scholarly journals Amiloride-sensitive cation channel 2 genotype affects the response to a carbon dioxide panic challenge

2017 ◽  
Vol 31 (10) ◽  
pp. 1294-1301 ◽  
Author(s):  
Nicole K Leibold ◽  
Daniel LA van den Hove ◽  
Wolfgang Viechtbauer ◽  
Gunter Kenis ◽  
Liesbet Goossens ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Healthy Volunteers ◽  
Emotional Response ◽  
Treatment Options ◽  
Genetic Research ◽  
Current Treatment ◽  
Cation Channel ◽  
Differential Sensitivity ◽  
Future Research ◽  
Genotype Effect

Until recently, genetic research into panic disorder (PD) has had only limited success. Inspired by rodent research, demonstrating that the acid-sensing ion channel 1a (ASIC1a) is critically involved in the behavioral fear response to carbon dioxide (CO2) exposure, variants in the human homologue gene amiloride-sensitive cation channel 2 (ACCN2) were shown to be associated with PD. However, the relationship between changes in brain pH and ACCN2, as done in rodents by CO2 exposure, has not been investigated yet in humans. Here, we examined this link between the ACCN2 gene and the response to CO2 exposure in two studies: in healthy volunteers as well as PD patients and using both behavioral and physiological outcome measures. More specifically, 107 healthy volunteers and 183 PD patients underwent a 35% CO2 inhalation. Negative affect was assessed using visual analogue scales and the panic symptom list (PSL), and, in healthy volunteers, cardiovascular measurements. The single nucleotide polymorphism rs10875995 was significantly associated with a higher emotional response in PD patients and with an increase in systolic as well as diastolic blood pressure in healthy subjects. In all measurements, subjects homozygous for the T-allele showed a heightened reactivity to CO2. Furthermore, a trend towards an rs685012 genotype effect on the emotional response was found in PD patients. We provide the first evidence that genetic variants in the ACCN2 are associated with differential sensitivity to CO2 in PD patients as well as healthy volunteers, further supporting ACCN2 as a promising candidate for future research to improve current treatment options.

scholarly journals Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Guohua An ◽  
Daryl J. Murry ◽  
Kiran Gajurel ◽  
Thanh Bach ◽  
Greg Deye ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Phase 1 ◽  
Treatment Options ◽  
Taenia Solium ◽  
Current Treatment ◽  
Pharmacokinetic Parameters ◽  
Serious Adverse Events ◽  
Dose Escalation Study ◽  
Content Type ◽  
Dose Dependent Decrease

ABSTRACT Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.)

scholarly journals Brown adipose tissue – A future treatment for obesity?

2019 ◽  
Vol 8 (3) ◽  
pp. 75-79
Author(s):  
Natasha Povey ◽  
Dr Fiona Curtis
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Treatment Options ◽  
Current Treatment ◽  
Current Understanding ◽  
Health Concern ◽  
Future Research ◽  
Future Treatment ◽  
Brown Adipose

Obesity is a major public health concern: in the United Kingdom (UK) over two thirds of the population are obese or overweight, the prevalence of obesity is growing exponentially, and current treatment options have limited success – making the need for novel therapies vital. Brown adipose tissue (BAT) has the ability to safely dissipate chemical energy as heat and in 2009 was found to be active in human adults, leading to hope that its therapeutic manipulation could contribute to weight loss. This review discusses methods proposed for BAT activation and potential pitfalls in our current understanding to evaluate if BAT can be used as a future treatment for obesity. To date, ơ3-adrenergic receptor (ơ3-AR) agonists and cold activation have been shown to be the most promising options to activate BAT. However, cold activation requires a high degree of patient cooperation and ơ3-AR agonists appear non-effective long-term. Nonetheless, ơ3-AR agonists are likely to be a more realistic treatment than cold activation, making our next challenge to understandand mitigate the mechanisms that inhibit BAT activation in long-term ơ3-AR agonist administration. Our assumptions about BAT activation are predominately from rodent studies and based on measurements from [18F]-fl uorodeoxyglucose (18F-FDG)-positron-emission tomography and computed tomography (PET/CT) imaging, both with their respective limitations. BAT has offered huge insight into weight homeostasis, with the potential of offering prospective therapeutics for obesity and beyond. Nevertheless, before we can truly understand the real possibilities of BAT we need to further our current understanding of the physiological controls of BAT, potentially leading to more suitable therapies. The focus for future research should be to improve and standardise the methodology used to measure BAT activation, enabling larger clinical trials and better comparisons.

scholarly journals Effect of Artificial Carbon Dioxide-Rich Water Immersion on Peripheral Blood Flow in Healthy Volunteers: Preliminary Study about Artificial Carbon Dioxide-Rich Water

2021 ◽  
Vol 9 (A) ◽  
pp. 527-531
Author(s):  
Andi Rizky Arbaim Hasyar ◽  
Haerani Rasyid ◽  
Irfan Idris ◽  
Irawan Yusuf
Keyword(s):  
Carbon Dioxide ◽  
Blood Flow ◽  
Healthy Volunteers ◽  
Peripheral Blood ◽  
Water Immersion ◽  
Treatment Options ◽  
Peripheral Blood Flow ◽  
Mixed Solution ◽  
Doppler Flowmetry ◽  
Improvement Effect

BACKGROUND: Peripheral blood circulation disorder is one of the global health problems. Balneotherapy that uses CO2 springs may be one of the complementary treatment options. The device to produce artificial CO2-rich water is needed to achieve an improvement effect, at least almost like the improvement effect of natural balneotherapy. AIM: This study aims to investigate the effect of artificial CO2-rich water immersion on peripheral blood flow using Bicarbonated JesC CREA BC-2000. METHODS AND MATERIALS: Thirty-nine healthy volunteers participated in this study. Each subject immersed both of their legs in a mixed solution from water and CO2 at temperature 38°C. This solution was mixed using a device, namely, “Bicarbonated JesC CREA BC-2000”. Peripheral blood flow was measured for 5 min before immersion (in this study, we denoted it as the mean basal blood flow), 10 min during immersion, and 5 min after immersion using pocket JMS laser Doppler flowmetry MBF-IIA. Repeated analysis of variance was used for statistical analysis. RESULTS: There is the difference in peripheral blood flow among before, during, and after immersing the legs into artificial CO2-rich water using Bicarbonated JesC CREA BC-2000 (p < 0.001). CONCLUSION: Bicarbonated JesC CREA BC-2000 may be used as the device to produce an artificial CO2-rich water bath that may affect peripheral blood flow in healthy volunteers.

scholarly journals Spider Phobia: Neural Networks Informing Diagnosis and (Virtual/Augmented Reality-Based) Cognitive Behavioral Psychotherapy—A Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonas Hinze ◽  
Anne Röder ◽  
Nicole Menzie ◽  
Ulf Müller ◽  
Katharina Domschke ◽  
...  
Keyword(s):  
Augmented Reality ◽  
Behavioral Therapy ◽  
Treatment Options ◽  
Brain Regions ◽  
Current Treatment ◽  
Narrative Review ◽  
Cognitive Behavioral ◽  
Future Research ◽  
Spider Phobia

Recent fMRI studies on specific animal phobias, particularly spider phobia (arachnophobia), have identified a large variety of specific brain regions involved in normal and disturbed fear processing. Both functional and structural brain abnormalities have been identified among phobic patients. Current research suggests that both conscious and subconscious fear processing play a crucial role in phobic disorders. Cognitive behavioral therapy has been identified as an effective treatment for specific phobias and has been associated with neuroplastic effects which can be evaluated using current neuroimaging techniques. Recent research suggests that new approaches using virtual (VR) or augmented reality (AR) tend to be similarly effective as traditional “in vivo” therapy methods and could expand treatment options for different medical or individual scenarios. This narrative review elaborates on neural structures and particularities of arachnophobia. Current treatment options are discussed and future research questions are highlighted.

scholarly journals Materials for the Spine: Anatomy, Problems, and Solutions

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 253 ◽  
Author(s):  
Brody Frost ◽  
Sandra Camarero-Espinosa ◽  
E. Foster
Keyword(s):  
Treatment Options ◽  
Total Disc Replacement ◽  
Population Based ◽  
Intervertebral Discs ◽  
Current Treatment ◽  
Future Research ◽  
Noninvasive Methods ◽  
Spinal Fusion Surgery ◽  
Problems And Solutions ◽  
Multiple Challenges

Disc degeneration affects 12% to 35% of a given population, based on genetics, age, gender, and other environmental factors, and usually occurs in the lumbar spine due to heavier loads and more strenuous motions. Degeneration of the extracellular matrix (ECM) within reduces mechanical integrity, shock absorption, and swelling capabilities of the intervertebral disc. When severe enough, the disc can bulge and eventually herniate, leading to pressure build up on the spinal cord. This can cause immense lower back pain in individuals, leading to total medical costs exceeding $100 billion. Current treatment options include both invasive and noninvasive methods, with spinal fusion surgery and total disc replacement (TDR) being the most common invasive procedures. Although these treatments cause pain relief for the majority of patients, multiple challenges arise for each. Therefore, newer tissue engineering methods are being researched to solve the ever-growing problem. This review spans the anatomy of the spine, with an emphasis on the functions and biological aspects of the intervertebral discs, as well as the problems, associated solutions, and future research in the field.

scholarly journals The Link between Aggrecan and Familial Osteochondritis Dissecans

Surgeries ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 128-138
Author(s):  
Samantha Ozere ◽  
Sami Chergui ◽  
Megan E. Cooke ◽  
Thierry Pauyo ◽  
Derek H. Rosenzweig
Keyword(s):  
Osteochondritis Dissecans ◽  
Animal Studies ◽  
Association Studies ◽  
Treatment Options ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Focal Lesions

Osteochondritis dissecans (OCD) is a chronic disease of the articular cartilage characterized by focal lesions of subchondral bone and overlaying cartilage. Through the growing number of reports describing the high prevalence of OCD in some families, the subcategory termed familial OCD (FOCD) was established. With the development of genetic approaches such as genome-wide association studies and sequencing, aggrecan (ACAN) has been identified as one of the genes of interest associated with FOCD. Aggrecan is a crucial protein for the preservation and function of cartilage. However, due to FOCD being characterized relatively recently, there is a paucity of literature on the subject. The purpose of this review is to explore the relationship between ACAN mutations and familial OCD as well as to explore current treatment options and avenues for future research. In vitro and animal studies have shown the importance of ACAN in the preservation of cartilage. However, the only human ACAN mutation related to OCD ever identified is a V2303M mutation in the G3 domain. Multiple treatments have been superficially explored, and some options such as growth hormone (GH) and gonadotrophin-releasing hormone agonists (GnRHa) show potential. Thus, further research on FOCD in needed to identify other ACAN mutations and determine optimal treatment modalities for this patient population.

scholarly journals Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives

2021 ◽  
Vol 2 ◽  
Author(s):  
Tiffani J. Mungoven ◽  
Luke A. Henderson ◽  
Noemi Meylakh
Keyword(s):  
Chronic Migraine ◽  
Current Knowledge ◽  
Treatment Options ◽  
Episodic Migraine ◽  
Current Treatment ◽  
Future Research ◽  
Socioeconomic Outcomes ◽  
Risk Factor Modification ◽  
Evidence Based Treatments ◽  
Migraine Pathophysiology

Chronic migraine is a disabling neurological disorder that imposes a considerable burden on individual and socioeconomic outcomes. Chronic migraine is defined as headaches occurring on at least 15 days per month with at least eight of these fulfilling the criteria for migraine. Chronic migraine typically evolves from episodic migraine as a result of increasing attack frequency and/or several other risk factors that have been implicated with migraine chronification. Despite this evolution, chronic migraine likely develops into its own distinct clinical entity, with unique features and pathophysiology separating it from episodic migraine. Furthermore, chronic migraine is characterized with higher disability and incidence of comorbidities in comparison to episodic migraine. While existing migraine studies primarily focus on episodic migraine, less is known about chronic migraine pathophysiology. Mounting evidence on aberrant alterations suggest that pronounced functional and structural brain changes, central sensitization and neuroinflammation may underlie chronic migraine mechanisms. Current treatment options for chronic migraine include risk factor modification, acute and prophylactic therapies, evidence-based treatments such as onabotulinumtoxinA, topiramate and newly approved calcitonin gene-related peptide or receptor targeted monoclonal antibodies. Unfortunately, treatments are still predominantly ineffective in aborting migraine attacks and decreasing intensity and frequency, and poor adherence and compliance with preventative medications remains a significant challenge. Novel emerging chronic migraine treatments such as neuromodulation offer promising therapeutic approaches that warrant further investigation. The aim of this narrative review is to provide an update of current knowledge and perspectives regarding chronic migraine background, pathophysiology, current and emerging treatment options with the intention of facilitating future research into this debilitating and largely indeterminant disorder.

scholarly journals Promising Drug Targets and Compounds with Anti-Toxoplasma gondii Activity

2021 ◽  
Vol 9 (9) ◽  
pp. 1960
Author(s):  
Marco Silva ◽  
Cátia Teixeira ◽  
Paula Gomes ◽  
Margarida Borges
Keyword(s):  
Drug Discovery ◽  
Toxoplasma Gondii ◽  
Drug Targets ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Protozoan Parasite ◽  
Acid Synthesis ◽  
Current Treatment ◽  
Future Research ◽  
World Population

Toxoplasmosis is a parasitic disease caused by the globally distributed protozoan parasite Toxoplasma gondii, which infects around one-third of the world population. This disease may result in serious complications for fetuses, newborns, and immunocompromised individuals. Current treatment options are old, limited, and possess toxic side effects. Long treatment durations are required since the current therapeutic system lacks efficiency against T. gondii tissue cysts, promoting the establishment of latent infection. This review highlights the most promising drug targets involved in anti-T. gondii drug discovery, including the mitochondrial electron transport chain, microneme secretion pathway, type II fatty acid synthesis, DNA synthesis and replication and, DNA expression as well as others. A description of some of the most promising compounds demonstrating antiparasitic activity, developed over the last decade through drug discovery and drug repurposing, is provided as a means of giving new perspectives for future research in this field.

How is Schizophrenia Treated?

Schizophrenia ◽  
2019 ◽  
Author(s):  
Stephen J. Glatt ◽  
Stephen V. Faraone ◽  
Ming T. Tsuang
Keyword(s):  
Side Effects ◽  
High Risk ◽  
Treatment Options ◽  
Current Treatment ◽  
Good Evidence ◽  
Future Research ◽  
Number Of Patients ◽  
The Many ◽  
The Brain ◽  
Good Number

In earlier chapters, we described the many advances in our understanding of schizophrenia. Unfortunately, we still do not have a detailed blueprint of what exactly goes wrong in the brain in schizophrenia, or a means for ‘fixing’ the brain. But even without a clear grasp of all the underlying, hidden facts, we have still made many gains. While we search for more clues, we need to use the facts on hand to help individuals with schizophrenia and their families to relieve their suffering. As the saying goes, ‘The perfect is the enemy of the good’, and some good treatment options exist. So while we work toward a perfect under­standing of schizophrenia and develop treatments that are targeted toward each individual’s personal form of the disorder, we must rely on the evidence for existing treatments to separate the ‘good’ from the ‘bad’. Bad treatments are those that are ineffective, counterproductive, or have a high risk of very serious side effects. Good treatments are those that have good evidence of helping a fair number of patients to reduce at least the positive symptoms of the disorder while having a relatively low risk of serious side effects. No current treatment for the disorder will work for all affected individuals, and we do not yet have a way of being able to tell before treatment what chance the affected individual has of improving with a given treatment. These are all goals for future research, including the discovery of brand new medicines. For now, we review the cur­rently available treatments with the best evidence of being able to help a good number of patients. The onset of schizophrenia can be frightening, for both affected individuals and their families. Affected individuals begin to express many odd beliefs: that people are trying to harm them— friends, relatives, strangers, or celebrities; that others can hear their thoughts as if spoken aloud; that voices talk to them, even when they are alone. In addition, they cannot express feelings and thoughts clearly and are frustrated by the doubts expressed by relatives and friends.

scholarly journals Phoenixin 20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial cells (HAECs): A Protective Implication in Atherosclerosis

2020 ◽  
Author(s):  
Hua-Song Lin ◽  
Xiao-Lan Wei ◽  
Bi-Rong Zheng ◽  
Ruo-Ting Lin ◽  
Ya-li Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Treatment Options ◽  
Current Treatment ◽  
Luciferase Reporter ◽  
Future Research ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
First Time ◽  
G Protein Coupled ◽  
Aortic Endothelial

Abstract Background: The cause of atherosclerosis is not known, and therefore the current treatment options are limited. In the present study, we aimed to investigate the effects of Phoenixin 20 and its receptor G protein-coupled receptor 173 (GPR173) against ox-LDL- induced endothelial dysfunction. Materials and Methods: Human aortic endothelial cells (HAECs) were treated with 10 μg/ml ox-LDL in the presence or absence of phoenixin 20. Gene expression of GPR173, ICAM-1, VCAM-1, IL-1β, IL-8, MCP-1, and NOX-4 were measured by real time PCR. Protein expression was assayed by western blot analysis. Secretions of pro-inflammatory cytokines were measured by ELISA. The attachment of THP-1 monocytes to HAECs was detected using calcein-AM staining. Transcriptional activity of NF-κB was measured using dual-luciferase reporter assay. Results: Our findings indicate that ox-LDL significantly lowered the expression of GPR173 in HAECs and triggered an increase in ROS, NOX-4, and proinflammatory cytokine expression. Importantly, we demonstrate that agonism of GPR173 using phoenixin 20 significantly ameliorated these harmful effects of ox-LDL. We also show that agonism of GPR173 can prevent the attachment of monocytes to endothelial cells, which is an important therapeutic approach to prevent atherogenesis. Conclusion: Here, for the first time to our knowledge, we provide a basis for future research on the role of GPR173 as a new potential treatment against atherosclerosis.

Sign in / Sign up

Export Citation Format

Share Document