Category Archives: Number

Risk Assessment of Failures in Generic Drug Development and Approval Procedure under Competitive Generic Drug Therapy and Patent Challenge Exclusivities Provided by the United States Food and Drug Administration

M Vivek Reddy1, GNK Ganesh1, B Babu2, Ramesh Jagadeesan3, Praharsh Kumar MR4

1. Department of Regulatory Affairs, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu-643001, India.
2. Department of Pharmaceutical Analysis, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu-643001, India.
3. Department of Analytical and Product development. Recipharm Pharmaservices, Bangalore, Karnataka-560002, India.
4. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu-643001, India.

DOI: 10.2478/amma-2022-0004

Objective: The United States Food and Drug Administration implemented two exclusivity programs Competitive generic therapy and Patent Challenge exclusivity to develop generic drugs, which provide a 180-day monopoly market for first generic applicants in the United States of America. The aim of the present study is to find the root cause of failures in developing and filing the first generic drugs under these exclusivities and to compare both the exclusivities to find the merits and demerits.
Methods: We used descriptive statistics for data analysis of both the exclusivities and Risk assessment was conducted on 14 industries to find the root cause of failures in every stage of the approval procedure by FMECA (Failure mode, Effects and Criticality Analysis).
Results: We found 44% of rejections in competitive generic therapy drugs and 30% of rejections in patent challenge exclusivity drugs. The risk analysis conducted on failures found that, in drug selection, 6% of failures are occurred due to rare diseases. In drug development, 9% of failures are occurred due to formulation failures. In pre-approval, 10% of failures are occurred due to secondary patents. In post-approval, 6% of failures are occurred due to product changes after approval.
Conclusion: We hope this study can give an idea for small and medium companies in developing countries for the early development of generic drugs for life-threatening diseases.

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Maturogenesis of an immature necrotic tooth with an extensive perirapical lesion using platelet rich fibrin

Bhaswati Chakraborty1, Ashwin Rao2

1. Department of Dentistry, Calcutta National Medical College and Hospital, West Bengal University of Health Sciences, Kolkata, West Bengal, India
2. Department of Paediatric and Preventive Dentistry, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India

DOI: 10.2478/amma-2022-0001

Introduction: Earlier, treatment of immature necrotic tooth focussed only on surgical endodontic management and apexification procedures. Regenerative endodontic therapies have called for a paradigm shift in management of such cases. Prognosis becomes challenging though at times due to chronicity of infection, inadequate disinfection of canal space and cytotoxic nature of irrigants used hindering the survival of the apical stem cells.
Case presentation: This report highlights the management of a long-standing case of an immature necrotic tooth with an extensive periapical lesion in a 12 year old male patient. The protocol of regenerative endodontic procedure using platelet rich fibrin (PRF) was followed. Follow up visits at 1week, 3months and 12 months revealed a successful clinical and radiological outcome leading to progressive maturogenesis of the tooth.
Conclusion: The case report favours the possibility of stem cells of apical papilla being viable even in chronic periapical lesions. Hence conservative approach involving regenerative endodontic therapies should always be sought for as first line of treatment in such cases.

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Ulnar-basilic arteriovenous fistula with multilocular gigantic aneurysmal dilatation: a case report

Emil-Marian Arbănași1, Eliza Russu1,2, Adrian Vasile Mureșan1,2, Eliza-Mihaela Arbănași3, Reka Kaller1

1. Clinic of Vascular Surgery, Emergency County Hospital, Târgu-Mureș, Romania
2. First Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2021-0035

Introduction: Arteriovenous fistula dysfunction has been associated with a range of problems such as thrombosis, stenosis, dilatation, and infection.
Case presentation: We present the case of a 64-year-old patient with chronic kidney disease on hemodialysis and with aneurysmal dilatation of the ulnar-basilic arteriovenous fistula, having an increased risk of rupture. A temporary dialysis catheter is placed in the left femoral vein, an aneurysmal basilic vein is ligated at the anastomosis, aneurysmal dilatation is emptied by compression, and a right radiocephalic arteriovenous fistula is performed. The patient undergoes hemodialysis on the second day and subsequently three times a week for six weeks until the new arteriovenous fistula develops. He returns for aneurysmal sac resection.
Conclusion: The purpose of this paper is the presentation and management of a 15-year-old ulnar-basilic arteriovenous fistula with multilocular aneurysmal development and an imminent rupture.

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Study of the anxiolytic effect of propranolol and dextromethorphan in mice using a model of psychogenic stress

Radion Garaz, Sorina Cucuiet, Gabriela Garaz-Pislariu, Raluca-Ioana Buliga

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

DOI: 10.2478/amma-2021-0034

Objective: To find the anxiolytic effects in a psychogenic stress model in mice, the present study has investigated the interaction between propranolol and dextromethorphan.
Methods: 50 Albino Swiss male mice were housed in groups of 10 per cage. The beta-adrenergic receptor blocker propranolol (20 mg/kg bw), the N-methyl-D-aspartate (NMDA) receptor dextromethorphan (30 mg/kg bw), and their combination were administered 10 minutes after exposure to predator odor. The treatments included diazepam as positive control and normal saline as negative control. Anxiety-like behaviors were evaluated using the elevated plus-maze test (EPM) 7 days after stress induction.
Results: Regarding the length of stay (F=25.53; p<0.0001)/ number of entries in the open arms (F=3.533; p=0.0416), time (F=6.127; p=0.0045)/ number of entries in the closed arms (F=5.690; p=0.0141), time in center-point (F=3.577; p=0,0295), and total distance traveled (F= 4.711; p=0.0145), there was a significant difference among the treated groups. Propranolol and dextromethorphan treated groups expressed lower time in the closed arms vs Placebo (p=0.0089, respectively p=0.0111). In addition, the time spent in the open arms was higher in propranolol group vs placebo group (p=0.0215).
Conclusions: Considering obtained data, there was a decrease of symptoms in the sympathetic nervous system and the psychological stress disappeared in mice applying a treatment of 20 mg/kg bw propranolol. Our findings indicated that dextromethorphan partially mediated the anxiolytic-like activity. However, the combination of these two drugs did not express anxiolytic effects.

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Relationship between obesity and psychosocial risk factors in hypertensive patients

Enikő Nemes-Nagy, Zoltán Preg, Kinga-Ilona Nyulas, Tünde Pál, Sándor Pál, Mariana Cornelia Tilinca, Márta Germán-Salló

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

DOI: 10.2478/amma-2021-0030

Introduction: Unhealthy lifestyle habits, including sedentary behaviour and improper diet are major risk factors for obesity. Overweight is very frequent in hypertensive and type 2 diabetic patients. Psychosocial factors are associated with multiple health behaviors related to overweight/obesity. The aim of the study was to evaluate the relationship between obesity and psychosocial risk factors in hypertensive patients having different levels of education.
Material and methods: 623 hypertensive patients, admitted to the Cardiovascular Rehabilitation Clinic in Tîrgu Mureș were evaluated by weight, height, waist circumference, laboratory analyses and psychosocial risk based on a validated questionnaire on nine topics. Non-paired Student t test was used for statistical evaluation of the obtained data.
Results: Obesity or overweight affected 86.9% of the studied hypertensive patients. Obesity was more frequent in subjects having type 2 diabetes as comorbidity. Mean BMI was significantly higher in the lower education group (p=0.007) compared to those with higher level of education. Average triglyceride and uric acid levels were significantly higher in obese subjects compared to those having lower BMI (p<0.0001). Patients living alone had significantly lower mean BMI (p=0.006) and waist circumference values (p=0.001) compared to those living with their spouse.
Conclusions: Weight excess in very frequent in the studied hypertensive patients, especially in those with type 2 diabetes as comorbidity and having lower educational level. Hypertriglyceridemia and hyperuricemia occurred more frequently in obese subjects compared to non-obese ones. Overweight is less frequent in patients living alone.

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Insulin resistance as risk factor for the development of type 2 diabetes mellitus: a systematic approach

Reka Annamaria Schmiedt1, Robert Aurelian Tiuca2,3, Raluca Maria Tilinca2, Lucia Mihaela Custura1, Oana Detesan1, Brigitta Iren Bacso1, Bianca Larisa Abalasei2, Andrew Corneliu Bell2, Maria Alexandra Streza2, Mariana Cornelia Tilinca1,2

1. Compartment of Diabetology, Emergency Clinical County Hospital of Targu Mures, Romania
2. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department of Endocrinology, Mures County Clinical Hospital, Romania

DOI: 10.2478/amma-2021-0033

Insulin resistance is a heterogenous condition with high prevalence in medical practice. As diabesity reaches epidemic levels worldwide, the role of insulin resistance is getting great importance. Contribution of risk factors like sedentary lifestyle, diets high in saturated fats and refined carbohydrates leads to this state with significant consequences. Besides its role in diabetes, insulin resistance is also associated with other several endocrine diseases, having not only a role in their development, but also to their treatment approach, evolution and even prognosis. The present review summarizes the current literature on the clinical significance of insulin resistance, as well as the possible underlying mechanisms and treatment options in order to achieve a high quality of life of these categories of patients. Deepening the role of inflammatory cytokines involved in insulin resistance paves the way for future research findings in this continuously evolving field.

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Emotional disorders associated to multiple sclerosis and psychological interventions: a literature review

Alina Schenk1, Cosmin Octavian Popa2, Cristiana Manuela Cojocaru1

1. The Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of Ethics and Social-Sciences, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2021-0042

Multiple sclerosis is an unpredictable neurologic disease affecting 2.8 million people worldwide. Individuals with MS experience multiple physical and psychological symptoms such as depression, anxiety, fatigue, and pain that impact their general functioning and quality of life. The aim of this review is to highlight the importance of psychological interventions in reducing depression and anxiety symptoms associated with the diagnosis of multiple sclerosis. Cognitive and behavioral techniques are also useful in relieving the specific symptoms of multiple sclerosis. However, few studies have captured the psychological processes involved in reducing the symptoms of depression and anxiety, which is why greater concern is recommended in future studies in order to develop better psychological interventions tailored for patients with multiple sclerosis.

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The antibacterial potential of biosynthesized silver nanoparticles using beech bark and spruce bark extracts

Anca Delia Mare1, Adrian Man1, Felicia Toma1, Bianca Tudor1, Lavinia Berța2, Corneliu Tanase3, Cristina Nicoleta Ciurea1

1. Department of Microbiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Department of General and Inorganic Chemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department of Pharmaceutical Botany, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2021-0043

Introduction: Lately, nanotechnology focuses on the green synthesis of AgNPs, using different plant materials, as this method is accessible, cost-efficient, and ecological. The study aimed to investigate the antibacterial potential of AgNPs synthesized using beech/spruce bark extracts (BBE/SBE) and silver salts (acetate/nitrate).
Method: The growth rates of Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 were evaluated in the presence of the AgNPs solutions. The checkerboard method was performed to evaluate if these solutions exert synergistic activity with gentamicin.
Results: For E. coli, synergistic effects were observed for the combination of gentamicin 0.25mg/L with AgNP BBE Nit (0.145mg/mL) and with AgNP SBE Ac (0,09mg/mL). For S. aureus, no synergistic effects were observed. Overall, the AgNP BBEs solutions combined with gentamicin presented lowest values of fractional inhibitory concentration than the ones registered for the combination of AgNP SBEs with gentamicin, for both bacterial strains. The growth rate of S. aureus was inhibited by all the tested AgNPs at the measured time points. For E. coli, after 24 hours of incubation, the growth rate was inhibited only in the presence of AgNP SBE Ac. After 6 hours of incubation, the growth rate of E. coli was almost stationary in the presence of AgNP BBE Nit.
Conclusions: The biosynthesis of AgNPs is a valuable choice for obtaining substances with antibacterial potential.

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