Dissertationen zum Thema „Vitamin A Therapeutic use Tanzania“

[Truncated abstract] An elevated total plasma homocysteine concentration (tHcy) is associated with an increased risk of myocardial infarction and ischemic stroke. Folic acid, vitamin B6 and B12 supplements significantly reduce tHcy even in people who are not overtly vitamin deficient. If homocysteine is a causal risk factor for atherothrombotic events, treatment with B-vitamins might prove a simple and cost-effective means to reduce cardiovascular risk. However, it remains unclear whether elevated tHcy causes atherosclerosis or is simply a risk marker. To prove that homocysteine is a modifiable risk factor for cardiovascular disease it is necessary to show that lowering tHcy reduces vascular risk. The aim of this study was to determine whether long-term homocysteine-lowering with B-vitamins would improve vascular structure and function in people with a history of stroke. This study was a cross-sectional sub-study of the Vitamins TO Prevent Stroke trial (VITATOPS), a multi-centre, randomised, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of B-vitamins (folic acid 2mg, vitamin B6 25mg and vitamin B12 0.5mg) in the prevention of vascular events in patients with a recent history of stroke or transient ischemic attack. 173 VITATOPS participants were recruited for the current study. Age, sex, stroke type, medications, cardiovascular risk factors and smoking history were recorded and blood pressure, height, weight, waist and hip girth were measured in all subjects at least two years after randomisation. ... After a mean treatment period of 3.9 ± 0.9 years, the subjects randomised to vitamin treatment had significantly lower tHcy than the subjects randomised to placebo (7.9mol/L, 95%CI 7.5, 8.4 versus 11.8mol/L, 95%CI 10.9, 12.8; p<0.001). There were no significant differences between groups in CIMT (0.84 ± 0.17mm vitamins versus 0.83 ± 0.18mm placebo; p=0.74) or FMD (median of 4.0%, IQR 0.9, 7.2, vitamins versus 3.0%, IQR 0.6, 6.6 placebo; p=0.48). Pooled estimates from the meta-analyses showed that B-vitamin treatment reduces CIMT by 0.10mm (95%CI –0.20, -0.01mm) and increases FMD by 1.4%, (95%CI 0.7, 2.2), although these estimates may have been influenced by positive publication bias. The improvement in FMD was significant in studies of less than eight weeks duration but not in studies with longer treatment periods. The association between tHcy and CIMT and FMD was eliminated by adjustment for renal function and long-term B-vitamin treatment did not alter the strong linear relationship between tHcy and cystatin C. Lowering tHcy did not alter arterial wall inflammation assessed by 18FDG-PET, although small subject numbers meant we were unable to exclude a minor treatment effect. Long-term homocysteine-lowering with B-vitamin treatment did not improve CIMT or FMD or reduce arterial wall inflammation in people with a history of stroke. The relationship between tHcy and these markers of vascular risk was eliminated by adjustment for renal function. Our data are consistent with the hypothesis that elevated tHcy is a risk marker for cardiovascular disease rather than a modifiable causal risk factor.

Considerable interest exists with regard to the putative therapeutic role of ascorbic acid in various conditions. A condition which has received much attention is cancer, as it is reported that ascorbic acid may be a prophylactic against cancer development. However, the actual involvement of ascorbic acid, an oxidizing/reducing agent, in the development and progression of tumours is presently a subject of much speculation. This study initially addressed the effect of ascorbic acid supplementation over a nutritional concentration range (0 - 100 μg/ml) on the in vitro growth of non-malignant LLCMK and malignant B16 cells. Ascorbic acid supplementation of these two cell types resulted in an overall decrease in the growth of both types of cells. The actual inhibitory mechanism of ascorbic acid on cell growth was not clear. Further study attempted to define and explain a mechanism responsible for this effect. Ascorbic acid has a role in the maintenance of tissue integrity and host defences, thus providing a rational basis for examining its relationship to cancer. Ascorbic acid is lcnown to be essential for the structural integrity of the intercellular matrix of the cells, the latter being a complex aqueous gel containing, amongst other compounds, fats and prostaglandins. Fats and prostaglandins have diverse effects on. membrane stability, enzyme activity and secondary messengers within cells. Hence, this study investigated the effect of ascorbic acid supplementation on certain enzymes and secondary metabolites within the cells, which had the potential to be involved in the control of cell growth. Throughout this study, emphasis was placed on the Bl6 melanoma cells as ascorbic acid supplementation did not significantly affect levels of secondary metabolites within the non-malignant LLCMK cells. Ascorbic acid supplementation of the B16 cells resulted in significant increases in adenylate cyclase activity and cyclic adenosine monophosphate levels, witb a significant decrease in Bl6 cell growth in that particular experiment. As cyclic adenosine monophosphate has a regulatory role in the cell cycle, this study suggested that the inhibitory effect of ascorbic acid supplementation on cell growth was mediated tbrough a final effect provided by the second messenger, cyclic adenosine monophosphate. However, clarification of tbe mechanism of tbe effect of ascorbic acid on adenylate cyclase activity was required. Hence, a further study investigated prostaglandin E₂ levels, as tbese affect adenylate cyclase activity. Prostaglandin E₂ levels were also found to be inversely related to Bl6 cell growth with ascorbic acid supplementation. It thus appeared tbat adenylate cyclase activity was dependent on prostaglandin E₂ levels in the B16 cells, and further study showed that tbis was indeed the case. Here, higher levels of prostaglandin E₂ supplementation of the Bl6 cells inhibited cell growth significantly and also significantly increased adenylate cyclase activity. Arachidonic acid is the precursor of prostaglandin E₂. In the presence of ascorbic acid supplementation, the percentage arachidonic acid composition of the Bl6 cells was inversely correlated with cell growth. Hence, prostaglandin E₂ levels in ascorbic acid supplemented B16 cells appeared dependent on tbe amount of precursor present. This was confirmed when Bl6 cells were supplemented with arachidonic acid. The latter had an inhibitory effect on Bl6 cell growth and also stimulated prostaglandin E₂ production. The cause of tbe inverse relationship between B16 cell growth and arachidonic acid composition with ascorbic acid supplementation was furtber investigated and found to be dependent on tbe uptake of arachidonic acid and other essential fatty acids from tbe medium. The enzymes phospholipase A₂ delta-5 and delta-6-desaturase, and elongase which could influence arachidonic acid levels were not affected to any extent by ascorbic acid supplementation and therefore did not influence the inverse relationship between B16 cell growth and arachidonic acid. Hence, it can be concluded that the effect of ascorbic acid supplementation on the BI6 cells is mediated, in part at least, by cyclic adenosine monophosphate. However, this is not the result of a direct effect of ascorbic acid supplementation. The initial effect of ascorbic acid supplementation concerns fatty acid - in particular arachidonic acid - uptake from the medium, with subsequent cascade effects On secondary metabolites, ultimately affecting the cellular levels of cyclic adenosine monophosphate.

Since vitamin D deficiency is common at birth, the objective of this study was to test if postnatal vitamin D supplementation would normalize bone mineralization. Forty guinea pigs were randomized to receive a diet with or without vitamin D3 during pregnancy. Newborn pups were randomized to receive 10 IU of vitamin D3 or a placebo daily until d28. Measurements at birth and d28 included whole body and regional bone mass, osteocalcin and deoxypyridinoline, plus biomechanical testing of excised tibias and femurs. Offspring from deficient sows had lower body weight, whole body and tibia bone mineral content (BMC) and lower osteocalcin and biomechanical integrity. By d28 this group had lower whole body bone density and femur BMC, unless supplemented. Interactions with gender showed males continued to have low 25(OH)D despite supplementation. Therefore, neonates born to sows with dietary vitamin D deficiency require supplemental vitamin D to support normal bone mineral accretion.

Objective: Acute lower respiratory infection (ALRI) is the leading cause of mortality in pediatric group all around the world. Vitamin D has been demonstrated to play a possible role in the prevention of ALRI in children because of its physiological importance in the immune system. This systematic review aims to explore the protective role of vitamin D on ALRIs among children and its preventive effectiveness by synthesizing RCTs. And the other objective is to determine dosage of vitamin D with the best effect by investigating the association of different level of vitamin D supplementation with risk of ALRIs. Methods: Studies were searched through three databases PubMed, ISI Web of Knowledge and Cochran Central Register of Controlled Trials and Cochran Library databases among publication from April2003 to April 2013 with a combination of key terms. Inclusion and exclusion criteria were used to select studies. And then CONSORT guideline and JADAD scale were used to assess quality of these studies. Data on outcome measurements including health outcomes (e.g. incidence of pneumonia and influenza A, duration of recovery of pneumonia and bronchiolitis, the risk of relapse of pneumonia, the number of parent-reported ARIs); and surrogate outcomes (e.g. measuring scores of ATAQ test) were extracted and tabulated. The association with vitamin D level of risk of ALRIs were explored as well. Results: Eight RCTs were found to be relevant and adopted in this systematic review of the 796 identified articles in English or Chinese. The findings were mixed, but most studies suggested vitamin D supplementation reduced risk or illness duration of ALRIs significantly among children with different levels of vitamin D deficiency. Four studies suggested statistically significant risk reduction on incidence of repeat pneumonia (by29%, 95%CI 6% to 46%), parent-reported ARIs (by 48%, 95%CI 11% to 69), influenza A (by 42%, 95%CI 1% to 66%), and asthma exacerbation triggered by ALRIs (P= 0.029), while one study showed an insignificant outcome. For recovery events and hospitalization of ALRIs, three studies suggested statistically significant reduction on recovery time from pneumonia (P= 0.008), severe asthma (P= 0.004) and bronchiolitis (P< 0.05), and two studies suggested significant decrease on duration of hospitalization for bronchiolitis (P< 0.05) and pneumonia (P= 0.005). The increasing changes in serum 25(OH)D were consistent with the significant difference of ALRIs events between intervention and control groups. Conclusion: Overall, the evidence is insufficient to conclude that vitamin D supplementation is beneficial to all kinds of children in preventing or assistant treating ALRIs. More number of high quality, large scale and unbiased RCTs should be conducted to confirm the effectiveness of vitamin D among children in Hong Kong and different areas in mainland China.
published_or_final_version
Public Health
Master
Master of Public Health

Early cortical injury has been attributed to the consequential effects of various factors, such as alcohol, drug addiction, smoking, and inadequate nutrient intakes during periods of pregnancy and lactation, or delivery of infants by forceps, and premature deliveries. These are only a few examples of circumstances, or "injury", that may result in disorders ranging from mild learning difficulties to aggressive behaviour. Injury to the cortex during the early years of development has been know to result in poor behavioural outcome into adulthood. Presently, the most common form of treatment includes a pharmacological agent, which may be accompanied with behavioral modification therapies supported by families. As an alternative form of therapy towards the treatment of early cortical injury, choline and a vitamin and mineral supplement (EM Power+) were used to determine the possibilities of nutrition intervention in an animal model. The injuries were incurred by aspiration lesion at days three, (Exp.1) and four, (Exp.2) and lesions were localized to the midline medial frontal cortex in some rats, while a different group of rats received lesions in the posterior parietal cortex. The pre-and postnatal choline treated animals showed favorable results for the medial frontal lesions, and the postnatal vitamin supplement treated animals showed favorable results for treatment in both medial frontal and posterior parietal lesions. All animals were tested in adulthood indicating that nutrition intervention is very beneficial for alleviating some of the functional deficits commonly seen from early cortical injury.
xiv, 191 leaves : ill. ; 28 cm.

The active form of Vitamin D (VD3) has been shown to induce pro-apoptotic and anti-proliferative effects in several mammalian cancer cell types. The molecular mechanisms of tumor suppression, however, are not clearly understood. Previous research has shown that head and neck squamous cell carcinoma (HNSCC) responds to VD3. This thesis used both in vivo and in vitro models to examine the effect of VD3 in HNSCC. Former work in the Albala laboratory showed that hamsters that received systemic VD3 and topical treatment of 7,12-dimethylbenz(a)anthracene (DMBA) to the buccal pouch showed no or delayed carcinogenesis over the 14-week study compared to DMBA-only treated hamsters. This research further investigated the effect of VD3 in this hamster model. Using immunohistochemical (IHC) and western blot analysis, we demonstrate that systemic application of VD3to hamsters downregulates Rad51 expression in the buccal pouch and hinders the onset of tumor formation. Rad51 is a protein that plays a critical role in cell proliferation and homologous recombinational DNA repair. In the in vitro model, we show that Rad51 expression decreased in response to 100nM VD3 in HNSCC cell lines. The dose and time-dependence of VD3 on these cells was also examined. Western blot analysis and comet assay investigations confirmed that the SCC25 cell line is most sensitive to 100nM VD3 than to other doses tested, and that VD3 impairs the DNA-damage response. SiRNA and co-immunoprecipitation studies examined the potential of Chk 1 and p38 MAPK as upstream regulators of Rad51. Rad51 protein expression was found to be associated with early carcinogenesis from HNSCC cancer patients using IHC studies of human carcinomas from the oral cavity. This study focused on further identifying the role of Rad51 in response to VD3 in HNSCC.

[Truncated abstract] Vitamin E is comprised of a family of tocopherols (TOH) and tocotrienols. The most studied of these is [alpha]-tocopherol ([alpha]-TOH), as this form is retained within the body and any deficiency of vitamin E is corrected with this supplement. [alpha]-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes and potentially acts as a defense against oxidative stress. Individuals who have a primary vitamin E deficiency such as low birth weight infants, secondary vitamin E deficiency due to fat malabsorption such as in abetalipoproteinaemia, or a genetic defect in TOH transport require supplementation. There is debate as to whether vitamin E supplementation in other patient groups is required. Vitamin E supplementation has been recommended for persons with FHBL, a rare disorder of lipoprotein metabolism that leads to low serum [alpha]-TOH and decreased LDL cholesterol and apolipoprotein B concentrations. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with heterozygous FHBL. We used HPLC with electrochemical detection to measure [alpha]- and [gamma]-TOH in serum, erythrocytes, and platelets, and GC-MS to measure urinary F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. Erythrocyte [alpha]-TOH was decreased, but we observed no differences in lipid-adjusted serum TOHs, erythrocyte [gamma]-TOH, platelet [alpha]- or [gamma]-TOH, urinary F2-isoprostanes, or TOH metabolites. Taken together, our findings do not support the recommendation that persons with heterozygous FHBL should receive vitamin E supplementation. ... Sesame lignans are natural components of sesame seed oil and there is evidence that these lignans can inhibit CYP450 enzymes, in particular, those responsible for vitamin E metabolism. We hypothesised that sesame seed ingestion would increase serum [gamma]-TOH, lower plasma lipids and inhibit platelet function in human subjects with at least one cardiovascular risk factor. We used HPLC with electrochemical detection to measure [alpha]- and -TOH in serum and GC-MS to measure F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. We used high-sensitive C-reactive protein as a measure of systemic inflammation. Platelet function was assessed using the PFA-100 platelet aggregation assay. Although serum [gamma]-TOH increased by 17%, we observed no effect on lipid metabolism, markers of inflammation, oxidative stress or platelet function following treatment with ~25 g/day sesame seeds for five weeks. Our findings challenge the hypothesis that sesame seed ingestion provides beneficial cardiovascular effects. In summary, we have studied the metabolism and transport of both [alpha]- and [gamma]-TOH in humans to evaluate the requirements for supplementation and the effects of vitamin E on platelet function and CYP3A4 activity. Specialised techniques using HPLC were developed to measure serum and cellular TOH concentrations both in supplemented and un-supplemented individuals. We also used GCMS to provide a sensitive, accurate assessment of TOH metabolites and midazolam pharmacokinetics in humans after vitamin E supplementation. We have examined the role vitamin E has on important biochemical endpoints, with emphasis on the implications for TOH supplementation in subjects at risk of CVD.

Male weanling inbred, mice were inoculated with fibrosarcoma cells (hindquarter) originally produced by 2-methylcholanthrene. Before inoculation, mice were randomly divided into three groups of 24 and one of 12 (control). After a one week acclimation period, each group was fed a diet containing either suboptimal vitamin B-6, 0.5 mg/kg diet; adequate, 7.0 mg/kg diet; or excess, 100 mg/kg diet. Controls were fed the adequate vitamin. B-6 diet. Twenty-four hours after tumor cell inoculation, a series of sodium selenite injections (0.5 μg/.10 mL) were given to half of each treatment group and all controls. Mice were sacrificed two wk after tumor inoculation. Tumors were excised and weighed. Selenium-treated mice had significantly smaller tumors as compared to untreated mice regardless of vitamin B-6 treatment. The smallest tumors were found in the selenium-treated group maintained on adequate B-6, while the largest tumors were developed by mice on the excess B-6 diet without selenium treatments. All groups had similar blood selenium levels as measured by gas chromatography. Tumor selenium levels, analyzed by atomic absorption, were significantly higher for untreated groups than selenium-treated groups (larger tumor size). The excess and adequate vitamin B-6 selenium-treated groups had significantly lower tumor selenium levels than the adequate vitamin B-6 untreated group. Plasma pyridoxal phosphate (concentrations) determined radiometrically and tumor vitamin B-6 levels determined microbiologically, related directly to dietary treatments. Sodium selenite injections and adequate vitamin B-6 diets reduced the size of fibrosarcomas in BALB/c inbred mice.
Master of Science

Falls in the older population have devastating consequences on the psychological and physiological health of the individual. Due to the complexity of interacting factors associated with ageing, pathology and falling episodes, determination of a primary cause or set of causes has been difficult to establish. Deficits in components of neuromuscular control have been widely studied with the coordinated interaction of sensory and motor system components being presented as a fundamental factor in the reduction of falling episodes. A causal relationship between deficits in vitamin D status and falling episodes has also been suggested. Furthermore, a relationship between poor vitamin D status, falling episodes and poor neuromuscular performance has been reported. The aims of the current study were designed to advance understanding in three aspects of the problem of falls prevention. Firstly an examination of the reliability of testing procedures commonly used in assessment of falls risk was undertaken. The Physiological Profile Assessment (PPA) testing procedure was selected as a commonly used tool and the reliability of its various components (sensory, motor and balance) was undertaken as an independent assessment of this approach to assessing falls propensity. Secondly, a case control study of fallers and non fallers was undertaken in which the neuromuscular tests evaluated in the reliability study were used to assess differences in neuromuscular control. The influence of vitamin D status on these measures was also considered. Thirdly, a 12-month randomised controlled trial of vitamin D/calcium supplementation or placebo/calcium was undertaken to identify the effect on falls outcome and individual measures of neuromuscular control.

Uvod: Hepatička osteodistrofija je termin koji obuhvata metaboličke bolesti kosti udružene sa hroničnim bolestima jetre. U alkoholnoj cirozi (AC) jetre postoji visoka zastupljenost deficijencije vitamina D proporcionalna stepenu disfunkcije jetre, ali njena uloga u patogenezi hepatičke osteodistrofije nije dovoljno objašnjena. Nivo 25(OH)D odražava status vitamina D. Kod AC jetre izmenjena je metabolička aktivnost kosti i suprimirano je formiranje kosti što dovodi do smanjenja koštane mase. U centru interesovanja je postizanje optimalnog statusa vitamina D. Stavovi o suplementaciji vitaminom D kod AC jetre nisu jasno definisani. Cilj rada: Utvrditi nivo vitamina D, ispitati metaboličku aktivnost kosti i mineralnu gustinu kosti kod bolesnika sa AC jetre. Utvrditi efekte suplementacije sa 1000 IU vitamina D3 na dan tokom godinu dana u odnosu na metaboličku aktivnost kosti i mineralnu gustinu kosti kod ispitivanih bolesnika. Bolesnici i metode: Istraživanje je sprovedeno na Klinici za gastroenterologiju i hepatologiju Kliničkog centra Vojvodine u Novom Sadu kao prospektivna intervencijska studija sa primenom suplementacije sa 1000 IU vitamina D3 na dan kod bolesnika sa AC jetre. Grupu bolesnika koja je uključena u istraživanje (1) činilo je 70 bolesnika muškog pola sa dijagnozom AC jetre. Bolesnici su imali četiri pregleda (P), odnosno tačke studije: P1-uključivanje bolesnika i započinjanje suplementacije vitaminom D; P2, P3 i P4 posle tri, šest i dvanaest meseci suplementacije vitaminom D, redom. Prilikom svakog pregleda rađene su analize funkcije jetre, metabolizma kosti i statusa vitamina D. Na početku (P1) i na kraju istraživanja (P4) vršeno je merenje mineralne gustine kosti (BMD) DXA metodom. Gubitak bolesnika od P1 do P4 bio je dvadeset, na različitim tačkama studije. Prvi deo istraživanja odnosi se na Grupu bolesnika koja je uključena u istraživanje (1) i završila prvi pregled (P1). Pedeset bolesnika je završilo kompletno istraživanje po predviđenom protokolu i oni se zbog realizacije svih pregleda i ponovljenih merenja posmatraju kao: Grupa bolesnika koja je završila istraživanje (2). Rezultati: (1): Kod bolesnika sa AC jetre utvrđena je deficijencija vitamina D, snižen nivo osteokalcina, normalni nivoi CrossLapsa, PTH, ukupnog i jonizovanog kalcijuma, fosfora i magnezijuma. Osteopeniju je imalo 42,65% a osteoporozu 14,71% ispitanika. Kod svih ispitanika najniži BMD izmeren je na vratu femura. (2): Suplementacija vitaminom D dovela je do značajnog porasta 25(OH)D. U odnosu na osteokalcin konstatovana je pozitivna razlika vrednosti P1/P4, iako je nivo ostao ispod donje granice normale. Kod nivoa CrossLapsa i PTH razlika P1/P4 je negativna, ali su nivoi u sva četiri merenja u okviru referentnih vrednosti. Na lumbalnoj kičmi došlo je do poboljšanja BMD za 0.87%, a pogoršanja su na vratu femura -1.87 % i kuku -1.65%. Konstatovano je i poboljšanje funkcije jetre. Zaključci: Kod bolesnika sa AC jetre poboljšanje statusa vitamina D dovodi do povećanja formiranja kosti i poboljšanja koštane mase na lumbalnoj kičmi. Neophodno je određivanje statusa vitamina D kod svih bolesnika sa AC jetre i uvođenje suplementacije vitaminom D kod bolesnika koji imaju nivo 25(OH)D < 80 nmol/l, uz tromesečne kontrole efekta. Kod postavljanja dijagnoze AC jetre potrebno je inicijalno određivanje BMD. Kod suplementacije vitaminom D nakon inicijalnog DXA pregleda sledeći se preporučuje nakon jedne do dve godine.
Introduction: The term Hepatic osteodystrophy defines a group of metabolic bone diseases associated with underlying chronic liver disease. Alcoholic liver cirrhosis (ALC) is characterized by high incidence of vitamin D deficiency that is proportional to the level of liver failure; however, its role in the pathogenesis of hepatic osteodystrophy has not yet been fully elucidated. The level of 25(OH)D best reflects the vitamin D status. ALC is characterized by changed bone metabolic activity and suppressed bone formation, resulting in the decrease in bone mass. The key topic of interest is the achievement of optimal vitamin D status. The attitude of health professionals towards vitamin D supplementation in alcoholic liver cirrhosis has not yet been clearly defined. The aim of the research: Determining of vitamin D levels, investigating the metabolic activity of the bone and bone mass in patients with alcoholic liver cirrhosis (ALC); Determining the effects of vitamin D3 supplementation at the dose 1000 IU/day during a one-year period in relation to metabolic activity of the bone and bone mineral density (BMD) in the investigated patient population. Patients and methods: The research was conducted at the Clinic for Gastroenterology and Hepatology of the Clinical Centre of Vojvodina in Novi Sad. The research was designed as a prospective interventional study implicating vitamin D3 supplementation at the dose 1000 IU/day to patients with ALC. The investigated patient population (1) encompassed 70 male patients diagnosed with ALC. The patients underwent four examinations (P), that is, research phases: P1 – inclusion of the patient into the study and introduction of vitamin D supplementation; P2, P3 and P4 after 3, 6 and 12 months of vitamin D supplementation treatment, respectively. Each examination included the analysis of liver function, bone metabolism and vitamin D status. At the beginning (P1) and at the end (P4) of the investigation period, bone mineral density (BMD) was measured by means of dual-energy x-ray absorptiometry (DXA) method. Twenty patients dropped out from the research at different stages throughout the investigation period (P1 to P4). The first part of the investigation pertains to the Group of patients who were included into the study (1) and completed the first examination (P1). Fifty patients have completed the entire research according to the foreseen protocol encompassing all examinations and repeated measurements. These patients are considered a Group of patients who completed the research (2) Results: (1): In ALC patients, vitamin D deficiency and decreased osteocalcin levels were established, as well as normal levels of CrossLaps, PTH, total and ionized calcium, phosphorus and magnesium. Osteopenia and osteoporosis were established in 42.65% and 14.71% of patients, respectively. The lowest BMD was measured in the femoral neck in all patients. (2): Vitamin D supplementation resulted in significant increase in 25(OH)D. Analysis of osteocalcin level revealed positive P1/P4 difference, even though the level remained below the lower normal limit. The levels of CrossLaps and PTH revealed negative P1/P4 difference; however, the levels determined at all four measurements were within the reference values. An improvement of BMD for 0.87% was established in lumbar spine, whereas a decrease was noticed in femoral neck (1.87%) and hip (1.65%). Furthermore, an improvement of liver function was established. Conclusions: Improvement of vitamin D status in ALC patients results in an increase of bone formation and improvement of body mass in lumbar spine. Determining the vitamin D status in all patients with ALC is of outmost importance, as well as the vitamin D supplementation of patients with levels of 25(OH)D < 80 nmol/l along with the monitoring of treatment outcome at three-month intervals. Establishment of the diagnosis of alcoholic liver cirrhosis should encompass initial measurement of BMD. In case of vitamin D supplementation treatment, the initial DXA examination should be repeated after the period of one to two years.

Despite numerous studies have demonstrated an association of type 2 diabetes mellitus (T2DM) and osteoporosis, the underlying mechanism connecting these two conditions remains elusive. Clinically, combined calcium and vitamin D supplement is the commonest osteoporosis therapy; however, recent studies have suggested an increase in cardiovascular risks associated with calcium plus vitamin D supplementation. Therefore, an alternative strategy in treating osteoporosis patients with T2DM is urgently needed. In this study, we hypothesized that combined administration of menaquinone-4 (vitamin K₂, biologically active form of vitamin K) and 1α,25-dihydroxyvitamin D₃ (vitamin D₃, biologically active form of vitamin D) as a novel therapy in treating osteoporosis of T2DM patients. Anabolic effect of vitamin K₂ and vitamin D₃, alone or in combination, was assessed on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (db⁺/m⁺) and obese/diabetic (db⁺/db⁺, leptin receptor-deficient) mice. Furthermore, the underlying cellular mechanism was also investigated. Serum undercarboxylated osteocalcin (an indication of vitamin K₂ level) level was higher whereas vitamin D₃ level was lower in db⁺/db⁺ mice, and sections of the iliac crests of db⁺/db⁺ mice illustrated extensive porous structures filled with enlarged adipocytes compared with db⁺/m⁺ mice. Lower levels of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4, type I collagen, OSX, alkaline phosphatase (ALP) activity, p-Smad1/5/8 and p-ERK1/2) were observed in the osteoblasts of db⁺/db⁺ mice. Acute vitamin D₃ (10 nM) application elicited a more sustained and greater magnitude of increase of [Ca²⁺]ᵢ in osteoblasts of db⁺/m⁺ mice when compared with db⁺/db⁺ mice. A significantly higher level of calcium deposits in osteoblasts was observed in db⁺/m⁺ mice when compared to db⁺/db⁺ mice. Co-administration of vitamin K₂ (10 nM) and vitamin D₃ (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K₂ and D₃ co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and transcription factors for bone formation, with a greater magnitude of increase observed in osteoblasts of db⁺/db⁺ mice. Suppressed expression of calcium-sensing receptor (CaSR), F-actin, V-ATPase, vitamin D receptor (VDR) and pregnane X receptor (PXR) observed in osteoblasts of db⁺/db⁺ mice were partially reversed by combined vitamins treatment. Moreover, combined vitamins K₂ plus D₃ treatment significantly enhanced migration and the appearance of surface microvilli and ruffles of osteoblasts of db⁺/db⁺ mice. Effects of combined vitamins K₂ plus D₃ treatment observed in osteoblasts of db⁺/db⁺ and db⁺/m⁺ mice were eradicated by warfarin (20 µM, a vitamin K epoxide reductase inhibitor). Thus, our results illustrate that vitamins K₂ plus D₃ supplementation is a novel therapeutic strategy in treating osteoporosis of T2DM patients.
儘管大量研究已證明第二類型糖尿病和骨質疏鬆症的關聯，連接這兩個病症的基本機制仍然是難以捉摸的。在臨床上，鈣和維生素D的綜合補充劑是最常見的骨質疏鬆症治療，然而最近的研究卻表明服用鈣和維生素D的綜合補充劑會增加患者的心血管風險，因此急切需要尋找可以給予同時患有骨質疏鬆症和第二類型糖尿病患者的替代治療。在本研究中，我們假設甲萘醌-4（維生素K₂，維生素K生物活性形式）和1α，25 - 二羥基維生素D₃（維生素D₃，維生素D的生物活性形式）可以嘗試在同時患有骨質疏鬆症和第二類型糖尿病患者身上作為一種革新的療法。本研究從C57BL/KsJ瘦削/非糖尿病 (db⁺/m⁺) 的小鼠和肥胖/帶有第二類型糖尿病基因 (db⁺/db⁺) 兼有瘦素受體缺陷的小鼠的髂嵴原始成骨細胞上對維生素K₂和維生素D₃單獨或組合使用的合成代謝作用進行了評估。此外，我們也對該成骨細胞的底層機制進行了一系列的研究。
在肥胖/帶有第二類型糖尿病基因的小鼠血清內低羧骨鈣素水平（維生素K₂水平的指標）較高而維生素D水平較低，另外，它們的髂嵴的部分與瘦削/非糖尿病的小鼠相比，呈現出比較廣泛的多孔結構並填滿了擴大的脂肪細胞。從肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞中，可以觀察到它們的骨合成代謝的標誌物和骨骼形成的轉錄因子 (骨鈣蛋白，Runx2，Dlx5，ATF4，第一類型骨膠原，OSX，鹼性磷酸酶 (ALP) 活性，p-Smad1/5/8和p-ERK1/2) 的水平比較低。急性維生素D₃ (10 nM) 的應用在瘦削/非糖尿病小鼠的成骨細胞比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞引起更持續和更大幅度的細胞內鈣變化增加。在瘦削/非糖尿病小鼠的成骨細胞中比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞有顯著較高的鈣沉積形成。維生素K₂ (10 nM) 和維生素D₃ (10 nM) 的綜合藥在兩種小鼠的成骨細胞中可以有效地增強鈣沉積的形成。維生素K₂和維生素D₃的綜合藥對增加骨合成代謝的標誌物和骨形成轉錄因子的水平有時間依賴性 (7，14和21日)，療程越長至21日，在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中有更大的幅度的增加。合併維生素治療能部分有效地逆轉在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中被抑制表達的鈣敏感受體 (CASR)，F-肌動蛋白，V-ATP酶，維生素D受體 (VDR) 和孕烷X受體 (PXR)。此外，結合維生素K₂加維生素D₃治療顯著增強了肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞的細胞遷移和增加了成骨細胞表面外觀的微絨毛和褶皺。在瘦削/非糖尿病小鼠的成骨細胞及肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞上結合維生素K₂加維生素D₃的治療效果被華法林 (20 μM，維生素K環氧化物還原酶抑製劑) 根除。因此，我們的結果証明了維生素K₂加維生素D₃補充劑的結合使用可有效地作為治療第二類型糖尿病患者並患有骨質疏鬆症的一種新的治療策略。
Poon, Chui Wa Christina.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2014.n5203
Includes bibliographical references (leaves 135-151).
Abstracts also in Chinese.
Title from PDF title page (viewed on 26, October, 2016).
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.

Patients with end-stage renal disease undergoing hemodialysis have a high incidence of oxidative stress-related diseases. This study evaluated oxidative stress and inflammatory markers in patients undergoing hemodialysis before and during vitamin E supplementation. Blood samples were obtained before and after dialysis during two separate dialysis sessions to establish baseline measurements. For the next two months, subjects consumed 400 IU RRR-α-tocopherol daily. At one month and two months of supplementation, blood samples were also obtained before and after dialysis. Circulating concentrations of α- and γ-tocopherols and their metabolites (carboxyethyl-hydroxychromans, α- and γ-CEHCs), vitamin C, and uric acid were determined by HPLC with electrochemical detection. C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using standard clinical assays. F₂-isoprostanes were evaluated using an enzyme immunoassay. Dietary vitamins E and C were assessed using two 24-hour recalls. In response to vitamin E supplementation, plasma α-tocopherol concentrations increased from 18 ± 1.7 μM to 31 ± 5.4 μM (p<0.0001), while γ-tocopherol concentrations decreased from 2.8 ±1.0 μM to 1.7 ± 0.6 μM (p=0.001). Additionally, serum vitamin E metabolites increased, α-CEHCs from 68 ± 20 pmol/ml to 771 ± 161 (p<0.0001) and γ-CEHC from 837 ± 161.8 pmol/ml to 1136 ± 225.9 (p=0.0083). Both CEHCs are well above reported normal values (p<0.0001). Dietary antioxidants (vitamins E and C) were low in most subjects; thus, plasma ascorbic acid levels were low in most subjects, but high in a few, resulting a wide range of responses (88 ± 84 μM). Nonetheless, ascorbic acid concentrations decreased significantly after dialysis to 33 ± 34 μM (p=0.0124), but were unaffected by vitamin E supplementation. Indeed, many parameters decreased significantly by dialysis but were unchanged by vitamin E supplementation, including plasma concentrations of uric acid and TNF-α. Both IL-6 and F₂-isoprostane concentrations were elevated in the subjects but were unaffected by either vitamin E supplementation or dialysis. CRP increased significantly after dialysis (p=0.0161, ANOVA main effect), but in the vitamin E supplemented subjects CRP concentrations were slightly lower before dialysis , but increased following dialysis (p=0.0041, ANOVA interaction). Taken together, the data suggest that there is a complex relationship between chronic inflammation and oxidative stress. Longer supplementation with vitamin E might be necessary in order to observe beneficial effects.
Graduation date: 2003

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
O impacto que o processo de envelhecimento tem sobre a aparência já é há muito conhecido. Daí que a pesquisa para encontrar a melhor solução anti-envelhecimento se revele uma viagem sem fim. No entanto, há um líder incontestável nesta procura: os retinóides tópicos. As evidências científicas disponíveis através de estudos clínicos randomizados provam que não só são eficazes em reparar danos solares, a um nível clínico e bioquímico, como também são eficazes na sua prevenção. Este tipo de efeitos não pode ser negligenciado, mesmo considerando a possível intensidade de reacções adversas que se podem sentir durante o tratamento. Isto forma uma das bases na qual a investigação com retinóides está a evoluir, garantindo o desenvolvimento futuro de agentes mais eficazes, estáveis e toleráveis, optimizando o tratamento do envelhecimento da pele. Adicionalmente, falarei da minha experiência durante os dois estágios que realizei na Farmácia Higiene de Esgueira e no Magium Farma. A sua descrição será feita na forma de uma análise SWOT, onde serão analisados os seguintes tópicos: Forças; Fraquezas; Oportunidades e Ameaças.No caso da Farmácia Higiene, a par da análise, será feita a descrição de dois casos clínicos pertinentes à experiência.Relativamente ao Magium Farma, foram incluídos exemplos dos trabalhos desenvolvidos durante o estágio, nos respectivos anexos.Concluindo, esta monografia fará uma descrição do trabalho que realizei nos últimos seis meses como aluna da Faculdade de Farmácia da Universidade de Coimbra.
The impact that the aging process has on one´s appearance has long been known. Hence, the search for the best antiaging solution has been a never-ending journey. However, there is one incontestable leader in this search: topical retinoids. The scientific evidence available through randomized clinical trials proves that not only they are efficacious in repairing the photodamage, at a clinical and biochemical level, as they are in its prevention. Such effects cannot be overlooked, even when considering the possible intensity of adverse effects that may be experienced during treatment. This forms one of the basis in which ongoing research concerning retinoids is evolving, ensuring the future development of more efficacious, stable and tolerable agents, and therefore optimizing the treatment of skin aging.Additionally, I will be speaking about my experience during the two internships that I enrolled in, namely in Pharmacy Higiene, in Esgueira, and in Magium Farma. The descriptions will be made in a SWOT analysis, where I will be analyzing the following topics: Strengths; Weaknesses; Opportunities and Threats.Regarding Pharmacy Higiene, along with the analysis, a description will also be made on two clinical cases important to the experience.When it comes to Magium Farma, a few examples of the work that I developed during this internship will be shown in the annex.Concluding, this dissertation will be describing the work that I developed during the last six months as a student in the Faculty of Pharmacy of the University of Coimbra.

The present study investigated whether vitamin E supplementation reduced oxidative stress in erythrocytes and improved vitamin E status in patients undergoing hemodialysis (HD). Plasma and erythrocyte α-tocopherol, plasma ascorbic acid, and iron status were determined in 11 regular HD patients prior to and post-dialysis, before and during oral supplementation of vitamin E, 400 IU daily for two months. HD patients were categorized into two groups according to their plasma ascorbic acid levels. We found that only the vitamin C sufficient group (>40 μM, Group I) had reliable measurements of erythrocyte α-tocopherol concentrations before vitamin E supplementation. In Group I prior to dialysis, erythrocyte α-tocopherol concentrations increased in response to vitamin E supplementation from 6.7 ± 0.7 μmol/L packed cells to 9.8 ± 0.6 (μmol/L packed cells (p<0.04). Moreover, there was a positive correlation (pGraduation date: 2003

Erythrocytic inclusion body syndrome (EIBS) was artificially established in selected stocks of juvenile fall and spring chinook salmon (Oncorhynchus tshawytscha), chum salmon (0. keta), coho salmon (0. kisutch), Atlantic salmon (Salmo salar), and rainbow trout (0. mykiss). Adult spring chinook salmon were also artificially infected with the EIBS virus. Adult male chinook had higher prevalences of EIBS inclusion bodies than females. Cytoplasmic inclusion bodies that are associated with EIBS were not observed in steelhead (0. mykiss), brown (Salmo trutta) nor brook (Salvelinus fontinalis) trout suggesting that these stocks are less susceptible to the EIBS virus. Coho salmon with EIBS were more susceptible to Flexibacter psychrophilus, the causative agent of cold water disease (CWD) than fish without EIBS. The fish with EIBS were most susceptible to F. psychrophilus during the first 20 days after virus exposure, when inclusion bodies were most prevalent. Coho salmon infected with both the EIBS virus and F. psychrophilus required a longer recovery period than fish exposed to either pathogen alone. Most investigations of EIBS require in vivo experimentation and artificial infections using diseased fish tissues. Heterologous tissue used to establish EIBS did not contribute to anemia nor mortality. Death was not attributed to the EIBS virus alone but to the combined effects of the virus and a secondary pathogen. The severity of EIBS may be reduced with dietary Vitamin C prophylaxis. Fish fed 1,000 mg ascorbic acid/ Kg of diet had the fewest signs of EIBS; they had the highest hematocrit values and the lowest incidence of cytoplasmic inclusion bodies. However, vitamin C therapy alone was not sufficient to prevent the disease.
Graduation date: 1992

This investigation was conducted to determine the effect of estrogen replacement therapy (ERT) on vitamin B-6 status of postmenopausal women. Nineteen postmenopausal women served as subjects. Nine (54.7 + 4.7 years) were taking ERT (experimental group); ten (56.8 + 2.3 years) were not (control group). For three consecutive days, subjects recorded their dietary intake and collected their 24-hour urine specimens. On the fourth day, a fasting blood sample was drawn from the subjects. The dietary intake of vitamin B-6, as well as the concentration of total vitamin B-6 in plasma (PB6; and urine (UB6) were measured. PB6 and UB6 were determined by a microbiological method with Saccharomyces uvarum as the assay organism. The mean age, height, hematocrit and hemoglobin values were similar for the two groups. The experimental group was significantly heavier than the control group (p<0.05). The experimental group had a lower mean PB6 than the control group: 47.7 ± 19.7 nmol/L vs. 56.2 + 20.6 nmol/L. These means were not significantly different (p=0.05). PB6 was positively correlated with dietary vitamin B-6 intake (p=0.0001) and vitamin B-6 to protein ratio (p=0.0021). When the means were adjusted for dietary vitamin B-6 and the vitamin B-6 to protein ratio, the mean PB6 of the experimental group (42.7 nmol/L) was significantly lower than that of the control group (60.6 nmol/L) (p<0.05). PB6 was not positively correlated with either age (r=0.20) or the vitamin B-6 dietary history score (r=0.15). UB6 was similar for the two groups. UB6 correlated positively with daily dietary intake of vitamin B-6 (r=0.51, p<0.05) and the ratio of vitamin B-6 to protein (r=0.47, p<0.05), UB6 was not significantly correlated to urine volume (r=0.05). The mean daily intakes of vitamin B-6 and protein were similar for the two groups. One of the 19 subjects had a vitamin B-6 intake that was less than 67 percent of the RDA. Most subjects' (89%) intake of vitamin B-6 was adequate when the ratio of 0.016 mg of vitamin B-6 per g of protein was used as the standard.
Graduation date: 1990

by Chan Tak Yee Bonita.
"July 2004."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2004.
Includes bibliographical references (p. 121-137).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.

M.Tech. (Homoeopathy)
Psychological stress refers to an individual’s interaction with what he perceives as adverse or threatening phenomena of the external environment (stimulus) and the ensuing physiological response that occurs within the body. Although the stimulus itself may not be harmful, the physiological reaction of the individual to the perceived threat may lead to health consequences. University students may experience greater levels of stress than the average population. They may also experience symptoms of anxiety, irritability, sleep disturbances and impaired memory due to psychological stress. These symptoms may be exacerbated by concomitant use of alcohol and stimulants such as nicotine and caffeine, which students may use as coping mechanisms. Conventional treatment for stress might include anti-depressants and anxiolytics that often have adverse effects. TranQuin® Day Formula is a combination vitamin and herbal supplement formulated to assist the body to cope with stress. Although each individual vitamin and herbal constituent of TranQuin® Day Formula has been thoroughly researched, to date, no research has been conducted on the efficacy of TranQuin® Day Formula dietary supplement for the treatment of psychological stress in university students. The aim of this study was to determine the efficacy of TranQuin® Day Formula supplement on psychological stress in university students, with the use of the Cohen’s Perceived Stress Scale-10 (PSS-10) and Goldberg’s General Health Questionnaire-28 (GHQ-28). Thirty participants, both male and female, between the ages of 18 and 49 years, who obtained a minimum score of 10 on the Cohen’s Perceived Stress Scale-10, were selected to participate in this six week, double-blind, placebo-controlled study. Participants were also requested to complete Goldberg’s General Health Questionnaire-28. The scores obtained by the participants on both stress scales were measured at the beginning of the study (week 0) to obtain a baseline score, in the middle of the study (week 3) and at the end of the study (week 6). The participants were randomly divided into the control and experimental groups. Participants were asked to take two capsules of the supplement or placebo, preferably in the morning after breakfast, or the first meal of the day, for the duration of the study period (6 weeks). Each participant received a daily data sheet which recorded capsules taken and any symptoms experienced, as well as any other medication taken. The results of the study were statistically analysed using the Mann-Whitney-U Test, the Shapiro-Wilk Test, the Wilcoxon Signed Ranks Test, Friedman Test and descriptive statistics.