Search results for: drug screening

Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

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The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

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Authors: Jully Handoko, B. Kuntoro, E. Saleh, Sadarman

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Most farmers in Bangkinang Seberang sub district raise Bali cattle in semi-intensive husbandry system. The farmers believe that raising such a way is economical and quite effective. The farmers do not need to provide forage and plant feed crops. Furthermore, the raising method is considered not to interfere with the main job. Screening for anemia in Bali cattle of Bangkinang Seberang subdistrict, Kampar regency, Riau, Indonesia, had been conducted. The aim of the study was to analyze hematological alterations in the anemic Bali cattle. A number of 75 Bali cattle were screened for anemia on the basis of Hemoglobin (Hb) concentration. The other hematological parameters that were measured including packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). The screening showed that 18 (24.00%) of Bali cattle were anemic. Levels of Hb, PCV, TEC, MCV, MCH and MCHC in anemic Bali cattle were 7.15±1.61 g/dl, 21.15±4.16%, 3.72±1.10x106/µl, 52.75±4.13 fl, 17.31±1.86 pg and 32.77±1.69 g/dl respectively. Hematological values of Hb, PCV, TEC, MCV, MCH and MCHC were significantly (p < 0.05) lower in anemic Bali cattle compared to non-anemic Bali cattle.

Keywords: anemia, Bali cattle, alterations, hematology

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Authors: Sandra Figueiredo

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To guarantee the well-being and the academic achievement it is crucial into the global society to develop techniques to assess language competence and control psychological aspects on the second language learning context. The current scenario of the war conflicts that are emerging mostly in Europe and Middle East have been resulting in forced immigration and refugees’ maladjustment. The inclusion is the priority for United Nations concerning the sustainability of societies. For inclusion, psychological screening tests and educational tools are urgent. Method: Approximately 100 refugees from Ukraine were assessed, in Portugal, under the administration of the PCL-5. This 20-item instrument evaluates the Post-Traumatic Disorder. Expected results: The statistical analysis will be performed with the International Database Analyzer and SPSS (v. 28). The results expected are the relationship between traumatic events caused by war and post-traumatic symptomatology (anxiety, hypervigilance, stress). Implications: The data will be discussed concerning the problems of belonging, the psychological constraints and educational attainment (language needs included) experienced by the individuals more recently arrived to the hosting societies. The refugees’ acculturation process and the emotional regulation will be addressed.

Keywords: refugees, immigration, educational needs, trauma, inclusion, second language.

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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Authors: Kwanputtha Arunprasert, Chaiyakarn Pornpitchanarong, Praneet Opanasopit, , Prasopchai Patrojanasophon

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Capsaicin, a recently FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like burning sensation and erythema leading to severe skin irritation and poor patient compliance. These unwanted side effects are due to the rapid penetration of capsaicin into the epidermis and low permeation to the dermis layer. The purpose of this study was to develop nanostructured lipid carriers (NLCs) that entrapped capsaicin for reducing dermal irritation. Solid lipid (glyceryl monostearate (GM), cetyl palmitate (CP), cetyl alcohol (COH), stearic acid (SA), and stearyl alcohol (SOH)) and surfactant (Tween®80, Tween®20, and Span®20) were varied to obtained optimal capsaicin-loaded NLCs. The formulation using CP as solid lipid and Tween®80 as a surfactant (F2) demonstrated the smallest size, excellent colloidal stability, and narrow range distribution of the particles as being analyzed using Zetasizer. The obtained capsaicin-loaded NLCs were then characterized by entrapment efficiency (EE) and loading capacity (LC). The release characteristics followed Higuchi kinetics, and the prolonged capsaicin release may result in the reduction in skin irritation. These results could demonstrate the potentials of capsaicinloaded lipid-based nanoparticles for topical drug delivery.

Keywords: capsaicin, lipid-based nanoparticles, nanostructured lipid carriers, topical drug delivery system

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Authors: Melkamu Tadesse Getachew

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Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Parsa Naji

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Following the Iran Islamic Revolution in 1979 and the subsequent formation of a theocratic regime, the new regime implemented stringent regulations and a complicated censorship system in the film industry. Thereupon, the screening of films showing the relationships between males and females encountered numerous limitations. Not only did these limits encompass the physical portrayal of the relationship between males and females, but also the dialogues containing explicit sexual or even passionate romantic themes, resulting in a film being permanently consigned to archival storage. However, despite these limitations, Iranian filmmakers persevered in creating their interesting cinematic works. Throughout the years after the revolution, Iranian directors have navigated a series of challenges and obstacles, employing innovative and unconventional methods to bypass the rigorous censorship system imposed by the government, ensuring the screening of their films. This study aims to analyze the creative approaches employed by Iranian filmmakers to circumvent governmental censorship regulations.

Keywords: censorship, Iranian cinema, Islamic revolution, male-female relationship

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Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

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Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

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Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: Malahat Rezaee, Mahiran Basri, Raja Noor Zaliha Raja Abdul Rahman, Abu Bakar Salleh

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Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that have been progressively considered in pharmaceutical science for transdermal delivery of drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils; contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research was aimed to study the effect of O/S ratio on stability and rheological behavior of sodium diclofenac loaded and unloaded palm kernel oil esters nanoemulsion systems. The effect of different O/S ratio of 0.25, 0.50, 0.75, 1.00 and 1.25 on stability of the drug-loaded and unloaded nanoemulsion formulations was evaluated by centrifugation, freeze-thaw cycle and storage stability tests. Lecithin and cremophor EL were used as surfactant. The stability of the prepared nanoemulsion formulations was assessed based on the change in zeta potential and droplet size as a function of time. Instability mechanisms including coalescence and Ostwald ripening for the nanoemulsion system were discussed. In comparison between drug-loaded and unloaded nanoemulsion formulations, drug-loaded formulations represented smaller particle size and higher stability. In addition, the O/S ratio of 0.5 was found to be the best ratio of oil and surfactant for production of a nanoemulsion with the highest stability. The effect of O/S ratio on rheological properties of drug-loaded and unloaded nanoemulsion systems was studied by plotting the flow curves of shear stress (τ) and viscosity (η) as a function of shear rate (γ). The data were fitted to the Power Law model. The results showed that all nanoemulsion formulations exhibited non-Newtonian flow behaviour by displaying shear thinning behaviour. Viscosity and yield stress were also evaluated. The nanoemulsion formulation with the O/S ratio of 0.5 represented higher viscosity and K values. In addition, the sodium diclofenac loaded formulations had more viscosity and higher yield stress than drug-unloaded formulations.

Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, rheoligy, stability

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Authors: Issam M Hajjaji, Adel Tajoury, Salah R Benhamid

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The MENA region has the highest prevalence of diabetes in the world. Various risk scores were developed, not all appropriate locally. The objective of this study is to apply the FINDRISC Score to adult Libyan males to determine its significance, sensitivity, specificity and Positive Predictive Values as an initial screening tool for type 2 diabetes, and suggest a cut-off point. Methods: 600 subjects answered the questionnaire at their place of work, and their waist, weight, height & BP were measured. Thereafter, after excluding those with known diabetes, an Oral Glucose Tolerance Test was done. Results: 414 subjects aged 19-78 completed the questionnaire and tests. 35 (8.4%) had impaired glucose tolerance (IGT) and 13 (3.1%) had diabetes (DM). The AUC-ROC for IGT was 0.614 (95% CI: 0.527-0.701), for DM 0.810 (95% CI: 0.709-0.911) and for both 0.689 (95% CI: 0.609-0.769). The Positive Predictive Value for a cut-off score of 5 were 15.5%, 11.7% & 5.7% for both conditions combined, prediabetes & diabetes respectively. The equivalent values for a cut-off score of 8 were 16.1%, 9.0% & 7.7%. The Negative Predictive Values were uniformly above 90%. Conclusions & Recommendations: The FINDRISC Score had a low predictive value for dysglycaemia in this sample and performed at a level of significance for IGT that is similar to other MENA countries, but did better for DM. A larger sample that included women is suggested, with a view of adjusting the Score to suit the local population.

Keywords: diabetes, FINDRISK, Libya, prediabetes

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Chayanika Rout, Debjani Chakraborty, Adrijit Goswami

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Our work presents an inventory model which illustrates imperfect production and imperfect inspection processes for deteriorating items. A cost-minimizing model is studied considering two types of inspection errors, namely, Type I error of falsely screening out a proportion of non-defects, thereby passing them on for rework and Type II error of falsely not screening out a proportion of defects, thus selling those to customers which incurs a penalty cost. The screened items are reworked; however, no returns are entertained due to deteriorating nature of the items. In more practical situations, certain parameters such as the demand rate and the deterioration rate of inventory cannot be accurately determined, and therefore, they are assumed to be triangular fuzzy numbers in our model. We calculate the optimal lot size that must be produced in order to minimize the total inventory cost for both the crisp and the fuzzy models. A numerical example is also considered to exemplify the procedure which is followed by the analysis of sensitivity of various parameters on the decision variable and the objective function.

Keywords: deteriorating items, EPQ, imperfect quality, rework, type I and type II inspection errors

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Authors: Khlood F. Salman, Richard Zoucha, Hani Nawafleh

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Introduction: Jordan ranks the fourth highest breast cancer prevalence after Lebanon, Bahrain, and Kuwait. Considerable evidence showed that cultural, ethnic, and economic differences influence a woman’s practice to early detection and prevention of breast cancer. Objectives: To understand women’s health beliefs and values in relation to early detection of breast cancer; and to explore the impact of these beliefs on their decisions regarding reluctance or acceptance of early detection measures such as mammogram screening. Design: A qualitative focused ethnography was used to collect data for this study. Settings: The study was conducted in the second largest city surrounded by a large rural area in Ma’an- Jordan. Participants: A total of twenty seven women, with no history of breast cancer, between the ages of 18 and older, who had prior health experience with health providers, and were willing to share elements of personal health beliefs related to breast health within the larger cultural context. The participants were recruited using the snowball method and words of mouth. Data collection and analysis: A short questionnaire was designed to collect data related to socio demographic status (SDQ) from all participants. A Semi-structured interviews guide was used to elicit data through interviews with the informants. Nvivo10 a data manager was utilized to assist with data analysis. Leininger’s four phases of qualitative data analysis was used as a guide for the data analysis. The phases used to analyze the data included: 1) Collecting and documenting raw data, 2) Identifying of descriptors and categories according to the domains of inquiry and research questions. Emic and etic data is coded for similarities and differences, 3) Identifying patterns and contextual analysis, discover saturation of ideas and recurrent patterns, and 4) Identifying themes and theoretical formulations and recommendations. Findings: Three major themes were emerged within the cultural and religious context; 1. Fear, denial, embarrassment and lack of knowledge were common perceptions of Ma’anis’ women regarding breast health and screening mammography, 2. Health care professionals in Jordan were not quick to offer information and education about breast cancer and screening, and 3. Willingness to learn about breast health and cancer prevention. Conclusion: The study indicated the disparities between the infrastructure and resourcing in rural and urban areas of Jordan, knowledge deficit related to breast cancer, and lack of education about breast health may impact women’s decision to go for a mammogram screening. Cultural beliefs, fear, embarrassments as well as providers lack of focus on breast health were significant contributors against practicing breast health. Health providers and policy makers should provide resources for the establishment health education programs regarding breast cancer early detection and mammography screening. Nurses should play a major role in delivering health education about breast health in general and breast cancer in particular. A culturally appropriate health awareness messages can be used in creating educational programs which can be employed at the national levels.

Keywords: breast health, beliefs, cultural context, ethnography, mammogram screening

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Authors: Massimiliano Panella, Sara Bortoluzzi, Sophia Russotto, Daniele Nicolini, Carmela Rinaldi

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Osteoporosis affects more than 200 million people worldwide. About 75% of osteoporosis cases are undiagnosed or diagnosed only when a bone fracture occurs. Since osteoporosis related fractures are significant determinants of the burden of disease and health and social costs of aging populations, we believe that this is the early identification and treatment of high-risk patients should be a priority in actual healthcare systems. Screening for osteoporosis by dual energy x-ray absorptiometry (DEXA) is not cost-effective for general population. An alternative is pulse-echo ultrasound (PEUS) because of the minor costs. To this end, we developed an early detection program for osteoporosis with PEUS, and we evaluated is possible impact and sustainability. We conducted a cross-sectional study including 1,050 people in Italy. Subjects with >1 major or >2 minor risk factors for osteoporosis were invited to PEUS bone mass density (BMD) measurement at the proximal tibia. Based on BMD values, subjects were classified as healthy subjects (BMD>0.783 g/cm²) and pathological including subjects with suspected osteopenia (0.783≤BMD>0.719 g/cm²) or osteoporosis (BMD ≤ 0.719 g/cm²). The responder rate was 60.4% (634/1050). According to the risk, PEUS scan was recommended to 436 people, of whom 300 (mean age 45.2, 81% women) accepted to participate. We identified 240 (80%) healthy and 60 (20%) pathological subjects (47 osteopenic and 13 osteoporotic). We observed a significant association between high risk people and reduced bone density (p=0.043) with increased risks for female gender, older ages, and menopause (p<0.01). The yearly cost of the screening program was 8,242 euros. With actual Italian fracture incidence rates in osteoporotic patients, we can reasonably expect in 20 years that at least 6 fractures will occur in our sample. If we consider that the mean costs per fracture in Italy is today 16,785 euros, we can estimate a theoretical cost of 100,710 euros. According to literature, we can assume that the early treatment of osteoporosis could avoid 24,170 euros of such costs. If we add the actual yearly cost of the treatments to the cost of our program and we compare this final amount of 11,682 euros to the avoidable costs of fractures (24,170 euros) we can measure a possible positive benefits/costs ratio of 2.07. As a major outcome, our study let us to early identify 60 people with a significant bone loss that were not aware of their condition. This diagnostic anticipation constitutes an important element of value for the project, both for the patients, for the preventable negative outcomes caused by the fractures, and for the society in general, because of the related avoidable costs. Therefore, based on our finding, we believe that the PEUS based screening performed could be a cost-effective approach to early identify osteoporosis. However, our study has some major limitations. In fact, in our study the economic analysis is based on theoretical scenarios, thus specific studies are needed for a better estimation of the possible benefits and costs of our program.

Keywords: osteoporosis, prevention, public health, screening

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Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite

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Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.

Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)

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Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

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Authors: Radhika S. Oke, Rebecca S. Thombre

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Medicinal plants and herbs have a great history of their utility as remedy for treatment of variety of ailments. Secondary metabolites present in these plants are responsible for their medicinal activity. In the present investigation, phytochemical screening of aqueous and alcoholic leaf extract of Anethum graveolens L. was performed. Total phenolic content and total antioxidant activity of the extracts was quantitatively estimated by Folin-Ciocalteau method and DPPH (1, 1-Diphenyl-2-picryl hydrazyl) method respectively. Qualitative tests suggested that Alkaloids, tannins and phenolic compounds were present in all the extracts of the plant. Aqueous extracts was found to have more phytochemicals as compared to alcoholic extracts. Extract of Anethum graveolens L. was found to contain good amount phenolics and exhibited antioxidant activity. The extracts also demonstrated potent antimicrobial activity against selected gram positive and negative bacteria. The study revealed the potential application of Anethum graveolens L. (Dill) in medicine and health.

Keywords: Anethum graveolens L., antioxidant, antimicrobial activity, medicine and health

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Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

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Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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Authors: Peter Yamoah, Frasia Oosthuizen

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Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

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An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

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Authors: Husham Bayazed

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A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Vera Sovkova, Andrea Mickova, Matej Buzgo, Karolina Vocetkova, Eva Filova, Evzen Amler

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PCL (poly-ε-caprolactone) nanofibrous scaffolds with adhered liposomes were prepared and tested as a possible drug delivery system for various synthetic growth factors. TGFβ, bFGF, and IGF-I have been shown to increase hMSC (human mesenchymal stem cells) proliferation and to induce hMSC differentiation. Functionalized PCL nanofibers were prepared with synthetic growth factors encapsulated in liposomes adhered to them in three different concentrations. Other samples contained PCL nanofibers with adhered, free synthetic growth factors. The synthetic growth factors free medium served as a control. The interaction of liposomes with the PCL nanofibers was visualized by SEM, and the release kinetics were determined by ELISA testing. The potential of liposomes, immobilized on the biodegradable scaffolds, as a delivery system for synthetic growth factors, and as a suitable system for MSCs adhesion, proliferation and differentiation in vitro was evaluated by MTS assay, dsDNA amount determination, confocal microscopy, flow cytometry and real-time PCR. The results showed that the growth factors adhered to the PCL nanofibers stimulated cell proliferation mainly up to day 11 and that subsequently their effect was lower. By contrast, the release of the lowest concentration of growth factors from liposomes resulted in gradual proliferation of MSCs throughout the experiment. Moreover, liposomes, as well as free growth factors, stimulated type II collagen production, which was confirmed by immunohistochemical staining using monoclonal antibody against type II collagen. The results of this study indicate that growth factors enriched liposomes adhered to surface of PCL nanofibers could be useful as a drug delivery instrument for application in short timescales, be combined with nanofiber scaffolds to promote local and persistent delivery while mimicking the local microenvironment. This work was supported by project LO1508 from the Ministry of Education, Youth and Sports of the Czech Republic

Keywords: drug delivery, growth factors, hMSC, liposomes, nanofibres

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Authors: Kwok W. Mui, Ling T. Wong, Tsz W. Tsang

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Many Hong Kong people nowadays spend most of their lifetime working indoor. Since poor Indoor Air Quality (IAQ) potentially leads to discomfort, ill health, low productivity and even absenteeism in workplaces, a call for establishing statutory IAQ control to safeguard the well-being of residents is urgently required. Although policies, strategies, and guidelines for workplace IAQ diagnosis have been developed elsewhere and followed with remedial works, some of those workplaces or buildings have relatively late stage of the IAQ problems when the investigation or remedial work started. Screening for IAQ problems should be initiated as it will provide information as a minimum provision of IAQ baseline requisite to the resolution of the problems. It is not practical to sample all air pollutants that exit. Nevertheless, as a statutory control, reliable, rapid screening is essential in accordance with a compromise strategy, which balances costs against detection of key pollutants. This study investigates the feasibility of using an IAQ index as a parameter of IAQ control in Hong Kong. The index is a screening parameter to identify the unsatisfactory workplace IAQ and will highlight where a fully effective IAQ monitoring and assessment is needed for an intensive diagnosis. There already exist a number of representative common indoor pollutants based on some extensive IAQ assessments. The selection of pollutants is surrogate to IAQ control consists of dilution, mitigation, and emission control. The IAQ Index and assessment will look at high fractional quantities of these common measurement parameters. With the support of the existing comprehensive regional IAQ database and the IAQ Index by the research team as the pre-assessment probability, and the unsatisfactory IAQ prevalence as the post-assessment probability from this study, thresholds of maintaining the current measures and performing a further IAQ test or IAQ remedial measures will be proposed. With justified resources, the proposed IAQ Index and assessment protocol might be a useful tool for setting up a practical public IAQ surveillance programme and policy in Hong Kong.

Keywords: assessment, index, indoor air quality, surveillance programme

Procedia PDF Downloads 267