scholarly journals CathROB: A Highly Compact and Versatile Remote Catheter Navigation System

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Laura Cercenelli ◽  
Barbara Bortolani ◽  
Emanuela Marcelli
Keyword(s):  
Navigation Systems ◽  
Cardiac Damage ◽  
Remote Navigation ◽  
Catheter Navigation ◽  
Set Up ◽  
Compact Design ◽  
The Right ◽  
Preclinical And Clinical Studies

Several remote catheter navigation systems have been developed and are now commercially available. However, these systems typically require specialized catheters or equipment, as well as time-consuming operations for the system set-up. In this paper, we present CathROB, a highly compact and versatile robotic system for remote navigation of standard tip-steerable electrophysiology (EP) catheters. Key features of CathROB include an extremely compact design that minimizes encumbrance and time for system set-up in a standard cath lab, a force-sensing mechanism, an intuitive command interface, and functions for automatic catheter navigation and repositioning. We report in vitro and in vivo animal evaluation of CathROB. In vitro results showed good accuracy in remote catheter navigation and automatic repositioning (1.5 ± 0.6 mm for the left-side targets, 1.7 ± 0.4 mm for the right-side targets). Adequate tissue contact was achieved with remote navigation in vivo. There were no adverse events, including absence of cardiac perforation or cardiac damage, indicative of the safety profile of CathROB. Although further preclinical and clinical studies are required, the presented CathROB system seems to be a promising solution for an affordable and easy-to-use remote catheter navigation.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

Enhanced Increases in Cytosolic Ca2+ in ADP-Stimulated Platelets from Patients with Delta-Storage Pool Deficiency – A Possible Indicator of Interactions between Granule-Bound ADP and the Membrane ADP Receptor

1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss
Keyword(s):  
Platelet Rich Plasma ◽  
Limited Range ◽  
Dense Granule ◽  
Receptor Desensitization ◽  
Fura 2 ◽  
Storage Pool ◽  
Low Levels ◽  
The Right

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.

Rapid, Refined, and Robust Method for Expression, Purification, and Characterization of Recombinant Human Amyloid-beta M1-42

2019 ◽  
Author(s):  
Priya Prakash ◽  
Travis Lantz ◽  
Krupal P. Jethava ◽  
Gaurav Chopra
Keyword(s):  
Amyloid Beta ◽  
Western Blots ◽  
Force Microscopy ◽  
E Coli ◽  
Atomic Force ◽  
Set Up ◽  
Short Time

Amyloid plaques found in the brains of Alzheimer’s disease (AD) patients primarily consists of amyloid beta 1-42 (Ab42). Commercially, Ab42 is synthetized using peptide synthesizers. We describe a robust methodology for expression of recombinant human Ab(M1-42) in Rosetta(DE3)pLysS and BL21(DE3)pLysS competent E. coli with refined and rapid analytical purification techniques. The peptide is isolated and purified from the transformed cells using an optimized set-up for reverse-phase HPLC protocol, using commonly available C18 columns, yielding high amounts of peptide (~15-20 mg per 1 L culture) in a short time. The recombinant Ab(M1-42) forms characteristic aggregates similar to synthetic Ab42 aggregates as verified by western blots and atomic force microscopy to warrant future biological use. Our rapid, refined, and robust technique to purify human Ab(M1-42) can be used to synthesize chemical probes for several downstream in vitro and in vivo assays to facilitate AD research.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Physiological Function ◽  
Functional Characterization ◽  
Site Directed Mutagenesis ◽  
In Vitro Assays ◽  
Cell Growth Inhibition ◽  
The Right

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

scholarly journals Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer

2021 ◽  
Vol 7 (3) ◽  
pp. eabc4897
Author(s):  
Catríona M. Dowling ◽  
Kate E. R. Hollinshead ◽  
Alessandra Di Grande ◽  
Justin Pritchard ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Triple Negative ◽  
Mitochondrial Apoptosis ◽  
Glycolytic Metabolism ◽  
Set Up ◽  
Screening Approaches

Triple-negative breast cancer (TNBC) is a subtype of breast cancer without a targeted form of therapy. Unfortunately, up to 70% of patients with TNBC develop resistance to treatment. A known contributor to chemoresistance is dysfunctional mitochondrial apoptosis signaling. We set up a phenotypic small-molecule screen to reveal vulnerabilities in TNBC cells that were independent of mitochondrial apoptosis. Using a functional genetic approach, we identified that a “hit” compound, BAS-2, had a potentially similar mechanism of action to histone deacetylase inhibitors (HDAC). An in vitro HDAC inhibitor assay confirmed that the compound selectively inhibited HDAC6. Using state-of-the-art acetylome mass spectrometry, we identified glycolytic substrates of HDAC6 in TNBC cells. We confirmed that inhibition or knockout of HDAC6 reduced glycolytic metabolism both in vitro and in vivo. Through a series of unbiased screening approaches, we have identified a previously unidentified role for HDAC6 in regulating glycolytic metabolism.

scholarly journals A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight

2017 ◽  
Vol 17 (2) ◽  
pp. 200-209 ◽  
Author(s):  
Thomson Patrick Joseph ◽  
Warren Chanda ◽  
Arshad Ahmed Padhiar ◽  
Samana Batool ◽  
Shao LiQun ◽  
...  
Keyword(s):  
Side Effects ◽  
Biological Activities ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Medicinal Mushrooms ◽  
Chemotherapy Drugs ◽  
Development Of Resistance ◽  
Preclinical And Clinical Studies

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, “mushrooms,” contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).

scholarly journals Pharmacologically mechanistic basis for the traditional uses of Rumex acetosa in gut motility disorders and emesis

2015 ◽  
Vol 10 (3) ◽  
pp. 548 ◽  
Author(s):  
Musaddique Hussain ◽  
Shahid Masood Raza ◽  
Khalid Hussain Janbaz
Keyword(s):  
Rumex Acetosa ◽  
Response Curves ◽  
Motility Disorders ◽  
Traditional Uses ◽  
Antiemetic Activity ◽  
Rabbit Jejunum ◽  
Mechanistic Basis ◽  
The Right

<p class="Abstract"><em>In vitro</em> and<em> in vivo</em> studies were undertaken to evaluate the pharmacologically mechanistic background to validate the traditional uses of <em>Rumex acetosa</em> in the treatment of emesis and gastrointestinal motility disorders such as constipation and diarrhea. In rabbit jejunum preparation, methanolic extract of <em>R. acetosa</em> (0.01-1.0 mg/mL) caused a transient spasmogenic effect, followed by the spasmolytic effect (3-10 mg/mL). In presence of atropine, spasmogenic effect was blocked while spasmolytic effect was emerged, suggesting that spasmogenic effect was mediated through activation of muscarinic receptors. Extract inhibited the K<sup>+ </sup>(80 mM)-induced contraction, suggesting Ca<sup>2+</sup>-cha-nnel blockade, which was further confirmed when pretreatment of tissue with extract shifted the Ca<sup>2+ </sup>concentration-response curves to the right, similarly as verapamil.<em> R. acetosa</em> also exhibited the significant antiemetic activity (p&lt;0.05) against different emetogenic stimuli, when compared with chlorpromazine. This study confirms the presence of gut modulator (spasmogenic and spasmolytic) and antiemetic activates, validating its traditional uses.</p><p> </p>

scholarly journals Amount of RNA secondary structure required to induce an alternative splice.

1987 ◽  
Vol 7 (9) ◽  
pp. 3194-3198 ◽  
Author(s):  
D Solnick ◽  
S I Lee
Keyword(s):  
Alternative Splicing ◽  
Secondary Structure ◽  
Alternative Splice ◽  
Rna Secondary Structure ◽  
Secondary Structures ◽  
Splice Sites ◽  
Perfect Complementarity ◽  
Set Up

We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular complementarity on alternative splicing in vivo. We found that an alternative splice was induced in vivo only when the introns contained more than approximately 50 nucleotides of perfect complementarity, that is, only when the secondary structure was much more stable than most if not all possible secondary structures in natural mRNA precursors. We showed further that intron insertions containing long complements to splice sites and a branch point inhibited splicing in vitro but not in vivo. These results raise the possibility that in cells most pre-mRNA secondary structures either are not maintained long enough to influence splicing choices, or never form at all.

scholarly journals Essential Oils as Treatment Strategy for Alzheimerʼs Disease: Current and Future Perspectives

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 239-248 ◽  
Author(s):  
Anju Benny ◽  
Jaya Thomas
Keyword(s):  
Essential Oils ◽  
Clinical Studies ◽  
Symptomatic Relief ◽  
Memory Loss ◽  
Clinical Trial Data ◽  
In Vivo Studies ◽  
Scientific Databases ◽  
Preclinical And Clinical Studies

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.

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