Category Archives: Original Research

Effect of Isoflurane Anesthesia on the Heart Rate and Blood Pressure Response to Autonomic Nervous System Stimulation and Inhibition in Rats

Ioana Alkora Balan1, Teodor Grigoraș2, Carmen Matei1, Alina Grigoraș1, Vasile Bogdan Halațiu1,2, Răzvan Constantin Șerban3, Alina Scridon1,4

1. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Emergency Clinical County Hospital Targu Mures, Romania
3. Emergency Institute for Cardiovascular Diseases and Transplantation, Targu Mures, Romania
4. Center for Advanced Medical and Pharmaceutical Research, Targu Mures, Romania

DOI: 10.2478/amma-2020-0016

Objective: Many experimental studies aim to assess the autonomic nervous system (ANS), but this is often hampered by interactions with anesthetic drugs. We aimed to evaluate whether isoflurane anesthesia is suitable for ANS evaluation in rats.
Methods: Six Wistar rats were anesthetized with isoflurane (4 L/min, 2.5%). Systolic blood pressure (SBP) and heart rate (HR) were measured at baseline and 20 min after sympathetic inhibition (propranolol, 5 mg/kg) and stimulation (isoproterenol, 2.5 mg/kg), and parasympathetic inhibition (atropine nitrate, 2 mg/kg) and stimulation (carbamylcholine, 0.4 mg/kg; acetylcholine, 0.1 mg/kg). Six additional rats were used to assess the effects of isoproterenol, carbamylcholine, and atropine nitrate in the absence of anesthesia.
Results: Propranolol significantly decreased the HR and the SBP, whereas isoproterenol significantly increased the HR (all p≤0.01) in the isoflurane-anesthetized rats. However, the HR response to sympathetic stimulation was significantly reduced in the anesthetized compared to the non-anesthetized rats (p=0.03). Carbamylcholine and acetylcholine significantly decreased both the HR and SBP (all p<0.05) in the anesthetized rats, but the response to carbamylcholine administration was significantly more pronounced in the non-anesthetized rats (p=0.03). Atropine nitrate significantly increased the HR (p<0.001) in the non-anesthetized rats, but it had no effect on either the HR or the SBP in the presence of isoflurane anesthesia (both p>0.05).
Conclusions: Isoflurane anesthesia appears to interfere with both components of the ANS and is therefore not an optimal approach for experimental ANS evaluation. Our data indicate autonomic receptors and/or post-receptor mechanisms as the most likely site for isoflurane-ANS interactions.

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Left Ventricular Function and Morphology after Cardiac Surgery for Severe Mitral Insufficiency – A Single Center Experience

Carmen Opris1, Horatiu Suciu2, Septimiu Voidazan3, Cosmin Opris1, Marius Harpa2, Alexandra Stoica1

1. Department of Adult and Children Cardiovascular Recovery, Emergency Institute for Cardio-Vascular Diseases and Transplantation, Targu Mures, Romania
2. Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Departament of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2020-0015

Introduction: Mitral insufficiency is a common valvular disease affecting 10% of the general population. The main treatment of the severe mitral regurgitation is surgical. We have analyzed the impact of cardiac surgery on the left ventricular performance and morphology, in patients treated for severe mitral insufficiency accordingly to the type of intervention, ischemic time and type of cardioplegia.
Methods: Ninety patients diagnosed with isolated severe mitral insufficiency that benefited from mitral valvular replacement or mitral valvuloplasty were retrospectively enrolled. The left ventricle, the left atrium, the right ventricle diameters and the left ventricle ejection fraction were measured by two-dimensional (2D) echocardiography before and after surgery. The influence of the myocardial ischemia time and the type of cardioplegia administered on the ventricular systolic function were also analyzed.
Results: Regardless the surgical technique chosen, after surgery we noticed a decreased size of the left ventricle (preoperative mean 54.91mm ±8.18 vs postoperative mean 51.94mm±8.15, p=0.035), right ventricle (preoperative mean 33.49mm±5,87 vs postoperative mean 32.41mm±6.03, p=0.0001), as well as the ejection fraction (preoperative mean 51.29%±8.51 vs postoperative mean 46.57%±8.71, p=0.0001).
Conclusions: Immediately after surgery, a decrease in the size of cardiac cavities as well as a decrease of the left ventricle ejection fraction is noticed.

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Correlation Study of Serum Zinc Concentration and Retina Layer Thickness in Hypertensive Patients

Robert Gabriel Tripon, Enikő Nemes-Nagy, Zoltán Preg, Karin Ursula Horváth, Beáta Baróti, Angela Borda, Márta Germán-Salló

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2020-0017

Objective: The aim of our study was to evaluate whether blood serum zinc concentration correlates with the thickness of human retina layers, in hypertensive patients with microvascular damage.
Methods: Retinas of elderly patients with arterial hypertension and microvascular damage were imaged using a swept-source ocular coherence tomography from Topcon. Automatic retinal segmentation was applied on a 6mm X 6mm scan protocol and average thickness for 5 examined layers was used for statistical analysis. Serum zinc concentration was measured using the Zinc Assay kit from Sentinel Diagnostics in a spectrophotometric method.
Results: The average age of the twenty-three enrolled patients was 70 years, varying between 62 and 76. The mean zinc value was 9.9 µmol/l ±1.62 (SD). All five examined layers of the retina presented inverse correlation with serum zinc concentration. The complex including the inner plexiform layer and ganglion cell layer indicated the Spearman’s (rho) correlation coefficient -0.42 and a significance level of p=0.04. Patients in high-Zn group (≥ 9.87 µmol/l) had thinner macular retina layers, most importantly in the inner-plexiform layer-ganglion cell layer complex (p=0.006).
Conclusions: Our study has found that serum zinc concentration is inversely correlated with the thickness of retina layers with statistical relevancy in the inner plexiform layer – ganglion cell layer complex. This finding emerges experimental studies in order to elucidate its clinical significance and to evaluate whether the fine architecture of the inner retina has the potential to benefit from oral zinc supplementation through modulating serum levels of zinc in patients with microvascular-damaging diseases.

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A Study of Heat Generation in Orthopaedic Bone Drilling Process

Flaviu Moldovan, Tiberiu Bataga

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2020-0009

Reconstruction and repair of a complete bone fracture requires surgical drilling of bone in order to create holes which support easy insertion of screws. The objective of the research is to optimize kinematic parameters when drilling bone in order to avoid bone necrosis and increase the capacity of bones to retain the surgical screws. In literature there are presented attempts to measure the temperature of bones by introducing thermocouples into bone near the drill path which is not a satisfactory method. In this research it is proposed a new method for measuring temperature by means of a digital infrared thermometer oriented on bone surface where holes are made. We have drilled animal bones and represented the experimental curves of temperature for a wide range of kinematic parameters that are supposed to be used during orthopaedic operations. It is concluded speeds ranges that can be used when drilling bone holes, which ensures good cutting conditions and temperatures at a level which does not affect the quality of the assembly.

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Enumerating the Yield and Purity of PfDNA from Archived, Newly Used mRDTs and Comparison with DBS from a Malaria-Endemic Focus

Olalere Shittu1, Oluyinka Ajibola Iyiola2, Olufunke Adenike Opeyemi1, Olusola Ajibaye3, Glory Ifeoma Chukwuka1, Motunrayo Idowu Adekunle1, Oluwatosin Fakayode4, Emeka Asogwa5, Mosunmola Rafiat Folorunsho4

1. Parasitology Unit, Dept. of Zoology, University of Ilorin, Nigeria
2. Cell Biology and Genetics Unit, Department of Zoology, University of Ilorin, Nigeria
3. Nutrition and Biochemistry Section, Nigeria Institute of Medical Research, Yaba, Nigeria
4. Kwara State Ministry of Health, Ilorin, Nigeria
5. Department of Biochemistry, University of Ilorin, Nigeria

DOI: 10.2478/amma-2020-0008

Objective: Archived malaria rapid diagnostic test strips (mRDTs) serves as an important source of plasmodium Deoxyribose Nucleic Acid (DNA) in epidemiological studies. The presence of Plasmodium falciparum DNA (PfDNA) in mRDTs (yr. 2016-2017) and newly used ones (yr. 2018) were enumerated with a view to establish the parasite’s optimum genomic DNA volume. Methods: A retrospective study to determine the yield and purity of used mRDTs was carried out on randomly selected mRDTs (2016 – 2018). Both positive and negative mRDTs samples were analyzed with nested Polymerase chain reaction (nPCR). Dried blood spots (DBS) were obtained from study enrolments and analyzed molecularly. nPCR and Agarose gel electrophoresis were used to determine P. falciparum DNA. Results: Agarose gel electrophoresis results showed that only 26 out of the 50 samples eligible for screening were PCR positive for P. falciparum. The following was observed; yrs.: 2016 – 17(34%) with 2.06 X 103 yield, 1.7235 purity; 2017 – 16(32%) with 1.03 X 103 yield, 1.7619 purity and 2018 – 17(34%) with 1.42 X 103 yield, 1.6194 purity. Molecular analysis (P.f. 18Ss rRNA) was determined to ascertain positive result that appeared negative using mRDTs or microscopy. The DNA yield of the DBS for 2018 was 1.66 X 103 and a purity (Optical Density 260/280) of 1.69. The purity was higher than that of the mRDTs with a DNA yield of 1.42 X 103 and 1.62 purity. Conclusion: PfDNA extraction is an important process for malaria PCR screening and the reliability is dependent on pureness and concentration.

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The relative bioavailability of two formulations containing 10 mg Dapagliflozin assessed under fasting conditions in a randomized crossover study in healthy Caucasian subjects

Monica Oroian1,2, Diana Ioana Pop1,2, Ana-Maria Gheldiu3, Sandeep Bhardwaj2, Adriana Marcovici2, Arshad Khuroo4, Laurian Vlase1

1. Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy „Iuliu Haţieganu”, Cluj-Napoca, Romania
2. Clinical Pharmacology and Pharmacokinetics Department, Terapia S.A – a Sun Pharma Company, Cluj-Napoca, Romania
3. Department of Pharmaceutical Botany, Faculty of Pharmacy, University of Medicine and Pharmacy „Iuliu Haţieganu”, Cluj-Napoca, Romania
4. Clinical Pharmacology and Pharmacokinetics Department, Gurugram, India

DOI: 10.2478/amma-2020-0006

Objective: The aim of the present study was to evaluate the relative bioavailability of two formulations containing 10 mg dapagliflozin in healthy Caucasian subjects under fasting conditions.
Materials and Methods: Forty-eight healthy Caucasian subjects were enrolled in a single-dose, crossover, balanced, open label, randomized clinical trial, with two treatment, two periods and two sequences. The wash-out period was of 7 days and thirty-eight subjects completed both study periods. Each subject received a single dose of 10 mg dapagliflozin as the reference product Farxiga® (AstraZeneca Pharmaceuticals LP, USA) and the test product developed by Sun Pharmaceutical Industries, India. Dapagliflozin plasma levels were determined from blood samples collected in both study periods before and after dosing until 48 hours by using a validated LC-MS/MS method. For pharmacokinetic analysis of data, the non-compartmental method was used (Phoenix® WinNonlin 6.3). The statistical analysis was performed by SAS software 9.1.3 for the logarithmically transformed values of maximum plasma concentration and area under the curve.
Results: The 90% confidence intervals for the evaluated pharmacokinetic parameters were found to be in the accepted interval for bioequivalence (80.00-125.00%).
Conclusion: The 10 mg dapagliflozin immediate release tablet newly developed by Sun Pharmaceutical Industries, India, is bioequivalent with the reference product Farxiga® under fasted state of the subjects.

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Thin layer chromatographic compatibility study in preformulation of new transdermal therapeutic systems

Octavia-Laura Moldovan1, Diana-Nicoleta Brihan1, Nicoleta Todoran2, Aura Rusu3

1. Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2020-0004

Objective: The compatibility of four binary active substances combinations adapalene – levofloxacin (ADP-LFX), adapalene – miconazole nitrate (ADP-MCZ), levofloxacin – meloxicam (LFX-MLX) and levofloxacin – miconazole nitrate (LFX-MCZ) was analysed to be comprised in new transdermal therapeutic systems. Also, the compatibility of selected active substances and four polymeric excipients (hydroxypropyl methylcellulose – HPMC 15000, hydroxypropyl methylcellulose – HPMC E5, ethyl cellulose – EC 10, and hydroxyethyl cellulose – HEC) was studied.
Methods: Thin layer chromatographic method (TLC) and four selected mobile phases were used. On the plate (in situ) were obtained the binary combinations (active substances and active substance-polymer).
Results: A good compatibility of ADP-LFX was found using ammonia : methanol : acetonitrile : methylene chloride 2:4:1:4 mobile phase. Using chloroform : acetone : glacial acetic acid 34:4:3 on the chromatogram of ADP-MCZ, only ADP spots appeared but without changes in the shape of the spots and Rf values. Any modifications of LFX and MLX spots (from LFX-MLX mixture) had been observed using toluene : glacial acetic acid : methanol 11:1:0.5 mobile phase, although LFX spots have remained on the baseline. Only LFX spots were visible from LFX-MLX and LFX-MCZ mixtures (ammonia : methanol : acetonitrile : methylene chloride 2:4:1:4 mobile phase). Distinctive spots were observed for ADP, LFX and MLX with variable results from no chemical interactions to limited chemical interactions when the compatibility with polymers was verified.
Conclusions: ADP-LFX and LFX-MLX mixtures were found to be compatible. ADP with HPMC polymers and LFX with HPMC E5 and HEC had presented excellent compatibility; for the other binary combinations, different analytical methods will be necessary.

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Comparative study of Clinical Characteristics in Patients with Mild and Severe Reflux Esophagitis

Melania Macarie1, Simona Maria Bataga1, Monica Pantea1, Razvan Opaschi1, Simona Mocan2, Ioan Macarie3

1. Department of Gastroenterology. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of Pathology, Targu Mures County Clinical Emergency Hospital, Romania
3. Department of Internal Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2020-0002

Objective: This study aims to determine the correlation between risk factors and erosive esophagitis development. Methods: We conducted a retrospective observational study on a consecutive series of 19.672 patients who underwent upper gastrointestinal endoscopy between 01.01.2011-31.12.2017. A total of 3005 patients, diagnosed with erosive esophagitis, were included in the present study and stratified according to Los Angeles classification. Results: During the studied period we found 3005 patients with erosive esophagitis, sex ratio male to female was 1.3/1, the most common forms of esophagitis being grade A and B: 74.54% patients with esophagitis grade A, 14.80% patients with grade B; 5.29% patients were with grade C and 5.35% patients with esophagitis grade D. In severe esophagitis the male predominance was more prevalent (249 males, 71 female), with a sex ratio 3.50/1. The correlation of male gender with severe esophagitis was highly statistically significant (p < 0.0001, OR 2.97; 95% CI 2.25-3.91). Hiatal hernia was diagnosed in 1171 patients, the presence of large hiatal hernias, being an important predictor, with statistical significance (p < 0.0001, OR 3.41; 95% CI 2.22-5.21), for severe esophagitis development. Incidence of Helicobacter pylori infection was 11.51%, in the entire study group, with no statistical significant difference between patients with mild or severe esophagitis (12.02% vs 7.18%). Conclusion: Erosive esophagitis is a frequent disease, the most common forms being grade A and B. Male gender and the presence of hiatal hernia are the most important risk factors for erosive esophagitis development, in our study group.

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Factors Involved in the Pathogenesis of Acne and Its Psycho-Social Impact

Septimiu Voidăzan1, Reka Toth1, Teodora Varo2

1. Department of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. County Emergency Clinical Hospital, Targu Mures, Romania

DOI: 10.2478/amma-2020-0001

With acne as one of the most common and frequent conditions of young adult patients, we looked for significant associations, associated conditions with influence on the skin condition with the idea of outlining a different approach of the acne patient. With a multifactorial, multidisciplinary etiopathogeny, the purpose of this study was to highlight the factors involved in the pathogenesis of this condition and to identify those that should be taken into account when prescribing the treatment.

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Fatal Road Traffic Accidents in Mureș County, Romania – A Retrospective Autopsy Based Study

Cosmin Carașca1, Timur Hogea2, Viorel Hădăreanu1

1. Institute of Legal Medicine, Tirgu Mures, Romania
2. County Emergency Clinical Hospital, Tirgu Mures, Romania

DOI: 10.2478/amma-2019-0024

Objective: The main objective of this study is to evaluate the medico-legal aspects of fatal road traffic accidents.
Methods: This is a retrospective study consisting of 80 forensic autopsies performed at the Institute of Legal Medicine – Tîrgu Mureș, Romania during a two years period, between January 1st, 2016 to December 31st, 2017. The information obtained was based on the medical records and the evaluation of autopsy reports.
Results: Male victims involved in road traffic accidents were nearly three times more numerous than women (72.5% vs. 27.5%). Divided into 3 age groups (under 35 years old, 36-59 years old and over 60 years old) we noticed a relatively uniform distribution of the victims, with a slight dominance of the 36-59 age group and the over 60 years of age group. The highest number of victims was among the pedestrians (36.25%), followed in decreasing order by the drivers (33.75%), passengers (17.5%), cyclists (7.5%) and motorcyclists (5%). Positive alcohol testing was found in 14 of drivers (81 %). The analysis of lesions found during necropsies of the deceased at the scene of the accident highlights some particularly life-incompatible injuries that resemble any rescue effort on the part of the medical crew moved to the scene of the accident.
Conclusion: Inappropriate road conditions and indiscipline in traffic of both drivers and pedestrians contribute to unacceptably high mortality.

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