Search results for: in vitro drug release

Authors: Ananda Perera

Abstract:

Diet therapy has a positive impact on many diseases in General Practice. If a meal plan can be generated as easily as writing a drug prescription for dyspepsia, then the evidence and practice gap in nutrition therapy can be narrowed. Meal plans of 50 diet prescriptions were compared with the criteria for a healthy diet given by Australian authorities. The energy value of each meal plan was compared with the recommended daily energy requirements of the authorities for Diet Prescription Generator (DPG) accuracy. Meal plans generated were within the criteria laid down by the Australian authorities for a healthy diet.

Keywords: dieting, obesity, diabetes, weight loss, computerized decision support systems, dieting software, CDSS, meal plans

Procedia PDF Downloads 143

Authors: Jai Myung Yang, Na Young Kim, Sung Ho Shin

Abstract:

The adverse reactions of current live smallpox vaccines and potential use of smallpox as a bioterror weapon have heightened the development of new effective vaccine for this infectious disease. In the present study, DNA vaccine vector was produced which was optimized for expression of the vaccinia virus L1 antigen in the mouse model. A plasmid IgM-tL1R, which contains codon-optimized L1R gene, was constructed and fused with an IgM signal sequence under the regulation of a SV40 enhancer. The expression and secretion of recombinant L1 protein was confirmed in vitro 293 T cell. Mice were administered the DNA vaccine by electroporation and challenged with vaccinia virus. We observed that immunization with IgM-tL1R induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Isotyping studies reveal that immunoglobulin G2 (IgG2) antibody predominated after the immunization, indicative of a T helper type 1 response. Our results suggest that an optimized DNA vaccine, IgM-tL1R, can be effective in stimulating anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

Keywords: DNA vaccine, electroporation, L1R, vaccinia virus

Procedia PDF Downloads 266

Authors: Khalid Achaat

Abstract:

It is difficult to speak about freedom of the press in Algeria without first talking to fifty-seven journalists killed in the country between 1993 and 1997 and the five missing journalists. No serious investigation was conducted to find the culprits. When a State is not able to guarantee law, there is no justice and violations of the law become "systematic". How to claim the freedom of press in Algeria, when death becomes "banal"? In these circumstances, can we talk of rights of the Algerian press? It is impossible to understand the problems of the press in Algeria, focusing solely legal issues. Take into account technical, financial and political. Their respective roles varies depending on whether one focuses on the collection of information, the regime of the newspaper company or publication and dissemination. Can we say that the Algerian press is "the freest in the Arab world", while the latter reflects only partially the real problems facing the country? While any newspaper company is subject, de facto, to an authorization scheme, permanently subjected to the constant threat of withdrawal of the authorization, suspension, prohibition or closure without it has the right to a remedy? Can it be free when the majority of "media owners", head of the largest daily newspapers are derived from the single party in power since independence? Some of this release does not it serves the interests of the Algerian power?

Keywords: freedom, press, power, closure, suspension

Procedia PDF Downloads 350

Authors: Ida Bagus Mandhara Brasika, I Dewa Gde Sathya Deva

Abstract:

Wolbachia is recently developed as the natural enemy of Dengue virus (DENV). It inhibits the replication of DENV in Aedes aegypti. Both DENV and its vector, Aedes aegypty, are sensitive to climate factor especially temperature. The changing of climate has a direct impact on temperature which means changing the vector transmission. Temperature has been known to effect Wolbachia density as it has an ideal temperature to grow. Some scenarios, which are known as Representative Concentration Pathways (RCPs), have been developed by Intergovernmental Panel on Climate Change (IPCC) to predict the future climate based on greenhouse gases concentration. These scenarios are applied to mitigate the future change of Aedes aegypti migration and how Wolbachia could control the virus. The prediction will determine the schemes to release Wolbachia-injected Aedes aegypti to reduce DENV transmission.

Keywords: Aedes aegypti, climate change, dengue virus, Intergovernmental Panel on Climate Change, representative concentration pathways, Wolbachia

Procedia PDF Downloads 300

Authors: Abhijit Trailokya

Abstract:

Background: Cardiovascular diseases (CVD’s) are the major cause of morbidity and mortality in both developed and developing countries. Many clinical trials have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, reduces the incidence of coronary and cerebrovascular events across a broad spectrum of patients at risk. Guidelines for the management of patients at risk have been established in Europe and North America. The guidelines have advocated progressively lower LDL-C targets and more aggressive use of statin therapy. In Indian patients, comprehensive data on dyslipidemia management and its treatment outcomes are inadequate. There is lack of information on existing treatment patterns, the patient’s profile being treated, and factors that determine treatment success or failure in achieving desired goals. Purpose: The present study was planned to determine the lipid control status in high-risk dyslipidemic patients treated with lipid-lowering therapy in India. Methods: This cross-sectional, non-interventional, single visit program was conducted across 483 sites in India where male and female patients with high-risk dyslipidemia aged 18 to 65 years who had visited for a routine health check-up to their respective physician at hospital or a healthcare center. Percentage of high-risk dyslipidemic patients achieving adequate LDL-C level (< 70 mg/dL) on lipid-lowering therapy and the association of lipid parameters with patient characteristics, comorbid conditions, and lipid lowering drugs were analysed. Results: 3089 patients were enrolled in the study; of which 64% were males. LDL-C data was available for 95.2% of the patients; only 7.7% of these patients achieved LDL-C levels < 70 mg/dL on lipid-lowering therapy, which may be due to inability to follow therapeutic plans, poor compliance, or inadequate counselling by physician. The physician’s lack of awareness about recent treatment guidelines also might contribute to patients’ poor adherence, not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style and the cost of medication. Statin was the most commonly used anti-dyslipidemic drug across population. The higher proportion of patients had the comorbid condition of CVD and diabetes mellitus across all dyslipidemic patients. Conclusion: As per the European Society of Cardiology guidelines the ideal LDL-C levels in high risk dyslipidemic patients should be less than 70%. In the present study, 7.7% of the patients achieved LDL-C levels < 70 mg/dL on lipid lowering therapy which is very less. Most of high risk dyslipidemic patients in India are on suboptimal dosage of statin. So more aggressive and high dosage statin therapy may be required to achieve target LDLC levels in high risk Indian dyslipidemic patients.

Keywords: cardiovascular disease, diabetes mellitus, dyslipidemia, LDL-C, lipid lowering drug, statins

Procedia PDF Downloads 201

Authors: Lorena G. Calvo, Marta Lores, Trinidad de Miguel

Abstract:

Natural extracts containing high polyphenolic concentration possess antibacterial and antifungal activity. The present research characterizes a hydro-organic extract with a high polyphenolic content as an antimicrobial candidate. As a result of this composition, the extract showed pronounced bioactivities with potential uses in agricultural, veterinary, pharmaceutical, and cosmetic industries. Polyphenol compounds were extracted by using hydro-organic solvent mixtures from the shrub Cytisus scoparius. The in vitro antimicrobial activity of this extract was evaluated on Gram-positive and Gram-negative bacteria and the fungus Candida albicans. Microbial species investigated, Bacillus cereus, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, are causing agents of several human and animal diseases. The extract showed activity against all tested species. So, it could be used for the development of biocides to control a wide range of pathogenic agents and contribute to the creation of economic and eco-friendly alternatives to antibiotics.

Keywords: antimicrobial properties, antioxidant properties, Cytisus scoparius, polyphenolic extract

Procedia PDF Downloads 146

Authors: Al-Mutary M., Alhimaidi A., Al-Ghadi M. Iwamoto D., Javed Ahmad. Abdulaziz A. Al-Khedhairy

Abstract:

The aim of the present study was to evaluate the effect of ovine follicular fluid supplementation during IVM of sheep oocytes on the resumption of meiosis, glutathione (GSH) content and expression of Bax, Bcl-2, and HSPB1 genes. Sheep ovaries were collected from Riyadh slaughterhouse, KSA. Oocytes were aspirated from 3-6 mm follicles. Ovine oocytes were cultured in maturation medium with 0% (control), 10%, 20%, 40% of ovine follicular fluid for 24 h. Results indicated that the rate of oocyte maturation was significantly (P≤0.05) decreased in 40% OFF (36.87%) versus the control (61.3%), 10% OFF (63.95%) and 20% OFF (64.08%). Supplementation of 10% OFF to IVM medium induced an intra-oocyte GSH concentration significantly higher than that found in ovine oocytes cultured with 20% OFF and 40% OFF and similar to the GSH content in oocytes cultured without FF. Real time polymerase chain reaction analysis for gene expression revealed no differences in Bax, Bcl-2, HSPB1 genes between control and 10% OFF group, whereas they were strongly expressed in 20% OFF and 40% OFF (P < 0.05) when compared to the control and 10% OFF. In conclusion the addition of 10% OFF to the IVM culture of sheep oocytes is recommended to support cytoplasmic maturation and increase oocytes competence.

Keywords: IVM, oocyte maturation, gene expression, follicular fluid

Procedia PDF Downloads 362

Authors: Malab Sana Balouch, Meenakshi Nayar

Abstract:

Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.

Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist

Procedia PDF Downloads 74

Authors: Sesethu G. Njokweni, Marelize Botes, Emile W. H. Van Zyl

Abstract:

An alternative strategy to the production of bioethanol is by examining the degradability of biomass in a natural system such as the rumen of mammals. This anaerobic microbial community has higher cellulolytic activities than microbial communities from other habitats and degrades cellulose to produce volatile fatty acids (VFA), methane and CO₂. VFAs have the potential to serve as intermediate products for electrochemical conversion to hydrocarbon fuels. In vitro mimicking of this process would be more cost-effective than bioethanol production as it does not require chemical pre-treatment of biomass, a sterile environment or added enzymes. The strategies of the carboxylate platform and the co-cultures of a bovine ruminal microbiota from cannulated cows were combined in order to investigate and optimize the bioconversion of agricultural biomass (apple and grape pomace, citrus pulp, sugarcane bagasse and triticale straw) to high value VFAs as intermediates for biofuel production in a consolidated bioprocess. Optimisation of reactor conditions was investigated using five different ruminal inoculum concentrations; 5,10,15,20 and 25% with fixed pH at 6.8 and temperature at 39 ˚C. The ANKOM 200/220 fiber analyser was used to analyse in vitro neutral detergent fiber (NDF) disappearance of the feedstuffs. Fresh and cryo-frozen (5% DMSO and 50% glycerol for 3 months) rumen cultures were tested for the retainment of fermentation capacity and durability in 72 h fermentations in 125 ml serum vials using a FURO medical solutions 6-valve gas manifold to induce anaerobic conditions. Fermentation of apple pomace, triticale straw, and grape pomace showed no significant difference (P > 0.05) in the effect of 15 and 20 % inoculum concentrations for the total VFA yield. However, high performance liquid chromatographic separation within the two inoculum concentrations showed a significant difference (P < 0.05) in acetic acid yield, with 20% inoculum concentration being the optimum at 4.67 g/l. NDF disappearance of 85% in 96 h and total VFA yield of 11.5 g/l in 72 h (A/P ratio = 2.04) for apple pomace entailed that it was the optimal feedstuff for this process. The NDF disappearance and VFA yield of DMSO (82% NDF disappearance and 10.6 g/l VFA) and glycerol (90% NDF disappearance and 11.6 g/l VFA) stored rumen also showed significantly similar degradability of apple pomace with lack of treatment effect differences compared to a fresh rumen control (P > 0.05). The lack of treatment effects was a positive sign in indicating that there was no difference between the stored samples and the fresh rumen control. Retaining of the fermentation capacity within the preserved cultures suggests that its metabolic characteristics were preserved due to resilience and redundancy of the rumen culture. The amount of degradability and VFA yield within a short span was similar to other carboxylate platforms that have longer run times. This study shows that by virtue of faster rates and high extent of degradability, small scale alternatives to bioethanol such as rumen microbiomes and other natural fermenting microbiomes can be employed to enhance the feasibility of biofuels large-scale implementation.

Keywords: agricultural wastes, carboxylate platform, rumen microbiome, volatile fatty acids

Procedia PDF Downloads 130

Authors: Ala Abobakr Abdulhafidh Al-Dubai

Abstract:

Biomaterials, specifically metals and ceramics, are indispensable components in the realm of medical science, shaping the landscape of implantology and prosthetics. This study delves into the intricate interplay between these materials and biological systems, aiming to scrutinize their suitability, performance, and biocompatibility. Employing a multi-faceted approach, a range of methodologies were meticulously employed to comprehensively characterize these biomaterials. Advanced material characterization techniques were paramount in this research, with scanning electron microscopy providing intricate insights into surface morphology, and X-ray diffraction unraveling the crystalline structures. These analyses were complemented by in vitro assessments, which gauged the biological response of cells to metals and ceramics, shedding light on their potential applications within the human body. A key facet of our investigation involved a comparative study, evaluating the corrosion resistance and osseointegration potential of both metals and ceramics. Through a series of experiments, we sought to understand how these biomaterials interacted with physiological environments, paving the way for informed decisions in medical applications

Keywords: metals, ceramics, biomaterials, biocompatibility, osseointegration

Procedia PDF Downloads 69

Authors: D. S. V. Barbieri, R. R. Gomes, G. D. Santos, P. F. Herkert, M. Moreira, E. S. Trindade, V. A. Vicente

Abstract:

The importance of yeast infections has increased in recent decades. The monitoring of Candida yeasts has been relevant in the study of groups and populations. This research evaluated 31 Candida spp. isolates from oral microbiota of 12 Brazilian schoolchildren coinfected with Streptococcus mutans. The isolates were evaluated for their ability to form biofilm in vitro and molecularly characterized based on the sequencing of intergenic spacer regions ITS1-5,8S-ITS2 and variable domains of the large subunit (D1/D2) regions of the rDNA, as well as ABC system genotyping. The sequencing confirmed 26 lineages of Candida albicans, three Candida tropicalis, one Candida guillhermondii and one Candida glabrata. Genetic variability and differences on in biofilm formation were observed among Candida yeasts lineages. At least one Candida strain from each caries activity child was C.albicans genotype A or Candida non-albicans. C. tropicalis was associated with highest cavities rates. These results indicate that the presence of C. albicans genotype A or multi-colonization by non albicans species seem to be associates to the potentialization of caries risk.

Keywords: biofilm, Candida albicans, oral microbiota, caries

Procedia PDF Downloads 510

Authors: Kwarciak-Kozlowska A., Slawik-Dembiczak L., Galwa-Widera M.

Abstract:

Complex and variable during operation of the landfill leachate composition prevents the use of a single universal method of their purification. Due to the presence of difficult biodegradable these substances in the wastewater, cleaning of them often requires the use of biological methods (activated sludge or anaerobic digestion), also often supporting by physicochemical processes. Currently, more attention is paid to the development of unconventional methods of disposal of sewage m.in ultleniania advanced methods including the use of ultrasonic waves. It was assumed that the ultrasonic waves induce change in the structure of organic compounds and contribute to the acceleration of biodegradability, including refractive substances in the leachate, so that will increase the effectiveness of their treatment in biological processes. We observed a marked increase in BOD leachate when subjected to the action of utradźwięowego. Ratio BOD / COD was 27% higher compared to the value of this ratio for leachate nienadźwiękawianych. It was found that the process of sonification leachate clearly influenced the formation and release of aliphatic compounds. These changes suggest a possible violation of the chemical structure of organic compounds in the leachate thereby give compounds of the chemical structure more susceptible to biodegradation.

Keywords: IR spectra, landfill leachate, organic pollutants, ultrasound

Procedia PDF Downloads 429

Authors: Olufunke Olufunmilayo Ilemobayo, Barakat. O Abdulazeez

Abstract:

Profit making among poultry egg farmers has been a challenge to efficient distribution of scarce farm resources over the years, due majorly to low capital base, inefficient management, technical inefficiency, economic inefficiency, thus poultry egg production has moved into an underperformed situation, characterised by low profit margin. Though previous studies focus mainly on broiler production and efficiency of its production, however, paucity of information exist in the areas of profit efficiency in the study area. Hence, determinants of profit efficiency among poultry egg farmers in Ondo State, Nigeria were investigated. A purposive sampling technique was used to obtain primary data from poultry egg farmers in Owo and Akure local government area of Ondo State, through a well-structured questionnaire. socio-economic characteristics such as age, gender, educational level, marital status, household size, access to credit, extension contact, other variables were input and output data like flock size, cost of feeder and drinker, cost of feed, cost of labour, cost of drugs and medications, cost of energy, price of crate of table egg, price of spent layers were variables used in the study. Data were analysed using descriptive statistics, budgeting analysis, and stochastic profit function/inefficiency model. Result of the descriptive statistics shows that 52 per cent of the poultry farmers were between 31-40 years, 62 per cent were male, 90 per cent had tertiary education, 66 per cent were primarily poultry farmers, 78 per cent were original poultry farm owners and 55 per cent had more than 5 years’ work experience. Descriptive statistics on cost and returns indicated that 64 per cent of the return were from sales of egg, while the remaining 36 per cent was from sales of spent layers. The cost of feeding take the highest proportion of 69 per cent of cost of production and cost of medication the lowest (7 per cent). A positive gross margin of N5, 518,869.76, net farm income of ₦ 5, 500.446.82 and net return on investment of 0.28 indicated poultry egg production is profitable. Equipment’s cost (22.757), feeding cost (18.3437), labour cost (136.698), flock size (16.209), drug and medication cost (4.509) were factors that affecting profit efficiency, while education (-2.3143), household size (-18.4291), access to credit (-16.027), and experience (-7.277) were determinant of profit efficiency. Education, household size, access to credit and experience in poultry production were the main determinants of profit efficiency of poultry egg production in Ondo State. Other factors that affect profit efficiency were cost of feeding, cost of labour, flock size, cost of drug and medication, they positively and significantly influenced profit efficiency in Ondo State, Nigeria.

Keywords: cost and returns, economic inefficiency, profit margin, technical inefficiency

Procedia PDF Downloads 129

Authors: Lewis J. Woollin, Robert I. Davidson, Paul Watson, Philip J. Hyde

Abstract:

Introduction: In-vitro testing of arthroplasty materials is of paramount importance when ensuring that they can withstand the performance requirements encountered in-vivo. One common machine used for in-vitro testing is a pin-on-plate tribometer, an early stage screening device that generates data on the wear characteristics of arthroplasty bearing materials. These devices test vertically loaded rotating cylindrical pins acting against reciprocating plates, representing the bearing surfaces. In this study, a pin-on-plate machine has been developed that provides several improvements over current technology, thereby progressing arthroplasty bearing research. Historically, pin-on-plate tribometers have been used to investigate the performance of arthroplasty bearing materials under conditions commonly encountered during a standard gait cycle; nominal operating pressures of 2-6 MPa and an operating frequency of 1 Hz are typical. There has been increased interest in using pin-on-plate machines to test more representative in-vivo conditions, due to the drive to test 'beyond compliance', as well as their testing speed and economic advantages over hip simulators. Current pin-on-plate machines do not accommodate the increased performance requirements associated with more extreme kinematic conditions, therefore a next-generation pin-on-plate tribometer has been developed to bridge the gap between current technology and future research requirements. Methodology: The design was driven by several physiologically relevant requirements. Firstly, an increased loading capacity was essential to replicate the peak pressures that occur in the natural hip joint during running and chair-rising, as well as increasing the understanding of wear rates in obese patients. Secondly, the introduction of mid-cycle load variation was of paramount importance, as this allows for an approximation of the loads present in a gait cycle to be applied and to test the fatigue properties of materials. Finally, the rig must be validated against previous-generation pin-on-plate and arthroplasty wear data. Results: The resulting machine is a twelve station device that is split into three sets of four stations, providing an increased testing capacity compared to most current pin-on-plate tribometers. The loading of the pins is generated using a pneumatic system, which can produce contact pressures of up to 201 MPa on a 3.2 mm² round pin face. This greatly exceeds currently achievable contact pressures in literature and opens new research avenues such as testing rim wear of mal-positioned hip implants. Additionally, the contact pressure of each set can be changed independently of the others, allowing multiple loading conditions to be tested simultaneously. Using pneumatics also allows the applied pressure to be switched ON/OFF mid-cycle, another feature not currently reported elsewhere, which allows for investigation into intermittent loading and material fatigue. The device is currently undergoing a series of validation tests using Ultra-High-Molecular-Weight-Polyethylene pins and 316L Stainless Steel Plates (polished to a Ra < 0.05 µm). The operating pressures will be between 2-6 MPa, operating at 1 Hz, allowing for validation of the machine against results reported previously in the literature. The successful production of this next-generation pin-on-plate tribometer will, following its validation, unlock multiple previously unavailable research avenues.

Keywords: arthroplasty, mechanical design, pin-on-plate, total joint replacement, wear testing

Procedia PDF Downloads 95

Authors: A. N. Gornostaeva, P. I. Bobyleva, E. R. Andreeva, L. B. Buravkova

Abstract:

Multipotent mesenchymal stromal cells (MSCs) possess immunomodulatory properties. The effect of MSCs on the crucial cellular immunity compartment – T-cells is of a special interest. It is known that MSC tissue niche and expected milieu of their interaction with T- cells are characterized by low oxygen concentration, whereas the in vitro experiments usually are carried out at a much higher ambient oxygen (20%). We firstly evaluated immunomodulatory effects of MSCs on T-cells at tissue-related oxygen (5%) after interaction implied cell-to-cell contacts and paracrine factors only. It turned out that MSCs under reduced oxygen can effectively suppress the activation and proliferation of PHA-stimulated T-cells and can provoke decrease in the production of proinflammatory and increase in anti-inflammatory cytokines. In hypoxia some effects were amplified (inhibition of proliferation, anti-inflammatory cytokine profile shift). This impact was more evident after direct cell-to-cell interaction; lack of intercellular contacts could revoke the potentiating effect of hypoxia.

Keywords: MSCs, T-cells, activation, low oxygen, cell-to-cell interaction, immunosuppression

Procedia PDF Downloads 382

Authors: Ishrat Jahan Saifi, Sheelu Shafiq Siddiqi, M. R. Ajmal

Abstract:

Glycation of protein is very important as well as a harmful process, which may lead to develop DM in human body. Human Serum Albumin (HSA) is the most abundant protein in blood and it is highly prone to glycation by the reducing sugars. 2-¬deoxy d-¬Ribose (dRib) is a highly reactive reducing sugar which is produced in cells as a product of the enzyme thymidine phosphorylase. It is generated during the degradation of DNA in human body. It may cause glycation in HSA rapidly and is involved in the development of DM. In present study, we did in¬vitro glycation of HSA with different concentrations of 2-¬deoxy d-¬ribose and found that dRib glycated HSA rapidly within 4h incubation at 37◦C. UV¬ Spectroscopy, Fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR) and Circular Dichroism (CD) technique have been done to determine the structural changes in HSA upon glycation. Results of this study suggested that dRib is the potential glycating agent and it causes alteration in protein structure and biophysical properties which may lead to development and progression of Diabetes mellitus.

Keywords: 2-deoxy D-ribose, human serum albumin, glycation, diabetes mellitus

Procedia PDF Downloads 210

Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li

Abstract:

Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis

Procedia PDF Downloads 225

Authors: Mohamed Ahmed Tony, Mohamed Hamoud

Abstract:

The present study was conducted to determine the effect of commercially coated slow-release sodium butyrate (CM3000®) as a feed additive on zootechnical performance, immune status and Clostridium perfringens severity after experimental infection. Three hundred 1-d-old broiler chicks (Cobb 500) were randomly distributed into 3 treatment groups (4 replicates each) using 25 chicks per replicate on floor pens. Control (C) birds were offered non-supplemented basal diets. Treatments 1 and 2 (T1 and T2) were fed diets containing CM3000® at 300 and 500 g/ton feed, respectively, during the entire experimental period (35 days). Feed and water were offered ad-libitum. Feed consumption and body weight were recorded weekly to calculate body weight gain and feed conversion. Blood samples were collected to evaluate the immune status of the birds against Newcastle disease vaccines using HI test. At the end of the experimental period, 20 birds were chosen randomly from each group (5 birds from each pen) to compare carcass yield. At day 16 of age 20 birds from each group (5 birds/replicate) were bacteriologically examined and proved to be free from Clostridium perfringens. The isolated birds were challenged orally with 1 ml buffer containing 106 CFU/ml Clostridium perfringens local isolate and prepared from necrotic enteritis (NE) diseased farms. Birds were observed on a regular basis daily for any signs of NE. Birds that died in the challenged group were necropsied to determine the cause of death. On day 28 of age, the surviving chickens were killed by cervical dislocation and necropsied immediately. Intestinal tracts were removed and intestinal lesions were scored. Tissue samples of the duodenum, jejunum, ileum and cecum for histopathological examination were collected. All collected data were statistically analyzed using IBM SPSS® version 19 software for personal computers. Means were compared by one-way ANOVA (P<0.05) followed by the Duncan Post Hoc test. The results revealed that body weight gain was significantly (P<0.05) improved in chicks fed on both doses of CM3000® compared to the control one. Final body weight gain in T1 and T2 were 2064.94 and 2141.37 g/bird, respectively, while in the control group, the weight gain showed 1952.78 g/bird. In addition, supplementation of diets with CM3000® increased significantly feed intake (P<0.05). Total feed intake in T1 and T2 were 3186.32 and 3273.29 g/bird, respectively; however, feed intake in the control group recorded 3081.95 g/bird. The best feed conversion was recorded in T2 group (1.53). Feed conversion in the control and T1 groups were 1.58 and 1.54, respectively. Dressing percentage, liver weights and the other carcasses yields were not different between treatments. The butyrate significantly enhanced immune responses measured against Newcastle disease vaccines. Sodium butyrate significantly reduced NE lesions and healthy improved the intestinal tissues in the samples collected from T1 and T2-challenged chickens versus those collected from the control group. In conclusion, exogenous administration of slow-release butyrate (CM3000®) is capable of improving performance, enhancing immunity and NE disease resistance in broiler chickens.

Keywords: sodium butyrate, broiler chicken, zootechnical performance, immunity, necrotic enteritis

Procedia PDF Downloads 85

Authors: Benyam Zenebe, Tesfaye Sisay, Gurja Belay, Workabeba Abebe

Abstract:

Background: The prevalence and antibiogram of pathogenic E. coli strains, which cause diarrhea vary from region to region, and even within countries in the same geographical area. In Ethiopia, diagnostic approaches to E. coli induced diarrhea in children less than five years of age are not standardized. The aim of this study was to determine the involvement of pathogenic E. coli strains in child diarrhea and determine the antibiograms of the isolates in children less than 5 years of age with diarrhea at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods: A purposive study that included 98 diarrheic children less than five years of age was conducted at Addis Ababa University College of Health Sciences, TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia to detect pathogenic E. coli biotypes. Stool culture was used to identify presumptive E. coliisolates. Presumptive isolates were confirmed by biochemical tests, and antimicrobial susceptibility tests were performed on confirmed E. coli isolates by the disk diffusion method. DNA was extracted from confirmed isolates by a heating method and subjected to Polymerase Chain Reaction or the presence of virulence genes. Amplified PCR products were analyzed by agarose gel electrophoresis. Data were collected on child demographics and clinical conditions using administered questionnaires. The prevalence of E. coli strains from the total diarrheic children, and the prevalence of pathogenic strains from total E. coli isolates along with their susceptibility profiles; the distribution of pathogenic E.coli biotypes among different age groups and between the sexes were determined by using descriptive statistics. Result: Out of 98 stool specimens collected from diarrheic children less than 5 years of age, 75 presumptive E. coli isolates were identified by culture; further confirmation by biochemical tests showed that only 56 of the isolates were E. coli; 29 of the isolates were found in male children and 27 of them in female children. Out of the 58 isolates of E. coli, 25 pathotypes belonging to different classes of pathogenic strains: STEC, EPEC, EHEC, EAEC were detected by using the PCR technique. Pathogenic E. coli exhibited high rates of antibiotic resistance to many of the antibiotics tested. Moreover, they exhibited multiple drug resistance. Conclusion: This study found that the isolation rate of E. coli and the involvement of antibiotic-resistant pathogenic E. coli in diarrheic children is prominent, and hence focus should be given on the diagnosis and antimicrobial sensitivity testing of pathogenic E. coli at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital. Among antibiotics tested, Cefotitan could be a drug of choice to treat E. coli.

Keywords: antibiotic susceptibility profile, children, diarrhea, E. coli, pathogenic

Procedia PDF Downloads 234

Authors: Annabelle Nelson

Abstract:

This literature review documents indigenous storytelling as it functions to help humans face adversity and find emotional strength by aligning with nature. Archetypes in stories can transform the inner world from a Jungian perspective. Joseph Campbell’s hero-heroine cycle depicts the structure of stories to include a call to adventure, tests, helpers, and a return as the transformed person can help him or herself and even help their communities. By showcasing certain character traits, such as bravery or perseverance or humility, stories give maps for humans to face adversity. The main characters or archetypes in stories, as Carl Jung posited, provide a vehicle that can open consciousness if a listener identifies with the character. As documented in the review, this has many benefits. First, it can open consciousness to the collective unconscious for insight and intuitive clarity, as well as healing and release emotional trauma. The resultant spacious quality of consciousness allows the spiritual self to present insights to conscious awareness. Research in applied youth development programs demonstrates the utility of storytelling to prompt healthy choices and transform difficult life experience into success.

Keywords: archetypes, learning, storytelling, transformation

Procedia PDF Downloads 188

Authors: Abdulmagid A. Khattabi, Ahmed A. Hablus, Osama Ab. M. Shafah

Abstract:

The goal of this work is to understand how the thermal influence of combustion chamber deposits can be utilized to expand the operating range of HCCI combustion. In order to do this, two main objectives must first be met; tracking deposit formation trends in an HCCI engine and determining the sensitivity of HCCI combustion to CCD. This requires testing that demonstrates the differences in combustion between a clean engine and one with deposits coating the chamber. This will involve a long-term test that tracks the effects of CCD on combustion. The test will start with a clean engine. One baseline HCCI operating point is maintained for the duration of the test during which gradual combustion chamber deposit formation will occur. Combustion parameters, including heat release rates and emissions will be tracked for the duration and compared to the case of a clean engine. This work will begin by detailing the specifics of the test procedure and measurements taken throughout the test. Then a review of the effects of the gradual formation of deposits in the engine will be given.

Keywords: fuels, fuel atomization, pattern factor, alternate fuels combustion, efficiency gas turbine combustion, lean blow out, exhaust and liner wall temperature

Procedia PDF Downloads 527

Authors: Dong Nyoung Heo, Il Keun Kwon

Abstract:

Three-dimensional (3D) technology is a promising method for bone tissue engineering. In order to enhance bone tissue regeneration, it is important to have ideal 3D constructs with biomimetic mechanical strength, structure interconnectivity, roughened surface, and the presence of chemical functionality. In this respect, a 3D printing system combined with cold atmospheric plasma (CAP) was developed to fabricate a 3D construct that has a rough surface with polar functional chemical groups. The CAP-etching process leads to oxidation of chemical groups existing on the polycaprolactone (PCL) surface without conformational change. The surface morphology, chemical composition, mean roughness of the CAP-treated PCL surfaces were evaluated. 3D printed constructs composed of CAP-treated PCL showed an effective increment in the hydrophilicity and roughness of the PCL surface. Also, an in vitro study revealed that CAP-treated 3D PCL constructs had higher cellular behaviors such as cell adhesion, cell proliferation, and osteogenic differentiation. Therefore, a 3D printing system with CAP can be a highly useful fabrication method for bone tissue regeneration.

Keywords: bone tissue engineering, cold atmospheric plasma, PCL, 3D printing

Procedia PDF Downloads 114

Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

Abstract:

Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

Procedia PDF Downloads 308

Authors: A. Aceranti, L. Moretti, S. Vernocchi, M. Colorato, P. Caristia

Abstract:

Irritable bowel syndrome (IBS) is the association between abdominal pain, abdominal distension and intestinal dysfunction for recurring periods. About 10% of the world's population has IBS at any given time in their life, and about 200 people per 100,000 receive an initial diagnosis of IBS each year. Persistent pain is recognized as one of the most pervasive and challenging problems facing the medical community today. Persistent pain is considered more as a complex pathophysiological, diagnostic and therapeutic situation rather than as a persistent symptom. The low efficiency of conventional drug treatments has led many doctors to become interested in the non-drug alternative treatment of IBS, especially for more severe cases. Patients and providers are often dissatisfied with the available drug remedies and often seek complementary and alternative medicine (CAM), a unique and holistic approach to treatment that is not a typical component of conventional medicine. Osteopathic treatment may be of specific interest in patients with IBS. Osteopathy is a complementary health approach that emphasizes the role of the musculoskeletal system in health and promotes optimal function of the body's tissues using a variety of manual techniques to improve body function. Osteopathy has been defined as a patient-centered health discipline based on the principles of interrelation between body structure and function, the body's innate capacity for self-healing and the adoption of a whole person health approach. mainly by practicing manual processing. Studies reported that osteopathic manual treatment (OMT) reduced IBS symptoms, such as abdominal pain, constipation, diarrhea, and improved general well-being. The focus in the treatment of IBS with osteopathy has gone beyond simple spinal alignment, to directly address the abnormal physiology of the body using a series of direct and indirect techniques. The topic of this study was chosen for different reasons: due to the large number of people involved who suffer from this disorder and for the dysfunction itself, since nowadays there is still little clarity about the best type of treatment and, above all, to its origin. The visceral component in the osteopathic field is still a world to be discovered, although it is related to a large part of patient series, it has contents that affect numerous disciplines and this makes it an enigma yet to be solved. The study originated in the didactic practice where the curiosity of a topic is marked that, even today, no one is able to explain and, above all, cure definitively. The main purpose of this study is to try to create a good basis on the osteopathic discipline for subsequent studies that can be exhaustive in the best possible way, resolving some doubts about which treatment modality can be used with more relevance. The path was decided to structure it in such a way that 3 types of osteopathic treatment are used on 3 groups of people who will be selected after completing a questionnaire, which will deem them suitable for the study. They will, in fact, be divided into three groups where: - the first group was given a visceral osteopathic treatment. - The second group was given a manual osteopathic treatment of neurological stimulation. - The third group received a placebo treatment. At the end of the treatment, questionnaires will be re-proposed respectively one week after the session and one month after the treatment from which any data will be collected that will demonstrate the effectiveness or otherwise of the treatment received. The sample of 50 patients examined underwent an oral interview to evaluate the inclusion and exclusion criteria to participate in the study. Of the 50 patients questioned, 17 people who underwent different osteopathic techniques were eligible for the study. Comparing the data related to the first assessment of tenderness and frequency of symptoms with the data related to the first follow-up shows a significant improvement in the score assigned to the different questions, especially in the neurogenic and visceral groups. We are aware of the fact that it is a study performed on a small sample of patients, and this is a penalizing factor. We remain, however, convinced that having obtained good results in terms of subjective improvement in the quality of life of the subjects, it would be very interesting to re-propose the study on a larger sample and fill the gaps.

Keywords: IBS, osteopathy, colon, intestinal inflammation

Procedia PDF Downloads 101

Authors: Moustafa Osman

Abstract:

Modeling of air pollutants from the accidental release is performed for quantifying the impact of industrial facilities into the ambient air. The mathematical methods are requiring for the prediction of the accidental scenario in probability of failure-safe mode and analysis consequences to quantify the environmental damage upon human health. The initial statement of mitigation plan is supporting implementation during production and maintenance periods. In a number of mathematical methods, the flow rate at which gaseous and liquid pollutants might be accidentally released is determined from various types in term of point, line and area sources. These emissions are integrated meteorological conditions in simplified stability parameters to compare dispersion coefficients from non-continuous air pollution plumes. The differences are reflected in concentrations levels and greenhouse effect to transport the parcel load in both urban and rural areas. This research reveals that the elevation effect nearby buildings with other structure is higher 5 times more than open terrains. These results are agreed with Sutton suggestion for dispersion coefficients in different stability classes.

Keywords: air pollutants, dispersion modeling, GIS, health effect, urban planning

Procedia PDF Downloads 374

Authors: Xiao-Li Liu, Ling-Yun Zhao, Xing-Jie Liang, Hai-Ming Fan

Abstract:

Owing to their unique properties, magnetic nanoparticles have been used as diagnostic and therapeutic agents for biomedical applications. Highly monodispersed magnetic nanoparticles with controlled particle size and surface coating have been successfully synthesized as a model system to investigate the effect of surface coating on the T2 relaxivity and specific absorption rate (SAR) under an alternating magnetic field, respectively. Amongst, by using mPEG-g-PEI to solubilize oleic-acid capped 6 nm magnetic nanoparticles, the T2 relaxivity could be significantly increased by up to 4-fold as compared to PEG coated nanoparticles. Moreover, it largely enhances the cell uptake with a T2 relaxivity of 92.6 mM-1s-1 for in vitro cell MRI. As for hyperthermia agent, SAR value increase with the decreased thickness of PEG surface coating. By elaborate optimization of surface coating and particle size, a significant increase of SAR (up to 74%) could be achieved with a minimal variation on the saturation magnetization (<5%). The 19 nm magnetic nanoparticles with 2000 Da PEG exhibited the highest SAR of 930 W•g-1 among the samples, which can be maintained in various simulated physiological conditions. This systematic work provides a general strategy for the optimization of surface coating of magnetic core for high performance MRI contrast agent and hyperthermia agent.

Keywords: magnetic nanoparticles, magnetic hyperthermia, magnetic resonance imaging, surface modification

Procedia PDF Downloads 510

Authors: H. Kadi, A. Moussaoui, A. Medah, N. Benayahia, Nahal Bouderba

Abstract:

For thousands of years, Punica granatum L. has been used in traditional medicine all over the world and predate the introduction of antibacterial drugs. The aim of the present study was to investigate the antibacterial activity of aqueous and ethanolic extracts of Punica granatum L. bark obtained by decoction and maceration. The different extracts of Punica granatum L. (Lythraceae) bark have been tested for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus stearothermophilus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) by disc diffusion method. The ethanolic macerate extract showed the strong in vitro antibacterial activity against Pseudomonas aeruginosa with zone inhibition of 24.4 mm. However, the results tests by disc diffusion method revealed the effectiveness of ethanolic decoctate against Gram-positive bacteria (Staphylococcus aureus and Bacillus stearothermophilus) with diameter zone of inhibition varying with 21.1mm and 23.75 mm respectively.

Keywords: Punica granatum L. bark, antibacterial activity, maceration, decoction

Procedia PDF Downloads 467

Authors: Delara Soltani, Sajad Alimohammadi, Tim Persoons

Abstract:

Microfluidic technology reveals a new area of research in drug delivery, biomedical diagnostics, and the food and chemical industries. Mixing is an essential part of microfluidic devices. There is a need for fast and homogeneous mixing in microfluidic devices. On the other hand, mixing is difficult to achieve in microfluidic devices because of the size and laminar flow in these devices. In this study, a hybrid passive micromixer of a curved channel with obstacles inside the channel is designed. The computational fluid dynamic method is employed to solve governing equations. The results show that using obstacles can improve mixing efficiency in spiral micromixers. the effects of Reynolds number, number, and position of baffles are investigated. In addition, the effect of baffles on pressure drop is presented. this novel micromixer has the potential to utilize in microfluidic devices.

Keywords: CFD, micromixer, microfluidics, spiral, reynolds number

Procedia PDF Downloads 91

Authors: Shanhua Hu

Abstract:

Social media as a critical propagandizing form of film, video games, and digital products has received substantial research attention, but there exists several critical barriers such as: (1) few studies exploring the internal and external connections of a product as part of the multimodal context that gives rise to readability and commercial return; (2) the lack of study of multimodal analysis in product’s official account of game publishers and its impact on users’ behaviors including purchase intention, social media engagement, and playing time; (3) no standardized ecologically-valid, game type-varying data can be used to study the complexity of official account’s postings within a time period. This proposed research helps to tackle these limitations in order to develop a model of readability study that is more ecologically valid, robust, and thorough. To accomplish this objective, this paper provides a more diverse dataset comprising different visual elements and messages collected from the official Twitter accounts of the Top 20 best-selling games of 2021. Video game companies target potential users through social media, a popular approach is to set up an official account to maintain exposure. Typically, major game publishers would create an official account on Twitter months before the game's release date to update on the game's development, announce collaborations, and reveal spoilers. Analyses of tweets from those official Twitter accounts would assist publishers and marketers in identifying how to efficiently and precisely deploy advertising to increase game sales. The purpose of this research is to determine how official game accounts use Twitter to attract new customers, specifically which types of messages are most effective at increasing sales. The dataset includes the number of days until the actual release date on Twitter posts, the readability of the post (Flesch Reading Ease Score, FRES), the number of emojis used, the number of hashtags, the number of followers of the mentioned users, the categorization of the posts (i.e., spoilers, collaborations, promotions), and the number of video views. The timeline of Twitter postings from official accounts will be compared to the history of pre-orders and sales figures to determine the potential impact of social media posts. This study aims to determine how the above-mentioned characteristics of official accounts' Twitter postings influence the sales of the game and to examine the possible causes of this influence. The outcome will provide researchers with a list of potential aspects that could influence people's judgments in limited-word posts. With the increased average online time, users would adapt more quickly than before in online information exchange and readings, such as the word to use sentence length, and the use of emojis or hashtags. The study on the promotion of official game accounts will not only enable publishers to create more effective promotion techniques in the future but also provide ideas for future research on the influence of social media posts with a limited number of words on consumers' purchasing decisions. Future research can focus on more specific linguistic aspects, such as precise word choice in advertising.

Keywords: engagement, official account, promotion, twitter, video game

Procedia PDF Downloads 76

Authors: Jyoti Singh, Ranju Bansal

Abstract:

Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

Procedia PDF Downloads 200