Search results for: drug administration

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

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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

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Authors: Meduranda Marco

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This paper aimed to discuss the Integrative Assessment (IA) initiative of the Schools Division Office - Navotas City. The introduction provided a brief landscape analysis of the current state of education, the context of SDO Navotas, and the rationale for the administration of Integrative Assessment (IA) in schools. The IA methodology, procedure, and implementation activities were also shared. Feedback and reports on IA showed positive results as all schools in the Division were able to operationalize IA and consequently foster academic ease for learners and parents. Challenges met after compliance were also documented and strategies to continuously improve the Integrative Assessment process were proposed.

Keywords: distance learning assessment, integrative assessment, academic ease, learning outcomes evaluation

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Authors: Charles A. Khamala

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In 2003, constrained by an absent “rule of law culture” and negative economic growth, the new Kenyan government chose to pursue incremental judicial reforms rather than comprehensive constitutional reforms. President Mwai Kibaki’s first administration’s judicial reform strategy was two pronged. First, to implement unprecedented “radical surgery,” he appointed a new Chief Justice who instrumentally recommended that half the purportedly-corrupt judiciary should be removed by Presidential tribunals of inquiry. Second, the replacement High Court judges, initially, instrumentally-endorsed the “radical surgery’s” administrative decisions removing their corrupt predecessors. Meanwhile, retention of the welfare-reducing Constitution perpetuated declining public confidence in judicial institutions culminating in refusal by the dissatisfied opposition party to petition the disputed 2007 presidential election results, alleging biased and corrupt courts. Fatefully, widespread post-election violence ensued. Consequently, the international community prompted the second Kibaki administration to concede to a new Constitution. Suddenly, the High Court then adopted a non-instrumental interpretation to reject the 2003 “radical surgery.” This paper therefore critically analyzes whether the Kenyan court’s inconsistent interpretations–pertaining to the constitutionality of the 2003 “radical surgery” removing corruption from Kenya’s courts–was predicated on political expediency or human rights principles. If justice “must also seen to be done,” then pursuit of the CJ’s, Judicial Service Commission’s and president’s political or economic interests must be limited by respect for the suspected judges and magistrates’ due process rights. The separation of powers doctrine demands that the dismissed judges should have a right of appeal which entails impartial review by a special independent oversight mechanism. Instead, ignoring fundamental rights, Kenya’s new Supreme Court’s interpretation of another round of vetting under the new 2010 Constitution, ousts the High Court’s judicial review jurisdiction altogether, since removal of judicial corruption is “a constitutional imperative, akin to a national duty upon every judicial officer to pave way for judicial realignment and reformulation.”

Keywords: administrative decisions, corruption, fair hearing, judicial review, (non) instrumental

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

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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

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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

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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

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Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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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

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Authors: Alkaben Patel

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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

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Authors: Szilvia Vincze, Zoltán Bács

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It has become increasingly important for institutions of higher education as well to use available resources as effectively as possible for the implementation of the institution’s strategic plans and, at the same time, to ensure a stable future. This is the responsibility of the management and administration of the institution. Having access to complete and comprehensive information is indispensable for making dynamic and well-founded decisions that consider the realization of objectives to be primary and that manage possibly emerging risks, etc. The present paper introduces the role of Management Information Systems (MIS) at the University of Debrecen, one of the largest institutions of higher education in Hungary, and also discusses the utilization of this and associated information systems in management functions.

Keywords: management information system (MIS), higher education, Hungary, strategy formulation

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

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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.

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Authors: Zakaria Baka, Halima Alem

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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

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

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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

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Authors: W. Hajuthman, R. Warner, S. Rahman, M. Abraham, H. Helliwell, D. Bodiwala

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Context: Prostate cancer is a prevalent cancer in males in Europe and the US, with diagnosis primarily relying on PSA testing, mpMRI, and subsequent biopsies. However, this diagnostic strategy may lead to complications for patients. Research Aim: The aim of this study is to assess compliance with trust guidelines for antibiotic prophylaxis in patients undergoing transperineal template biopsies of the prostate and evaluate the rate of post-procedure complications. Methodology: This study is conducted retrospectively over an 8-month period. Data collection includes patient demographics, compliance with trust guidelines, associated risk factors, and post-procedure complications such as infection, haematuria, and urinary retention. Findings: The audit includes 100 patients with a median age of 66.11. The compliance with pre-procedure antibiotics was 98%, while compliance with antibiotic prophylaxis recommended by trust guidelines was 68%. Among the patients, 3% developed post-procedure sepsis, with 2 requiring admission for intravenous antibiotics. No evident risk factors were identified in these cases. Additionally, post-procedure urinary retention occurred in 3% of patients and post-procedure haematuria in 2%. Theoretical Importance: This study highlights the increasing use of transperineal template biopsies across UK centres and suggests that having a standardized protocol and compliance with guidelines can reduce confusion, ensure appropriate administration of antibiotics, and mitigate post-procedure complications. Data Collection and Analysis Procedures: Data for this study is collected retrospectively, involving the extraction and analysis of relevant information from patient records over the specified 8-month period. Question Addressed: This study addresses the following research questions: (1) What is the compliance rate with trust guidelines for antibiotic prophylaxis in transperineal template biopsies of the prostate? (2) What is the rate of post-procedure complications, such as infection, haematuria, and urinary retention? Conclusion: Transperineal template biopsies are becoming increasingly prevalent in the UK. Implementing a standardized protocol and ensuring compliance with guidelines can reduce confusion, ensure proper administration of antibiotics, and potentially minimize post-procedure complications. Additionally, considering that studies show no difference in outcomes when prophylactic antibiotics are not used, the reminder to follow trust guidelines may prompt a re-evaluation of antibiotic prescribing practices.

Keywords: prostate, transperineal template biopsies of prostate, antibiotics, complications, microbiology, guidelines

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Authors: Balakumar Pitchai, Xiang Llan Ang, Sunil Prajapati, Varatharajan Rajavel, Sundram Karupiah, Mohd Baidi Bahari

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The study examined the pretreatment and post-treatment effects of low-doses of fenofibrate and rosuvastatin in gentamicin-induced acute nephrotoxicity in rats. Gentamicin (100 mg/kg/day, i.p.) was administered to rats for 8 days. In the pretreatment protocol, low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) treatments were started a day before the administration of gentamicin and continued for 8 days. In the post-treatment protocol, rats administered gentamicin were treated with low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) for 6 days after the completion of 8 days protocol of gentamicin administration. Gentamicin-associated acute nephrotoxicity in rats was assessed in terms of biochemical analysis and renal histopathological studies. Gentamicin-administered rats showed marked renal functional changes as assessed in terms of a significant increase in serum creatinine and urea levels as compared to normal rats. The renal dysfunction noted in gentamicin administered rats was accompanied with elevated serum uric acid level as compared to normal rats while there was no significant change in lipid profile. Low-dose fenofibrate pretreatment in gentamicin-administered rats afforded a significant renal functional improvements and renoprotection while its post-treatment showed no significant renoprotection. On the other hand, pretreatment with low-dose rosuvastatin partially reduced gentamicin-induced increase in serum creatinine level, but its post-treatment did not afford renal functional improvements in gentamicin-administered rats. However, all pre and post-treatments with low-doses of fenofibrate or rosuvastatin significantly reduced the elevated serum uric acid concentration in gentamicin-administered rats. Renal histopathological analysis showed a discernible incidence of acute tubular necrosis in gentamicin-administered rats which were markedly reduced by low-dose fenofibrate or low-dose rosuvastatin pretreatments; but, not by their post-treatments. In conclusion, low-dose fenofibrate pretreatment considerably prevented gentamicin-induced acute tubular necrosis and renal functional abnormalities in rats while its post-treatment resulted in no significant renoprotective action. In spite of effective prevention of gentamicin-induced acute tubular necrosis, the pretreatment with low-dose rosuvastatin had only a partial and fractional protection on renal functional abnormalities. The post-treatment with low-dose rosuvastatin was ineffective in affording a renoprotection in gentamicin-administered rats.

Keywords: gentamicin-nephrotoxicity, low-dose fenofibrate, low-dose rosuvastatin, renoprotection

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

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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

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Authors: Priti S. Tidke, Chandragouda R. Patil

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The present study was designed to investigate the effect of Magnesia phosphorica, a biochemical medicine on urine screeing, biochemical, histopathological, and electron microscopic images in ethylene glycol induced nepholithiasis in rats.Male Wistar albino rats were divided into six groups and were orally administered saline once daily (IR-sham and IR-control) or Magnesia phosphorica 100 mg/kg twice daily for 24 days.The effect of various dilutions of biochemical Mag phos3x, 6x, 30x was determined on urine output by comparing the urine volume collected by keeping individual animals in metabolic cages. Calcium oxalate urolithiasis and hyperoxaluria in male Wistar rats was induced by oral administration of 0.75% Ethylene glycol p.o. daily for 24 days. Simultaneous administration of biochemical 3x, 6x, 30xMag phos (100mg/kg p.o. twice a day) along with ethylene glycol significantly decreased calcium oxalate, urea, creatinine, Calcium, Magnesium, Chloride, Phosphorus, Albumin, Alkaline Phosphatase content in urine compared with vehicle-treated control group.After the completion of treatment period animals were sacrificed, kidneys were removed and subjected to microscopic examination for possible stone formation. Histological estimation of kidney treated with biochemical Mag phos (3x, 6x, 30xMag phos 100 mg/kg, p.o.) along with ethylene glycol inhibited the growth of calculi and reduced the number of stones in kidney compared with control group. Biochemical Mag phos of 3x dilution and its crude equivalent also showed potent diuretic and antiurolithiatic activity in ethylene glycol induced urolithiasis. A significant decrease in the weight of stones was observed after treatment in animals which received biochemical Mag phos of 3x dilution and its crude equivalent in comparison with control groups. From this study, it can be proposed that the 3x dilution of biochemical Mag phos exhibits a significant inhibitory effect on crystal growth, with the improvement of kidney function and substantiates claims on the biological activity of twelve tissue remedies which can be proved scientifically through laboratory animal studies.

Keywords: Mag phos, Magnesia phosphorica, ciochemic medicine, urolithiasis, kidney stone, ethylene glycol

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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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: 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

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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

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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: Nathalie Stephenne, Mathieu Veschkens, Stéphane Palm, Christophe Charlemagne, Jacques Defoux

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According to Europe’s first River basin Management Plans (RBMPs), 56% of European rivers failed to achieve the good status targets of the Water Framework Directive WFD. In Central European countries such as Belgium, even more than 80% of rivers failed to achieve the WFD quality targets. Although the RBMP’s should reduce the stressors and improve water body status, their potential to address multiple stress situations is limited due to insufficient knowledge on combined effects, multi-stress, prioritization of measures, impact on ecology and implementation effects. This paper describes a webGis prototype developed for the Walloon administration to improve the communication and the management of sediment dredging actions carried out in rivers and lakes in the frame of RBMPs. A large number of stakeholders are involved in the management of rivers and lakes in Wallonia. They are in charge of technical aspects (client and dredging operators, organizations involved in the treatment of waste…), management (managers involved in WFD implementation at communal, provincial or regional level) or policy making (people responsible for policy compliance or legislation revision). These different kinds of stakeholders need different information and data to cover their duties but have to interact closely at different levels. Moreover, information has to be shared between them to improve the management quality of dredging operations within the ecological system. In the Walloon legislation, leveling dredged sediments on banks requires an official authorization from the administration. This request refers to spatial information such as the official land use map, the cadastral map, the distance to potential pollution sources. The production of a collective geodatabase can facilitate the management of these authorizations from both sides. The proposed internet system integrates documents, data input, integration of data from disparate sources, map representation, database queries, analysis of monitoring data, presentation of results and cartographic visualization. A prototype of web application using the API geoviewer chosen by the Geomatic department of the SPW has been developed and discussed with some potential users to facilitate the communication, the management and the quality of the data. The structure of the paper states the why, what, who and how of this communication tool.

Keywords: sediments, web application, GIS, rivers management

Procedia PDF Downloads 405

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

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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

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Authors: Josine Beek, S. Agten, R. Del Pozo, B. Balis

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The objective of the present study was to compare the safety of intramuscular administration of Zuprevo® (tildipirosin, 40 mg/mL) with Draxxin® (tulathromycin, 100 mg/mL) in the treatment of swine respiratory disease at weaning age. The trial was carried out in two farrow-to-finish farms with 300 sows (farm A) and 500 sows (farm B) in a batch-production system. Farm A had no history of respiratory problems, whereas farm B had a history of respiratory outbreaks with increased mortality ( > 2%) in the nursery. Both farms were positive to Pasteurella multocida, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Haemophilus parasuis. From each farm, one batch of piglets was included (farm A: 644 piglets; farm B: 963 piglets). One day before weaning (day 0; 18-21 days of age), piglets were identified by an individual ear tag and randomly assigned to a treatment group. At day 0, Group 1 was treated with a single intramuscular injection with Zuprevo® (tildipirosin, 40 mg/mL; 1 mL/10 kg) and group 2 with Draxxin® (tulathromycin, 100 mg/mL; 1 mL/40 kg). For practical reasons, dosage of the product was adjusted according to three weight categories: < 4 kg, 4-6 kg and > 6 kg. Within each farm, piglets of both groups were comingled at weaning and subsequently managed and located in the same facilities and with identical environmental conditions. Our study involved the period from day 0 until 10 weeks of age. Safety of treatment was evaluated by 1) visual examination for signs of discomfort directly after treatment and after 15 min, 1 h and 24 h and 2) mortality rate within 24 h after treatment. Efficacy of treatment was evaluated based on mortality rate from day 0 until 10 weeks of age. Each piglet that died during the study period was necropsied by the herd veterinarian to determine the probable cause of death. Data were analyzed using binary logistic regression and differences were considered significant if p < 0.05. The pig was the experimental unit. In total, 848 piglets were treated with tildipirosin and 759 piglets with tulathromycin. In farm A, one piglet with retarded growth ( < 1 kg at 18 days of age) showed an adverse reaction after injection of tildipirosin: lateral recumbence and dullness for ± 30 sec. The piglet recovered after 1-2 min. This adverse reaction was probably due to overdosing (12 mg/kg). No adverse effect of treatment was observed in any other piglet. There was no mortality within 24 h after treatment. No significant difference was found in mortality rate between both groups from day 0 until 10 weeks of age. In farm A, overall mortality rate was 0.3% (2/644). In farm B, mortality rate was 0.2% (1/502) in group 1 (tildipirosin) and 0.9% (4/461) in group 2 (tulathromycin)(p=0.60). The necropsy of piglets that died during the study period revealed no macroscopic lesions of the respiratory tract. In conclusion, Zuprevo® (tildipirosin, 40 mg/mL) was shown to be a safe and efficacious alternative to Draxxin® (tulathromycin, 100 mg/mL) for the early treatment of swine respiratory disease at weaning age.

Keywords: antibiotic treatment, safety, swine respiratory disease, tildipirosin

Procedia PDF Downloads 395

Authors: Talal Alqahtani

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For all institutions, either public or private, communication is important now more than ever. This is because the importance of communication has grown over the years, and it has the ability to either break or make an organization. With globalization, the changing technology, and other emergent issues that affect organizations, the communication given out has had to be better, sharper, and both proactive and reactive. This is the reason why the importance of public relations has been on the increase. Institutions realize the importance of having a good image and having public relations experts who can effectively manage communication in an institution easily in times of crisis. Public relations itself is not, however, effective, and this has led to the adoption of rhetoric in communication. Rhetoric use has had a long transformation because, in the past, it was only used in politics. Rhetoric in communication has come to be appreciated and adopted by many diverse fields and sectors. This study looks at the job of rhetoric in public relations practice and how it can identify with the administration of an institution's notoriety.

Keywords: communication, notoriety, rhetoric, public relation

Procedia PDF Downloads 234

Authors: Salah Belaidi

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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 34

Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

Procedia PDF Downloads 76

Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

Procedia PDF Downloads 88

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

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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

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

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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

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Authors: Aistis ZekevicIus

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Biopolitical theory, which was first developed by Michel Foucault, takes into consideration the administration of life by implying a style of government based on the regulation of populations as its subject. The intensification of the #BlackLivesMatter movement and popular outcries against racial discrimination in the US health system have prompted us to reconsider the relationship between biopolitics and race in the face of the COVID-19 pandemic. Based on works by Foucault, Achille Mbembe and Nicholas Mirzoeff that transcend the boundaries of poststructuralism, critical theory and postcolonial studies, the paper suggests that the global pandemic has highlighted new aspects of the interplay between biopower and race by encouraging the search for scapegoats, deepening the structural racial inequality, and thus producing necropolitical regimes of exclusion.

Keywords: biopolitics, biopower, necropolitics, pandemic, race

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Authors: Ali Ghorbanipour

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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