ABSTRACT
In recent decades, the interest in responsive fibrous structures has surged, propelling them into diverse applications: from wearable textiles that adapt to their surroundings, to filtration membranes dynamically altering selectivity, these structures showcase remarkable versatility. Various stimuli, including temperature, light, pH, electricity, and chemical compounds, can serve as triggers to unleash physical or chemical changes in response. Processing methodologies such as weaving or knitting using responsive yarns, electrospinning, as well as coating procedures, enable the integration of responsive materials into fibrous structures. They can respond to these stimuli, and comprise shape memory materials, temperature-responsive polymers, chromic materials, phase change materials, photothermal materials, among others. The resulting effects can manifest in a variety of ways, from pore adjustments and altered permeability to shape changing, color changing, and thermal regulation. This review aims to explore the realm of fibrous structures, delving into their responsiveness to external stimuli, with a focus on temperature, light, and pH.
ABSTRACT
We exhibit examples of high-dimensional unimodal posterior distributions arising in nonlinear regression models with Gaussian process priors for which Markov chain Monte Carlo (MCMC) methods can take an exponential run-time to enter the regions where the bulk of the posterior measure concentrates. Our results apply to worst-case initialized ('cold start') algorithms that are local in the sense that their step sizes cannot be too large on average. The counter-examples hold for general MCMC schemes based on gradient or random walk steps, and the theory is illustrated for Metropolis-Hastings adjusted methods such as preconditioned Crank-Nicolson and Metropolis-adjusted Langevin algorithm. This article is part of the theme issue 'Bayesian inference: challenges, perspectives, and prospects'.
ABSTRACT
This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) by comparing the effects of alternating and random frequencies in an animal model of persistent inflammatory hyperalgesia. The model was induced by Freund's complete adjuvant (CFA) intraplantar (i.pl.) injection. Mice were treated with different protocols of time (10, 20, or 30 min), ear laterality (right, left or both), and frequency (alternating or random). Mechanical hyperalgesia was evaluated, and some groups received i.pl. WRW4 (FPR2/ALX antagonist) to determine the involvement. Edema, paw surface temperature, and spontaneous locomotor activity were evaluated. Interleukin-1ß, IL-6, IL-10, and IL4 levels were verified by enzyme-linked immunosorbent assay. AnxA1, FPR2/ALX, neutrophil, M1 and M2 phenotype macrophage, and apoptotic cells markers were identified using western blotting. The antihyperalgesic effect pVNS with alternating and random frequency effect is depending on the type of frequency, time, and ear treated. The pVNS random frequency in the left ear for 10 min had a longer lasting antihyperalgesic effect, superior to classical stimulation using alternating frequency and the FPR2/ALX receptor was involved in this effect. There was a reduction in the levels of pro-inflammatory cytokines and an increase in the immunocontent of AnxA1 and CD86 in mice paw. pVNS with a random frequency in the left ear for 10 min showed to be optimal for inducing an antihyperalgesic effect. Thus, the random frequency was more effective than the alternating frequency. Therefore, pVNS may be an important adjunctive treatment for persistent inflammatory pain.
Subject(s)
Annexin A1 , Animals , Mice , Annexin A1/chemistry , Annexin A1/genetics , Annexin A1/metabolism , Electric Stimulation , Hyperalgesia/complications , Hyperalgesia/therapy , Hyperalgesia/metabolism , Inflammation/complications , Inflammation/metabolism , Pain , Receptors, Formyl Peptide , Vagus Nerve/metabolismABSTRACT
JUSTIFICACIÓN: recientes estudios promovidos por la Federación Dental Internacional y el Consejo General de Dentistas demuestran que existe una relación bidireccional entre la salud oral y la diabetes tipo 2 (DM2). Tanto en la periodontitis como en la DM2, los procesos inflamatorios están aumentados, lo que produce alteraciones microvasculares que provocan que la presencia de una de las dos afecte y empeore el cuadro de la otra enfermedad, lo que puede llevar a un aumento del 20 % del riesgo cardiovascular en estos pacientes. La labor del farmacéutico comunitario podría ayudar a detectar de manera precoz los problemas gingivales y con ello prevenir futuras complicaciones sistémicas derivadas de una enfermedad periodontal (EP) no controlada.OBJETIVO: diseño de un protocolo de cribado para la detección de EP en pacientes con DM2.MATERIAL Y MÉTODOS: se elaboró un protocolo sistematizado "ad hoc" para el desarrollo de una entrevista demográfica, además de una recogida de variables y síntomas de alarma. Fueron seleccionados tras la consulta de documentos hallados mediante una búsqueda bibliográfica en PUBMED, Biblioteca Cochrane Plus y documentos del grupo de Epidemiología de la Sociedad Española de Diabetes. En el registro se incorporaron variables correspondientes a las características de los pacientes: demográficas (edad y sexo), relacionadas con el hábito tabáquico y clínicas (años de tratamiento de la DM2, grupo de fármaco antidiabético, tratamiento cardiovascular, salud dental y sintomatología asociada). RESULTADOS Población diana: pacientes mayores de 18 años que en su plan de tratamiento presenten al menos un medicamento antidiabético frente a DM2. (AU)
Subject(s)
Humans , Diabetes Mellitus , 35170 , Periodontitis , Pharmacists , Diabetes Mellitus, Type 2 , Patients , TherapeuticsABSTRACT
Hydatid disease is a parasitic zoonosis caused by genotypes of the genus Echinococcus. This disease inflicts economic loses in livestock and cause public health burden in resource poor mostly in developing countries. The aim of this study was to determine the prevalence and identity of the genotypes responsible for hydatid cysts in cattle, goats and pigs slaughtered at selected abattoirs of southern provinces of Mozambique. Cysts were collected from liver and lungs and hydatid confirmation was made by cystic membrane observation and visualization of protoscoleces by light microscope. Thirty-two hydatid cysts from 817 cattle and two from 68 pigs were collected from local slaughterhouses and slabs. DNA was extracted from protoscoleces of each cyst together with the cystic membrane and amplified based on the mitochondrial subunit 1 of the cox1 and nad1 gene. The overall prevalence of hydatid cysts was 3.9% in cattle, 2.9% in pigs and none of the goats were found with cysts. All cysts collected from cattle and pigs were identified as Echinococcus ortleppi (G5) with a minimum homology of 99% on BLAST analysis. Our results confirm the presence of E. ortleppi in cattle and pigs in southern Mozambique at a low prevalence and further studies are recommended to determine the risk factors favoring the transmission of this zoonotic parasite in the resource-poor livestock farming communities of this region.
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Currently, photobiomodulation therapy (PBMT) is gaining space in the scientific and clinical environment. To help elucidate the importance of irradiance, this study evaluated the effect of two different PBMT irradiances (3.5 and 90 mW/cm2), given a fixed wavelength of 630 nm and a dose of 2 J/cm2, on mechanical hyperalgesia following Complete Freund's Adjuvant (CFA) intraplantar (i.pl.) injection in mice. Additionally, we investigated the role of peripheral opioid and endothelin-B receptors (ETB-R), as well as sex differences in treatment outcome. Different groups of male or female mice were evaluated 6 and 96 h after CFA. Mechanical hyperalgesia was evaluated 30 min after treatments. Naloxone or Bq-788 administration, fifteen minutes before PBMT or Sarafotoxin S6c, helped determine the involvement of peripheral opioid and ETB-Rs on PBMT. Lastly, ETB-Rs skin immunocontent in both sexes was quantified after PBMT consecutive daily treatments. PBMT at an irradiance of 90 mW/cm2, was more effective than 3.5 mW/cm2. Bq-788 and naloxone administration prevented the effects of PBMT and SRTX S6c; however, PBMT did not influence peripheral ETB-Rs immunocontent. The results suggest that irradiance influences PMBT effect; and that activation of ETB-R play a role in peripheral PBMT opioid induced analgesia. Lastly, PMBT effects do not appear to be sex-dependent.
Subject(s)
Analgesics, Opioid/radiation effects , Hyperalgesia/radiotherapy , Low-Level Light Therapy/methods , Receptor, Endothelin B/radiation effects , Animals , Dose-Response Relationship, Radiation , Female , Male , Mice , Naloxone/pharmacology , Oligopeptides/pharmacology , Piperidines/pharmacology , Radiation Exposure , Sex Factors , Time Factors , Viper Venoms/metabolismABSTRACT
The taeniid Echinococcus is the causative agent of the zoonotic disease echinococcosis/hydatidosis and is associated with economic losses in livestock production. This review summarizes available scientific literature on circulating species of Echinococcus in humans, wild and domestic animals in countries of Southern Africa Development Community, and identifies knowledge gaps and recommend research priorities. Data were systematically accessed from Google Scholar, MEDLINE/PubMed and from library resources from December 2017 to June 2019. Meta-analysis was conducted in STATA program and heterogeneity and prevalence values were pooled by host species with 95% confidence interval. In intermediate hosts, the overall prevalence of Echinococcus by meat inspection was 10% (CI: 9-11%) in small ruminants, 7% (CI: 5-8%) in cattle, 1% (CI: 0-1%) in pigs and 9% (CI: 0-29%) in wild herbivores. In canids by CoproAg-ELISA and necropsy the prevalence was of 10% (CI: 8-10%) and 6% (CI: 3-10%) respectively. A high level of heterogeneity (I2â¯>â¯65%) was observed for all study groups. Echinococcus equinus, E. canadensis, E ortleppi and E. felidis were reported from wildlife and E. ortleppi, E. granulosus s. s. and E. canadensis from humans. There is paucity of research in echinococcosis and gaps in prevalence reports over time in both humans and animals in the SADC region and we recommend an increase in future studies on the epidemiology of disease, risk factors for transmission in animals and humans and its relation with human health specially in the advent of HIV pandemic following a "One Health" approach.
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Fibromyalgia (FM) is a chronic pain syndrome, characterised by several symptoms. One of the most prevalent symptoms in FM is balance impairment that compromise the autonomy, function and performance status of patients.Purpose: The main objective of the present study was to evaluate the effect of sensory stimulation provided by the use of a low additional thickness of 0.8 mm placed under the great toes bilaterally on the centre of pressure (CoP) measures in patients with FM. It was hypothesised that postural ability would change with a low focal additional thickness used to compute these measures.Materials and Method: Twenty-four patients with FM voluntarily participated in this study. Postural performance during quiet standing was investigated through the CoP displacements recorded using a force-plate. Sensory stimulation was provided by a small additional thickness of 0.8 mm placed under the great toe bilaterally and two conditions were compared: additional thickness 0 (control) and 0.8 mm.Results: An improvement of body balance through spatial parameters with sensory cutaneous stimulation applied under the great toe bilaterally were observed in patients with FM. Our results showed a significant decrease of surface area and mean speed of CoP, associated to a significant decrease of variance of speed. An additional observation is that sagittal (Y) mean position of the CoP gets more anterior (+ 5 mm) relative to control condition.Conclusion: These findings brings new clinical perspectives in the development of intervention strategies in the management of patients with FM and balance disorders, completing validated therapeutic strategies.
Subject(s)
Feedback, Sensory/physiology , Fibromyalgia/physiopathology , Postural Balance/physiology , Touch Perception/physiology , Adult , Biomechanical Phenomena/physiology , Female , Hallux/physiology , Humans , Male , Middle Aged , Physical StimulationABSTRACT
Let ð¢ be a compact group and let fij∈C(ð¢). We define the Non-Unique Games (NUG) problem as finding g1, ,gn∈ð¢ to minimize ∑i,j=1nfijgigj-1. We introduce a convex relaxation of the NUG problem to a semidefinite program (SDP) by taking the Fourier transform of fij over ð¢. The NUG framework can be seen as a generalization of the little Grothendieck problem over the orthogonal group and the Unique Games problem and includes many practically relevant problems, such as the maximum likelihood estimator to registering bandlimited functions over the unit sphere in d-dimensions and orientation estimation of noisy cryo-Electron Microscopy (cryo-EM) projection images. We implement a SDP solver for the NUG cryo-EM problem using the alternating direction method of multipliers (ADMM). Numerical study with synthetic datasets indicate that while our ADMM solver is slower than existing methods, it can estimate the rotations more accurately, especially at low signal-to-noise ratio (SNR).
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Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to mimic CRPS-I. Animals received ankle joint mobilization 48h after the IR procedure, and response to mechanical stimuli was evaluated. For biochemical analyses, mitochondrial function as well as oxidative stress thiobarbituric acid reactive substances (TBARS), protein carbonyls, antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels were determined. IR induced mechanical hyperalgesia which was subsequently reduced by acute MT treatment. The concentrations of oxidative stress parameters were increased following IR with MT treatment preventing these increases in malondialdehyde (MDA) and carbonyls protein. IR diminished the levels of SOD and CAT activity and MT treatment prevented this decrease in CAT but not in SOD activity. IR also diminished mitochondrial complex activity, and MT treatment was ineffective in preventing this decrease. In conclusion, repeated sessions of MT resulted in antihyperalgesic effects mediated, at least partially, through the prevention of an increase of MDA and protein carbonyls levels and an improvement in the antioxidant defense system.
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The Municipality of Londrina is located in the northern region of the State of Paraná, and is inserted in the Atlantic Forest Biome, which is considered a hotspot for world conservation. This biome suffers from the loss of natural areas mainly due to urbanization, agriculture and livestock farming. Therefore, it is imperative to improve the knowledge of species occurring in the region for their efficient conservation. Due to its large area and lack of herpetological studies, most of the northern region of the state of Paraná presents gaps in snake records. The present study aims to review the records of snake species for the area of Londrina based on the literature and specimens deposited in scientific collections. Thirty-two (32) snake species were reported, belonging to the families Anomalepididae (1), Boidae (1), Colubridae (4), Dipsadidae (18), Elapidae (2), Typhlopidae (1) and Viperidae (4). In addition, we present an artificial key to the identification of the reported species.
ABSTRACT
The Municipality of Londrina is located in the northern region of the State of Paraná, and is inserted in the Atlantic Forest Biome, which is considered a hotspot for world conservation. This biome suffers from the loss of natural areas mainly due to urbanization, agriculture and livestock farming. Therefore, it is imperative to improve the knowledge of species occurring in the region for their efficient conservation. Due to its large area and lack of herpetological studies, most of the northern region of the state of Paraná presents gaps in snake records. The present study aims to review the records of snake species for the area of Londrina based on the literature and specimens deposited in scientific collections. Thirty-two (32) snake species were reported, belonging to the families Anomalepididae (1), Boidae (1), Colubridae (4), Dipsadidae (18), Elapidae (2), Typhlopidae (1) and Viperidae (4). In addition, we present an artificial key to the identification of the reported species.
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A community-based intervention combining health education (HE) and treatment of pigs for control of porcine cysticercosis (PC), gastrointestinal (GI) helminths, African swine fever (ASF) and external parasites was tested involving six villages of resource-poor smallholder pig farmers. Farmers and pigs of six rural villages were randomly allocated into group 1 (HE), which served as controls, and group 2 (HE + OFZ) pigs received a single oral dose of 30 mg/kg OFZ. Farmers were trained in pig health, housing and feeding. The proportion of farmers with confined pigs, the adoption rate of the introduced pig pen, the sero-prevalence of PC and ASF, the prevalence and intensity of GI nematodes and the prevalence of ectoparasites were measured at 9, 15 and 24 months after initiation and compared to a baseline survey to seek the effectiveness of the interventions. There was no clear effect of the intervention on the sero-prevalence of PC, but analysis of the rate of change in prevalence between the two groups showed significant effect with the rate of change to lower prevalence in the HE + OFZ group compared to the HE group. Although HE managed to improve the farmer's knowledge in the control and prevention of ASF and ectoparasites, there was no significant reduction in the sero-prevalence of ASF and the prevalence of ectoparasites throughout the two-year period. The reported ineffectiveness of the intervention in this study suggested that more research is needed to develop more effective methods for controlling PC, ASF and pig parasites.
Subject(s)
African Swine Fever/prevention & control , Benzimidazoles/pharmacology , Cysticercosis/prevention & control , Swine Diseases/prevention & control , African Swine Fever/epidemiology , Animal Husbandry/methods , Animals , Cysticercosis/epidemiology , Cysticercosis/veterinary , Farmers , Female , Health Education/methods , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/prevention & control , Male , Mozambique/epidemiology , Parasites , Prevalence , Rural Population , Swine , Swine Diseases/epidemiology , Swine Diseases/parasitologyABSTRACT
Taenia solium taeniasis/cysticercosis is a neglected parasitic zoonosis with significant economic and public health impacts. Control measures can be broadly grouped into community health education, improvements in hygiene and sanitary conditions, proper meat handling at household and community level, improved standards of meat inspection, pig management, treatment of individual patients and possibly human populations, and treatment and/or vaccination of porcine populations. This manuscript looks critically into currently existing control options and provides suggestions on which (combination of) tools would be most effective in the control of T. solium taeniasis/cysticercosis in sub-Saharan Africa. Field data and disease transmission simulations suggest that implementation of a single intervention control strategy will not lead to a satisfactory reduction of disease morbidity or transmission. A feasible strategy to combat T. solium taeniasis/cysticercosis would include a combination of approaches focussing on both human (health education and treatment) and animal host (management, treatment and vaccination), which can vary for different communities and different geographical locations. Selection of the specific strategy depends on cost-effectiveness analyses based on solid field data, currently unavailable, though urgently needed; as well as on health priorities and resources of the country. A One Health approach involving medical, veterinary, environmental and social sectors is essential for T. solium to be controlled and eventually eliminated. Finally the success of any intervention is largely dependent on the level of societal and political acceptance, commitment and engagement.
Subject(s)
Anthelmintics/therapeutic use , Cysticercosis/drug therapy , Meat/parasitology , Swine Diseases/drug therapy , Taenia solium/drug effects , Taeniasis/drug therapy , Zoonoses/drug therapy , Adolescent , Adult , Africa South of the Sahara/epidemiology , Aged , Aged, 80 and over , Animals , Cysticercosis/epidemiology , Cysticercosis/prevention & control , Female , Health Education , Humans , Male , Middle Aged , Public Health , Sus scrofa/parasitology , Swine , Swine Diseases/epidemiology , Swine Diseases/parasitology , Swine Diseases/prevention & control , Taeniasis/epidemiology , Taeniasis/prevention & control , Vaccination , Young Adult , Zoonoses/prevention & controlABSTRACT
The little Grothendieck problem consists of maximizing Σ ij Cijxixj for a positive semidef-inite matrix C, over binary variables xi ∈ {±1}. In this paper we focus on a natural generalization of this problem, the little Grothendieck problem over the orthogonal group. Given C ∈ â dn × dn a positive semidefinite matrix, the objective is to maximize [Formula: see text] restricting Oi to take values in the group of orthogonal matrices [Formula: see text], where Cij denotes the (ij)-th d × d block of C. We propose an approximation algorithm, which we refer to as Orthogonal-Cut, to solve the little Grothendieck problem over the group of orthogonal matrices [Formula: see text] and show a constant approximation ratio. Our method is based on semidefinite programming. For a given d ≥ 1, we show a constant approximation ratio of αâ(d)2, where αâ(d) is the expected average singular value of a d × d matrix with random Gaussian [Formula: see text] i.i.d. entries. For d = 1 we recover the known αâ(1)2 = 2/π approximation guarantee for the classical little Grothendieck problem. Our algorithm and analysis naturally extends to the complex valued case also providing a constant approximation ratio for the analogous little Grothendieck problem over the Unitary Group [Formula: see text]. Orthogonal-Cut also serves as an approximation algorithm for several applications, including the Procrustes problem where it improves over the best previously known approximation ratio of [Formula: see text]. The little Grothendieck problem falls under the larger class of problems approximated by a recent algorithm proposed in the context of the non-commutative Grothendieck inequality. Nonetheless, our approach is simpler and provides better approximation with matching integrality gaps. Finally, we also provide an improved approximation algorithm for the more general little Grothendieck problem over the orthogonal (or unitary) group with rank constraints, recovering, when d = 1, the sharp, known ratios.
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The diagnosis of neurocysticercosis (NCC) requires expensive neuroimaging techniques that are seldom affordable for people in endemic countries. Accordingly, there is a need for new low-cost diagnostic methods that offer high sensitivity and specificity. In this study, we evaluated Western blot analysis of the previously described recombinant antigen Tsol-p27 in relation to a commercial or in-house enzyme-linked immunosorbent assay (ELISA) for NCC, and compared the results with those provided by a commercial enzyme-linked immunoelectrotransfer blot (EITB) assay, which was regarded as the reference standard method. The analysed serum samples were obtained from 165 people, 18 of whom were confirmed to be NCC positive by EITB. Comparing our Western blot analysis of Tsol-p27 with a previous evaluation performed in Central America showed similar specificity (96.69% versus 97.8%) and sensitivity (85.71% versus 86.7%). The present results indicate that the recombinant Tsol-p27 antigen provides good sensitivity and specificity, and might be preferable as a diagnostic antigen in poorly equipped laboratories in endemic countries.
Subject(s)
Antibodies, Helminth/blood , Antigens, Helminth/immunology , Neurocysticercosis/diagnosis , Serologic Tests/methods , Enzyme-Linked Immunosorbent Assay , Immunoblotting , Mozambique , Sensitivity and SpecificityABSTRACT
INTRODUCTION: The anti-atrial fibrillation (AF) effects of GS-458967 (GS-967), a selective, potent inhibitor of cardiac late Na(+) current (I(Na)), were evaluated in a novel model of AF induction that does not require electrical stimuli. METHODS AND RESULTS: In 6 closed-chest anesthetized pigs, AF was induced by intrapericardial acetylcholine (1 mL of 100 mM solution) followed within 1 minute by epinephrine (20 µg/kg, i.v., bolus over 1 min). Effects of GS-967 (0.4 mg/kg, i.v., infused over 30 min) on inducibility and duration of AF were analyzed. Administration of acetylcholine followed by epinephrine elicited spontaneous AF that persisted for 12.03 ± 1.22 minutes (mean ± SEM) in all 6 pigs. Following GS-967, AF did not occur in 5 of 6 pigs when plasma concentration was 383 ± 150 nM. In the single animal in which AF could still be induced, the arrhythmia lasted 6.3 minutes. Partial return of AF inducibility occurred in 2 of 6 animals at 90 minutes, when plasma concentration of GS-967 was 228 ± 35 nM. GS-967 reduced the QT interval (P = 0.004), consistent with cardiac late I(Na) inhibition, but did not affect heart rate, mean arterial pressure, QRS duration, or PR interval. Epinephrine infusion alone, tested in a separate group (N = 6), did not provoke AF. CONCLUSION: Selective cardiac late I(Na) inhibition with GS-967 suppresses spontaneous induction of AF in a novel model that does not require provocative electrical stimuli. Because this mode of action has only a mild on effect on contractility, it offers an advantage over contemporary anti-AF agents, which can have negative inotropic actions.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/prevention & control , Autonomic Nervous System Diseases/prevention & control , Pyridines/therapeutic use , Sodium Channel Blockers/therapeutic use , Triazoles/therapeutic use , Acetylcholine , Animals , Anti-Arrhythmia Agents/pharmacokinetics , Arterial Pressure/drug effects , Atrial Fibrillation/chemically induced , Atrial Fibrillation/physiopathology , Autonomic Nervous System Diseases/complications , Autonomic Nervous System Diseases/physiopathology , Electric Stimulation , Electrocardiography/drug effects , Epinephrine , Heart Rate/drug effects , Male , Pyridines/pharmacokinetics , Sodium Channel Blockers/pharmacokinetics , Sus scrofa , Swine , Triazoles/pharmacokineticsABSTRACT
BACKGROUND: Catecholamines can elicit early and delayed afterdepolarizations (EADs and DADs), resulting in ventricular tachyarrhythmias. OBJECTIVE: As inhibition of the cardiac late sodium current (I(Na)) suppresses EADs and DADs, we examined whether GS-458967 (GS-967), a potent inhibitor of this current that is devoid of beta-adrenergic blocking action, can prevent epinephrine-induced ventricular tachycardia (VT) induction in an intact porcine model. METHODS: In 12 closed-chest anesthetized pigs, spontaneous VT was induced by epinephrine administration (2.0 µg/kg, intravenous, bolus over 1 minute). Effects of GS-967 (0.4 mg/kg, intravenous, infused over 30 minutes) on VT incidence, T-wave alternans (TWA) level, and hemodynamic and electrophysiologic parameters before and after epinephrine were analyzed (N = 6). Effects of vehicle control were investigated in 6 animals. TWA was measured using the Modified Moving Average method. RESULTS: Epinephrine elicited spontaneous hemodynamically significant nonsustained VT in all 6 pigs and increased TWA by 28-fold compared to baseline (P < .001). GS-967 reduced mean 3- to 7-beat VT incidence by 55% (from 9.5 ± 2.72 to 4.3 ± 0.76 beats/min, P = .020) and ≥8-beat VT incidence by 56% (from 1.6 ± 0.47 to 0.7 ± 0.42 beats/2 min, P = .033) and eliminated the VT-associated hypotension, with no changes in chronotropic and minimal attenuation of the inotropic responses to epinephrine. Concurrently, GS-967 at 30, 60, and 90 minutes reduced the magnitude of the epinephrine-induced surge in TWA by 56% (from 140 ± 13.2 to 62 ± 12.1 µV, P < .01), 62% (to 53 ± 8.3 µV, P < .01), and 51% (to 69 ± 14.0 µV, P < .01) (means ± SEM), respectively. CONCLUSION: Selective cardiac late INa inhibition with GS-967 confers significant protection against catecholamine-induced VT and TWA.
Subject(s)
Pyridines/therapeutic use , Tachycardia, Ventricular/prevention & control , Triazoles/therapeutic use , Animals , Blood Pressure/drug effects , Disease Models, Animal , Electrocardiography , Epinephrine , Heart Rate/drug effects , Swine , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/physiopathologyABSTRACT
During aging processes, there is a range of functional changes, where we can highlight the disease related to the central nervous system, such as Alzheimer disease and others forms of dementia. This study investigated the effects of transcranial light emitting diode (LED) on cerebral blood flow in healthy elderly women analyzed by transcranial Doppler ultrasound (TCD) of the right and left middle cerebral artery and basilar artery. Twenty-five noninstitutionalized elderly women (mean age 72 years old), with a cognitive status >24, were assessed using transcranial Doppler ultrasound on two separate occasions: pre-irradiation and post-transcranial LED therapy (TCLT). Prior to this, they answered two questionnaires: the perceived stress scale and the general health questionnaire. TCLT (627 nm, 70 mW/cm(2), 10 J/cm(2)) was performed at four points of the frontal and parietal region for 30 s each, totaling 120 s two times per week for 4 weeks. Paired t-test results showed that there was a significant improvement after TCLT with increase in the systolic and diastolic velocity of the left middle cerebral artery (25 and 30%, respectively) and basilar artery (up to 17 and 25%), as well as a decrease in the pulsatility index and resistance index values of the three cerebral arteries analyzed (p < 0.05). TCD parameters showed improvement in the blood flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women.