Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolitesʼ variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.

Objectification of the evaluation of a pharmacological test with alpha-adrenergic blocking agents during uroflowmetry

The tactics of treating dysuric disorders are largely determined by the pathophysiological and morpho-clinical basis: infravesical obstruction, impaired bladder contractility, complex neurogenic urination disorders, etc. Among the diseases that most often cause infravesical obstruction in men, the most common pathologies are benign prostatic hyperplasia, prostate cancer, prostate sclerosis, obstructive processes of the bladder neck (contractures, fibrosis), urethral strictures of various etiologies. The use of a comprehensive urodynamic study makes it possible to differentiate the causes of urinary disorders. One of the most common and non-invasive methods used in the urologist’s clinical practice is uroflowmetry. The use of the fuzzy logic algorithm described in the article for making a decision on the presence of obstructive urination allows one to assess the urodynamic situation using the home uroflow monitoring technique. Analytical urodynamics in conjunction with the fuzzy logic block increases the accuracy of describing the examination results, and the introduction of the proposed model into the software simplifies the work with diagnostic urological equipment and increases the efficiency of the examination.

Phytochemical and Antihypertensive Tests of Celery (Apium graveolens L.) and Garlic (Allium sativum L.) Formula

Hypertension is also the leading cause of death worldwide. Treatment and control of hypertension help prevent cardiovascular death. Traditionally celery and garlic have been used as ingredients to lower high blood pressure by the people of South Sulawesi. Phytochemical testing was carried out to provide information about compounds' content in the formula of celery and garlic. Furthermore, the determination of the levels of alkaloids and saponins was carried out gravimetrically, the decision of the stories of phenols with a UV-Visible spectrophotometer, and the conclusion of the levels tannins with a UV spectrophotometer. Pharmacological testing using 25 white male rats were treated with doses of celery and garlic formula given to rats, namely 185 mg/ 200 g BW, 370 mg/ 200 g BW, 740 mg/ 200 g BW orally as test material. In the negative control, the rats were only given distilled water alone, and in the positive control, it was induced using 8% NaCl and 0.05% prednisone orally. The test solution was given for 21 days. The results of the phytochemical test showed that the celery and garlic ingredients contained positive alkaloids, saponins, phenols, tannins with levels of 1.8917 % alkaloids, 0.5885 % saponins, 1.6138 % phenols, and 1,3485 % tannins. Pharmacological test results showed systolic blood pressure and diastolic blood pressure decreased significantly (p < 0.05).

Could specific EKG markers identify a pharmacologically induced type 1 Brugada pattern? Insights from a large, single-centre cohort

Funding Acknowledgements Type of funding sources: None. Background. Pharmacological (Ajmaline) induction of a type 1 Brugada pattern is currently considered mandatory for the diagnosis of Brugada syndrome. However, performing the test requires time and healthcare resources. Some EKG markers have been proposed as predictors of positive result at Ajmaline test. Aim. To evaluate in a large population the predictive value of multiple EKG markers for Ajmaline test results. Methods. We retrospectively analysed consecutive patients (pts) referred to our Centre to perform Ajmaline test. All pts had type 2 Brugada pattern detected at a conventional EKG or were relatives of pts with positive Ajmaline test, with or without type 2 Brugada pattern at EKG. All pts performed the Ajmaline pharmacological test (1 mg/Kg iv) with EKG "superior" right precordial unipolar derivations monitoring. To determine whether clinical parameters (age, gender, cardiomyopathy, history of arrhythmias, symptoms, familiarity) and EKG markers (heart rate (HR), PR duration, R1V1 and SV6 duration and amplitude, QRSV1/QRSV6 duration, V1 and V2 ST amplitude (coved or saddle back pattern) were independently associated to positivity at Ajmaline test, a logistic regression model was applied. Results. From January 2010 to December 2019 we evaluated 442 consecutive pts: mean age 40.1 ± 14.5 years; 273 (65%) male; 352 (80%) pts were included because of type 2 Brugada pattern at EKG and 90 (20%) for familial screening. The Ajmaline test was positive in 150 (34%) pts. At multivariate logistic regression analysis adjusted for baseline confounders, age &gt; 45 years (OR= 1.64, 95%CI: 1.03 to 2.54; p = 0.0385), female gender (OR = 1.79, 95%CI: 1.12 to 2.85; p = 0.0141), HR &gt; 60 bpm (OR = 2.44, 95%CI: 1.48 to 4.03; p = 0.0005), QRSV1/QRSV6 duration (msec) &gt;1 (OR = 5.34, 95%CI: 3.28 to 8.69; p &lt; 0.0001) and non isoelectric pattern (coved/saddle back) in V2 (OR = 1.93, 95%CI: 1.03 to 3.63, p = 0.0416) remained associated with a positive Ajmaline test. The percentage of pts with positive Ajmaline test increased according to the presence of significant EKG markers in their risk profile: 11.3% (8 out 71, absence of both QRSV1/QRSV6 duration (msec) &gt;1 and V2 non isoelectric pattern), 24.3% (50 out 206, presence of only V2 non isoelectric pattern), 48.5% (16 out 33, presence of only QRSV1/QRSV6 duration (msec) &gt;1), 57.6% (76 out 132, presence of both factors). Conclusions. In our large population: 1) we confirmed the positive predictive power of QRSV1/QRSV6 duration (msec) &gt;1 and of a non isoelectric pattern (coved/saddle back) in V2 for a pharmacologically induced type 1 Brugada pattern; 2) we observed a non-negligible percentage of pts who would not be correctly diagnosed for type 1 Brugada pattern, if selected according to an EKG parameters-based prescreening.

The Evaluation of Patient Demographics, Etiologies and Apraclonidine Test Results in Adult Horner's Syndrome

Purpose: We aimed to demonstrate the patient demographics, etiologies and apraclonidine test results in adult Horner's syndrome Methods: This retrospective study was performed by the analysis of medical data of patients who were given 0.5% apraclonidine test. Patients' past medical history, demographic data, etiologies, accompanying neurological findings, and pharmacological test results were assessed.Results: Forty patients (21 females and 19 males) with a mean age of 50.3 ± 11.6 years were evaluated. Apraclonidine 0.5% test was positive in 37 patients (92.5%). An etiology could be identified in 20 patients (central (9 patients, 45%), preganglionic (9 patients, 45%), and postganglionic (2 patients, 10%)). Neurological findings accompanying Horner’s syndrome were present in 9 patients.Conclusion: Despite detailed investigations, in a significant number of patients with Horner's syndrome an underlying cause may not be detected. Among the identifiable lesions, central and preganglionic involvements are still the first leading causes of Horner's syndrome. In addition, apraclonidine test may not be positive in all patients and a negative response does not exclude Horner's syndrome.

Features of Diagnostics and Differential Diagnostics of Chronic Heart Failure in Outpatient Clinics

The Chapter contains information about the prevalence of heart failure (HF) among patients in outpatient practice. The causal structure of HF, the prevalence of risk factors for HF, and the occurrence of a reduced ejection fraction are described. It describes the frequency of overdiagnosis of HF, the disease most often simulating its symptoms. The difficulties associated with laboratory and instrumental diagnostics of this syndrome are discussed. A pharmacological test for differential diagnosis of the causes of dyspnea in patients with suspected HF is described. Information is provided on the incidence of depressive and anxiety among the patients with this disease.

Safety and Effectiveness of Volumetric Computed Tomography of the Heart in Combination with a PharmacologicaTest with Adenosine Triphosphate in the Diagnosis of Coronary Heart Disease

Aim To evaluate safety and efficacy of sodium adenosine triphosphate (ATP) as a vasodilator in assessment of left ventricular (LV) myocardial perfusion and in verification of ischemia by cardiac volumetric computed tomography (CT).Material and methods The study included 58 patients with suspected ischemic heart disease (IHD). For all included patients, cardiac volumetric CT with a pharmacological ATP test was performed. The rate of adverse effects was analyzed during the ATP infusion. Results of the study were compared with data from using other noninvasive methods for IHD diagnosis by calculating Cohen’s kappa, the measure of agreement between two variables.Results The test performed during CT showed good tolerability of the ATP infusion, a low rate of moderate adverse reactions (8.6 %), and the absence of severe side effects. Results of diagnosing IHD with cardiac volumetric CT with the ATP pharmacological test were comparable with data from using other methods for noninvasive verification of LV myocardial ischemia (bicycle ergometry, treadmill test, stress echocardiography) in combination with coronarography or CT coronarography.Conclusion ATP appears a safe pharmacological agent for diagnosing transient LV myocardial ischemia. ATP can be recommended as a vasodilator for evaluation of perfusion using cardiac volumetric CT.

Analysis of the links between endothelium-dependent vasodilation indicators and the levels of high-sensitivity C-reactive protein and fractalkine/CX3CL1 in patients with acute coronary syndrome

Objective: to study and analyze the links between endothelium-dependent vasodilation (EDV) indicators and the levels of fractalkine (FN/CX3CL1) and high sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome (ACS).Materials and methods: among the examined individuals with ACS, 63 patients had acute myocardial infarction (MI); 41 patients had unstable angina (UA), represented by first – time angina in 15 people and 26 people had progressive angina. Control group included 20 healthy control individuals. Pharmacological test with 5% acetylcholine (AcH) was used to assess the functional state of the vascular endothelium. Enzyme-linked immunosorbent assay was used to determine the levels of FN/CX3CL1 and hs-CRP.Results: all the examined patients with ACS showed statistically significant changes in EDV indicators compared to the control group, as well as an increase in the level of FN/CX3CL1 and hs-CRP. The most pronounced changes of the values of EDV indicators and the levels of FN/CX3CL1 and hs-CRP, from the examined patients, were detected among patients with acute MI. Th e presence of correlations between the studied indicators was revealed. Th e strength of the identified links was greater among patients with acute MI, compared to patients with UA. Th e strength of the links found in patients with both UA and acute MI was greater between EDV indicators and FN/CX3CL1 levels, than between EDV indicators and hs-CRP levels.Conclusions:all the examined patients with ACS had the EDV disorders associated with the severity of systemic infl ammation. In the group of patients with acute MI, the severity of EDV disorders was greater than in patients with UA, which was apparently due to the infl uence of the resorption-necrotic syndrome, which potentiates increased systemic infl ammation and damage to the endothelium of microvessels with EDV disorders, which was confirmed by the results of correlation analysis. A positive link was found between the levels of FN/CX3CL1 hs-CRP.

The study of myocardial perfusion by cardiac volumetric computed tomography, combined with adenosine triphosphate test, in a patient with painless myocardial ischemia and atherosclerosis of the coronary arteries

The presented clinical observation demonstrates the diagnostic capabilities of cardiac volumetric computed tomography (CT) with a pharmacological test by a vasodilator adenosine triphosphate (ATP) in the simultaneous assessment of coronary anatomy and changes in left ventricular myocardial perfusion (LV) in a patient with painless myocardial ischemia and coronary atherosclerosis. A 68-year-old patient with coronary heart disease (CHD) and atherosclerotic changes in the coronary arteries underwent cardiac volumetric CT in combination with a ATP pharmacological test. The study was performed on a Aquilion ONE 640 Vision Edition computer tomograph (Toshiba, Japan). Assessment of LV myocardial perfusion was carried out in comparison with other clinical, laboratory and instrumental examination methods. The results of clinical and instrumental examination of a patient with a low pre-test probability of coronary heart disease are presented. From the standpoint of modern recommendations on stable coronary heart disease, false-negative results of single-photon emission computed tomography of the heart and stress-echocardiography are discussed. Clinical observation demonstrates the feasibility of diagnosing LV myocardial ischemia by cardiac volumetric CT combined with ATP pharmacological test, confirmed by an invasive determination of the fractional flow reserve. The given clinical example represents the advantage of cardiac volumetric CT, combined with the ATP pharmacological test, as a method for visualizing LV myocardial perfusion in detecting myocardial ischemia.

Discovery of Novel α-Amylase Inhibitors as Type Two Diabetes Mellitus Therapy through Fragment-Based Drug Design

Diabetes is one of the top causes of death in the world, with 425 million sufferers reported in 2017. About 90% of diabetics suffer from Type 2 Diabetes Mellitus (T2DM). Recent studies show that inhibiting the α-amylase enzyme can significantly decrease the postprandial blood glucose levels through blocking carbohydrate hydrolysis. Therefore, it can be a promising strategy for T2DM treatment. This research was aimed to find the new potential inhibitor for the α-amylase from lead-like compounds Molecular Operating Environment (MOE) database through fragment-based drug design, combining with structure-based pharmacophore design method to obtain new drug candidate for T2DM. There were 653,214 lead-like compounds which were obtained from MOE database and screened based on the Astex Rules of Three along with toxicity filter to gain lead-like fragments. The filtered fragments were docked into the binding site of the α-amylase utilizing MOE 2014.09 software. Potential lead-like fragments were grown to generate 25,600 new ligands by utilizing DataWarrior v5.0.0 software, based on the Lipinski’s Rule of Five and toxicity filter. Molecular docking simu-lation and pharmacological test was performed on the ligand libraries to acquire the best ligand, namely BGOJI which were chosen according to the lowest ΔG binding score, RMSD value < 2, good molecular interaction, ADME/T test result.