Development Of Disease Research Articles

Body Composition and Senescence: Impact of Polyphenols on Aging-Associated Events

Aging is a dynamic and progressive process characterized by the gradual accumulation of cellular damage. The continuous functional decline in the intrinsic capacity of living organisms to precisely regulate homeostasis leads to an increased susceptibility and vulnerability to diseases. Among the factors contributing to these changes, body composition—comprised of fat mass and lean mass deposits—plays a crucial role in the trajectory of a disability. Particularly, visceral and intermuscular fat deposits increase with aging and are associated with adverse health outcomes, having been linked to the pathogenesis of sarcopenia. Adipose tissue is involved in the secretion of bioactive factors that can ultimately mediate inter-organ pathology, including skeletal muscle pathology, through the induction of a pro-inflammatory profile such as a SASP, cellular senescence, and immunosenescence, among other events. Extensive research has shown that natural compounds have the ability to modulate the mechanisms associated with cellular senescence, in addition to exhibiting anti-inflammatory, antioxidant, and immunomodulatory potential, making them interesting strategies for promoting healthy aging. In this review, we will discuss how factors such as cellular senescence and the presence of a pro-inflammatory phenotype can negatively impact body composition and lead to the development of age-related diseases, as well as how the use of polyphenols can be a functional measure for restoring balance, maintaining tissue quality and composition, and promoting health.

Apelin from Perivascular Adipose Tissue Is Involved in the Regulation of Vasorelaxation and Renal Function in Metabolic Syndrome

The perivascular adipose tissue (PVAT) regulates the arterial tone by releasing vasoactive molecules. PVAT dysfunction favoring the vasorelaxation response could contribute to the development of kidney disease in metabolic syndrome (MetS). Previously, we demonstrated that overactivation of angiotensin II signaling in the PVAT deteriorates the compensatory PVAT effects in rats with MetS (SHRSP.Z-Leprfa/IzmDmcr (SPZF) and SHR/NDmcr-cp (CP) rats). Apelin is an endogenous regulator of angiotensin II. Therefore, we investigated whether changes in apelin levels in the PVAT alter PVAT function and impair kidney function in MetS. Twenty-three-week-old male and female SPZF and CP rats were used. In the female CP rats, apelin mRNA levels in renal arterial PVAT, enhancing effects of the PVAT on acetylcholine-induced relaxation in renal arteries, and estimated glomerular filtration rate (eGFR) were the highest, and urine protein levels and homeostasis model assessment of insulin resistance (HOMA-IR) were the lowest. Apelin mRNA levels were positively correlated with the enhancing effects of the PVAT on vasorelaxation and eGFR but negatively correlated with urine protein levels and HOMA-IR. Moreover, apelin levels positively correlated with mRNA levels of angiotensin-converting enzyme 2 and angiotensin II type 1 receptor-associated protein, which are negative regulators of angiotensin II. This study suggests that a decline in apelin levels in the PVAT, probably owing to angiotensin II, is associated with PVAT dysfunction on vascular tone, resulting in impaired kidney function in MetS.

Autoimmune and Neoplastic Outcomes After the mRNA Vaccination: The Role of T Regulatory Cell Responses

A plethora of autoimmune disease incidences occured after COVID-19 mRNA injections were rolled out. Aggressive cancer cases have occurred in the bodies of recipients at sites where the mRNA was injected and at distant metastatic sites. The mRNA vaccines cause thymic involution (shrinking) and dysregulation of the T regulatory (Treg) and T effector (Teff) homeostatic cell balance. Activated immune cells deliver spike protein to the thymic epithelial cells, damaging them. The Treg/Teff balance may determine the fate of autoimmunity and/or cancer and is different for patients with cancer versus those without any cancerous tissues. Repeated mRNA injections lead to empirical evidence of impaired immune functions (elevated IgG4, PD-L1), associated with increased autoimmunity and cancer risks, and decreased resistance to infections. In the with-cancer recipients, the mRNA vaccine may be associated with either autoimmunity or further progression of the cancer(s) depending on the immunotherapy treatment the patient receives. When an antigen stimulates the immune system, specific T regulatory (Treg) and T effector (Teff) subpopulations develop from naïve T cells. An imbalance between Treg and Teff cells can lead to either cancer or autoimmunity. Treg cells are beneficial in that they protect from autoimmunity. However, they suppress the immune response to tumors. In this review, we analyze Treg responses after SARS-CoV-2 mRNA vaccination and find distinct pathological responses under differing conditions. Injection with modified mRNA can lead to a delayed but highly active immune response, resulting in overactivation of the inflammasome. The mRNA “vaccine” induces a very strong IgG antibody response, while suppressing CD8+ T cell activation. Exosomes distribute the recombinant, synthetic spike protein and the mRNA encoding it throughout the organism. In cancer patients, disease progression depends on the starting point of the cancer patient at the time of injection and the type of cancer treatment underway. Migration of circulating dendritic cells and Treg cells back to the thymus, while they are carrying spike protein, damages the medullary thymic epithelial cells and accelerates thymic involution, a direct cause of inflammaging and immunosenescence. In summary, the Treg responses to mRNA injections and subsequent mRNA-encoded SARS-CoV-2 spike protein expression may disrupt immune capacities resulting in accelerated development of autoimmune disease and cancer. The processes discussed here are consistent with both epidemiological findings and case reports.

The relationship between micronutrients and cognitive ability in an elderly population with mild cognitive impairment and Alzheimer’s disease: a cross-sectional study

BackgroundMild cognitive impairment (MCI) and Alzheimer’s disease (AD) are significant neurodegenerative disorders with increasing prevalence worldwide. Lifestyle and dietary factors, including micronutrients, have been suggested as modifiable risk factors for disease development. This study aims to investigate the association between micronutrients and cognitive ability in these diseases.MethodsA cross-sectional study involving 105 participants with MCI and AD was conducted. Dietary assessments were performed using a validated food frequency questionnaire (FFQ), and micronutrient intake was calculated based on nutrient content. Disease severity was evaluated using the Functional Assessment Staging Tool (FAST). Statistical analyses, including correlation coefficients and multiple regression models, were employed to examine the association between micronutrients and disease progression.ResultsThe results revealed significant correlations between disease severity and several micronutrients, including omega-3 fatty acids (B = -0.2, P = 0.01), carotenoids (B = -0.19, P = 0.02), dietary antioxidant compounds, including vitamins A, C, D, E (B = -0.19, P = 0.02), selenium (B = -0.17, P = 0.03), alpha-carotene (B = -0.16, P = 0.04), beta-carotene (B = -0.17, P = 0.03), and lycopene (B = -0.16, P = 0.04). Multivariate regression analysis showed that higher intake of omega-3 fatty acids was associated with slower disease progression. Furthermore, the levels of these micronutrients declined in advanced stages of the disease.ConclusionOmega-3 fatty acids and carotenoids may affect the cognitive ability and disease progression. Further longitudinal studies are warranted to establish causality and explore the therapeutic implications of these findings for the prevention and management of MCI and AD.

17β-Estradiol Stimulates Oxidative Stress Components and Thyroid Specific Genes in Porcine Thyroid Follicular Cells: Potential Differences Between Sexes

17β-estradiol plays a crucial role in regulating cellular processes in both reproductive and non-reproductive tissues, including the thyroid gland. It modulates oxidative stress and contributes to sexual dimorphism in thyroid diseases, with ROS production, particularly H2O2, generated by NOX/DUOX enzymes. This study aimed to investigate the effects of 17β-estradiol (10 nM or 100 nM) on the expression of NOX/DUOX, thyroid-specific genes, and endoplasmic reticulum (ER) stress-related genes in male and female porcine thyroid follicular cells. Expression of the studied genes was evaluated by RT-PCR before and after treatment with 17β-estradiol alone or with the addition of NOX4 inhibitor (GKT-136901). Additionally, the level of ROS was measured by flow cytometry analysis. Our results show that 17β-estradiol significantly upregulates thyroid-specific genes, particularly TPO, and stimulates NOX/DUOX expression, affecting the redox state of thyroid cells. It also stimulates ER stress-related genes such as CHOP. In conclusion, estrogen excess may contribute to thyroid disease development via such possible mechanisms as the upregulation of key thyroid-specific genes, particularly TPO, and of genes involved in the cellular response to ER stress, especially CHOP, as well as by the stimulation of the NOX/DUOX system with consequent ROS overproduction. These mechanisms may play a certain role in the higher prevalence of thyroid diseases in women.

Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.

The first anti-tumour necrosis factor (TNF) monoclonal antibody, infliximab (Remicade), celebrated its 25th anniversary of FDA approval in 2023. Inhibitors of TNF have since proved clinically efficacious at reducing inflammation associated with several autoimmune diseases, including rheumatoid arthritis, psoriasis and Crohn's disease. The success of TNF inhibitors raised unrealistic expectations for targeting other members of the TNF superfamily (TNFSF) of ligands and their receptors, with difficulties in part related to their more limited, variable expression and potential redundancy. However, there has been a resurgence of interest and investment, with many of these cytokines or their cognate receptors now under clinical investigation as targets for modulation of autoimmune and inflammatory diseases, as well as cancer. This Review assesses TNFSF-targeted biologics currently in clinical development for immune system-related diseases, highlighting ongoing challenges and future directions.

Cardio-oncology: a cardiologist's view on the problem of endovascular treatment of patients with coronary artery disease and severe aortic valve stenosis combined with cancer: a literature review

Cardio-oncology is a new medical direction which is responsible for the prevention of development, diagnosis and treatment of cardiovascular disease (CVD) in patients with cancer. The prevalence of cardiac pathology in cancer patients turned out to be unexpectedly high, while only half of the patients with pathology of two systems are referred to a cardiologist for consultation and receive optimal therapy. The coincidence of risk fa­ctors for CVD and cancer suggests that these diseases have common underlying biological and molecular mechanisms. Antitumor therapy and radiation therapy can also contribute to the onset and progression of CVD. Diagnosis of coronary artery disease (CAD) in patients with cancer is difficult, since this group of patients often lacks typical angina pain, and the most common complaint is dyspnea. Endovascular surgery for CAD and severe aortic valve stenosis can be an effective and safe method for treating patients with concomitant cancer. However, given the heterogeneity of cancer diseases and the fact that these patients were not included in most randomized trials studying the CVD treatment, further research is required in this area.Aim. To analyze the literature on the etiopathogenesis of CVD in cancer patients, as well as the clinical features of CAD and aortic valve stenosis in cancer patients and the potential of innovative endovascular technologies.Conclusion. For management and treatment of such severe comorbid patients, the participation of a multidisciplinary team and a personalized approach to each patient are necessary.

Inflammation and resolution in obesity.

Inflammation is an essential physiological defence mechanism, but prolonged or excessive inflammation can cause disease. Indeed, unresolved systemic and adipose tissue inflammation drives obesity-related cardiovascular diseaseand type 2 diabetes mellitus. Drugs targeting pro-inflammatory cytokine pathways or inflammasome activation have been approved for clinical use for the past two decades. However, potentially serious adverse effects, such as drug-induced weight gain and increased susceptibility to infections, prevented their wider clinical implementation. Furthermore, these drugs do not modulate the resolution phase of inflammation. This phase is an active process orchestrated by specialized pro-resolving mediators, such as lipoxins, and other endogenous resolution mechanisms. Pro-resolving mediators mitigate inflammation and development of obesity-related disease, for instance, alleviating insulin resistance and atherosclerosis in experimental disease models, so mechanisms to modulate their activity are, therefore, of great therapeutic interest. Here, we review current clinical attempts to either target pro-inflammatory mediators (IL-1β,NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3)inflammasome,tumour necrosis factor (TNF)and IL-6) or utilize endogenous resolution pathways to reduce obesity-related inflammation and improve cardiometabolic outcomes. A remaining challenge in the field is to establish more precise biomarkers that can differentiate between acute and chronic inflammation and to assess the functionality of individual leukocyte populations. Such advancements would improve the monitoring of drug effects and support personalized treatment strategies that battle obesity-related inflammation and cardiometabolic disease.

The effects of cannabinoids on the kidney.

Cannabinoids are a class of drugs derived from the Cannabis plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2-arachidonoylglycerol (2-AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed.

A mathematical model describing the tip-stalk regulation in angiogenesis

Angiogenesis is the process of new blood vessel growth from existing vessels, involving extensive cell signaling. Under normal conditions, new vessels are robust and organized, with a balance among angiogenesis factors. In abnormal conditions, such as tumor development, vessels are stunted and tangled due to an imbalance of these factors. Pathological angiogenesis stimulates rapid vessel growth to feed the oxygen and nutriente starved tumor. Inhibiting angiogenesis can cause side effects like hypertension, thrombosis, and fatigue. To better understand this process, significant effort has gone into studying signaling pathways, contributing to drug development for diseases like cancer. This study presents a mathematical model describing angiogenesis on a microscopic scale, comparing its results with experimental data on vascular network topology. The model, implemented in MatLab®, uses ordinary differential equations to represent cell behavior. Results show that altering VEGF (Vascular Endothelial Growth Factor) disrupts system balance, impacting angiogenesis and possibly explaining differences in network topology seen experimentally.

New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?

The classical BCR::ABL-negative myeloproliferative neoplasms (MPN) include Polycythemia Vera (PV), Essential Thrombocytemia (ET), and Primary Myelofibrosis (PMF). They are acquired clonal disorders of the hematopoietic stem cells (HSC) leading to hyperplasia of one or several myeloid lineages. MPN are caused by three main recurrent mutations, JAK2V617F and mutations in the calreticulin (CALR) and the thrombopoietin receptor (MPL) genes. Here, we review the general diagnosis, the complications, and the management of MPN. Second, we explain the physiopathology of the natural disease development and its regulation, which contributes to MPN heterogeneity. Thirdly, we describe the new paradigm of the MPN development highlighting the early origin of driver mutations decades before the onset of symptoms and the consequence on early detection of MPN cases in the general population for early diagnosis and better medical management. Finally, we present the interferon alpha (IFNα) therapy as a potential early disease-modifying drug after reporting its good hematological and molecular efficacies in ET, PV and early MF in clinical trials as well as its mechanism of action in pre-clinical studies. As a result, we may expect that, in the future, MPN patients will be diagnosed very early during the course of disease and that new selective therapies under development, such as IFNα, JAK2V617F inhibitors and CALRmut monoclonal antibodies, would be able to intercept the mutated clones.

Emerging concepts and success stories in type 1 diabetes research: a roadmap for a bright future.

Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration (FDA) approval of teplizumab to delay disease development. In this Perspective article, we discuss four major conceptual and practical issues that emerged as key to further advance type 1 diabetes research and therapies. First, collaborative networks leveraging the synergy between the type 1 diabetes research and care community members are key to fostering innovation, know-how and translation into the clinical arena worldwide. Second, recent clinical trials in presymptomatic stage 2 and recent-onset stage 3 disease have shown the promise, and potential pitfalls, of using immunomodulatory and/or beta-cell protective agents to achieve sustained remission or prevention. Third, the increasingly appreciated heterogeneity of clinical, immunological, and metabolic phenotypes and disease trajectories is of critical importance to advance the decision-making process for tailored type 1 diabetes care and therapy. Fourth, the clinical benefits of early diagnosis of beta-cell autoimmunity warrant consideration of general population screening for islet autoantibodies, which requires further efforts to address the technical, organizational and ethical challenges inherent to a sustainable program. Efforts are underway to integrate these four concepts into the future directions of type 1 diabetes research and therapy.

Viral Infections and the Glutathione Peroxidase Family: Mechanisms of Disease Development.

Significance: The glutathione peroxidase (GPx) family is recognized for its essential function in maintaining cellular redox balance and countering the overproduction of reactive oxygen species (ROS), a process intricately linked to the progression of various diseases including those spurred by viral infections. The modulation of GPx activity by viruses presents a critical juncture in disease pathogenesis, influencing cellular responses and the trajectory of infection-induced diseases. Recent Advances: Cutting-edge research has unveiled the GPx family's dynamic role in modulating viral pathogenesis. Notably, GPX4's pivotal function in regulating ferroptosis presents a novel avenue for the antiviral therapy. The discovery that selenium, an essential micronutrient for GPx activity, possesses antiviral properties has propelled us toward rethinking traditional treatment modalities. Critical Issues: Deciphering the intricate relationship between viral infections and GPx family members is paramount. Viral invasion can precipitate significant alterations in GPx function, influencing disease outcomes. The multifaceted nature of GPx activity during viral infections suggests that a deeper understanding of these interactions could yield novel insights into disease mechanisms, diagnostics, prognostics, and even chemotherapeutic resistance. Future Directions: This review aims to synthesize current knowledge on the impact of viral infections on GPx activity and expression and identify key advances. By elucidating the mechanisms through which GPx family members intersect with viral pathogenesis, we propose to uncover innovative therapeutic strategies that leverage the antioxidant properties of GPx to combat viral infections. The exploration of GPx as a therapeutic target and biomarker holds promise for the development of next-generation antiviral therapies. Antioxid. Redox Signal. 00, 000-000.

CMAGN: circRNA–miRNA association prediction based on graph attention auto-encoder and network consistency projection

Background: As noncoding RNAs, circular RNAs (circRNAs) can act as microRNA (miRNA) sponges due to their abundant miRNA binding sites, allowing them to regulate gene expression and influence disease development. Accurately identifying circRNA–miRNA associations (CMAs) is helpful to understand complex disease mechanisms. Given that biological experiments are time consuming and labor intensive, alternative computational methods to predict CMAs are urgently needed. Results: This study proposes a novel computational model named CMAGN, which incorporates several advanced computational methods, for predicting CMAs. First, similarity networks for circRNAs and miRNAs are constructed according to their sequences. Graph attention autoencoder is then applied to these networks to generate the first representations of circRNAs and miRNAs. The second representations of circRNAs and miRNAs are obtained from the CMA network via node2vec. The similarity networks of circRNAs and miRNAs are reconstructed on the basis of these new representations. Finally, network consistency projection is applied to the reconstructed similarity networks and the CMA network to generate a recommendation matrix. Conclusion: Five-fold cross-validation of CMAGN reveals that the area under ROC and PR curves exceed 0.96 on two widely used CMA datasets, outperforming several existing models. Additional tests elaborate the reasonability of the architecture of CMAGN and uncover its strengths and weaknesses.

Primary and residual cardiometabolic risk factors among young adults in a Russian city

BackgroundCardiovascular diseases are a leading cause of mortality and a significant contributor to temporary and permanent disabilities worldwide. This study aimed to investigate the burden of primary and residual cardiometabolic risk factors in a sample of young adults in the Russian city of Kazan.MethodsThis case-control study used the Cardiometabolic Disease Staging (CMDS) classification system, which has been validated in several countries. The study included 191 individuals aged 25–44 years who met the inclusion criteria but did not meet any exclusion criteria. Data collection involved a patient card with questions from the World Health Organization’s STEPS instrument, face-to-face patient interviews, and a physical examination. Anthropometric assessments included height, weight, and waist circumference measurements. Body composition was evaluated using bioelectrical impedance measurements. Patients also underwent in-depth laboratory biochemical analyses.ResultsThe study cohort was comprised of 97 females (50.8%) and 94 males (49.2%). The median age of participants was 35.00 years [IQR: 30.00–39.00]. The study cohort showed an increase in all anthropometric parameters, with abdominal obesity and overweight reaching 100% in the CMDS 3. Apart from atherogenic lipids and raised blood pressure, other risk factors that precipitate residual risk and were not part of CMDS, such as insulin levels, insulin resistance, leptin values, and hyperuricemia, increased as CMDS levels increased.ConclusionsThe prevalence of cardiometabolic risk factors was high in young adults in Kazan. This study highlights the need for the early identification and management of cardiometabolic risk factors in young adults to prevent the development of cardiovascular diseases later in life.

Pemphigoid Gestationis - literature review

Introduction and Objective: Pemphigoid gestationis (PG) is a rare, self-limiting autoimmune disorder, typically appearing in the second or third trimester of pregnancy. It can lead to postpartum exacerbations, and studies suggest an increased risk of preterm birth and the development of Graves' disease in the mother. The aim of this article is to gather the latest information on pemphigoid gestationis. Review Methods: A review of studies available in the PubMed database was conducted using the keywords "pemphigoid gestationis" and "dermatoses of pregnancy" in order to find publications from the last 8 years. Brief Description of the State of Knowledge: Pemphigoid gestationis (PG) is characterized by the production of IgG1 antibodies against bullous pemphigoid antigen 180 (BP180). The primary symptom of PG is intense itching, which often occurs before skin lesions develop. Diagnosis is typically confirmed through direct immunofluorescence (DIF) of perilesional skin. Treatment focuses on relieving itching and preventing new blister formation, usually starting with topical corticosteroids for mild cases, while systemic corticosteroids are reserved for more severe presentations. Recent research indicates that biologic therapies may also offer effective management options for PG. Summary: The authors highlight the need for further research due to the limited sample sizes in existing studies, as well as the potential complications during pregnancy and long-term health effects.

From Cells to Plaques: The Molecular Pathways of Coronary Artery Calcification and Disease

Coronary artery calcification (CAC) is a hallmark of atherosclerosis and a critical factor in the development and progression of coronary artery disease (CAD). This review aims to address the complex pathophysiological mechanisms underlying CAC and its relationship with CAD. We examine the cellular and molecular processes that drive the formation of calcified plaques, highlighting the roles of inflammation, lipid accumulation, and smooth muscle cell proliferation. Additionally, we explore the genetic and environmental factors that contribute to the heterogeneity in CAC and CAD presentation among individuals. Understanding these intricate mechanisms is essential for developing targeted therapeutic strategies and improving diagnostic accuracy. By integrating current research findings, this review provides a comprehensive overview of the pathways linking CAC to CAD, offering insights into potential interventions to mitigate the burden of these interrelated conditions.

Grapevines grown from canes having spent 10 months in space: study of their downy mildew susceptibility

The control of plant diseases represents a significant challenge in agriculture, particularly with the current emphasis on reducing pesticide use, necessitating alternative approaches. Among them, resistant plant breeding programs offer a promising alternative. Considering the stressful conditions in space, space conditions emerge as an innovative method for advancing crop improvement. This study explored the unique potential of the International Space Station (ISS) environment to induce beneficial modifications in grapevine, resulting in plants with reduced susceptibility to diseases. Canes of two Vitis vinifera L. cultivars, Cabernet Sauvignon (CS) and Merlot (Me), have undergone a 10-month space journey on-board the ISS, while others stayed on Earth (Ground Control, GC). We conducted a 2-year analysis of the response to downy mildew (Plasmopara viticola) of plants developed from ISS and GC canes, called Mother plants. The disease development of progenies produced from Merlot Mother plants was also evaluated. A higher proportion of individuals with low-susceptibility was noted in the ISS Mother group compared to the controls for both cultivars. This trend was also observed for the Merlot progenies. Finally, 11% of Merlot individuals (Mother and progenies, and for the 2 years of study) were distributed in the low susceptibility class. This study suggests that grapevine canes exposure to ISS conditions resulted in an enhanced percentage of plants showing reduction of susceptibility to downy mildew.

Gut‑liver axis in liver disease: From basic science to clinical treatment (Review).

Incidence of a number of liver diseases has increased. Gut microbiota serves a role in the pathogenesis of hepatitis, cirrhosis and liver cancer. Gut microbiota is considered 'a new virtual metabolic organ'. The interaction between the gut microbiota and liver is termed the gut‑liver axis. The gut‑liver axis provides a novel research direction for mechanism of liver disease development. The present review discusses the role of the gut‑liver axis and how this can be targeted by novel treatments for common liver diseases.

Rare but relevant: Methamphetamine and Parkinson's disease.

Evidence from a number of paradigms suggests that methamphetamine use is associated with increased risk for the development of Parkinson's disease and parkinsonism, and that it may be associated with the premature development of Parkinson's disease. Prevalence of Parkinson's disease and parkinsonism is greater in both methamphetamine users and people who previously used methamphetamine, and evidence from animal studies provides a plausible mechanism for this observation. Despite this increased risk, Parkinson's disease is rarely diagnosed in methamphetamine users. Reasons for this may include under-detection, premature mortality, and individual and substance use characteristics which moderate the risk, including higher rates of smoking. Clinicians should be vigilant to signs and symptoms of Parkinson's disease and parkinsonism in methamphetamine users.