Forgotten mysteries in the early history of vitamin D.
(9/1331)
In the early 1920s, workers in both England and the US had discovered that rats on a rachitic diet would remain healthy if irradiated with ultraviolet light. However, they also found, to their surprise, that "control" rats too would recover if either their jar was irradiated without the rat in it or if a cage-mate was removed for irradiation and then returned. The ideas that either air or material objects that had been irradiated continued themselves to convey healthful secondary radiations were investigated but not confirmed. There was then the commercially important finding that with irradiation, some rachitic diets would become anti-rachitic. However, this effect did not explain all the previous findings. Consumption of either small irradiated fecal particles or of feces from irradiated rats was the likely explanation for the recovery of nonirradiated rats, but this was not tested by direct experiment, and it now appears unlikely that feces from irradiated rats would show significant antirachitic activity. It is suggested that an alternative possibility--activity of grease from irradiated fur--deserves investigation. (+info)
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.
(10/1331)
For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold. (+info)
Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction.
(11/1331)
Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal-epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity. (+info)
Characterization of Pseudomonas aeruginosa bacteriophage UNL-1, a bacterial virus with a novel UV-A-inducible DNA damage reactivation phenotype.
(12/1331)
UNL-1, a lytic virus of Pseudomonas aeruginosa, was observed to express a novel inducible DNA damage reactivation activity in UV-A-irradiated P. aeruginosa host cells. The expression of bacteriophage reactivation was quantified in hosts exposed to either UV-C or UV-A radiation. While reactivation of UV-C-damaged UNL-1 was not inducible in UV-C-irradiated host cells, an approximately 13-fold induction was observed in UV-A-irradiated host cells. When host cells were exposed to sunlight, reactivation of damaged UNL-1 virus increased eightfold. The UV-A induction of UNL-1 DNA damage reactivation was supported in hosts lacking recA gene function. This report is the first description of a recA-independent, UV-inducible virus DNA damage repair system. Our findings suggest that a combination of both host and virus DNA repair processes contribute to the persistence and sustained replication of some bacterial viruses in aquatic environments. (+info)
Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey.
(13/1331)
We analyzed data from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study to test the hypothesis that vitamin D from sunlight exposure, diet, and supplements reduces the risk of breast cancer. We identified 190 women with incident breast cancer from a cohort of 5009 white women who completed the dermatological examination and 24-h dietary recall conducted from 1971-1974 and who were followed up to 1992. Using Cox proportional hazards regression, we estimated relative risks (RRs) for breast cancer and 95% confidence intervals, adjusting for age, education, age at menarche, age at menopause, body mass index, alcohol consumption, and physical activity. Several measures of sunlight exposure and dietary vitamin D intake were associated with reduced risk of breast cancer, with RRs ranging from 0.67-0.85. The associations with vitamin D exposures, however, varied by region of residence. The risk reductions were highest for women who lived in United States regions of high solar radiation, with RRs ranging from 0.35-0.75. No reductions in risk were found for women who lived in regions of low solar radiation. Although limited by the relatively small size of the case population, the protective effects of vitamin D observed in this prospective study are consistent for several independent measures of vitamin D. These data support the hypothesis that sunlight and dietary vitamin D reduce the risk of breast cancer. (+info)
Etiologic clues to lip cancer from epidemiologic studies on farmers.
(14/1331)
OBJECTIVES: This study examined the risk factors for lip cancer among farmers. METHODS: A series of meta-analyses of peer-reviewed studies of lip cancer and farming were performed using 21 studies published between 1981 and 1997. Prior to the meta-analyses, all the studies were reviewed and evaluated for heterogeneity and publication bias. Combined relative risks (RR) were calculated using the random effect model. RESULTS: The combined RR for lip cancer was 2.0 [95% confidence interval (95% CI) 1.74-2.30] for all the studies and 1.28 (95% CI 0.79-2.08) for studies involving female farmers. Additional meta-analyses were undertaken on a subset of studies reporting on skin cancer among farmers. The combined RR for nonmelanotic skin cancer was 1.0 (95% CI 0.89-1.14), and for malignant melanoma it was 0.88 (95% CI 0.74-1.05). CONCLUSIONS: The findings suggest that male farmers have a significantly elevated risk for lip cancer. Lip cancer and skin cancer do not share a common etiologic factor. Besides sunlight exposure, other factors such as viral infection or reduced immunity may play a role in the etiology of lip cancer. (+info)
Generation of active oxygen species from advanced glycation end-products (AGEs) during ultraviolet light A (UVA) irradiation and a possible mechanism for cell damaging.
(15/1331)
Advanced glycation end-products (AGEs) have been reported to be accumulated in dermal skin. However, the role of AGEs in the photoaging of human skin remains unknown, and for this reason, we have examined the interaction between AGEs and ultraviolet A light (UVA) from both the chemical and biological aspects. Previously, we reported that exposing human dermal fibroblasts to UVA in the presence of AGEs that were prepared with bovine serum albumin (BSA) decreased the cell viability due to superoxide anion radical s (.O2(-)) and hydroxyl radicals (.OH) generated by AGEs under UVA irradiation, and active oxygen species are detected with ESR spin-trapping. To identify the active oxygen species in detail and to clarify the cell damaging mechanism, we performed several experiments and the following results were obtained. (1) In ESR spin-trapping, by addition of dimethyl sulfoxide and superoxide dismutase, ESR signals due to .O2(-) -derived DMPO-OOH and .OH-derived DMPO-OH adducts, respectively, were detectable. (2) UVA-irradiated AGEs elevated the lipid peroxide levels in both fibroblasts and liposomes. But the peroxidation in liposomes was inhibited by addition of deferoxamine. (3) Survival of fibroblasts exposed to UVA in the presence of AGEs was elevated by addition of deferoxamine. And finally, (4) survival of fibroblasts was found to be regulated by the level of H2O2. On the basis of these results, we propose a possible mechanism in which AGEs under UVA irradiation generate active oxygen species involving .O2(-), H2O2, and .OH, and the .OH species plays a harmful role in promoting cell damage. (+info)
Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.
(16/1331)
Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis. (+info)