RESUMEN
In the 1-year double-blind placebo-controlled intervention trial, it was shown that daily supplementation of patients with gastric premalignant lesions (intestinal metaplasia, IM) with a complex, containing Ester-C with antioxidantsand (2100 mg of Ca-ascorbate + 340 mg of bioflavonoids), produced a sharp decrease of abnormally high ornithine decarboxylase activity in IM gastric mucosa that was accom panied by practically total IM regression in 11 of 18 (61%) patients.
Asunto(s)
Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Gastritis Atrófica/dietoterapia , Gastritis Atrófica/tratamiento farmacológico , Infecciones por Helicobacter/dietoterapia , Infecciones por Helicobacter/tratamiento farmacológico , Adulto , Anciano , Enfermedad Crónica , Método Doble Ciego , Femenino , Mucosa Gástrica/enzimología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis Atrófica/enzimología , Gastritis Atrófica/patología , Infecciones por Helicobacter/enzimología , Humanos , Intestinos/enzimología , Intestinos/patología , Masculino , Metaplasia/dietoterapia , Metaplasia/tratamiento farmacológico , Metaplasia/enzimología , Metaplasia/patología , Persona de Mediana Edad , Ornitina Descarboxilasa/metabolismoRESUMEN
It was shown that the 3-month supplementation of patients having colon polyps with folic acid (5 mg/day) led to a 35% decrease in abnormally high ornithine decarboxylase activity in polyps that was accompanied by a 43% increase of S-adenosylmethionine content in polyps.
Asunto(s)
Pólipos Adenomatosos/metabolismo , Pólipos del Colon/metabolismo , Ácido Fólico/farmacología , Proteínas de Neoplasias/biosíntesis , Ornitina Descarboxilasa/biosíntesis , S-Adenosilmetionina/metabolismo , Pólipos Adenomatosos/enzimología , Pólipos del Colon/enzimología , Progresión de la Enfermedad , Método Doble Ciego , Inducción Enzimática/efectos de los fármacos , Femenino , Ácido Fólico/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Proteínas de Neoplasias/genética , Ornitina Descarboxilasa/genéticaRESUMEN
The effect of high doses of vitamin E (Vit.E; 400 units/ day) on ornithine decarboxylase (ODC) activity and regression of small intestinal metaplasia (SIM) was studied in a 1-year double-blind intervention trial. Biochemical and morphological parameters were estimated in 14 evaluable SIM patients of 18 in the Vit.E group and in 16 of 18 intestinal metaplasia patients enrolled in control group (placebo). In the control group, there were no statistically significant changes in Vit.E content in blood plasma, ODC activity, and the rate of SIM in multiple biopsies from antrum gastric mucosa. In the Vit.E group, after 6 and 12 months of intervention, the initial content of Vit.E in blood plasma increased from 6.4 +/- 0.9 up to 17.0 +/- 1.8 and 21.2 +/- 2.3 micrograms/ml, respectively, and the initial abnormally high activity of ODC, 62.6 +/- 7.8 units, decreased by 53 and 65%, respectively. Histological analysis of multiple biopsies, taken from the gastric antrum of patients supplemented with Vit.E, revealed that in 8 of 14 patients (57%) after 6 months and in 10 of 14 patients (71%) after 12 months, no signs of SIM were observed; gastroscopic dye procedure confirmed the regression of SIM in these cases and showed the presence of only small isolated stained areas identified as SIM.
Asunto(s)
Transformación Celular Neoplásica/efectos de los fármacos , Ornitina Descarboxilasa/metabolismo , Lesiones Precancerosas/patología , Neoplasias Gástricas/patología , Vitamina E/administración & dosificación , Adulto , Anciano , Biopsia , Transformación Celular Neoplásica/patología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/enzimología , Mucosa Gástrica/patología , Gastritis/enzimología , Gastritis/patología , Gastroscopía , Infecciones por Helicobacter/enzimología , Infecciones por Helicobacter/patología , Helicobacter pylori , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Lesiones Precancerosas/enzimología , Neoplasias Gástricas/enzimologíaRESUMEN
The effect of beta-carotene and DL-alpha-tocopheryl acetate (alpha-TAc) on the activity of ornithine decarboxylase (ODC) in human atrophic stomach mucosa and intestinal metaplasia (IM) was studied in a double-blind intervention trial. Persons (227) with upper gastrointestinal symptoms and/or atrophic gastritis (AG) were examined. It was found that ODC activity in the biopsies of antral mucosa increased gradually from normal mucosa (7.2 +/- 1.8 units) to superficial gastritis (22.7 +/- 5.9 units) and to AG (54.2 +/- 6.9 units). Enzyme activity in cases of IM did not differ from atrophic mucosa without IM (56.1 +/- 8.0 versus 51.4 +/- 5.6 units; P > 0.05). For the intervention trial, 3 groups of 20 patients with AG were studied. Patients were supplemented daily for 1 year with beta-C (20 mg; group 1), alpha-TAc (55 mg; group 2), or placebo (group 3). No significant change in ODC activity was observed in placebo-treated subjects during 1-year follow-up. During the first 3 months, beta-C supplementation resulted in about a 50% decrease in ODC activity in atrophic mucosa. A moderate decrease in ODC activity of approximately 18% was observed after 6 months supplementation with alpha-TAc. The possible role of ODC in gastric carcinogenesis is discussed.
Asunto(s)
Antioxidantes/uso terapéutico , Carotenoides/uso terapéutico , Mucosa Gástrica/enzimología , Gastritis Atrófica/tratamiento farmacológico , Ornitina Descarboxilasa/efectos de los fármacos , Vitamina E/análogos & derivados , alfa-Tocoferol/análogos & derivados , Adulto , Anciano , Antioxidantes/administración & dosificación , Biopsia , Carotenoides/administración & dosificación , Intervalos de Confianza , Método Doble Ciego , Esquema de Medicación , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastritis Atrófica/patología , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Ornitina Descarboxilasa/metabolismo , Tocoferoles , Resultado del Tratamiento , Vitamina E/administración & dosificación , Vitamina E/uso terapéuticoRESUMEN
Increase of ornithine decarboxylase (ODC) activity is known to be associated with cell proliferation and, very likely, with tumour promotion. This prompted us to study the activity of ODC in gastric mucosa of patients with chronic atrophic gastritis that has been considered as a precursor of stomach cancer. Examination of 124 patients with this disease revealed the considerable increase in ODC activity in atrophic mucosa (29.8 +/- 2.9 vs 7.9 +/- 1.8 units in normal mucosa, p = 0.001). Supplementation of the patient's diet with beta-carotene (20 mg daily during 3 weeks) results in a statistically significant decrease in ODC activity in gastric mucosa. The data obtained confirm the possibility of application of ODC determination to the detection of early premalignant lesions and suggest the antipromoter activity of beta-carotene in gastric carcinogenesis.
Asunto(s)
Carotenoides/administración & dosificación , Mucosa Gástrica/enzimología , Gastritis Atrófica/enzimología , Ornitina Descarboxilasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Mucosa Gástrica/efectos de los fármacos , Gastritis Atrófica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Ornitina Descarboxilasa/efectos de los fármacosRESUMEN
Activity of ornithine decarboxylase was significantly increased, reaching the maximal values in malignant gastric tissues, in mucosal membrane and polypous tissue of patients with atrophic gastritis as compared with normalcy. Any alterations in the enzymatic activity were not observed in the gastric mucosal membrane of 19 patients with atrophic gastritis within 3 weeks. At the same time, statistically significant decrease of the abnormal high activity of ornithine decarboxylase was detected in atrophic gastric mucosal membrane of 12 patients among 20 patients examined, which were treated with 20 mg of beta-carotene daily within 3 weeks; the enzyme activity was decreased also in polypous tissue of 5 patients in the group of 9 patients studied. Decrease in the ornithine decarboxylase activity after beta-carotene treatment involved improvement of the mucosal membrane state, where hemorrhage disappeared and inflammation reduced. Since the high activity of ornithine decarboxylase is related to promotion of cancerogenesis, beta-carotene appears to exhibit an anticarcinogenic effect as it decreases the enzymatic activity in gastric mucosal membrane.
Asunto(s)
Carotenoides/farmacología , Mucosa Gástrica/enzimología , Ornitina Descarboxilasa/metabolismo , Pólipos/enzimología , Estómago/patología , Adulto , Anciano , Femenino , Gastritis Atrófica/enzimología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Ornitina Descarboxilasa , beta CarotenoRESUMEN
Effect of beta-carotene on content of some metabolites of lipid peroxidation and activity of ornithine decarboxylase was studied in rat gastric mucosal membrane during gastric carcinogenesis developed after administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Intragastric administration of MNNG led to a significant increase in content of diene ketones and malonic dialdehyde in the gastric mucosal membrane within a day, while beta-carotene normalized or decreased considerably the MNNG produced accumulation of these lipid peroxidation products. In acute experiments with MNNG beta-carotene administered per os at a dose of 0.5 mg per animal did not affect the pronounced activation of ornithine decarboxylase in the gastric mucosal membrane. However, in chronic experiments with MNNG repeated administration of beta-carotene led to statistically significant decrease of the constitution-dependent enzymatic activation in the gastric mucosal membrane and to inhibition of locus formation with abnormally high activity of ornithine decarboxylase. The findings suggest that anticarcinogenic effect of the natural antioxidant beta-carotene was shown at the step of carcinogenesis promotion.
Asunto(s)
Carotenoides/uso terapéutico , Neoplasias Experimentales/prevención & control , Neoplasias Gástricas/prevención & control , Animales , Mucosa Gástrica/enzimología , Mucosa Gástrica/metabolismo , Cetonas/metabolismo , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Metilnitronitrosoguanidina , Neoplasias Experimentales/inducido químicamente , Ornitina Descarboxilasa/metabolismo , Ratas , Ratas Wistar , Neoplasias Gástricas/inducido químicamente , beta CarotenoRESUMEN
Riboflavin supply was studied in 164 adult inhabitants of the Kara-Kalpak ASSR where a high incidence of cancer of the esophagus and precancer changes of the esophageal mucosa were recorded. Endoscopy was used to investigate the morphological picture of the esophageal mucosa. A standard method for evaluation of the activation coefficient (AC) of erythrocytic glutathion-reductase (EC1.6.4.2) in the presence of FAD was used as a criterion of the body supply with riboflavin. Pronounced riboflavin deficiency (AC greater than or equal to 1.30) and B2 hypovitaminosis (AC = 1.20-1.29) were observed in 17 and 23% of the cases, respectively. Statistical analysis of the data obtained evidences that insufficient supply with riboflavin is recorded, on an average, 3.5-5.5 times more frequently in subjects with pronounced catarrhal esophagitis, combined with or without leukoplakia, than in the control group of subjects with out pronounced changes in the esophageal mucosa. No positive statistically significant association between low supply of the body with riboflavin and atrophic esophagitis has been established.
Asunto(s)
Esófago/patología , Deficiencia de Riboflavina/complicaciones , Eritrocitos/enzimología , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/patología , Glutatión Reductasa/sangre , Humanos , Membrana Mucosa/patología , Deficiencia de Riboflavina/epidemiología , Deficiencia de Riboflavina/patología , Factores de Riesgo , UzbekistánRESUMEN
A comparative study of the esophageal mucosa versus vitamin status in the adult male population of Muinak District of the Karakalpak ASSR, characterized by high incidence of esophageal cancer, established a significantly high frequency of chronic esophagitis. The differential evaluation of different pathologies of the esophageal mucosa suggested a link between catarrhal and erosive esophagitis and vitamin B2 deficiency and atrophic esophagitis and vitamin A deficit.
Asunto(s)
Neoplasias Esofágicas/epidemiología , Esófago/patología , Deficiencia de Riboflavina/complicaciones , Deficiencia de Vitamina A/complicaciones , Adulto , Anciano , Enfermedad Crónica , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/patología , Esofagitis/epidemiología , Esofagitis/etiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , UzbekistánRESUMEN
Parenteral administration of vitamins PP and B6 at the initiation stage of natulan-induced carcinogenesis was shown to significantly inhibit formation of lung adenomas. The preventive effect was found to depend on treatment schedule. Biochemical aspects of anticarcinogenic action of the vitamins require special investigation.
Asunto(s)
Adenoma/tratamiento farmacológico , Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , Niacinamida/uso terapéutico , Procarbazina/toxicidad , Piridoxina/uso terapéutico , Adenoma/inducido químicamente , Adenoma/metabolismo , Animales , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Femenino , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Niacinamida/farmacocinética , Procarbazina/farmacocinética , Piridoxina/farmacocinética , Factores de TiempoRESUMEN
It is shown that at the initiating stage of procarbazine carcinogenesis in F1 female mice the parenteral administration of nicotinamide or pyridoxine results in a significant decrease in the lung adenoma rate from 77% to 18 or 46%, respectively. Pyridoxal, pyridoxal-5'-phosphate and L-penicillamine did not influence the lung adenoma frequency.
Asunto(s)
Neoplasias Experimentales/prevención & control , Niacinamida/uso terapéutico , Procarbazina/toxicidad , Piridoxina/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/epidemiología , Penicilamina/uso terapéuticoRESUMEN
New derivatives of 2-C-/(indolyl-3)methyl/-beta-L-threo-L-glycero-3-hexulofuranosono- 1,4-lactone, vis. 1'-ethylascorbigen, 1'-benzylascorbigen and 1',2'-dimethyl-5'-methoxyascorbigen were obtained. In aquous solutions at physiological temperature and pH values ascorbigens disintegrate rather rapidly to yield L-ascorbic acid, the rate of the latter's formation depending on the substituent in the indole nucleus and increasing with growth of pH and temperature. Intraperitoneal injection of 1'-methylascorbigen to mice leads to steady rise of L-ascorbic acid level in blood plasma.
Asunto(s)
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/administración & dosificación , Indoles/síntesis química , Animales , Ácido Ascórbico/sangre , Ácido Ascórbico/síntesis química , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacología , Fenómenos Químicos , Química , Preparaciones de Acción Retardada , Indoles/metabolismo , Indoles/farmacología , Cinética , Espectroscopía de Resonancia Magnética , RatonesAsunto(s)
Cicloserina/farmacología , Glicina Hidroximetiltransferasa/antagonistas & inhibidores , Piridoxal/análogos & derivados , Transferasas/antagonistas & inhibidores , Compuestos de Vinilo/farmacología , Animales , Antimetabolitos/farmacología , Sinergismo Farmacológico , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos BALB C , Polímeros , Piridoxal/farmacología , Bazo/enzimologíaRESUMEN
Activity of pyridoxal kinase (per 1 g of tissue or per 1 mg of protein) varied in the range from 7 to 39 un or from 0.079 to 0.4 un in human malignant neoplasm tissues (adenocarcinoma of various localization, squamatous cell carcinoma of lungs, skin melanoma). The direction of alterations in the pyridoxal kinase activity differed in various tumors studied as compared with the respective controls (unimpaired tissues used for growing malignant cells).