Category Archives: Current

Design, development and optimization of gastro-retentive floating in-situ gels loaded with carvedilol microspheres using response surface methodology

Latha Kukati1, Aisha Rahman1, Aymen Fatima1, Vyshak R Menon1, Lakshmi SVVNSM2

1. G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad, Telangana, India
2. Department of pharmacognosy, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Medak, Telangana, India

DOI: 10.2478/amma-2025-0011

Aim: The goal of this study was to formulate and optimize gastro-retentive floating in-situ gel comprising optimized microspheres by Box-Behnken design.
Methods: Gellan gum, k-carrageenan were used as gelling polymers and calcium carbonate as complexing and gas generating agent. For optimization X1 (concentration of k-carrageenan), X2 (concentration of calcium carbonate) and X3 (concentration of tri sodium citrate) were considered as factors and Y1 (viscosity), Y2 (floating lag time), Y3 (drug release at 8 hrs) as responses. 17 formulations obtained from the design were prepared and evaluated for various parameters.
Results and discussion: The optimized floating in-situ gel formulation obtained from the design was milky white liquid with viscosity of 355.13 cP, showed buoyancy lag time of 104 seconds and remained buoyant for >24 hrs. 27.49 % drug was released from the in-situ gel at 8 hrs indicating controlled drug release. From the stability studies which were conducted for 4 weeks, it was determined that the optimized floating in-situ gel formulation was stable.
Conclusion: This study highlights the potential utilization of microspheres in the gastro-retentive floating in-situ gel.

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The influence of multiple-dose oxcarbazepine on the metabolism of single-dose quetiapine. In vivo experiment in rats

Iulia-Maria Ciocotișan1, Dana Maria Muntean1, Luciana-Mădălina Gherman2, Laurian Vlase1

1. Department of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2. Experimental Centre, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.2478/amma-2025-0010

Objective: Psychiatric and neurologic disorders are susceptible to polypharmacy having a higher risk of developing drug-drug interactions. Quetiapine, a frequently used atypical antipsychotic, is extensively metabolized by cytochrome P450 3A4 isoenzyme, while oxcarbazepine, an antiepileptic drug, analog of carbamazepine, is a mild-to-moderate inducer of the same isoenzyme. This study aimed to evaluate the pharmacokinetic interaction between a single dose of quetiapine and multiple doses of oxcarbazepine, as pretreatment, compared to quetiapine single-dose alone in rats.
Methods: The in vivo experiment was carried out on two groups consisting of 12 Wistar albino rats each. The control group was given a single oral dose of quetiapine 85 mg/kg. The test group received oxcarbazepine 80 mg/kg/day orally, for 5 days followed by a single dose of quetiapine 85 mg/kg. A validated liquid chromatography with tandem mass spectrometry method was employed to simultaneously measure the plasma concentrations of quetiapine and its active metabolite, norquetiapine. Non-compartmental analysis was used to determine the pharmacokinetic parameters of both quetiapine and norquetiapine.
Results: Short-term administration of oxcarbazepine determined a significant increase in the systemic exposure of norquetiapine by increasing its peak plasma concentration and the total area under the concentration-time curve by 88.85% and 5.29-fold. The expected enzyme-inducing properties of oxcarbazepine were not visible on the quetiapine’s pharmacokinetic profile, producing, although statistically insignificant, an increase in its exposure.
Conclusions: The present experiment showed that the administration of oxcarbazepine can determine some changes in the pharmacokinetics of quetiapine and norquetiapine in vivo.

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Evaluating the role of vitamin D metabolites and intact parathyroid hormone across chronic kidney disease stages

Rafal Haider Hussain1, Nazar S. Haddad1, Ali Jasim Alsultani2

1. Department of Biochemistry, College of Medicine, Basrah University, Basrah, Iraq
2. Department of Internal Medicine, College of Medicine, University of Babylon, Babylon, Iraq

DOI: 10.2478/amma-2025-0009

Background: Chronic kidney disease (CKD) is defined as abnormal kidney structure or function that last over three months.  Its prevalence increases with age, affecting 38% of individuals aged 65 years and older. Key biomarkers for assessing CKD severity include a low estimated glomerular filtration rate (eGFR) and increased albumin levels in urine, determined by the albumin-to-creatinine ratio (ACR). 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are impaired in CKD patients due to reduced renal function, leading to deficiencies in active vitamin D forms and contributing to secondary hyperparathyroidism (SHPT). This study evaluated the role of vitamin D metabolites and intact parathyroid hormone levels in different stages of CKD.
Subjects and Methods: This cross-sectional study was performed at the Al-Imam Al-Sadiq Hospital in Babil, Iraq. This study included 164 patients (84 males and 80 females) with CKD stages 2-5. Patients were divided into groups based on CKD stage: 20 patients with stage 2 and 36 patients with stages 3a, 3b, 4, and 5. Blood samples were collected for the serum analysis of urea, creatinine, 25 (OH) D, 1,25 (OH)2 D, and intact PTH levels. Urine samples were collected to assess microalbuminuria. ELISA was used for vitamin D and PTH measurements, while standard biochemical methods were employed for the other parameters.
Results: 1,25 (OH)2 D and 25 (OH) D levels   significantly declined with advancing CKD stage (p ≤ 0.001), while iPTH levels increased significantly (p ≤ 0.001). The 1,25VitD/iPTH ratio decreased significantly across the CKD stages (p ≤ 0.001).
Conclusion: The study concluded an important association between deteriorating CKD (renal destruction), declining vitamin D metabolites (25 OH D, 1,25 OH D), and elevated iPTH levels.

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Endovascular intervention in hemorrhage from oropharyngeal tumors: Case presentation of embolization of the lingual artery with coils

Despina Maria Hedes1, Monica Manisor1,2, Marius Rosian1,2, Petru Coltea1,2

1. Faculty of Medicine, Lucian Blaga University of Sibiu, Romania
2. Radiology and Medical Imaging Compart-ment, County Clinical Emergency Hospital of Sibiu, Romania

DOI: 10.2478/amma-2025-0008

Oropharyngeal tumors represent a multidisciplinary challenge in terms of localization, potential local invasion, and associated symptoms. When patients present with active bleeding from the tumor, endovascular intervention may be essential to control the bleeding and stabilize the patient. Lingual neoplasm is a complex entity associated with significant morbidity, especially when it progresses with ulceration. In cases where the oropharyngeal tumor presents with active hemorrhage, endovascular embolization is an important therapeutic option for immediate hemorrhage control, thus contributing to hemodynamic stabilization and allowing the initiation of oncological treatment strategies.
This case report presents a 60-year-old chronic smoker with a known lingual neoplasm who presented to the emergency department with active oropharyngeal hemorrhage. On examination, the patient showed signs of significant bleeding from the base of the tongue and had an ECOG-PS of 3 (Eastern Cooperative Oncology Group Performance Status). Immediate intervention was necessary to control the bleeding and prevent further complications. After initial stabilization, the patient underwent angiographic evaluation, which identified active bleeding from the right lingual artery. Following the failure of conventional hemostatic methods, selective embolization of the lingual artery with permanent coil embolization material was decided. Post-procedural monitoring confirmed the absence of bleeding.
This case highlights the importance of prompt and precise multidisciplinary management of complex cases, which has a significant impact on patient outcomes. Initial management focused on hemorrhage control, which could impede the use of conventional oncological therapy known for its potential to negatively affect the healing process and tissue integrity. As an alternative to invasive surgical treatments and as a preliminary step in transitioning to oncological therapy, this paper recommends embolization as a valuable therapeutic option in similar circumstances. By effectively controlling hemorrhage, this procedure allows oncologists to proceed with cancer treatment strategies, minimizing delays and reducing the risk of further complications. Given the high incidence of smoking, increasing awareness and the use of these advanced interventional techniques are crucial for improving outcomes and reducing associated complications.

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The impact of microRNA-596 on oral cancer: Insights into tumor biology and treatment strategies

Shereen Farhana P1, Ameya K P2, Ashikha Shirin Usman P P2, Durairaj Sekar2

1. Department of Prosthodontics, Saveetha Dental 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-2025-0007

Objectives: Despite advancements in treatment, oral squamous cell carcinoma (OSCC) remains a major global health issue with stagnant survival rates. MicroRNAs (miRNAs), particularly miR-596, play critical roles in cancer, acting as both oncogenes and tumor suppressors. This study aims to clarify miR-596’s function in OSCC and assess its potential as a therapeutic target or diagnostic biomarker.
Methods: A thorough bioinformatics analysis utilising information from The Cancer Genome Atlas (TCGA) led to the selection of miR-596 for investigation. After extracting its sequence from miRBase, RNAfold was used to evaluate the secondary structure’s functional characteristics. MiRNA expression levels were measured by quantitative reverse transcription PCR (qRT-PCR) on a total of 30 tissue samples, including OSCC and healthy controls. With TargetScan, the miR-596 gene targets were predicted.
Results: miR-596 is significantly downregulated in OSCC tissues compared to healthy controls. TargetScan analysis indicates that miR-596 regulates key genes involved in cell proliferation, metastasis, and apoptosis, suggesting its crucial role in these pathways. Additionally, the predicted secondary structure of miR-596 indicates high stability.
Conclusion: Based on its activity as a tumor suppressor, the study suggests that miR-596 may be an important factor in the development of OSCC. Its potential use as a therapeutic target or diagnostic biomarker is highlighted by the downregulation of miR-596 in OSCC. Validating these results and investigating the therapeutic applications of miR-596 in OSCC treatment require more investigation.

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Effectiveness of calcium carbonate from
non-cultivated pearl oyster shells (Pinctada Maxima) in socket preservation

Ainun Isnaeni Ilham, Arni Irawaty Djais, Asdar Gani, Sri Oktawati, Dian Setiawati, Surijana Mappangara

Department of Periodontology, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia

DOI: 10.2478/amma-2025-0006

Introduction: One of the marine biota that can be used as an alternative for bone regeneration is the non-cultivated pearl oyster shell (Pinctada maxima). Calcium carbonate found in the Nacre layer has biocompatible, biodegradable, and osteogenic properties, thereby encouraging bone formation.
Objective: to investigate the impact of calcium carbonate derived from Pinctada maxima non-cultivated (PMNC) on socket preservation, focusing on RANKL expression.
Method: Using experimental laboratory research tests and clinical trials with a post-test only control group design. Mandibular right anterior tooth extraction was performed on 27 Cavia Cobaya then divided into three groups, namely the treatment group given calcium carbonate powder of non-cultivated Pinctada maxima (PMNC-P), positive control given BATAN xenograft (PC), and negative control not given bone graft (NC). The experimental animals were sacrificed on days 7, 14, and 21 then immunohistochemical examination was performed with the examination indicator being RANKL. The results of the statistical test used the ANOVA test and the Tukey Posthoc test.
Results: RANKL expression decreased significantly in the group PMNC-P and group PC on days 7, 14, and 21 and conversely slightly increased in the negative control group. However, there was no significant difference between the group PMNC-P and group PC.
Conclusion: Calcium carbonate from non-cultivated pearl oyster shells (Pinctada maxima) can reduce RANKL expression in bone regeneration.

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Transcatheter balloon valvuloplasty for children with severe pulmonary valve stenosis: A single-center experience

Munaf Jarallah Yaseen1, Sura Abd Alwahab1, Nabeeha Najatee Akram2, Wassan Nori3

1. Department of Pediatrics, College of Medicine, Baghdad University, Baghdad, Iraq
2. Department of Pediatrics, College of medicine, Mustansiriyah university, Baghdad, Iraq
3. Department of Obstetrics and Gynecology, College of medicine, Mustansiriyah university, Baghdad, Iraq

DOI: 10.2478/amma-2025-0005

Objectives: this study aim to assess the effectiveness of the Transcatheter balloon valvoplasty (BVP) of severe Pulmonary stenosis (PS) and identify possible complications and predictors for the outcome.
Methods: A retrospective study was conducted at the Iraqi Center of Cardiac Diseases for a 2-year duration in the period from 2021 to the end of 2023; the patients with confirmed severe PS of both genders within the age equal to or less than 18 years were included. For every patient included in the present study, the following data were collected: Demographic data, Echocardiographic criteria Hemodynamic parameters pre- and post-Cath, Catheterization data including the site of vascular access, need for general anesthesia and tracheal intubation, number and size of balloons used, any complications recorded at therapeutic session obtained from Cath lab archive.
Results: After BVP, the pressure gradient across the valve reduced from 105±25 to 32 ± 11(mmHg), (P<0.001); the systemic right ventricular pressure dropped from 120 ± 25 (mmHg) before to 54 ± 14 (mmHg) after (P<0.001). A significant increase in the systemic pulmonary pressure from 18 ± 4 (mmHg) before to 22 ± 3(mmHg) (P<0.001). Tricuspid valve regurgitation (TVR) reduced significantly (P=0.002). Pulmonary incompetence (PI) changed from mild to moderate and severe in 12 cases (P=0.001). Nine cases (20%) developed complications; 6 (13.3%) supraventricular tachycardia and 3 (6.7%) Cardiac arrest and cardiopulmonary resuscitation. The strongest association to complication occurrence was pulmonary valve annulus size with r= 0.417 and TVR and PI severity with P=0.001, 0.017, respectively.
Conclusion: Transcatheter BVP is an effective procedure for severe PS cases but carry a risk of cardiac complications. The complication rate was linked to the patients’ demographical characteristics and PV annulus size and degree of TVR and PI severity.

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The role of ferritin and carboxyhemoglobin as inflammatory biomarkers in sepsis and septic shock

Bianca-Liana Grigorescu1, Oana Coman2, Adina Huțanu3,4, Raluca-Ștefania Fodor1

1. Department of Anaesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of Simulation Applied in Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4. Centre for Advanced Medical and Pharmaceutical Research, Immunology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2025-0004

ions as a potential indicator of disease progression in sepsis remains unclear.
Objective: This study evaluates carboxyhemoglobin as a biomarker in sepsis and septic shock, comparing it with ferritin, C-reactive protein, and procalcitonin while assessing its potential as a bedside indicator for disease severity and mortality.
Material and Methods: We conducted a pilot, prospective, and observational study involving 52 patients diagnosed with sepsis or septic shock based on the SEPSIS 3 Consensus criteria. Clinical and laboratory parameters were monitored on days 1 and 5 following inclusion in the study.
Results: We observed a statistically significant variation in C-reactive protein and the severity scores for the sepsis and septic shock groups, and in carboxyhemoglobin, procalcitonin and one severity score for the survivor and non-survivor groups. In the survivor group we observed a statistically significant correlation between ferritin and the C-reactive protein, while for non-survivors, ferritin correlated with the APACHE II severity score. For all the studied groups we observed a statistically significant correlation between both studied severity scores.
Conclusions: Carboxyhemoglobin shows potential as a biomarker for monitoring sepsis progression, with its trends offering more clinical value than absolute cutoff values. Ferritin remains a dependable marker of inflammation and, when analyzed alongside carboxyhemoglobin and other known inflammatory biomarkers, provides a comprehensive view of sepsis progression, aiding in effective management.

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The link between the fatal cases with SARS-CoV-2 infection and multimorbidity: Our single institution experience

Laura Chinezu1,2, George Radu3, Paula-Roxana Adi2, Rareș Chinezu4, Timur Hogea2,5

1. Department of Histology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania
2. Institute of Forensic Medicine, Targu Mures, Romania
3. Pathology Department, Mures Clinical County Hospital, Targu Mures, Romania
4. Department of Neurosurgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania
5. Department of Forensic Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania

DOI: 10.2478/amma-2025-0003

Objective: During the pandemic, the SARS-CoV-2 infection with its different variants had determined high morbidity and mortality. As the clinical autopsies were reduced in our country, complete forensic autopsies had provided important valuable information regarding the pathological changes and pathophysiological mechanisms associated with SARS-CoV-2 infection. Our aim was to focus on different variants of SARS-CoV-2, trying to determine the contribution of SARS-CoV-2 infection to the lethal outcome and to establish the cause of death.
Methods: Complete autopsies were performed on cases confirmed by polymerase chain reaction for SARS-CoV-2 infection. All autopsies findings and the patient’s comorbidities were analyzed.
Results: Forty-nine cases were studied. Twenty were female (41%), and 29 were male (59%). The median age at death was 63 years (range 26-93 years), with an upward trend during the four variants of SARS-CoV-2. The age of the cases that died due to their comorbidities and were associated with SARS-Cov-2 infection was higher compared to the age of the cases that died due to SARS-CoV-2 infection. Two thirds of cases died at hospital, most of them with less than one week of hospitalization and one third of them were found dead at home. Most cases without significant health conditions died at home.
Conclusions: The immediate cause of death for many of our cases was of respiratory origin and most of them died of diffuse alveolar damage. The cases without evident comorbidities were less represented, that highlight the importance of multimorbidity in the development of critical illness.

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