Search results for: in silico drug designing

Authors: S. Rajeswari

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Medicinal Plant extracts and their bioactive compounds have been used for antimicrobial activities and have significant remedial properties. In the recent years, a wide range of investigations have been carried out throughout the world to confirm antimicrobial properties of different medicinally important plants. A number of plants showed efficient antimicrobial activities, which were comparable to that of synthetic standard drugs or antimicrobial agents. The large family Euphorbiaceae contains nearly about 300 genera and 7,500 speciesand one among is Ricinus communis or castor plant which has high traditional and medicinal value for disease free healthy life. Traditionally the plant is used as laxative, purgative, fertilizer and fungicide etc. whereas the plant possess beneficial effects such as anti-oxidant, antihistamine, antinociceptive, antiasthmatic, antiulcer, immunomodulatory anti diabetic, hepatoprotective, anti inflammatory, antimicrobial, and many other medicinal properties. This activity of the plant possess due to the important phytochemical constituents like flavonoids, saponins, glycosides, alkaloids and steroids. The presents study includes the phytochemical properties of Ricinus communis and to prediction of the anti-microbial activity of Ricinus communis using DNA gyrase of Staphylococcus aureus as molecular target. Docking results of varies chemicals compounds of Ricinus communis against DNA gyrase of Staphylococcus aureus by maestro 9.8 of Schrodinger show that the phytochemicals are effective against the target protein DNA gyrase. our studies suggest that the phytochemical from Ricinus communis such has INDICAN (G.Score 4.98) and SUPLOPIN-2(G.Score 5.74) can be used as lead molecule against Staphylococcus infections.

Keywords: euphorbiaceae, antimicrobial activity, Ricinus communis, Staphylococcus aureus

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Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang

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Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.

Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing

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Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

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Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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Authors: Krishna Dahiya

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Introduction: Labour pain has been described as the most severe pain experienced by women in their lives. Pain management in labour is one of the most important challenges faced by the obstetrician. The opioids are the primary treatment for patients with moderate and severe pain but these drugs are not always tolerated and are associated with dose-dependent side effects. Nonsteroidal anti-inflammatory drugs, too, are associated with variable adverse effects. Considering these factors, our study compared the efficacy and side effect of intravenous tramadol and paracetamol. Objective: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of tramadol for intrapartum analgesia. Methods: In a randomized prospective study at Pt. BDS PGIMS, 200 women in active labor were allocated to received either paracetamol (n=100) or tramadol (n=100). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events. Results: The mean age of cases were 25.55 ± 3.849 years and 25.60 ± 3.655 years respectively As recorded by the VAS score, there was significant pain reduction at 30 minutes, and at 1 and 2 hours in both groups (P<0.01). In comparison, between group I and II, a significantly higher rate of nausea and vomiting in tramadol group (14% vs 8%; P < 0.03) patients. Similarly, drowsiness (0% vs 11%; P<0.01), dry mouth (0% vs 8%; P<0.04) and dizziness (0% vs 9%; P<0.02) was also significant in group II. Conclusion: Due to difficulty in administering epidural analgesia to all parturients, administration of paracetamol and tramadol infusion for analgesia is simple and less invasive alternative. In the present study, both paracetamol and tramadol were equally effective for labour analgesia but paracetamol has emerged as safe alternative as compared to tramadol due to a low incidence of side effects.

Keywords: paracetamol, tramadol, labor, analgesia

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Authors: Meenakshi Chaudhary, V .S. Randhawa, M. Jais, R. Dutta

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Introduction: An outbreak of Multi drug resistant S. Typhi (i.e. resistance to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) occurred in 1990's in India which peaked in 1992-93 and resulted in the change of drug of choice from chloramphenicol to ciprofloxacin for enteric fever. Currently an emergence of Ciprofloxacin susceptible S. Typhi isolates in the region is being reported which appears to be chromosomally mediated. Methodology: Six hundred sixty four strains were randomly selected from the time period between January 2008-December 2011 at the National Salmonella Phage Typing Centre, LHMC, New Delhi. The strains were representative of the north, central and south zones of India. All isolates were subjected to serotyping, biotyping, phage typing and then to antimicrobial susceptibility testing by CLSI disk diffusion (CLSI) technique to Ciprofloxacin, Cefotaxime, Ampicillin, Chloramphenicol, Trimethoprim-Sulfomethoxazole and Tetracycline. Subsequently MIC of the isolates was determined by E-test (AB-Biodisc). Results: More than 80% of the tested strains had intermediate susceptibility to ciprofloxacin. The E test revealed the MIC (Ciprofloxacin) of these strains to be in the range of 0.12 to 0.5 µg/ml. Sixty nine percent of ciprofloxacin intermediate susceptible strains belonged to Phage type E1 and fourteen percent of these were Vi- Negative i.e these could not be typed by the phage typing scheme of Craigie and Yen. All the strains remained susceptible to cefotaxime. Conclusion: Predominant isolation of intermediate susceptible S. Typhi strains from India would alter the recommendations of empiric treatment of enteric fever in the region. Alternative to the low cost ciprofloxacin will have to be sought or increased dosage and/or duration of ciprofloxacin will have to be recommended. The reasons for the trend of increase in percentage of intermediate susceptible S. Typhi strains are not clear but may be attributed partly to the revision of CLSI guidelines in 2013.

Keywords: salmonella typhi, decreased ciprofloxacin susceptibility, ciprofloxacin, minimum inhibitory concentration

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Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu

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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.

Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition

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Authors: Karem H. Alzoubi, Ahmad S. Alkofahi, Omar F. Khabour, Nizar M. Mhaidat

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Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. In here, selected medicinal plant extracts from Jordan with high antioxidative capacity were tested for their protective effect against oxidative DNA damage using in vitro 8-hydroxydeoxyguanisine and sister chromatid exchanges (SCEs) assays in cultured human lymphocytes. The following plant extracts were tested Cupressus sempervirens L., Psidium guajava (L.) Gaerth., Silybum marianum L., Malva sylvestris L., Varthemia iphionoides Boiss., Eminium spiculatum L. Blume, Pistachia palaestina Boiss., Artemisia herba-alba Asso, Ficus carica L., Morus alba Linn , Cucumis sativus L., Eucalyptus camaldulensis Dehnh., Salvia triloba L., Zizyphus spina-christi L. Desf., and Laurus nobilis L. A fractionation scheme for the active plant extracts of the above was followed. Plants extract fractions with best protective properties against DNA damage included hexane fraction of S. marianum L. (aerial parts), chloroform fractions of P. palaestina Boiss. (Fruits), ethanolic fractions of E. camaldulensis Dehnh (leaves), S. triloba L. (leaves), and ethanolic fractions of Z. spina-christi L. Desf. (Fruits/leaves). On the other hand, the ethanolic extracts of V. iphionoides Boiss was found to increase oxidative DNA damage. Results of the SCEs are undergoing. In conclusion, plant extracts with antioxidative DNA damage properties might have clinical applications in cancer prevention.

Keywords: medicinal plants extract, fractionation, oxidative DNA damage, 8-hydroxydeoxyguanisine, SCEs, Jordan

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Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

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Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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Authors: S. Ahmed John

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Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

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Authors: Jorn Fricke, Frans Melissen

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Citizens in urban areas are prone to increased levels of stress due to urbanization, inadequate and overburdened infrastructure and services, and environmental degradation. Moreover, communities are fragile and subject to shocks and stresses through various social and political processes. A loss of (a sense of) community is often seen as related to increasing political and civic disintegration. Feelings of community can manifest themselves in various ways but underlying all these manifestations is the need for trust between people. One of the main drivers of trust between individuals is (shared) experiences. It is these shared experiences that may play an important role in building resilience, i.e., the ability of a community and its members to adapt to and deal with stresses, as well as ensure the ongoing development of a community. So far, experience design, as a discipline and academic field, has mainly focused on designing products or services. However, people-to-people experiences are the ones that play a pivotal role in building inclusiveness, safety, and resilience in communities. These experiences represent challenging objects of design as they develop in an interactive space of spontaneity, serendipity, and uniqueness that is based on intuition, freedom of expression, and interaction. Therefore, there is a need for research to identify which elements are required in designing the social and physical environment (or ‘experience scape’) to increase the chance for people-to-people experiences to be successful and what elements are required for these experiences to help in building resilience in urban communities that can resist shocks and stresses. By means of a comparative case study approach in urban areas in Germany and the Netherlands, using a range of qualitative research methods such as in-depth interviews, focus groups, participant observation, storytelling techniques, and life stories, this research identifies relevant actors and their roles in creating building blocks of optimal experience scrapes for building resilience in communities.

Keywords: community development, experiences, experience scapes, resilience

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Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake

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Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.

Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

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Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

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Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Iuliia Zarubiieva, Joyun Tseng, Vishwesh Kulkarni

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Recent researches has focused on nucleic acids as a substrate for designing biomolecular circuits for in situ monitoring and control. A common approach is to express them by a set of idealised abstract chemical reaction networks (ACRNs). Here, we present new results on how abstract chemical reactions, viz., catalysis, annihilation and degradation, can be used to implement circuit that accurately computes logarithm function using the method of Arithmetic-Geometric Mean (AGM), which has not been previously used in conjunction with ACRNs.

Keywords: chemical reaction networks, ratio computation, stability, robustness

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Authors: Naylya Djumaeva

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Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Purnima Pandit

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Malaria remains one of the world’s most deadly infectious disease and arguably, the greatest menace to modern society in terms of morbidity and mortality. To choose the right treatment and to ensure a quality of life suitable for a specific patient condition, early and accurate diagnosis of malaria is essential. It reduces transmission of disease and prevents deaths. Our work focuses on designing an efficient, accurate fuzzy inference system for malaria diagnosis.

Keywords: fuzzy inference system, fuzzy logic, malaria disease, triangular fuzzy number

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Gadia Duhita, Noorhana, Tjhin Wiguna

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Background: ADHD is the most common behavioural disorder in Indonesia. A stimulant, specifically methylphenidate, has been the first drug of choice for an ADHD treatment more than half a century. During the last decade, non-stimulant therapy (atomoxetine) for ADHD treatment has been developing. Growing evidence of its efficacy and the difference in its side effects profile to stimulant therapy have made methylphenidate’s position as a first line therapy for ADHD in need of re-evaluation. Both methylphenidate and atomoxetine have proven themselves against placebos in reducing core symptoms of ADHD. More recent studies directly compare the efficacy of methylphenidate and atomoxetine. Objective: The objective of this paper is to find out if either methylphenidate or atomoxetine is superior to another. This paper will assess the validity, importance, and applicability of current available evidence which compare the effectivity, efficacy, and safety of methylphenidate to atomoxetine for treatment in children and adolescents with ADHD. Method: The articles were searched for through the PubMed and Cochrane databases with “attention deficit/hyperactivity disorder OR adhd”, “methylphenidate”, and “atomoxetine” as the search keywords. Two articles which were relevant and eligible were chosen by using inclusion and exclusion criterias to be critically appraised. Result: The study by Hazel et al. showed that the efficacy of methylphenidate and atomoxetine are comparable for treatment in child and adolescent ADHD. The result shows 53.6% (95% CI 48.5%-58.4%) of the patient responded to the treatment by atomoxetine and 54.4% (95% CI 47.6%-61.1%) patients responded to methylphenidate, with the difference in proportion of–0.9% (95% CI –9.2%-7.5%). The other study by Hanwella et al. also showed that the efficacy of atomoxetine was not inferior to metilphenidate (SMD = 0.09, 95% CI –0.08-0.26) (Z = 1.06, p = 0.29). However, the sub-group analysis showed that OROS methylphenidate is more effective compared to atomoxetine (SMD = 0.32, 95% CI 0.12-0.53) (Z = 3.05, p < 0.02). Conclusion: The efficacy of methylphenidate and atomoxetine in reducing symptoms of ADHD is comparable. None is proven inferior to another. The choice of pharmacological tratment children and adolescents with ADHD should be made based on contraindication and the side effects profile of each drug.

Keywords: attention deficit/hyperactivity disorder, ADHD, atomoxetine, methylphenidate

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Kiana Zeighami, Morteza Ozlati Moghadam

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Designing a high accuracy and high precision motion controller is one of the important issues in today’s industry. There are effective solutions available in the industry but the real-time performance, smoothness and accuracy of the movement can be further improved. This paper discusses a complete solution to carry out the movement of three stepper motors in three dimensions. The objective is to provide a method to design a fully integrated System-on-Chip (SOC)-based motion controller to reduce the cost and complexity of production by incorporating Field Programmable Gate Array (FPGA) into the design. In the proposed method the FPGA receives its commands from a host computer via wireless internet communication and calculates the motion trajectory for three axes. A profile generator module is designed to realize the interpolation algorithm by translating the position data to the real-time pulses. This paper discusses an approach to implement the linear interpolation algorithm, since it is one of the fundamentals of robots’ movements and it is highly applicable in motion control industries. Along with full profile trajectory, the triangular drive is implemented to eliminate the existence of error at small distances. To integrate the parallelism and real-time performance of FPGA with the power of Central Processing Unit (CPU) in executing complex and sequential algorithms, the NIOS II soft-core processor was added into the design. This paper presents different operating modes such as absolute, relative positioning, reset and velocity modes to fulfill the user requirements. The proposed approach was evaluated by designing a custom-made FPGA board along with a mechanical structure. As a result, a precise and smooth movement of stepper motors was observed which proved the effectiveness of this approach.

Keywords: 3-axis linear interpolation, FPGA, motion controller, micro-stepping

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Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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Authors: Mbuso Siwela

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Background: The Sub-Saharan Africa region has the greatest number of people eligible to receive antiretroviral treatment (ART). Multi-month Drug dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. In Eswatini, however, few children and adolescents are on MMD. Young Heroes is implementing an HIV program that aims to avert new HIV infections in children and youth and improve treatment outcomes for children and adolescents living with HIV (C/ALHIV: 0-19 Years) and OVC caregivers with HIV prevention and impact mitigation interventions that prevent new HIV infections and reduce vulnerability. Aim of the study: The study aimed to ascertain factors that are associated with the assignment of the MMD model on C/ALHIVs. Methodology: The project provides treatment adherence support through well-trained community cadres (Home Visitors - HVs) at both community and health facility levels. During door-to-door visits, HVs track all C/ALHIV enrolled in the project monthly and refer any who might have stopped or interrupted treatment. C/ALHIV with unsuppressed viral load is supported through case conferencing and teen clubs. A quantitative cross-sectional analysis was conducted using STATA for children and adolescents living with HIV enrolled in the project. Bivariate analysis was conducted, and the Logistic Regression model was used to ascertain the effects of duration on ART on the choice of MMD model. Results: Data for 544 C/ALHIV (0-19 Years) was analyzed in STATA. Results show a strong association between (duration on ART, Age, being in teen club) and enrolment in an MMD model. Duration on ART is a major predictor for the choice of MMD model at (95% CI: 0.0012905 – 0.0039812; P = <0.0001). C/ALHIV who have been on ART for less than a year are less likely to be on MMD. C/ALHIVs who are 1 or more years on ART are more likely to be in 3 months dispensing, while those who are 5 years or more are most likely to be in 6 months model.

Keywords: C/ALHIV, OVC, HIV, treatment

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Authors: Enny Suswati, Supangat Supangat

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Background. Ready-to-eat food products are becoming increasingly popular because consumers are increasingly busy, competitive, and changing lifestyles. Examples of ready-to-eat foods include crispy fried chicken. Escherichia coli is one of the most important causes of food-borne diseases and the most frequent antibiotic-resistant pathogen globally. This study assessed the prevalence and antibiotic resistance profile of E. coli from ready-to-eat crispy fried chicken in Jember city, Indonesia. Methodology. This cross-sectional study was conducted from November 2020 to April 2021 by collecting 81crispy fried chicken samples from 27 food stalls in campus area using a simple random sampling method. Isolation and determination of E. coli use were performed by conventional culture method. An antibiotic susceptibility test was conducted using Kirby Bauer disk diffusion method on the Mueller–Hinton agar. Result. Out of 81crispy fried chicken samples, 77 (95.06%) were positive for E. coli. High E. coli drug resistance was observed on ampicillin, amoxicillin (100%) followed by cefixime (98.72%), erythromycin (97.59%), sulfamethoxazole (93.59%), azithromicin (83.33%), cefotaxime (78.28%), choramphenicol (75.64%), and cefixime (74.36%). On the other hand, there was the highest susceptibility for ciprofloxacin (64.10%). The multiple antibiotic resistance indexes of E. coli isolates varied from 0.4 to 1. The predominant antimicrobial resistance profiles of E. coli were CfmCroAmlAmpAzmCtxSxtCE (n=17), CfmCroAmlCipAmpAzmCtxSxtCE (n=16), and CfmAmlAmpAzmCtxSxtCE (n=5), respectively. Multidrug resistance was also found in the isolates' 76/77 (98.70%). Conclusion. The resistance pattern CfmCroAmlAmpAzmCtxSxtCE was the most common among the E. coli isolates, with 17 showing it. The multiple antibiotic index (MAR index) ranged from 0.4 to 1. Hygienic measures should be rigorously implemented and monitoring resistance of E. coli is required to reduce the risks related to the emergence of multi-resistant bacteria

Keywords: antibacterial drug, ready to eat, crispy fried chicken, escherichia coli

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Authors: Mohammed Aijaz

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In industries, to transfer fragile materials like glasses, a holding, lifting, and manipulation system are required. In this report, we designed and analysed a suction cup holding, lifting, and manipulation system that is attached to a head plate and must be able to grip/hold securely, the largest glass panel with 3m x 2.5m x 20mm thick with a mass of 115 kg. The system is able to rotate the panel through 180 degrees in the X, Y, and Z axis in any direction from the outer reach of the robotic arm. The structural analysis is performed to verify the structural strength of the suction cup’s head plate system.

Keywords: designing, mechanical, engineering, suction

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