Pediatric Obesity: Influence on Drug Dosing and Therapeutics

Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of US children and adolescents. Severe obesity (³120% of the 95th percentile of BMI-for-age, or a BMI of ³35 kg/m2) is the fastest growing subgroup and now approaches 6% of all US youth. Health consequences (e.g., type 2 diabetes, coronary heart disease) are related in a dose-dependent manner to severity of obesity. Since therapeutic interventions are less effective in severe obesity, prevention is a high priority. Treatment plans involving combinations of behavioral therapy, nutrition and exercise achieve limited success. Only one drug, orlistat, is FDA-approved for long-term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as pathophysiology of obesity and comorbidities. Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat storage disorder is fundamentally inaccurate. The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity

New Lipid Lowering Therapies for Cardiovascular and Metabolic Diseases: Lessons from the Past and Future Challenges

This book illustrates some of the most recent research efforts that have been made in lowering plasma cholesterol levels in patients with CVD. Selected articles aimed to illuminate advances and urgent challenges in the management of CVD, including disease management using statin-combined therapeutic strategies

Treatment of Nonalcoholic Fatty Liver Disease through Changes in Gut Microbiome and Intestinal Epithelial Barrier

Nonalcoholic fatty liver disease (NAFLD) is a leading liver disease worldwide with a prevalence of approximately 25% among adult population. The highest prevalence is observed in Middle East and the lowest prevalence in Africa. NAFLD is a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Pro-inflammatory diet, overweight/obesity, inflammation, insulin resistance, prediabetes, type 2 diabetes, dyslipidemia, disrupted gut microbiome, and impaired intestinal barrier function are important risk factors associated with and/or contributing to NAFLD. Gut microbiome is a complex and diverse microbial ecosystem essential for the maintenance of human health. It is influenced by several factors including diet and medications. Gut microbiome can be disrupted in NAFLD. Intestinal epithelial barrier is the largest and most important barrier against the external environment and plays an important role in health and disease. Several factors including diet and gut microbiome impact intestinal barrier function. NAFLD can be associated with impaired intestinal barrier function (increased intestinal permeability). There are no specific drugs that directly treat NAFLD. The first-line therapy of NAFLD is currently lifestyle intervention. Weight loss is an important component in the treatment of NAFLD subjects who have excess body weight. Gut microbiome and intestinal epithelial barrier are becoming promising targets for the treatment of several diseases including NAFLD. In the absence of approved pharmacotherapy for the treatment of NAFLD/NASH, in addition to lifestyle intervention and weight loss (in case of excess body weight), focus should also be on correcting gut microbiome and intestinal permeability (directly and/or through gut microbiome modulation) using diet (e.g., low-fat diet, high-fiber diet, and Mediterranean diet), prebiotics (nondigestible food ingredients), probiotics (nonpathogenic living microorganisms), synbiotics (combination of prebiotics and probiotics), and fecal microbiota transplantation (transfer of healthy stool)

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress and chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these health conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources with potential therapeutic beneficial effects being shown to potentially support and, in some cases, replace pharmacological treatments, especially for individuals who do not qualify for conventional pharmacological treatments. This review delves into the burgeoning field of nutraceutical-based pharmacological modulation as a promising strategy for attenuating oxidative stress and inflammation in metabolic and cardiometabolic disorders. Drawing from an extensive body of research, the review showcases various nutraceutical agents, such as polyphenols, omega-3 fatty acids, and antioxidants, which exhibit antioxidative and anti-inflammatory properties. All these can be classified as novel nutraceutical-based drugs that are capable of regulating pathways to mitigate oxidative-stress- and inflammation-associated metabolic diseases. By exploring the mechanisms through which nutraceuticals interact with oxidative stress pathways and immune responses, this review highlights their potential to restore redox balance and temper chronic inflammation. Additionally, the challenges and prospects of nutraceutical-based interventions are discussed, encompassing bioavailability enhancement, personalized treatment approaches, and clinical translation. Through a comprehensive analysis of the latest scientific reports, this article underscores the potential of nutraceutical-based pharmacological treatment modulation as a novel avenue to fight oxidative stress and inflammation in the complex landscape of metabolic disorders, particularly accentuating their impact on cardiovascular health

A look to the future in non-alcoholic fatty liver disease: are glucagon-like peptide-1 analogues or sodium-glucose co-transporter-2 inhibitors the answer?

The increasing prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD) is a growing public health concern associated with significant morbidity, mortality and economic cost, particularly in those who progress to cirrhosis. Medical treatment is frequently limited, with no specific licensed treatments currently available for people with NAFLD. Its association with diabetes raises the possibility of shared mechanisms of disease progression and treatment. With the ever-growing interest in the non-glycaemic effects of diabetes medications, studies and clinical trials have investigated hepatic outcomes associated with the use of drug classes used for people with type 2 diabetes (T2D), such as glucagon-like peptide-1 (GLP-1) analogues or sodium-glucose co-transporter-2 (SGLT2) inhibitors. Studies exploring the use of GLP-1 analogues or SGLT2 inhibitors in people with NAFLD have observed improved measures of hepatic inflammation, liver enzymes and radiological features over short periods. However, these studies tend to have variable study populations and inconsistent reported outcomes, limiting comparison between drugs and drug classes. As these drugs appear to improve biomarkers of NAFLD, clinicians should consider their use in patients with NAFLD and T2D. However, further evidence with greater participant numbers and longer trial durations is required to support specific licensing for people with NAFLD. Larger trials would allow reporting of major adverse hepatic events, akin to cardiovascular and renal outcome trials, to be determined. This would provide a more meaningful evaluation of the impact of these drugs in NAFLD. Nevertheless, these drugs represent a future potential therapeutic avenue in this difficult-to-treat population and may beget significant health and economic impacts

Diseases of Renal Parenchyma

Clinical nephrology is an evolving speciality in which the amount of information is growing daily. This book gives quick access to some important clinical conditions encountered in nephrology including the diseases of glomeruli, tubules and interstitium. It presents the latest information on pathophysiology, diagnosis and management of important diseases of renal parenchyma. The information is presented in a very user friendly and accessible manner while the treatment algorithms enable the reader to quickly access expert advice on arriving at the most appropriate treatment regimen. The book discusses the renal involvement in various systemic diseases including diabetes and autoimmune diseases. Diabetic nephropathy is fast becoming the commonest cause of end stage renal disease all over the globe and is discussed in this book. The editors believe that this book will be a valuable addition to the reader's library

Ischemic Heart Disease in the Context of Different Comorbidities

Ischemic heart disease is a cardiovascular condition with very high prevalence worldwide and a major source of morbidity and mortality, especially in the geriatric population. The management of coronary artery disease is one that requires high-level expertise. The presence of comorbidities, usually multiple at advanced ages, makes the diagnosis and therapy very challenging. In this setting, the effort of a multidisciplinary team is urgently needed to achieve integrated management of these cases, being the only one capable of leading to the best results for the patient.The purpose of this reprint is to bring together the experience of specialists in treating ischemic heart disease in the presence of major related conditions that require particular modulations of diagnostic and therapeutic interventions. The chapters address difficult areas of interference between ischemic heart disease and frailty, cancer, liver diseases, inflammatory bowel disease and the new SARS-CoV-2 infection. Special consideration is granted to cardiac remodeling and progression to heart failure. Niche topics such as acute coronary syndromes triggered by carbon monoxide poisoning are present as well. The book also contains a particularly interesting chapter dedicated to the genetic substrate of ischemic heart disease, which once again emphasizes the need for a multidisciplinary team approach to this disease.We consider the reprint an excellent source of information for medical practitioners who have to solve complex cases of ischemic heart disease

Atherogenesis

This monograph will bring out the state-of-the-art advances in the dynamics of cholesterol transport and will address several important issues that pertain to oxidative stress and inflammation. The book is divided into three major sections. The book will offer insights into the roles of specific cytokines, inflammation, and oxidative stress in atherosclerosis and is intended for new researchers who are curious about atherosclerosis as well as for established senior researchers and clinicians who would be interested in novel findings that may link various aspects of the disease

Incorporating standardised drift-tube ion mobility to enhance non-targeted assessment of the wine metabolome (LC×IM-MS)

Liquid chromatography with drift-tube ion mobility spectrometry-mass spectrometry (LCxIM-MS) is emerging as a powerful addition to existing LC-MS workflows for addressing a diverse range of metabolomics-related questions [1,2]. Importantly, excellent precision under repeatability and reproducibility conditions of drift-tube IM separations [3] supports the development of non-targeted approaches for complex metabolome assessment such as wine characterisation [4]. In this work, fundamentals of this new analytical metabolomics approach are introduced and application to the analysis of 90 authentic red and white wine samples originating from Macedonia is presented. Following measurements, intersample alignment of metabolites using non-targeted extraction and three-dimensional alignment of molecular features (retention time, collision cross section, and high-resolution mass spectra) provides confidence for metabolite identity confirmation. Applying a fingerprinting metabolomics workflow allows statistical assessment of the influence of geographic region, variety, and age. This approach is a state-of-the-art tool to assess wine chemodiversity and is particularly beneficial for the discovery of wine biomarkers and establishing product authenticity based on development of fingerprint libraries