Variety Of Chronic Disease States Research Articles

Evaluation of Anti-aging Effects of Gemfibrozil on D-galactose induced Aging Mouse Model

Background: Aging is the sequential or progressive changes in the organisms that is associated with increasing susceptibility to disease and death. Advanced age is associated with increased incidence of a variety of chronic disease states that share oxidative stress and inflammation as causative role players. Accumulating evidence in published literature showed that the use of antioxidant and anti-inflammatory agents is an effective approach to alleviate or reverse aging-related changes with consequent reduction of the aging rate and related disease. Gemfibrozil, as a peroxisome proliferator-activated alpha receptor ligand (PPARα), is reported to have antioxidant and inflammatory activity. Aim of the study: Evaluate the anti-aging effect of gemfibrozil on many parameters associated with the aging process on the D-galactose induced aging mice model. Method: The current work was an experimental randomized controlled study in which 60 albino male mice weighing between 25 to 40 gm were randomly divided into 6 groups (10 mice each group). group1 apparently healthy group, receive normal saline orally. Group 2 (age induction group receive D-galactose 500 mg/kg) orally only for 6 weeks, group 3 (+D-galactose 500 mg/kg + vitc 100 mg/kg orally for 6 weeks) group 4 (D-galactose 500 mg/kg for 6 weeks then vitc 100 mg/kg for another 6 consecutive weeks group 5 (D-galactose 500 mg/kg + gemfibrozil 7.5 mg/kg concomitantly for 6 weeks) group 6 (D-galactose 500 mg/kg for 6 weeks then gemfibrozil 7.5 mg/kg for another 6 consecutive weeks. Then animals were sacrificed, liver and kidney were weighed for organ index measurement and tissue sections and heart homogenate were prepared for ELISA assay (measurement of TN alpha, IL1beta, SOD, GPX) and histopathological analysis of myocardial tissue. Results: results showed a significant rise in liver and kidney indices in animals that received gemfibrozil orally administered (during and after induction) compared to aged group, with a dramatic decrease in inflammatory and oxidative stress mediator level and a marked reversal effect on myocardial hypertrophy induced by D-galactose. Conclusion: Gemfibrozil oral administration alleviates aging-associated atrophic changes in liver and kidney, oxidative stress and inflammatory state in myocardial tissue and reverses aging-related myocardial hypertrophic changes.

Exercise is Medicine: The Prevalence of Exercise Prescription‐related Course Offerings in U.S. Physician Assistant Program Curricula

Exercise has proven to be beneficial in the prevention of chronic disease. In addition, exercise can improve the pathogenesis and symptoms associated with a variety of chronic disease states and can also attenuate drug-induced adverse effects. Hence, exercise has been described as a drug-free polypill. Exercise is Medicine®, a joint initiative between the American Medical Association and the American College of Sports Medicine, was launched in 2007 to call on all health care providers to counsel patients and prescribe exercise in the prevention and treatment of chronic disease. However, based on self-reported data, 51% of American adults still do not meet the national physical activity guidelines. Even more, the prevalence of inactivity has been reported to be much higher when the data is based off of objective measures, such as accelerometry. The high prevalence of inactivity is likely due to multiple factors, including under-education of medical professionals on how to council patients and develop exercise prescriptions. In the U.S. only 32.4% of patients seen by clinicians in 2010 received physical activity counseling that year. Therefore, the aim of the study was to determine the prevalence of required course offerings in U.S. physician assistant program curricula regarding training in exercise prescription (Rx). Program websites were accessed in 2020 for information regarding course offerings in Master of Physician Assistant Studies programs. Only those programs whose course descriptions of all the required courses were accessible online were included in the analysis. Three individuals independently analyzed course titles, course descriptions, and topics (if provided) of all programs for the search terms “exercise Rx”, “exercise”, “fitness”, and “physical activity”. After the analysis was complete, the data was combined and discrepancies were spot checked by a fourth individual. The study aimed to determine how many programs offered courses with the terms “exercise Rx”, “exercise”, “fitness”, and/or “physical activity” in the course title, course description, or course topics. Ninety one percent (165) of U.S. programs were included in the analysis. Only one program offered a required course with the term “exercise Rx” in the title, description, or course topics. This was a two credit course entitled Public Health. Five programs offered courses with the terms “exercise”, “fitness”, or “physical activity” in the title, description, or topics. These courses ranged between 1.0-2.5 credits. Three of the five courses were named Health Promotion and Disease Prevention. The data suggests that physician assistant students may be under-educated in the area of exercise Rx, which may contribute to the high prevalence of inactivity.

The Prevalence of Exercise Prescription‐related Course Offerings in U.S. Medical School Curricula: Exercise is Medicine®

Exercise training has proven to be beneficial in the prevention of disease. In addition, exercise can improve the pathogenesis and symptoms associated with a variety of chronic disease states and can attenuate drug‐induced adverse effects. Exercise is a drug‐free polypill. Exercise is Medicine®, a joint initiative between the American Medical Association and the American College of Sports Medicine, was launched in 2007 to call on all health care providers to counsel patients and prescribe exercise in the prevention and treatment of chronic disease states. However, according to the Behavioral Risk Factor Surveillance System data, 48% of Americans still do not meet the national physical activity guidelines. The cause behind the high prevalence is unknown and likely multifactorial. One factor may be under‐education of medical professionals on how to council patients and develop exercise prescriptions. Therefore, the aim of the study was to determine the prevalence of course offerings in U.S. medical school curricula regarding training in exercise prescription. School websites were accessed for information regarding course offerings in MD and OD programs. Only those programs whose course descriptions of their full curriculum were accessible online were included in the analysis. The search terms used were exercise prescription, exercise, fitness, and physical activity. 61% (86/141) and 69% (24/35) of MD and OD granting programs were included in the analysis, respectively. Four programs offered courses with the term “exercise prescription” in the course title or description. Only 4 programs offered courses with the terms “exercise, fitness, or physical activity” in the course title. 36% of programs offered courses with the terms “exercise prescription, exercise, fitness, or physical activity” in the course description or course topics, with only 17% of those programs offering required courses. The data suggests that medical students may be under‐educated in the area of exercise prescription, which may contribute to the high prevalence of inactivity.

Evaluation of Diabetes Education and Pharmacist Interventions in a Rural, Primary Care Setting.

Diabetes affects 29.1 million Americans, or 9.3% of the U.S. population, and is associated with significant costs to the health care system (1). The estimated total cost of diabetes increased from $132 billion in 2002 to $245 billion in 2012. Average medical expenditures are 2.3 times higher in patients with diabetes compared to those without diabetes (1). Diabetes self-management education (DSME) is the ongoing process of facilitating the knowledge, skills, and ability necessary for diabetes self-care (2). Patients with diabetes make multiple decisions every day about their health management. The literature supports the effectiveness of diabetes education to improve clinical outcomes and quality of life in this complicated patient population (3). General practice providers have limited time to spend with patients for diabetes education (4). To overcome this barrier, an interprofessional approach to care has been used to give patients the tools they need to achieve glycemic targets. Because of their medication expertise in a variety of chronic disease states, pharmacists are well positioned to provide comprehensive diabetes services, including basic education and counseling on diabetes topics such as blood glucose management, diet, and exercise. Pharmacists also have the ability to monitor patients’ laboratory testing values and to recommend therapies for hypertension, dyslipidemia, cardiovascular disease, and microvascular complications, which are often seen with advanced diabetes (5). Diabetes regimens have become more involved as multiple new therapies have become available within the past several years (6). Patient counseling is imperative regarding new medications such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium–glucose cotransporter 2 inhibitors, and concentrated insulins. With multidrug regimens that include new agents, the risk of adverse effects and hypoglycemia increases. Pharmacists can draw on their training and expertise to improve both clinical and economic outcomes related to diabetes medications (5). Because of the versatility of …

The prevalence of exercise prescription-related course offerings in United States pharmacy school curricula: Exercise is Medicine.

Exercise training has proven to be beneficial in the prevention of disease. In addition, exercise can improve the pathogenesis and symptoms associated with a variety of chronic disease states and can attenuate drug-induced adverse effects. Exercise is a drug-free polypill. Because the benefits of exercise are clear and profound, Exercise is Medicine, a joint initiative between the American Medical Association and American College of Sports Medicine, was launched in 2007 to call on all health care providers to counsel patients and prescribe exercise in the prevention and treatment of chronic disease states. Pharmacists play an increasing role in direct patient care and are the most accessible health care providers in the community. Thus, pharmacists should be knowledgeable in counseling patients on the frequency, intensity, time, and type of exercise that is appropriate for various conditions and disease states. The aim of the present study was to determine the prevalence of didactic course offerings in United States pharmacy school curricula regarding training in exercise prescription. School websites were accessed for information regarding course offerings in PharmD programs. No United States pharmacy schools offered courses that were dedicted to the role of exercise in disease prevention or exercise prescription in disease management. Ninety percent of pharmacy schools did not offer courses with the keywords "exercise," "fitness, or "physical activity" in the title or description. The data suggest that student pharmacists are not adequately trained to counsel patients on the benefits of exercise or exercise prescription.

Endoplasmic Reticulum (ER) Stress Induces p44/42 Mitogen‐Activated Protein Kinase (MAPK) Signaling, Inflammation and Renin‐Angiotensin System (RAS) Activity in Forebrain and Contributes to Sympathetic Nerve Activity in Heart Failure Rats

The unfolded protein response to ER stress, induced by an excessive accumulation of unfolded proteins in the ER lumen, activates a series of downstream signal transduction pathways including MAPK signaling. ER stress has been implicated in the pathophysiology of a variety of chronic disease states including diabetes mellitus, obesity and cardiovascular diseases. A role for brain ER stress in angiotensin II ‐induced hypertension in mice was recently reported. We have found that ER stress is upregulated in the subfornical organ (SFO) and hypothalamic paraventricular nucleus (PVN) of rats with ischemia‐induced heart failure (HF). We have also found that MAPK signaling is upregulated in the SFO and PVN of these HF rats and contributes to sympathetic excitation. The present study sought to determine whether brain ER stress induces p44/42 MAPK signaling and the upregulation of excitatory/inflammatory mediators in SFO and PVN and increased sympathetic nerve activity in HF. HF and SHAM rats were produced by coronary artery ligation or sham ligation, respectively. HF rats received a 4‐week intracerebroventricular (ICV) infusion (0.25 μl/hr) of vehicle (VEH) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10μg/day). SHAM rats received ICV VEH for 4 weeks. Total and phosphorylated p44/42 MAPK in the SFO and PVN were measured by Western blot. Immunofluorescence for phosphorylated p44/42 MAPK in the SFO and PVN was visualized by confocal microscopy. The mRNA levels of inflammatory mediators tumor necrosis factor (TNF) ‐α, interleukin (IL)‐1β, cyclooxygenase (COX) ‐2, COX‐1 and RAS components renin angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1‐R) in SFO and PVN were measured by real‐time PCR. Plasma norepinephrine (NE) was measured by ELISA. Compared with SHAM rats, VEH‐treated HF rats had higher (*p<0.05, n=6 in each group) levels of phosphorylated p44/42 MAPK (normalized to total p44/42 MAPK) in SFO and PVN. In HF rats treated with TUDCA, phosphorylated p44/42 MAPK was lower in the SFO and PVN by Western blot (~45 %*) and by immunofluorescent imaging. VEH‐treated HF rats had significantly elevated (2.2–3.6 fold*) mRNA levels for TNF‐α, IL‐1β, COX ‐2, ACE and AT1‐R in the SFO and PVN, compared with VEH‐treated SHAM rats, but these levels were markedly reduced (37–51%*, n=6 in each group) in the TUDCA‐treated HF rats. The plasma NE level (ng/ml) was higher in VEH‐treated HF (38.86 ± 2.35*) than SHAM (18.64 ± 2.59) rats; this increase was significantly attenuated in the HF rats treated with TUDCA. These data demonstrate that brain ER stress induces MAPK signaling, inflammation and RAS activity in key cardiovascular regulatory regions of the brain and contributes to the sympathetic activation in HF. Brain ER stress is a potential target for therapeutic intervention in HF.Support or Funding InformationSupported by NIH RO1 HL096671 and R01 HL073986

Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes.

Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera) derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation.

Vitamin D Supplementation and Health-Related Quality of Life: A Systematic Review of the Literature

Vitamin D deficiency and insufficiency are highly prevalent worldwide and thought to potentiate a variety of chronic disease states, including diabetes, cancer, and depression. Routine vitamin D supplementation is often needed to meet vitamin D requirements. Little is known regarding the effect of vitamin D supplementation on quality of life. The purpose of this article was to systematically review the literature regarding quality-of-life outcomes from vitamin D supplementation in healthy and clinical populations. Clinical trials of vitamin D supplementation, where quality-of-life outcomes were reported, were selected from Medline and Web of Science databases. Inclusion criteria were English language articles available online (published between 1950 and May 2014), primary research articles, studies conducted on human beings, and treatment/supplementation with vitamin D. Articles were excluded if they involved topical vitamin D application or implicit cotreatment with other vitamins (eg, multivitamins). Articles selected for review were examined for process and methodologic quality using validated methodologies. A total of 15 articles met the inclusion criteria for review. Interventions were highly variable in terms of study population (eg, healthy/diseased, children/elderly, and baseline vitamin D status) vitamin D dose, and duration of follow-up. Vitamin D supplementation ranged from 400 IU/day for an average of 7.1 years, to a single 300, 000 IU dose. The main tools used to capture quality of life were adaptations of validated, questionnaires (Medical Outcomes Study Short Form 36-item questionnaire and EuroQOL five dimension questionnaire). Vitamin D supplementation was not associated with significant changes in quality of life. Studies that reported changes in quality of life as a result of vitamin D supplementation were in clinical populations on short-term vitamin D. Most articles reviewed displayed poor methodologic quality (eg, no randomization/blinding, dropout description, or vitamin D assessment). Current evidence indicates that vitamin D supplementation may have a small to moderate effect on quality of life when used on a short-term basis in diseased populations. However, the evidence for a beneficial effect of long-term vitamin D supplementation on health-related quality of life is lacking.

How clinical pharmacists can improve outpatient diabetes care

team members and unified messaging to patients are sometimes challenging in team care environments, recent advances in the use of electronic health records (EHRs) and other communications technology have improved key aspects of patient-centered care coordination across a range of care providers [4,5]. In addition to increased involvement by other diabetes care providers, pharmacists have been playing an increasingly prominent role in outpatient diabetes care. The value of pharmacist care has been widely recognized [6], and pharmacist-provided medication therapy management (MTM) services have been successful in reducing direct medical costs, improving clinical outcomes, achieving quality measures and resolving medication-related problems in a variety of chronic disease states, including diabetes and hypertension, and among medically complex patients [7]. It is important to note that nearly all patients with diabetes are on multiple medications [8], and most see a pharmacist multiple times each year to obtain their medications and supplies. Therefore, pharmacists have a natural opportunity to add substantial value to the care of large numbers Uncontrolled diabetes creates major cost and care burdens on the healthcare system. Management of diabetes is time and resource intensive, medically complex and requires patient engagement to be fully effective [1]. Despite improvement in the last decade, outpatient diabetes care is far from optimal [2]. Especially in the context of an escalating number of Americans with diabetes, the current influx of newly insured patients into the primary care system, and increasing scarcity of primary care providers, it is important to consider new strategies to provide high-quality care to the more than 25 million Americans with diabetes mellitus [3]. The value of team-based, well-coordinated care and unified messaging to patients has long been recognized as a cornerstone of chronic disease management [4], and diabetes educators, nutritionists, diabetes nurse clinicians and other care providers have joined with primary care providers, diabetologists, endocrinologists and others to provide team-based diabetes care. Each team member brings an important skill set and perspective that may be helpful to patients with diabetes. While clear communication among

Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism

The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

Efficacy of a meal replacement diet plan compared to a food-based diet plan after a period of weight loss and weight maintenance: a randomized controlled trial

BackgroundObesity has reached epidemic proportions in the United States. It is implicated in the development of a variety of chronic disease states and is associated with increased levels of inflammation and oxidative stress. The objective of this study is to examine the effect of Medifast's meal replacement program (MD) on body weight, body composition, and biomarkers of inflammation and oxidative stress among obese individuals following a period of weight loss and weight maintenance compared to a an isocaloric, food-based diet (FB).MethodsThis 40-week randomized, controlled clinical trial included 90 obese adults with a body mass index (BMI) between 30 and 50 kg/m2, randomly assigned to one of two weight loss programs for 16 weeks and then followed for a 24-week period of weight maintenance. The dietary interventions consisted of Medifast's meal replacement program for weight loss and weight maintenance, or a self-selected, isocaloric, food-based meal plan.ResultsWeight loss at 16 weeks was significantly better in the Medifast group (MD) versus the food-based group (FB) (12.3% vs. 6.9%), and while significantly more weight was regained during weight maintenance on MD versus FB, overall greater weight loss was achieved on MD versus FB. Significantly more of the MD participants lost ≥ 5% of their initial weight at week 16 (93% vs. 55%) and week 40 (62% vs. 30%). There was no difference in satiety observed between the two groups during the weight loss phase. Significant improvements in body composition were also observed in MD participants compared to FB at week 16 and week 40. At week 40, both groups experienced improvements in biochemical outcomes and other clinical indicators.ConclusionsOur data suggest that the meal replacement diet plan evaluated was an effective strategy for producing robust initial weight loss and for achieving improvements in a number of health-related parameters during weight maintenance, including inflammation and oxidative stress, two key factors more recently shown to underlie our most common chronic diseases.Trial RegistrationClinicalTrials.gov NCT01011491

Clinical Effects of Colonic Cleansing for General Health Promotion: A Systematic Review

The practice of colonic cleansing to promote general health and well-being continues to generate interest among the lay population. These practices are widely touted as adjuncts to improve vitality and as therapeutic modalities to minimize the symptoms, or prevent the actual development, of a variety of chronic disease states. The data supporting colonic cleansing and body "detoxification" have not been studied well in a systematic manner. This report describes a systematic review of the published literature of both the traditional and complementary and alternative medicine arenas that was performed in an attempt to qualify and quantify the value of colonic cleansing. The investigators concluded that there are no methodologically rigorous controlled trials of colonic cleansing to support the practice for general health promotion. Conversely, there are multiple case reports and case series that describe the adverse effects of colonic cleansing. The practice of colonic cleansing to improve or promote general health is not supported in the published literature and cannot be recommended at this time.

Metabolic consequences of physical inactivity

Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.

Regulation of muscle cathepsin B proteolytic activity in protein-depleted patients with chronic diseases

Background & aims: The lysosomal cathepsin system contributes to degrading cellular skeletal muscle proteins in many catabolic diseases. We have assessed the relationships between cathepsin B mRNA levels and the enzyme activity for this protease in the skeletal muscle of acutely ill patients with severe trauma ( n=7) and in patients with a variety of chronic disease states (hemodialysis, n=3; nervous anorexia, n=1; type 2 diabetes, n=2; prolonged immobilization, n=1). Methods: Muscle biopsies were taken from the vastus lateralis muscle in patients and controls to assess tissue levels of cathepsin B mRNA by competitive–quantitative polymerase chain reaction, cathepsin B proteolytic activity and myofibrillar protein content as alkali-soluble protein to DNA ratio (ASP/DNA). In the trauma patients, muscle protein loss was assessed by the arteriovenous balance technique as rate of phenylalanine release from leg muscle. Results: The acute trauma patients exhibited a significant net phenylalanine release from leg muscle (33±4 nmol phenylalanine/min/100 ml leg volume) despite a continuous nutritional support. The muscle ASP/DNA ratio was lower ( P<0.05) in the patients with chronic diseases (383±33) than in groups of healthy controls (554±41) or of uncomplicated, moderately obese subjects (525±26). Cathepsin B mRNA levels were 6–10 times greater ( P<0.05) in the patients with acute trauma or chronic catabolic diseases than in the healthy subjects. Cathepsin B enzymatic activity were 2–3 times greater ( P<0.05) in the chronic and acute patients than in the group of uncomplicated, moderately obese subjects. Regression analysis between cathepsin B mRNA and cathepsin B enzymatic activity indicates a significant direct correlation ( r=0.84; P<0.05) in the chronic catabolic conditions, but not in the acute trauma patients ( r=−0.05). Conclusions:In skeletal muscle of patients with stable chronic catabolic diseases, cathepsin B activity is directly related to cathepsin B mRNA levels, suggesting that in these patients this enzyme could be mainly regulated at the level of gene transcription.