Vitamin C,cancer and aging

Oxidative damage to DNA, proteins and lipids appears to be a major contributing factor in aging and the degenerative processes that accompany it, including cancer, heart disease, cataracts, and cognitive dysfunction. Numerous epidemiologic studies have found that persons with lower intake of antioxidant nutrients or the fruits and vegetables that provide them have a higher risk of almost every type of cancer. In many studies, those with low intake had twice the risk of those with high intake. A large-scale follow-up study found that persons with a low vitamin C intake had a statistically significantly higher risk of heart disease mortality and total mortality over the subsequent 10 years. In addition, several studies have found that persons with low intake of antioxidant nutrients such as vitamin C and carotene had significantly increased risk of developing age-related eye diseases such as cataracts. Although many older people consume more antioxidants than younger people, very substantial proportions of older persons have very low intakes and blood levels. Among white men 65–74 in the U.S., 15% have blood ascorbate levels below 0.4 mg/dl, the lower boundary of “normal.” Among black men of that age, 25% have levels below 0.4 mg/dl. Persons with high intakes of dietary vitamin C or citrus fruit have repeatedly been found to have a lower risk of developing cancer. In addition, recent research indicates an important role in heart disease and other disabilities of aging. This paper will summarize the epidemiologic literature briefly, and provide data on intake of this vitamin in the United States. Vitamin C has numerous biologic functions, including collagen, hormone and neurotransmitter synthesis. Its role as an antioxidant and free radical scavenger may be of primary importance in many of its roles in disease prevention. Oxidative and free radical damage to DNA and cell membranes is an important factor in cancer initiation, and it is clear that ascorbic acid can help prevent such damage.     

Branching out: a molecular fingerprint of endothelial differentiation into tube-like structures generated by Affymetrix oligonucleotide arrays

The process of endothelial differentiation into a network of tube-like structures with patent lumens requires an integrated program of gene expression. To identify genes upregulated in endothelial cells during the process of tube formation, RNA was prepared from several different time points (0, 4, 8, 24, 40, and 48 hours) and from three different experimental models of human endothelial tube formation: in collagen gels and fibrin gels driven by the combination of PMA (80), bFGF (40 ng/ml) and bFGF (40 ng/ml) or in collagen gels driven by the combination of HGF (40 ng/ml) and VEGF (40 ng/ml). Gene expression was evaluated using Affymetrix Gene Chip oligonucleotide arrays. Over 1000 common genes were upregulated greater than twofold over baseline at one or more time points in the three different models. In the present study, we discuss the identified genes that could be assigned to major functional classes: apoptosis, cytoskeleton, proteases, matrix, and matrix turnover, pumps and transporters, membrane lipid turnover, and junctional molecules or adhesion proteins.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.     

Correction to: Working Overtime: Altered Functional Connectivity in Working Memory Following Regular Cannabis Use in Young Adults

International Journal of Mental Health and Addiction - The caption for Fig.&nbsp;1 was incorrect in this article as originally published.     

Histamine reduces gap junctional communication of human tonsil high endothelial cells in culture

The regulation of gap junctional communication by histamine was studied in primary cultures of human tonsil high endothelial cells (HUTECs). We evaluated intercellular communication, levels, state of phosphorylation, and cellular distribution of gap junction protein subunits, mainly connexin (Cx)43. Histamine induced a time-dependent reduction in dye coupling (Lucifer yellow) associated with reduction in connexin43 localized at cell-cell appositions (immunofluorescence), without changes in levels and phosphorylation state of connexin43 (immunoblots). These effects were prevented with chlorpheniramine, an H1 receptor blocker; indomethacin, a cyclooxygenase blocker; or GF109203X, a protein kinase C inhibitor. Treatment with phorbol myristate acetate, a protein kinase C activator, and 4bromo (4Br)-A23187, a calcium ionophore, mimicked the histamine-induced effects on dye coupling. 8Bromo-cAMP doubled the dye coupling extent and prevented the histamine-induced reduction in incidence of dye coupling. After 24-h histamine treatment, known to desensitize H1 receptors, reapplication of histamine increased cell coupling in a way prevented by ranitidine, an H2 receptor blocker. Thus, activation of H1 and H2 receptors, which increase intracellular levels of free Ca2+ and cAMP, respectively, may affect gap junctional communication in opposite ways. Stabilization of actin filaments with phalloidine diminished but did not totally prevent histamine-induced cell shape changes and reduction in dye coupling. Hence, the histamine-induced reduction in gap junctional communication between HUTEC is mediated by cytoskeleton-dependent and -independent mechanisms and might contribute to modulate endothelial function in lymphoid tissue.