Search results for: therapeutic results

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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Authors: Haris Karnezi, Kevin Tierney

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Cognitive Behaviour Drama is a research-based intervention model that brought together the science of psychology with the art form of drama to create an unobtrusive and exciting approach that would provide children on the higher end of the autism spectrum the motivation to explore the rules of social interaction and develop competencies associated with communicative success. The method involves engaging the participants in exciting fictional scenarios and encouraging them to seek various solutions on a number of problems that will lead them to an understanding of causal relationships and how a different course of action may lead to a different outcome. The sessions are structured to offer opportunities to the participants to practice target behaviours and understand the functions they serve. The study involved six separate interventions and employed both single case and group designs. Overall 8 children aged between 6 to 13 years, diagnosed with ASD participated in the study. Outcomes were measured using theory of mind tests, executive functioning tests, behavioural observations, pre and post intervention standardised social competence questionnaires for parents and teachers. Collectively, the results indicated positive changes in the self esteem and behaviour of all eight participants. In particular, improvements in the ability to solve theory of mind tasks were noted in the younger group; and qualitative improvements in social communication, in terms of verbal (content) and non verbal expression (body posture, vocal expression, fluency, eye contact, reduction of ritualistic mannerisms) were noted in the older group. The need for reliable impact measures to assess the effectiveness of the model in generating global changes in the participants’ behaviour outside the therapeutic context was identified.

Keywords: autism, drama, intervention, social skills

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Authors: Elaheh Hosseini, Otmar Bock, Monika Thomas

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The purpose of the present study was to determine the effect of climbing therapy on the components of attention of children with attention-deficit hyperactivity disorder (ADHD). Forty children with ADHD were assigned to either an intervention group or a control group. The exercise group participated in a climbing therapy program for ten weeks, whereas no intervention was administered to the control group. All two groups were then assessed with the same battery of attention tests used in our earlier study. We found that compared to the ‘intervention’ group, performance was higher in the ‘control’ group on tests of sustained, divided and distributed attention, on all four tests. The intervention group showed a significant improvement in components of attention after ten weeks. From this we conclude that climbing therapy can improve the attention of children with ADHD and can be considered as a promising intervention and a standalone treatment for children with ADHD.

Keywords: ADHD, climbing therapy, distributed attention, divided attention, selective attention, sustained attention

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Authors: N. Hoosain, S. Nene, B. Pearce, C. Jacobs, M. Du Plessis, M. Benjeddou

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Organic Cation Transporters play a vital role in the absorption, tissue distribution and elimination of various substrates. Numerous studies have suggested that variations in non-synonymous single nucleotide polymorphisms (SNPs) of SLC22A2 could influence an individual’s response to various treatments, including clinically important drugs. This study is the first to determine the baseline frequency distribution for twenty SNPs of SLC22A2in the Zulu population. DNA was collected from 101 unrelated “healthy” Zulu participants. Genotypes of all samples were determined using a multiplex PCR and SNaPshot assay followed by the generation of the haplotype structure. This is the first time that the baseline frequency distribution of SNPs is reported for the Zulu population. Data from this study could be used in in vitro and in vivo pharmacogenetic and pharmacokinetic studies to evaluate the potential role the studied SNPs play in the therapeutic efficacy of clinically important drugs.

Keywords: SLC22A2 gene, SNaPshot assay, PCR, Zulu population

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Authors: Jenyu Peng

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Incestuous abuse can be considered a form of domestic violence that exemplifies gender inequality. It challenges the common image of home as “haven of safety”. In Taiwan, even after years of feminist NGOs’ effort to encourage victims to speak up, the shared cultural representations of family, still praising piety towards the parents, seem to keep the incest trauma in secret. As clinical practitioners have observed, most devastating psychological sequels of incest trauma are often related to silencing. Thus one can expect that in families centered cultures, the difficulties for victims to disclose are greater, and the traumatic consequences more severe. This poses crucial therapeutic issues for clinicians working in those cultures. Since 2009, the author, a trained psychoanalyst and researcher, has been conducting “clinical fieldwork” on incest trauma in Taiwan. Employing ethnographical method, our theoretical references are both psychoanalytical and anthropological. The necessity of interdisciplinary efforts in incest trauma research will be addressed and discussed. The analyses of the present paper will focus on five incestuous families: four Han families, and one aboriginal. Although Taiwanese aboriginal peoples have been pretty much sinicized since decades, it is worth observing the convergent and divergent aspects in these two cultures. Moreover, findings of a previous research conducted in France during 2002-2004 will serve as background for the purpose of comparison. The results will be presented along with three questions: 1) How the perception of family influences the process of disclosure? 2) How the incestuous experience comes into play with victims’ gender identity and sexuality, pivotal for the subjectification? 3) How victims more successful in gendered subjectification modify their dynamics with their traumatizing family? This research finds that most victims tend to defend their own incestuous families, and that victims’ subjectivity and agency are actually entangled in the power structure of incestuous family.

Keywords: incestuous family, subjectification, gender identity, agency

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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Authors: Manal Ahmed, Amal Shehata, Shereen Deeb

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The study's purpose was to determine the effect of the perioperative protocol of care on clinical outcomes among patients undergoing coronary artery bypass graft. Subjects: A sample of 100 adult patients who were planned for coronary artery bypass graft, were selected and divided alternatively and randomly into two equal groups (50 study -50 control).The study was carried out at National heart Institute in Cairo and open heart surgical intensive care unit in Shebin El-Kom Teaching Hospital. Instruments: Four instruments were used for data collection: Interviewing questionnaire, dyspnea analogue scale, Biophysiological measurement instrument, and Compliance assessment sheet. Results: There were statistically significant differences between both groups regarding most respiratory system assessment findings at discharge. More than two-thirds of the study group of the current study had a continuous and regular commitment to diet regimen, which ranked first followed by the compliance of daily living activities then quitting smoking. Conclusions: The perioperative protocol of care has a significant improving effect on respiratory findings, dyspnea degree, duration of mechanical ventilation, length of hospital stay, compliance to diet, therapeutic regimen, daily living activities, and quit smoking among study group undergoing CABG. Recommendations: Perioperative protocol of care should be carried out for CABG patients at open-heart surgical units as well as an illustrative colored booklet about CAD, CABG and perioperative care should be available and distributed to all CABG patients.

Keywords: perioperative, effect, clinical outcomes, coronary artery, bypass graft, protocol of care

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Authors: Daniele Zullino, Gabriel Thorens, Léonice Furtado, Federico Seragnoli, Radu Iuga, Louise Penzenstadler

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Context: Since the start of the 21st century, there has been a resurgence of interest in psychedelics, marked by a renewed focus on scientific investigations into their therapeutic potential. While psychedelic therapy has gained recognition for effectively treating depression and anxiety disorders, notable progress has been made in the clinical development of substances like psilocybin. Moreover, mounting evidence suggests promising applications of Lysergic acid diethylamide (LSD) and psilocybin in the field of addiction medicine. In Switzerland, compassionate treatment with LSD and psilocybin has been permitted since 2014 through exceptional licenses granted by the Federal Office of Public Health. This treatment approach is also available within the Geneva treatment program, extending its accessibility to patients undergoing opioid-assisted treatment involving substances like morphine and diacetylmorphine. The aim of this study is to assess the feasibility of psychedelic-assisted therapy in patients with opioid use disorder who are undergoing opioid-assisted treatment. This study addresses the question of whether psychedelic-assisted therapy can be successfully implemented in patients with opioid use disorder. It also explores the effects of psychedelic therapy on the patient's experiences and outcomes. Methodology: This is an open case series on six patients who have undergone at least one session with either LSD (100-200 micrograms) or psilocybin (20-40 mg). The patients were assessed using the Five Dimensional Altered States of Consciousness (5D-ASC)-Scale. The data were analyzed descriptively to identify patterns and trends in the patients' experiences. Results: The patients experienced substantial positive psychedelic effects during the psychedelic sessions without significant adverse effects. The patients reported positive experiences and improvements in their condition. Conclusion: The findings of this study support the feasibility and potential efficacy of psychedelic-assisted therapy in patients undergoing opioid-assisted treatment.

Keywords: psychedelics, psychedelic-assisted treatment, opioid use disorder, addiction, LSD, psilocybin

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Authors: Ali Kassem

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Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Laura Cochrane

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The United States Centers for Disease Control and Prevention has established three categories of biological agents based on their ease of spread and the severity of the disease they cause. Category A biological agents are the highest priority because of their high degree of morbidity and mortality, ease of dissemination, the potential to cause social disruption and panic, special requirements for public health preparedness, and past use as a biological weapon. Despite the threat of Category A biological agents, opportunities for medical intervention exist. This work summarizes public information, consolidated and reviewed across the situational usefulness and disease awareness to offer discussion to three specific Category A agents: anthrax (Bacillus anthracis), botulism (Clostridium botulinum toxin), and smallpox (variola major), and provides an overview on the management of medical countermeasures available to treat these three (3) different types of pathogens. The medical countermeasures are discussed in the setting of pre-exposure prophylaxis, post-exposure prophylaxis, and therapeutic treatments to provide a framework for requirements in public health preparedness.

Keywords: anthrax, botulism, smallpox, medical countermeasures

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: Danila Zuffetti, Lorenzo Chiesa

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Background: A hospice narrative interview aims at putting the sick at the core of disease and treatment allowing them to explore their most intimate facets. The aim of this work is to favor authentic narration by leading towards awareness and acceptance of terminality and to face death with serenity. Narration in palliative care aims at helping to reduce the chaos generated by the disease and to elaborate interpretations on the course of reality, besides, the narration delivered to the doctor is fundamental and communicates the meaning given to symptoms. Methods: The narrative interview has become a regular activity in the Castellini Foundation since 2017. Patients take part every week, and for more days, in one hour sessions, in a welcoming and empathic setting and the interaction with the operator leads to a gradual awareness of their terminality. Patients are submitted with free answer questions with the purpose of facilitating and stimulating self-narration. Narration has not always been linear, but patients are left free to shift in time to revisit their disease process by making use of different tools, such as digital storytelling. Results: The answers provided by the patients show to which extent the narrative interview is an instrument allowing the analysis of the stories and gives the possibility to better understand and deepen the different implications of patient and caregiver’s background. Conclusion: The narration work in the hospice demonstrates that narrative medicine is an added value. This instrument has proven useful not only in the support of patients but also for the palliative doctor to identify wishes for accompanying them to the end with dignity and serenity. The narrative interview favors the construction of an authentic therapeutic relationship. The sick are taken wholly in charge, and they are guaranteed a high quality of life until their very last instant.

Keywords: construction of an authentic therapy relationship, gradual awareness of their terminality, narrative interview, reduce the chaos generated by the desease

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Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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Authors: Deepak Mohan, Sushma Sharma

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Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

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Authors: Akulov M. A., Orlova O. R., Zaharov V. O., Tomskij A. A.

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Introduction: One of the common postoperative complications of posterior cranial fossa (PCF) and cerebello-pontine angle tumor treatment is a facial nerve palsy, which leads to multiple and resistant to treatment impairments of mimic muscles structure and functions. After 4-6 months after facial nerve palsy with insufficient therapeutic intervention patients develop a postparalythic syndrome, which includes such symptoms as mimic muscle insufficiency, mimic muscle contractures, synkinesis and spontaneous muscular twitching. A novel method of treatment is the use of a recent local neuromuscular blocking agent– botulinum toxin A (BTA). Experience of BTA treatment enables an assumption that it can be successfully used in late facial nerve palsy complications to significantly increase quality of life of patients. Study aim. To evaluate the efficacy of botulinum toxin A (BTA) (Xeomin) treatment in patients with late facial nerve palsy complications. Patients and Methods: 31 patients aged 27-59 years 6 months after facial nerve palsy development were evaluated. All patients received conventional treatment, including massage, movement therapy etc. Facial nerve palsy developed after acoustic nerve tumor resection in 23 (74,2%) patients, petroclival meningioma resection – in 8 (25,8%) patients. The first group included 17 (54,8%) patients, receiving BT-therapy; the second group – 14 (45,2%) patients continuing conventional treatment. BT-injections were performed in synkinesis or contracture points 1-2 U on injured site and 2-4 U on healthy side (for symmetry). Facial nerve function was evaluated on 2 and 4 months of therapy according to House-Brackman scale. Pain syndrome alleviation was assessed on VAS. Results: At baseline all patients in the first and second groups demonstrated аpostparalytic syndrome. We observed a significant improvement in patients receiving BTA after only one month of treatment. Mean VAS score at baseline was 80,4±18,7 and 77,9±18,2 in the first and second group, respectively. In the first group after one month of treatment we observed a significant decrease of pain syndrome – mean VAS score was 44,7±10,2 (р<0,01), whereas in the second group VAS score was as high as 61,8±9,4 points (p>0,05). By the 3d month of treatment pain syndrome intensity continued to decrease in both groups, but, the first group demonstrated significantly better results; mean score was 8,2±3,1 and 31,8±4,6 in the first and second group, respectively (р<0,01). Total House-Brackman score at baseline was 3,67±0,16 in the first group and 3,74±0,19 in the second group. Treatment resulted in a significant symptom improvement in the first group, with no improvement in the second group. After 4 months of treatment House-Brockman score in the first group was 3,1-fold lower, than in the second group (р<0,05). Conclusion: Botulinum toxin injections decrease postparalytic syndrome symptoms in patients with facial nerve palsy.

Keywords: botulinum toxin, facial nerve palsy, postparalytic syndrome, synkinesis

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Authors: Ioannis Panagiotopoulos, Efstathios Kastritis, Anastasia Katinioti, Georgios Efthymiadis, Argyrios Doumas, Maria Koutelou

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Introduction: Transthyretin amyloidosis (ATTR) is a rare but serious infiltrative disease. Myocardial scintigraphy with DPD has emerged as the most effective, non-invasive, highly sensitive, and highly specific diagnostic method for cardiac ATTR amyloidosis. However, there are cases in which additional laboratory investigations reveal AL amyloidosis or other diseases despite a positive DPD scintigraphy. We describe the experience from the Onassis Cardiac Surgery Center and the monitoring center for infiltrative myocardial diseases of the cardiology clinic at AHEPA. Materials and Methods: All patients with clinical suspicion of cardiac or extracardiac amyloidosis undergo a myocardial scintigraphy scan with Tc-99m DPD. In this way, over 500 patients have been examined. Further diagnostic approach based on clinical and imaging findings includes laboratory investigation and invasive techniques (e.g., biopsy). Results: Out of 76 patients in total with positive myocardial scintigraphy Grade 2 or 3 according to the Perugini scale, 8 were proven to suffer from AL Amyloidosis during the investigation of paraproteinemia. Among these patients, 3 showed Grade 3 uptake, while the rest were graded as Grade 2, or 2 to 3. Additionally, one patient presented diffuse and unusual radiopharmaceutical uptake in soft tissues throughout the body without cardiac involvement. These findings raised suspicions, leading to the analysis of κ and λ light chains in the serum, as well as immunostaining of proteins in the serum and urine of these specific patients. The final diagnosis was AL amyloidosis. Conclusion: The value of DPD scintigraphy in the diagnosis of cardiac amyloidosis from transthyretin is undisputed. However, positive myocardial scintigraphy with DPD should not automatically lead to the diagnosis of ATTR amyloidosis. Laboratory differentiation between ATTR and AL amyloidosis is crucial, as both prognosis and therapeutic strategy are dramatically altered. Laboratory exclusion of paraproteinemia is a necessary and essential step in the diagnostic algorithm of ATTR amyloidosis for all positive myocardial scintigraphy with diphosphonate tracers since >20% of patients with Grade 3 and 2 uptake may conceal AL amyloidosis.

Keywords: AL amyloidosis, amyloidosis, ATTR, myocardial scintigraphy, Tc-99m DPD

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Jamal Alasiri, Naif Hakeem, Saoud Almaslmani

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Background: Patients with humeral shaft fractures have two different treatment options. Surgical therapy has lesser risks of non-union, mal-union, and re-intervention than non-surgical therapy. These positive clinical outcomes of the surgical approach make it a preferable treatment option despite the risks of radial nerve palsy and additional surgery-related risk. We aimed to evaluate patients’ outcomes and return to work after surgical vs. non-surgical management of shaft humeral fracture. Methods: We used databases, including PubMed, Medline, and Cochrane Register of Controlled Trials, from 2010 to January 2022 to search for potential randomised controlled trials (RCTs) and cohort studies comparing the patients’ related outcome measures and return to work between surgical and non-surgical management of humerus fracture. Results: After carefully evaluating 1352 articles, we included three RCTs (232 patients) and one cohort study (39 patients). The surgical intervention used plate/nail fixation, while the non-surgical intervention used a splint or brace procedure to manage shaft humeral fracture. The pooled DASH effects of all three RCTs at six (M.D: -7.5 [-13.20, -1.89], P: 0.009) I2:44%) and 12 months (M.D: -1.32 [-3.82, 1.17], p:0.29, I2: 0%) were higher in patients treated surgically than in non-surgical procedures. The pooled constant Murley score at six (M.D: 7.945[2.77,13.10], P: 0.003) I2: 0%) and 12 months (M.D: 1.78 [-1.52, 5.09], P: 0.29, I2: 0%) were higher in patients who received non-surgical than surgical therapy. However, pooled analysis for patients returning to work for both groups remained inconclusive. Conclusion: Altogether, we found no significant evidence supporting the clinical benefits of surgical over non-surgical therapy. Thus, the non-surgical approach remains the preferred therapeutic choice for managing shaft humeral fractures due to its lesser side effects.

Keywords: shaft humeral fracture, surgical treatment, Patient-related outcomes, return to work, DASH

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Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

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The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

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Authors: A. Jamsheera, F. Arjmand, D. K. Mohapatra

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Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.

Keywords: dipeptide Cu(II) and Zn(II) complexes, DNA binding profile, pBR322 DNA cleavage, in vitro anticancer activity

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Authors: Katharigatta N. Venugopala, Fernando Albericio, Bander E. Al-Dhubiab, T. Govender

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Recent years have witnessed a renaissance in the field of peptides that are obtained from various natural sources such as many bacteria, fungi, plants, seaweeds, vertebrates, invertebrates and have been reported for various pharmacological properties such as anti-TB, anticancer, antimalarial, anti-inflammatory, anti-HIV, antibacterial, antifungal, and antidiabetic, activities. In view of the pharmacological significance of natural peptides, serious research efforts of many scientific groups and pharmaceutical companies have consequently focused on them to explore the possibility of developing their potential analogues as therapeutic agents. Solid phase and solution phase peptide synthesis are the two methodologies currently available for the synthesis of natural or synthetic linear or cyclic depsi-peptides. From a synthetic point of view, there is no doubt that the solid-phase methodology gained added advantages over solution phase methodology in terms of simplicity, purity of the compound and the speed with which peptides can be synthesised. In the present study total synthesis, purification and structural elucidation of analogues of natural anti-TB cyclic depsi-peptides such as depsidomycin, massetolides and viscosin has been attempted by solid phase method using standard Fmoc protocols and finally off resin cyclization in solution phase method. In case of depsidomycin, synthesis of linear peptide on solid phase could not be achieved because of two turn inducing amino acids in the peptide sequence, but total synthesis was achieved by convergent solid phase peptide synthesis followed by cyclization in solution phase method. The title compounds obtained were in good yields and characterized by NMR and HRMS. Anti-TB results revealed that the potential title compound exhibited promising activity at 4 µg/mL against H37Rv and 16 µg/mL against MDR strains of tuberculosis.

Keywords: total synthesis, cyclic depsi-peptides, anti-TB activity, tuberculosis

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Authors: Abdullah Alyoussef

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Folliculitis decalvans is a rare inflammatory scalp disorder. This paper gives an update to patient management and treatment modalities. Folliculitis decalvans is classified as primary neutrophilic cicatricial alopecia and predominantly occurs in middle-aged adults. The cause of folliculitis decalvans (FD) remains unknown. Staphylococcus aureus and a deficient host immune response seem to play an important role in the development of this disfiguring scalp disease. Lesions occur mainly in the vertex and occipital area. Clinically, the lesions present with follicular pustules, lack of ostia, diffuse and perifollicular erythema, follicular tufting, and, oftentimes, hemorrhagic crusts and erosions. Histology displays a mainly neutrophilic inflammatory infiltrate in early lesions and additionally lymphocytes and plasma cells in advanced lesions. Treatment is focused on the eradication of S. aureus and anti-inflammatory agents. Although the etiology of FD is unclear, S. aureus is almost always isolated from affected areas, and eradication is an important part of therapeutic management, in combination with systemic and ⁄ or topical anti-inflammatory treatment.

Keywords: cicatricial alopecia, folliculitis decalvans, tufted folliculitis, erosion

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Authors: Emmanuel Ikechuckwu Onwubuya, Afees Adebayo Oladejo

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Background: The use of medicinal plants in the treatment of chronic diseases especially myocardial infarction, is gaining wide acceptance globally. Andrographis paniculata (Acanthaceae) is a medicinal plant commonly known as the king of bitters in Nigeria and has been acclaimed for several therapeutic activities. Materials and methods: This study investigated the cardio-protective effect of the leaf extract of A. paniculata in isoproterenol-induced myocardial infarction. Fresh green leaves of A paniculata were harvested from the Faculty of Agriculture farmland, Nnamdi Azikiwe University, Awka, Nigeria. Identification and authentication of the plant were carried out at the Department of Botany, Nnamdi Azikiwe University and a voucher specimen was deposited at the herbarium. The plant material was then shredded, air-dried under shade and pulverized. The fine powders obtained were weighed and extraction was done via a solvent combination of water and ethanol (3:7) for 72 hr via maceration. The filtrate gotten was evaporated to dryness to obtain the ethanol extract, which was used for further bioassay study. The bioactive constituents of the plant extract were quantitatively analyzed by Gas chromatography-mass spectrometry (GC-MS). The animals were administered the extract of A. paniculata orally for seven days at a divided dose of 100 mg/kg, 200 mg/kg and 400 mg/kg body weights. On the eighth day, myocardial infarction was induced through subcutaneous administration of isoproterenol at a dose of 150 mg/kg/day diluted in 2 ml of saline on two consecutive days. Subsequently, the blood pressures were monitored and blood was collected for bioassay studies. Results: The results of the study showed that the leaf extract of A. paniculata was rich in Dodecanoic acid (8.261%), 4-Dibenzofuranamine (6.03%), Cyclotrisiloxane (4.679 %). The findings also showed a significant decrease (p>0.05) in the Mean arterial blood pressure, heart rate, aspartate transaminase, alanine transaminase, creatinine kinase and lactate dehydrogenase activities of the treatment group compared with the untreated control group while the antioxidant (superoxide dismutase, catalase and glutathione) activities were significantly increased in the treatment group, compared with the untreated control group. Conclusion: The findings of this work have shown that the leaf of A. paniculata was rich in bioactive compounds, which could be synthesized to produce plant-based products to fight cardiovascular diseases, especially myocardial infarction.

Keywords: cardiovascular disease, myocardial infarction, medicinal plant, andrographis paniculata, isoproterenol

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Authors: Rita Emília Szabó, Róbert Polanek, Tünde Tőkés, Zoltán Szabó, Szabolcs Czifrus, Katalin Hideghéty

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Purpose: Several feature of zebrafish are making them amenable for investigation on therapeutic approaches such as ionizing radiation. The establishment of zebrafish model for comprehensive radiobiological research stands in the focus of our investigation, comparing the radiation effect curves of neutron and photon irradiation. Our final aim is to develop an appropriate vertebrate model in order to investigate the relative biological effectiveness of laser driven ionizing radiation. Methods and Materials: After careful dosimetry series of viable zebrafish embryos were exposed to a single fraction whole-body neutron-irradiation (1,25; 1,875; 2; 2,5 Gy) at the research reactor of the Technical University of Budapest and to conventional 6 MeV photon beam at 24 hour post-fertilization (hpf). The survival and morphologic abnormalities (pericardial edema, spine curvature) of each embryo were assessed for each experiment at 24-hour intervals from the point of fertilization up to 168 hpf (defining the dose lethal for 50% (LD50)). Results: In the zebrafish embryo model LD50 at 20 Gy dose level was defined and the same lethality were found at 2 Gy dose from the reactor neutron beam resulting RBE of 10. Dose-dependent organ perturbations were detected on macroscopic (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, micrognathia, pericardial edema, and inhibition of yolk sac resorption) and microscopic (marked cellular changes in skin, cardiac, gastrointestinal system) with the same magnitude of dose difference. Conclusion: In our observations, we found that zebrafish embryo model can be used for investigating the effects of different type of ionizing radiation and this system proved to be highly efficient vertebrate model for preclinical examinations.

Keywords: ionizing radiation, LD50, relative biological effectiveness, zebrafish embryo

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Authors: Yunusa Aliyu Hadejia

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Cholera is a gastrointestinal disease caused by a bacterium called Vibrio Cholerae which spread as a result of eating food or drinking water contaminated with feaces from an infected person. In this work we proposed and analyzed the impact of isolating infected people and give them therapeutic treatment, the specific objectives of the research was to formulate a mathematical model of cholera transmission incorporating treatment class, to make analysis on stability of equilibrium points of the model, positivity and boundedness was shown to ensure that the model has a biological meaning, the basic reproduction number was derived by next generation matrix approach. The result of stability analysis show that the Disease free equilibrium was both locally and globally asymptotically stable when R_0< 1 while endemic equilibrium has locally asymptotically stable when R_0> 1. Sensitivity analysis was perform to determine the contribution of each parameter to the basic reproduction number. Numerical simulation was carried out to show the impact of the model parameters using MAT Lab Software.

Keywords: mathematical model, treatment, stability, sensitivity

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Authors: Asma A. Ben Ahmed, Hajer M. Alborawy, Alaa A. Mashina, Pradeep K. Velautham, Abdulmonem Gobassa, Emhemmed Elgallal, Mohamed N. El Attug

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Generic medicines are those where patent protection has expired, and which may be produced by manufacturers other than the innovator company. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Generic medicines are typically 20 – 90 % cheaper than originator equivalents. Physicians often continue to prescribe brand-name drugs to their patients even when less expensive pharmacologically equivalent generic drugs are available. Because generics are less expensive than their brand-name counterparts, the cost-savings to the patient is not the only factor that physicians consider when choosing between generic and brand-name drugs. Unfortunately Physicians in general and Libyan Physicians in particular tend to prescribe brand-name drugs, even without evidence of their therapeutic superiority, because neither they nor their insured patients bear these drugs’ increased cost with respect to generic substitutes. This study is to compare the quality of five different prednisolone tablets of the same strength from different companies under different trade names: Julphar, October pharma, Akums, Actavis, Pfizer compared them with pure prednisolone reference (BPCRS).

Keywords: quality control, pharmaceutical analysis, generic medicines, prednisolone

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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