Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.

Maternal omega-3 polyunsaturated fatty acids supplementation in pregnancy decreases MMP-1 levels in breastmilk: a cross-sectional study.

INTRODUCTION: Anti-inflammatory properties of fish-oil are well known and suggested during pregnancy. MMP-1 is involved in inflammation and tissue remodelling. There have been studies focused on anti-inflammatory effect of maternal omega use on human milk while little is known about the effect of omega use on breastmilk proteases. Leptin is an important hormone that influences MMP levels in various tissues and exerts its metabolic effects. In our study we assessed the levels of MMP-1, TIMP-1, leptin, IL-6 and FA's including PUFA in breastmilk from women who used omega-3. MATERIALS AND METHODS: Our study was a cross-sectional study included 67(Group 1, n = 32, omega user; Group 2 n = 35, non-user)lactating women and their infan MMP-1, TIMP-1, leptin, IL-6 and FA's were evaluated in breastmilk of both groups. MMP-1, TIMP-1, IL-6 and leptin were measured by enzyme-linked immunoabsorbent assay (ELISA) method. Breastmilk fatty acids were measured by gas chromatography flame ionisation detector (GC-FID). RESULTS: Matrix metalloproteinase-1 (MMP-1) levels in breastmilk were significantly lower in breastmilk from omega users (mean ± SD, 0.455 ± 0.1) than non-users (mean ± SD, 0.677 ± 0.289) (p=.0001). MMP-1 and omega 6:3 ratio were positively correlated (r: 0.301, p=.01). MMP levels were correlated with IL-6 (Pearson's r: 0.411, p<.001). MMP-1 and leptin levels were positively correlated (r: .388, p=.001). CONCLUSION: MMP-1 levels in breastmilk, may be modified by maternal omega use in pregnancy which may help to redirect extracellular matrix remodelling and metabolic programming in early infancy.

From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM.

Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide - CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity.

Vitamin D levels and parathyroid hormone variations of children living in a subtropical climate: a data mining study.

BACKGROUND: Vitamin D and intact parathyroid hormone (iPTH) play a crucial role in calcium homeostasis and bone health of children. Serum level of 25-hydroxyvitamin D (25-OHD) is considered to be the most accurate marker for vitamin D status. However, there have only been a few studies, with limited number of subjects, investigating the relationship between 25-OHD and parathyroid hormone (PTH) in children. The aim of this study was to evaluate the seasonal 25-OHD levels and its associations with intact parathyroid hormone (iPTH) in Turkish children at all pediatric ages; and then to define a critical decision threshold level for 25-OHD deficiency in Turkish children. METHODS: A retrospective record review of 90,042 children, was performed on serum 25-OHD and for 3525 iPTH levels. They were measured by mass spectrometry method and by electrochemiluminescence immunoassay simultaneously. RESULTS: 25-OHD levels showed a sinusoidal fluctuation througout the year; being significantly higher in summer and autumn (p < 0,01). 25-OHD levels decreased with respect to age. The significant inverse relationship that was found between iPTH and 25-OHD suggests that the inflection point of serum 25-OHD level for maximal suppression of PTH is at 30 ng/ml. CONCLUSION: As the rate of vitamin D deficiency decreases in the early years due to vitamin D supplementation, the recommendation should be set due to a clinical threshold level of 30 ng/ml for 25-OHD based on PTH levels in children of our population.

The association of residential mold exposure and adenotonsillar hypertrophy in children living in damp environments.

BACKGROUND: There are many consequences of mold exposure related to respiratory system health of children This retrospective cohort study aims to find the association between adenoid hypertrophy and mold exposure in children living in damp environments. METHODS: Children with history of recurrent respiratory tract infections were enrolled in the study between June 2012 and June 2013 and were followed up for adenoid hypertrophy from June 2013 to June 2016. One hundred and forty two children were residents of moldy houses and 242 were living in normal houses. Skin prick test results for 60 common allergens, vitamin D levels, IgE levels, age, presence of comorbidities such as urticaria, atopic dermatitis, allergic conjunctivitis, allergic rhinitis, asthma, frequency of upper respiratory tract infections and lower respiratory tract infections, were evaluated in both groups. RESULTS: A total of 384 children (mean age ± standard deviation = 53.37 ± 36 months; 198 males and 186 females) were included. The children were classified into 2 groups (1)Children living normal houses (n = 242) (2); Children living in damp houses (n = 142) according to mold exposure. Children with adenoid hypertrophy (p < 0,001) and higher IgE levels (p < 0,001) were more common in mold exposed group. Lower respiratory tract infections were more common in children with mold exposure (p < 0,05). Bivariate correlation analysis showed no significant association between IgE levels and adenoid hypertrophy. Multiple linear regression analysis was performed to evaluate IgE levels, vitamin D levels, and presence of adenoid as independent variables; age as dependent variable among two groups and was found statistically significant (p < 0,001). Dermatophagoid sensitive group living in damp houses had a significant increase in adenoid hypertrophy (p = 0,01). Housedustmite sensitive children with recurrent lower respiratory tract infection and upper respiratory tract infection were mainly residents of damp houses (p < 0,001). Allergic comorbidities were significantly more in damp environment group (p < 0,001), but there was no significant increase in any of the subgroups. CONCLUSIONS: Children with mold exposure had significantly increased adenoid hypertrophy regardless of their atopic nature, however, they may have become more sensitized due to other environmental triggers and genetic factors. In damp environments, sensitization to dermatophagoids, was significantly increased in children with adenoid hypertrophy. During the period of infancy, when children were mostly vitamin D supplemented, they were not sensitized and had normal adenoids. As children with recurrent respiratory tract infections grow, they tend to have lower vitamin D levels, become more atopic and tend to have adenoid hypertrophy.