[Homocysteine in blood. Deficiency marker and risk marker].
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Mortality from colorectal cancer, a leading cause of death in the U.S.A. and other western countries, has remained unchanged over the past 45 years. Therefore, the search for strategies to prevent the development and progression of colorectal cancer has markedly intensified. Chemoprevention is one such strategy. Accumulating evidence suggests that folic acid, a water soluble vitamin, could be an effective chemopreventive agent for colorectal cancer. Results from several studies have demonstrated that a diet deficient in folic acid may be associated with an increased risk of colonic neoplasia, whereas dietary supplementation of this nutrient may be chemopreventive. Although the mechanisms by which folic acid exerts its chemopreventive role in colorectal carcinogenesis remain to be fully elucidated, supplemental folic acid has been shown to arrest the loss of heterozygosity (LOH) of the tumor suppressor gene DCC (deleted in colorectal cancer) and to stabilize its protein in normal appearing rectal mucosa of patients with colorectal adenomas. Data from in vitro studies utilizing colon cancer cell lines suggest that supplemental folic acid or its metabolite 5-methyltetrahydrofolate (5-MTF) attenuates the expression and activation of EGF-receptor (EGFR) as well as proliferation of cells. The folic acid mediated reduction of EGFR function could partly be the result of suppression of EGFR gene through increased methylation of CpG sequences within its promoter.
Non-anemic women attending a public antenatal clinic were given, daily, a multivitamin tablet containing 78 mg. of elemental iron. The follow-up studies included an analysis of their diets. A total of 311 patients were included, of which one group received a supplement of 0.5 mg. folic acid and 0.005 mg. vitamin B(12). The incidence of megaloblastic bone marrow change in the unsupplemented group was 26% and of low blood folates approximately 50%. The incidence of megaloblastic changes was sharply reduced in the supplemented group and the blood folates were elevated to supranormal levels, indicating that the dose of folic acid used may have been above the minimal requirement. Formiminoglutamic acid (FIGLU) excretion could not be correlated with other parameters of folate deficiency. Neutrophil lobe counts did not relate to megaloblastic changes or low folate levels unless there was more than 5% hypersegmentation. The dietary intake was suboptimal in total calories, iron and food folate.
Dietary folacin deficiency in the presence and absence of dietary sulfonamides was studied in the guinea pig for the purpose of relating the growth and hematologic effects of folacin deficiency to tissue and biochemical changes. Six-week old female guinea pigs fed control and folacin deficient diets with and without 0.1% sulfonamides for 6 to 7 weeks. Growth was significantly reduced in both groups fed the folacin deficient diets, and 25% of all deficient animals died. Macrocytic anemia was not present, but reduced leukocyte numbers were observed in folacin deficiency. Plasma and red blood cell folacin activities were reduced by about 50% in deficient guinea pigs in the presence and absence of dietary sulfonamides. Both liver total folacin activity and urinary formiminoglutamic acid excretion were not significantly altered by the degree of folacin deficiency obtained in this study.
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OBJECTIVES: To study the prevalence of iron and vitamin deficiencies, endocrine disorders and immunological parameters in patients with primary Sjogren's syndrome (1 degree SS). DESIGN AND SUBJECTS: At the time of the establishment of the diagnosis of 1 degree SS in 43 consecutive patients, a clinical examination including haematological analyses was performed. The patients' medical records were also reviewed. SETTING: Patients referred for diagnosis to The University Hospital, Linköping, a secondary or tertiary referral hospital serving the middle part of southern Sweden. RESULTS: In total, current or previously treated iron and vitamin deficiencies were registered for 63% of the 1 degree SS patients (iron 51%, vitamin B12 25%, folate 9%). Current low ferritin was noted in 24%, low iron saturation in 37%, decreased vitamin B12 in 13% and folate in 9%. Thyroid disease was found in a total of 33% and 30% had had autoimmune thyroiditis. Three patients (7%) had verified diabetes mellitus. Erythrocyte sedimentation rate (ESR) was raised in 65% of the patients and 84% had a polyclonal increase of Ig. Rheumatoid factor (RF) was detected in 85%, antinuclear antibody (ANA) in 74%, anti-SS-A in 88% and anti-SS-B in 73% of the patients. CONCLUSION: Iron and vitamin deficiencies and thyroid diseases are common in patients with 1 degree SS. Since these disorders often are treatable and may affect the patients' distress as well as their immune and exocrine function, an active, recurrent search for deficiencies, endocrine diseases and other frequently recorded disorders is recommended.
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Although tumor development with methyl donor-deficient diets has been well established, the biochemical and molecular mechanisms which predispose to tumor development are not yet understood. In the present study, DNA damage and nucleotide metabolism associated with DNA synthesis and repair were evaluated in splenic lymphocytes from rats fed a basal diet low in methionine and lacking in choline and folate or a supplemented control diet for a period of 3 wk. The accumulation of DNA strand breaks, as assessed by DNA unwinding in alkali, was found to be significantly elevated in lymphocytes from rats fed the methyl donor-deficient diet and was associated with an increase in mitogen-stimulated incorporation of [3H]-thymidine via the salvage pathway for thymidylate synthesis. In addition, a significant decrease in the DNA repair-associated pyridine nucleotide, NAD, was observed in lymphocytes from the deficient group and was associated with a decrease in total spleen cell numbers. These results suggest that alterations in nucleotide metabolism and DNA damage are induced when methyl donor pools are stressed by dietary deficiency.
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Putatively preneoplastic, pancreatic atypical acinar cell foci (AACF) and nodules (AACN), collectively termed atypical acinar cell lesions (AACL), were induced in male Lewis rats by L-azaserine (300 mg/kg body weight [bw] in divided doses). Rats given carcinogen and then fed a lipotrope deficient (LD) diet developed a significantly greater number of larger lesions than animals fed complete diet throughout the experiment. It is suggested that lipotrope deficiency plays a promoting role in this model of pancreatocarcinogenesis. Ultrastructural morphometric studies of AACF, when compared to control tissues, revealed the following significant results: 1) a decrease in surface area of cell cytoplasm with no change in nuclear area, and hence increased nucleus/cytoplasm (N/C) ratio; 2) a reduction in size and uniformity of zymogen granules; and 3) an increase in number of granules per microns 2 of cell. The results suggest that arrested development of the AACF cells is associated with reduced cytoplasm and zymogen production per cell. AACL may be eosinophilic due to an overall increased concentration of zymogen in these hyperplastic lesions and not because individual acinar cells in the AACL contain an increased amount of zymogen or are "zymogen-rich," as has been reported.
In 1996, were studied in Costa Rica 961 children with ages between one and six years, with representation for metropolitan, urban and rural zones of the country. The classification approaches applied were emitted by the Pan-American Health Organization and the World Health Organization. The preschooler population presented in the national environment a prevalence of anemia of 26.3% (children from 1 to 4 years with hemoglobin < 11.0 g/dL and those from 5 to 6 years old with hemoglobin < 12.0 g/dL). The prevalence of Iron depletion (Ferritin < 12 ng/mL) and iron deficiency (Ferritin < 24 ng/mL) were 24.4% and 53.8%, respectively. The folate deficiency (< 6.0 ng/mL) was 11.4%. The iron deficiency was higher in children smaller than 4 years, being the maximum deficiency in the 1 year-old (75%). More than 40% of the preschool children presented sub-clinical deficiency of iron; of them, 10% showed severe deficiency of iron without presence of anemia. The children from the rural area presented the highest prevalence of anemia and iron depletion, while the metropolitan area met more frequency with iron deficiency. The nutritional anemias still constitute a moderate problem of public health in Costa Rica. The main cause is iron deficiency, associated in small proportion with folate deficiency and other factors associated with the erythropoiesis.
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A balanced diet that provides an adequate supply of vitamins and minerals is essential for normal fetal development. Maternal morbidity is also lower, since such complications of pregnancy as preeclampsia and premature birth occur less frequently. Consideration should be given to folate deficiency--in particular during the periconceptive period--and iron deficiency during pregnancy. For the structural development of the fetus, long-chain polyunsaturated fatty acids also appear to have a major role to play. Daily iodine supplementation should be used to avoid goiter in mother and child. Calcium appears to have a protective effect against preeclampsia and hypertension, as also do vitamins E and C. The tocolytic action of magnesium can help reduce the incidence of premature birth. Such noxae as alcohol and nicotine should be avoided completely during the entire pregnancy.
Estimation of serum folate was carried out in 74 patients with various neurological disorders. Levels less than normal were detected in 63 of them, with mainly peripheral neuritis, cerebellar syndromes and/or psychological disorders. The role of certain etiological factors was demonstrated, e.g. alcoholism, malnutrition, diarrhea, anti-epileptic treatment. Links between these neurological disorders and the folate deficiency remain to be demonstrated. In at least 8 cases, treatment with folic acid seems to have had a favourable influence on the course of these disorders.