Category Archives: Review

Utilization of lipoxins and other specialised pro-resolving mediators in the prevention and treatment of diabetic nephropathy and diabetic cardiovascular disease

Ivan Bergo1, Ylenia Pastorello2

1. Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Campus Hamburg, Hamburg, Germany
2. Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș, Romania

DOI: 10.2478/amma-2024-0037

Diabetes mellitus type 2 is a chronic disease caused by insulin resistance. Whilst first originating in the adipose tissue, this pathophysiological process later affects the muscles and the liver as well. This induces high plasma levels of glucose and fatty acids, leading to the inflammatory-related chronic complications of diabetes, such as diabetic nephropathy and diabetic cardiovascular disease. Specialized pro-resolving mediators are lipid mediators responsible for resolving inflammation and could therefore be beneficial in the management of chronic diabetes complications. The aim of this review is to assess if specialised pro-resolving mediators have the potential to attenuate the chronic complications of diabetes. Specialised pro-resolving mediators, especially lipoxins, can modulate both diabetic nephropathy and diabetic cardiovascular disease. In mice it was demonstrated that, at the glomerular level, lipoxins reduced collagen deposition and expression of pro-inflammatory markers. In human saphenous vein smooth muscle cells instead, lipoxins were able to reduce collagen deposition and vascular smooth muscle cells proliferation and chemotaxis. Aspirin is a medication that could be used to modulate specialised pro-resolving mediator levels, as aspirin triggered-specialised pro-resolving mediators exist. Aspirin triggered-specialised pro-resolving mediators are pro-resolving substances with similar effects, but synthetised in a different way, requiring the partial blockage of the cyclooxygenase 2 enzyme. These results demonstrate how such substances could be useful in the treatment of diabetic patients and why further research is needed to create efficient and economical medications.

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The genetic landscape of early and late-onset Alzheimer’s disease: A review

Paula Denisa Saragea

Department of Biology, “Alexandru Ioan Cuza” University of Iasi, Romania

DOI: 10.2478/amma-2024-0030

Alzheimer’s disease(AD) is a multifactorial neurodegenerative disorder characterized by the progressive loss of neurons and synaptic dysfunction, primarily affecting the cortex and hippocampus. The etiology of AD is complex, involving the continuous and intricate interaction between genetic and non-genetic environmental factors. Genetic predisposition plays a significant role, with approximately 60-80% of AD risk attributed to hereditary factors. Familial early-onset AD(EOAD), with autosomal-dominant mutations in APP, PSEN1, and PSEN2, represents about 1-5% of cases and typically manifests before age 65. Rare autosomal-recessive mutations, like A673V(APP gene), are also implicated. Late-onset AD(LOAD), more common, is influenced by a combination of genetic and environmental factors, with the APOE ε4 allele being a major risk factor. Protective factors, such as the APOE ε2 allele and rare mutations like Ala673Thr, can reduce AD risk. The interplay between genetic variants, environmental influences, and pathological processes underpins the disease’s progression. This study highlights the importance of understanding the genetic and non-genetic determinants of AD to advance personalized treatment and early detection strategies. Future research and personalized medicine approaches are essential for mitigating AD risks and improving management outcomes.

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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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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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Smart science: How artificial intelligence is revolutionizing pharmaceutical medicine

Swapna B V1, Shibani Shetty2, Manjunath Shetty3, Smitha Sammith Shetty4

1. Department of Prosthodontics, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
2. Department of Oral Pathology and Microbiology, MR Ambedkar Dental College and Hospital. Bangalore, Karnataka, India
3. Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
4. Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

DOI: 10.2478/amma-2024-0002

Artificial intelligence (AI) is a discipline within the field of computer science that encompasses the development and utilization of machines capable of emulating human behavior, particularly regarding the astute examination and interpretation of data. AI operates through the utilization of specialized algorithms, and it includes techniques such as deep (DL), and machine learning (ML), and natural language processing (NLP). As a result, AI has found its application in the study of pharmaceutical chemistry and healthcare. The AI models employed encompass a spectrum of methodologies, including unsupervised clustering techniques applied to drugs or patients to discern potential drug compounds or appropriate patient cohorts. Additionally, supervised ML methodologies are utilized to enhance the efficacy of therapeutic drug monitoring. Further, AI-aided prediction of the clinical outcomes of clinical trials can improve efficiency by prioritizing therapeutic intervention that are likely to succeed, hence benefiting the patient. AI may also help create personalized treatments by locating potential intervention targets and assessing their efficacy. Hence, this review provides insights into recent advances in the application of AI and different tools used in the field of pharmaceutical medicine.

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Maternal sepsis – challenges in diagnosis and management: A mini-summary of the literature

Mihaela Alexandra Budianu1, Andrada Ioana Crişan1, Septimiu Voidăzan2

1. Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania
2. Department of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania

DOI: 10.2478/amma-2024-0001

Sepsis is still one of the leading causes of maternal mortality and morbidity, being the third most common cause of maternal death, after hemorrhage and hypertensive disorders. Maternal sepsis may appear due to obstetric causes such as: chorioamnionitis, endometritis, abortion-related uterine infections, and wound infections. For non-obstetric causes of maternal sepsis, the most common are urinary tract infections and respiratory tract infections. This mini summary presents the challenges in early diagnosis and prompt management, caused by pregnancy physiological changes. Physiological alterations during pregnancy, like an increase in white cell count, heart rate, and respiratory rate, associated with a decrease in blood pressure are also known signs of infection, making the diagnosis of sepsis during pregnancy more difficult. The three pillars of sepsis treatment are early antibiotics, vital organ support and fluid therapy, the last one being controversial. A more restrictive approach for fluid resuscitation could be more suitable for pregnant women, considering the risk of fluid overload and pulmonary edema. Criteria for early recognition and appropriate management customized for maternal sepsis are mandatory.

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Psychotherapy, pharmacotherapy, and their combination in the treatment of major depressive disorder: How well are we making use of available therapies?

Ingrid Karina Nădășan, Gabriel Hancu

Department of Pharmaceutical and Therapeutic Chemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania

DOI: 10.2478/amma-2023-0042

Major depressive disorder stands as a profound challenge in the realm of psychiatric illnesses disrupting the well-being and daily existence of affected individuals. This heterogeneous condition continues to baffle researchers due to the elusive nature of its full neurological mechanisms. This review delves into the complex landscape of major depressive disorder, exploring the diverse therapeutic avenues available, from the nuanced realms of psychotherapy to the pharmacological and non-pharmacological approaches that have been the focus of extensive research. In the relentless pursuit of relief for those afflicted, substantial efforts and resources are tirelessly channeled into the exploration of novel antidepressants and the refinement of existing therapeutic protocols. This review juxtaposes the efficiencies of existing treatments, unraveling their comparative effectiveness, and shedding light on their respective strengths and limitations. Even so, the question remains, how well are we managing the treatment of major depressive disorder, and which is the best option not only to treat this condition but also to reach full remission. Consequently, we have compiled findings on treatment selections and how efficient they are in relation to each other. The more we understand how to treat depression effectively the more we can improve the quality of life of individuals affected by this disorder. By comprehensively evaluating the diverse modalities, this review aims to guide clinicians and researchers toward evidence-based decisions, facilitating the formulation of individualized and targeted treatment protocols.

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Current screening and diagnostic approaches of
retinoblastoma in limited setting

Nunki Puspita Utomo1, Devie Kristiani2, Sri Mulatsih3, Pande Komang Wahyu Pradana1

1.Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia
2. Department of Pediatric Hematology and Oncology, Bethesda Hospital, Yogyakarta, Indonesia
3. Department of Pediatric Hematology and Oncology, Sardjito Hospital, Yogyakarta, Indonesia

DOI: 10.2478/amma-2023-0032

As the most common intraocular malignancy in children, retinoblastoma poses a vision, globe, and life-threatening risk and hence requires thorough evaluation and surveillance. While the disease is one of the most curable malignancies in established countries, children of lower-middle-income countries are not so fortunate, especially those with familial history of retinoblastoma. The delay of diagnosis proposes a grave prognosis, thus screening is a must. This study aimed to review the literature on various screening programs and applications described for the early detection of retinoblastoma, especially in a setting where genetic examination performance is limited. A literature search across PubMed®, ProQuest, and EbscoHost (MEDLINE Full text) with the topic of current methods and programs of retinoblastoma screening in neonates, infants, and children were carried out denoting various guideline and recommendations but the implementation is not uniform. Examination under anesthesia and red-reflex tests are among the most frequently conducted but the practices vastly vary especially in a place with low resources. Recent updates in mobile phone freeware should be rigorously upgraded due to its current inadequate sensitivity and specificity in detecting retinoblastoma but pose a promising future for retinoblastoma screening and diagnosis, especially in lower-middle-income countries.

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Vagus Nerve Stimulation (VNS) Therapy System in pharmacoresistant epilepsy: A literature review

Valentin Moroșanu1, Iulian Roman-Filip1, Sanda Petruțiu1, Rodica Bălașa1,2

1. Neurology 1 Clinic, Emergency Clinical Hospital Mures, Targu Mures, Romania
2. Deparment of Neurology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2023-0027

Epilepsy affects approximately 50 million of people worldwide and 30% of them are resistant to drugs. Neuromodulation is becoming a key option in patients with drug-resistant epilepsy who are not feasible for resective surgery. Vagus nerve stimulation (VNS) is the most commonly used adjunctive neuromodulatory method in every patient aged 4 years and older who is unsuitable for resective surgery. It is a minimally invasive, non-teratogenic, extracranial pacemaker-like device which delivers electrical stimuli to the vagus nerve and desynchronize aberrant cerebral rhythms involved in epileptogenesis. In this review we approached the information and clinical data of VNS development history, clinical applications and possible mechanism of action. We will also review optimal stimulation parameters and information about closed and open loop devices. Vagus nerve stimulation is safe, efficient with no significant side effects and substantial cost-saving benefit, that also shows an important improvement in mood, behavior, cognition and quality of life. The overall responder rate was observed in more than 50% of patients. On the other hand, it is not clear which patients will respond to this method of treatment and why the response is not immediate, there are no available biomarkers or other features like age, sex, seizure type/epileptic syndrome to predict response to vagus nerve stimulation therapy. The VNS Therapy System continues to be an important prospect in the treatment of pharmacoresistant epilepsy, that requires further studies in order to ensure the most advantageous therapeutic response.

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The role of diet in modulating the intestinal microbiota in healthy adults: Is the evidence enough?

Florina Ruta1, Elena Mardale2, Andrada Pintea1, Calin Avram1

1. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Regina Maria Health Network, Civic Center, Brasov, Romania

DOI: 10.2478/amma-2023-0025

The diet is an important factor that can influence the structures and function of the population of germs that compose the intestinal microbiota. This review presents current data on the response of the intestinal microbiota depending on the diet. While many studies have shown that the intestinal microbiota is influenced by macronutrient and micronutrient compounds of the diet, the studies on healthy human subjects were fewer and showed only to a small extent the influence of cooked food on the intestinal microbiota. Additional research is still needed regarding the effect of the way food is cooked can have on the intestinal microbiota, before beneficial dietary recommendations can be made.

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