Search results for: drug regimens

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: Sara Segura, Diego Nuñez, Miryam Villamil

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In this work, we studied the microscale interaction of foreign substances with blood inside an artificial transparent artery system that represents medium and small muscular arteries. This artery system had channels ranging from 75 μm to 930 μm and was fabricated using glass and transparent polymer blends like Phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide, Poly(ethylene glycol) and PDMS in order to be monitored in real time. The setup was performed using a computer controlled precision micropump and a high resolution optical microscope capable of tracking fluids at fast capture. Observation and analysis were performed using a real time software that reconstructs the fluid dynamics determining the flux velocity, injection dependency, turbulence and rheology. All experiments were carried out with fully computer controlled equipment. Interactions between substances like water, serum (0.9% sodium chloride and electrolyte with a ratio of 4 ppm) and blood cells were studied at microscale as high as 400nm of resolution and the analysis was performed using a frame-by-frame observation and HD-video capture. These observations lead us to understand the fluid and mixing behavior of the interest substance in the blood stream and to shed a light on the use of implantable devices for drug delivery at arteries with different Endothelial dysfunction. Several substances were tested using the artificial artery system. Initially, Milli-Q water was used as a control substance for the study of the basic fluid dynamics of the artificial artery system. However, serum and other low viscous substances were pumped into the system with the presence of other liquids to study the mixing profiles and behaviors. Finally, mammal blood was used for the final test while serum was injected. Different flow conditions, pumping rates, and time rates were evaluated for the determination of the optimal mixing conditions. Our results suggested the use of a very fine controlled microinjection for better mixing profiles with and approximately rate of 135.000 μm3/s for the administration of drugs inside arteries.

Keywords: artificial artery, drug delivery, microfluidics dynamics, arteriosclerosis

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Authors: Igor A. Bessmertny, Bidru C. Enkomaryam

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Active involving patients and communities in health decisions can improve both people’s health and the healthcare system. Adopting artificial intelligence can lead to more accurate and complete patient record management. This review aims to identify the current state of researches conducted using artificial intelligence techniques to improve patient engagement and wellbeing, medical domains used in patient engagement context, and lastly, to assess opportunities and challenges for patient engagement in the wellness process. A search of peer-reviewed publications, reviews, conceptual analyses, white papers, author’s manuscripts and theses was undertaken. English language literature published in 2013– 2022 period and publications, report and guidelines of World Health Organization (WHO) were also assessed. About 281 papers were retrieved. Duplicate papers in the databases were removed. After application of the inclusion and exclusion criteria, 41 papers were included to the analysis. Patient counseling in preventing adverse drug events, in doctor-patient risk communication, surgical, drug development, mental healthcare, hypertension & diabetes, metabolic syndrome and non-communicable chronic diseases are implementation areas in healthcare where patient engagement can be implemented using artificial intelligence, particularly machine learning and deep learning techniques and tools. The five groups of factors that potentially affecting patient engagement in safety are related to: patient, health conditions, health care professionals, tasks and health care setting. Active involvement of patients and families can help accelerate the implementation of healthcare safety initiatives. In sub-Saharan Africa, using digital technologies like artificial intelligence in patient engagement context is low due to poor level of technological development and deployment. The opportunities and challenges available to implement patient engagement strategies vary greatly from country to country and from region to region. Thus, further investigation will be focused on methods and tools using the potential of artificial intelligence to support more simplified care that might be improve communication with patients and train health care professionals.

Keywords: artificial intelligence, patient engagement, machine learning, patient involvement

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Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer

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Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.

Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths

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Authors: Jonathan Ogwal, Louis H. Kamulegeya, John M. Bwanika, Davis Musinguzi

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Introduction: Community retail Pharmacy drug distribution points (CRPDDP) were implemented in the Lango sub-region as part of the Ministry of Health’s response to improving access and adherence to antiretroviral treatment (ART). Clients received their ART refills from nearby local pharmacies; as such, the need for continuous engagement through mobile phone appointment reminders and health messages. We share learnings from the implementation of mobile text reminders and voice call follow-ups among ART clients attending the CRPDDP program in northern Uganda. Methods: A retrospective data review of electronic medical records from four pharmacies allocated for CRPDDP in the Lira and Apac districts of the Lango sub-region in Northern Uganda was done from February to August 2022. The process involved collecting phone contacts of eligible clients from the health facility appointment register and uploading them onto a messaging platform customized by Rapid-pro, an open-source software. Client information, including code name, phone number, next appointment date, and the allocated pharmacy for ART refill, was collected and kept confidential. Contacts received appointment reminder messages and other messages on positive living as an ART client. Routine voice call follow-ups were done to ascertain the picking of ART from the refill pharmacy. Findings: In total, 1,354 clients were reached from the four allocated pharmacies found in urban centers. 972 clients received short message service (SMS) appointment reminders, and 382 were followed up through voice calls. The majority (75%) of the clients returned for refills on the appointed date, 20% returned within four days after the appointment date, and the remaining 5% needed follow-up where they reported that they were not in the district by the appointment date due to other engagements. Conclusion: The use of mobile text reminders and voice call follow-ups improves the attendance of community retail pharmacy refills.

Keywords: antiretroviral treatment, community retail drug distribution points, mobile text reminders, voice call follow-up

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Authors: Peyman Mosberian-Tanha, Mona Rezaei

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Aquaculture sector is the fastest growing food sector with annual growth rate of about 10%. The sustainability of aquaculture production, however, has been debated mainly in relation to the feed ingredients used for farmed fish. The industry has been able to decrease its dependency on marine-based ingredients in line with policies for more sustainable production. As a result, plant-based ingredients have increasingly been incorporated in aquaculture feeds, especially in feeds for popular carnivorous species, salmonids. The effect of these ingredients on salmonids’ health and performance has been widely studied. In most cases, plant-based diets are associated with varying degrees of health and performance issues across salmonids, partly depending on inclusion levels of plant ingredients and the species in question. However, aquaculture sector is facing another challenge of concern. Environmental challenges in association with climate change is another issue the aquaculture sector must deal with. Data from trials in salmonids subjected to environmental challenges of various types show adverse physiological responses, partly in relation to stress. To date, there are only a limited number of studies reporting the interactive effects of adverse environmental conditions and dietary regimens on salmonids. These studies have shown that adverse environmental conditions exacerbate the detrimental effect of plant-based diets on digestive function and health in salmonids. This indicates an additional challenge for the aquaculture sector to grow in a sustainable manner. The adverse environmental conditions often studied in farmed fish is the change in certain water quality parameters such as oxygen and/or temperature that are typically altered in response to climate change and, more specifically, global warming. In a challenge study, we observed that the in the fish fed a plant-based diet, the fish’s ability to absorb dietary energy was further reduced when reared under low oxygen level. In addition, gut health in these fish was severely impaired. Some other studies also confirm the adverse effect of environmental challenge on fish’s gut health. These effects on the digestive function and gut health of salmonids may result in less resistance to diseases and weaker performance with significant economic and ethical implications. Overall, various findings indicate the multidimensional negative effects of climate change, as a major environmental issue, in different sectors, including aquaculture production. Therefore, a comprehensive evaluation of different ways to cope with climate change is essential for planning more sustainable strategies in aquaculture sector.

Keywords: aquaculture, climate change, sustainability, salmonids

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Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

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Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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Authors: Shorena Sadzaglishvili, Teona Gotsiridze, Ketevan Lekishvili, Darejan Javakhishvili, Alida Bouris

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Globally, adolescents and young people experience high levels of HIV vulnerability and risk. Estimates suggest that AIDS-related deaths among young people are increasing, suggesting poor prioritization of adolescents in national plans for HIV testing and treatment services. HIV/AIDS is currently the sixth leading cause of death in people aged 10-24 years. Among young people, street connected youth are clearly distinguished as being among the most at risk for HIV infection. The present study recognizes the urgent need to scale up effective HIV responses that are tailored to the unique needs of street connected youth for the global HIV agenda and especially, the former Soviet country - Georgia, where 'street kids' are a new phenomenon and estimated to be about 2,500. During two months trained interviewers conducted individual semi-structured qualitative interviews with 22 key informants from the local governmental and nongovernmental service organizations, including psychologists, social workers, peer educators, mobile health workers, and managers. Informants discussed social network characteristics influencing street connected youth’s sexual risk behaviors. Data were analyzed using Dedoose. It was revealed that there are three types of homogeneous networks of street-connected youth aged 10-19 based on ethnical background: (1) Georgians; (2) migrant kids of Azeri-Kurdish origin, and (3) local Roma-Moldavian kids. These networks are distinguished with various HIV risk through both risky sexual and drug-related behaviors. In addition, there are several cases of HIV infection identified through reactive social services. Street connected youth do not have basic information about the HIV related sexual, alcohol and drug behaviors nor there are any systematic programs providing HIV testing and consultation for reducing the vulnerability of HIV infection. There is a need to systematically examine street-connected youth risk-taking behaviors by applying an integrated, multilevel framework to a population at great risk of HIV. Acknowledgment: This work was supported by Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [#FR 17_31], Ilia State University.

Keywords: street connected youth, social networks, HIV/AIDS, HIV testing

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

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In this study, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of ¹⁷⁷Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, compartmental modeling, ¹⁷⁷Lu, Octreotide

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Authors: Arunas Burinskas, Aurelija Burinskiene

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On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

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Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

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Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Diego Liberati

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Standard molecular modeling is traditionally done through Schroedinger equations via the help of powerful tools helping to manage them atom by atom, often needing High Performance Computing. Here, a full portfolio of new tools, conjugating statistical inference in the so called eXplainable Artificial Intelligence framework (in the form of Machine Learning of understandable rules) to the more traditional modeling and simulation control theory of mixed dynamic logic hybrid processes, is offered as quite a general purpose even if making an example to a popular chemical physics set of problems.

Keywords: understandable rules ML, k-means, PCA, PieceWise Affine Auto Regression with eXogenous input

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Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.

Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones

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Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

Procedia PDF Downloads 125

Authors: Christopher Holroyd

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With the various terrorist organizations and drug cartels that are currently active, there is a myriad of security concerns facing countries around the world. Organizations that focus their attacks on others through terror, such as what is seen with the Islamic State of Iraq and the Levant (ISIS), have no boundaries when it comes to doing what is needed to fulfill their desired intent. For countries such as Iraq, who have been trying to rebuild their country since the fall of the Saddam Hussein Regime, organizations such as Al-Qaeda and ISIS have been impeding the country’s efforts toward peace and stability. One method utilized by terrorist organizations around the world is human trafficking. This method is one that is seen around the world; modern slavery is still exploited by those who have no concern for human decency and morality, their only concern is to achieve their goals by any means. It is understandable that some people may not have even heard of 'modern slavery', or they just might not believe that it is even an issue in today’s world. Organizations such as ISIS are not the only ones in the world that seek to benefit from the immoral trading of humans. Various drug cartels in the world, such as those seen in Mexico and Central America, have recently begun to take part in the trade – moving humans from state to state, or country to country, to better fuel their overall operations. This now makes the possibility of human trafficking more real for those in the United States because of the proximity of the cartels to the southern border of the country. An issue that, at one time, might have only seen as a distant threat, is now close to home for those in the United States. Looking at these two examples is how we begin to understand why human trafficking is utilized by various organizations around the world. This trade of human beings and the violation of basic human rights is a plague that effects the entire world and not just those that are in a country other than your own. One of the security issues that stem from the trade includes the movement and recruitment of members of the organizations. With individuals being smuggled from one location to another in secrecy, this only puts those trying to combat this trade at a disadvantage. This creates concern over the accurate number of potential recruits, combatants, and other individuals who are working against the host nation, and for the mission of the cartel or terrorist organization they are a part of. An uphill battle is created, and the goals of peace and stability are now harder to reach. Aside from security aspects, it cannot be forgotten that those being traded and forced into slavery, are being done so against their will. Families are separated, children trained to be fighters or worse. This makes the goal of eradicating human trafficking even more dire and important.

Keywords: human trafficking, reconstruction, security, terrorism

Procedia PDF Downloads 132

Authors: Igbakura I. Luga, Alex A. Adikwu

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A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21^st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus

Procedia PDF Downloads 458

Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada

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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.

Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking

Procedia PDF Downloads 454

Authors: Amr Saeb, Khalid Al-Rubeaan, Mohamed Abouelhoda, Manojkumar Selvaraju, Hamsa Tayeb

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Background: P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, P. mirabilis is a common cause of chronic osteomyelitis in diabetic foot ulcer (DFU) patients. Methodology: P. mirabilis SCDR1 was isolated from a diabetic ulcer patient. We examined P. mirabilis SCDR1 levels of resistance against nano-silver colloids, the commercial nano-silver and silver containing bandages and commonly used antibiotics. We utilized next generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and pathogenomics in the identification and characterization of the infectious pathogen. Results: P. mirabilis SCDR1 is a multi-drug resistant isolate that also showed high levels of resistance against nano-silver colloids, nano-silver chitosan composite and the commercially available nano-silver and silver bandages. The P. mirabilis-SCDR1 genome size is 3,815,621 bp with G+C content of 38.44%. P. mirabilis-SCDR1 genome contains a total of 3,533 genes, 3,414 coding DNA sequence genes, 11, 10, 18 rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required pathogenicity and virulence factors to establish a successful infection. P. mirabilis SCDR1 isolate is a potential virulent pathogen that despite its original isolation site, wound, it can establish kidney infection and its associated complications. P. mirabilis SCDR1 contains several mechanisms for antibiotics and metals resistance including, biofilm formation, swarming mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis SCDR1 is the spontaneous nano-silver resistant bacterial strain. P. mirabilis SCDR1 strain contains all reported pathogenic and virulence factors characteristic for the species. In addition, it possesses several mechanisms that may lead to the observed nano-silver resistance.

Keywords: Proteus mirabilis, multi-drug resistance, silver nanoparticles, resistance, next generation sequencing techniques, genome analysis, bioinformatics, phylogeny, pathogenomics, diabetic foot ulcer, xenobiotics, multidrug resistance efflux, biofilm formation, swarming mobility, resistome, glutathione S-transferase, copper/silver efflux system, altruism

Procedia PDF Downloads 334

Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

Procedia PDF Downloads 99

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 114

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

Procedia PDF Downloads 102

Authors: Marius Sebastian Secula, Mihaela Darie, Gabriela Carja

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Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) and is among the most frequently detected pharmaceuticals in environmental samples and among the most widespread drug in the world. Its concentration in the environment is reported to be between 10 and 160 ng L-1. In order to improve the abatement efficiency of this compound for water source prevention and reclamation, the development of innovative technologies is mandatory. AOPs (advanced oxidation processes) are known as highly efficient towards the oxidation of organic pollutants. Among the promising combined treatments, photo-Fenton processes using layered double hydroxides (LDHs) attracted significant consideration especially due to their composition flexibility, high surface area and tailored redox features. This work presents the self-supported Fe, Mn or Ti on ZnFeAl LDHs obtained by co-precipitation followed by reconstruction method as novel efficient photo-catalysts for Fenton-like catalysis. Fe, Mn or Ti/ZnFeAl LDHs nano-hybrids were tested for the degradation of a model pharmaceutical agent, the anti-inflammatory agent ibuprofen, by photocatalysis and photo-Fenton catalysis, respectively, by means of a lab-scale system consisting of a batch reactor equipped with an UV lamp (17 W). The present study presents comparatively the degradation of Ibuprofen in aqueous solution UV light irradiation using four different types of LDHs. The newly prepared Ti/ZnFeAl 4:1 catalyst results in the best degradation performance. After 60 minutes of light irradiation, the Ibuprofen removal efficiency reaches 95%. The slowest degradation of Ibuprofen solution occurs in case of Fe/ZnFeAl 4:1 LDH, (67% removal efficiency after 60 minutes of process). Evolution of Ibuprofen degradation during the photo Fenton process is also studied using Ti/ZnFeAl 2:1 and 4:1 LDHs in the presence and absence of H2O2. It is found that after 60 min the use of Ti/ZnFeAl 4:1 LDH in presence of 100 mg/L H2O2 leads to the fastest degradation of Ibuprofen molecule. After 120 min, both catalysts Ti/ZnFeAl 4:1 and 2:1 result in the same value of removal efficiency (98%). In the absence of H2O2, Ibuprofen degradation reaches only 73% removal efficiency after 120 min of degradation process. Acknowledgements: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, project number PN-II-RU-TE-2014-4-0405.

Keywords: layered double hydroxide, advanced oxidation process, micropollutant, heterogeneous Fenton

Procedia PDF Downloads 229

Authors: Sheng-Yu Lee

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Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

Procedia PDF Downloads 106

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

Procedia PDF Downloads 128

Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 89

Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

Procedia PDF Downloads 196

Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

Abstract:

Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

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