suppress the cytotoxicity of NK cells was prevented by selenium supplementation. NK cells play an important role in the innate immune response and have the ability to kill tumor cells. Therefore, we hypothesized that selenium may prevent the higher susceptibility to urethane-induced lung carcinogenesis that has been observed in mice treated with P. aquilinum. The immunosuppressive effects of ptaquiloside have been associated with a higher number of urethane-induced lung nodules in mice. Hence, we assessed the effects of P. aquilinum-induced immunosuppression on urethane-induced lung carcinogenesis in C57BL/6 mice that had been supplemented with selenium. For these experiments, mice were treated with both an aqueous extract of P. aquilinum (20 g/kg/day) and selenium (1.3 mg/kg) by gavage once daily for 14 days followed by a once-weekly intraperitoneal injection of urethane (1 g/kg) for 10 weeks that was accompanied by gavage 5 days a week. Lung adenomas in mice that had been treated with P. aquilinum plus urethane occurred with a frequency that was 44% higher than that in mice that had been treated with only urethane. In mice that had been supplemented with selenium and treated with P. aquilinum plus urethane, the occurrence of lung adenomas was reduced to 26%. These results suggest that selenium prevents the immunosuppressive effects of P. aquilinum on urethane-induced lung carcinogenesis.

Crotalus durissus terrificus venom as a source of antitumoral agents

The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV) and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumoral effect on benign (pituitary adenoma) and malignant (glioblastoma multiforme) tumors with IC50 values of 0.96 ± 0.11 ìg/mL and 2.15 ± 0.2 ìg/mL, respectively. This antitumoral effect is cell-cycle-specific and dependent on extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumoral effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumoral dose established in vitro was not found to be toxic to the analyzed animals. These results indicate the biotechnological potential of CV as a source of pharmaceutical templates for cancer therapy.(AU)

Lung tumor development in the presence of sphingosine 1-phosphate agonist FTY720.

Urethane is a chemical carcinogen which causes lung tumorigenesis in mice with similarities to human adenocarcinoma (AC). The sphingosine 1-phosphate agonist FTY720 administered to mice in doses above 5 mg/kg/day has been able to prevent hepatocellular carcinoma and bladder cancer. We used BALB/c mice in urethane-induced lung cancer model to investigate the effects of a lower dose of FTY720 (1 mg/kg/day). The benefits of FTY720 were associated with the time point of the compound administration. FTY720 30 Group presented lower incidence and smaller area of lung nodules, decreased PCNA and increased Caspase-3 expressions. The findings in FTY720 0 Group (nodule multiplicity and area, PCNA expression) were similar to Urethane Group suggesting that the administration of the compound at early time point did not affect lung tumor development. FTY720 90 Group presented the biggest nodule area which was associated with increased PCNA and decreased Caspase-3 expressions. FTY720 (30 days and 90 days) administration decreased CD4 + splenocytes and blood lymphocytes which caused opposite effects in lung tumor development - impairment and improvement respectively.In conclusion, FTY720 in low dose did not provide lung tumor inhibition in mice but its administration 30 days after the chemical carcinogen (Urethane) injection was associated with impaired tumor development.

FTY720 and lung tumor development.

FTY720 has been shown to prevent cancer development in experimental models but there is no report whether this beneficial effect is associated with the time point of the drug administration. Lung adenoma was induced in mice by urethane injection followed by different periods of FTY720 administration in order to evaluate lung tumor development. BALB/c mice received urethane intraperitoneally in two doses of 1.5 g/kg and were submitted to five daily doses of FTY720 (1 mg/kg/day) starting just after urethane injection (G2 n=5), 4 weeks after urethane injection (G3 n=10), 8 weeks after urethane injection (G4 n=10) and no FTY720 administration (G1 n=5). Twenty-four weeks after urethane administration mice were evaluated for the number of leukocyte in blood, lymphocytes in spleen, and lungs were evaluated for changes in histology, PCNA and VEGF expression. Lung nodules were present in higher numbers both in non treated (G1; 0.0-7.0) and FTY720 treated 8 weeks after urethane injection (G4; 0.0-6.0). G4 Group also presented the highest number of papillary nodules. G1 and G4 groups presented the lower number of splenocytes and neutrophils. In early time FTY720 treated mice (G2) we observed a slight decrease in PCNA staining and also the lower percentage of VEGF intense staining. Therefore, our data suggest that the benefits of FTY720 treatment are time-dependent and when administered in early periods after lung tumor induction this drug could impair cancer development.

Thyroid cancer, thyroiditis and dietary iodine: a review based on the Salta, Argentina model.

Factors that should be considered when studying the effect of dietary iodine in the development of thyroid cancer include pathological criteria, diagnostic techniques, screening programs, radioactive fallout, and standard of medical care in the studied population. In most surveys, papillary carcinoma forms the largest group of thyroid malignancies, both before and after iodine prophylaxis where an increase in the papillary:follicular carcinoma ratio is also noted. Undifferentiated carcinomas decrease after salt prophylaxis. In Salta, Argentina, the increasing incidence of clinically significant papillary thyroid cancer and the decrease of undifferentiated carcinoma after iodine prophylaxis are probably due to better access to health centers and consequent earlier detection of differentiated precursor tumors. Autoimmune focal and diffuse or Hashimoto's thyroiditis are linked to dietary iodine. Pathological studies made in different regions indicate that these types of thyroiditis occur more frequently in areas of iodine sufficiency than in areas of iodine deficiency, and increase after iodine prophylaxis both in non-goitrous and iodine-deficient areas like Salta, Argentina. An increase of lymphocytic thyroiditis could be linked to an increased incidence of primary thyroid lymphoma, and thyroiditis is more commonly associated with papillary carcinoma than with other types of thyroid follicular or C-cell derived carcinomas regardless of iodine intake.

Inhibitory effects of Pfaffia paniculata (Brazilian ginseng) on preneoplastic and neoplastic lesions in a mouse hepatocarcinogenesis model.

Studies have been demonstrating Pfaffia paniculata root (Brazilian ginseng) anticarcinogenic activities. We evaluated its chemopreventive effects on preneoplastic hepatic lesions. BALB/c aged-15 days received 10mug/g of diethylnitrosamine carcinogen, i.p. They were fed with the powdered root added to the diet: 0.5, 2 or 10% during 27 weeks. After being sacrificed, the macroscopic lesions in the livers were examined. Preneoplastic or neoplastic lesions were measured, quantified and classified morphologically. The treatment reduced the incidence, mean area and number of lesions, indicating an inhibitory effect of these roots on hepatocarcinogenesis promotion or progression steps.

[Etiology of colorectal cancer]. / Etiología del cancer colorectal.

Colorectal cancer affect the 15% of general population in developed countries. Cancer is a multistep process in which multiple genetic alterations must usually occur in several years. The premalignant step consists of one or multiple aberrant crypts due to hyperproliferation of cells and its shift from the deep third of the crypt to its surface. It has been suggested that abnormality in the APC gene is responsible for this. Furthermore, there exists DNA hypometilation, activation of the gene K-ras and ornithine decarboxylase activity. There is also a loss of MCC gene, that seems to interact with the APC gene. Entire alterations described make possible the Class I adenoma formation. This adenoma, needs the loss of the DCC gene (late stage in the carcinogenesis process), to become a Class II adenoma. The following alteration is deleted and mutation of the p53 gene. There is also an activation of the c-myc oncogene. These two genes are important mechanisms for the conversion of a benign adenoma to a malignant one, adenoma with in situ carcinoma or Class III adenoma. This type of adenoma becomes carcinoma and metastatic stage, throughout inactivation of several tumor suppressor genes. Besides the hereditary APC alteration and other acquired genetic changes as described above there are other associated genetics, antigenics, and enzymes that have an important role in the adenoma-carcinoma sequence. Several carcinogenic factors have been described which also contribute in the adenoma and carcinoma formation: ulcerative colitis, acromegaly, familial history of colonic neoplasia, certain professions, smoking and drinking, consumption of red or processed meat, etc.(ABSTRACT TRUNCATED AT 250 WORDS)