The association between vitamin K2 intake and glucose homeostasis in individuals with and without chronic kidney disease

Thesis (Master's)--University of Washington, 2016-08

The importance of improving diet in "Securing Scotland's Health" : progress towards the Scottish dietary goals

Background: In 2013, the Revised Dietary Goals for Scotland (SDGs) were published to “indicate the direction of travel, and assist policy development to reduce the burden of obesity and diet-related disease in Scotland”. They include recommendations for foods (fruit and vegetables, oily fish and red meat) and nutrients (energy, energy density, total fat, saturated fat, trans fatty acids, sugar, salt and fibre). Progress towards the SDGs is monitored using a combination of surveys, principally the secondary analysis of the Living Costs and Food Survey (LCFS). Objective: To obtain estimates of food consumption and nutrient intake for Scotland using LCFS data from 2001 to 2013. Results: For SDGs measured using LCFS data there was little progress towards meeting the goals between 2001 and 2013. This was apparent even amongst least deprived households. Despite evidence of progress for fruit and vegetables up to 2010, consumption subsequently dropped; and there was no change in oil rich fish consumption. Mean total red meat consumption meets the SDG and a significant reduction was found between 2001 and 2013, which was partly accounted for by a fall in red meat products such as sausages and burgers. Energy density increased significantly over time despite a dip in 2012. Saturated fat, total fat and sugar intakes remained considerably higher than the SDGs. Overall there were small but significant decreases in the percentage of food energy from saturated fat and sugars, although intakes appear to have risen since 2011. There was no change in fibre intake. Conclusion: The results presented support work by Food Standards Scotland and the Scottish Government to facilitate improvements to the diet to help prevent obesity. Whilst some very small improvements were observed however, new approaches are required to encourage the population towards a healthier diet to secure Scotland’s health in the future. Funded by Food Standards Scotland, Project Number FS424018. Data provided by DEFRA, Scottish Neighbourhood Statistics, ONS and the UK Data Archive.

Health-related quality of life and determinant factors in celiac disease: a population-based analysis of adult patients in Spain

Background: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. Methods: An observational, cross-sectional study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD-QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. Results: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 ± 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 ± 19.56 points, followed by limitations with 52.3 ± 23.43 points; health problems, with 51.6 ± 26.08 points, and inadequate treatment, with 36.1 ± 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten-free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. Conclusions: The HRQL level of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet.

Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

Background: Patients with lupus nephritis could progress to endstage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis.

Urinary Tract Infection In Renal Transplant Recipients: Incidence, Risk Factors, And Impact On Graft Function.

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival.

Essential regulatory elements for NHE3 gene transcription in renal proximal tubule cells

The objectives of the present study were to identify the cis-elements of the promoter absolutely required for the efficient rat NHE3 gene transcription and to locate positive and negative regulatory elements in the 5’-flanking sequence (5’FS), which might modulate the gene expression in proximal tubules, and to compare this result to those reported for intestinal cell lines. We analyzed the promoter activity of different 5’FS segments of the rat NHE3 gene, in the OKP renal proximal tubule cell line by measuring the activity of the reporter gene luciferase. Because the segment spanning the first 157 bp of 5’FS was the most active it was studied in more detail by sequential deletions, point mutations, and gel shift assays. The essential elements for gene transcription are in the region -85 to -33, where we can identify consensual binding sites for Sp1 and EGR-1, which are relevant to NHE3 gene basal transcription. Although a low level of transcription is still possible when the first 25 bp of the 5’FS are used as promoter, efficient transcription only occurs with 44 bp of 5’FS. There are negative regulatory elements in the segments spanning -1196 to -889 and -467 to -152, and positive enhancers between -889 and -479 bp of 5’FS. Transcription factors in the OKP cell nuclear extract efficiently bound to DNA elements of rat NHE3 promoter as demonstrated by gel shift assays, suggesting a high level of similarity between transcription factors of both species, including Sp1 and EGR-1.

Perspectives of vaccination in Chagas disease revisited

The perspectives for a Chagas Disease vaccine 30 years ago and today are compared. Antigens and adjuvants have improved, but logistic problems remain the same. Sterilizing vaccines have not been produced and animal models for chronic Chagas have not been developed. Vector control has been successful and Chagas incidence has come to a halt. We do not have a population candidate to vaccination now in Brazil. And if we had, we would not know how to evaluate the success of vaccination in a short time period. A vaccine may not seem important at the moment. However, scientific reasons and incertitudes about the future recommend that a search for a vaccine be continued.

ECG scar quantification correlates with cardiac magnetic resonance scar size and prognostic factors in Chagas' disease

Objective To test the hypothesis that 12-lead ECG QRS scoring quantifies myocardial scar and correlates with disease severity in Chagas' heart disease. Design Patients underwent 12-lead ECG for QRS scoring and cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) to assess myocardial scar. Setting University of Sao Paulo Medical School, Sao Paulo, Brazil. Patients 44 Seropositive patients with Chagas' disease without a history of myocardial infarction and at low risk for coronary artery disease. Main outcome measures Correlation between QRS score, CMR-LGE scar size and left ventricular ejection fraction. Relation between QRS score, heart failure (HF) class and history of ventricular tachycardia (VT). Results QRS score correlated directly with CMR-LGE scar size (R=0.69, p<0.0001) and inversely with left ventricular ejection fraction (R=-0.54, p=0.0002), which remained significant in the subgroup with conduction defects. Patients with class II or III HF had significantly higher QRS scores than those with class I HF (5.1 +/- 3.4 vs 2.1 +/- 3.1 QRS points (p=0.002)) and patients with a history of VT had significantly higher QRS scores than those without a history of VT (5.3 +/- 3.2% vs 2.6 +/- 3.4 QRS points (p=0.02)). A QRS score >= 2 points had particularly good sensitivity and specificity (95% and 83%, respectively) for prediction of large CMR-LGE, and a QRS score >= 7 points had particularly high specificity (92% and 89%, respectively) for predicting significant left ventricular dysfunction and history of VT. Conclusions The wide availability of 12-lead ECG makes it an attractive screening tool and may enhance clinical risk stratification of patients at risk for more severe, symptomatic Chagas' heart disease.

Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 mg/kg) or B2 receptor (HOE140, 200 mg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism ( R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1b transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI.

Cellulose modified fibres in cement based composites

The objective of the present work is to evaluate the effect of surface modification of cellulose pulp fibres on the mechanical and microstructure of fibre-cement composites. Surface modification of the cellulose pulps was performed with Methacryloxypropyltri-methoxysilane (MPTS) and Aminopropyltri-ethoxysilane (APTS) in an attempt to improve their durability into fibre-cement composites. The surface modification showed significant influence on the microstructure of the composites on the fibre-matrix interface and in the mineralization of the fibre lumen as seen by scanning electron microscopy (SEM) with back-scattered electron (BSE) detector. Accelerated ageing cycles decreased modulus of rupture (MOR) and toughness (TE) of the composites. Composites reinforced with MPTS-modified fibres presented fibres free from cement hydration products, while APTS-modified fibres presented accelerated mineralization. Higher mineralization of the fibres led to higher embrittlement of the composite after accelerated ageing cycles. These observations are therefore very useful for understanding the mechanisms of degradation of fibre-cement composites. (C) 2009 Elsevier Ltd. All rights reserved.

Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats

We have described a new compound (trans-[RuCl([15]ane N(4))NO](2+)), which in vitro releases NO by the action of a reducing agent such as catecholamines. We investigated the effect of this NO donor in lowering the mean arterial pressure (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured before and after intravenous in bolus injection of the compound in conscious 2K-1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70 +/- 8.70 mmHg, n=5), the MAP was reduced in -34.25 +/- 13.50 mmHg(P < 0.05) 6 h after administration of 10 mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no effect. We have also studied the effect of the injection of 0.1 mmol/L/Kg in normotensive (basal 118.20 +/- 11.25 mmHg, n = 4), moderate (basal 160.90 +/- 2.30 mmHg, n = 6), and severe hypertensive rats (basal 202.46 +/- 16.74 mmHg, n = 6). The compound at the dose of 0.1 mmol/L/Kg did not have effect (P> 0.05) on MAP of normotensive and moderate hypertensive rats. However, in the severe hypertensive rats (basal 202.46 +/- 16.70 mmHg, n = 6) there was a significant reduction on the MAP of -28.64 +/- 12.45 mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10 mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1 mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1 mmol/LKg that produced the maximum relaxation. (C) 2008 Elsevier Inc. All rights reserved.

Test–retest repeatability of self-reported environmental exposures in Parkinson’s disease cases and healthy controls

There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson’s disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test–retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age-and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for ‘lifestyle’ exposures, such as smoking and coffee/tea consumption (kappas 0.70–1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39–0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.

Targeting c-Myb expression in human disease

c-Myb is a transcription factor employed in the haematopoietic system and gastrointestinal tract to regulate the exquisite balance between cell division, differentiation and survival. In its absence, these tissues either fail to form, or show aberrant biology. Mice lacking a functional c-myb gene die in utero by day 15 of development. When inappropriately expressed, as is common in leukaemia and epithelial cancers of the breast, colon and gastro-oesophagus, c-Myb appears to activate gene targets of key importance to cancer progression and metastasis. These genes include cyclooxygenase-2 (COX-2), Bcl-2, Bcl-X-L and c-Myc, which influence diverse processes such as angiogenesis, proliferation and apoptosis. The clinical potential for blocking c-Myb expression in malignancies is based upon strong preclinical data and some trial-based evidence. The modest clinical experience to date has been with haematopoietic malignancies, but other disease classes may be amenable to similar interventions. The frontline agents to achieve this are nuclease-resistant oligodeoxynucleotides (ODNs), which are proving to be acceptable therapeutic reagents in terms of tolerable toxicities and delivery. Nevertheless, further effort must be focused on improving their efficacy, eliminating non-specific toxicity and optimising delivery. Optimisation issues aside, it would appear that anti-c-Myb therapies will be used with most success when combined with other agents, some of which will be established cytotoxic and differentiation-inducing drugs. This review will explore the future strategic use of ODNs in vivo, focusing on a wide spectrum of diseases, including several beyond the haematopoietic malignancies, in which c-Myb appears to play a role.