Search results for: sedative drugs

Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Adnan Lanjawi

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This paper is carried out to investigate the management of hazardous waste in the chemistry section which belongs to Dubai Police forensic laboratory. The chemicals are the main contributor toward the accumulation of hazardous waste in the section. This is due to the requirement to use it in analysis, such as of explosives, drugs, inorganic and fire debris cases. This leads to negative effects on the environment and to the employees’ health and safety. The research investigates the quantity of chemicals there, the labels, the storage room and equipment used. The target is to reduce the need for disposal by looking at alternative options, such as elimination, substitution and recycling. The data was collected by interviewing the top managers there who have been working in the lab more than 20 years. Also, data was collected by observing employees and how they carry out experiments. Therefore, a survey was made to assess their knowledge about the hazardous waste. The management of hazardous chemicals in the chemistry section needs to be improved. The main findings illustrate that about 110 bottles of reference substances were going to be disposed of in 2014. These bottles were bought for about 100,000 UAE Dirhams (£17,600). This means that the management of substances purchase is not organised. There is no categorisation programme in place, which makes the waste control very difficult. In addition, the findings show that chemical are segregated according to alphabetical order, whereas the efficient way is to separate them according to their nature and property. In addition, the research suggested technology and experiments to follow to reduce the need for using solvents and chemicals in the sample preparation.

Keywords: control, hazard, laboratories, waste,

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Md. Danish Eqbal, Venkat Gundabala

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Microparticles and microcapsules are basically used as a carrier for cells, tissues, drugs, and chemicals. Due to its biocompatibility, non-toxicity and biodegradability, alginate based microparticles have numerous applications in drug delivery, tissue engineering, organ repair and transplantation, etc. The production of uniform monodispersed microparticles was a challenge for the past few decades. However, emergence of microfluidics has provided controlled methods for the generation of the uniform monodispersed microparticles. In this work, we present a successful method for the generation of both microparticles and microcapsules (single and double core) using merging approach of two droplets, completely inside the microfluidic device. We have fabricated hybrid glass- PDMS (polydimethylsiloxane) based microfluidic device which has coflow geometry as well as the T junction channel. Coflow is used to generate the single as well as double oil-alginate emulsion in oil and T junction helps to form the calcium chloride droplets in oil. The basic idea is to match the frequency of the alginate droplets and calcium chloride droplets perfectly for controlled generation. Using the merging of droplets technique, we have successfully generated the microparticles and the microcapsules having single core as well as double and multiple cores. The cores in the microcapsules are very stable, well separated from each other and very intact as seen through cross-sectional confocal images. The size and the number of the cores along with the thickness of the shell can be easily controlled by controlling the flowrate of the liquids.

Keywords: double-core, droplets, microcapsules, microparticles

Procedia PDF Downloads 241

Authors: Soo Hong Da, Ng Zheng Yao, Burra Venkata Durga Kumar

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The Healthcare sector is a business that consists of providing medical services, manufacturing medical equipment and drugs as well as providing medical insurance to the public. Most of the time, the data stored in the healthcare database is to be related to patient’s information which is required to be accurate when it is accessed by authorized stakeholders. In distributed systems, one important issue is concurrency in the system as it ensures the shared resources to be synchronized and remains consistent through multiple read and write operations by multiple clients. The problems of concurrency in the healthcare sector are who gets the access and how the shared data is synchronized and remains consistent when there are two or more stakeholders attempting to the shared data simultaneously. In this paper, a framework that is beneficial to distributed healthcare sector concurrent environment is proposed. In the proposed framework, four different level nodes of the database, which are national center, regional center, referral center, and local center are explained. Moreover, the frame synchronization is not symmetrical. There are two synchronization techniques, which are complete and partial synchronization operation are explained. Furthermore, when there are multiple clients accessed at the same time, synchronization types are also discussed with cases at different levels and priorities to ensure data is synchronized throughout the processes.

Keywords: resources, healthcare, concurrency, synchronization, stakeholders, database

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Authors: Prasanthi Malapati, R. Reshma, Vijay Soni, Perumal Yogeeswari, Dharmarajan Sriram

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In the present study, we attempted to develop Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose, glutamate racemase (coded by MurI gene) was selected. This enzyme racemize L-glutamate to D-glutamate required for the construction of peptidoglycan in the bacterial cell wall synthesis process. Furthermore this enzyme is neither expressed nor its product, D-glutamate is normally found in mammals, and hence designing inhibitors against this enzyme will not affect the host system as well act as potential antitubercular drugs. A library of BITS in house compounds were screened against Mtb MurI enzyme. Based on docking score, interactions and synthetic feasibility one hit lead was identified. Further optimization of lead was attempted and its derivatives were synthesized. Forty eight derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7 cell line. Chemical derivatization of the lead resulted in compounds NR-1213 AND NR-1124 as the potent M. tuberculosis glutamate racemase inhibitors with IC50 of 4-5µM which are remarkable and were found to be non-cytotoxic. Molecular dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.

Keywords: cell wall biosynthesis, dormancy, glutamate racemase, tuberculosis

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Authors: Argaw Amare, Abbuna Fuffa, Stringer Andy

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Improving public knowledge and changing their attitudes towards antibiotic use will be a crucial early strategy to contain Antibiotic resistance. The current study was undertaken from November 2015 to June 2016. A cross-sectional survey using a pretested questionnaire was conducted on 392 residents (330 male and 62 female) aged 18 and above. Participants were selected randomly. Data was analyzed using simple descriptive statistics; the Chi-square test was used to determine any significant difference. The majority of participants (81%) were farmers in their occupation. Most of the respondents (76%) were not able to define the difference between antimicrobials and antibiotics. Furthermore, (61%) of participants were not able to define what antibiotics and for what purpose they are used. Thirty-four percent of participants do not know the names of antibiotics they have used for their animals and for themselves. Nearly 68% have no knowledge about the disease they have been treated for. The majority of participants (73.5%) agree to complete their course of treatment even if they feel better. About 72.5% of participants disagree that antibiotics are safe and can be used to treat different diseases, without prescription. Most of the participants (95%) treat their animals after diagnosis; more than 80% of them agree to not purchase veterinary drugs from local traders. This study showed that the participants have poor knowledge and good attitude, with an average score of 41.3±16.1% and 79.6±16, respectively. Knowledge and attitude are significantly correlated (p<0.01). The participants in this study had a good attitude toward the rational use of antibiotics. Whereas they lack knowledge with regard to the kinds of antibiotics and the diseases they are prescribed for. Therefore, further educational interventions are necessary to improve their understanding of the antibiotics currently available and the major bacterial diseases they are prescribed.

Keywords: AMR, knoweledge, attitude, perception

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Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

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Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

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Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

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Authors: Jawad Alzeer

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Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

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Authors: Mona Mahmoud Abou Samra, Alaa Hamed Salama, Ghada Awad, Soheir Said Mansy

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Proniosomes are well documented for topical drug delivery and preferred over other vesicular systems because they are biodegradable, biocompatible, non-toxic, possess skin penetration ability and prolong the release of drugs by acting as depot in deeper layers of skin. Proniosome drug delivery was preferred due to improved stability of the system than niosomes. The present investigation aimed at formulation development and performance evaluation of proniosomal gel as a vesicular drug carrier system for antifungal drug tolnaftate. Proniosomes was developed using different nonionic surfactants such as span 60 and span 65 with cholesterol in different molar ratios by the Coacervation phase separation method in presence or absence of either lecithin or phospholipon 80 H. Proniosomal gel formulations of tolnaftate were characterized for vesicular shape & size, entrapment efficiency, rheological properties and release study. The effect of surfactants and additives on the entrapment efficiency, particle size and percent of drug released was studied. The selected proniosomal formulations for topical delivery of tolnaftate was subjected to a microbiological study in male rats infected with Trichophyton rubrum; the main cause of Tinea Pedis compared to the free drug and a market product and the results was recorded.

Keywords: fungal infection, proniosome, tolnaftate, trichophyton rubrum

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Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

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Authors: Chowdhury Md. Navim Kabir

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Renal impairment is one of the most severe non-communicable diseases around the world. Especially patients with diagnosed/newly diagnosed renal impairment who need surgery are more focused on preoperative and postoperative preparation. Serum creatinine is the prime biochemical marker for assessing renal function, and the level of impairment is widely measured by this marker as well as Glomerular Filtration Rate (GFR). Objective: Factors responsible for fluctuating serum creatinine during preoperative and postoperative periods and minimizing the process of serum creatinine is the ultimate goal of this study. Method: 37 patients participated in this cross-sectional study who were previously diagnosed/newly diagnosed. They were admitted to different tertiary-level hospitals for emergency or elective surgery. Fifteen patients were admitted in the renal function impairment stage and 22 were admitted as normal patients’. Values of creatinine at the pre-admission stage and 2nd/3rd post-admission follow-up were compared. Results: 0.41 was the average of 22 patients' creatinine between pre-admission and 2nd/3rd follow-up. The responsible factor like prolonged staying, immobilization, co-morbidities, different preoperative antibiotics and Non-Steroidal Anti Inflammatory Drugs (NSAIDs) were also inducers for creatinine elevation. After postoperative hemodialysis rapid decrease of creatinine is seen in normal patients, but this decrease is very much minor in Chronic Kidney Disease (CKD) diagnosed patients.

Keywords: CKD, Meropenam, NSAID, comorbidities, immobilized

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Authors: Rajni Kant Panik, Deependra Singh, Manju Singh

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Despite significant advances in the treatment of severe burn injury, infection and sepsis persist as frequent causes of morbidity and mortality for burn victims due to extensive compromise of the skin and contiguous tissue that serve as a protective barrier against microbial invasion. In the setting of a burn wound infection, Staphylococcus aureus is the most commonly isolated pathogens from bloodstream infections in burn care hospitals. We aimed to develop a biocompatible system of Poly vinyl alcohol (PVA)-sodium alginate hydrogel carrying multiple drugs- catalase and mupirocin in controlled manner for effective and complete burn wound healing. PLGA nanoparticles of Catalase and mupirocin were prepared by homogenization method and optimized system was incorporated in PVA-sodium alginate slurry. PVA-sodium alginate hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. The study clearly showed the beneficial effect of antioxidant enzyme and antibiotic in the treatment of infected burn wound, as evidenced by the reduced incidence of wound infection and the shortening of healing time.

Keywords: burn wound, catalase, mupirocin, wound healing

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Authors: C. C. Igwe

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Several parts of Neem tree (Azadirachta indica) are used in traditional medicine in many West African countries for the treatment of various human diseases. The leaf, stem - bark and seed were air dried for 8, 5 and 7 days, respectively. The shells were carfully separated from the seeds, each powdered sample obtained with mechanical miller and 250 mm sieve. The neem samples were individually subjected to extraction with acetone, n-hexane for 48hr and 72 hr, respectively. Physico-chemical and antibacterial evaluation were carried out using standard methods. Results of physico - chemical analyses of the extracted oil from the seed shows that it has a brownish colour, with a smell similar to garlic while the moisture content, refractive index are 0.76% and 1.47 respectively. Other vital chemical results obtained from the neem oil such as saponification value (234.62), acid value (10.84 %), free fatty acid (5.84 %) and peroxide value (10.52%) indicated the oil extracted satisfied standard oils parameters for quality soap and cosmetics production. The antibacterial screening by disc diffusion revealed the oil demonstrated high activity against Staphylococcus aureus. Both the physio-chemical and antibacterial of samples have been certified by National Agency for Food and Drugs Administration and Control. The preliminary results of this study may validate the medicinal value of the plant. Further studies are in progress to clarify the in vivo potentials of neem extracts in the management of human communicable diseases and this is a subject of investigation in our group.

Keywords: anti-bacterial, neem extract, physico-chemical analyses, staphylococcus aureus

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Authors: Mahmoud Hassanin, Amita Gupta

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Background: During current practice, Thiopentone is not cost-effectively added to resources wastage, risk of drug error with antibiotics, short shelf life, infection risk, and risk of delay while preparing during category one cesarean section. There is no significant difference or preference to the other alternative as per current use. Aims and Objectives: Patient safety, Cost-effective use of trust resources, problem awareness, Consider improvising on the current practice. Methods: In conjunction with the local department survey results, many studies support the change. Results: More than 50%(15 from 29) are already using Propofol, more than 75% of the participant are willing to shift to Propofol if it becomes standard, and the cost analysis also revealed that Thiopentone 10 X500=£60 Propofol 10X200= £5.20, Cost of Thiopentone/year =£2190. Approximately GA in a year =35-40 could cost approximately £20 Propofol, given it is a well-established practice. We could save not only money, but it will be environmentally friendly also to avoid adding any carbon footprints. Recommendation: Thiopentone is rarely used as an induction agent for the category one Caesarean section in our obstetric emergency theatres. Most obstetric anesthetists are using Propofol. Keep both Propofol and thiopentone(powder not withdrawn) in the cat one cesarean section emergency drugs tray ready until the department completely changes the practice protocol. A further retrospective study is required to compare the outcomes for these induction agents through the local database.

Keywords: thiopentone, propofol, category 1 caesarean, induction agents

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Authors: Zohra Benfodda, Valentin Duvauchelle, Chaimae Majdi, David Bénimélis, Catherine Dunyach-Remy, Patrick Meffre

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New antibiotics are necessary to treat microbial pathogens, especially ESKAPE pathogens that are becoming increasingly resistant to available treatment. Despite the medical need, the number of newly approved drugs continues to decline. The majority of antibiotics under clinical development are natural products or derivatives thereof. 43 juglone/naphthazarin derivatives were synthesized using Minisci-type direct C–H alkylation and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA. Different compounds of the synthesized series showed promising activity against clinical and reference MSSA (MIC: 1–8 μg/ml) and good efficacy against clinical MRSA (MIC: 2–8 μg/ml) strains. The synergistic effects of active compounds were evaluated with reference antibiotics (vancomycin and cloxacillin), and it was found that the antibiotic combination with those active compounds efficiently enhanced the antimicrobial activity and consequently the MIC values of reference antibiotics were lowered up to 1/16th of the original MIC. These synthesized compounds did not present hemolytic activity on sheep red blood cells. In addition to the in silico prediction of ADME profile parameter which is promising and encouraging for further development.

Keywords: juglone, naphthazarin, antibacterial, clinical MRSA, synergistic studies, MIC determination

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Authors: Farzad Doostishoar, Abbas Pardakhty, Abdolreza Hassanzadeh, Sudeh salarpour, Elham Sharif

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Background: Sericin is a protein extracted from silk and has antioxidant, antimicrobial, antineoplastic, wound healing and moisturizing properties. Different cosmetic formulation of sericin is available in different countries such as Japan and the other south-eastern Asian countries. We formulated and evaluated the sunscreen properties of topical formulations of sericin by an in vitro method. Method: Niosomes composed of sorbitan palmitate (Span 40), polysorbate 40 (Tween 40) and cholesterol (300 µmol, 3.5:3.5:3 molar ratio) were prepared by film hydration technique. Sericin was dissolved in normal saline and the lipid hydration was carried out at 60°C and the niosomes were incorporated in a Carbomer gel base. A W/O cream was also prepared and the release of sericin was evaluated by using Franz diffusion cell. Particle size analysis, sericin encapsulation efficiency measurement, morphological studies and stability evaluation were done in niosomal formulations. SPF was calculated by using Transpore tape in vitro method for both formulations. Results: Niosomes had high stability during 6 months storage at 4-8°C. The mean volume diameter of niosomes was less than 7 µm which is ideal for sustained release of drugs in topical formulations. The SPF of niosomal gel was 25 and higher than sericin cream with a diffusion based release pattern of active material. Conclusion: Sericin can be successfully entrapped in niosomes with sustained release pattern and relatively high SPF.

Keywords: sericin, niosomes, sun protection factor, cream, gel

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Ilham Benali, Nasser Hajji, Nawfel Acha

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The pharmaceutical sector is ongoing different constraints related to the Research and Development (R&D) costs, the patents extinction, the demand pressing, the regulatory requirement and the generics development, which drive leading firms in the sector to undergo technological change and to shift to biotechnological paradigm. Based on a large literature review, we present a background of innovation trajectory in pharmaceutical industry and reasons behind this technological transformation. Then we investigate the role that Information and Communication Technology (ICT) is playing in this revolution. In order to situate pharmaceutical firms in developing countries in this trajectory, and to examine the degree of their involvement in the innovation process, we did not find any previous empirical work or sources generating gathered data that allow us to analyze this phenomenon. Therefore, and for the case of Morocco, we tried to do it from scratch by gathering relevant data of the last five years from different sources. As a result, only about 4% of all innovative drugs that have access to the local market in the mentioned period are made locally which substantiates that the industrial model in pharmaceutical sector in developing countries is based on the 'license model'. Finally, we present another alternative, based on ICT use and big data tools that can allow developing countries to shift from status of simple consumers to active actors in the innovation process.

Keywords: biotechnologies, developing countries, innovation, information and communication technology, pharmaceutical firms

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Authors: M. Błoch, P. Karpiński, P. Gasperowicz, R. Płoski, A. Lebioda, P. Skiba, A. Rozensztrauch, D. Patkowski, R. Śmigiel

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Introduction: The cause of the isolated form of esophageal atresia has been yet unknown. Objectives: The primary objective of this study was to indicate epigenetic factors which may play an important role in the etiopathogenesis of esophageal atresia. Methods: We recruited a group of 6 pairs of twins, among whom one of the twins developed EA. The selection of such a group for testing allows for excluding external factors (e.g., infections, drugs, toxins) as the cause of the birth defect. The analyzes were performed with the use of genetic material isolated from the whole blood and esophagus tissue of a patient with EA. The reduced representation bisulphite sequencing (RRBS) technique was used to study the change in the genomic imprinting -a change in the expression of genes, which may be the epigenetic cause of EA. Results: In the course of the analyzes, significant hypomethylation and hypermethylation regions were identified. 65 genes with probably increased expression and 65 with decreased expression were selected. These genes have not been marked in literature as possibly pathogenic in esophageal atresia. However, their participation in the pathogenesis of esophageal atresia cannot be clearly excluded. Conclusion: We suggest a role of hypomethylation or hypermethylation of selected genes as one of the possible epigenetic factors in EA pathogenesis. The use of the RRBS technique in the search for the cause of EA is pioneer research; therefore, it seems necessary to extend the research group to new patients with EA. Acknowledgment: The work was supported by the National Science Centre, Poland, under research project 2016/21/N/NZ5/01927.

Keywords: esophageal atresia, epigenetics, embryonic development, surgery, genes expression, twins

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Authors: Erika Price, Lisa Johnson

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Cognitive and dispositional empathy is decreasing among students worldwide, particularly those at university. This paper looks at the effects of encouraging empathetic positioning in divisive topics by teaching listening skills and moral discovery to university students. Two groups of university students were given the assignment to interview individuals they disagreed with on social issues (e.g. abortion, gun control, legalization of drugs, involvement in Ukraine, etc.). One group completed the assignment with no other instruction. The second group completed the assignment after receiving instruction in active listening and Jonathan Haidt’s theory of moral foundations in politics. Results show that when students are given both active listening techniques and awareness of moral foundations, they are significantly more likely to have socially positive interactions with those they disagree with on issues as compared to those who listen passively to ideological opponents. As students interacted with those they disagreed with, they evidenced prosocial behaviors of acknowledgement, validation, and even commonalities with their opponents’ viewpoints, signifying a heartening trend of empathetic connection that is waning in students. The research suggests that empathy is a skill that can be nurtured by active listening but that it is more fully cultivated when paired with the concept of moral foundations underpinning political ideologies. These findings shed light on how to create more effective pedagogies for social and emotional learning, as well as inclusion.

Keywords: empathy, listening skills, moral discovery, pedagogy, prosocial behavior

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Authors: Mai M. Helmy

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Although the role of either nitric oxide (NO) or endothelin receptors modulation in the severity of cisplatin-induced nephrotoxicity has been recognized in previous studies including our own, the possible interaction between the two pathways remains obscure. In this study, we tested the possible interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats. Sprague Dawley male rats (200 to 250 g) were divided into four groups: Control (given a single dose of normal saline, i.p.), cisplatin (6 mg/kg, i.p.), cisplatin+Sildenafil (2 mg/kg, i.p.), cisplatin+Sildenafil+BQ-123 (1 mg/kg, i.p.). Each of the co-administered drugs was given in two doses; one hour before and one day after the cisplatin dose. Acute cisplatin administration resulted in significant increases in BUN and serum creatinine levels at 96 h following cisplatin injection. Increased levels of MDA, TNF-α and caspase-3, decreased nitrite/nitrate level and SOD activity in kidney homogenates were also observed following cisplatin injection. According to the obtained results, the co-adminstration of sildenafil alone with cisplatin offered a reno-protective effect comparable to that obtained following the concurrent administration of both sildenafil and the selective ETAR antagonist BQ-123. Thus, the current study is the first to reveal that the presence of an intact NO/cGMP system may offer a moderate reno-protective effect against cisplatin-induced nephrotoxicity even in the presence of ETAR-mediated vasoconstriction, suggesting the absence of obvious functional interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats.

Keywords: BQ-123, cisplatin, endothelin-1, nephrotoxicity, sildenafil

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Authors: Wen-Yu Lin, Yi-Ching Chung, Jhao-Ren Lin, Tzyy-Rong Jinn

Abstract:

It is well known that enterovirus 71(EV71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. And, several enterovirus 71 (EV71) of hand foot and mouth disease (HFMD) with high mortalities occurred in Asia country, such as Hong Kung (1985), Malaysia (1997), Taiwan (1998) and China (2008) that EV71 results in severe neurological complications and sudden death in infants and young children. However, there are still no effective drugs and vaccines to reduce and inhibit EV71 infection. Therefore, the development of specific and effective antiviral strategies against EV71 has become an urgent issue for the protection of children from the hazards of the HFMD. As reported, amantadine is effective in prophylaxis and treatment of the EV71 infections. Thus, the aim of this study was to further evaluate the synergistic antiviral activity of amantadine coupled with magnesium lithospermate B (MLB) against enterovirus 71 infection. In a preliminary test, it is shown that the infected RD cells were treated with amantadine after virus absorption, at concentrations of 3 and 5µM of amantadine suppressed EV71-induced CPE to 13% and 23%, respectively at MOI of 3. Alternatively, at concentrations of 5µg/ml of MLB combined with 3 and 5 µM of amantadine apparently suppressed EV71-induced CPE to 45% and 63%, respectively at MOI of 3. Thus, amantadine coupled with MLB may have the potential for further study to development as the chemopreventive reagents against EV71 infection.

Keywords: amantadine, Enterovirus 71, magnesium lithospermate B, RD cells, synergistic effects

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Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

Abstract:

Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

Abstract:

Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: Noha Ibrahim, Eman S. Elzanfaly, Said A. Hassan, Ahmed E. El Gendy

Abstract:

Objectives: The purpose of the study is to develop a sensitive synchronous spectrofluorimetric method with multivariate calibration after studying and optimizing the different variables affecting the native fluorescence intensity of amlodipine and olmesartan implementing an experimental design approach. Method: In the first step, the fractional factorial design used to screen independent factors affecting the intensity of both drugs. The objective of the second step was to optimize the method performance using a Central Composite Face-centred (CCF) design. The optimal experimental conditions obtained from this study were; a temperature of (15°C ± 0.5), the solvent of 0.05N HCl and methanol with a ratio of (90:10, v/v respectively), Δλ of 42 and the addition of 1.48 % surfactant providing a sensitive measurement of amlodipine and olmesartan. The resolution of the binary mixture with a multivariate calibration method has been accomplished mainly by using partial least squares (PLS) model. Results: The recovery percentage for amlodipine besylate and atorvastatin calcium in tablets dosage form were found to be (102 ± 0.24, 99.56 ± 0.10, for amlodipine and Olmesartan, respectively). Conclusion: Method is valid according to some International Conference on Harmonization (ICH) guidelines, providing to be linear over a range of 200-300, 500-1500 ng mL⁻¹ for amlodipine and Olmesartan. The methods were successful to estimate amlodipine besylate and olmesartan in bulk powder and pharmaceutical preparation.

Keywords: amlodipine, central composite face-centred design, experimental design, fractional factorial design, multivariate calibration, olmesartan

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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

Abstract:

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: Shekoufeh Behdad, Sahar Yadegari, Alireza Ghehrazad, Amirhossein Yadegari

Abstract:

Background: In this study, we compared the effect of intravenous dexamethasone with placebo on hemodynamic variables and hypotension in patients undergoing cesarean section under spinal anesthesia. Materials and methods: This double-blind, randomized clinical trial was conducted with the approval of the university ethics committee. Written informed consent was obtained from all participating patients. Before spinal anesthesia, patients were randomly assigned to receive either dexamethasone (8 mg IV) or placebo (normal saline). Hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate, were measured before drug administration and every 3 minutes until the birth of the neonate and then every 5 minutes until the end of surgery. Side effects such as hypotension, bradycardia, nausea, and vomiting were assessed and recorded for all the patients. Results: There were no significant differences in mean systolic, diastolic, and mean arterial blood pressures before and after administration of the studied drugs in both groups (P.Value>0.05), but heart rate and the incidence of hypotension in the dexamethasone group were less than placebo significantly. Conclusions: Intravenous administration of 8 mg dexamethasone before spinal anesthesia in females undergoing cesarean section can reduce the incidence of post-spinal hypotension without causing serious side effects.

Keywords: cesarean section, hypotension, spinal anesthesia, dexamethasone

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