Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades.
Blotting, Western ; Calcium Channel Blockers/pharmacology ; Calcium Signaling* ; Drug Synergism ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Epinephrine/pharmacology ; G-Protein, Inhibitory Gi/metabolism* ; GTP-Binding Proteins/metabolism* ; Human ; Phospholipase C/metabolism* ; Phospholipase C/antagonists & inhibitors ; Platelet Aggregation/physiology ; Platelet Aggregation/drug effects* ; Serotonin/pharmacology ; Signal Transduction

AIM: S. tibetica Vatke is a herb distributed in the tropical and subtropical regions of the world, including Tibet, China, and India. In India it is found in the cold desert regions of Kargil, Ladakh Valley, and in the mountains of Himachal Pradesh. The traditional practitioners in the Kargil and Ladakh use the natural medicine Stachys tibetica for the treatment of various mental disorders and phobias. The present study is aimed at evaluating the anxiolytic effects of the methanolic extract of the root, stem, leaf, and whole plant material of Stachys tibetica Vatke in rats. METHODS: Powdered materials (1 kg) of each plant part were subjected to extraction in a Soxhlet apparatus with methanol (95%); to yield 12.8%, 8.3%, 17.2%, and 19.6% W/W extractives, respectively. Extracts were evaluated for their anxiolytic effects using the elevated plus maze (EPM) test in rats. RESULTS: In the present study, it was found that the methanolic extracts (200 and 400 mg·kg(-1)) of the root, stem, leaf and whole plant of Stachys tibetica Vatke and diazepam (DZ) increased the time spent and the number of entries in the open arm significantly (**P < 0.01), while they decreased the time spent and the number of entries in the closed arm. At the same time, all of the extracts and DZ decreased the time spent at the center of the maze (latency), along with closed arm returns. The head dip counts increased significantly in the rats treated with DZ, SMR400, SML400 and SMW400 in the open arm of EPM, which was a sign of reduction anxiety. The DZ and SMW did not show the fecal bolus, while other groups had reduced fecal bolus (**P < 0.01) as compared to control. These allied parameters helped to assess the anxiolytic potential of Stachys tibetica Vatke. Whole plant and leaf materials have shown the maximum activity, the root intermediate while the stem had the least anxiolytic activity (*P < 0.05, **P < 0.01) in EPM. CONCLUSION The results strongly justify the use of this plant for the treatment of anxiety. Further studies are in progress in this laboratory to isolate and identify the components responsible for the anxiolytic activity and the mechanism of action involved.
Animals ; Anti-Anxiety Agents ; administration & dosage ; Anxiety ; drug therapy ; psychology ; Behavior, Animal ; Female ; Humans ; Male ; Maze Learning ; drug effects ; Phytotherapy ; Plant Extracts ; administration & dosage ; Rats ; Rats, Wistar ; Stachys ; chemistry

Objectives: To access the knowledge of undergraduate and postgraduate students of the dental college on basic anatomy, physiology, clinical examination, and pathology of the temporomandibular joint (TMJ). Materials and Methods: A total of 610 undergraduate and postgraduate students of dental college, were included in this study. The questionnaire was pretested for validation and distributed online through Google forms. Results: A pairwise comparison showed that the percentage of correct answers for interns significantly differed from that of IV Bachelor of Dental Surgery (P=0.050) and postgraduate students (P=0.048) (below average: up to 6 correct answers, good: 7-11 correct answers, excellent: 12 or more correct answers). Conclusion TMJ diseases are common in daily life but frequently go undiagnosed and untreated due to a lack of clinical expertise. This demonstrates the necessity of providing instructions that give students in-depth knowledge and abilities for TMJ issues in clinical practice.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.