Author Archives: administrare

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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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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Merkel cell carcinoma- particularities and morphological aspect of a unique and rare entity

Andreea Cătălina Tinca1,2, Bianca Andreea Lazar2, Ovidiu Simion Cotoi1,2

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

DOI: 10.2478/amma-2024-0008

Introduction: Merkel cell carcinoma is a very rare malignant neoplasm which presents high aggressivity, high recurrence rate and has metastatic potential. Our purpose is to present the histological and immunohistochemical particularities of Merkel Cell Carcinoma while reviewing potential differential diagnoses and challenges that we can encounter in daily practice.
Case presentation: We present the case of an 86-year-old female patient who presented with a nodular tumour located in the left forearm, raising suspicion of a soft tissue tumour. The histological appearance of this unique type of cancer is highlighted on the Haematoxylin-eosin stain as a solid tumour composed of nests and chords of monomorphic cells. The nuclei of these tumoral cells appear characteristically as enlarged with dispersed chromatin. The immunohistochemical reactions have been performed and it was observed that the tumoral cells exhibited positivity for synaptophysin, CD56, NSE, EMA, as well as a “dot-like” expression for CK20. These histopathological and immunohistochemical features were consistent with a diagnosis of MCC, stage pT3, based on the assessment of tumour size.
Conclusions: Sometimes, differentiating this tumour from other primary malignant neoplasms of the skin or even cutaneous metastases can be difficult. Immunohistochemistry remains the most important tool of diagnosis, especially for differentiating this neoplasm from metastatic neuroendocrine tumours that can affect the skin.

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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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Co-infection with Mycobacterium tuberculosis and Mycobacterium avium in an HIV-positive patient – Case Report

Aura-Alisia Roman1, Ioana Tripon1, Bianca Tudor2

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 Targu Mures, Romania

DOI: 10.2478/amma-2024-0006

Introduction: The association between Mycobacterium tuberculosis and the Human Immunodeficiency Virus can accelerate the deterioration of immunological functions. The risks are even more accentuated in the situation of a Non-tuberculous Mycobacterium and Mycobacterium tuberculosis co-infection.
Case presentation: We present the case of a 59-year-old male patient, who was admitted at the hospital with non-specific symptoms. Further investigations reveal a remarkable particularity about the case: The infection with Mycobacterium tuberculosis was urogenital, whereas the one with Non-tuberculous mycobacteria was pulmonary.
Conclusion: Both Mycobacterium tuberculosis and Non-tuberculous strains can exist within the same infection, posing great difficulties for diagnosis, as well as the treatment scheme.

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