Category Archives: Original Research

Risk factors associated with long-term radio-cephalic arteriovenous fistula failure in dialysis patients

Adrian Vasile Mureșan1,2, Réka Bartus1,2, Emil-Marian Arbănași1,2,3,4, Eliza-Mihaela Arbănași3,4, Alexandru Ludovic Szanto2, Elena Florea2, Cătălin Mircea Coșarcă2, Marius Mihai Harpa5,6, Ioan Hosu7, Claudiu Constantin Ciucanu1,2,3, Nicolae Alexandru Lazar2, Ionela Georgiana Bodiu2, Eliza Russu1,2

1. Department of Vascular Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Clinic of Vascular Surgery, Mures County Emergency Hospital, Targu Mures, Romania
3. Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania
4. Regenerative Medicine Laboratory, Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5. Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, Romania
6. Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania
7. Department of Nephrology, Mures County Emergency Hospital, Targu Mures, Romania

DOI: 10.2478/amma-2025-0001

Objective: The aim of this study is to analyze the risk factors associated with long-term radio-cephalic arteriovenous fistula failure in dialysis patients.
Methods: This retrospective observational study enrolled 81 patients diagnosed with end-stage kidney disease requiring arteriovenous fistula. Patients were categorized into two groups based on the long-term permeability of vascular access. The hospital’s electronic database was used to collect demographic data, risk factors, comorbidities, pre-operative laboratory data, and pre-operative vascular mapping characteristics.
Results: Among the patients with arteriovenous fistula failure, we observed a lower incidence of men (p=0.009), a higher incidence of diabetes mellitus (p=0.036), and a higher incidence of active smoking (p=0.009). At ROC-curve analysis we identified an optimal cut-off value of 128.2 for glucose (AUC: 0.715, 66.7% Sensitivity, and 78.1% Specificity), 1.17 for leukocyte glucose index (AUC: 0.692, 60.0% Sensitivity, and 81.2% Specificity), and 7.33 for interleukin-6 (AUC: 0.925, 90.0% Sensitivity, and 84.6% Specificity). In Kaplan-Meier survival curve analysis, there was a higher incidence of arteriovenous fistula failure among females (p=0.033), smokers (p<0.001), and patients undergoing hemodialysis via a central venous catheter at the time of admission (p=0.047). Cox-regression analysis indicates that female sex (HR: 3.43, p=0.033) and active smoking (HR: 5.02, p=0.002) are predictors of vascular access dysfunction. Additionally, elevated values of glucose (HR: 1.89, p=0.004), Interleukin-6 (HR: 2.78, p=0.001), and leukocyte glucose index (HR: 1.95, p=0.008) are associated with arteriovenous fistula failure.
Conclusions: In conclusion, female sex, active smoking, high baseline glucose levels, Interleukin-6, and leukocyte glucose index are linked to long-term failure of arteriovenous fistula failure.

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Technique presentation: The combination of Pectoralis and Serratus Plane Nerve Blocks for cardiac implantable devices

Mihaela Butiulca1,2, Lenard Farczadi3, Alexandra Lazar1,2

1. Department of Anesthesiology and Intensive Care Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of Anesthesiology and Intensive Care Medicine, Emergency County Hospital, Târgu Mureș, Romania
3. Chromatography and Mass Spectrometry Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0038

Cardiac resynchronization therapy devices, implantable cardioverter defibrillators, and pacemakers are used to treat advanced systolic heart failure, ventricular tachyarrhythmias, and bradyarrhythmia. Over the past ten years, there has been a notable rise in the number of cardiac implanted electronic device implants because of mounting evidence of better survival and quality of life among specific patient populations. Appropriate analgesia and sedation throughout the implantation procedure is crucial for the patient’s stability. This paper aims to describe the advantages of both interpectoral plane block (PECS I) and interpecto-seratus plane block (PECS II) for the implantation of cardiac devices.
Combining PECS I and PECS II blocks provides advantages for the thoracic wall procedures. While the PECS I block anesthetizes the medial and lateral pectoral nerves, PECS II extends coverage to upper intercostal nerves (T2-T7), as well as the long thoracic and thoracodorsal nerves, covering areas that are not anesthetize adequately by PECS I alone. Minimizing the need for opioids, leading to fewer opioid related side effects contributing to shorter recovery time and nonetheless creating less discomfort for the patient.
This combined regional technique offers comfort to the patient due to its sole puncture needed for performance and by offering an extensive anesthesia at the site of the procedure.

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Preliminary study to obtain some fluoroquinolone-tetracycline hybrids

Ioana-Andreea Lungu1, Lénárd Farczádi2, Zoltán-István Szabó3, Șerban Andrei Gâz4, Octavia-Laura Moldovan1, Aura Rusu5

1. Medicine and Pharmacy Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Pharmaceutical Industry and Management Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4. Organic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5. Pharmaceutical and Therapeutic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0034

Objective: This paper aimed to synthesize hybrids of fluoroquinolones with tetracycline class representatives and conduct their preliminary characterization.
Methods: A reaction between tetracycline representatives (doxycycline, tetracycline), formaldehyde (acting as a molecular connector) and fluoroquinolone representatives (ciprofloxacin, moxifloxacin, and norfloxacin) was attempted through a classical reflux synthesis with an electrical heating source (heating mantles) and a microwave-assisted reflux synthesis. One synthesis group also used cupric chloride dihydrate as a catalyst. The samples were analyzed using Differential Scanning Calorimetry, Electrospray Ionization Mass Spectrometry, or High-Performance Liquid Chromatography.
Results: The results indicated the formation of a compound different from the parent components in the case of doxycycline-norfloxacin and possibly tetracycline-norfloxacin hybrids.
Conclusions: Both synthesis methods yielded similar results. The influence of the catalyst did not seem to have been significant. The synthesis method is simple and one-step, using non-toxic solvents. Future studies involving molecular docking and microbiology could be employed to further explore the mechanism of action and the microbiological effects of the hybrids.

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The association between decay missing filled tooth index and body mass index in a group of preschool children

Liana Beresescu1, Denisa Oprea2, Florina Ruta3, Raluca Sabau4, Alexandra Mihaela Stoica5

1. Department of Preventive and Community Dentistry, Faculty of Dental Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Faculty of Dental Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department Community Nutrition and Food Safety, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4. Private practice, Targu Mures, Romania
5. Department of Odontology and Oral Pathology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0033

Background: Dental caries and obesity are prevalent chronic conditions across all age groups, with common multifactorial causes such as diet and socioeconomic status.
Objective: The aim of this study was to determine if there is a correlation between the decay missing filled tooth (DMFT) index and body mass index (BMI) in preschool children.
Materials and Methods: The study included 390 children aged 4 to 6 years, comprising 262 boys and 128 girls. The DMFT indices were assessed by two dentists, while anthropometric measurements were conducted by a nutritionist. BMI was calculated using the WHO AnthroPlus application.
Results: Most children were of normal weight (332), with 28 being underweight and 30 overweight. There were no obese children. Underweight children had a mean DMFT index of 3.7 ± 3.56, significantly higher than those of normal weight (2.0 ± 1.88) and overweight children (1.9 ± 1.60).
Conclusions: This study highlighted an association between the DMFT index and BMI in preschool children, with underweight children having a higher DMFT index compared to those of normal weight and overweight.

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Food-effect study on the pharmacokinetics of indapamide prolonged-release tablets

Maria Codreanu1,2, Diana Iacob3, Maria Ioana Onofrei4,5, Ana-Maria Vlase6, Dana Maria Muntean1, Laurian Vlase1

1. Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania
2. Regulatory Affairs Department, Antibiotice SA, Iași, Romania
3. Center for Drug Evaluation, Antibiotice SA, Iași, Romania
4. Clinic of Infectious Diseases, “Sf. Parascheva” Clinical Hospital of Infectious Diseases, Iasi, Romania
5. Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
6. Department of Pharmaceutical Botany, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania

DOI: 10.2478/amma-2024-0032

Objective: A comparative study was performed to evaluate the food impact on the pharmacokinetics of indapamide 1.5 mg prolonged release tablets (SR).
Methods: The data evaluated were collected from 2 randomized, single dose, 2-way crossover bioequivalence studies with administration of indapamide to healthy Caucasian volunteers under fasting and fed conditions, respectively. Forty-four eligible subjects aged 19–39 years were enrolled in both studies: 22 subjects received indapamide under fasting (study 1) and the other 22 under fed (study 2) conditions. Blood samples were collected following the same schedule before and up to 96.0 hours after drug administration. Blood concentration of indapamide were quantified by a validated LC-MS/MS method. A non-compartmental analysis was used to calculate the pharmacokinetic parameters. Mathematical deconvolution was applied to assess indapamide absorption. Statistical significance for differences in key pharmacokinetic parameters was evaluated using an ANOVA test, with a significance threshold of p < 0.05.
Results: In total, 44 subjects were included in analysis. The outcomes demonstrated that ingestion of food independently reduced the mean of tmax by 4.64 h and increased the value of Cmax by 19.7 ng/mL, while the AUC remained unchanged.
Conclusions: Notably, differences in drug absorption rate obtained after co-administration of indapamide with food had no significant influence in safety and efficacy of the drug.

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Bio efficacy of methanol leaf extracts of Cissampelos pareira Linn., Lantana camara Linn. and Ocimum gratissimum Linn. against fever in Wistar rats

Susan Nyawira Kimuni1, Stephen Maina Gitahi2, Mathew Piero Ngugi1, Eliud Mwaniki Njagi1

1. Department of Biochemistry, Microbiology and Biotechnology, Kenyatta University, Nairobi, Kenya
2. Department of Natural Sciences, Catholic University of Eastern Africa, Nairobi, Kenya

DOI: 10.2478/amma-2024-0031

Objective: This study evaluated antipyretic potency of methanol extracts of Cissampelos pareira, Lantana camara and Ocimum gratissimum in Wistar rats.
Methods: The leaves samples were obtained from Embu County, Kenya. Quantitative phytochemical analysis of the extracts was conducted using LC-MS and GC-MS methods. The study was performed in eight sets each with 5 Wistar rats (n = 5): positive control, normal control, negative control as well as experimental. Group I (normal control) rats were injected intraperitoneally with a solution of Dimethyl sulfoxide (DMSO) only. Group II (negative control) constituted rats initiated with fever using turpentine alongside DMSO. Group III, (positive control) rats were induced with pyrexia and then administered with aspirin. Groups IV, V, VI, VII, and VIII composed of turpentine-induced pyretic rats that were intraperitoneally injected with various extracts dosages. The data was analysed using Statistical Package for Social Sciences (v25) software.
Results: The plant extracts possess antipyretic activities that are comparable to the standard therapy, aspirin. Quantitative phytochemistry showed that the extracts contained bioactive principles such as terpenoids, flavonoids, and alkaloids which exert antipyretic activity.
Conclusion: The studied plants are rich in secondary metabolites that have antipyretic efficacies in rats. Hence, this study validates the folkloric use of the tested plants to manage fever among the Mbeere community in Kenya.

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Predictors of mortality in patients with early versus late onset of septic shock. A prospective, observational and comparative pilot study

Ioana Denisa Botoș1, Carmen Pantiș1, Marcel Ovidiu Negrău1, Constantin Bodolea2, Mihai Octavian Botea1, Elisabeta Ioana Hirișcău3, Cosmin Ion Puia1,4

1. Faculty of Medicine and Pharmacy. University of Oradea, Oradea, Romania
2. Department of Anesthesia and Intensive Care, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Romania
3. Department of Nursing, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Romania
4. Department of Surgery, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj Napoca. Romania

DOI: 10.2478/amma-2024-0027

Introduction: Outcome and predictors of early- and late-onset septic shock are still controversial. The aim of the study was to compare the relevant predictors of 28-day mortality in early- and late-onset septic shock and other non-septic critical illnesses.
Material and Methods: We conducted a prospective, observational, pilot study. A group of 46 patients with early septic shock and 42 non-septic critically ill patients from the emergency department and 56 patients with late septic shock from the hospital were enrolled. On admission to the ICU, the most important potential predictors of 28-day mortality were assessed.
Results: In terms of predicting 28-day mortality, a higher mNUTRIC score was the only common predictor for all three groups. Multi-drug resistant (MDR) bacterial aetiology was a common predictor in both forms of septic shock. Older age, female gender, increased neutrophil-to-lymphocyte ratio (NLR) and increased need for vasoactive agents were common predictors in late septic shock and non-septic critically ill patients. Increased red blood cell distribution width coefficient of variation (RDW-CV) was predictor in early septic shock and non-septic critically ill patients. Central venous-arterial carbon dioxide difference (Pcv-aCO2) was predictor in patients with early septic shock. Inflammatory index and MDR carrier status were predictors in non-septic critically ill patients.
Conclusions:A higher mNUTRIC score is a predictor of 28-day mortality in early and late septic shock and in critically ill non-septic patients. MDR aetiology was predictive of 28-day all-cause mortality in both types of septic shock, and Pcv-aCO2 was predictive in patients with early septic shock.

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Helicobacter pylori and autoimmunity in atrophic gastritis – comparison of clinical, endoscopic and histopathological features

Ana-Maria Filip1, Sabrina-Nicoleta Munteanu2, Simona Mocan3, Dragoș Huțanu4, Monica Pantea2, Anca Negovan2

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

DOI: 10.2478/amma-2024-0028

Objective: This study aims to investigate the clinical, endoscopic, biologic and histopathological differences between Helicobacter pylori-associated and autoimmune gastric atrophy.
Methods: A retrospective analysis was conducted on 95 patients diagnosed with either H. pylori-related corporal and antral atrophy (43 patients) or autoimmune corporal atrophic gastritis (52 patients).
Results: A significant male predisposition for H. pylori-associated atrophic changes in both the antrum and corpus regions (p=0.007, OR=3.24) was observed in comparison with autoimmune etiology of atrophy. While comorbidities and lifestyle factors showed similar distributions across groups, only unintentional self-reported weight loss demonstrated a significant association with H. pylori atrophy (p=0.0177, OR=3.94). Corporal erosions were strongly associated with antral and corporeal atrophic gastritis (p=0.04, OR=8.27), but the rest of mucosal lesions are comparable among groups. Interestingly, patients with H. pylori-related pangastric atrophy exhibited lower frequencies of altered triglyceride (p=0.018) and cholesterol (p=0.029) levels compared to the autoimmune group. Linear regression analysis identified low triglyceride levels as an independent predictor for H. pylori-associated antral and corporal atrophic gastritis (p=0.04) in endoscopic population with atrophy, but no hematological or clinical parameters were predictive for these changes.
Conclusions: Male patients are more likely to present with corpus atrophic gastritis associated with H. pylori infection than with an autoimmune etiology. Patients with atrophic gastritis tend to have similar clinical characteristics, except for dyslipidemia, which is more prevalent in those with H. pylori pangastritis. Corporal erosions are associated with active H. pylori infection in atrophic mucosa.

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Determination of caffeine by micellar electrokinetic chromatography in different beverages

Alexandra Uilăcan, Denisa Gabriela Stroia, Gabriel Hancu

Department of Pharmaceutical and Therapeutic Chemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0026

A fast, simple and cost-effective capillary electrophoresis (CE) method was developed for caffeine determination in different beverages (energy drinks, soft drinks). Because caffeine is neutral from electrophoretic point of view and migrates with the electroosmotic flow (EOF), micellar electrokinetic chromatography (MEKC) was chosen as the separation method. The optimum separation conditions consisted of 25 mM sodium tetraborate, 100 mM sodium dodecyl sulphate, pH 9.30, 20°C temperature, 20 kV voltage, 50 mbar/sec hydrodynamic injection, UV detection at 270 nm. Employing the optimized conditions caffeine was quantified in less than 3 minutes. The analytical performances of the method were verified in terms of accuracy, linearity, limit of detection and quantification, precision and robustness. The method was applied also to detect caffeine in coffee and tea. The advantage of MEKC over other analytical methods, particularly compared with the more frequently used HPLC methods, lies in its lower operating costs and higher environmental friendliness.

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Identification and expression of microRNA-34a-3p and its target Rapamycin-insensitive companion of mTOR (RICTOR) in polycystic ovarian syndrome in South Indian population

Manya Saravanan1, Ameya K P2, Ashikha Shirin Usman P P2, Durairaj Sekar2

1. Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Science (SIMATS), Saveetha University, Chennai, India
2. RNA Biology Lab, Saveetha Dental College and Hospital, Saveetha Institute of Medical And Technical Science (SIMATS), Saveetha University, Chennai, India

DOI: 10.2478/amma-2024-0025

Objectives: Polycystic Ovarian Syndrome (PCOS) is a complex condition affecting 4% to 26% of the world-wide population and is characterized by enlarged ovaries and cysts. These cysts are actually immature ovarian follicles that have failed to mature and release an egg, which is a process known as anovulation. This study aims to explore the potential of miRNA as therapeutic and diagnostic biomarkers for PCOS, focusing on the identification and expression analysis of novel candidates like miR-34a-3p and its target Rapamycin-insensitive companion of mTOR (RICTOR). The objective is to enhance our understanding of the molecular mechanisms associated with PCOS, particularly the roles of miRNAs in its pathogenesis. In future, we plan to test miR-34a-3p mimics/inhibitors and RICTOR downregulation to improve insulin sensitivity and ovarian function. We will also explore combined therapies and conduct trials to assess their efficacy and safety in PCOS patients, aiming to develop practical treatments for PCOS.
Methods: National Centre for Biotechnology Information (NCBI) database, TargetScan, and miRbase were explored to identify the novel miRNA candidates, resulting in the discovery of miR-34a-3p. Secondary structure was constructed using RNA Fold, and Ct and melt curve analysis assessed its statistical expression levels. Additionally, similar research was conducted to analyze the expression levels of RICTOR, a target of miR-34a-3p.
Result: The secondary structure showed miR-34a-3p has a minimum free energy of -47.20 kcal. Additionally shows dysregulation in both miR-34a-3p and RICTOR in individuals with PCOS. Furthermore, overexpression of RICTOR and decrease in miR-34a-3p levels suggest their possible role in the pathogenesis of PCOS.
Conclusion: In PCOS, miR-34a-3p is downregulated, and there’s an inverse relationship between miR-34a-3p and RICTOR levels. qRT-PCR results showed high RICTOR expression in PCOS patients. RICTOR plays a crucial role in the mTOR pathway, affecting insulin signaling, metabolism, and cellular growth, which are all implicated in PCOS.

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