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Individual,Geographical And Environmental Determinants Of Calcium,Phosphorus And Vitamin D Metabolism

Posted on:2018-06-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:J L ShenFull Text:PDF
GTID:1314330542465172Subject:Bone surgery
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Part ?.Survey of the vitamin D status in the health males and theassociated factorsObjective: To investigate the Vitamin D status in health male persons of Northern Europe and find out the risk factors of vitamin D deficiency and the association between vitamin D and other metabolic indexes.Methods: About one hundred and ten health male persons from Northern Europe were included in the study.A questionnaire was used to obtain subjects personal characteristics like gender,age,height,weight,or smoking behavior.Also,health related questions will be included like questions on general health,medication,or intake of food supplements.The vitamin D related questions will cover degree of sun avoidance,duration of recent outdoor activities,intake of vitamin D supplements,recent travel activity,and main where abouts on the day before blood sample taking,and nutritional data.The blood analysis included 25(OH)D,Calcium,Phosphate,Parathyroid hormone,Creatinine,Albumin,Alanine aminotransferase,Glucose,C-reactive protein,Thyrotropic hormone,Sodium and Potassium.Define of Vitamin D deficiency was determined by the standard of International Osteoporosis Foundation.Prism 6.0 was used to analyze the data.The risk factors of vitamin D deficiency were determined by multi-variation logistic regression.The association of vitamin D and the metabolic index was analyzed by spearman correlation coefficient.Results: The mean of plasma 25(OH)D level is 39.46±16.56 nmol/L,about 60.9% of persons are defined as Vitamin D deficiency and only 4.5% of persons have an enough vitamin D(>75nmol/L).Intake of milk(50ml/day)can significant increase the plasma level of vitamin D,while age,blood pressure,BMI,smoking and physical activities have no significant effect on vitamin D level.The plasma level of vitamin D was positive associated with Ca and Crea and negative associated with PTH and Glucose.No significant association was found between Plasma vitamin D level vitamin D and CRP,Alb,ALAT,TSH,sodium and Potassium.The mean of plasma vitamin D levels was lower in the elevated PTH group(PTH>6.9pmol/L)than that in normal PTH group.Conclusion: The plasma level of vitamin D in health male persons of Northern Europe is very low and more than half of persons were defined as vitamin deficiency.Vitamin D is very importance in calcium and bone metabolism,Vitamin D is very important in calcium and bone metabolism,while Vitamin D level is significant positive association with Ca but negative association with PTH.Moreover,vitamin D may also involve in the metabolism of creatinine.Intake of milk(>50ml/day)can significant increase the plasma vitamin D level.Part ?.The effect of latitude on calcium,vitamin D status andvitamin D receptorObjective: In general,the vitamin D status is lower in high latitude than that in low latitude.Contrary to expectation,the issue appears different in Europe.The aim of this study is to investigate the influence of latitude on calcium,vitamin D status and vitamin D-related signal transduction in Northern Europe.Methods: The study will take place along the 24 th Eastern meridian on the Northern hemisphere: in Tallinn,Estonia;Kaunas,Lithuania;Athens,Greece.In addition in Ikaria,Greece(26 degrees East)at the same latitude as Athens samples will be taken.At each location 30 healthy individuals between 30 and 50 will be investigated.Investigations will be performed in blood plasma,and circulating blood cells.The blood tests are the same with first part.Western Blot and Q-PCR were used to test the VDR protein and m RNA expression in peripheral blood mononuclear cells.Results: There is a downward trend of plasma vitamin D level from a higher latitude to a lower latitude(Tallinn,N 59°;Kaunas,N 55°;Athens,N 38°).But it is only significant different between Tallinn(49.79±3.543nmol/L)and Athens(31.95± 2.241nmol/L)(P<0.05).For the same latitude,the vitamin D level of Athens is lower than that in Ikaria(46.78±2.124nmol/L)(P<0.001).The trend of Ca and Crea level are similar to the trend of vitamin D between different latitude.However a upward trend was detected in the CRP and TSH level from Tallinn to Athens.It is different between the expression of VDR m RNA and VDR protein.Only the expression of VDR protein is significant positive associated with plasma vitamin D level.We also found that intake of milk would upregulate the expression of VDR protein without affecting VDR m RNA expression.Moreover,the expression level of VDR in higher PTH level(>6.9pmol/L)was lower than that in normal PTH group(<6.9pmol/L).Conclusion: Contrary to expectations,we found a positive association between latitude and mean 25(OH)D,with lower concentration in city with low latitude than that with high latitude.This contrary result may due to the different environment and living habits.Vitamin D may stabilize the VDR by protecting it from proteasomal degradation,not by increasing the expression of VDR m RNA.Intake of mike can also increase the protein expression of VDR without affecting the VDR m RNA expression.Part ?.Effect of Bisphenol A exposure on Calcium,phosphorusand Vitamin D metabolismObjective: A recent study suggested that environmental exposure to BPA may altered circulating levels of total 25(OH)D in adults.However,no studies have assessed the effect of BPA on Vitamin D endocrine system in mice.As the chronic exposure is most relevant to humans exposed environmentally,the objective of the present study was to investigate the effects of long-term BPA exposure on Vitamin D endocrine system and Ca homeostasis.Methods: The pregnant mice were randomly divided into three groups: control and two BPA exposure groups(0.5?g and 5?g BPA /kg/day).After weaning,the male offspring from each group were administered with the same water as their mother.Samples of kidney and blood were obtained from the mice at week 8 and 10 month Plasma levels of Ca,Phophate(P),Parathyroid Hormone(PTH),25(OH)D and 1,25(OH)D in blood circulation were measured sequentially.The expression levels of 1.25(OH)D/VDR,Ca and P transport protein in kidney were also tested.Results: Plasma levels of Ca,P and 1,25(OH)D were decreased in mice treated with BPA(0.5?g and 5?g BPA /kg/day)at 10-month,but no remarkable different was detected in plasma levels of PTH and 25(OH)D.The m RNA expression levels of transient receptor potential cation channel,subfamily V,member 5(TRPV5),calbindin-D9k(Ca Bp-9k),calbindin-D28k(Ca Bp-28k),Na/Ca2 exchanger(NCX1)and the type IIa Na Pi cotransporters(Npt2a),which in kidney were decreased after treatment with BPA.The protein and gene expression of active vitamin D synthesis enzyme(CYP27B1)and vitamin D receptor(VDR)were also reduced by BPA in 10-month mice.However,BPA exhibits a nonmonotonic dose response in 8-week mice with human relevant exposure of BPA(0.5?g/kg/day),which have significant negative effect on calcium,P and Vitamin D metabolism,while the High human relevant exposure of BPA(5?g/kg/day)did not significantly alter any end point of calcium,Pi and Vitamin D metabolism.Conclusion: Our results suggested that long-term exposure to low dose BPA had negative effects on gene involved in 1,25(OH)2D/VDR system and Ca transfer,which would disturb Ca reabsorption in kidney can result in a reduction of serum Ca levels in mice.
Keywords/Search Tags:health male persons, vitamin D, calcium, parathyroid hormone, latitude, peripheral blood mononuclear cells, vitamin D receptor, bisphenol A, phosphate, 1,25(OH)D/VDR system, renal reabsorption
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