Steven F Moss — Page 2

PubMed2002

Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.

Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.

Adult↗

PubMedDate not supplied

Gastroesophageal reflux disease: then and now.

Although Galen first described esophagitis almost 2000 years ago, its relation to acid was only recognized in the 19th century by Rokitansky. Considerably more interest in the symptoms and complications of esophagitis has been evident over the last century, as gastroesophageal reflux disease displaced peptic ulceration and became the principal acid-related disease of our times. Of particular interest has been the recognition of the clinical significance of the previously overlooked extraesophageal manifestations of the disease such as laryngitis, asthma, and sleep disturbance. The evolution of highly effective medical therapy has over the last decade drastically reduced the need for surgical intervention for control of symptoms except under select conditions, especially volume-related reflux and children with refractory symptoms. The proton pump inhibitor class of drugs is indisputably the most effective overall form of management, while individual proton pump inhibitors appear to be equivalent in their efficacy. Issues that remain to be resolved include the management of nonerosive gastroesophageal reflux disease, the long-term dependence of many patients on acid-suppressing medication, and the recognition of atypical manifestations and rare but serious complications of gastroesophageal reflux disease. In this respect, Barrett's esophagus still presents a major biologic and management conundrum for the physicians and scientists alike.

Barrett Esophagus↗