Category Archives: Original Research

The effects of pearl oyster shell-derived bone grafts on TNF-alfa levels: An in vivo study in Cavia porcellus

Sri Oktawati1, Nurlindah Hamrun2, Muthmainnah Muthmainnah1, Dian Setiawati1, Andi Sitti Hajrah Yusuf3

1. Department of Periodontology, Faculty of Dentistry Hasanuddin University, Makassar, Indonesia
2. Department of Oral Biology, Faculty of Dentistry Hasanuddin University, Makassar, Indonesia
3. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Hasanuddin University, Makassar, Indonesia

DOI: 10.2478/amma-2024-0015

Objective: This study aims to assess the effect of bone graft materials derived from pearl oyster shells on the tumor necrosis factor-alpha (TNF-α) level.
Methods: This research utilized a bone graft containing hydroxyapatite Pinctada maxima (HPM) powder obtained from pearl oyster shells. Material testing was conducted on 30 male guinea pigs aged 8-10 weeks, divided into three groups: the negative control group, the group treated solely with HPM, and the group treated with HPM combined with platelet-rich fibrin (PRF). Each treatment group was observed for 7 and 14 days. The results were analyzed using One-way ANOVA with a significance level of p<0.05.
Results: The findings demonstrated a decrease in the average TNF-α levels across all groups. On observation days 7 and 14, the HPM group exhibited a significant difference compared to the negative control group, indicating reduced TNF-α levels. However, no significant difference was observed when comparing the HPM group with the HPM and PRF groups.
Conclusions: Bone grafts derived from pearl oyster shells possess high levels of hydroxyapatite, and the addition of PRF into the bone graft effectively reduces TNF-α.

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Exploring the impact of high shear mixing process parameters on the physical characteristics of excipient powder blend by design of experiments

Béla Kovács1,2, Erzsébet Orsolya Tőkés2,3, Éva Katalin Kelemen2, Katalin Zöldi2, Edit Suba2, Boglárka Kovács-Deák3, István Székely-Szentmiklósi2,3, Francisc Boda4, Tibor Casian5

1. Department F1, Biochemistry and Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Gedeon Richter Romania, Targu Mures, Romania
3. Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4. Department F1, General and Inorganic Chemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5. Department of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.2478/amma-2024-0016

Objective: Dry-route manufacturing technology development poses challenges to pharmaceutical technology research specialists, relying on active substance characteristics, excipient selection, and parameter optimization. Amongst various technological possibilities high shear mixing generally ensures dosage uniformity and tablet dissolution through influential shear forces, potentially enhancing dry powder blend processability. This study explores the processability of a placebo formulation within the quality by design framework to address some of the aforementioned challenges.
Methods: A 2^4 full-factorial experimental design was used to assess the manufacturability of a placebo formulation via high shear mixing. The effect of impeller and chopper speed, high shear mixing time, and homogenization/lubrication times on powder blend rheology and compression properties was investigated.
Results: The findings of the present study showed that product critical quality attributes like resistance to crushing or disintegration time are mainly dependent on the mixing efficiency translated by the impeller speed and high shear mixing time. Software augmented process development enabled the attainment of the design space, ensuring the fulfilment of desired product performance criteria. Furthermore, the study has also shown that the careful selection of excipients is crucial in the case of dry-route manufacturing technologies, as sodium lauryl sulphate can noticeably influence the processability of powder blends due to its lubricant properties.
Conclusions: Considering the advantages and challenges raised by high-shear mixing, software aided data analysis can further augment the formulation, scale-up and lifecycle management of products developed using this technological process.

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Beyond the gut – Atypical presentation of Salmonella spp. infection

Anca Cighir1,2, Corina Eugenia Budin2,3, Teodora Cighir2, Anca Delia Mare1,2, Adrian Man1,2

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

DOI: 10.2478/amma-2024-0014

Salmonella is a Gram-negative, non-spore-forming, motile, facultative anaerobic rod. The most studied species are Salmonella typhi and paratyphi (causing typhoid fever) and non-typhi Salmonella species (which can cause different clinical syndromes – gastroenteritis, disseminated infections, etc.). A 61-year-old male patient with multiple comorbidities (including myelofibrosis) presented to the Pulmonology outpatient department, Clinical County Hospital of Târgu Mureș, with a mucopurulent nocturnal cough. Paraclinical examinations showed the presence of a pleural empyema, which was evacuated in local anesthesia. The pleural fluid was sent to the Microbiology Department for bacteriological testing, where a fluoroquinolone-resistant strain of Salmonella spp. was detected. The patient received antibiotic treatment according to the antibiotic susceptibility testing. Due to the persistence of the symptoms, the patient returned two weeks later, when another puncture was performed. Salmonella was isolated again, but the strain showed a higher resistance to antibiotics. The two strains were compared using molecular methods of diagnosis (Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction – ERIC-PCR), the results showing a similarity of 92%. The occurrence of an extra amplicon band in ERIC-PCR suggests an important change in the bacterial genetic material, potentially related to acquisition of antibiotic resistance factors.

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Prognostic value of leukocyte-glycemic index in long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment

Adrian Vasile Mureșan1,2, Emil-Marian Arbănași1,2,3,4, Reka Bartus1,2, Lucian Mărginean5, Bogdan Andrei Cordoș4,6, Claudiu Constantin Ciucanu1,2,3, Eliza Russu1,2

1. Department of Vascular Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 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 (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5. Interventional Radiology Department, Mures County Emergency Hospital, Targu Mures, Romania
6. Centre for Experimental Medical and Imaging Studies, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0013

Objective: The aim of this article is to determine the predictive value of the leukocyte-glycemic index in the long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment.
Methods: This retrospective observational study enrolled 127 diabetic patients diagnosed with peripheral arterial disease requiring endovascular treatment. Patients were categorized into two groups based on the severity of the infrapopliteal atherosclerotic lesions identified during the pre-operative Computer Tomography Angiography examination. Group 1 includes patients without severe damage to the infrapopliteal artery, while Group 2 includes patients with severe infrapopliteal artery damage, identified by stenosis greater than 70% on all infrapopliteal arteries. The primary outcome was to assess the association between leukocyte-glycemic index value at baseline and the severity of infrapopliteal atherosclerotic lesions and long-term major amputation after percutaneous transluminal angioplasty.
Results: Patients in Group 2 had a higher incidence of cardiovascular events (p=0.009), stage IV Leriche-Fontaine (p=0.016), and incidence of major amputation (p<0.001), as well as an increased value of leukocyte-glycemic index (p=0.004). During the follow-up, patients with above-median leukocyte-glycemic index value have a higher risk of major amputation (p=0.034), as seen in the Kaplan-Meier analysis. Moreover, at cox-regression, elevated biomarker values were associated with long-term risk of major amputation, independent of age, sex, cardiovascular risk factors, and below-the-knee arterial occlusion (HR:2.69, p=0.001).
Conclusions: Elevated values of leukocyte-glycemic index are associated with the severity of infrapopliteal atherosclerotic lesions and major amputation in the long term.

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Ex vivo permeability study and in vitro solubility characterization of oral Canagliflozin self-nanomicellizing solid dispersion using Soluplus® as a nanocarrier

Nizar Awish Jassem1, Shaimaa Nazar Abd Alhammid2

1. Department of Pharmaceutics , College of Pharmacy, Al-Ayen Iraqi University, Thi-Qar, Iraq
2. Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq

DOI: 10.2478/amma-2024-0011

Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability.
Materials and Methods: Soluplus® was chosen as a nanocarrier to improve canagliflozin solubility after screening several polymers using a phase solubility study. The solvent evaporation method was selected for preparing the solid dispersion. The optimal formula was characterized through ex vivo permeability and in vitro studies.
Results: The CFZ-SNMSD formula, with a particle size PS of 60.77±1.00 nm and polydispersity index PDI of 0.06±0.02, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.40±4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.20% compared to DE30, pure drug = 18.28%). Studies show that canagliflozin’s permeability increases exponentially over time due to Soluplus® dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers.
Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of canagliflozin medication.

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Beneficial effects of Anemone palmata extracts on male rabbit fertility and reproduction

Asma Meziani1, Hinda Hafid1, Noua Allaoua1, Souad Boulahbel2, Yasmina Bentayeb1, Yasmina Moumen1, Amina Siouani2, Noureddine Gherraf1

1. Laboratory of Natural Resources and Management of Sensitive Environments, University of Oum El-Bouaghi, Algeria
2. Laboratory of Bimolecular and Plant Breeding, Department of Life Sciences and Nature, Faculty of Exact Sciences, Life Sciences and Nature, University, Oum El-Bouaghi, Algeria

DOI: 10.2478/amma-2024-0010

Objective: The current study is intended to offer an insight on positive benefits of the herb Anemone palmate belonging to Ranunculaceae family, as an enhancing agent of male rabbit’s fertility.
Methods: Twelve male rabbits, in the growth stage, were divided randomly into four equal groups: one serving as the control and three subjected to different treatments. Anemone palmata extracts (50, 100, and 200 mg/kg) were administered orally to the groups. Blood samples were collected to measure the serum levels of testosterone four weeks later. The weight of the testis and epididymis, sperm count, and sperm motility were determined histologically.
Results: The findings revealed a significant increase in the relative weights of the reproductive organs (testis and epididymis) and plasma testosterone levels in the groups that received the 100 and 200 mg/kg doses. Moreover a notable enhancement in the spermatozoa biology, including concentration, motility, and speed, was observed in the groups treated with 100 and 200 mg/kg doses compared to the control and the group treated with 50mg/kg. The histological study revealed some changes in the spermatogenesis and the structure of the organs, involving the presence of the spermatid phase. A significant increase in the thickness of seminiferous walls, a decrease in the interstitial space, and a reduction in the lumen and intra-tubular spaces were observed as well.
Conclusions: it is well indicated that Anemone palmata could improve fertility factors, and exhibit good effects on gonad and sperm parameters in rabbits.

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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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