Category Archives: Original Research

Assessing the control of the disease on current treatments available in Romania for hereditary angioedema patients

Noemi Anna Bara1,2, Iris Nadasan3, Valentin Nadasan4, Diana Deleanu1,5,6,7

1. Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș, Romania
2. Hereditary Angioedema Expertise Centre, Sângeorgiu de Mureș, România
3. General medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș, Romania
4. Hygiene Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș, Romania
5. Department of Allergology and Immunology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania
6. Department of Allergology, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
7. Department of Internal Medicine, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, România

DOI: 10.2478/amma-2024-0009

Background: Acute treatment must be permanently accessible for every patient diagnosed with hereditary angioedema (HAE). In many cases this type of therapy does not provide/offer sufficient control of the disease, so long-term prophylaxis (LTP) is recommended. In the case of regular and prolonged/extended administration of drugs, the route of administration is essential. The aim of the investigation was to assess the control of HAE among patients in Romania receiving the available medications, while also examining potential correlations within the outcomes.
Material and methods: A phone call was made to all adult patients registered in the Romanian HAE Registry. Patients with confirmed diagnosis of HAE who had at least one angioedema attack in the last three months were asked to complete, online, the angioedema control test (AECT) for one- and three months respectively. AECT scores were calculated according to the authors’ instructions.
Results: A total of 121 patients were contacted. Of these, 83 complies with the eligibility criteria and 56 completed the questionnaires (response rate 67.4%), 18 (32.1%) men and 38 (67.9%) women. Acute, home administered treatment with Icatibant or pdC1-INH was available for every patient during the study time. Nine (14.5%) participants used LTP too, with pdC1-INH. These treatments ensured an adequate control of the disease in only 13 patients (21%) in case of the three-month AECT, of whom 2 used LTP. The one-month questionnaire showed a well-controlled disease in 14 patients (23%), from which only 1 was on prophylactic therapy.
Conclusion: In most Romanian HAE patients, the available drugs do not offer a proper control of the disease. Even though a first-line drug for LTP is available, its administration route by intravenous injections makes it inconvenient for many patients, highlighting the necessity for new, easy-to administer drugs for HAE patients from our country.

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Effect of carbamazepine-beta-cyclodextrin inclusion complex on seizure-like events in an in vitro model of temporal lobe epilepsy

Rita-Judit Kiss1, Ágnes Csüdör2, Máté Sárosi2, Zsolt András Nagy2, Ádám Szentes2, Zsolt Gáll3, Tibor Szilágyi1, Károly Orbán-Kis1

1. Physiology Department, 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. Pharmacology and Clinical Pharmacy Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0007

Objective: Pharmacoresistant epilepsy represents a significant global health challenge, necessitating novel therapeutic approaches. Despite advances in antiseizure medications, many patients remain treatment-resistant partially due to complex pharmacokinetic issues. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers potential solutions by forming inclusion complexes, thereby improving anti-seizure medication’s efficacy. This study aimed to investigate the effect of beta-cyclodextrin and beta-cyclodextrin-complexed carbamazepine on epileptiform activities, using an in vitro model of temporal lobe epilepsy.
Methods: Seizure-like neuronal activity was induced using the low-magnesium model. Local field potentials were recorded from transverse rat hippocampal slices immersed in epileptogenic artificial cerebrospinal fluid, followed by the administration of either beta-cyclodextrin or carbamazepine, the latter in 100 micromolar concentration.
Results: Beta cyclodextrin, applied alone, significantly reduced the duration of interictal and ictal phases while increasing the frequency of seizure-like events. Carbamazepine exhibited an important anticonvulsant effect, significantly reducing ictal and postictal phase durations. However, the frequency of seizure-like events was increased. Notably, in some of the slices, carbamazepine completely suppressed epileptiform activity.
Conclusions: Beta cyclodextrin had an effect on its own; it shortened seizure durations and increased their frequency. Carbamazepine in complexed form, as used in our study, exhibited anticonvulsant efficacy, emphasizing the feasibility of solubility enhancement by this method. This study provides insights into potential therapeutic strategies for pharmacoresistant temporal lobe epilepsy, improving the pharmacological properties of the drugs. As cyclodextrins emerge as promising excipients for antiepileptic drugs with poor solubility, more effort is needed in order to elucidate the underlying mechanisms of their effects.

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Anti-obesity and Antioxidant Effects of Ethanol Extract of Fingerroot Rhizomes (Boesenbergia pandurata Roxb.) on High-Carbohydrate Diet-induced Mice

Ari Yuniarto1, Abdul Aziz Setiawan2, Wulan Safitri1, Emir Rizky Taptajani2

1. Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Muhammadiyah A.R. Fachruddin University, Tangerang, Indonesia
2. Department of Pharmaceutical Technology and Natural Products, Faculty of Pharmacy, Muhammadiyah A.R. Fachruddin University, Tangerang, Indonesia

DOI: 10.2478/amma-2024-0005

Objective: Obesity is defined as the abnormal and excessive accumulation of fat. Enlargement of white adipose tissue due to obesity activates the sympathetic nervous system to stimulate lipolysis to break down fat extensively. This causes a lot of free fatty acids to circulate in the body. Excessive circulating free fatty acids affect many cells and produce oxidative stress, which spreads throughout the body. This research purpose is to determine the anti-obesity and antioxidant activities of ethanol extract of B. pandurata rhizome (EEBP).
Methods: Fingerroot rhizomes were extracted using maceration and the extract was used for in vivo, antioxidant, and total flavonoid concentration tests. Anti-obesity test was carried out by dividing mice into 6 groups such as normal controls, obese controls, standard groups, and extract-treated groups (100, 200, 400 mg/kg b.w). The in vivo test parameters observed included measurement of body weight and also liver, kidney, spleen, and retroperitoneal fat index measurement. Furthermore, in this research antioxidant test was performed using the DPPH method.
Results: In vivo test showed that the giving of EEBP at a dose of 400 mg/kg b.w. effectively decreased body weight and retroperitoneal fat, but slightly affected the organ index of mice such as the liver, renal, and spleen. Furthermore, the antioxidant test showed that the IC50 EEBP results obtained were 37,05 µg/ml. In addition, the total flavonoid content found in the EEBP is 15,775 mgQE/g.
Conclusion: The present study showed that EEBP may have a considerable potential anti-obesity agent and also has a very strong antioxidant effect.

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Biological profiles of Q. cerris, Q. dalechampii, and Q. robur bark extracts: A characterization study

Adrian Nisca1, Sanziana Sisea2, Nastaca Alina Coman1, Mihai Babota3, Oleg Frumuzachi3, Corneliu Tanase2,4

1. Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of Pharmaceutical Botany, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
4. Research Center of Medicinal and Aromatic Plants, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania.

DOI: 10.2478/amma-2024-0003

Objective: The main objective of the present study was to characterize the extracts obtained from the bark of three oak species in order to assess their use in potential cosmetic products.
Methods: The extracts were obtained from the oak barks (periderm and rhytidome) using ultrasound-assisted extraction. The total polyphenolic content was assessed afterward, using the Folin–Ciocâlteu method, while the antioxidant capacity was determined using methods based on the neutralization of the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radicals. To assess the tyrosinase inhibitory effect, a protocol using L–DOPA as the substrate of the enzyme was employed.
Results: The extracts presented high levels of polyphenolic compounds, with Q. cerris having the highest content. Because of the high concentration of the extracts in polyphenolic compounds, they revealed a great reducing capacity against both DPPH and ABTS radicals, but unfortunately the tyrosinase inhibitory activity of the tested extracts was very weak compared to the positive control.
Conclusions: The extracts may have beneficial effects when used in cosmetic products because of the antioxidant effects, but more studies must be conducted for the determination of the main phytochemical compounds comprised in the extracts and their correlation to the biological effects.

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Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in Mureș County, Romania: Incidence and impact of reclassification over a six-year period (2016-2021)

Adela Nechifor-Boilă, Ancuța Cota, Emoke-Andrea Szasz, Ramona Cătană, Angela Borda

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

DOI: 10.2478/amma-2023-0048

Objective: In 2016 a group of expert endocrine pathologists proposed a new terminology, NIFTP (Non-invasive follicular thyroid neoplasm with papillary-like nuclear features) for a histological subtype of thyroid carcinoma (encapsulated follicular variant of papillary thyroid carcinoma, non-invasive type). In this study, we aimed to assess on a retrospective basis the epidemiological trend and overall incidence of NIFTP in Mureș county, Romania, over a six-year period (2016-2021).
Methods: All NIFTPs registered between 2016-2021 in Târgu-Mureş Pathology Departments were reevaluated. NIFTP’s incidence was calculated by dividing the number of NIFTPs with the number of papillary thyroid carcinomas (PTCs). Further on, we compared NIFTP’s incidence between 2016-2018 with NIFTP’s incidence between 2019-2021, as the diagnostic criteria of NIFTP were revised in 2018.
Results: Forty-six cases of NIFTP were registered in our departments between 2016-2021, resulting in an overall NIFTP incidence of 17.9 % [CI (95%): 7.6-32.5] among the 257 PTCs. When we compared the NIFTP’ incidence between the two study periods (2016-2018 versus 2019-2021), our data revealed that the NIFTP’s overall incidence has dropped from 21.4 % [CI (95%): -14.5-60.1] to 15% [CI (95%): -8.2-43] in the second evaluated period (p=0.034).
Conclusion: The overall NIFTP incidence was low in our departments between 2016-2021. Moreover, NIFTP’s incidence decreased after 2018, following revision of the diagnostic criteria. Our results highlight that very stringent morphologic criteria need to be apply when making a diagnosis of NIFTP, in order to avoid a misdiagnosis and/or an overtreatment of a tumor with indolent behavior.

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Determination of isohydrafural and methyluracil in ear drops by high performance liquid chromatography

Livia Uncu

Department of Pharmaceutical and Toxicological Chemistry; Scientific Center of Medicines “Nicolae Testemițanu” State University of Medicine and Pharmacy of the Republic of Moldova

DOI: 10.2478/amma-2023-0049

Objective: The aim of current study was the development and validation of a reversed-phase high-pressure liquid chromatography (RP-HPLC) method for the quantitative determination of two active ingredients, isohydrafural (IHF) and methyluracil (MU) in fixed dose combination ear drops.
Methods: An efficient separation of the two compounds was achieved on a Teknokroma C1 5μm (150*4,6mm) column, with a methanol: water 60:40 (V: V) mobile phase, at 300C temperature and 0.6 mL/min flow-rate. The total analysis time was 5.5 min.
Result: The verified validation parameters were: linearity, selectivity, specificity, precision (repeatability and reproducibility), robustness, limit of detection and quantification.
Conclusions: Good separation and lack of interference from other chromatographic peaks, rapidanalysis times were obtained. The newly developed chromatographic method can be applied for the analysis of fixed dose combination ear drops with isohydrafural and methyluracil.

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Packed cell volume and its relation to obesity, gender and smoking status

Bushra Khairuddin Abdulqader

Department of Medical Physiology, College of Medicine, University of Mosul, Mosul, Iraq

DOI: 10.2478/amma-2023-0047

Objective: Our aim was to evaluate the packed cell volume (PCV) correlation with body mass index, body fat percentage, also differences between genders and smokers & non-smokers, among Iraqi students.
Methods: A cross-sectional study was done on 112 healthy individuals (from which 52.7% were males), aged between 18-23 years old, in December 2022. A short informative history was taken through a questionnaire, anthropometric measures were taken to calculate body mass index and body fat percentage, and the determination of packed cell volume was done by the Microhematocrit method.
Results: Packed cell volume among males was higher 47.45±3.409% than for females 39.90±3.169%, with a difference statistically significant (p=0.000), also the correlation of PCV revealed direct significance with body mass index (p=0.011) and indirect statistically significant with body fat percentage (p=0.000). The prevalence rate of smoking was 13.4% and the level of PCV among smokers was 46.80±6.085%, significantly higher (p=0.015) than among non-smokers 43.43±4.702%.
Conclusion: Packed cell volume showed a direct correlation with body mass index, an inverse one with the body fat percentage, and was significantly higher among young smokers, emphasising the idea that this parameter can help to evaluate the health risk and to be included in preventive programs and assessment protocols.

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The outcome in critically ill patients admitted for thoracic trauma – A single center analysis over one year

Oana Elena Branea1, Konrád Ottó Kiss2, Mihai Pui2, Vlad Dimitrie Cehan2, Oana Frandes2, Anca Gabriela Vlad2, Ioan Alexandru Branea3, Andrei Cristian Fulop4, Monica Chis5, Alexandra Elena Lazar1

1. Department of Anesthesia and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Clinic of Anesthesia and Intensive Care, Emergency Clinical County Hospital of Targu Mures, Romania
3. Emergency Medicine Department, Emergency Clinical County Hospital of Targu Mures, Romania
4. Clinic of Radiology, Emergency Clinical County Hospital of Targu Mures, Romania
5. Rheumatology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2023-0046

Objective: The main objective of the current study was to examine the outcome of critically ill patients in relation to clinical and thoracic injuries. The secondary objectives were to assess the role of CT in the evaluation of the diaphragm and to provide an analysis of prognostic abilities with respect to diaphragm changes.
Methods: This single-center retrospective observational cohort study was conducted in the ICU of Târgu Mureș County Emergency Clinical Hospital, Romania. This study identified 52 critically ill blunted or penetrating chest trauma patients admitted to the ICU from 01 January 2021 to 31 December 2021. CT scan was used to identify thorax injuries and diaphragm thickness. The outcome of all patients was analyzed.
Results: Most of the patients experienced traffic accidents (44.23%) or falls (26.93%). The predominant characteristics associated with chest trauma were rib fractures (92.30%), lung contusions (63.50%), and pneumothorax (53.80%). The most common injury seen in the study was rib fractures, accounting for 92.30% of cases. This was followed by lung contusions, which were present in 63.50% of patients, and pneumothorax, which occurred in 53.80% of cases. It was examined ROC AUC for thickness of the right and the left diaphragm and severity scores. When assessing the thickness of the diaphragm in deceased and survivors, no statistically significant differences were found.
Conclusion: Although no significant differences were found regarding the prognosis between the survivors and the deceased, diaphragm thickness might potentially serve as a predictor for the severity of the injury.

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Development of semisolid pharmaceutical forms with mometasone furoate

Emőke Margit Rédai1, Boglárka Jakab1, Robert Alexandru Vlad1, Paula Antonoaea1, Nicoleta Todoran1, Emese Sipos2, Adriana Ciurba1

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

DOI: 10.2478/amma-2023-0045

Objective: This study aims to develop semisolid pharmaceutical forms for the topical administration of mometasone furoate.
Methods: Two creams (O1 and O2) and four hydroxypropyl methylcellulose-based hydrogels were prepared (H3-H6). Two different sorts of hydroxypropyl methylcellulose were used in concentrations of 15 and 20%. Consistency, spreadability, viscosity, and pH were measured. In vitro drug release was determined by a vertical, Franz diffusion cell. Mathematical models were applied for a better understanding of release phenomena.
Results: O1 and O2 presented lower values for penetration depth and spreadability. Hydrogel viscosity is influenced by the type and concentration of the gel-forming agent. Viscosity decreases in the order H6, H5, H4, and H3. pH varies between 4.6 to 5.92, fulfilling the requirements of European Pharmacopiea. Creams showed 5.49 and 6.59% of mometasone released after 6 hours. The lowest viscosity hydrogel presented the best dissolution of 40.11% mometasone after 6 hours.
Conclusions: H3 hydrogel releases the highest amount of mometasone furoate after 6 hours. The release is best described by the Korsmeyer-Peppas model explained by water diffusion and polymeric chain relaxation happen during the swelling of the polymer.

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Epidemiological and histological characteristics of cutaneous squamous cell carcinoma and its precursor lesions – A single-center study

Iuliu Gabriel Cocuz1,2, Maria-Cătălina Popelea2, Andrei Manea3, Raluca Niculescu1,2, Adrian-Horațiu Sabău1,2, Ovidiu Simion Cotoi1,2

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

DOI: 10.2478/amma-2023-0043

Objective: Cutaneous squamous cell carcinoma (cSCC) is a skin malignancy that is one of the non-melanocytic skin cancers (NMSCs). The objective of our study was to highlight the epidemiological and histological characteristics of cSCC diagnosed in a clinical county hospital.
Methods: A retrospective cross-sectional study was performed of histopathologically diagnosed cases of cSCC from the clinical Pathology Department of the Mures Clinical County Hospital, Târgu Mureș, Romania. We included 96 cases that were diagnosed between January 1, 2017, and December 31, 2020.
Results: Of the 96 cases included in the study, 82 were identified as cSCC, 5 as Bowen Disease, and 9 as keratoacanthoma. The majority of the cases were diagnosed in 2018 (n = 30; 31.25%) and 2019 (n=36; 37.50%). The median age of the patients was 63.0 years. Slightly over half of the patients were male (n=50; 52.08) and 49 patients (51.04%) grew up in urban areas. Forty-six cases (56.10%) were well differentiated; 25 (30.49%) moderately differentiated, and 11 (13.41%) poorly differentiated. Almost all of the lesions (93; 96.88%) were removed within the safety excision margins.
Conclusion: Most of the patients were diagnosed with cSCC in 2018 and 2019 and were over 70 years old. The majority were males who grew up in urban areas. Even though most of the lesions were well differentiated and completely excised surgically, the differential diagnoses between cSCC and other skin malignancies were made based on the morphological aspects of the lesions, followed by an immunohistochemical profile when necessary.

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