Performance Enhancement of Diffusion-Based Molecular Communication.

Inter-Symbol Interference (ISI) is one of the challenges of bio-inspired diffusion-based molecular communication. The degradation of the remaining molecules from a previous transmission is the solution that biological systems use to mitigate this ISI. While most prior work has proposed the use of enzymes to catalyze the molecules degradation, enzymes also degrade the molecules carrying the information, which drastically decreases the signal strength. In this paper, we propose the use of photolysis reactions, which use the light to instantly transform the emitted molecules so they no longer be recognized after their detection. The light will be emitted in an optimal time, allowing the receiver to detect as many molecules as possible, which increases both the signal strength and ISI mitigation. A lower bound expression on the expectation of the observed molecules number at the receiver is derived. Bit error probability expression is also formulated, and both expressions are validated with simulation results, which show a visible enhancement when using photolysis reactions. The performance of the proposed method is evaluated using Interference-to-Total-Received molecules metric (ITR) and the derived bit error probability.

Improved human gingival fibroblast response to titanium implants coated with ultraviolet-irradiated vitamin D precursor and vitamin E.

BACKGROUND AND OBJECTIVE: Ultraviolet (UV)-irradiated 7-dehydrocholesterol (7-DHC) and vitamin E (VitE)-coated titanium (Ti) implants have a beneficial effect on bone cells. Human gingival fibroblasts (HGFs) are the most abundant cells in periodontal tissues and are involved in the wound healing and repair. The objective of this study was to evaluate the response of HGFs to Ti implants coated with UV-irradiated 7-DHC and VitE, for improved soft-tissue integration of dental implants. MATERIAL AND METHODS: Ti surfaces were coated with 7-DHC and VitE, irradiated with UV light and incubated for 48 h at 23°C to allow cholecalciferol (D3 ) synthesis from 7-DHC onto the Ti surface. HGFs were cultured on the modified surfaces and the influence of the coating on these cells was evaluated through the analysis of: (i) biocompatibility; (ii) the mRNA levels of genes involved in the composition and turnover of the extracellular matrix, the inflammatory response, periodontal bone resorption and wound healing; and (iii) the levels of MMP-1 and TIMP-1 proteins. RESULTS: We found a beneficial effect of UV-irradiated 7-DHC:VitE-coated Ti implants on HGFs. Besides being biocompatible with HGFs, the UV-irradiated 7-DHC and VitE coating increased the levels of collagen III α1 and fibronectin mRNAs. and decreased the level of interleukin-8 mRNA. TIMP-1 was increased at both mRNA and protein levels in HGFs cultured on UV-irradiated 7-DHC:VitE-coated Ti implants. Finally, the UV-irradiated 7-DHC and VitE coating decreased the level of RANKL mRNA in HGFs. CONCLUSION: UV-irradiated 7-DHC:VitE-coated Ti implants have a positive effect on HGFs in vitro by reducing the inflammatory response and extracellular matrix breakdown.

UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts.

Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants.

UV photoactivation of 7-dehydrocholesterol on titanium implants enhances osteoblast differentiation and decreases Rankl gene expression.

Vitamin D plays a central role in bone regeneration, and its insufficiency has been reported to have profound negative effects on implant osseointegration. The present study aimed to test the in vitro biological effect of titanium (Ti) implants coated with UV-activated 7-dehydrocholesterol (7-DHC), the precursor of vitamin D, on cytotoxicity and osteoblast differentiation. Fourier transform infrared spectroscopy confirmed the changes in chemical structure of 7-DHC after UV exposure. High-pressure liquid chromatography analysis determined a 16.5±0.9% conversion of 7-DHC to previtamin D(3) after 15min of UV exposure, and a 34.2±4.8% of the preD(3) produced was finally converted to 25-hydroxyvitamin D(3) (25-D(3)) by the osteoblastic cells. No cytotoxic effect was found for Ti implants treated with 7-DHC and UV-irradiated. Moreover, Ti implants treated with 7-DHC and UV-irradiated for 15min showed increased 25-D(3) production, together with increased ALP activity and calcium content. Interestingly, Rankl gene expression was significantly reduced in osteoblasts cultured on 7-DHC-coated Ti surfaces when UV-irradiated for 15 and 30min to 33.56±15.28% and 28.21±4.40%, respectively, compared with the control. In conclusion, these findings demonstrate that UV-activated 7-DHC is a biocompatible coating of Ti implants, which allows the osteoblastic cells to produce themselves active vitamin D, with demonstrated positive effects on osteoblast differentiation in vitro.

Vitamin D: the light side of sunshine.

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

In vitro model of vitamin D3 (cholecalciferol) synthesis by UV radiation: dose-response relationships.

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.

Effect of clothing varieties on solar photosynthesis of previtamin D3: an in vitro study.

BACKGROUND/PURPOSE: Vitamin D3 plays important roles in the absorption of calcium and phosphorus from the gastrointestinal tract and in the treatment of rickets; in addition, it facilitates the deposition of minerals in bones, thus minimizing the possibility of developing osteomalacia. Sunlight naturally induces vitamin D3 photosynthesis. Such a process is affected by a number of factors such as age, geographical location, skin color, sunscreen application and clothing. It is intended in the present investigation to study in vitro the effect of clothing on the solar photoproduction of vitamin D3. METHODS: Fifteen different fabric samples were tested for their effect on the efficiency of the in vitro solar conversion of 7-dehydrocholesterol (7-DHC) to vitamin D3. 7-DHC was dissolved in methanol to give a concentration of 2.6 x 10(-4) M. Solutions were exposed to sunlight in quartz containers for predetermined periods either uncovered or covered with the fabric sample under test. Changes in the concentrations of 7-DHC and the photoproducts were monitored by HPLC. Fabrics were graded as the number of threads per square inch (in(2)), and their sunlight attenuation was determined. RESULTS: 7-DHC is transformed to previtamin D3 upon exposure to sunlight, and the amount generated exhibited an almost linear relationship. When fabric-covered samples of 7-DHC were irradiated, photoproducts were also detected and their concentrations depended on the degree of sunlight attenuation imposed by the fabric. Generally, the higher the number of threads per in(2) the more the light attenuation produced. CONCLUSION: Clothing plays an important role in attenuating sunlight, thus leading to diminished vitamin D3 production to an extent that would require dietary compensation.

Demonstration of UVB-induced synthesis of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis.

Cutaneous vitamin D(3) (VD(3)) is generated by UVB-induced photolysis of 7-dehydrocholesterol (7-DHC). VD(3) then undergoes sequential hydroxylation to calcidiol (25-OHD(3)) in the liver and to hormonally active calcitriol (1 alpha,25-(OH)(2)D(3)) in the kidney. Recently, we have described the epidermal VD(3) metabolic pathway by demonstrating the autochthonous formation of calcitriol in cultured keratinocytes. In this study we sought to determine whether photolysis of 7-DHC induced by irradiation of human skin with monochromatic UVB at 300 nm results in epidermal synthesis of calcitriol in vivo. Using a microdialysis technique we demonstrated that UVB irradiation results in a dose- and time-dependent increase in the calcitriol concentration in the extracellular fluid of UVB-irradiated skin. Topical treatment of skin with an ointment containing 2% ketoconazole immediately after irradiation suppressed UVB-induced intraepidermal calcitriol synthesis. This study demonstrates for the first time UVB-triggered synthesis of calcitriol in human skin in vivo. The link between UVB irradiation and synthesis of calcitriol in the skin may be of great importance for regulation of biological processes such as cell growth, differentiation, apoptosis and immunological reactions.

Provitamins and vitamins D2and D3in Cladina spp. over a latitudinal gradient: possible correlation with UV levels.

Provitamin D2, vitamin D2 and vitamin D3 were identified in the thallus of a lichen species, Cladina arbuscula (Wallr.) Hale and W.L. Culb. The identification of vitamin D3 was supported by: (1) co-chromatography in both reverse and straight phase HPLC (high performance liquid chromatography), (2) ultraviolet absorption spectrum, and (3) molecular ion peaks demonstrated by ESI (electrospray ionisation) mass spectrometry. The contents of vitamin D3 range from 0.67 to 2.04 µg g⁻¹ dry matter in the thalli of C. arbuscula specimens grown under different natural conditions, while provitamin D3 could not be detected. The ranges for provitamin D2 and vitamin D2 were 89-146 and 0.22-0.55 µg g⁻¹ dry matter, respectively, while the contents of provitamin D3 were below the detection limit (0.01 microg g(-1) dry matter). When C. arbuscula thalli collected at different latitudes from northern Finland to Greece were compared, a positive correlation of vitamin D2 and D3 contents with modelled UV-B radiation at the collection sites was found. A single sample of C. rangiferina from northern Finland gave much higher values for the vitamins. A possible reason could be the lower content of UV-B absorbing pigment in the latter species.

The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa.

AIMS: To assess the effect of season and latitude on the in vitro formation of previtamin D3 and vitamin D3 from 7-dehydrocholesterol (7-DHC) by sunlight in two cities in South Africa, Cape Town and Johannesburg. METHODS: An in vitro study utilising vials containing 7-DHC, which were exposed to sunlight for a period of 1 hour between 8:00 and 17:00 on 1 day a month for a year. Previtamin D3 and vitamin D3 were separated from 7-DHC by high-performance liquid chromatography, and the amounts formed were calculated with the use of external standards. RESULTS: A marked seasonal variation in vitamin D3 production was noted in Cape Town, with very little being formed during the winter months of April through September. In Johannesburg, in vitro formation changed little throughout the year, and was similar to that found in Cape Town during the summer. During sunlit hours, vitamin D3 production was maximal at midday and small quantities were still being formed between 8:00 and 9:00, and between 16:00 and 17:00 during the summer. During winter in Cape Town, peak formation at midday was less than one-third of that in Johannesburg, and negligible amounts were formed before 10:00 and after 15:00. CONCLUSIONS: The previously documented seasonal variation in serum 25-hydroxyvitamin D recorded in patients in Johannesburg is probably a consequence of the increased clothing worn and the decreased time spent out of doors during winter, rather than decreased ultraviolet radiation reaching the earth. The limited in vitro formation of vitamin D3 during winter in Cape Town may have clinical implications insofar as the management of metabolic bone diseases like rickets and osteoporosis is concerned. Breast-fed infants resident in the area are likely to suffer from vitamin D deficiency rickets unless vitamin D supplements are provided, or the mothers are encouraged to take their children out of doors.

Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin.

Sunlight has long been recognized as a major provider of vitamin D for humans; radiation in the UVB (290-315 nm) portion of the solar spectrum photolyzes 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted by a thermal process to vitamin D3. Latitude and season affect both the quantity and quality of solar radiation reaching the earth's surface, especially in the UVB region of the spectrum, but little is known about how these influence the ability of sunlight to synthesize vitamin D3 in skin. A model has been developed to evaluate the effect of seasonal and latitudinal changes on the potential of sunlight to initiate cutaneous production of vitamin D3. Human skin or [3 alpha-3H]7-dehydrocholesterol exposed to sunlight on cloudless days in Boston (42.2 degrees N) from November through February produced no previtamin D3. In Edmonton (52 degrees N) this ineffective winter period extended from October through March. Further south (34 degrees N and 18 degrees N), sunlight effectively photoconverted 7-dehydrocholesterol to previtamin D3 in the middle of winter. These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.

Effect of u.v. rays on 7-dehydrocholesterol content in rat skin.

Long-term exposure of rat to ultraviolet irradiation affected the cholesterol metabolism in the skin. The 7-dehydrocholesterol content was increased to 1.6 times of non-irradiated rat. However, the cholesterol content was not altered. Ultraviolet-induced precholecalciferol and cholecalciferol bound with an activator protein of delta 5,7 sterol-delta 7-reductase. This observation suggested that precholecalciferol and cholecalciferol bound with an activator protein of delta 5,7 sterol-delta 7-reductase. This observation suggested that precholecalciferol and cholecalciferol inhibit the conversion of 7-dehydrocholesterol to cholesterol and accumulate 7-dehydrocholesterol. The action of ultraviolet rays on the cholesterol metabolism in the skin may be explained as the action of ultraviolet-induced precholecalciferol and cholecalciferol.

Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin.

The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.

Identification of vitamin D3 and 7-dehydrocholesterol in cow's milk by gas chromatography-mass spectrometry and their quantitation by high-performance liquid chromatography.

Identification of vitamin D3 and 7-dehydrocholesterol (7-DHC) in cow's milk by gas chromatography-mass spectrometry (GC-MS) and their quantitation by high-performance liquid chromatography (HPLC) were investigated. When vitamin D and provitamin D fractions purified from a sample of commercial cow's milk were applied to GC-MS, the results showed that the fractions contained vitamin D3 and 7-DHC, respectively, while neither vitamin D2 nor ergosterol could be detected in the milk. HPLC methods for the determination of vitamin D3 and 7-DHC in cow's milk were then proposed as routine methods. The method for assaying vitamin D3 included the isolation of lipids from milk according to the directions of Bell and Christie (5), saponification, isolation of unsaponifiable matter, digitonin-Celite column chromatography, preparative thin-layer chromatography (TLC) and application to HPLC. On the other hand, 7-DHC in milk could be simultaneously determined without the purification by digitonin-Celite column chromatography. The peak corresponding to either vitamin D3 or 7-DHC in the respective HPL-chromatograms was clearly separated from possible interfering substances and the recovery experiments for both vitamin D3 and 7-DHC gave satisfactory results. When the proposed methods were applied to 10 samples of commercial cow's milk, the assayed values of vitamin D3 and 7-DHC were 19--79 I.U./liter and 14--56 microgram/liter, respectively.