Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors

Local environmental signals regulate the growth and development of both normal and malignant breast epithelium. Members of the insulin-like growth factor (IGF) family likely influence both of these processes. The localization of IGF2 to stroma specifically surrounding malignant breast epithelium indicates that this growth factor may play a critical role in the genesis or maintenance of this transformed phenotype. Recent studies have sought to understand the mechanism by which IGF2 expressing fibroblasts are localized to the periphery of malignant breast cancer cells. In addition, the consequences of the expression of IGF-signaling components likely expand beyond their direct effects on mitogenesis. Indirect effects predominantly associated with the IGF2 receptor could also influence the invasive potential of breast tumor cells.     

TREATMENT OF PALMOPLANTER HYPERHIDROSIS BY IONTOPHORESIS

Twenty-seven patients with idiopathic palmoplanter hyperhidrosis were treated with Iontotherapy over a one year period. In twenty-four cases there was a good response but maintenance therapy was required every 3-4 weeks.KEY WORDS: Iontophoresis, Palmoplanter hyperhidrosis     

Sonography of tendons

Recent advances in ultrasound technology and the development of high-resolution ultrasound transducers have enabled detailed depiction of superficial musculoskeletal structures. While in the past considered as complementary to magnetic resonance (MR) imaging, modern ultrasound has clearly become competitive. It is now the imaging modality of choice for evaluating tendon pathology. The major advantages of ultrasound include dynamic evaluation of structures, low cost and wide availability. The main disadvantage is a high degree of operator dependency. This article discusses the current ultrasound characteristics of normal tendon, the artefacts that may mimic tendon disease and reviews the applications of ultrasound to the evaluation of tendon disorders, including tendon tears, tendinitis, tenosynovitis, ganglion cysts and bursitis.     

The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians

The human plasma-cell membrane differentiation antigen-1 (PC-1) has been shown to inhibit insulin receptor tyrosine kinase activity. Recently, a K121Q polymorphism in the human PC-1 gene was found in a Sicilian population and was shown to be strongly associated with insulin resistance. The objectives of the present investigation were to examine in the Danish Caucasian population whether the K121Q variant was associated with type 2 diabetes or, in glucose-tolerant subjects, with impaired whole-body insulin sensitivity. We genotyped 404 Danish type 2 diabetic patients and found that the allele frequency of the variant was 0.14 (95% CI 0.12-0.16), whereas the allele frequency was 0.16 (95% CI 0.13-0.19) among 237 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, there were no significant differences among wild-type, heterozygous, or homozygous subjects in regard to 1) serum insulin and plasma glucose levels at fasting, 60 min, or 120 min during an oral glucose tolerance test (OGTT) or 2) the estimates of insulin resistance obtained from the homeostasis model assessment (HOMA). Furthermore, we investigated the impact of the variant in 2 other Danish population samples that comprised 356 young healthy subjects and 226 glucose-tolerant offspring of type 2 diabetic probands, respectively. In all of the study populations, the polymorphism was not associated with an altered insulin sensitivity index as estimated from an intravenous glucose tolerance test in combination with an intravenous injection of tolbutamide. In addition, among the 226 offspring, the variations in serum insulin and serum C-peptide responses measured during an OGTT were not related to the PC-1 genotype. In conclusion, the K121Q polymorphism of the human PC-1 gene is not associated with type 2 diabetes or insulin resistance among Danish Caucasians.     

Pulmonary function affects the quantification of rCBF by non-invasive xenon methods

Estimates of regional cerebral blood flow (rCBF) by non-invasive xenon methods (133-xenon inhalation, xenon-enhanced computed tomography (Xe/CT) and 133-xenon iv injection) are frequently applied in the diagnosis and evaluation of patients suffering from diseases which cause disturbances in the cerebrovascular circulation. These methods all depend on an estimate of the arterial xenon concentration curve derived non-invasively from measurements of the end-tidal xenon concentration curve and used as brain input function in the Kety equation. We have studied the influence of impaired pulmonary gas exchange on the end-tidal and arterial xenon concentration curves in nine anaesthetized pigs by simultaneously measurements of both the end-tidal xenon and arterial xenon concentration curves. Computer simulations were performed to determine the deviations in the calculated rCBF values when using the end-tidal as compared to the arterial xenon concentration curve as brain input function. The results indicated that impairment of the pulmonary gas exchange caused a significant further 'delay' in the arterial xenon concentration curve in comparison to the end-tidal xenon concentration curve. The time constants of arterial curve delay were 11.9 s in the normal pulmonary group, 21 s in the right lung atelectasis group, and 19.7 s in the left pulmonary artery occlusion group. Accordingly, computer simulations indicated a statistically significant 'underestimation' of rCBF due to: (1) pulmonary gas exchange; (2) high or low levels of rCBF; (3) partition coefficient (lambda) of gray and white matter; and (4) xenon inhalation protocols. Our results indicate that quantitative measurements of rCBF by non-invasive xenon methods are markedly affected by deviations between the end-tidal and arterial xenon concentration curve, so that estimates of flow thresholds for infarction are problematic under conditions of impaired pulmonary gas exchange.