Search results for: drug affordability

Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

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Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of ¹⁷⁷Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: compartmental modeling, human absorbed dose, ¹⁷⁷Lu-DOTATOC, Syrian rats

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Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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Authors: Samaneh Abedini, Diana Urajnik, Nicole Naccarato

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A high prevalence of mental health problems was observed in marginalized youth living in underserved regions of Ontario during the COVID-19 pandemic. To address this issue, a growing number of community-based traditional mental health services are offering digital mental health resources due to their accessibility, affordability, and scalability. The feasibility of providing these resources in underserved regions has been examined by researchers rather than by representatives of effective services within a mental health system. Indeed, digitalized mental health contents are not routinely embedded within local mental health organizations' services in Northern Ontario, where they can make a substantial impact. To date, many technology-based mental health initiatives have not been effectively implemented in this region. The obstacles associated with implementing digitalized mental health resources in Northern Ontario may be unique to that region. Thus, specific context-based considerations might need to be applied for developing and implementing digital resources by regional mental health organizations in Northern Ontario. The target population was child-serving organizations situated in northeastern Ontario, specifically within Greater Sudbury and the Sudbury District. A sample of six organizations were selected with representation from the mental health, social, and healthcare sectors. The project supervisor was in a unique position to access the organizations by virtue of existing relationships with the practice and lay communities at large. Thus, recruitment was conducted through professional outreach in partnership with the Center for Rural and Northern Health Research (CRaNHR). Semi-structured interviews were conducted with 1-2 key personnel (e.g., administrator, clinician) from participating organizations. Audio recordings from the semi-structured interviews were transcribed verbatim and thematically analyzed supported by NVivo. Thematic analysis of the data resulted in a total of 13 excerpts which were categorized into two major themes including 1) digital mental health services as a valuable resource for organizations both during and after the pandemic, and 2) barriers and facilitators to a successful implementation of digital mental health resources in northern Ontario. Four secondary themes were identified: 1) perceived barriers to implementation of digital mental health resources to the offered services by mental health agencies; 2) acceptability and feasibility of digital health sources for people living in northern Ontario; 3) data security, safety, and risk; and 4) connecting with clients. The employees of mental health organizations in northern Ontario considered digital mental health resources as generally acceptable to youth. However, they raised several concerns that may affect their implementation into routine practice and service delivery. The implementation of digital systems should be simple and straightforward and should enhance rather than hinder clinical workflows for staff. A clear plan for implementing technological services is also required for the successful adoption of digital systems. For successful adoption and implementation of digital systems, staff views must be considered.

Keywords: COVID-19 pandemic, digital mental health resources, Ontario, underserved

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Payal Mazumdar, Sunita Rattan, Monalisa Mukherjee

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Polymer nanocomposites are a special class of materials having unique properties and wide application in diverse areas such as EMI shielding, sensors, photovoltaic cells, membrane separation properties, drug delivery etc. Recently the nanocomposites are being investigated for their use in biomedical fields as biosensors. Though nanocomposites with carbon nanoparticles have received worldwide attention in the past few years, comparatively less work has been done on nanographite although it has in-plane electrical, thermal and mechanical properties comparable to that of carbon nanotubes. The main challenge in the fabrication of these nanocomposites lies in the establishment of homogeneous dispersion of nanographite in polymer matrix. In the present work, attempts have been made to synthesize the nanocomposites of polystyrene and nanographite using click chemistry. The polymer and the nanographite are functionalized prior to the formation of nanocomposites. The polymer, polystyrene, was functionalized with alkyne moeity and nanographite with azide moiety. The fabricating of the nanocomposites was accomplished through click chemistry using Cu (I)-catalyzed Huisgen dipolar cycloaddition. The functionalization of filler and polymer was confirmed by NMR and FTIR. The nanocomposites formed by the click chemistry exhibit better electrical properties and the sensors are evaluated for their application as biosensors.

Keywords: nanocomposites, click chemistry, nanographite, biosensor

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Authors: Aneta Nitsch-Osuch, Damian Okrucinski, Magdalena Dawgialło, Izabela Gołębiak, Ernest Kuchar

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The Hospital Antibiotic Policy (HAP) should be implemented to rationalize the antibiotic use and to decrease the risk of spreading of spreading of resistant bacteria. The aim of our study was to describe the antibiotic consumption patterns at the single oncosurgery ward before and after implementation of the HAP. We conducted a retrospective analysis of the antibiotic use at the Oncosurgery Ward in Warsaw (Poland) in years 2011-2016. Calculations were based on daily defined doses (DDDs), DDDs/100 hospitalizations and DDDs/100 person-days, drug utilization rates (DU 90% and DU 100%) were also analysed. After implementation of the HAP, the total antibiotic consumption increased (365.35 DDD in 2011 vs. 1359,22 DDD in 2016). The significant change was observed in antibiotic consumption patterns: the use of amoxicillin clavulanate and carbapenems or glycopeptides decreased significantly (p < 0,05), while the use of ciprofloxacin and aminoglycosides increased (p < 0,05). The DU100% rate varied from 6 in 2011 to 12 in 2016; while DU 90% rate varied from 2 in 2011 to 3-5 in 2013-2016. Although the implementation of the HAP did not result in the decreased total antibiotic consumption, it provided favorable changes in the antibiotic consumption patterns.

Keywords: antibiotics, hospital, policy, stewardship

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Authors: Farah Ali, Tehreem Fiayyaz, Laeeq Akbar Lodhi, Imran Mirza

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The present work was undertaken to investigate effects of various extracts of W. somnifera (WS) for anti-diabetic activity in alloxan induced diabetic rabbits. Animals were divided into nine groups of six rabbits each. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and WS root powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of WS in the doses of 100, 150, 200 mg/kg and its aqueous (AWS) and ethanol extracts (EWS) (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively orally for three weeks (day 1-20 o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was given metformin (200 mg/kg) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3 as compared to normal control (NC) group (1). WS (100, 150, 200 mg/kg, p.o) decreased the fasting serum glucose concentration, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. These results indicate that metformin (reference control), (AWS) and (EWS) significantly antagonized the diabetic effects of alloxan.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat

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Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.

Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma

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Authors: S. Boulenouar, M. Sefir, M. Benahmed

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All facilities need medication and other pharmaceuticals for their operation. Management and supply is therefore to provide the different services of the facility goods and services in required quantity and quality. The permanent availability of drugs in the facilities is very difficult because most face many difficulties at the inventory management and drug supplies. Therefore, it is necessary for each health facility to know the causes for the malfunction of its management system to cope with them. It is in this context that we have undertaken to conduct this study to know the causes which should be taken into consideration by the concerned authorities to carry out their mission, which is to provide quality health care for the population. In terms of financial resources, the budget for medicines represents a significant part of the budget of the pharmacy. Our study shows that the share of the hospital budget reserved for the drugs procurement represent on average 70% of the budget of the pharmacy. The results show a state of lack of anticancer drugs at Oran teaching hospital. The analysis of the management process allowed us to know the level that the problem of stock-outs of anti-cancer drugs is at. Suggestions were made to that effect to improve the availability for these products and to respond better to the needs of patients.

Keywords: anticancer drugs, health care facility, budget, hospital pharmacist, hospital service

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Authors: M. R. Phadatare, J. V. Meshram, S. H. Pawar

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Conversion of electromagnetic energy into heat by nanoparticles (NPs) has the potential to be a powerful, non-invasive technique for biomedical applications such as magnetic fluid hyperthermia, drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this paper, an attempt has been made to increase the efficiency of magnetic, thermal induction by NPs. To increase the efficiency of magnetic, thermal induction by NPs, one can take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the NP and maximize the specific absorption rate, which is the gauge of conversion efficiency. In order to examine the tunability of magnetocrystalline anisotropy and its magnetic heating power, a representative magnetically hard material (CoFe₂O₄) has been coupled to a soft material (Ni₀.₅Zn₀.₅Fe₂O₄). The synthesized NPs show specific absorption rates that are of an order of magnitude larger than the conventional one.

Keywords: magnetic nanoparticles, surface functionalization of magnetic nanoparticles, magnetic fluid hyperthermia, specific absorption rate

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Authors: Kathryn Watson

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In 2020 North Carolina passed legislation mandating all educators be trained in identifying, referring, and supporting students showing signs of mental health issues, drug use, suicidal ideation, and sex trafficking. This study collected survey responses from 226 educators in North Carolina to better understand their perspectives on the legislation and their self-efficacy in supporting student mental health needs. Key findings of the study reveal that the mandated trainings increased educator awareness of student mental health, and higher awareness was linked to higher self-efficacy in supporting student mental health needs. Additionally, the results showed that educators who identify as Black had lower levels of self-efficacy in supporting student mental health. Additionally, rural educators were least likely to support the legislation in comparison to their urban and suburban counterparts. These findings can help inform policymakers in evaluating the policy and district decision-makers in selecting and implementing school-based mental health training.

Keywords: school-based mental health, education policy, student health, North Carolina, K-12 education

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Authors: Dmitriy Babenko, Sergey Yegorov, Ilya Korshukov, Aidana Sultanbekova, Valentina Barkhanskaya, Tatiana Bashirova, Yerzhan Zhunusov, Yevgeniya Li, Viktoriya Parakhina, Svetlana Kolesnichenko, Yeldar Baiken, Aruzhan Pralieva, Zhibek Zhumadilova, Matthew S. Miller, Gonzalo H. Hortelano, Anar Turmuhambetova, Antonella E. Chesca, Irina Kadyrova

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Introduction: The rapidly evolving COVID-19 pandemic, along with the re-emergence of pathogens causing acute respiratory infections (ARI), has necessitated the development of novel diagnostic tools to differentiate various causes of ARI. MALDI-MS, due to its wide usage and affordability, has been proposed as a potential instrument for diagnosing SARS-CoV-2 versus non-SARS-CoV-2 ARI. The aim of this study was to investigate the potential of MALDI-MS in conjunction with a machine learning model to accurately distinguish between symptomatic infections caused by SARS-CoV-2 and non-SARS-CoV-2 during both the early and later phases of the pandemic. Furthermore, this study aimed to analyze mass spectrometry (MS) data obtained from nasal swabs of healthy individuals. Methods: We gathered mass spectra from 252 samples, comprising 108 SARS-CoV-2-positive samples obtained in 2020 (Covid 2020), 7 SARS-CoV- 2-positive samples obtained in 2023 (Covid 2023), 71 samples from symptomatic individuals without SARS-CoV-2 (Control non-Covid ARVI), and 66 samples from healthy individuals (Control healthy). All the samples were subjected to RT-PCR testing. For data analysis, we employed the caret R package to train and test seven machine-learning algorithms: C5.0, KNN, NB, RF, SVM-L, SVM-R, and XGBoost. We conducted a training process using a five-fold (outer) nested repeated (five times) ten-fold (inner) cross-validation with a randomized stratified splitting approach. Results: In this study, we utilized the Covid 2020 dataset as a case group and the non-Covid ARVI dataset as a control group to train and test various machine learning (ML) models. Among these models, XGBoost and SVM-R demonstrated the highest performance, with accuracy values of 0.97 [0.93, 0.97] and 0.95 [0.95; 0.97], specificity values of 0.86 [0.71; 0.93] and 0.86 [0.79; 0.87], and sensitivity values of 0.984 [0.984; 1.000] and 1.000 [0.968; 1.000], respectively. When examining the Covid 2023 dataset, the Naive Bayes model achieved the highest classification accuracy of 43%, while XGBoost and SVM-R achieved accuracies of 14%. For the healthy control dataset, the accuracy of the models ranged from 0.27 [0.24; 0.32] for k-nearest neighbors to 0.44 [0.41; 0.45] for the Support Vector Machine with a radial basis function kernel. Conclusion: Therefore, ML models trained on MALDI MS of nasopharyngeal swabs obtained from patients with Covid during the initial phase of the pandemic, as well as symptomatic non-Covid individuals, showed excellent classification performance, which aligns with the results of previous studies. However, when applied to swabs from healthy individuals and a limited sample of patients with Covid in the late phase of the pandemic, ML models exhibited lower classification accuracy.

Keywords: SARS-CoV-2, MALDI-TOF MS, ML models, nasopharyngeal swabs, classification

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Authors: Yaa Asuaba Duopah, Lisa Moran, Khalifa Elmusharaf, Dervla Kelly

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Background: Research has identified a strong link between stress and drug use behaviours. Also, it has been established that the prolonged use of crack cocaine stimulates emotional, cognitive, neurological, and social changes. This paper examines the psychosocial stressors associated with crack cocaine use. Methodology: The study is qualitative and adopts a critical realist approach. Data was collected through 26 face-to-face, in-depth, semi-structured interviews with people who use crack cocaine. Study participants were recruited through two addiction services using purposive. Participants consisted of 15 males and 11 females between the ages of 24-57 years. Data were analysed using thematic analysis. Results: Cravings, financial hardship, family breakdown, and emotional stimulation were revealed as psychosocial stressors associated with crack cocaine use. Conclusion: Addressing the psychosocial stressors identified in this paper through targeted interventions and supportive policies is crucial for improving the well-being of persons who use crack cocaine. Collaboration between addiction, mental health, and support services is recommended to develop and deliver these interventions.

Keywords: psychological stress, substance misuse disorder, mental health, coping

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Authors: Jan C. Droste, Justine Burns, Nithin Narayan

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Introduction: Life-threatening detrimental effects of inappropriate adrenaline (epinephrine) administration, e.g., by giving the wrong dose, in the context of anaphylaxis management is well documented in the medical literature. Half of the fatal anaphylactic reactions in the UK are iatrogenic, and the median time to a cardio-respiratory arrest can be as short as 5 minutes. It is therefore imperative that hospital doctors of all grades have active and accurate knowledge of the correct route, site, and dosage of administration of adrenaline. Given this time constraint and the potential fatal outcome with inappropriate management of anaphylaxis, it is alarming that surveys over the last 15 years have repeatedly shown only a minority of doctors to have accurate knowledge of adrenaline administration as recommended by the UK Resuscitation Council guidelines (2008 updated 2012). This comparison of survey results of the medical workforce over several years in a small NHS District General Hospital was conducted in order to establish the effect of the employment of multiple educational methods regarding adrenaline administration in anaphylaxis in adults. Methods: Between 2010 and 2017, several education methods and tools were used to repeatedly inform the medical workforce (doctors and advanced clinical practitioners) in a single district general hospital regarding the treatment of anaphylaxis in adults. Whilst the senior staff remained largely the same cohort, junior staff had changed fully in every survey. Examples included: (i) Formal teaching -in Grand Rounds; during the junior doctors’ induction process; advanced life support courses (ii) In-situ simulation training performed by the clinical skills simulation team –several ad hoc sessions and one 3-day event in 2017 visiting 16 separate clinical areas performing an acute anaphylaxis scenario using actors- around 100 individuals from multi-disciplinary teams were involved (iii) Hospital-wide distribution of the simulation event via the Trust’s Simulation Newsletter (iv) Laminated algorithms were attached to the 'crash trolleys' (v) A short email 'alert' was sent to all medical staff 3 weeks prior to the survey detailing the emergency treatment of anaphylaxis (vi) In addition, the performance of the surveys themselves represented a teaching opportunity when gaps in knowledge could be addressed. Face to face surveys were carried out in 2010 ('pre-intervention), 2015, and 2017, in the latter two occasions including advanced clinical practitioners (ACP). All surveys consisted of convenience samples. If verbal consent to conduct the survey was obtained, the medical practitioners' answers were recorded immediately on a data collection sheet. Results: There was a sustained improvement in the knowledge of the medical workforce from 2010 to 2017: Answers improved regarding correct drug by 11% (84%, 95%, and 95%); the correct route by 20% (76%, 90%, and 96%); correct site by 40% (43%, 83%, and 83%) and the correct dose by 45% (27%, 54%, and 72%). Overall, knowledge of all components -correct drug, route, site, and dose-improved from 13% in 2010 to 62% in 2017. Conclusion: This survey comparison shows knowledge of the medical workforce regarding adrenaline administration for treatment of anaphylaxis in adults can be considerably improved by employing a variety of educational methods.

Keywords: adrenaline, anaphylaxis, epinephrine, medical education, patient safety

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Authors: Amina Bayazid, Habiba Fetati, Houari Toumi

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Introduction: The clinical value of vitamin K antagonists (VKA) has been widely demonstrated in numerous indications. Unfortunately, VKA are not devoid of drawbacks and risk of serious bleeding. The iatrogenic induced by these drugs is a major public health problem. Patients & Methods: We conducted a retrospective study period extending from February 2012 to August 2013 in the pharmacovigilance service of EHUO (clinical pharmacology unit). The prescription of painkillers was analyzed in patients on VKA followed at our level. The influence of these analgesics on the evolution of the INR is an important component in our work. Results: We counted a total of 195 patients, of whom 32 (or 16.41% of the total population) had received analgesic treatment. The frequencies of different categories of analgesics administered were: • Analgesics opioids: 0% • Analgesics weak opioids: Tramadol: 21.87% • The non-opioid analgesics: -AINS: 71.87% (indomethacin: 68.75% ibuprofen: 3.12%) - Paracetamol: 6.25% -Salicyles (Acetylsalicylic acid): 0%. Conclusion: The management of pain in patients under vitamin K antagonists has special features, given their many drug interactions with analgesics and their influence on the evolution of the INR which can have dramatic consequences. As such, special attention must be paid to the use of analgesics in this type of patient.

Keywords: vitamin K antagonists, pain killers, interactions, INR

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Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

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Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

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Authors: M. Salvador, J. C. Martinez-Garcia, A. Moyano, M. C. Blanco-Lopez, M. Rivas

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Biosensors play a crucial role in the detection of molecules nowadays due to their advantages of user-friendliness, high selectivity, the analysis in real time and in-situ applications. Among them, Lateral Flow Immunoassays (LFIAs) are presented among technologies for point-of-care bioassays with outstanding characteristics such as affordability, portability and low-cost. They have been widely used for the detection of a vast range of biomarkers, which do not only include proteins but also nucleic acids and even whole cells. Although the LFIA has traditionally been a positive/negative test, tremendous efforts are being done to add to the method the quantifying capability based on the combination of suitable labels and a proper sensor. One of the most successful approaches involves the use of magnetic sensors for detection of magnetic labels. Bringing together the required characteristics mentioned before, our research group has developed a biosensor to detect biomolecules. Superparamagnetic nanoparticles (SPNPs) together with LFIAs play the fundamental roles. SPMNPs are detected by their interaction with a high-frequency current flowing on a printed micro track. By means of the instant and proportional variation of the impedance of this track provoked by the presence of the SPNPs, quantitative and rapid measurement of the number of particles can be obtained. This way of detection requires no external magnetic field application, which reduces the device complexity. On the other hand, the major limitations of LFIAs are that they are only qualitative or semiquantitative when traditional gold or latex nanoparticles are used as color labels. Moreover, the necessity of always-constant ambient conditions to get reproducible results, the exclusive detection of the nanoparticles on the surface of the membrane, and the short durability of the signal are drawbacks that can be advantageously overcome with the design of magnetically labeled LFIAs. The approach followed was to coat the SPIONs with a specific monoclonal antibody which targets the protein under consideration by chemical bonds. Then, a sandwich-type immunoassay was prepared by printing onto the nitrocellulose membrane strip a second antibody against a different epitope of the protein (test line) and an IgG antibody (control line). When the sample flows along the strip, the SPION-labeled proteins are immobilized at the test line, which provides magnetic signal as described before. Preliminary results using this practical combination for the detection and quantification of the Prostatic-Specific Antigen (PSA) shows the validity and consistency of the technique in the clinical range, where a PSA level of 4.0 ng/mL is the established upper normal limit. Moreover, a LOD of 0.25 ng/mL was calculated with a confident level of 3 according to the IUPAC Gold Book definition. Its versatility has also been proved with the detection of other biomolecules such as troponin I (cardiac injury biomarker) or histamine.

Keywords: biosensor, lateral flow immunoassays, point-of-care devices, superparamagnetic nanoparticles

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Authors: Mohana Babu Amberkar, Meena Kumari K, Ravi, Arjun, Christopher Rockson

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The aim of this research is to evaluate the hepatoprotective activity of Terminalia paniculata (Tp) against ATT induced hepatic damage in rats.Three hepatotoxic ATT drugs Isoniazid + Rifampicin + Pyrazinamide, silymarin as standard hepatoprotective drug and 0.5% carboxymethylcellulose (CMC) as a control were used. Tp extract and silymarin were administered orally with ATT drugs for 90 days. Two doses 250 and 500 mg/kg of Tp extract, ATT drugs and silymarin were administered as suspensions with 0.5% CMC. ATT treated rats showed a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxides in the serum vs. control. Treatment of silymarin and Tp (250mg/kg) extract showed hepatoprotective activity against the hepatic damage by ATT. This was evident from significant reduction in serum liver enzymes levels, and also there was a significant increase in serum proteins, albumin and total liver tissue thiols as compared to the ATT treated groups. Tp was found to possess hepatoprotective property.

Keywords: antitubercular drugs, hepatoprotective, liver enzymes, Terminalia paniculata

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Authors: Eric Chappel, Dimitry Dumont-Fillon, Hugo Musard, Harald van Lintel

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A microfluidic radial diffuser typically comprises a hole in a membrane, a small gap and pillar centred with the hole. The fluid is forced to flow radially in this gap between the membrane and the pillar. Such diffusers are notably used to form flow control valves, wherein several holes are machined into a flexible membrane progressively deflecting against pillars as the pressure increases. The fluidic modelling of such diffuser is made difficult by the presence of a transition region between the hole and the diffuser itself. An experimental investigation has been conducted using SOI wafers to form membranes with only one centred hole and Pyrex wafers for the substrate and pillars, both wafers being anodically bonded after alignment. A simple fluidic model accounting for the specific geometry of the diffuser is proposed and compared to experimental results. A good match is obtained, for Reynolds number in the range 0.5 to 35 using the analytical formula of a radial diffuser in the laminar regime with an effective inner radius that is 40% smaller than the real radius, in order to simulate correctly the flow constriction at the entrance of the diffuser.

Keywords: radial diffuser, flow control valve, numerical modelling, drug delivery

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Authors: Neda Sinaei, Davood Zare, Mehrdad Azin

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Polyhydroxyalkanoates (PHAs) are biocompatible and biodegradable polymers produced by a wide range of bacterial strains. These biopolymers are significantly studied for drug delivery and tissue engineering applications because of their fascinating physicochemical properties. Polyhydroxybutyrate (PHB) scaffold that has been extracted from a novel bacteria using oil wastewater was selected to study. Some physical parameters affecting scaffold properties such as PHB concentration, solvent evaporation speed, and ultrasonic time were investigated. Scanning electron microscopy was used to evaluate the porosity. Afterward, the biocompatibility of PHB scaffold was assessed. Initial results showed the highly porous PHB scaffold structure with a variety of pore sizes. Subsequent results indicated that more unique pore sizes can be obtained by optimizing physical factors. It would be noticed that the morphology of the pore structure was accordingly affected by ultrasonic time. Hence, In vitro cell viability tests on the PHB scaffold using human foreskin fibroblasts revealed strong cell attachment and proliferation supports. Therefore, it can be concluded that the cost-effective PHB scaffold has the potential using as a biomaterial cell adhesion substrate in therapeutic applications.

Keywords: Polyhydroxybutyrate, biocompatible, scaffold, porous, tissue engineering

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Authors: Pajaree Donkhampa, Fuangfa Unob

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Ceftazidime is an antibiotic drug commonly used to treat several human and veterinary infections. However, the presence of ceftazidime residues in the environment may induce microbial resistance and cause side effects to humans. Therefore, monitoring the level of ceftazidime in environmental resources is important. In this work, a melamine foam platform was proposed for simultaneous extraction and colorimetric detection of ceftazidime based on the azo dye formation on the surface. The melamine foam was chemically modified with polyethyleneimine (PEI) and characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Ceftazidime is a sample that was extracted on the PEI-modified melamine foam and further reacted with nitrite in an acidic medium to form an intermediate diazonium ion. The diazotized molecule underwent an azo coupling reaction with chromotropic acid to generate a red-colored compound. The material color changed from pale yellow to pink depending on the ceftazidime concentration. The photo of the obtained material was taken by a smartphone camera and the color intensity was determined by Image J software. The material fabrication and ceftazidime extraction and detection procedures were optimized. The detection of a sub-ppm level of ceftazidime was achieved without using a complex analytical instrument.

Keywords: colorimetric detection, ceftazidime, melamine foam, extraction, azo dye

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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Authors: Islah Ud Din, Amna Bibi

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The current study was carried out to examine the perceived social support, resilience and relapse risk in recovered addicts. A purposive sampling technique was used to collect data from recovered addicts. A multidimensional scale of perceived social support by was used to measure the perceived social support. The brief Resilience Scale (BRS) was used to assess resilience. The Stimulant Relapse Risk Scale (SRRS) was used to examine the relapse risk. Resilience and Perceived social support have substantial positive correlations, whereas relapse risk and perceived social support have significant negative associations. Relapse risk and resilience have a strong inverse connection. Regression analysis was used to check the mediating effect of resilience between perceived social support and relapse risk. The findings revealed that perceived social support negatively predicted relapse risk. Results showed that Resilience plays a role as partial mediation between perceived social support and relapse risk. This Research will allow us to explore and understand the relapse risk factor and the role of perceived social support and resilience in recovered addicts. The study's findings have immediate consequences in the prevention of relapse. The study will play a significant part in drug rehabilitation centers, clinical settings and further research.

Keywords: perceived social support, resilience, relapse risk, recovered addicts, drugs addiction

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Authors: Noshaba Dilbar, Maria Jabbar

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Medicinal plants are considered to be the richest source of drug discovery. The main cause of medicinal properties of plants is the presence of bioactive compounds in them. Phytochemical screening is the valuable process that detects bioactive compounds(secondary metabolites) in plants. The present study was carried out to determine phytochemical profile and ethnobotanical importance of Capparidaceae species. ( Capparis spinosa and Dipterygium glaucum). The selection of plants was made on basis of traditional knowledge of their usage in ayurvedic medicines. Different type of solvents(ethanol, methanol, chloroform, benzene and petroleum ether) were used to make extracts of dry and fresh plants. Phytochemical screening was made by using various standard techniques. Results reveal the presence of large range of bioactive compounds i.e alakloids, saponins, flavonoids, terpenoids, glycosides, phenols and steroids. Methanol, petroleum ether and chloroform extracts showed high extractability of bioactive compounds. The results obtained ensure these plants a reliable source of pharmacological industry and can be used in making of various biological friendly drugs.

Keywords: bioactive compounds, Capparidaceae, phytochemical screening, secondary metabolites

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Authors: Danielle Page

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Foregoing studies, statistics, and medical evaluations have established a relationship between Posttraumatic stress disorder (PTSD) and criminal justice involvement in Vietnam veterans. War is highly trauma inducing and can leave combat veterans with mental disorders ranging from psychopathic thoughts to suicidal ideation. The majority of those suffering are unaware that they have PTSD, and as a coping mechanism, they often turn to self isolation. Beyond isolation, many veterans with symptomatic PTSD turn to aggression and substance abuse to cope with their internal agony. The most common crimes committed by veterans with PTSD fall into the assault and drug/alcohol abuse categories. Thus, a relationship is established between veteran populations and the criminal justice system. This dissertation aims to define the relationship between PTSD and criminal justice involvement in veterans, explore the mediating factors in this relationship, and analyze numerous court cases in this subject area. Further, it will examine the ways in which crime rates can be reduced for veterans with symptoms of PTSD. This ranges from the improvement of healthcare systems to the implementation of special courts to handle veteran cases.

Keywords: psychotraumatology, forensic psychology, PTSD, vietnam veterans

Procedia PDF Downloads 82

Authors: Rachel F. Ajayi, Unathi Sidwaba, Usisipho Feleni, Samantha F. Douman, Ezo Nxusani, Lindsay Wilson, Candice Rassie, Oluwakemi Tovide, Priscilla G.L. Baker, Sibulelo L. Vilakazi, Robert Tshikhudo, Emmanuel I. Iwuoha

Abstract:

Pyrazinamide (PZA) is among the first-line pro-drugs in the tuberculosis (TB) combination chemotherapy used to treat Mycobacterium tuberculosis. Numerous reports have suggested that hepatotoxicity due to pyrazinamide in patients is due to inappropriate dosing. It is therefore necessary to develop sensitive and reliable techniques for determining the PZA metabolic profile of diagnosed patients promptly and at point-of-care. This study reports the determination of PZA based on nanobiosensor systems developed from disuccinimidyl octanedioate modified Cytochrome P450-2E1 (CYP2E1) electrodeposited on gold substrates derivatised with (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs nanocomposites. The rapid and sensitive amperometric PZA detection gave a dynamic linear range of 2 µM to 16 µM revealing a limit of detection of 0.044 µM and a sensitivity of 1.38 µA/µM. The Michaelis-Menten parameters; KM, KMapp and IMAX were also calculated and found to be 6.0 µM, 1.41 µM and 1.51 µA respectively indicating a nanobiosensor suitable for use in serum.

Keywords: tuberculosis, cytochrome P450-2E1, disuccinimidyl octanedioate, pyrazinamide

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Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

Procedia PDF Downloads 358

Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

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There is a growing interest in the modeling and simulation of magnetic nanoalloys by various computational methods. Magnetic crystalline/amorphous nanoparticles (NP) are interesting materials from both the applied and fundamental points of view, as their properties differ from those of bulk materials and are essential for advanced applications such as high-performance permanent magnets, high-density magnetic recording media, drug carriers, sensors in biomedical technology, etc. As an important magnetic material, Fe-Ni based nanoalloys have promising applications in the chemical industry (catalysis, battery), aerospace and stealth industry (radar absorbing material, jet engine alloys), magnetic biomedical applications (drug delivery, magnetic resonance imaging, biosensor) and computer hardware industry (data storage). The physical and chemical properties of the nanoalloys depend not only on the particle or crystallite size but also on composition and atomic ordering. Therefore, computer modeling is an essential tool to predict structural, electronic, magnetic and optical behavior at atomistic levels and consequently reduce the time for designing and development of new materials with novel/enhanced properties. Although first-principles quantum mechanical methods provide the most accurate results, they require huge computational effort to solve the Schrodinger equation for only a few tens of atoms. On the other hand, molecular dynamics method with appropriate empirical or semi-empirical inter-atomic potentials can give accurate results for the static and dynamic properties of larger systems in a short span of time. In this study, structural evolutions, magnetic and electronic properties of Fe-Ni based nanoalloys have been studied by using molecular dynamics (MD) method in Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and Density Functional Theory (DFT) in the Vienna Ab initio Simulation Package (VASP). The effects of particle size (in 2-10 nm particle size range) and temperature (300-1500 K) on stability and structural evolutions of amorphous and crystalline Fe-Ni bulk/nanoalloys have been investigated by combining molecular dynamic (MD) simulation method with Embedded Atom Model (EAM). EAM is applicable for the Fe-Ni based bimetallic systems because it considers both the pairwise interatomic interaction potentials and electron densities. Structural evolution of Fe-Ni bulk and nanoparticles (NPs) have been studied by calculation of radial distribution functions (RDF), interatomic distances, coordination number, core-to-surface concentration profiles as well as Voronoi analysis and surface energy dependences on temperature and particle size. Moreover, spin-polarized DFT calculations were performed by using a plane-wave basis set with generalized gradient approximation (GGA) exchange and correlation effects in the VASP-MedeA package to predict magnetic and electronic properties of the Fe-Ni based alloys in bulk and nanostructured phases. The result of theoretical modeling and simulations for the structural evolutions, magnetic and electronic properties of Fe-Ni based nanostructured alloys were compared with experimental and other theoretical results published in the literature.

Keywords: density functional theory, embedded atom model, Fe-Ni systems, molecular dynamics, nanoalloys

Procedia PDF Downloads 243