scholarly journals Cannabinoid Receptor Agonist Inhibits Atrial Electrical Remodeling in a Tachypaced Ex Vivo Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Danielle I. Lee ◽  
Michael Murninkas ◽  
Sigal Elyagon ◽  
Yoram Etzion ◽  
Hope D. Anderson
Keyword(s):  
Cannabinoid Receptor ◽  
Ex Vivo ◽  
Clinical Value ◽  
Rate Dependent ◽  
Rat Hearts ◽  
Before And After ◽  
New Treatment ◽  
Set Up ◽  
The Right ◽  
Peripheral Activation

Introduction: Atrial fibrillation (AF) leads to rate-dependent atrial changes collectively defined as atrial remodelling (AR). Shortening of the atrial effective refractory period (AERP) and decreased conduction velocity are among the hallmarks of AR. Pharmacological strategies to inhibit AR, thereby reducing the self-perpetual nature of AF, are of great clinical value. Cannabinoid receptor (CBR) ligands may exert cardioprotective effects; CB13, a dual CBR agonist with limited brain penetration, protects cardiomyocytes from mitochondrial dysfunction induced by endothelin-1. Here, we examined the effects of CB13 on normal physiology of the rat heart and development of tachypacing-induced AR.Methods: Rat hearts were perfused in a Langendorff set-up with CB13 (1 µM) or vehicle. Hemodynamic properties of non-paced hearts were examined conventionally. In a different set of hearts, programmed stimulation protocol was performed before and after atrial tachypacing for 90 min using a mini-hook platinum quadrupole electrode inserted on the right atrium. Atrial samples were further assessed by western blot analysis.Results: CB13 had no effects on basal hemodynamic properties. However, the compound inhibited tachypacing-induced shortening of the AERP. Protein expression of PGC1α was significantly increased by CB13 compared to vehicle in paced and non-paced hearts. Phosphorylation of AMPKα at residue threonine 172 was increased suggesting upregulation of mitochondrial biogenesis. Connexin43 was downregulated by tachypacing. This effect was diminished in the presence of CB13.Conclusion: Our findings support the notion that peripheral activation of CBR may be a new treatment strategy to prevent AR in patients suffering from AF, and therefore warrants further study.

Evaluation of Freezing Methods by Low Temperature X-Ray Diffraction

1977 ◽  
Vol 35 ◽  
pp. 330-333
Author(s):  
T. Gulik-Krzywicki ◽  
M.J. Costello
Keyword(s):  
Biological Materials ◽  
Molecular Organization ◽  
X Ray Diffraction ◽  
Glass Capillary ◽  
X Ray ◽  
Rate Dependent ◽  
Before And After ◽  
Freeze Etching ◽  
Diffraction Patterns ◽  
Set Up

Freeze-etching electron microscopy is currently one of the best methods for studying molecular organization of biological materials. Its application, however, is still limited by our imprecise knowledge about the perturbations of the original organization which may occur during quenching and fracturing of the samples and during the replication of fractured surfaces. Although it is well known that the preservation of the molecular organization of biological materials is critically dependent on the rate of freezing of the samples, little information is presently available concerning the nature and the extent of freezing-rate dependent perturbations of the original organizations. In order to obtain this information, we have developed a method based on the comparison of x-ray diffraction patterns of samples before and after freezing, prior to fracturing and replication.Our experimental set-up is shown in Fig. 1. The sample to be quenched is placed on its holder which is then mounted on a small metal holder (O) fixed on a glass capillary (p), whose position is controlled by a micromanipulator.

Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig

1992 ◽  
Vol 68 (05) ◽  
pp. 500-505 ◽  
Author(s):  
Ch M Samama ◽  
Ph Bonnin ◽  
M Bonneau ◽  
G Pignaud ◽  
E Mazoyer ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Femoral Artery ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Flow Reduction ◽  
Cyclic Flow ◽  
Left Femoral Artery ◽  
Before And After ◽  
The Right ◽  
Induced Aggregation

SummaryWe investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin did not significantly prevent cyclic flow reductions which occurred in all animals after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel appears as a more potent antithrombotic drug than aspirin in this model, in treating and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening bleeding time.

Ischemia-induced and reperfusion-induced arrhythmias: importance of heart rate

1989 ◽  
Vol 256 (1) ◽  
pp. H21-H31 ◽  
Author(s):  
M. Bernier ◽  
M. J. Curtis ◽  
D. J. Hearse
Keyword(s):  
Heart Rate ◽  
Coronary Occlusion ◽  
Ischemia And Reperfusion ◽  
Rate Of Development ◽  
Rate Dependent ◽  
Rat Hearts ◽  
Wide Range ◽  
The Right ◽  
The Relationship ◽  
Isolated Rat

The relationship between heart rate and ischemia-induced and reperfusion-induced arrhythmias was studied using 573 isolated rat hearts. Hearts (12/group), subjected to 7 min of coronary occlusion and 10 min reperfusion, were paced at 300, 330, 360, 390, 420, 480, or 540 beats/min. Pacing either throughout the experiment or during ischemia alone led to a rate-dependent increase in the incidence of reperfusion-induced ventricular fibrillation (VF) from 25% in the unpaced hearts to greater than 90% when the rate was 420 beats/min or higher. However, pacing during reperfusion alone did not increase the incidence of reperfusion-induced VF. In separate hearts, the right atrium was removed to permit examination of both low and high rates (167 +/- 2, 240, 336 +/- 3, or 480 beats/min throughout the experiment) over a wide range of durations of occlusion (3, 5, 7, 10, 15, 20, or 40 min). Ischemia-induced VF incidence was critically dependent on heart rate, low rates being protective. During reperfusion, the incidence of VF was also highly rate dependent if reperfusion was initiated within 10 min of the onset of ischemia (ranging from 8% when rate was 167 +/- 2 beats/min to 100% when rate was 480 beats/min) but was unrelated to heart rate when reperfusion occurred at later times (ranging from 33 to 50% when ischemia duration was 40 min). Heart rate can therefore influence susceptibility to ischemia- and reperfusion-induced arrhythmias, probably as a result of an effect on the rate of development of ischemic injury.

Evaluation of three automatic jetting races for control of the sheep body louse Bovicola ovis

1996 ◽  
Vol 36 (1) ◽  
pp. 45 ◽  
Author(s):  
PW Johnson ◽  
KL Dawson ◽  
R Dixon
Keyword(s):  
Arithmetic Mean ◽  
The Body ◽  
Body Louse ◽  
Merino Sheep ◽  
Before And After ◽  
Set Up ◽  
The Right

Fine wool Merino sheep with short (4 mm) or long (30-80 mm) wool and moderate to heavy infestations of lice (Bovicola ovis) were treated with cyhalothrin at a concentration of 50 mg/L, applied using Alison, Aussie Dip and Boral Cyclone Superace automatic jetting races. Each machine was set up and operated by representatives of the manufacturer. With all 3 machines, arithmetic mean louse counts before and after treatment showed that in the sheep with short wool, lice numbers were reduced by > 98% at 8-12 weeks after treatment but were not eliminated. In the sheep with long wool, the maximum reductions in mean louse counts were 79, 68 and 98% for Alison, Aussie Dip and Boral Cyclone Superace machines at 7, 5 and 8 weeks after treatment, respectively. The Alison and Aussie Dip machines were each tested in alternative configurations which affected the disposition of the jetting fluid on the fleece. The distribution of live lice on the bodies of the shorn sheep after treatment using the Alison machine and 1 configuration of the Aussie Dip machine, indicated that more insecticide may have been delivered to the left side of the body than to the right. There were no significant differences between sides in sheep treated in the Boral Cyclone Superace machine. Our results suggest that the jetting races tested would control infestations of lice for at least 12 weeks in sheep treated within 2 weeks after shearing, but would be unlikely to eradicate lice from an infested flock. The machines differed markedly in their ability to control moderate to heavy infestations of lice in sheep with long (30-80 mm) wool, but in all cases there was evidence of a resurgence in lice numbers beyond 12 weeks after treatment.

Effects of Obstruction on Single-Kidney Function Clinical and Experimental Results with 131I-Hippurate and 99mTc-DMSA

1980 ◽  
Vol 19 (06) ◽  
pp. 257-262 ◽  
Author(s):  
D. Jocham ◽  
M. Beer ◽  
U. Büll ◽  
E. Moser
Keyword(s):  
Kidney Function ◽  
Small Difference ◽  
Total Clearance ◽  
Clinical Value ◽  
Renal Imaging ◽  
Before And After ◽  
Ureteral Fistula ◽  
The Difference ◽  
The Right ◽  
Single Kidney

SummaryIn 35 patients, renography with 131I-o-hippurate (OIH) and static renal imaging with 99mTc-dimercaptosuccinic acid (DMSA) were used to measure differential renal function (DRF). The results were compared. Depth correction was applied in both methods. In non-obstructed kidneys (19 patients), both methods revealed nearly identical kidney function (r = 0.98). For completely obstructed kidneys (16 patients), OIH gave a significantly better DRF (14 ml/min) than DMSA. This small difference was of no clinical value. Because DMSA is reported to give unreliable results in unilateral obstructed kidneys, the right ureter was ligated in 8 dogs for 10 days and DRF was measured before and after opening an ureteral fistula. The difference in DRF was about 1% and could be accounted for by the amount of urinary radioactivity collected from the pelvic system after the ligature had been opened. Although DMSA appears to give reliable values in determining DRF, even in obstructed kidneys, OIH is preferred since total clearance values and postrenal urinary dynamics can be determined simultaneously.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Ridogrel Inhibits Systemic and Renal Formation of Thromboxane A2 and Antagonizes Platelet Thromboxane A2/Prostaglandin Endoperoxide Receptors upon Chronic Administration to Man

1992 ◽  
Vol 68 (02) ◽  
pp. 214-220 ◽  
Author(s):  
C Weber ◽  
J R Beetens ◽  
F Tegtmeier ◽  
P Van Rooy ◽  
E Vercammen ◽  
...  
Keyword(s):  
Uric Acid ◽  
Potent Inhibitor ◽  
Ex Vivo ◽  
Thromboxane A2 ◽  
Chronic Administration ◽  
Response Curves ◽  
Clinically Significant ◽  
Synthase Inhibitor ◽  
The Right ◽  
Steady State Plasma Level

SummaryThe effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b. i. d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (>99%) while that of PGE2 and PGF2α is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

EFEKTIVITAS METODE DEMONSTRASI DALAM MENINGKATKAN HASIL BELAJAR SISWA SEKOLAH MENENGAH KEJURUAN PADA PENGAJARAN SISTEM KOLOID

2013 ◽  
Vol 19 (1) ◽  
pp. 28
Author(s):  
Hamda Situmorang ◽  
Manihar Situmorang
Keyword(s):  
High School ◽  
High School Students ◽  
Abstract Concept ◽  
Vocational High School ◽  
School Students ◽  
Lecture Method ◽  
Colloid System ◽  
Before And After ◽  
The Right ◽  
And Control

Abstract Implementation of demonstration method in the teaching of chemistry is assigned as the right strategy to improve students’ achievement as it is proved that the method can bring an abstract concept to reality in the class. The study is conducted to vocational high school students in SMKN1 Pargetteng getteng Sengkut Pakfak Barat at accademic year 2013. The teaching has been carried out three cycles on the teaching of chemistry topic of colloid system. In the study, the class is divided into two class, experiment class and control class. The demontration method is used to teach students in experimental class while the teaching in control class is conducted with lecture method. Both are evaluated by using multiple choise tests before and after the teaching procedures, and the ability of students to answer the problems are assigned as students’ achievements. The results showed that demonstration method improved students’ achievement in chemistry. The students in experimental class who are taughed with demonstration method (M=19.08±0.74) have higher achievements compare with control class (M=12.91±2.52), and both are significantly different (tcalculation 22.85 > ttable 1.66). The effectivity of demostration method in experimental class (97%) is found higer compare to conventional method in control class (91%).

Interactions between programmable shunt valves and magnetically controlled growing rods for scoliosis

2020 ◽  
Vol 26 (6) ◽  
pp. 667-670
Author(s):  
Thomas Larrew ◽  
Mohammed Alshareef ◽  
Robert F. Murphy ◽  
Ramin Eskandari ◽  
Libby Kosnik Infinger
Keyword(s):  
Remote Control ◽  
Ex Vivo ◽  
Shunt Valve ◽  
Growing Rods ◽  
Growing Rod ◽  
Before And After ◽  
Magnetically Controlled Growing Rods ◽  
Ex Vivo Study

OBJECTIVEAlthough the advent of magnetic growing rod technology for scoliosis has provided a means to bypass multiple hardware lengthening operations, it is important to be aware that many of these same patients have a codiagnosis of hydrocephalus with magnet-sensitive programmable ventricular shunts. As the magnetic distraction of scoliosis rods has not previously been described to affect the shunt valve setting, the authors conducted an investigation to characterize the interaction between the two devices.METHODSIn this ex vivo study, the authors carried out 360 encounters between four different shunt valve types at varying distances from the magnetic external remote control (ERC) used to distract the growing rods. Valve settings were examined before and after every interaction with the remote control to determine if there was a change in the setting.RESULTSThe Medtronic Strata and Codman Hakim valves were found to have setting changes at distances of 3 and 6 inches but not at 12 inches. The Aesculap proGAV and Codman Certas valves, typically described as MRI-resistant, did not have any setting changes due to the magnetic ERC regardless of distance.CONCLUSIONSAlthough it is not necessary to check a shunt valve after every magnetic distraction of scoliosis growing rods, if there is concern that the magnetic ERC may have been within 12 inches (30 cm) of a programmable ventricular shunt valve, the valve should be checked at the bedside with a programmer or with a skull radiograph along with postdistraction scoliosis radiographs.

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