Category Archives: Original Research

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ­-Kindled Rats

Zsolt Gáll1, Szabolcs Koncz1, Orsolya Gáll2, Melinda Kolcsár1

1. Faculty of Pharmacy, Department of Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy of Tirgu Mures, Romania
2. Emergency Clinical County Hospital of Targu Mures, Romania

DOI: 10.1515/amma-2017-0037

Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modified Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed.
Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZ-kindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg).
Results: The maximal severity of seizures decreased and the latency to stage 3-­5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported.
Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.

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Risk Factors Associated with Acute Coronary Syndrome after Successful Percutaneous Coronary Intervention

Violeta Dinesch1, Mihail Dinesch2, Ileana Voichita Sirbu3, Cosmin Macarie3, Mircea Buruian4

1. University of Medicine and Pharmacy Tîrgu Mures, Romania
2. Department of Cardiology, Institute for Cardiovascular Disease and Heart Transplant, Tîrgu Mures, Romania
3. Department of Internal Medicine M3, University of Medicine and Pharmacy, Tîrgu Mures, Romania
4. Department of Morphologic Sciences M1, University of Medicine and Pharmacy Tîrgu Mures, Romania

DOI: 10.1515/amma-2017-0036

Objective: Admission for acute coronary syndrome after successful percutaneous coronary intervention is a delicate situation for the patient and doctor. Predictors of these cases are poorly described.
Methods: We retrospectively analysed the files of post-percutaneous coronary intervention patients admitted to the Department of Cardiology of the Institute for Cardiovascular Disease and Heart Transplant in Tirgu Mures between January 2012 and December 2015. Analyses using the t-test, chi-square test, and Fisher test were performed to compare demographics, clinical and angiographic characteristics of patients with acute coronary syndrome, patients with stable angina, and those without symptoms.
Results: One hundred eighty post-percutaneous coronary intervention patients were readmitted; 46 patients (25.55%) were readmitted for acute coronary syndrome. Histories of arterial hypertension and renal dysfunction at hospital admission were associated with acute coronary syndrome. Bare metal stent in-stent restenosis and localisation of bare metal stent in-stent restenosis of the left descendent coronary artery were angiographic predictors of acute coronary syndrome.
Conclusion: Several clinical and angiographic factors identify patients at high risk for acute coronary syndrome after successful percutaneous coronary intervention. Recognition and treatment of these factors may prevent readmission for such a dangerous condition and may improve outcomes.

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The Relation of Dysfunctional Cognitive Schemas and Personality Dimensions in Generalized Anxiety Disorder

Cosmin Octavian Popa1, Adrian V. Rus2, Cathleen Skinner2, Zsolt S. Jakab3

1. University of Medicine and Pharmacy Tirgu Mures, Romania, Department of Ethics and Social Sciences
2. Southwestern Christian University, Department of Social and Behavioral Sciences, Bethany, OK, USA
3. University of Medicine and Pharmacy Tirgu Mures, Department of Counseling and Career Guidance, Romania

DOI: 10.1515/amma-2017-0035

Objective: This study investigated whether differences exist in the structural personality dimensions and eighteen maladaptive cognitive schemas among in- and out-patients (Clinical Group) diagnosed with Generalized Anxiety Disorder (GAD) and people from the general population without any psychiatric diagnostic (Control Group).
Methods: The Generalized Anxiety Disorder (GAD) sample (N = 100) included 35 (35%) men and 65 (65%) women, with a mean age of 36.4 years (SD = 10.86; age range 18-69). The control sample (N = 100), included 28 (28%) men and 72 (72%) women, with a mean age of 27.1 years (SD = 9.8; age range 19-60). Data were simultaneously analyzed with one-way multivariate analysis of covariance (MANCOVA) to measure the effect of group membership on personality dimensions and on dysfunctional cognitive schemas, controlling for participants’ age. Next, univariate analyses of covariance (ANCOVAs) were done on each item with covariate-adjusted post-hoc comparisons.
Results: The results indicate that the Clinical Group participants had unfavorable scores on all five personality dimensions (i.e., Openness, Extraversion; Conscientiousness; Agreeability; and Emotional Stability – Neuroticism) and for almost all of the dysfunctional cognitive schemas in comparison with participants in the Control Group.
Conclusions: These results have general implications in understanding Generalized Anxiety Disorder (GAD) clients and their personality characteristic’s profile and dysfunctional/maladaptive cognitive schemas.

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Validation of High Performance Liquid Chromatography Methods for Determination of Meloxicam and Tenoxicam from Transdermal Therapeutic Systems

Paula Antonoaea, Anca Gabriela Cârje, Adriana Ciurba, Nicoleta Todoran, Alexandru Robert Vlad, Daniela Lucia Muntean

University of Medicine and Pharmacy from Tirgu Mures, Romania

DOI: 10.1515/amma-2017-0033

Objective: The aim of this study was to develop and validate two HPLC methods for the quantification of meloxicam and tenoxicam from transdermal therapeutic systems.
Methods: Based on 1.0% hydroxypropyl methylcellulose 15000, transdermal patches containing meloxicam or tenoxicam were prepared by solvent evaporation technique. Analytical performances of the HPLC methods for the quantification of meloxicam and tenoxicam from such systems were assessed in terms of specificity, linearity, detection limit, quantification limit, recovery and precision.
Results and discussion: The linearity of the method was assessed through a calibration curve in the 1.0 – 75.0 μg∙mL-¹ concentration range, with a regression coefficient higher than 0.999. The detection limit and the quantification limit were found to be 0.46 μg∙mL-¹ and 1.39 μg∙mL-¹, for meloxicam; and 0.88 μg∙mL-¹, respectively 2.64 μg∙mL-¹ for tenoxicam. According to the European Pharmacopeia 5.0 the mean recovery was found to be between 75% and 125%. As performance criteria for precision was used the RSD% which were lower than 2.0% for both methods.
Conclusions: The proposed liquid chromatography methods provide selective, linear and precise results for the quantification of meloxicam and tenoxicam from transdermal therapeutic systems. The presence of a single peak in the chromatograms of the analyzed transdermal patches with meloxicam or tenoxicam, certify the successful determination of the active pharmaceutical ingredient in the prepared patches.

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Could Codeine Containing OTC Analgesics Sold in Romania be Used as Recreational Drugs?

Croitoru Mircea Dumitru, Fogarasi Erzsébet, Varga Erzsébet, Chelaru Adelina, Căliman Monica-Simina, Fülöp Ibolya

University of Medicine and Pharmacy Tirgu Mures, Romania

DOI: 10.1515/amma-2016-0031

By the request of corresponding author Fogarasi Erzsébet, the article „Could Codeine Containing OTC Analgesics Sold in Romania be Used as Recreational Drugs?” published in Acta Medica Marisiensis, 2016;62(3):309-312 (DOI 10.1515/amma-2016-0031) was retracted, due to identified Conflicts of Interest.
As an immediate consequence of the aforementioned retraction, the accompanying editorial “The Culprit Coffee Filter and Freezer?” published in Acta Medica Marisiensis, 2016;62(3) had to be retracted for lack of object. This does not mean that we deny or back off the content of the editorial.

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Immersive VR in Phantom Limb Pain Therapy of Amputee Patients Due to Critical Limb Ischemia

Ana-Maria Zanfir1, Domnita Ilea Georgescu2, Sergiu Cristian Turturica3, Mihaela Eczedi1, Aurel Mironiuc4

1 County Clinical Emergency Hospital of Cluj-Napoca, Romania
2 Individual Office of Clinical Psychology and Psychotherapy, Cluj-Napoca, Romania
3 “Niculae Stancioiu” Heart Institute of Cluj-Napoca, Romania
4 University of Medicine and Pharmacie “Iuliu Hatieganu”, Cluj-Napoca, Romania

DOI: 10.1515/amma-2017-0031

Introduction: Phantom limb pain (PLP) occurs in approximately 75% of patients who undergo limb amputation. In identifying the etiopathogenic mechanisms, multidisciplinary approaches are increasingly important in explaining the causality based on neurological and psychological factors. PLP has many negative effects on the amputee’s physical and mental integrity, which is why a variety of treatments have been conceived, whose effectiveness is rather limited.
Objective: The purpose of this study is to evaluate the effectiveness of an immersive virtual reality (IVR) intervention program using the mirror therapy principles in decreasing PLP.
Method: Twenty participants suffering from PLP were randomly assigned to one of the two intervention groups: IVR and kinesiotherapy, respectively. Pre- and post-intervention measurements were performed both on pain level and on several psychological variables: depression and anxiety symptoms, pain catastrophizing, quality of life, body representation and coping strategies.
Results: Preliminary data show a significant pain relief in patients in the IVR group compared to those in the kinesiotherapy group. Besides, significant improvement was found in the case of the patients in the IVR group, in terms of life quality improvement, reducing irrational pain catastrophizing-related thoughts and positive coping strategies (positive refocusing and reappraisal). There were no differences identified between the two groups in terms of anxiety and depression symptoms. Despite expectations, patients in the IVR group experienced a significant increase in one negative coping strategy: rumination.
Conclusions: The results obtained are advocating the use of IVI intervention as a method phantom limb pain alleviation, with positive consequences on patients’ life quality.

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A Standardized Dissection Protocol to Generate Aortic Valvular Scaffolds from Porcine Hearts

Ionela Movileanu1, Marius Harpa1, Klara Branzaniuc1, Horatiu Suciu1, Ovidiu S. Cotoi1, Peter Olah1, Dan Simionescu2

1 University of Medicine and Pharmacy of Tirgu Mureş, Romania
2 University of Medicine and Pharmacy of Tirgu Mureş, Romania , Biocompatibility and Tissue Regeneration Laboratories, Department of Bioengineering, Clemson University, Clemson, USA

DOI: 10.1515/amma-2017-0029

Objective: To describe a particular harvesting procedure for isolating intact porcine aortic heart valve roots as potential sources for biologic scaffolds.
Methods: Fresh porcine hearts were brought to the Tissue Engineering and Regenerative Medicine Laboratory at the University of Medicine and Pharmacy in Targu Mures. The aortic roots were extracted from the porcine hearts by anatomical dissection. For this purpose, we used a basic surgical instrument kit. This initial phase was the first step in obtaining acellular extracellular matrix as a biologic scaffold material.
Results: Aortic roots were isolated with preservation of the ascending aorta as well as the intact aortic sinus and coronaries together with the adjacent myocardial tissue and anterior leaflet of the mitral valve. This approach allowed for safe mounting of roots into mounting rings for perfusion decellularization.
Conclusions: The described procedure is a feasible protocol for obtaining intact biological valvular scaffolds from porcine hearts. Reduced requirements regarding tools and personnel underline the easiness of aortic root harvesting using this particular procedure.

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Ultrasound Guidance Versus Peripheral Neurostimulation for Brachial Plexus Block Anesthesia with Axillary Approach and Multiple Injection Technique

Alexandra Lazar, János Szederjesi, Elena Iftenie, Leonard Azamfirei

University of Medicine and Pharmacy Tîrgu Mureș, Romania

DOI: 10.1515/amma-2017-0025

Introduction: There are several approaches for brachial plexus anesthesia: supraclavicular, infraclavicular, interscalenic and axillary. Out of these, the axillary approach is considered to be the safest because of the low risk of lesioning the adjacent structures, low risk of phrenic nerve blockade or of producing an iatrogenic pneumothorax. The block can be performed by one single injection at the site, by two injections or by several injection, among each nerve of the plexus. Ultrasound was introduced in regional anesthesia since 1978, being used initially as an auxiliary method to peripheral neurostimulator.
Objectives: The evaluation of ultrasound efficiency as an auxiliary method for brachial plexus block performance, in terms of success rate, vascular punctures. The influence of obesity on performing time, total duration of the block, and success rate of brachial plexus block.
Material and method: Prospective, randomized study which enrolled adult patients, scheduled for surgical emergency or elective surgical intervention on upper limb with brachial plexus block by axillary approach, using either the peripheral nerve stimulation or the ultrasound guidance.
Results: We enrolled 160 patients, grouped in two sets- the ultrasound group= 82 patients (US) the neurostimulation group = 78 patients (NS). Vascular punctures were statistically significant different p= 0, 04. The success rate was not influenced by the obesity.
Conclusions: Ultrasound guidance makes axillary brachial plexus block safer, we can recommend ultrasound guidance as routine for axillary brachial plexus block. The obese patient can beneficiate by both methods of brachial plexus blockage.

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Assessment of Post-Occlusive Reactive Hyperaemia in the Evaluation of Endothelial Function in Patients with Lower Extremity Artery Disease

Cosmin Carasca1, Annamaria Magdas2, Ioan Tilea3, Alexandru Incze2

1 University of Medicine and Pharmacy of Tirgu Mureş, Romania
2 Department of Internal Medicine IV, University of Medicine and Pharmacy of Tirgu Mureş, Romania
3 Cardiovascular Rehabilitation Clinic, Department of Family Medicine, Institute of Cardiovascular Diseases and Transplantation Tîrgu-Mures, Romania, University of Medicine and Pharmacy of Tirgu Mureş, Romania

DOI: 10.1515/amma-2017-0024

Background: The aim was to assess endothelial function with photoplethysmography (PPG), by post-occlusive reactive hyperaemia (PORH) combined with alprostadil challenge test in patients with peripheral artery disease (PAD).
Methods: Forty-nine PAD patients stage II-III Fontaine (39 male, 10 female, mean age 68.45±5.86 years) and a control group of 49 healthy individuals (24 male, 25 female; mean age 25.1±3.8 for a young subgroup; 71.0±0.16 years for an elderly subgroup) were included. Ankle-brachial index (ABI) was assessed at baseline, peripheral perfusion (PP) and PORH were assessed at baseline and after the 30 minutes administration of parenteral alprostadil.
Results: After 3 minutes of arterial occlusion, peripheral perfusion increased from 0.69±0.94 mV/V to 2.27±2.42 mV/V (p<0.0001). After alprostadil challenge, peripheral perfusion increased from 0.84±1.24 mV/V to 4.52±3.52 mV/V (p<0.0001). In controls PP was 2.4±1.7 mV/V versus 3.8±1.5 mV/V, p<0.0001.
Conclusion: In patients with PAD, an increase in PORH after alprostadil challenge due to the release of nitric oxide (NO), provides information on the endothelial function and could reflect the presence of collaterals. In the healthy control group, the increase in PORH could reflect the integrity of main arterial branch. In PAD patients with an increase in PORH, conservative therapy should be preferred over surgical revascularisation.

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Letrozole Determination by Capillary Zone Electrophoresis and UV Spectrophotometry Methods

Aura Rusu1, Maria-Alexandra Sbanca2, Nicoleta Todoran3, Camil-Eugen Vari4

1 Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy of Tîrgu Mureş
2 University of Medicine and Pharmacy of Tîrgu Mureş
3 Department of Pharmaceutical Technology, University of Medicine and Pharmacy of Tîrgu Mureş
4 Department of Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş

DOI: 10.1515/amma-2017-0022

Objective: Letrozole is a highly potent oral nonsteroidal aromatase inhibitor triazole derivative. The aim of this study was to quantify letrozole from bulk, pharmaceutical formulation, and spiked urine samples by developing a simple, rapid and cost effective capillary electrophoresis method. Methods: A capillary zone electrophoresis method was optimized and validated. Additionally, an UV spectrophotometry method was used for comparing results. Results:The capillary zone electrophoresis method using a 90 mM sodium tetraborate background electrolyte proved to be an efficient method for determination of letrozole in a very short time, less than 2 minutes, using 20 kV voltage, 50 mbar/2 seconds pressure and 50°C temperature as optimum parameters. Additionally, the UV spectrophotometry method proved to be simple and efficient to quantify letrozole from bulk material and pharmaceutical formulation with linearity of response between 5 to 20 µg·mL-1 concentrations. For both methods, validation parameters, including linearity, detection and quantification limits were determined. Also we proved that our electrophoretic method has potential in analyzing letrozole from biological samples, obtaining encouraging results on estimation of letrozole from spiked urine samples without any special treatment. Conclusions: To quantify letrozole from bulk material, pharmaceutical preparations, and spiked urine samples the capillary zone electrophoresis method using a tetraborate sodium background electrolyte has proven to be simple and appropriate. Also a simple UV spectrophotometric method has been developed and validated for the same purposes.

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