scholarly journals Physical simulation of intra-arterial circulation using an experimental bench

Author(s):  
O. A. Germanova ◽  
V. A. Germanov ◽  
Yu. V. Shchukin ◽  
A. V. Germanov ◽  
A. E. Burmistrov ◽  
...  

The article describes the device and possibilities of application of the original device developed by us for simulation of intra-arterial circulation. The principles of operation of the device, a wide range of experimental and clinical studies in which it can be applied are outlined. The use of this useful model is illustrated by clinical examples.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Germanova ◽  
V A Germanov ◽  
Y V Shchukin ◽  
A V Germanov ◽  
G Galati

Abstract Purpose of study Using an original device for modeling of intra-arterial blood circulation, to study the features of intravascular hemodynamics with a regular heart rhythm and with various rhythm disturbances. Material and methods We used an original device developed by us to simulate intra-arterial circulation (Document of invention No. RU 202780 U1). The main part of the device is a glass tube of a rotameter with a length of 365 mm, an inlet end with a diameter of 20 mm, an outlet end of 16.5 mm, which is a model of an arterial vessel. Flexible silicone tubes are attached to the rotameter on both sides, with free ends connected to an electric pump, with various modes of operation (imitation of pulse waves with regular rhythm, premature ventricular contractions (PVCs), atrial fibrillation (AF). An aqueous solution of glycerin was introduced into a closed system diluted with water corresponding to the viscosity of the blood. A 5 mm long silk thread was alternately installed inside the tube, an intravascular piezoelectric crystal pressure probe connected to an oscilloscope. Also it was injected inside the tube a dye - clerical ink. Results With electric pump, we simulated the spreading of the pulse wave in regular heart rate, PVCs and AF. We observed the effect of a pressure wave (deflection of a silk thread, the appearance of a turbulent flow when using a dye) on the walls of the rotameter, with the formation of standing, reflected waves during the PVCs and AF. The pressure probe registered an increase in pressure inside the tube during the spread of the 1st post-extrasystolic contraction wave up to 58%, the wave after a long pause of more than 2 seconds with AF by 44% compared to the regular rhythm. Conclusion A device for modeling of intra-arterial circulation allows a wide range of experimental work in cardiology, normal and pathological physiology, and biophysics. FUNDunding Acknowledgement Type of funding sources: None.


2020 ◽  
Vol 4 (1) ◽  
pp. 50-58
Author(s):  
Matthias  Tietsch ◽  
Amir Muaremi ◽  
Ieuan Clay ◽  
Felix Kluge ◽  
Holger Hoefling ◽  
...  

Analyzing human gait with inertial sensors provides valuable insights into a wide range of health impairments, including many musculoskeletal and neurological diseases. A representative and reliable assessment of gait requires continuous monitoring over long periods and ideally takes place in the subjects’ habitual environment (real-world). An inconsistent sensor wearing position can affect gait characterization and influence clinical study results, thus clinical study protocols are typically highly proscriptive, instructing all participants to wear the sensor in a uniform manner. This restrictive approach improves data quality but reduces overall adherence. In this work, we analyze the impact of altering the sensor wearing position around the waist on sensor signal and step detection. We demonstrate that an asymmetrically worn sensor leads to additional odd-harmonic frequency components in the frequency spectrum. We propose a robust solution for step detection based on autocorrelation to overcome sensor position variation (sensitivity = 0.99, precision = 0.99). The proposed solution reduces the impact of inconsistent sensor positioning on gait characterization in clinical studies, thus providing more flexibility to protocol implementation and more freedom to participants to wear the sensor in the position most comfortable to them. This work is a first step towards truly position-agnostic gait assessment in clinical settings.


2020 ◽  
Vol 3 (4) ◽  
pp. 257-264
Author(s):  
Catherine J Hutchings

Abstract Antibodies are now well established as therapeutics with many additional advantages over small molecules and peptides relative to their selectivity, bioavailability, half-life and effector function. Major classes of membrane-associated protein targets include G protein-coupled receptors (GPCRs) and ion channels that are linked to a wide range of disease indications across all therapeutic areas. This mini-review summarizes the antibody target landscape for both GPCRs and ion channels as well as current progress in the respective research and development pipelines with some example case studies highlighted from clinical studies, including those being evaluated for the treatment of symptoms in COVID-19 infection.


2005 ◽  
Vol 48 (spe2) ◽  
pp. 145-152 ◽  
Author(s):  
David Wareham ◽  
J. Michael ◽  
Satya Das

Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticals


1977 ◽  
Vol 21 (1) ◽  
pp. 78-82
Author(s):  
Robert J. Hall ◽  
James C. Sanderlin

This paper reviews recent studies of human factors design criteria for transilluminated displays and the development of a computerized data base and modeling tools to supplement human engineering design criteria for visual displays. The inherent limitations of present military standards for dealing with a wide range of variables in a variety of operational environments and the need to include changes in the state-of-the-art are addressed. Data base design and computer modeling are suggested as an intermediate approach between out of date standards and costly physical simulation.


2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Sara Assadpour ◽  
Mohammad Reza Shiran ◽  
Peyman Asadi ◽  
Javad Akhtari ◽  
Amirhossein Sahebkar

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.


Homeopathy ◽  
2021 ◽  
Author(s):  
Raj Kumar Manchanda ◽  
Meeta Gupta ◽  
Ankit Gupta ◽  
Robbert van Haselen

Abstract Background Signaling molecules such as cytokines and interleukins are key mediators for the immune response in responding to internal or external stimuli. Homeopathically prepared signaling molecules have been used therapeutically for about five decades. However, these types of products are not available in many countries and their usage by homoeopaths is also infrequent. The aim of this scoping review is to map the available pre-clinical and clinical data related to the therapeutic use of homeopathically prepared signaling molecules. Methods We conducted a scoping review of clinical and pre-clinical studies of therapeutically used signaling molecules that have been prepared in accordance with an officially recognized homeopathic pharmacopoeia. Articles in peer-reviewed journals reporting original clinical or pre-clinical research of homeopathically prepared signaling molecules such as interleukins, cytokines, antibodies, growth factors, neuropeptides and hormones, were eligible. Non-English language papers were excluded, unless we were able to obtain an English translation. An appraisal of eligible studies took place by rating the direction of the outcomes on a five-point scale. The quality of the papers was not systematically assessed. Results Twenty-eight eligible papers, reporting findings for four different manufacturers' products, were identified and reviewed. Seventeen papers reported pre-clinical studies, and 11 reported clinical studies (six experimental, five observational). A wide range of signaling molecules, as well as normal T-cell expressed specific nucleic acids, were used. A majority of the products (21 of 28) contained two or more signaling molecules. The most common clinical indications were psoriasis, vitiligo, rheumatoid arthritis, respiratory allergies, polycystic ovary syndrome, and herpes. The direction of the outcomes was positive in 26 papers and unclear in two papers. Conclusion This scoping review found that there is a body of evidence on the use of homeopathically prepared signaling molecules. From a homeopathy perspective, these substances appear to have therapeutic potential. Further steps to explore this potential are warranted.


2021 ◽  
pp. 1-26
Author(s):  
E. Arvidsson Nordström ◽  
C. Teixeira ◽  
C. Montelius ◽  
B. Jeppsson ◽  
N. Larsson

This review aims to provide a comprehensive overview of the in vitro, animal, and clinical studies with the bacterial strain Lactiplantibacillus plantarum 299v (L. plantarum 299v; formerly named Lactobacillus plantarum 299v) published up until June 30, 2020. L. plantarum 299v is the most documented L. plantarum strain in the world, described in over 170 scientific publications out of which more than 60 are human clinical studies. The genome sequence of L. plantarum 299v has been determined and is available in the public domain (GenBank Accession number: NZ_LEAV01000004). The probiotic strain L. plantarum 299v was isolated from healthy human intestinal mucosa three decades ago by scientists at Lund University, Sweden. Thirty years later, a wealth of data coming from in vitro, animal, and clinical studies exist, showing benefits primarily for gastrointestinal health, such as reduced flatulence and abdominal pain in patients with irritable bowel syndrome (IBS). Moreover, several clinical studies have shown positive effects of L. plantarum 299v on iron absorption and more recently also on iron status. L. plantarum 299v is safe for human consumption and does not confer antibiotic resistance. It survives the harsh conditions of the human gastrointestinal tract, adheres to mannose residues on the intestinal epithelial cells and has in some cases been re-isolated more than ten days after administration ceased. Besides studying health benefits, research groups around the globe have investigated L. plantarum 299v in a range of applications and processes. L. plantarum 299v is used in many different food applications as well as in various dietary supplements. In a freeze-dried format, L. plantarum 299v is robust and stable at room temperature, enabling long shelf-lives of consumer healthcare products such as capsules, tablets, or powder sachets. The strain is patent protected for a wide range of indications and applications worldwide as well as trademarked as LP299V®.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A94-A94
Author(s):  
Sebastian Dziadek ◽  
Anton Kraxner ◽  
Wei-Yi Cheng ◽  
Mike Flores ◽  
Noah Theiss ◽  
...  

BackgroundFibroblast activation protein alpha (FAP) is frequently over-expressed in the tumor microenvironment (TME) while exhibiting limited expression in normal tissues. FAP expression was reported to be immunosuppressive in tumor mouse models and generally associated with worse prognosis in clinical studies. Therefore, it is important to understand the context in which FAP both exhibits immunosuppressive characteristics and be a useful target for immunotherapy.MethodsComprehensive immunohistochemistry (IHC) analyses on formalin-fixed paraffin-embedded tissue specimens with emphasis on lymph nodes and primary and metastatic tumor lesions spanning a wide range of indications were undertaken in this study. FAP staining of tumor tissues was performed with an optimized IHC robust-prototype-assay (RPA) and manually scored. The area (normal stroma & neoplastic) staining positively relative to the total tumor area at each intensity level was recorded and an H-score calculated (FAP-intensity score).These were supplemented by gene expression analysis using public as well as Roche phase 1, 2 and 3 cancer immunotherapy (CIT) clinical trial data sets.ResultsAnalysing FAP expression on normal tissue confirmed the general absence of FAP apart from a subset of pancreatic islet cells. Unlike the more homogenous expression of typical protein targets on tumor cells, FAP expression in the TME is heterogeneous in both pattern and intensity, requiring the analysis of a large sample set. Therefore, we evaluated 1216 samples from 23 tumor indications and 70 sub-indications. FAP expression exhibited a significant spread ranging from indications with highly abundant expression to those with low coverage.Using data from matching IHC and gene expression samples we confirmed FAP mRNA expression to significantly correlate with RPA H-scores (Spearman correlation: 0.62) (N=289, P=1.2E-31). Gene expression data from 12 atezolizumab clinical studies, including standard of care (SOC) randomized studies, with more than 6000 samples from 4 major indications were interrogated for the association between FAP expression and clinical response as evaluated by overall and progression free survival. This analysis suggests that FAP expression is generally associated with higher hazard ratios across all atezolizumab-treated samples (OS: 95% CI 1.04–1.09; PFS: 1.04–1.08), with the highest effect observed in Renal Cell Carcinoma (OS: 95% CI 1.08–1.31; PFS: 1.05–1.21), indicating a potential role of FAP in limiting CIT.ConclusionsData from these analyses can tailor indication and patient enrichment strategies for achieving optimal FAP-targeting. We propose to select indications with FAP-levels that are high enough to enable drug accumulation, yet low enough to reduce immunosuppressive effects that can hamper successful immunotherapy.


Author(s):  
A. Dziaková ◽  
A. Valenčáková ◽  
E. Hatalová ◽  
J. Kalinová

Gene therapy is strategy based on using genes as pharmaceuticals. Gene therapy is a treatment that involves altering the genes inside body's cells to stop disease. Genes contain DNA- the code controlling body form and function. Genes that do not work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve the ability of the body to fight disease. Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Various types of genetic material are used in gene therapy; double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), plasmid DNA and antisense oligodeoxynucleotides (ASON). The success of gene therapy depends on assuring the entrance of the therapeutic gene to targeted cells without any form of biodegradation. Commonly used vectors in gene therapy are: adenoviruses (400 clinical studies; 23.8%), retroviruses (344 clinical studies; 20.5%), unenveloped/plasmid DNA (304 clinical studies, 17.7%), adenoassociated viruses (75 clinical studies; 4.5%) and others. In this paper, we have reviewed the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors.


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