Category Archives: Number

In vitro modulation of seizure-like activity with beta-cyclodextrin-complexed rufinamide

Rita-Judit Kiss1, Zsolt András Nagy2, Ádám Szentes2, Ágnes Csüdör2, Andrea Máthé2, Henrietta Makó2, Előd Bomher2, Ádám József Berki3, Zsolt Gáll4, 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. Department of Neurology, Semmelweis University, Budapest, Hungary
4. Pharmacology and Clinical Pharmacy Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0020

Objective: The global health concern of pharmacoresistant epilepsy necessitates innovative therapeutic strategies. Drug resistance often arises due to complex pharmacokinetic challenges. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers a potential solution for improving the efficacy of antiseizure medications. This study aims to investigate the impact of beta-cyclodextrin-complexed rufinamide on seizure-like activity using an in vitro model of temporal lobe epilepsy.
Methods: Seizure-like neuronal activity was induced using a low-magnesium model. Local field potentials were recorded from transverse rat hippocampal slices. Rufinamide was solubilized using beta-cyclodextrin and administered at 100 micromolar concentration. The impact on various seizure-like parameters and time-resolved phase-amplitude coupling was assessed.
Results: Rufinamide increased the duration of the preictal phase while reducing the duration of ictal and postictal phases. The frequency of seizure-like events was higher in rufinamide. No significant change was observed in the firing rate of the first 10 ictal spikes, but the firing frequency of the second set of 10 ictal spikes was higher during rufinamide perfusion. Time-resolved phase-amplitude coupling maximum analysis did not reveal significant differences between the control and rufinamide treatment.
Conclusions: Beta-cyclodextrin-solubilized rufinamide significantly modulates seizure-like event dynamics, exhibiting both anticonvulsant and proconvulsant effects. While the compound shortened seizure-like activity, it increased the frequency of seizure-like events. Our observations suggest a need for further investigation into the solubilization method and its impact on rufinamide’s bioavailability. Dose-dependent effects and underlying molecular mechanisms should also be explored to enhance the pharmacological properties of antiseizure medications.

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Purple sweet potato (Ipomoea batatas L.) reduces the wound temperature and erythema in STZ-induced diabetic rats

Ratih Paramita Suprapto1, Heri Kristianto2

1. Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Jl Veteran, East Java, Indonesia
2. School of Nursing, Faculty of Health Science, Universitas Brawijaya, Puncak Dieng Eksklusif, East Java, Indonesia.

DOI: 10.2478/amma-2024-0018

Objective: Wound temperature is one of the wound biomarkers representing the wound healing progress. The diabetic wound is associated with a prolonged inflammation phase marked by an increasing wound temperature and erythematous wound. Purple sweet potato extract (PSP), an anthocyanin-rich plant, improved wound healing in both diabetic and non-diabetic wounds in animal studies. This study aims to know the effect of purple sweet potato ethanol extract on wound temperature and erythema in streptozotocin-induced diabetic rats.
Methods: Rats were divided into four groups: normal rats + gel placebo; diabetic rats + gel placebo; diabetic rats + PSP 10%; and diabetic rats + PSP 15%. Diabetes mellitus was induced by streptozotocin injection. After diabetic confirmation, the back of the rats was excised and the gel was administered daily for 14 days. The wound temperature was measured at the wound surface using infrared thermography on days 0, 3, 7, and 14. The wounds were photographed and erythema analysis was conducted using Corel Photo paint®.
Results: Diabetic wounds exhibited higher surface temperature compared with the normal wound (37.08°C ± 0.29 vs 35.13°C ± 0.46) on day 14 of examination and topical application the purple sweet potato ethanol extract gel 10% and 15% markedly decreased the wound temperature at day 7 and 14 compared with the diabetes wound (p<0.0001). Wound erythema was significantly reduced in the PSP 10% and 15% diabetic wound treatment groups on day 14 (p<0.05).
Conclusion: Purple sweet potato extract gel treatment was found to have the potential to reduce inflammation in diabetic wounds.

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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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The gut-skin axis: Investigating gut microbiota
dysbiosis in pemphigus and bullous pemphigoid

Nicoleta Arnaut1, Cristina Nicoleta Ciurea2,3, Anca Cighir2,3

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

DOI: 10.2478/amma-2024-0017

Gut microbiota dysbiosis has been linked with numerous autoimmune disorders and inflammatory skin pathologies. The present study is a narrative review aiming to examine dysregulations in the gut microbiota of patients with pemphigus and bullous pemphigoid, exploring how these alterations may contribute to diseases’ development and/or progression. Significant alterations in the composition of intestinal microbiota were identified in patients with pemphigus and bullous pemphigoid: reduction in short-chain fatty acid-producing bacteria: Faecalibacterium prausnitzii, Lachnospiraceae and Coprococcus spp., which are known for their anti-inflammatory effects, and increased abundance of Escherichia coli, Shigella spp., Klebsiella spp., Bacteroides fragilis and Flavonifractor spp., which are recognized for their pro-inflammatory impact. The composition of gut microbiota might influence the pathogenesis of autoimmune bullous diseases. Modified levels of bacteria could become innovative biomarkers for the detection of high-risk individuals, monitoring disease progression and predicting response to treatment. Furthermore, regulating bacterial levels might have therapeutic effects in diminishing inflammation and disease advancement, potentially serving as future therapeutic strategies.

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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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Cannabidiol, a promising therapy for post-traumatic stress disorder and depression. A mini-review

George Jîtcă

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

DOI: 10.2478/amma-2024-0012

Post-traumatic stress disorder (PTSD) is a mental health disorder, manifesting in people who have endured traumatic events like violence, war, natural disasters, accidents, or other life-threatening situations. Essentially, PTSD is a chronic and debilitating disorder, significantly impacting mental health and psychosocial well-being, necessitating the exploration of novel treatment approaches. Although conventional therapies like psychotherapy and antidepressants have demonstrated efficacy for certain individuals, their effectiveness is limited for some and minimal for others. Consequently, researchers and clinicians are investigating alternative therapeutic methods for these conditions. Among these emerging treatments, cannabidiol (CBD) has shown promising results. Nevertheless, early studies suggest that CBD might yield positive outcomes in mitigating symptoms related to both depression and PTSD.

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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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