Search results for: drug synergy

Authors: Zhala Ahmad, Zainab Lazim, Haider Hamzah

Abstract:

Bacterial resistance is a pressing global health issue, with multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains to pose a serious threat. In this context, researchers are investigating effective, safe, and affordable metabolites to combat these pathogens. This study focuses on gum essential oil (GEO) extracted from Pistacia atlantica and its activity and the mechanism of action against XDR Gram-negative Acinetobacter baumannii. GEO was extracted by hydrodistillation and analyzed using GC-MS. Eleven A. baumannii isolates were collected from the ward environment of Burn and Plastic Surgery Hospital in Al Sulaymaniyah City, Iraq. They were identified using the VITEK 2 system, 16S rRNA gene, and confirmed with the blaₒₓₐ₋₅₁ gene; A. baumannii ATCC 19606 was used as a reference strain. The isolates were identified as resistant to twelve different antibiotics spanning six distinct antibiotic classes while showing susceptibility to tetracycline and trimethoprim. Over 40 chemical constituents were detected in the gum's essential oils, with α-pinene being the most abundant. GEO was found to inhibit the growth of A. baumannii isolates; the minimum inhibitory concentration (MIC) of GEO was 2.5 µl/ml. GEO induced protein leakage, phosphate, and potassium ion efflux, distorted cell morphology, and cell death in the tested bacteria. GEO exhibited bacterial clearance and anti-adhesion activity using Band-Aids. This study's findings suggest that GEO could be used as a potential alternative treatment for infectious diseases caused by XRD pathogens, shedding further light on the importance of GEO in biomedical applications. Future studies must focus on generating clinically feasible sources of GEO for testing in small animal models before proceeding to human trials, ensuring safe and effective translation from the laboratory to the clinic.

Keywords: antibiotic resistance, Acinetobacter baumannii, essential oils, Pistacia atlantica, alpha-pinene

Procedia PDF Downloads 71

Authors: Icy Vinod Sanghvi

Abstract:

In the light of rising modernism within the residential design industry, a significant growth of the western concepts of maximalism or minimalism is observed in the Indian housings. Although dynamism in design styles is natural due to the constant emergence of new innovations, it is imperative that local houses reflect cultural identity. This paper highlights the importance of ‘Indian Modernism’, and how to incorporate the same in residential design. Thus, helping the Indian culture to flourish and become a significant part of housing design in the future. A literature review was conducted to analyze and derive effective methods to build cultural value whilst catering to the urban and contemporary design industry. Alongside, a questionnaire survey was conducted to observe how the local houses are designed and to understand the preferences of people with regards to the design styles incorporated in their homes. In addition, their opinions on the excessive use of contemporary styles in home designs was recorded. The results of the same provided a better understanding of the local audience, their demands, and their willingness to adapt to contemporary designs. Studying color, materials, ornamentation, symbolism, detail, and structure offers an in-depth understanding of the essence of traditional Indian homes. These variables further provided effective solutions for design ideation and mockups for efficient traditional yet contemporary spaces. Design interventions like these can build a revolutionary set of practices that involve creating a balance between contemporary and traditional styles. The emergence of this synergy will not only make contemporary homes communicative but also allow India to compete within the global residential architecture industry with a strong foundation of its rich heritage.

Keywords: balance, contemporary design, cultural identity, Indian modernism

Procedia PDF Downloads 139

Authors: Sofiqul Islam, V. Murugan, Prema Kumari, Hari

Abstract:

Gentamicin is a broad spectrum water-soluble aminoglycoside antibiotics produced by the fermentation process of microorganism known as Micromonospora purpurea. It is widely used for the treatment of infection caused by both gram positive and gram negative bacteria. Gentamicin consists of a mixture of aminoglycoside components like C1, C1a, C2a, and C2. The molecular structure of Gentamicin and its related substances showed that it has lack of presence of chromophore group in the molecule due to which the detection of such components were quite critical and challenging. In this study, a simple Reversed Phase-High Performance Liquid Chromatographic (RP-HPLC) method using ultraviolet (UV) detector was developed and validated for quantification of the related substances present in Gentamicin drug substances. The method was achieved by using Thermo Scientific Hypersil Gold analytical column (150 x 4.6 mm, 5 µm particle size) with isocratic elution composed of methanol: water: glacial acetic acid: sodium hexane sulfonate in the ratio 70:25:5:3 % v/v/v/w as a mobile phase at a flow rate of 0.5 mL/min, column temperature was maintained at 30 °C and detection wavelength of 330 nm. The four components of Gentamicin namely Gentamicin C1, C1a, C2a, and C2 were well separated along with the related substance present in Gentamicin. The Limit of Quantification (LOQ) values were found to be at 0.0075 mg/mL. The accuracy of the method was quite satisfactory in which the % recovery was resulted between 95-105% for the related substances. The correlation coefficient (≥ 0.995) shows the linearity response against concentration over the range of Limit of Quantification (LOQ). Precision studies showed the % Relative Standard Deviation (RSD) values less than 5% for its related substance. The method was validated in accordance with the International Conference of Harmonization (ICH) guideline with various parameters like system suitability, specificity, precision, linearity, accuracy, limit of quantification, and robustness. This proposed method was easy and suitable for use for the quantification of related substances in routine analysis of Gentamicin formulations.

Keywords: reversed phase-high performance liquid chromatographic (RP-HPLC), high performance liquid chromatography, gentamicin, isocratic, ultraviolet

Procedia PDF Downloads 162

Authors: G. Ramya

Abstract:

Value engineering is a systematic approach, widely used to optimize the design or process or product in the designing stage. It used to achieve the client's obligation by increasing the functionality and attain the targeted cost in the cost planning. Value engineering effectiveness and benefits decrease along with the progress of the project since the change in the scope of the work and design will account for more cost all along the lifecycle of the project. Integrating the value engineering with other project management activities will promote cost minimization, client satisfaction, and ensure early completion of the project in time. Previous research studies suggested that value engineering can integrate with other project delivery activities, but research studies unable to frame a model that collaborates the project management activities with the job plan of value engineering approach. I analyzed various project management activities and their synergy between each other. The project management activities and processes like a)risk analysis b)lifecycle cost analysis c)lean construction d)facility management e)Building information modelling f)Contract administration, collaborated, and project delivery model planned along with the RIBA plan of work. The key outcome of the research is a value-driven project delivery model, which will succeed in dealing with the economic impact, constraints and conflicts arise due to the COVID-19 outbreak in the Indian construction sector. Benefits associated with the structured framework is construction project delivery that ensures early contractor involvement, mutual risk sharing, and reviving the project with a cost overrun and delay back on track ,are discussed. Keywords: Value-driven project delivery model, Integration, RIBA plan of work Themes: Design Economics

Keywords: value-driven project delivery model, Integration, RIBA

Procedia PDF Downloads 119

Authors: Sina Mahdavi

Abstract:

Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

Procedia PDF Downloads 94

Authors: Sungmin Park, Gyungmok Nam, Seungpyo Woo, Young Choi, Sangheon Park, Sang-Hee Yoon

Abstract:

Puncturing human skin with microneedles is critically important for microneedle-mediate drug delivery. Despite of extensive efforts in the past decades, the scale-up fabrication of sharp-tipped and high-aspect-ratio microneedles, especially made of biodegradable polymers, is still a long way off. Here, we present a UV dose insensitive and cost-effective microfabrication method for the biodegradable polymer microneedles with sharp tips and long lengths which can pierce human skin with low insertion force. The biodegradable polymer microneedles are fabricated with the polymer solution casting where a poly(lactic-co-glycolic acid) (PLGA, 50:50) solution is coated onto a SU-8 mold prepared with a reverse, ramped, and rotational (R3) UV exposure. The R3 UV exposure is modified from the multidirectional UV exposure both to suppress UV reflection from the bottom surface without anti-reflection layers and to optimize solvent concentration in the SU-8 photoresist, therefore achieving robust (i.e., highly insensitive to UV dose) and cost-effective fabrication of biodegradable polymer microneedles. An optical model for describing the spatial distribution of UV irradiation dose of the R3 UV exposure is also developed to theoretically predict the microneedle geometry fabricated with the R3 UV exposure and also to demonstrate the insensitiveness of microneedle geometry to UV dose. In the experimental characterization, the microneedles fabricated with the R3 UV exposure are compared with those fabricated with a conventional method (i.e., multidirectional UV exposure). The R3 UV exposure-based microfabrication reduces the end-tip radius by a factor of 5.8 and the deviation from ideal aspect ratio by 74.8%, compared with conventional method-based microfabrication. The PLGA microneedles fabricated with the R3 UV exposure pierce full-thickness porcine skins successfully and are demonstrated to completely dissolve in PBS (phosphate-buffered saline). The findings of this study will lead to an explosive growth of the microneedle-mediated drug delivery market.

Keywords: R³ UV exposure, optical model, UV dose, reflection, solvent concentration, biodegradable polymer microneedle

Procedia PDF Downloads 167

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

Procedia PDF Downloads 223

Authors: Zakieh Rostamzadeh, Zahra Shirmohammadi

Abstract:

Human cytomegalovirus is a species of the cytomegalovirus family of viruses, which in turn is a member of the viral family known as herpesviridae or herpesviruses. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised such as HIV-infected persons, organ transplant recipients, or newborn infants. After infection, HCMV has an ability to remain latent within the body over long periods. Cytomegalovirus (CMV) causes infection in immunocompromised, hemophilia patients and those who received blood transfusion frequently. This study aimed at determining the prevalence of cytomegalovirus (CMV) antibodies in hemophilia patients. Materials and Methods: A retrospective observational study was carried out in Urmia, North West of Iran. The study population comprised a sample of 50 hemophilic patients born after 1985 and have received blood factors in West Azerbaijan. The exclusion criteria include: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling. All samples were evaluated with the method of ELISA, with a certain kind of kit and by a certain laboratory. Results: Fifty hemophiliacs from 250 patients registered with Urmia Hemophilia Society were enrolled in the study including 43 (86%) male, and 7 (14%) female. The mean age of patients was 10.3 years, range 3 to 25 years. None of patients had risk factors mentioned above. Among our studied population, 34(68%) had hemophilia A, 1 (2%) hemophilia B, 8 (16%) VWF, 3(6%) factor VII deficiency, 1 (2%) factor V deficiency, 1 (2%) factor X deficiency, 1 (2%). Sera of 50 Hemodialysis patients were investigated for CMV-specific immunoglobulin G (IgG) and IgM. % 91.89 patients were anti-CMV IgG positive and %40.54 was seropositive for anti-CMV IgM. 37.8% patient had serological evidence of reactivation and 2.7% of patients had the primary infection. Discussion: There was no relationship between the antibody titer and: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling.

Keywords: bioinformatics, biomedicine, cytomegalovirus, immunocompromise

Procedia PDF Downloads 357

Authors: Sunitha Sampathi, Pankaj Kumar Tiriya, Sonia Gera, Sravanthi Reddy Pailla, V. Likhitha, A. J. Maruthi

Abstract:

Surgical site infections (SSIs) are the most common nosocomial infections localized at the incision site. With an estimated 27 million surgical procedures each year in USA, approximately 2-5% rate of SSIs are predicted to occur annually. SSIs are treated with antibiotic medication. Current trend suggest that the direct drug delivery from the suture to the scared tissue can improve patient comfort and wound recovery. For that reason coating the surface of the medical device such as suture and catguts with broad spectrum antibiotics can prevent the formation of bactierial colonies with out comprimising the mechanical properties of the sutures.Hence, the present study was aimed to develop and evaluate a surgical suture coated with an antibiotic Ciprofloxacin hydrochloride loaded on gold nanoparticles. Gold nanoparticles were synthesized by chemical reduction method and conjugated with ciprofloxacin using Polyvinylpyrolidone as stabilizer and gold as carrier. Ciprofloxacin conjugated gold nanoparticles were coated over an absorbable surgical suture made of Polyglactan using sodium alginate as an immobilising agent by slurry dipping technique. The average particle size and Polydispersity Index of drug conjugated gold NPs were found to be 129±2.35 nm and 0.243±0.36 respectively. Gold nanoparticles are characterized by UV-Vis absorption spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy and Transmission electron microscopy. FT-IR revealed that there is no chemical interaction between drug and polymer. Antimicrobial activity for coated sutures was evaluated by disc diffusion method on culture plates of both gram negative (E-coli) and gram positive bacteria (Staphylococcus aureus) and results found to be satisfactory. In vivo studies for coated sutures was performed on Swiss albino mice and histological evaluation of intestinal wound healing parameters such as wound edges in mucosa, muscularis, presence of necrosis, exudates, granulation tissue, granulocytes, macrophages, restoration, and repair of mucosal epithelium and muscularis propria on day 7 after surgery were studied. The control animal group, sutured with plain suture (uncoated suture) showed signs of restoration and repair, but presence of necrosis, heamorraghic infiltration and granulation tissue was still noticed. Whereas the animal group treated with ciprofloxacin and ciprofloxacin gold nanoparticle coated sutures has shown promising decrease in terms of haemorraghic infiltration, granulation tissue, necrosis and better repaired muscularis layers on comparision with plain coated sutures indicating faster rate of repair and less chance of sepsis. Hence coating of sutures with broad spectrum antibiotics can be an alternate technique to reduce SSIs.

Keywords: ciprofloxacin hydrochloride, gold nanoparticles, surgical site infections, sutures

Procedia PDF Downloads 256

Authors: Mahsa Ahmadi, Mehdi Mehdikhani-Nahrkhalaji, Jaleh Varshosaz, Shadi Farsaei

Abstract:

Gelatin and hyaluronic acid are commonly used in skin tissue engineering scaffolds, but because of their low mechanical properties and high biodegradation rate, adding a synthetic polymer such as polycaprolactone could improve the scaffold properties. Therefore, we developed a gelatin-hyaluronic acid-polycaprolactone scaffold, containing 0.5 % atorvastatin loaded nanostructured lipid carriers (NLCs) for skin tissue engineering. The atorvastatin loaded NLCs solution was prepared by solvent evaporation method and freeze drying process. Synthesized atorvastatin loaded NLCs was added to the gelatin and hyaluronic acid solution, and a membrane was fabricated with solvent evaporation method. Thereafter it was coated by a thin layer of polycaprolactone via spine coating set. The resulting scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. Moreover, mechanical properties, in vitro degradation in 7 days period, and in vitro drug release of scaffolds were also evaluated. SEM images showed the uniform distributed NLCs with an average size of 100 nm in the scaffold structure. Mechanical test indicated that the scaffold had a 70.08 Mpa tensile modulus which was twofold of tensile modulus of normal human skin. A Franz-cell diffusion test was performed to investigate the scaffold drug release in phosphate buffered saline (pH=7.4) medium. Results showed that 72% of atorvastatin was released during 5 days. In vitro degradation test demonstrated that the membrane was degradated approximately 97%. In conclusion, suitable physicochemical and biological properties of membrane indicated that the developed gelatin-hyaluronic acid-polycaprolactone nanocomposite scaffold containing 0.5 % atorvastatin loaded NLCs could be used as a good candidate for skin tissue engineering applications.

Keywords: atorvastatin, gelatin, hyaluronic acid, nano lipid carriers (NLCs), polycaprolactone, skin tissue engineering, solvent casting, solvent evaporation

Procedia PDF Downloads 252

Authors: Syeda Hira, Muhammad Gulfraz

Abstract:

Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

Procedia PDF Downloads 62

Authors: Wenjie Wu, Peng Cheng, Zehua Zhang, Fei Luo, Feng Wu, Min Zhong, Jianzhong Xu

Abstract:

Background: There has been limited research into the therapeutic efficacy of rapid diagnosis of spinal tuberculosis complicated with pulmonary tuberculosis. We attempted to discover whether the utilization of a DNA microarray assay to detect multidrug-resistant spinal tuberculosis complicated with pulmonary tuberculosis can improve clinical outcomes. Methods: A prospective study was conducted from February 2006 to September 2015. One hundred and forty-three consecutive culture–confirmed, clinically and imaging diagnosed MDR-TB patients with spinal tuberculosis complicated by pulmonary tuberculosis were enrolled into the study. The initial time to treatment for MDR-TB, the method of infection control, radiological indicators of spinal tubercular infectious foci, culture conversion, and adverse drug reactions were compared with the standard culture methods. Results: Of the total of 143 MDR-TB patients, 68 (47.6%) were diagnosed by conventional culture methods and 75 (52.4%) following the implementation of detection using the DNA microarray. Patients in the microarray group began rational use of the second-line drugs schedule more speedily than sufferers in the culture group (17.3 vs. 74.1 days). Among patients were admitted to a general tuberculosis ward, those from the microarray group spent less time in the ward than those from the culture group (7.8 vs. 49.2 days). In those patients with six months follow-up (n=134), patients in the microarray group had a higher rate of sputum negativity conversion at six months (89% vs. 73%). In the microarray group, the rate of drug adverse reactions was significantly lower (22.2% vs. 67.7%). At the same time, they had a more obvious reduction of the area with spinal tuberculous lesions in radiological examinations (77% vs. 108%). Conclusions: The application of the CapitalBio™ DNA Microarray assay caused noteworthy clinical advances including an earlier time to begin MDR-TB treatment, increased sputum culture conversion, improved infection control measures and better radiographical results

Keywords: tuberculosis, multidrug-resistant, tuberculous spondylitis, DNA microarray, clinical outcomes

Procedia PDF Downloads 288

Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

Abstract:

Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

Procedia PDF Downloads 176

Authors: Anupam Chanda

Abstract:

Presently Packaging plays a significant role for drug discoveries. The process of selecting materials and the type of packaging also offers an opportunity for the Packaging scientist to look for biological delivery choices. Most injectable protein products were supplied in some sort of glass vial, prefilled syringe, cartridge. Those product having high Ph content there is a chance of “delamination “from inner surface of glass vial. With protein-based drugs, the biggest issue is the effect of packaging derivatives on the protein’s threedimensional and surface structure. These are any effects that relate to denaturation or aggregation of the protein due to oxidation or interactions from contaminants or impurities in the preparation. The potential for these effects needs to be carefully considered in choosing the container and the container closure system to avoid putting patients in jeopardy. Cause of Delamination : -Formulations with a high pH include phosphate and citrate buffers increase the risk of glass delamination. -High alkali content in glass could accelerate erosion. -High temperature during the vial-forming process increase the risk of glass delamination. -Terminal sterilization (irradiated at 20-40 kGy for 150 min) also is a risk factor for specific products(veterinary parenteral administration),could cause delamination. -High product-storage temperatures and long exposure times can increase the rate and severity of glass delamination. How to prevent Delamination -Treating the surface of the glass vials with materials, such as ammonium sulfate or siliconization can reduce the rate of glass erosion. -Consider alternative sterilization methods only in rare cases. -The correct specification for the glass to ensure its suitability for the pH of the product. -Use Cyclic olefin copolymer(COC)/Cyclic olefin Polymer(COP) Adsorption of protein and Solutions: Option#1 Coat with linear methoxylated polyglycerol and hyperbranchedmethoxylated polyglycerol. Option#2 Thehyperbranched non-methoxylated coating performed best. Option#3 Coat with hyperbranched polyglycerol Option#4 Right selection of Sterilization of glass vial/syringe.

Keywords: delamination of glass, ptrotien adoptions inside the glass surface, extractable & leachable solutions, injectable designs for new drugs

Procedia PDF Downloads 94

Authors: Alkaben Patel

Abstract:

The proposed RP-HPLC method is easy, rapid, economical, precise and accurate stability indicating RP-HPLC method for simultaneous estimation of Astorvastatin and Methylcobalamine in their combined dosage form has been developed.The separation was achieved by LC-20 AT C18(250mm*4.6mm*2.6mm)Colum and water (pH 3.5): methanol 70:30 as mobile phase, at a flow rate of 1ml/min. wavelength of this dosage form is 215nm.The drug is related to stress condition of hydrolysis, oxidation, photolysis and thermal degradation.

Keywords: RP- HPLC, atorvastatin, methylcobalamine, method, development, validation

Procedia PDF Downloads 336

Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

Abstract:

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

Procedia PDF Downloads 458

Authors: Zakaria Baka, Halima Alem

Abstract:

Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

Procedia PDF Downloads 196

Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

Abstract:

The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

Procedia PDF Downloads 167

Authors: Shobha Rani R. Hiremath, Keerthana R., Madhuvan H. S.

Abstract:

BACKGROUND: Type 2 Diabetes is a chronic health condition where the body cannot effectively use the insulin it produces, leading to elevated blood sugar levels It is often associated with lifestyle factors and insulin resistance. Globally, diabetes is on the rise, with urban areas like Bangalore seeing a surge due to lifestyle changes, stress, and dietary habits. To manage diabetes effectively, over 50 medications are available, each serving to regulate blood sugar through different mechanisms. This reflects the complex and individualized nature of diabetes treatment. Given the increase in medications for Type 2 diabetes mellitus, it is important to evaluate their effectiveness and safety so that clinicians can make informed choices while treating their patients. OBJECTIVES: To evaluate the effectiveness of various anti-diabetic medications used in the hospital in Type 2 diabetes patients by monitoring their HbA1c levels. To assess the safety of these medications by monitoring Adverse drug reactions if any. METHODOLOGY Design : Prospective Cohort study, Study period: 8 months, Sample Size: 100 patients, Inclusion Criteria: Patients above 18 years of both genders who were diagnosed with T2DM and who were prescribed oral hypoglycaemic agents. Exclusion Criteria: Diabetic patients with hepatic/renal failure, patients prescribed with insulin /not prescribed with OHAs and patients who were terminally ill, pregnant and lactating patients. Source of Data: Prescriptions, lab reports, ECG reports. Data collection forms were used to collect data which consisted of patient demographic details, drugs prescribed, laboratory investigations such as HbA1C, FBS, PPBS , ECG and any ADRs experienced. Data was collected at baseline, 3 months, and 6 months. It was statistically analyzed using SPSS (version 26) software. RESULTS: Greater number of patients (46%) were in the age group of greater than 61 years. 43 patients had no co-morbidities whereas 51 patients had Hypertension as the co morbidity. Basically 5 Drug combinations were prescribed as follows. Combination 1: Tablet Metformin HCL + Glimepiride (500, 2 mg) : 1-0-1, Combination 2: Tablet Sitagliptin + Metformin HCL (50, 500 mg) : 1-0-1, Combination 3: Tablet Vildagliptin + Metformin HCL (50, 500 mg): 1-0-1, Combination 4: Tablet Voglibose+ Glimepiride+ Metformin HCL (0.2 ,2 ,500mg): : 1-0-1, Combination 5: Tablet Voglibose+ Glimepiride+ Metformin HCL (0.2, 2 ,500mg): : 1-0-1 and T. Sitagliptin +Metformin HCL (50, 500 mg): 0-1-0. Combination 5 (Voglibose, Glimepiride, Metformin, Sitagliptin) was most effective in reducing HbA1c levels, showing a significant decrease (-0.00682, p = 0.001), followed by Combinations 4 and 3. However, Combination 5 also had the highest incidence of gastrointestinal side effects (72.7%) and ECG abnormalities (27.3%). Combination 1 (Metformin + Glimepiride) had the highest occurrence of hypoglycemia due to Glimepiride's insulin-stimulating effects. Weight loss was most notable in Combination 5, affecting 36.36% of patients. CONCLUSION: The enhanced effectiveness of Combinations 3, 4, and 5 suggests that a multi-drug approach that incorporates different mechanisms of action is more effective in managing HbA1c levels in patients with diabetes. Adverse effect profiles should be considered for personalized treatment strategies.

Keywords: type 2 diabetes, safety, oral anti diabetic medications, effectiveness

Procedia PDF Downloads 9

Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

Abstract:

Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

Procedia PDF Downloads 83

Authors: Molly Parker

Abstract:

Unintended pregnancy rates in Australia are amongst the highest in the developed world. Women with Substance Use Disorder often have riskier sexual behavior with nil contraceptive use and face disproportionately higher unintended pregnancies and Sexually Transmitted Infections, alongside Substance Use in Pregnancy (SUP) climbing at an alarming rate. In an inner-city Drug and Alcohol (D&A) service, significant barriers to sexual and reproductive health services have been identified, aligning with research. Rapid pathways were created for women seeking D&A treatment to be referred to Sexual and Reproductive Health services for the administration of Long-acting reversible contraception (LARC) and sexual health screening. For clients attending a D&A service, this is an opportunistic time to offer sexual and reproductive health services. Collaboration and multidisciplinary team input between D&A and sexual health and reproductive services are paramount, with rapid referral pathways being identified as the main strategy to improve access to sexual and reproductive health support for this population. With this evidence, a rapid referral pathway was created for women using the D&A service to access LARC, particularly in view of fertility often returning once stable on D&A treatment. A closed-ended survey was used for D&A staff to identify gaps in reproductive health knowledge and views of referral accessibility. Results demonstrated a lack of knowledge of contraception and appropriate referral processes. A closed-ended survey for clients was created to establish the need and access to services and to quantify data. A follow-up data collection will be reviewed to access uptake and satisfaction of the intervention from clients. Sexual health screening access was also identified as a deficit, particularly concerning due to the higher rates of STIs in this cohort. A rapid referral pathway will be undergoing implementation, reducing risks of untreated STIS both pre and post-conception. Similarly, pre and post-intervention structured surveys will be used to identify client satisfaction from the pathway. Although currently in progress, the research and pathway aim to be completed by December 2023. This research and implementation of sexual and reproductive health pathways from the D&A service have significant health and well-being benefits to clients and the wider community, including possible fetal/infancy outcomes. Women now have rapid access to sexual and reproductive health services, with the aim of reducing unplanned pregnancies, poor outcomes associated with SUP, client/staff trauma from termination of pregnancy, and client/staff trauma following the assumption of care of the child due to substance use, the financial cost for out of home care as required, the poor outcomes of untreated STIs to the fetus in pregnancy and the spread of STIs in the wider community. As evidence suggests, the implementation of a streamlined referral process is required between D&A and sexual and reproductive health services and has positive feedback from both clinicians and clients in improving care.

Keywords: substance use in pregnancy, drug and alcohol, substance use disorder, sexual health, reproductive health, contraception, long-acting reversible contraception, neonatal abstinence syndrome, FASD, sexually transmitted infections, sexually transmitted infections pregnancy

Procedia PDF Downloads 65

Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

Abstract:

The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

Procedia PDF Downloads 117

Authors: Aurica P. Chiriac, Vera Balan, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Elena Stoleru, Loredana E. Nita, Iordana Neamtu, Alina Diaconu, Liliana Mititelu-Tartau

Abstract:

The interest for studying ‘smart’ materials is entirely justified and in this context were realized investigations on poly(2-hydroxyethylmethacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane), which is a macromolecular compound with sensibility at pH and temperature, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability. Physico-chemical characteristics in terms of the molecular weight, temperature-sensitive abilities and thermal stability, as well rheological, dielectric and spectroscopic properties were evaluated in correlation with further coupling capabilities. Differential scanning calorimetry investigation indicated Tg at 36.6 °C and a melting point at Tm=72.8°C, for the studied copolymer, and up to 200oC two exothermic processes (at 99.7°C and 148.8°C) were registered with losing weight of about 4 %, respective 19.27%, which indicate just processes of thermal decomposition (and not phenomena of thermal transition) owing to scission of the functional groups and breakage of the macromolecular chains. At the same time, the rheological studies (rotational tests) confirmed the non-Newtonian shear-thinning fluid behavior of the copolymer solution. The dielectric properties of the copolymer have been evaluated in order to investigate the relaxation processes and two relaxation processes under Tg value were registered and attributed to localized motions of polar groups from side chain macromolecules, or parts of them, without disturbing the main chains. According to literature and confirmed as well by our investigations, β-relaxation is assigned with the rotation of the ester side group and the γ-relaxation corresponds to the rotation of hydroxy- methyl side groups. The fluorescence spectroscopy confirmed the copolymer structure, the spiroacetal moiety getting an axial conformation, more stable, with lower energy, able for specific interactions with molecules from environment, phenomena underlined by different shapes of the emission spectra of the copolymer. Also, the copolymer was used as template for indomethacin incorporation as model drug, and the biocompatible character of the complex was confirmed. The release behavior of the bioactive compound was dependent by the copolymer matrix composition, the increasing of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer amount attenuating the drug release. At the same time, the in vivo studies did not show significant differences of leucocyte formula elements, GOT, GPT and LDH levels, nor immune parameters (OC, PC, and BC) between control mice group and groups treated just with copolymer samples, with or without drug, data attesting the biocompatibility of the polymer samples. The investigation of the physico-chemical characteristics of poly(2-hydrxyethyl methacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) in terms of temperature-sensitive abilities, rheological and dielectrical properties, are bringing useful information for further specific use of this polymeric compound.

Keywords: bioapplications, dielectric and spectroscopic properties, dual sensitivity at pH and temperature, smart materials

Procedia PDF Downloads 282

Authors: Fatima Zohra Belghait, Nawal Cheikh, Oscar Palacios, Ramon Barnadas, Pau Bayon

Abstract:

Metalloporphyrin and its derivatives play an important role in different scientific areas due to its tetradentate vacant site in the center that is suitable for metal coordination. Metalosomes (MTS) are supramolecular aggregates (similar to liposomes) generated by the self-assembly of compounds similar to phospholipids (with a polar and a hydrophobic part), but incorporating, as part of their membrane, molecules that contain bound metals. The aim of our work is to synthesise metalosomes containing catioinc amphiphilic porphyrin and their complexes with Fe and Cu to study their therapeutical applications. All synthesized compounds were confirmed with Dynamic Light Scattering; elemental analysis, Ultraviolet–visible spectroscopy

Keywords: metalloporphyrin, amphiphilique porphyrin, metalosomes, supramolecular

Procedia PDF Downloads 0

Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

Abstract:

Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

Procedia PDF Downloads 204

Authors: Lily Chimuanya, Ehioghae Esther

Abstract:

Language, a versatile and sophisticated tool, is fundamentally sacrosanct to mankind especially within the realm of politics. In this dynamic world, political leaders adroitly use language to engage in a strategic show aimed at manipulating or mechanising the opinion of discerning people. This nuanced synergy is marked by different rhetorical strategies, meticulously synced with contextual factors ranging from cultural, ideological, and political to achieve multifaceted persuasive objectives. This study investigates the (de)legitimation strategies inherent in African presidential inaugural speeches, as African leaders not only state their policy agenda through inaugural speeches but also subtly indulge in a dance of legitimation and delegitimation, performing a twofold objective of strengthening the credibility of their administration and, at times, undermining the performance of the past administration. Drawing insights from two different legitimation models and a dataset of 4 African presidential inaugural speeches obtained from authentic websites, the study describes the roles of authorisation, rationalisation, moral evaluation, altruism, and mythopoesis in unmasking the structure of political discourse. The analysis takes a mixed-method approach to unpack the (de)legitimation strategy embedded in the carefully chosen speeches. The focus extends beyond a superficial exploration and delves into the linguistic elements that form the basis of presidential discourse. In conclusion, this examination goes beyond the nuanced landscape of language as a potent tool in politics, with each strategy contributing to the overall rhetorical impact and shaping the narrative. From this perspective, the study argues that presidential inaugural speeches are not only linguistic exercises but also viable weapons that influence perceptions and legitimise authority.

Keywords: CDA, legitimation, inaugural speeches, delegitmation

Procedia PDF Downloads 69

Authors: Salah Belaidi

Abstract:

We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

Procedia PDF Downloads 35

Authors: Wan-Ling Jiang, Hsin Chi, Jia-Lu Cheng, Ming-Fang Cheng

Abstract:

Background: Investigating the risk factors for the fecal carriage of third-generation cephalosporin-resistant E.coli could contribute to further disease prevention. Previous research on third-generation cephalosporin-resistant prevalence in children in different regions of Taiwan is limited. This project aims to explore the risk factors and regional differences in the prevalence of third-generation cephalosporin-resistant and other antibiotic-resistant E. coli in the northern, southern, and eastern regions of Taiwan. Methods: We collected data from children aged 0 to 18 from community or outpatient clinics from July 2022 to May 2023 in southern, northern, and eastern Taiwan. The questionnaire was designed to survey the characteristics of participants and possible risk factors, such as clinical information, household environment, drinking water, and food habits. After collecting fecal samples and isolating stool culture with E.coli, antibiotic sensitivity tests and MLST typing were performed. Questionnaires were used to analyze the risk factors of third-generation cephalosporin-resistant E. coli in the three different regions of Taiwan. Results: In the total 246 stool samples, third-generation cephalosporin-resistant E.coli accounted for 37.4% (97/246) of all isolates. Among the three different regions of Taiwan, the highest prevalence of fecal carriage with third-generation cephalosporin-resistant E.coli was observed in southern Taiwan (42.7%), followed by northern Taiwan (35.5%) and eastern Taiwan (28.4%). Multi-drug resistant E. coli had prevalence rates of 51.9%, 66.3%, and 37.1% in the northern, southern, and eastern regions, respectively. MLST typing revealed that ST131 was the most prevalent type (11.8%). The prevalence of ST131 in northern, southern, and eastern Taiwan was 10.1%, 12.3%, and 13.2%, respectively. Risk factors analysis identified lower paternal education, overweight status, and non-vegetarian diet as statistical significance risk factors for third-generation cephalosporin-resistant E.coli. Conclusion: The fecal carriage rates of antibiotic-resistant E. coli among Taiwanese children were on the rise. This study found regional disparities in the prevalence of third-generation cephalosporin-resistant and multi-drug-resistant E. coli, with southern Taiwan having the highest prevalence. Lower paternal education, overweight, and non-vegetarian diet were the potential risk factors of third-generation cephalosporin-resistant E. coli in this study.

Keywords: Escherichia coli, fecal carriage, antimicrobial resistance, risk factors, prevalence

Procedia PDF Downloads 67

Authors: Afzal Hussain, Mohammad A. Altamimi, Syed Sarim Imam, Mudassar Shahid, Osamah Abdulrahman Alnemer

Abstract:

Exhaustive application of sulfamethoxazole (SUX) became as a global threat for human health due to water contamination through diverse sources. The addressed combined application of Hansen solubility (HSPiP software) parameters and Quality by Design tool for developing various green nanoemulsions. HSPiP program assisted to screen suitable excipients based on Hansen solubility parameters and experimental solubility data. Various green nanoemulsions were prepared and characterized for globular size, size distribution, zeta potential, and removal efficiency. Design Expert (DoE) software further helped to identify critical factors responsible to have direct impact on percent removal efficiency, size, and viscosity. Morphological investigation was visualized under transmission electron microscopy (TEM). Finally, the treated was studied to negate the presence of the tested drug employing ICP-OES (inductively coupled plasma optical emission microscopy) technique and HPLC (high performance liquid chromatography). Results showed that HSPiP predicted biocompatible lipid, safe surfactant (lecithin), and propylene glycol (PG). Experimental solubility of the drug in the predicted excipients were quite convincing and vindicated. Various green nanoemulsions were fabricated, and these were evaluated for in vitro findings. Globular size (100-300 nm), PDI (0.1-0.5), zeta potential (~ 25 mV), and removal efficiency (%RE = 70-98%) were found to be in acceptable range for deciding input factors with level in DoE. Experimental design tool assisted to identify the most critical variables controlling %RE and optimized content of nanoemulsion under set constraints. Dispersion time was varied from 5-30 min. Finally, ICP-OES and HPLC techniques corroborated the absence of SUX in the treated water. Thus, the strategy is simple, economic, selective, and efficient.

Keywords: quality by design, sulfamethoxazole, green nanoemulsion, water treatment, icp-oes, hansen program (hspip software

Procedia PDF Downloads 82

Authors: Ali Ghorbanipour

Abstract:

The aim of this study is to investigate the drug resistance pattern and the value of the MIC (minimum inhibitory concentration)method to reduce the impact of infectious diseases and the slow development of resistance. Method: The study was conducted on clinical specimens collected between 2018 to 2021. identification of isolates and antibiotic susceptibility testing were performed using conventional biochemical tests. Antibiotic resistance was determined using kibry-Bauer disk diffusion and MIC by E-test methods comparative with microdilution plate elisa method. Results were interpreted according to CLSI. Results: Out of 249600 different clinical specimens, 18720 different pathogenic bacteria by overall detection ratio 7.7% were detected. Among pathogen bacterial were Gram negative bacteria (70%,n=13000) and Gram positive bacteria(30%,n=5720).Medically relevant gram-negative bacteria include a multitude of species such as E.coli , Klebsiella .spp , Pseudomonas .aeroginosa , Acinetobacter .spp , Enterobacterspp ,and gram positive bacteria Staphylococcus.spp , Enterococcus .spp , Streptococcus .spp was isolated . Conclusion: Our results highlighted that the resistance ratio among Gram Negative bacteria and Gram positive bacteria with different infection is high it suggest constant screening and follow-up programs for the detection of antibiotic resistance and the value of MIC drug susceptibility reporting that provide a new way to the usage of resistant antibiotic in combination with other antibiotics or accurate weight of antibiotics that inhibit or kill bacteria. Evaluation of wrong medication in the expansion of resistance and side effects of over usage antibiotics are goals. Ali ghorbanipour presently working as a supervision at the microbiology department of Massoud medical laboratory. Iran. Earlier, he worked as head department of pulmonary infection in firoozgarhospital, Iran. He received master degree in 2012 from Fergusson College. His research prime objective is a biologic wound dressing .to his credit, he has Published10 articles in various international congresses by presenting posters.

Keywords: antimicrobial profile, MIC & MBC Method, microplate antimicrobial assay, E-test

Procedia PDF Downloads 133