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Cells Nov 2023Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management... (Review)
Review
Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.
Topics: Humans; Calcitonin Gene-Related Peptide; Gastrointestinal Hormones; Migraine Disorders; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Secretin; Vasoactive Intestinal Peptide
PubMed: 37998384
DOI: 10.3390/cells12222649 -
The American Journal of Tropical... Jul 2023To establish a Cox regression model predicting risk factors for mortality in patients with severe fever with thrombocytopenia syndrome (SFTS), a total of 109 SFTS...
To establish a Cox regression model predicting risk factors for mortality in patients with severe fever with thrombocytopenia syndrome (SFTS), a total of 109 SFTS patients treated at The Second Hospital of Nanjing between June 2016 and October 2020 were included in this study. The patients were categorized into survival (n = 82) and death (n = 27) groups, and the clinical manifestations on admission and laboratory examination were collected. The factors associated with the mortality risk of SFTS patients were explored by univariate and binary logistic regression analyses. The receiver operating characteristic curve was used to evaluate the predictive value of independent influencing factors and the STFS scoring system. Univariate screening showed that the putative influencing factors were age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, invasive mechanical ventilation, continuous renal replacement therapy, application of vasoactive medications, absolute count of lymphocytes, count of platelets, and levels of albumin and D-dimer (P < 0.05). Binary logistic regression showed that age (P = 0.042), APACHE II score (P = 0.030), and vasoactive medications (P = 0.035) were independent risk factors in SFTS patients. The combined prediction equation for the mortality risk of SFTS patients was "Combined predictor = age + 3.162 × APACHE II score + 22.306 × vasoactive medications," and the predictive value of combined predictor was greater than that of age (P = 0.004) or APACHE II score (P < 0.001). The combination of age, APACHE II score, and vasoactive medications had the highest ability to predict the risk of death. The STFS scoring system could make the clinical application of independent risk factors feasible.
Topics: Humans; Child, Preschool; Severe Fever with Thrombocytopenia Syndrome; Prognosis; Retrospective Studies; APACHE; ROC Curve; Risk Factors; Intensive Care Units
PubMed: 37253446
DOI: 10.4269/ajtmh.22-0667 -
Nutrition in Clinical Practice :... Oct 2023Children with congenital heart disease often require admission to the cardiac intensive care unit at some point in their lives, either after elective surgical or... (Review)
Review
Children with congenital heart disease often require admission to the cardiac intensive care unit at some point in their lives, either after elective surgical or catheter-based procedures or during times of acute critical illness. Meeting both the macronutrient and micronutrient needs of children in the cardiac intensive care unit requires complex decision-making when considering gastrointestinal perfusion, vasoactive support, and fluid balance goals. Although nutrition guidelines exist for critically ill children, these cannot always be extrapolated to children with congenital heart disease. Children with congenital heart disease may also suffer unique circumstances, such as chylothoraces, heart failure, and the need for mechanical circulatory support, which greatly impact nutrition delivery. Guidelines for neonates and children with heart disease continue to be developed. We provide a synthesized narrative review of current literature and considerations for nutrition evaluation and management of critically ill children with congenital heart disease.
Topics: Infant, Newborn; Child; Humans; Critical Illness; Heart Defects, Congenital; Nutritional Status; Nutrients; Nutrition Assessment
PubMed: 37721463
DOI: 10.1002/ncp.11046 -
Life Sciences Nov 2023Vasoactive intestinal peptide (VIP) is an abundant neurotransmitter in the lungs and other organs. Its discovery dates back to 1970. And VIP gains attention again due to... (Review)
Review
Vasoactive intestinal peptide (VIP) is an abundant neurotransmitter in the lungs and other organs. Its discovery dates back to 1970. And VIP gains attention again due to the potential application in COVID-19 after a research wave in the 1980s and 1990s. The diverse biological impacts of VIP extend beyond its usage in COVID-19 treatment, encompassing its involvement in various pulmonary and systemic disorders. This review centers on the function of VIP in various lung diseases, such as pulmonary arterial hypertension, chronic obstructive pulmonary disease, asthma, cystic fibrosis, acute lung injury/acute respiratory distress syndrome, pulmonary fibrosis, and lung tumors. This review also outlines two main limitations of VIP as a potential medication and gathers information on extended-release formulations and VIP analogues.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Vasoactive Intestinal Peptide; Lung Diseases
PubMed: 37742737
DOI: 10.1016/j.lfs.2023.122121 -
Dimensions of Critical Care Nursing :...Aortic regurgitation (AR) is a valvular disease characterized by retrograde blood flow from the aorta to the left ventricle. Various etiologies result in either an acute... (Review)
Review
Aortic regurgitation (AR) is a valvular disease characterized by retrograde blood flow from the aorta to the left ventricle. Various etiologies result in either an acute or chronic clinical presentation of AR and affect the severity of disease progression. Acute AR is a medical emergency caused by sudden increases in left ventricular volume. Immediate surgical intervention, vasoactive agents, and antibiotics are crucial for management. Chronic AR progresses gradually, leading to heart failure symptoms due to left ventricular remodeling. Diagnoses of both acute and chronic AR rely on electrocardiography, chest radiographs, and echocardiography. Cardiac magnetic resonance imaging may be incorporated in chronic AR diagnosis. Medical management of chronic AR aims to control hypertension and delay left ventricular dysfunction. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and potentially calcium-channel blockers are recommended for chronic AR. β-Blockers are cautioned against because of their potential negative effects. This article emphasizes the importance of early diagnosis and prompt surgical intervention in AR. This review provides a comprehensive overview of the pathophysiology and clinical manifestations of acute and chronic AR and a medication regimen for treating chronic AR in the adult population.
Topics: Adult; Humans; Aortic Valve Insufficiency; Ventricular Dysfunction, Left; Hemodynamics
PubMed: 38271313
DOI: 10.1097/DCC.0000000000000628 -
Expert Opinion on Investigational Drugs 2023Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Approved treatment options currently primarily target abnormal cell signaling... (Review)
Review
INTRODUCTION
Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Approved treatment options currently primarily target abnormal cell signaling pathways involved in vasoconstriction and proliferation, such as those mediated by prostacyclin, cyclic guanosine monophosphate, and endothelin.
AREAS COVERED
Recent advancements have led to new applications and modes of delivery of currently approved PAH medications. At the same time, novel drugs targeting specific molecular pathways involved in PAH pathogenesis have been developed and are being investigated in clinical trials. This review summarizes investigational drug trials for PAH gathered from a comprehensive search using PubMed and ClinicalTrials.gov between 2003 and 2023. It includes both currently approved medications studied at different doses or new administration forms and experimental drugs that have not yet been approved.
EXPERT OPINION
Approved treatments for PAH target imbalances in pulmonary vasoactive pathways that work primarily on enhancing pulmonary vasodilation with less salient effects on pulmonary vascular remodeling. The advent of more locally acting inhaled medications offers additional therapeutic options that may improve the ease of drug delivery and reduce adverse systemic effects. The more recent emphasis on developing and applying therapeutics that directly impact the aberrant signaling pathways implicated in PAH appears more likely to advance the treatment of this devastating disease.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Drug Delivery Systems; Drugs, Investigational; Vasodilation
PubMed: 37881882
DOI: 10.1080/13543784.2023.2274439 -
Biology Jul 2023The overwhelming increase in the prevalence of obesity and related disorders in recent years is one of the greatest threats to the global healthcare system since it... (Review)
Review
The overwhelming increase in the prevalence of obesity and related disorders in recent years is one of the greatest threats to the global healthcare system since it generates immense healthcare costs. As the prevalence of obesity approaches epidemic proportions, the importance of elucidating the mechanisms regulating appetite, satiety, body metabolism, energy balance and adiposity has garnered significant attention. Currently, gastrointestinal (GI) bariatric surgery remains the only approach capable of achieving successful weight loss. Appetite, satiety, feeding behavior, energy intake and expenditure are regulated by central and peripheral neurohormonal mechanisms that have not been fully elucidated yet. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) are members of a family of regulatory peptides that are widely distributed in parallel with their specific receptors, VPAC1R, VPAC2R and PAC1R, in the central nervous system (CNS) and in the periphery, such as in the gastrointestinal tract and its associated organs and immune cells. PACAP and VIP have been reported to play an important role in the regulation of body phenotype, metabolism and homeostatic functions. The purpose of this review is to present recent data on the effects of PACAP, VIP, VPAC1R, VPAC2R and PAC1R on the modulation of appetite, satiety, metabolism, calorie intake and fat accumulation, to evaluate their potential use as therapeutic targets for the treatment of obesity and metabolic syndrome.
PubMed: 37508442
DOI: 10.3390/biology12071013 -
Bioelectronic Medicine Dec 2023Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further... (Review)
Review
Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS' success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.
PubMed: 38087375
DOI: 10.1186/s42234-023-00128-z -
Current Opinion in Allergy and Clinical... Aug 2024Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing... (Review)
Review
PURPOSE OF REVIEW
Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing various reactions beyond IgE-mediated responses. This review aims to present recent advancements in knowledge regarding the mechanisms and pathophysiology of perioperative anaphylaxis.
RECENT FINDINGS
Emerging evidence highlights the role of the mast-cell related G-coupled protein receptor X2 pathway in direct mast cell degranulation, shedding light on previously unknown mechanisms. This pathway, alongside traditional IgE/FcεRI-mediated reactions, contributes to the complex nature of anaphylactic reactions. Investigations into the microbiota-anaphylaxis connection are ongoing, with potential implications for future treatment strategies. While serum tryptase levels serve as mast cell activation indicators, identifying triggers remains challenging. A range of mediators have been associated with anaphylaxis, including vasoactive peptides, proteases, lipid molecules, cytokines, chemokines, interleukins, complement components, and coagulation factors.
SUMMARY
Further understanding of clinical endotypes and the microenvironment where anaphylactic reactions unfold is essential for standardizing mediator testing and characterization in perioperative anaphylaxis. Ongoing research aims to elucidate the mechanisms, pathways, and mediators involved across multiple organ systems, including the cardiovascular, respiratory, and integumentary systems, which will be crucial for improving patient outcomes.
Topics: Anaphylaxis; Humans; Perioperative Period; Mast Cells; Animals; Immunoglobulin E; Cell Degranulation; Tryptases; Receptors, IgE; Microbiota; Nerve Tissue Proteins; Receptors, Neuropeptide; Receptors, G-Protein-Coupled
PubMed: 38743470
DOI: 10.1097/ACI.0000000000000994