Search results for: non steridol anti inlfammatory agents

Authors: B.S. Roopa

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Objectives: To investigate the prevalence of concomitant use of GPDs in patients treated with NSAIDs and GPDs in recommended dose and frequency as prophylaxis. And also to know the association between risk factors and prescription of GPDs in patients treated with NSAIDs. Methods: Study was a prospective, observational, cross-sectional survey. Data from patients with prescription of NSAIDs at the out-patient departments of secondary care Hospital, Nilgiris, India were collected in a specially designed proforma for a period of 45 days. Analysis using χ2 tests for discrete variables. Factors that might be associated with prescription of GPD with NSIADs were assessed in multiple logistic regression models. Results: Three hundred and three patients were included in this study, and the rate of GPD prescription was 89.1%. Most of the patients received H2-receptor antagonist, and, to a lesser degree, antacid and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much more likely to be co-prescribed GPD than those who had no history of GI disorders .Compared with patients who were managed in general outpatient clinic, those managed in Secondary care hospital in Nilgrisis, India were more likely to receive GPD. Conclusions: The prescription rate of GPD with NSAIDs is high. Patients were prescribed with H2RA with dose of 150mg twice daily, which are not effective in reducing the risk of NSAIDs induced gastric ulcer. Only the frequency of NSAIDs prescription was considered significant determinant for the co-prescription with GPAs in patients who are < 65 years and ≥ 65 years old.

Keywords: gastro protective agents, non steridol anti inlfammatory agents

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: Palwinder Singh

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Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Sunil Kumar

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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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Authors: Ashish Jain, Satish Nayak

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Transdermal iontophoretic drug delivery system is viable drug delivery platform technology and has a strong market worldwide. Transdermal drug delivery system is particularly desirable for therapeutic agents that need prolonged administration at controlled plasma level. This makes appropriateness to antihypertensive and anti-diabetic agents for their transdermal development. Controlled zero order absorption, easily termination of drug delivery and easy to administration also support for popularity of transdermal delivery. In this current research iontophoretic delivery of various anti diabetic agents like glipizide, glibenclamide and glimepiride were carried out. The experiments were carried out at different drug concentrations and different current densities using cathodal iontophoresis. Diffusion cell for iontophoretic permeation study was modified according to Glikfield Design. Pig skin was used for in vitro permeation study and for the in-vivo study New Zealand rabbits were used. At all concentration level iontophoresis showed enhanced permeation rate compared to passive controls. Iontophoretic transports of selected drugs were found to be increased with the current densities. Results showed that target permeation rate for selected drugs could be achieved with the aid of iontophoresis by increasing the area in an appreciable range.

Keywords: transdermal, iontophoresis, pig skin, rabbits, glipizide, glibeclamide

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Authors: Niranjan Koirala, Sumangala Darsandhari, Hye Jin Jung, Jae Kyung Sohng

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Sakuranetin, an antifungal agent and genkwanin, an anti-inflammatory agent, are flavonoids with several potential pharmaceutical applications. To produce such valuable flavonoids in large quantity, an Escherichia coli cell factory has been created. E. coli harboring O-methyltransferase (SaOMT2) derived from Streptomyces avermitilis was employed for regiospecific methylation of naringenin and apigenin. In order to increase the production via biotransformation, metK gene was overexpressed and the conditions were optimized. The maximum yield of sakuranetin and genkwanin under optimized conditions was 197 µM and 170 µM respectively when 200 µM of naringenin and apigenin were supplemented in the separate cultures. Furthermore, sakuranetin was purified in large scale and used as a substrate for in vitro glycosylation by YjiC to produce glucose and galactose derivatives of sakuranetin for improved solubility. We also found that unlike naringenin, sakuranetin effectively inhibits α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in B16F10 melanoma cells. In addition, genkwanin more potently inhibited angiogenesis than apigenin. Based on our findings, we speculate that these compounds warrant further investigation in vivo as potential new therapeutic anti-carcinogenic, anti-melanogenic and anti-angiogenic agents.

Keywords: anti-carcinogenic, anti-melanogenic, glycosylation, methylation

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Saleh Alkarri, Dimple Sharma, Teresa M. Bergholz, Muhammad Rabnawaz

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Aims: Develop a methodology for the fabrication of anti-microbial polypropylene (PP) surfaces with (i) leachable copper, (II) chloride dihydrate (CuCl₂·₂H₂O) and (ii) non-leachable magnesium hydroxide (Mg(OH)₂) biocides. Methods and Results: Two methodologies are used to develop anti-microbial PP surfaces. One method involves melt-blending and subsequent injection molding, where the biocide additives were compounded with PP and subsequently injection-molded. The other method involves the thermal embossing of anti-microbial agents on the surface of a PP substrate. The obtained biocide-bearing PP surfaces were evaluated against E. coli K-12 MG1655 for 0, 4, and 24 h to evaluate their anti-microbial properties. The injection-molded PP bearing 5% CuCl2·₂H₂O showed a 6-log reduction of E. coli K-12 MG1655 after 24 h, while only 1 log reduction was observed for PP bearing 5% Mg(OH)2. The thermally embossed PP surfaces bearing CuCl2·2H2O and Mg(OH)₂ particles (at a concentration of 10 mg/mL) showed 3 log and 4 log reduction, respectively, against E.coli K-12 MG1655 after 24 h. Conclusion: The results clearly demonstrate that CuCl₂·2H₂O conferred anti-microbial properties to PP surfaces that were prepared by both injection molding as well as thermal embossing approaches owing to the presence of leachable copper ions. In contrast, the non-leachable Mg(OH)₂ imparted anti-microbial properties only to the surface prepared via the thermal embossing technique. Significance and Impact of The Study: Plastics with leachable biocides are effective anti-microbial surfaces, but their toxicity is a major concern. This study provides a fabrication methodology for non-leachable PP-based anti-microbial surfaces that are potentially safer. In addition, this strategy can be extended to many other plastics substrates.

Keywords: anti-microbial activity, E. coli K-12 MG1655, copper (II) chloride dihydrate, magnesium hydroxide, leachable, non-leachable, compounding, thermal embossing

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Authors: Saleh Alkarri, Dimple Sharma, Teresa M. Bergholz, Muhammad Rabnawa

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Aims: Develop a methodology for the fabrication of anti-microbial polypropylene (PP) surfaces with (i) leachable copper (II) chloride dihydrate (CuCl2·2H2O) and (ii) non-leachable magnesium hydroxide (Mg(OH)2) biocides. Methods and Results: Two methodologies are used to develop anti-microbial PP surfaces. One method involves melt-blending and subsequent injection molding, where the biocide additives were compounded with PP and subsequently injection-molded. The other method involves the thermal embossing of anti-microbial agents on the surface of a PP substrate. The obtained biocide-bearing PP surfaces were evaluated against E. coli K-12 MG1655 for 0, 4, and 24 h to evaluate their anti-microbial properties. The injection-molded PP bearing 5% CuCl2·2H2O showed a 6-log reduction of E. coli K-12 MG1655 after 24 h, while only 1 log reduction was observed for PP bearing 5% Mg(OH)2. The thermally embossed PP surfaces bearing CuCl2·2H2O and Mg(OH)2 particles (at a concentration of 10 mg/mL) showed 3 log and 4 log reduction, respectively, against E.coli K-12 MG1655 after 24 h. Conclusion: The results clearly demonstrate that CuCl2·2H2O conferred anti-microbial properties to PP surfaces that were prepared by both injection molding as well as thermal embossing approaches owing to the presence of leachable copper ions. In contrast, the non-leachable Mg(OH)2 imparted anti-microbial properties only to the surface prepared via the thermal embossing technique. Significance and Impact of The Study: Plastics with leachable biocides are effective anti-microbial surfaces, but their toxicity is a major concern. This study provides a fabrication methodology for non-leachable PP-based anti-microbial surfaces that are potentially safer. In addition, this strategy can be extended to many other plastics substrates.

Keywords: anti-microbial activity, E. coli K-12 MG1655, copper (II) chloride dihydrate, magnesium hydroxide, leachable, non-leachable, compounding, thermal embossing

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Authors: Funmilola O. Omoya, Abdul O. Momoh

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Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Sharareh Sharifi

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In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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Authors: Mohamed El Moctar Abeidi

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The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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Authors: Saba Kamalledin Moghadam, Amir M. Mortazavian, Aziz Homayouni-Rad

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In the recent decade, bioactive-enriched foods, as well as natural health products, have caught the intention of the general and health-conscious population. In this regard, naturally occurring beneficial microorganisms have been successfully added to various dairy products during fermentation. Bifidobacteria, known as probiotics with a broad range of bioactivities, are commonly used in the dairy industry to naturally enrich dairy products. These bioactive metabolites are industrially and commercially important due to health-promoting activities on the consumers (e.g., anti-hypertensive, anti-diabetic, anti-oxidative, immune-modulatory, anti-cholesterolemic, or microbiome modulation, etcetera). This review aims to discuss the potential of bifidobacteria for the elaboration of dairy foods with functional properties and added value.

Keywords: dairy, probiotic, postbiotic, bifidobacteria, bifidobacterial postbiotic

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Authors: Recep Keşli, Cengiz Demir, Onur Türkyılmaz

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Objective: The aim of this study was to determine the prevalence of Mycoplasma hominis and Ureaplasma urealyticum as the causative agents in men with non-gonococcal urethtritis, and anti-bacterial resistance rates. Methods: The Study was carried out in the two Medical Microbiology Laboratories belonging to: Konya Education and Research Hospital and ANS Practice and Research Hospital, Afyon Kocatepe University, between January 2012 and December 2015. Urethral samples were obtained from patients by using a swab. Mycoplasma hominis and Ureaplasma urealyticum were detected by using Mycoplasma IST-2 kit (bio-Mérieux, Marcy l'Étoile, France). Neisseria gonorrhoea was excluded by Gram staining and culture methods. Results: Of all the one hundred and eighty-eight male patients with urethritis, forty M. hominis and forty two U. urealyticum were detected. Resistance rates of M. hominis strains against to doxycycline, ofloxacin, erythromycin, tetracycline, ciprofloxacin, azithromycin, clarithromycin, and pristinamycin were found as 5 %, 65 %, 25 %, 5 %, 80 %, 20 %, 20 %, 20 %, 5 %, respectively. Resistance rates of U. urealyticum strains against to doxycycline, ofloxacin, erythromycin, tetracycline, ciprofloxacin, azithromycin, clarithromycin, and pristinamycin were found as 4.7 %, 66.6 %, 23.8 %, 4.75 %, 81 %, 19 %, 19 %, 4.7 % respectively. No resistance was detected against to josamycin, for both the strains. Conclusions: It was concluded that; ciprofloxacin and ofloxacin had the weakest; josamycin, doxycycline, and tetracycline had the strongest in vitro anti-bacterial activity, for treatment of the NGU. So josamycin, doxycycline, and tetracycline should be preferred as the first choice of anti-bacterial agents, for treatment of the patients with non-gonococcal male urethritis.

Keywords: antimicrobial resistance, Mycoplasma hominis, non-gonococcal urethritis, Ureaplasma urealyticum

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Authors: Azar Mahmoudi

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Despite the rise of global anti-corruption movements and the strong emergence of international and national anti-corruption laws, corrupt practices are still prevalent in most places, and countries still struggle to translate these laws into practice. On the other hand, in most countries, political and economic elites oppose anti-corruption reforms. In such a situation, the role of external actors, like the other States, international organizations, and transnational actors, becomes essential. Among them, Transnational Corporations [TNCs] can develop their own regime-like framework to govern their internal activities, and through this, they can contribute to the regimes established by State actors to solve transnational issues. Among various regimes, TNCs may choose to comply with the transnational anti-corruption legal regime to avoid the cost of non-compliance with anti-corruption laws. As a result, they decide to strenghen their anti-corruption compliance as they expand into new overseas markets. Such a decision extends anti-corruption standards among their employees and third-party agents and within their projects across countries. To better address the challenges posed by corruption, TNCs have adopted a comprehensive anti-corruption toolkit. Among the various instruments, anti-corruption clauses have become one of the most anti-corruption means in international commercial agreements. Anti-corruption clauses, acting as a due diligence tool, can protect TNCs against the engagement of third-party agents in corrupt practices and further promote anti-corruption standards among businesses operating across countries. An anti-corruption clause allows parties to create a contractual commitment to exclude corrupt practices during the term of their agreement, including all levels of negotiation and implementation. Such a clause offers companies a mechanism to reduce the risk of potential corruption in their dealings with third parties while avoiding civil and administrative penalties. There have been few attempts to examine the role of anti-corruption clauses in the fight against corruption; therefore, this paper aims to fill this gap and examine anti-corruption clauses in a specific sector where corrupt practices are widespread and endemic, i.e., the petroleum industry. This paper argues that anti-corruption clauses are a positive step in ensuring that the petroleum industry operates in an ethical and transparent manner, helping to reducing the risk of corruption and promote integrity in this sector. Contractual anti-corruption clauses vary in terms of the types commitment, so parties have a wide range of options to choose from for their preferred clauses incorporated within their contracts. This paper intends to propose a categorization of anti-corruption clauses in the petroleum sector. It examines particularly the anti-corruption clauses incorporated in transnational hydrocarbon contracts published by the Resource Contract Portal, an online repository of extractive contracts. Then, this paper offers a quantitative assessment of anti-corruption clauses according to the types of contract, the date of conclusion, and the geographical distribution.

Keywords: anti-corruption, oil and gas, transnational corporations, due diligence, contractual clauses, hydrocarbon, petroleum sector

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Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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Authors: Yousef Alwashahi, Ahmed Almoqbali, Mayar Albahrani, Asma Alajmi

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We report a rare case of a 49-year-old Omani woman who is a known case of primary anti-phospholipid syndrome, glucose-6-phosphate dehydrogenase deficiency, and iron deficiency anaemia. During cannulation, she was found to develop bulla that progressed to ulcerations. With chronicity and recurrent abscess formation that usually increase after surgical intervention, a pathergy phenomenon was postulated. High suspicion of pyoderma gangrenosum was considered. Fortunately, the rapid progression of the disease was slowed down with corticosteroids, cyclosporin, and biological agents.

Keywords: anti-phospholipid syndrome, pyoderma gangrenosum, bullous pyoderma gangrenosum, pathergy, pathergy phenomenon

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Authors: Jyoti Singh, Ranju Bansal

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

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

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Authors: Husham Bayazed

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A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Rini Jarial, Puranjan Mishra, Lakhveer Singh, Sveta Thakur, A. W. Zularisam, Mimi Sakinah

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The aim of the present study was to assess the biological properties of Camellia sinensis and to identify its functional compounds. The methanolic leaves-extract (MLE) of commercial green tea (Camellia sinensis) was assessed for anti-bacterial activities by measuring inhibition zones against a panel of pathogenic bacterial strains using agar diffusion method. The flavonoid (5.0 to 8.0 mg/ml) and protein content (10 to 15 mg/ml) of the MLE were recorded. MLE at a concentration of 25 μg/ml showed marked anti-bacterial activity against all bacterial strains (11-30 mm zone of inhibition) and was maximum against Staphylococcus aureus (30 mm). The MLE of Camellia sinensis had the best MIC values of 2.25 and 0.56 mg/ml against S. aureus and Enterobacter sp., respectively. The MLE also possessed good anti-lipolytic activity (65%) against a Porcine pancreatic lipase (PPL) and cholesterol oxidase inhibition (79%). The present study provided strong experimental evidences that the MLE of Camellia sinensis is not only a potent source of natural anti-oxidants and anti-bacterial activity but also possesses efficient cholesterol degradation and anti-lipolytic activities that might be beneficial in the body weight management.

Keywords: anti-oxidant, anti-bacterial activity, anti-lipolytic activity, Camellia sinensis, phyto-chemicals

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Authors: M. Rahimi, F. Corman

Abstract:

This paper study the travel behavior of passengers in a public transport disruption under information provision strategies. We develop a within-day approach for multi-agent simulation to evaluate the behavior of the agents, under comprehensive scenarios through various information exposure, equilibrium, and non-equilibrium scenarios. In particular, we quantify the effects of information strategies in disruption situation on passengers’ satisfaction, number of involved agents, and the caused delay. An agent-based micro-simulation model (MATSim) is applied for the city of Zürich, Switzerland, for the purpose of activity-based simulation in a multimodal network. Statistic outcome is analysed for all the agents who may be involved in the disruption. Agents’ movement in the public transport network illustrates agents’ adaptations to available information about the disruption. Agents’ delays and utility reveal that information significantly affects agents’ satisfaction and delay in public transport disruption. Besides, while the earlier availability of the information causes the fewer consequent delay for the involved agents, however, it also leads to more amount of affected agents.

Keywords: agent-based simulation, disruption management, passengers’ behavior simulation, public transport

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: M. M. Rahman, A. Liu, A. Frostegard, J. Frostegard

Abstract:

The human immune system plays an essential role in cardiovascular disease (CVD) and atherosclerosis. Our earlier studies showed that major immunocompetent cells including T cells are activated by phosphorylcholine epitope. Further, we have determined for the first time in a clinical cohort that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with the development of atherosclerosis and thus a low risk of cardiovascular diseases. It is still unknown whether activated T cells play a role in anti-PC production. Here we aim to clarify the role of T cells in anti-PC production. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured in polystyrene plates to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plates. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti-HLA 2 antibody were cultured for 6 days. Anti-PC IgM was detected by ELISA in independent experiments. More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plates, there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti-HLA 2 blocking antibody in mixed B and CD3 T cells culture. In addition, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC IgM is a protection marker for atherosclerosis development. Understanding the mechanism involved in the anti-PC IgM regulation could play an important role in strategies to raise anti-PC IgM. Studies suggest that anti-PC is T-cell independent antibody, but our study shows the major role of T cell in anti-PC IgM production. Activation of helper T cells by immunization could be a possible mechanism for raising anti-PC levels.

Keywords: anti-PC, atherosclerosis, aardiovascular diseases, phosphorylcholine

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Authors: Deeba N. Baig, Ateeqa Ijaz, Saloome Rafiq

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Camel is a religious and culturally significant animal in Asian and African regions. In Pakistan Dromedary and Bactrian are common camel breeds. Other than the transportation use, it is a pivotal source of milk and meat. The quality of its milk and meat is predominantly dependent on the geographical location and variety of vegetation available for the diet. Camel milk (CM) is highly nutritious because of its reduced cholesterol and sugar contents along with enhanced minerals and vitamins level. The absence of beta-lactoglobulin (like human milk), makes CM a safer alternative for infants and children having Cow Milk Allergy (CMA). In addition to this, it has a unique probiotic profile both in raw and fermented form. Number of Lactic acid bacteria (LAB) including lactococcus, lactobacillus, enterococcus, streptococcus, weissella, pediococcus and many other bacteria have been detected. From these LAB Lactobacilli, Bifidobacterium and Enterococcus are widely used commercially for fermentation purpose. CM has high therapeutic value as its effectiveness is known against various ailments like fever, arthritis, asthma, gastritis, hepatitis, Jaundice, constipation, postpartum care of women, anti-venom, dropsy etc. It also has anti-diabetic, anti-microbial, antitumor potential along with its robust efficacy in the treatment of auto-immune disorders. Recently, the role of CM has been explored in brain-gut axis for the therapeutics of neurodevelopmental disorders. In this connection, a lot of grey area was available to explore the probiotics and therapeutics latent in the CM available in Pakistan. Thus, current study was designed to explore the predominant probiotic flora and antimicrobial potential of CM from different local breeds of Pakistan. The probiotics have been identified through biochemical, physiological and ribo-typing methods. In addition to this, bacteriocins (antimicrobial-agents) were screened through PCR-based approach. Results of this study revealed that CM from different breeds of camel depicted a number of similar probiotic candidates along with the range of limited variability. However, the nucleotide sequence analysis of selected anti-listerial bacteriocins exposed least variability. As a conclusion, the CM has sufficient probiotic availability and significant anti-microbial potential.

Keywords: bacteriocins, camel milk, probiotics potential, therapeutics

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Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

Procedia PDF Downloads 117

Authors: A. Abdenbi, B. Dennai, B. Touati, M. Bouaaza, A. Saad

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The essential oils of many plants have become popular in recent years and their bioactive principles have recently won several industry sectors, however their use as antibacterial and anti fungal agents has been reported. This study focuses on the physico chemical and phyto chemical with a study of the antimicrobial activity of essential oils of aromatic and medicinal plant of southwest Algeria, this essential oil was obtained by hydro-distillation of aerial parts of Cotula cinerea, belonging to the Asteraceae family, it is very extensive in the spring season in a region called Kenadza road, located 12km from Bechar. Variable anti fungal activity of the essential oil of Cotula cinerea (yield 2%) were revealed about four fungal strains, the minimum inhibitory concentrations of essential oils were determined by the method of dilution in agar. Significant fungal sensitivity of Penicillium sp with an inhibition of 32.3 mm area.

Keywords: Cotula cinerea, essential oil, physico- chemical analysis and phyto- chemical, anti fungal power

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Authors: Malgorzata Kurleto

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This study is trying to analyse the organization of the anti-doping system globally (particularly in Poland). The analysis is going to show the concept of doping, indicating the types of doping, and list of banned substances and methods. The paper discusses ethical aspects of the global anti-doping system. The analysis is focusing on organization of global Anti-Doping Agency. The paper will try to describe the basic assumptions of regulations adopted by WADA, called "standards” as well organization and functioning of the Polish Anti-Doping Agency (including the legal basis: POLADA). The base for this discuss will be the Polish 2018 annual report, which shows the most important assumptions, implementation and the number of anti-doping proceedings conducted in Poland. The aim of this paper is to show ethical arguments on anti-doping management strategies.

Keywords: anti-doping, ethical dilemmas, sports doping, WADA, POLADA

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Authors: Salma Mirza, Syeda Asma Naqvi, Khalid Mohammed Khan, M. Iqbal Choudhary

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In this study twenty-five (25) newly synthesized compounds substituted aryl thiazoles (SAT) 1-25 were synthesized, and in vitro cytotoxicity of these compounds was evaluated against four cancer cell lines namely, MCF-7 (ER+ve breast), MDA-MB-231 (ER-ve breast), HCT116 (colorectal), and, HeLa (cervical) and compared with the standard anticancer drug doxorubicin with IC50 value of 1.56 ± 0.05 μM. Among them, compounds 1, 4-8 and 19 were found to be active against all four cell lines. Compound 20 was found to be selectively active against MCF7 cells with IC50 value of 40.21 ± 4.15 µM, whereas compound 19 was active against only MCF7 and HeLa cells with IC50 values of 46.72 ± 1.8 and 19.86 ± 0.11 μM, respectively. These results suggest that aryl thiazoles 1 and 4 deserve to be investigated further in vivo as anti-cancer agents.

Keywords: anticancer agents, breast cancer cell lines (MCF7, MDA-MB-231), colorectal cancer cell line (HCT-116), cervical cancer cell line (HeLa), Thiazole derivatives

Procedia PDF Downloads 271