scholarly journals Engineering Gain-of-Function Analogues of the Spider Venom Peptide HNTX-I, A Potent Blocker of the hNaV1.7 Sodium Channel

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 358 ◽  
Author(s):  
Yunxiao Zhang ◽  
Qiuchu Yang ◽  
Qingfeng Zhang ◽  
Dezheng Peng ◽  
Minzhi Chen ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Medical Condition ◽  
Human Life ◽  
Hydrophobic Surface ◽  
Well Being ◽  
Charged Surface ◽  
Multiple Site ◽  
Wild Type ◽  
Voltage Gated ◽  
Normal Human

Pain is a medical condition that interferes with normal human life and work and reduces human well-being worldwide. The voltage-gated sodium channel (VGSC) human NaV1.7 (hNaV1.7) is a compelling target that plays a key role in human pain signaling. The 33-residue peptide µ-TRTX-Hhn2b (HNTX-I), a member of NaV-targeting spider toxin (NaSpTx) family 1, has shown negligible activity on mammalian VGSCs, including the hNaV1.7 channel. We engineered analogues of HNTX-I based on sequence conservation in NaSpTx family 1. Substitution of Asn for Ser at position 23 or Asp for His at position 26 conferred potent activity against hNaV1.7. Moreover, multiple site mutations combined together afforded improvements in potency. Ultimately, we generated an analogue E1G–N23S–D26H–L32W with >300-fold improved potency compared with wild-type HNTX-1 on hNaV1.7 (IC50 0.036 ± 0.007 µM). Structural simulation suggested that the charged surface and the hydrophobic surface of the modified peptide are responsible for binding affinity to the hNaV1.7 channel, while variable residues may determine pharmacological specificity. Therefore, this study provides a profile for drug design targeting the hNaV1.7 channel.

Sequence of the voltage-gated sodium channel β1-subunit in wild-type and in quivering mice

1996 ◽  
Vol 42 (2) ◽  
pp. 222-226 ◽  
Author(s):  
Christie L.S. Grosson ◽  
Stephen C. Cannon ◽  
David P. Corey ◽  
James F. Gusella
Keyword(s):  
Sodium Channel ◽  
Wild Type ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Knowledge, Awareness, Prevalence and Frequency of Daily Physical Activity and Its Association with Stroke in Young Adult Population

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 507-513
Author(s):  
Sai Sanjith A ◽  
Karthik Ganesh Mohanraj
Keyword(s):  
Physical Activity ◽  
Medical Condition ◽  
Human Life ◽  
Adult Population ◽  
Well Being ◽  
Health Condition ◽  
The Body ◽  
Daily Physical Activity ◽  
Medical Emergency ◽  
The Brain

Stroke is a medical condition affecting the brain. It occurs when the blood supply to the brain or part of the brain is stopped or reduced, preventing the brain cells from getting oxygen. As the neurons are the most sensitive cells in the body, they tend to die after cessation of oxygen supply for a very few minutes. Several remedial measures are available for this medical emergency at the time of stroke and even after that. It is believed that the stroke recurs after time and thus preparatory and cautionary steps to be carried out for survival. Among that daily physical activity seems to have a greater positive approach towards stroke survivors. In general, physical activity is an essential part of human life which many people neglect. But it has an underlying significance for human life and healthy well-being. It maintains the body's health condition free of certain diseases too. Thus, this study attempts to analyze the awareness and to knowledge the people about the association between stroke and daily physical activity.

Abstract P081: Voltage-Gated TTX-Sensitive Nav1.1 Brain Sodium Channels Are Important for Cardiac Contractile Function

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Susan T Varghese ◽  
Stephanie Humphrey ◽  
An Xie ◽  
Andrew P Escayg ◽  
Samuel C Dudley
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Contractile Function ◽  
Wild Type ◽  
Cardiac Contractile Function ◽  
Isolated Cells ◽  
Voltage Gated ◽  
Cardiac Contractile ◽  
Lv Mass ◽  
Whole Heart

Background: Mutations in voltage gated brain sodium channel Nav1.1 have been linked to many disorders, including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). Recent studies have identified TTX- sensitive Nav1.1 brain sodium channels in the SA node and ventricular T-tubules of the heart, though their role in cardiac function is still controversial. We tested the functional significance of Nav1.1 sodium channels in the heart by creating a novel knock-in of human epilepsy GEFS+ mutation SCN1A-R1648H at the Scn1a locus of a C57BL/6J X 129 mouse. Method: In vivo 2-D echocardiography was performed on 2 week old (juvenile) and 8 week old (adult) wild-type and heterozygote (Scn1aRH/+) mice after extracardiac neuronal block through intraperitoneal injections of atropine and propranolol (2.5mg/kg each). Calcium and contractility studies on adult ventricular cardiomyocytes isolated from the wild type and Scn1aRH/+ mice paced at 0.5Hz were followed by administration of TTX (100nM, a brain sodium channel inhibitor) and pacing at 2Hz. qRT-PCR and Western blot of the isolated cells and whole heart samples was also done. Results: A decrease in Nav1.1 gene expression in the Scn1aRH/+ juvenile (by 31%, 0.69 of 1) and adult (by 60%, 0.4 of 1) whole heart samples and isolated cells (p<0.05) was seen. Echocardiography revealed concentric hypertrophy in the juvenile Scn1aRH/+ mice by a significant increase in LV mass, LV mass/body weight ratio, and relative wall thickness (p<0.05). In the adult Scn1aRH/+ mice, systolic isovolumic contraction time (IVCT) was reduced (p=0.03) and decrease in diastolic function was evident through significant decreases in isovolumic relaxation time (IVRT) and E’/A’ ratio, and increase in E/E’ ratio. Isolated adult ventricular Scn1aRH/+ cardiomyocytes showed significant reduction in percent sarcomere shortening, maximum rate of contraction and relaxation, and time to peak contraction, exaggerated with TTX and pacing at 2Hz (p<0.5). Conclusions: Our study demonstrates the importance of voltage gated TTX-sensitive Nav1.1 brain sodium channels in cardiac contractile function and their possible role in cardiac complications in epilepsy.

scholarly journals Permasalahan Kesehatan Mental di Masa Covid-19

2021 ◽  
Vol 1 (2) ◽  
pp. 170-185
Author(s):  
Athiyyah ◽  
Harri Santoso
Keyword(s):  
Mental Health ◽  
Mental Health Problems ◽  
Virus Disease ◽  
Human Life ◽  
Well Being ◽  
Health Problems ◽  
Life Patterns ◽  
Library Research ◽  
Normal Human ◽  
Drug And Alcohol

The beginning of 2020 was the year when people recognized a terrible virus which is now known as Corona Virus Disease 2019 (COVID-19). The length of time that Covid-19 attacks the health of even the lives of people in the world cause changes in normal human life patterns. These changes bring an impact on human mental well-being because they have to experience the detrimental effects caused by the virus. This article aims to describe the mental health problems that occurred during the Covid-19 period and ways to maintain mental health during this pandemic. The technique used is library research by collecting several previous articles. Thus, the results obtained indicate that mental health problems that exist in society are panic buying, anxiety, stress, fear, depression, toxic masculinity, drug and alcohol abuse, psychosomatic disorders, etc. Ways to maintain mental health and prevent it from problems include consuming nutritious foods, building good relationships with family and friends, doing meditation to control anxiety, wisely sorting information, asking for professional help, and so on.

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

(Preprint)

2018 ◽  
Author(s):  
Natalia Banasik ◽  
Dariusz Jemielniak ◽  
Wojciech P?dzich
Keyword(s):  
Medical Condition ◽  
Extended Period ◽  
Well Being ◽  
Marginal Effect ◽  
Life Duration ◽  
Significant Difference ◽  
The Mean ◽  
Academic Teachers ◽  
Length Of Life ◽  
The Impact

BACKGROUND There have been mixed results of the studies checking whether prayers do actually extend the life duration of the people prayed for. Most studies on the topic included a small number of prayers and most of them focused on people already struggling with a medical condition. Intercessory prayer’s influence on health is of scholarly interest, yet it is unclear if its effect may be dependent on the number of prayers for a named individual received per annum. OBJECTIVE We sought to examine if there is a noticeable increased longevity effect of intercessory prayer for a named individual’s well-being, if he receives a very high number of prayers per annum for an extended period. METHODS We retrieved and conducted a statistical analysis of the data about the length of life for 857 Roman Catholic bishops, 500 Catholic priests, and 3038 male academics from the US, France, Italy, Poland, Brazil, and Mexico. We obtained information for these individuals who died between 1988 and 2018 from Wikidata, and conducted an observational cohort study. Bishops were chosen for the study, as they receive millions of individual prayers for well being, according to conservative estimates. RESULTS There was a main effect for occupation F(2, 4391) = 4.07, p = .017, ηp 2 = .002, with pairwise comparisons indicating significant differences between the mean life duration of bishops (M=30489) and of priests (M=29894), but none between the academic teachers (M=30147) and either of the other groups. A comparison analysis between bishops from the largest and the smallest dioceses showed no significant difference t(67.31)=1.61, p = .11. Our main outcome measure is covariance of the mean length of life in each of the categories: bishops, priests, academic teachers, controlled for nationality. CONCLUSIONS The first analysis proved that bishops live longer than priests, but due to a marginal effect size this result should be treated with caution. No difference was found between the mean length of life of bishops from the largest and the smallest dioceses. We found no difference between bishops and male academics. These results show that the impact of intercessory prayers on longevity is not observable.

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