Evaluation of a new paclitaxel-coated balloon catheter in an in vivo porcine peripheral venous model: Feasibility, safety, and drug deliverability.

PURPOSE: To evaluate in vivo the feasibility, safety, and paclitaxel (PTX) deliverability of a newly developed non-commercially available Paclitaxel-Coated Balloon (PCB) catheter in the swine healthy peripheral vein model. MATERIALS AND METHODS: In total 12 PCBs were deployed in 12 venous segments. Primary feasibility endpoint was the successful application of the devices to the veins of the animals. Primary efficacy endpoint was the determination of the drug content in the venous tissue at 24 h and 7 days after balloon expansion, as assessed by analysis of the vein tissue with High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry. Primary safety endpoint was freedom from any major adverse event. Secondary endpoint was the investigation of any independent factor affecting the primary endpoints. RESULTS: Paclitaxel was detected in five out of six tissue samples 24 h post-intervention and five out of six tissues at 7 days following the procedure (10 tissue samples out of 12). The mean weight of tissue that was examined was 0.20604 ± 0.29822 g (range: 1.02823-0.03377 g) and the mean PTX concentration detected was 8.4 ± 13.1 µg/g (range: 0-36.1 µg/g). The average drug content detected at 24 h (17.1 ± 17.1 µg/g) was numerically superior, but non-statistically significant, compared to 7 days (3.1 ± 3.6 µg/g). An average of 33.8% of the drug remained on the balloon after retrieval. According to the multiple linear regression analysis, there was no significant correlation between transition time, PTX remaining on the balloon, time of analysis (24 h/7 days) and PTX tissue concentration. No abnormalities were noted during autopsy. CONCLUSION: The newly developed PCB successfully delivered within the healthy venous wall a dose of Paclitaxel that inhibits neointimal hyperplasia. No safety issues were raised at short-term follow-up.

Increased Body Mass Index (BMI) and Sunscreen Use Are Associated with Inadequate Vitamin D Status in Greek Adults in Winter : BMI, Sunscreen Use and Vitamin D Status in Greek Adults.

Vitamin D deficiency is common even in sunny countries like Greece, especially during winter and is associated with skeletal disorders and additionally with increased risk for chronic diseases and adipose metabolic diseases such as obesity and diabetes. The purpose of this pilot study was the determination of vitamin D status in Greek adults and the investigation of possible correlation with lifestyles and somatometric characteristics. The study was conducted during winter and included 36 members (20 women and 16 men) of a university community in central Greece (latitude 39.6° North). Their age was 36.2 ± 16.3 years, body mass index (BMI) 26.4 ± 4.8 (women 26.6 ± 5.6, men 26.3 ± 3.8), and waist circumference 85.7 ± 13.3 cm (women 81.5 ± 13.0, men 90.7 ± 12.4) (mean ± SD). Mean serum 25(OH)D concentration was 20.1 ± 7.3 ng/mL (women 19.7 ± 7.6, men 20.7 ± 7.1). More than half of the participants had 25(OH)D levels below the 20 ng/mL (50 nmol/L) threshold of deficiency. There was a significant negative association between the use of sunscreen during summer and serum 25(OH)D concentrations during winter and a significant positive association between physical exercise and serum 25(OH)D. Levels of 25(OH)D tended to decrease with increasing BMI in persons with a BMI over 25.0. There is a high prevalence of vitamin D insufficiency in Greek adults during winter. Serum 25(OH)D levels in winter are positively associated with exercise and negatively associated with high BMI and the use of sunscreen during summer.

Use of Fortified Bread for Addressing Vitamin D Deficiency.

Vitamin D deficiency due to inadequate sun exposure and/or inadequate intake from food is very common worldwide, consisting a major public health problem. As prolonged exposure to ultraviolet radiation involves risks, food fortification of staple foods emerges as a favorable solution for addressing vitamin D deficiency. Bread is a suitable candidate for fortification as it is consumed often and is the main carbohydrate source in European countries.The purpose of this study was the evaluation of the bioavailability of vitamin D from a fortified Greek-type bread that was developed as a means for addressing vitamin D deficiency, by comparing the absorption curve of vitamin D in fortified bread in relation to that of plain vitamin supplementation. Two groups of clinically healthy volunteers consumed 25,000 international units (IU) of vitamin D3 (cholecalciferol) either in fortified bread (Group A) or in a plain supplement form (Group B). The baseline plasma concentrations of cholecalciferol were 8.1 ± 6.0 ng/mL and 6.8 ± 3.4 ng/mL in Groups A and B, respectively. After 12, 24, and 48 h, the concentrations of cholecalciferol in Group A were 16.7 ± 4.8, 15.3 ± 8.3 and 11.9 ± 6.0 ng/mL, respectively, and in Group B, 15.2 ± 3.3, 11.6 ± 2.4, and 9.6 ± 3.6 ng/mL, respectively. In both groups, the concentrations of cholecalciferol at 12 and 24 h were significantly higher than the baseline concentrations (p < 0.01). There were no statistically significant differences between the concentrations of cholecalciferol between Groups A and B, at each time point.Cholecalciferol is bioavailable from Greek-type fortified bread and bread could be used for addressing vitamin D deficiency.

Vitamin D fortification of foods and prospective health outcomes.

Vitamin D is essential for bone health and has significant roles in non-skeletal health and organ function. Dermal synthesis through exposure to ultraviolet B light is the major natural source of vitamin D, while only a small portion of the necessary amount can be acquired by a diet without fortified foods. In recent years, vitamin D deficiency as a result of lifestyles with inadequate sun exposure, has received increased attention due to its association with the increased risk of serious chronic diseases. This review summarizes our current understanding of food fortification strategies with vitamin D and the resulting health impact. Conventional and biotechnological approaches can be used for the production of new and novel vitamin D rich or vitamin D fortified foods. The availability of a wider range of every-day consumed fortified foods as part of a "Daily D" public health policy can contribute to the improvement of vitamin D status and to prevention of vitamin D deficiency.

Endothelin-1 (ET-1) induces resistance to bortezomib in human multiple myeloma cells via a pathway involving the ETB receptor and upregulation of proteasomal activity.

PURPOSE: Bortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. METHODS: NCI-H929 and RPMI-8226 (human MM cell lines) were cultured with or without ET-1, BTZ, and inhibitors of the endothelin receptors. ET-1 levels were determined by ELISA, while the protein levels of its receptors and of the PI3K and MAPK pathways' components by western blot. Effects of ET-1 on cell proliferation were studied by MTT and on the ubiquitin proteasome pathway by assessing the chymotryptic activity of the 20S proteasome in cell lysates. RESULTS: Endothelin receptors A and B (ETAR and ETBR, respectively) were found to be expressed in both cell lines, with the RPMI-8226 cells that are considered resistant to BTZ, expressing higher levels of ETBR and in addition secreting ET-1. Treatment of the NCI-H929 cells with ET-1 increased proliferation, while co-incubation of these cells with ET-1 and BTZ decreased BTZ efficacy with concomitant upregulation of 20S proteasomal activity. Si-RNA silencing or chemical blockade of ETBR abrogated the protective effects of ET-1. Finally, data suggest that the predominant signaling pathway involved in ET-1/ETBR-induced BTZ resistance in MM cells may be the MAPK pathway. CONCLUSION: Our data suggest a possible role of the ET-1/ETBR axis in regulating the sensitivity of MM cells to BTZ. Thus, combining bortezomib with strategies to target the ET-1 axis could prove to be a novel promising therapeutic approach in MM.