Category Archives: Original Research

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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Surgical procedure for acellular vascular xenografts testing in sheep carotid artery

Marius Mihai Harpa1, Alexandra Iulia Puscas2, Emanuel David Anitei3, Dan Teodor Simionescu4, Raluca Ionela Truta1, Hamida Al-Hussein2, Ionela Cotfas1, Claudiu Ghiragosian2, Cosmin Marian Banceu2, Tudor Capilna2, Horatiu Suciu2, Hussam Al-Hussein2

1. Regenerative Medicine Laboratory, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, Romania
4. Biocompatibility and Tissue Regeneration Laboratories, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA

DOI: 10.2478/amma-2024-0024

Objective: The objective of this study is to demonstrate the safety and reproducibility of our surgical technique for implanting decellularized vascular xenografts in the carotid artery of sheep.
Methods: Acellular porcine carotid arteries were implanted as interposition xenografts in seven sheep. An intravascular shunt was used for cerebral protection, and a flowmeter was utilized to assess graft performance.
Results: There were no intraoperative deaths or postoperative neurological complications observed. Acute graft thrombosis occurred in one sheep during surgery, but was successfully managed with thrombectomy to restore blood flow. Post-implantation flowmetry and Doppler ultrasound confirmed graft functionality.
Conclusions: Our study demonstrates the successful application of our surgical method for implanting decellularized vascular xenografts in the carotid artery of sheep. The implanted grafts maintained patency, normal blood flow, and favorable wound healing and neurological outcomes post-surgery.

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Qualitative phytochemical screening and in vitro antioxidant activities of aqueous extracts of Rhaphiolepis bibas (Lour.) Galasso & Banfi

Ibrahim Waweru Kariuki, Mathew Ngugi, John Maingi

Kenyatta University, Nairobi, Kenya

DOI: 10.2478/amma-2024-0022

Reactive oxygen species causes harm to cell membranes and biomolecules, wherefore chronic diseases develop. Antioxidants scavenge such free radicals combating oxidative stress. This research aimed to determine the antioxidant potential of the aqueous stem bark, root and leaf extracts of Rhaphiolepis bibas against standards. DPPH radical scavenging activity was high from th stem bark extract at 72.33% with root extract at 65.85% and leaf extract at 55.91%, while ascorbic acid scavenged 89.53% of DPPH radicals. The leaf extract had the highest H2O2 scavenging activity of 91.92% with stem bark at 91.17% and the root extracts at 89.12%. The aqueous root extract of R. bibas had a significantly higher FRAP capacity in comparison to the leaf extracts and the stem bark. The abilities to chelate iron by the leaf extract were statistically higher compared to the root and stem bark extracts. Stem bark extracts had the highest phenol content of about 149.44 followed by the root extract at 141.14 and the least amount of phenol was found in the aqueous leaf extract having 73.012 Gallic acid equivalent/g. The root extracts had the highest total flavonoid 377.66-milligram quercetin equivalent/gram dry weight followed by stem bark extract at 255.72 and the least amount was found in aqueous leaf extract having 164.52 mgQE/g of sample dry weight. The existence of secondary metabolites linked to antioxidant action was shown by the qualitative phytochemical screening.

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