34 research outputs found
Primary prevention of diabetes mellitus type 2 and cardiovascular diseases using a cognitive behavior program aimed at lifestyle changes in people at risk: Design of a randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>The number of people with cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) is growing rapidly. To a large extend, this increase is due to lifestyle-dependent risk factors, such as overweight, reduced physical activity, and an unhealthy diet. Changing these risk factors has the potential to postpone or prevent the development of T2DM and CVD. It is hypothesized that a cognitive behavioral program (CBP), focused in particular on motivation and self-management in persons who are at high risk for CVD and/or T2DM, will improve their lifestyle behavior and, as a result, will reduce their risk of developing T2DM and CVD.</p> <p>Methods</p> <p>12,000 inhabitants, 30-50 years of age living in several municipalities in the semi-rural region of West-Friesland will receive an invitation from their general practitioner (n = 13) to measure their own waist circumference with a tape measure. People with abdominal obesity (male waist â„ 102 cm, female waist â„ 88 cm) will be invited to participate in the second step of the screening which includes blood pressure, a blood sample and anthropometric measurements. T2DM and CVD risk scores will then be calculated according to the ARIC and the SCORE formulae, respectively. People with a score that indicates a high risk of developing T2DM and/or CVD will then be randomly assigned to the intervention group (n = 300) or the control group (n = 300).</p> <p>Participants in the intervention group will follow a CBP aimed at modifying their dietary behavior, physical activity, and smoking behavior. The counseling methods that will be used are <it>motivational interviewing </it>(MI) and <it>problem solving treatment </it>(PST), which focus in particular on intrinsic motivation for change and self-management of problems of the participants. The CBP will be provided by trained nurse practitioners in the participant's general practice, and will consists of a maximum of six individual sessions of 30 minutes, followed by 3-monthly booster sessions by phone. Participants in the control group will receive brochures containing health guidelines regarding physical activity and diet, and how to stop smoking. The primary outcome measures will be changes in T2DM and CVD risk scores. Secondary outcome measures will be changes in lifestyle behavior and cost-effectiveness and cost-utility ratios. All relevant direct and indirect costs will be measured, and there will be a follow-up of 24 months.</p> <p>Discussion</p> <p>Changing behaviors is difficult, requires time, considerable effort and motivation. Combining the two counseling methods MI and PST, followed by booster sessions may result in sustained behavioral change.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN59358434</p
Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts
Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).
Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of âtotal Alâassumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold.
The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2âąâ, generate Al superoxides [Al(O2âą)](H2O5)]+ 2. Semireduced AlO2âą radicals deplete mitochondrial Fe and promote generation of H2O2, O2 âą â and OHâą. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates.
Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants.
The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances
Chemical characteristics for optimizing CYP2E1 inhibition
Cytochrome P450 2E1 (CYP2E1) expression and activity in the liver is associated with the degree of liver damage in patients with alcoholic steatohepatitis (ASH) as well as non-alcoholic steatohepatitis (NASH). CYP2E1 is known to generate reactive oxygen species, which leads to oxidative stress, one of the hallmarks of both diseases. Apart from ROS, toxic metabolites can be formed by CYP2E1 metabolism, further potentiating liver injury. Therefore, CYP2E1 is implicated in the pathogenesis of ASH and NASH. The aim of this study was to determine the chemical characteristics of compounds that are important to inhibit CYP2E1. To this end, structurally related analogues that differed in their lipophilic, steric and electronic properties were tested. In addition, homologues series of aliphatic primary alcohols, secondary alcohols, aldehydes, ketones and carboxylic acids were tested. It was found that inhibition of the CYP2E1 activity is primarily governed by lipophilicity. The optimal log D7.4 (octanol/water distribution coefficient at pH 7.4) value for inhibition of CYP2E1 was approximately 2.4. In the carboxylic acids series the interaction of the carboxylate group with polar residues lining the CYP2E1 active site also has to be considered. This study sketches the basic prerequisites in the search for inhibitors of CYP2E1, which would strengthen our therapeutic armamentarium against CYP2E1 associated diseases, such as ASH and NASH
The flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside is able to protect endothelial cells by a direct antioxidant effect
The flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) is an effective protector against doxorubicin induced toxicity which has been related to the antioxidant activity of monoHER. The present study examines the potential relevance of the direct scavenging activity of the flavonoid. The potency of the direct antioxidant effect was confirmed by its instantaneous protection against intracellular oxidative stress in human umbilical vein endothelial cells at therapeutically achievable concentrations (EC50= 60 nM) underpinning the involvement of a direct scavenging activity. This direct effect of monoHER is substantiated by (i) its site specific scavenging effect, i.e. on a molecular level monoHER is positioned at the location of radical formation, (ii) its position in the antioxidant network, i.e. on a biochemical level oxidized monoHER quickly reacts with ascorbate or glutathione, (iii) its location in the vascular system, i.e. on a cellular level monoHER is localized in the endothelial and smooth muscle cells in the vascular wall. It is concluded that the flavonoid monoHER can display a physiologically important direct antioxidant effect
The flavonoid monoHER promotes the adaption to oxidative stress during the onset of NAFLD
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. An evidence-based pharmacological treatment for NAFLD is still lacking, but flavonoids have shown therapeutic potential. The present study was designed to investigate the effect of the flavonoid monoHER on the onset of NAFLD in Ldlr(-/-) mice on a high-fat and high-cholesterol diet. The focus was put on the effect on oxidative stress as well as the adaptive response. Wild type mice served as a control and the effect of monoHER was compared to that of a placebo. In the Ldlr(-/-) group, monoHER provided only a mild protection against oxidative stress. In the placebo Ldlr(-/-) group an adaptive response elicited by the NRF2 antioxidant defense system was observed, evidenced by a higher HO-1 and Gpx3 gene expression, as well as an increased redox status, evidenced by the higher GSH/GSSG ratio. In the monoHER treated Ldlr(-/-) group both the adaptive response as well as the increase in redox status tended to be higher, although this did not reach significance on a group level. Unexpectedly, a strong within animal relationship was found that links a high adaptive response to a low redox status in the monoHER Ldlr(-/-) group. This correlation was absent in the placebo and wild type group. The concept that emerges is that a thiol-reactive oxidation product of monoHER, formed during oxidative stress, selectively induces the NRF2 pathway and enforces the endogenous antioxidant shield, to provide protection against NAFLD
Elevated citrate levels in non-alcoholic fatty liver disease: The potential of citrate to promote radical production
AbstractPlasma citrate levels were found to be elevated in non-alcoholic fatty liver disease (NAFLD) patients. Cellular experiments indicated that increased citrate levels might originate from an excess of fatty acids. The impact of elevated citrate levels on oxidative stress was examined. It was found that citrate stimulated hydrogen peroxide induced intracellular oxidative stress in HepG2 cells. This was related to the promotion of iron mediated hydroxyl radical formation from hydrogen peroxide by citrate. The stimulating effect of citrate on the reactivity of iron promotes oxidative stress, a crucial process in the progression of NAFLD
Equity-specific effects of 26 Dutch obesity-related lifestyle interventions
Context Reducing health inequalities is a policy priority in many developed countries. Little is known about effective strategies to reduce inequalities in obesity and its underlying behaviors. The goal of the study was to investigate differential effectiveness of interventions aimed at obesity prevention, the promotion of physical activity or a healthy diet by SES. Evidence acquisition Subgroup analyses in 2010 and 2011 of 26 Dutch studies funded by The Netherlands Organization for Health Research and Development after 1990 (n=17) or identified by expert contact (n=9). Methodologic quality and differential effects were synthesized in harvest plots, subdivided by setting, age group, intensity, and time to follow-up. Evidence synthesis Seven lifestyle interventions were rated more effective and four less effective in groups with high SES; for 15 studies no differential effects could be demonstrated. One study in the healthcare setting showed comparable effects in both socioeconomic groups. The only mass media campaign provided modest evidence for higher effectiveness among those with high SES. Individually tailored and workplace interventions were either more effective in higher-SES groups (n=4) or no differential effects were demonstrated (n=9). School-based studies (n=7) showed mixed results. Two of six community studies provided evidence for better effectiveness in lower-SES groups; none were more effective in higher-SES groups. One high-intensity community-based study provided best evidence for higher effectiveness in low-SES groups. Conclusions Although for the majority of interventions aimed at obesity prevention, the promotion of physical activity, or a healthy diet, no differential effectiveness could be demonstrated, interventions may widen as well as reduce socioeconomic inequalities in these outcomes. Equity-specific subgroup analyses contribute to needed knowledge about what may work to reduce socioeconomic inequalities in obesity and underlying health behaviors
A cluster-randomized controlled trial to study the effectiveness of a protocol-based lifestyle program to prevent type 2 diabetes in people with impaired fasting glucose
<p>Background: Effective diabetes prevention strategies that can be implemented in daily practice, without huge amounts of money and a lot of personnel are needed. The Dutch Diabetes Federation developed a protocol for coaching people with impaired fasting glucose (IFG; according to WHO criteria: 6.1 to 6.9 mmol/l) to a sustainable healthy lifestyle change: 'the road map towards diabetes prevention' (abbreviated: Road Map: RM). This protocol is applied within a primary health care setting by a general practitioner and a practice nurse. The feasibility and (cost-) effectiveness of care provided according to the RM protocol will be evaluated.</p><p>Methods/Design: A cluster randomised clinical trial is performed, with randomisation at the level of the general practices. Both opportunistic screening and active case finding took place among clients with high risk factors for diabetes. After IFG is diagnosed, motivated people in the intervention practices receive 3-4 consultations by the practice nurse within one year. During these consultations they are coached to increase the level of physical activity and healthy dietary habits. If necessary, participants are referred to a dietician, physiotherapist, lifestyle programs and/or local sports activities. The control group receives care as usual. The primary outcome measure in this study is change in Body Mass Index (BMI). Secondary outcome measures are waist circumference, physical activity, total and saturated fat intake, systolic blood pressure, blood glucose, total cholesterol, HDL cholesterol, triglycerides and behaviour determinants like risk perception, perceived knowledge and motivation. Based on a sample size calculation 120 people in each group are needed. Measurements are performed at baseline, and after one (post-intervention) and two years follow up. Anthropometrics and biochemical parameters are assessed in the practices and physical activity, food intake and their determinants by a validated questionnaire. The cost-effectiveness is estimated by using the Chronic Disease Model (CDM). Feasibility will be tested by interviews among health care professionals.</p><p>Discussion: The results of the study will provide valuable information for both health care professionals and policy makers. If this study shows the RM to be both effective and cost-effective the protocol can be implemented on a large scale.</p><p>Trial registration: ISRCTN41209683. Ethical approval number: NL31342.075.10.</p>