Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population

2016 ◽  
Vol 7 (8) ◽  
pp. 3609-3616 ◽  
Author(s):  
Daniel Veach ◽  
Holly Hosking ◽  
Kiara Thompson ◽  
Abishek Bommannan Santhakumar
Keyword(s):  
Shikimic Acid ◽  
Ex Vivo ◽  
Sedentary Population ◽  
Phenolic Metabolite ◽  
Thrombogenic Potential

Thisex vivostudy was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite.

scholarly journals Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mira Choi ◽  
Soon-Jin Choi ◽  
Sunhyae Jang ◽  
Hye-In Choi ◽  
Bo-Mi Kang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Organ Culture ◽  
Human Hair ◽  
Hair Growth ◽  
Shikimic Acid ◽  
Ex Vivo ◽  
Hair Follicles ◽  
Anagen Hair

AbstractShikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.

In Vivo Cleavage of Recombinant VWF Upon Intravenous Administration in Preclinical and Clinical Settings

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1222-1222
Author(s):  
Katalin Varadi ◽  
Hanspeter Rottensteiner ◽  
Jutta Schreiner ◽  
Herbert Gritsch ◽  
Hartmut J. Ehrlich ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Ex Vivo ◽  
Dose Range ◽  
Molecular Size ◽  
Immunoblot Analysis ◽  
Animal Origin ◽  
Drug Candidate ◽  
Thrombogenic Potential

Abstract Abstract 1222 Von Willebrand factor (VWF) is composed of a series of multimers with a molecular size ranging from 600 to 20,000 kDa. The ultra-high molecular weight (UHMW) portion of VWF multimers is more efficient in platelet interactions than the lower molecular weight portion, and as such it might have a thrombogenic potential under certain pathologic conditions. The concentration of UHMW multimers in healthy individuals' blood is low because the circulating specific metalloprotease ADAMTS13 rapidly cleaves UHMW VWF upon its release into the circulation. A recombinant VWF (rVWF) expressed in CHO cells has been developed as a new drug candidate for treating patients with VWF deficiency. Since this protein is not cleaved by ADAMTS13 during the expression phase, it has a high portion of UHMW multimers, similar to the human VWF stored in Weibel-Palade bodies of endothelial cells. During the development phase of rVWF in vitro experiments showed that when treated under mild denaturing conditions or under shear, the molecule was susceptible to ADAMTS13 of human or animal origin. Here we present data from preclinical studies where analyzing the ex vivo samples showed the ADAMTS13-mediated cleavage of intravenously applied UHMW-containing rVWF. In good correlation with the in vitro results, studies in rabbits and cynomolgus monkeys showed that the ADAMTS13-specific cleavage fragments appeared as soon as 15 minutes after application, as visualized by immunoblot analysis. The appearance of cleavage bands coincided with the decrease in multimer numbers, indicating that rVWF had been specifically cleaved by endogenous ADAMTS13 in the circulation. The effect was species-dependent, only a low or minimal cleavage was observed in different mice strains. A recently completed Phase I clinical study clearly demonstrated that rVWF administered intravenously to severe VWD patients in a dose-range of 7.5 to 50 VWF:RCo U/kg body weight was rapidly processed in the circulation, resulting in the disappearance of the UHMW multimers with visible cleavage fragments, as shown by immunoblot and high resolution multimer analysis. No thrombotic adverse events were seen during the study, underlying the suitability of the UHMW-containing rVWF for treating VWD patients. Disclosures: Varadi: Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Schreiner:Baxter Innovations GmbH: Employment. Gritsch:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment.

scholarly journals The ex vivo antiplatelet activation potential of fruit phenolic metabolite hippuric acid

2015 ◽  
Vol 6 (8) ◽  
pp. 2679-2683 ◽  
Author(s):  
Abishek Bommannan Santhakumar ◽  
Roger Stanley ◽  
Indu Singh
Keyword(s):  
Conformational Change ◽  
Platelet Activation ◽  
Active Metabolite ◽  
Hippuric Acid ◽  
Ex Vivo ◽  
Activation Potential ◽  
Phenolic Metabolite ◽  
Polyphenol Intake

Active metabolite of polyphenol intake, hippuric acid, reduces platelet activation-related conformational change and de-granulationex vivothereby alleviating thrombogenesis.

Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

1989 ◽  
Vol 47 ◽  
pp. 886-887
Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Retention Data ◽  
Vascular Prostheses ◽  
Group 4 ◽  
Human Fibronectin ◽  
Insufficient Time ◽  
Group 3 ◽  
Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

The Shikani HME: A New Tracheostomy Heat and Moisture Exchanger

2020 ◽  
Vol 63 (9) ◽  
pp. 2921-2929
Author(s):  
Alan H. Shikani ◽  
Elamin M. Elamin ◽  
Andrew C. Miller
Keyword(s):  
Ex Vivo ◽  
Moisture Loss ◽  
Speaking Valve ◽  
Time Zero ◽  
In Series ◽  
Turbulent Airflow ◽  
The Difference ◽  
Loss Efficiency ◽  
Heat And Moisture ◽  
Lung Simulation

Purpose Tracheostomy patients face many adversities including loss of phonation and essential airway functions including air filtering, warming, and humidification. Heat and moisture exchangers (HMEs) facilitate humidification and filtering of inspired air. The Shikani HME (S-HME) is a novel turbulent airflow HME that may be used in-line with the Shikani Speaking Valve (SSV), allowing for uniquely preserved phonation during humidification. The aims of this study were to (a) compare the airflow resistance ( R airflow ) and humidification efficiency of the S-HME and the Mallinckrodt Tracheolife II tracheostomy HME (M-HME) when dry (time zero) and wet (after 24 hr) and (b) determine if in-line application of the S-HME with a tracheostomy speaking valve significantly increases R airflow over a tracheostomy speaking valve alone (whether SSV or Passy Muir Valve [PMV]). Method A prospective observational ex vivo study was conducted using a pneumotachometer lung simulation unit to measure airflow ( Q ) amplitude and R airflow , as indicated by a pressure drop ( P Drop ) across the device (S-HME, M-HME, SSV + S-HME, and PMV). Additionally, P Drop was studied for the S-HME and M-HME when dry at time zero (T 0 ) and after 24 hr of moisture testing (T 24 ) at Q of 0.5, 1, and 1.5 L/s. Results R airflow was significantly less for the S-HME than M-HME (T 0 and T 24 ). R airflow of the SSV + S-HME in series did not significant increase R airflow over the SSV or PMV alone. Moisture loss efficiency trended toward greater efficiency for the S-HME; however, the difference was not statistically significant. Conclusions The turbulent flow S-HME provides heat and moisture exchange with similar or greater efficacy than the widely used laminar airflow M-HME, but with significantly lower resistance. The S-HME also allows the innovative advantage of in-line use with the SSV, hence allowing concurrent humidification and phonation during application, without having to manipulate either device.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

102 Functional and metabolic phenotyping of the murine heart using an ex vivo perfusion system and 13C-substrates

2003 ◽  
Vol 2 (1) ◽  
pp. 12
Author(s):  
M KHAIRALLAH ◽  
B BOUCHARD ◽  
J MCDUFF ◽  
F LABARTHE ◽  
G DANIALOU ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Perfusion System ◽  
Metabolic Phenotyping ◽  
Ex Vivo Perfusion
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