Search results for: anti apoptotic drug

Authors: Mia I. Allen, Bernard N. Johnson, Gagan Deep, Yixin Su, Sangeeta Singth, Ashish Kumar, , Michael A. Nader

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With no FDA-approved treatments for cocaine use disorders (CUD), research has focused on the behavioral and neuropharmacological effects of cocaine in animal models, with the goal of identifying novel interventions. While the majority of people with CUD also use tobacco/nicotine, the majority of preclinical cocaine research does not include the co-use of nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys. In Experiment 1, male rhesus monkeys (N=3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and cocaine+nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward shift and significant increase in peak break point. In Experiment 2, socially housed female and male cynomolgus monkeys (N=14) self-administered cocaine under a concurrent drug-vs-food choice schedule. Combining nicotine significantly decreased cocaine choice ED50 values (i.e., shifted the cocaine dose-response curve to the left) in females but not in males. There was no evidence of social rank differences. In delay discounting studies, the co-use of nicotine and cocaine required significantly larger delays to the preferred drug reinforcer to reallocate choice compared with cocaine alone. Overall, these results suggest drug interactions of nicotine and cocaine co-use is not simply a function of potency but rather a fundamentally distinctive condition that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.

Keywords: polydrug use, animal models, nonhuman primates, behavioral pharmacology, drug self-administration

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Chuan Yin

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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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Authors: Daniel Kliewe, Arno Kühn, Roman Dumitrescu, Jürgen Gausemeier

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This paper examines the system protection for cyber-physical systems (CPS). CPS are particularly characterized by their networking system components. This means they are able to adapt to the needs of their users and its environment. With this ability, CPS have new, specific requirements on the protection against anti-counterfeiting, know-how loss and manipulation. They increase the requirements on system protection because piracy attacks can be more diverse, for example because of an increasing number of interfaces or through the networking abilities. The new requirements were identified and in a next step matched with existing protective measures. Due to the found gap the development of new protection measures has to be forced to close this gap. Moreover a comparison of the effectiveness between selected measures was realized and the first results are presented in the paper.

Keywords: anti-counterfeiting, cyber physical systems, intellectual property (IP), knowledge management, system protection

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Authors: Deepak Mohan, Sushma Sharma, Mohammad Asif

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Diclofenac sodium being one of the most common non-steroidal anti-inflammatory drugs is normally used as painkiller and to reduce inflammation. The drug is known to alter the enzymatic activities of acid and alkaline phosphatase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminases. The drug also results in change in the concentration of proteins and lipids in the body. The present study is an attempt to study different biochemical changes electrophoretically due to administration of different doses of diclofenac (4mg/kg/body weight and 14mg/kg/body weight) on liver and testes of mice from 7-28 days of investigation. Homogenization of the tissue was done, supernatant separated was loaded in the gel and native polyacrylamide gel electrophoresis was conducted. Diclofenac administration resulted in alterations of all these biochemical parameters which were observed in native polyacrylamide gel electrophoretic studies. The severe degenerative changes as observed during later stages of the experiment showed correlation with increase or decrease in the activities of all the enzymes studied in the present investigation. Image analysis of gel in liver showed a decline of 7.4 and 5.3 % in low and high dose group after 7 days whereas a decline of 9.6 and 7.5% was registered after 28 days of investigation. Similar analysis for testis also showed an appreciable decline in the activity of alkaline phosphatase after 28 days. Gel analysis of serum was also performed to find a correlation in the enzymatic activities between the tissue and blood.

Keywords: diclofenac, inflammation, polyacrylamide, phosphatase

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

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

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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Authors: Mohammed Albakariyu Kabir

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There is a trend in development discourse to understand and explain the level of corruption in Nigeria, its anti-corruption crusade and why it is failing, as well as its level of compliance with International standards of United Nations Convention against Corruption (UNCAC) & African Union Convention on Converting and Preventing Corruption) to which Nigeria is a signatory. This paper discusses the legal and Constitutional provisions relating to corrupt practices and safeguards in Nigeria, as well as the obstacles to the implementation of these Conventions.The paper highlights the challenges posed to the Anti-Corruption crusade by analysing the loopholes that exist both in administrative structure and in scope of the relevant laws. The paper argues that Nigerian Constitution did not make adequate provisions for the implementation of the conventions, hence a proposal which will ensure adequate provision for implementing the conventions to better the lives of Nigerians. The paper concludes that there is the need to build institutional parameters, adequate constitutional and structural safeguards, as well as to synergise strategies, collaborations and alliances to facilitate the timely domestication and implementation of the conventions.

Keywords: anti-corruption, corruption, convention, domestication, poverty, state parties

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Edna Gnomblerou

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Given the current scale of corruption epidemic in West African economies, governments are seeking for immediate and effective measures to reduce the likelihood of the plague within the region. Generally, accountants and auditors are expected to help organizations in detecting illegal practices. However, their role in the fight against corruption is sometimes limited due to the collusive nature of corruption. The Denmark anti-corruption model shows that the implementation of additional controls over public accounts and independent efficient audits improve transparency and increase the probability of detection. This study is aimed at reviewing the existing anti-corruption policies of the Economic Commission of West African States (ECOWAS) as to observe the role attributed to accounting, auditing and other managerial practices in their anti-corruption drive. It further discusses the usefulness of accounting and auditing in helping anti-corruption commissions in controlling misconduct and increasing the perception to detect irregularities within public administration. The purpose of this initiative is to identify and assess the relevance of accounting and auditing in curbing corruption. To meet this purpose, the study was designed to answer the questions of whether accounting and auditing processes were included in the reviewed anti-corruption strategies, and if yes, whether they were effective in the detection process. A descriptive research method was adopted in examining the role of accounting and auditing in West African anti-corruption strategies. The analysis reveals that proper recognition of accounting standards and implementation of financial audits are viewed as strategic mechanisms in tackling corruption. Additionally, codes of conduct, whistle-blowing and information disclosure to the public are among the most common managerial practices used throughout anti-corruption policies to effectively and efficiently address the problem. These observations imply that sound anti-corruption strategies cannot ignore the values of including accounting and auditing processes. On one hand, this suggests that governments should employ all resources possible to improve accounting and auditing practices in the management of public sector organizations. On the other hand, governments must ensure that accounting and auditing practices are not limited to the private sector, but when properly implemented constitute crucial mechanisms to control and reduce corrupt incentives in public sector.

Keywords: accounting, anti-corruption strategy, auditing, ECOWAS

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Authors: Shirin Jalili, Sadegh Hasannia, Hadi Shirzad, Afshin Khara

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Morphine is one of the most medicinally important analgesics and narcotics. Structurally, it is classified as an alkaloid because of the presence of nitrogen. Its structure is similar to that of codeine, thebaine, and heroin. An immunoassay to accurately discriminate between these analogous alkaloids would be highly beneficial. A key factor for such an assay is specificity with high sensitivity, which is totally dependent on the antibody employed. However, most antibodies against haptens are polyclonal serum antibodies that exhibit significant cross-reactivities with closely related compounds. The camel-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity, possessing unique properties compared to other conventional antibodies. In this study, a library containing the VHH genes of a camel immunized with with morphine conjugated BSA following phage display technology was generated. By screening the camel-derived variable region of the heavy chain cDNA phage display library with the ability to bind the desired hapten, we obtained some nanobodies that recognize this hapten. Phage display expression of the Nbs from this library and pannings against this hapten resulted in a clear enrichment of four distinct Nb-displaying phages with specificity for morphine that could be a potential target site for the development of new strategies for the development of a biosensor for detecting illicit drug.

Keywords: phage display, nanobody, Morphine-3, glucuronide, ELISA, biosensor

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Authors: Janneth Gonzalez, Marco Avila, George Barreto

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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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Authors: Camilla Trevor, Matthew K. Higgins, Andrea Gonzalez-Munoz, Mark Carrington

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Trypanosomiasis is a devastating disease affecting both humans and livestock in sub-Saharan Africa. The diseases are caused by infection with African trypanosomes, protozoa transmitted by tsetse flies. Treatment currently relies on the use of chemotherapeutics with ghastly side effects. Here, we describe the development of effective antibody-drug conjugates that target the T. brucei transferrin receptor. The receptor is essential for trypanosome growth in a mammalian host but there are approximately 12 variants of the transferrin receptor in the genome. Two of the most divergent variants were used to generate recombinant monoclonal immunoglobulin G using phage display and we identified cross-reactive antibodies that bind both variants using phage ELISA, fluorescence resonance energy transfer assays and surface plasmon resonance. Fluorescent antibodies were used to demonstrate uptake into trypanosomes in culture. Toxin-conjugated antibodies were effective at killing trypanosomes at sub-nanomolar concentrations. The approach of using antibody-drug conjugates has proven highly effective.

Keywords: antibody-drug conjugates, phage display, transferrin receptor, trypanosomes

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Authors: S. S. Patil, B. U. Janugade, S. V. Patil

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Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery thus increasing patient compliance. These systems are designed according to the circadian rhythm of the body. Chronotherapeutics is the discipline concerned with the delivery of drugs according to inherent activities of a disease over a certain period of time. It is becoming increasingly more evident that the specific time that patients take their medication may be even more significant than was recognized in the past. The tradition of prescribing medication at evenly spaced time intervals throughout the day, in an attempt to maintain constant drug levels throughout a 24-hour period, may be changing as researcher’s report that some medications may work better if their administration is coordinated with day-night patterns and biological rhythms. The potential benefits of chronotherapeutics have been demonstrated in the management of a number of diseases. In particular, there is a great deal of interest in how chronotherapy can particularly benefit patients suffering from allergic rhinitis, rheumatoid arthritis and related disorders, asthma, cancer, cardiovascular diseases, and peptic ulcer disease.

Keywords: pulsatile drug delivery, chronotherapeutics, circadian rhythm, asthma, chronobiology

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Authors: S. L. J. Tan, N. Billa, C. J. Roberts

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Oral delivery of amphotericin B (AmpB) potentially eliminates constraints and side effects associated with intravenous administration, but remains challenging due to the physicochemical properties of the drug such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated so as to impart sluggish transit of the NLC along the gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. The AmpB-loaded NLC formulation was successfully formulated via high shear homogenisation and ultrasonication. A chitosan coating was adsorbed onto the formed NLC. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency (%EE), aggregation states and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were examined. The particle size of the freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential change towards positivity. Interestingly, the chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) showed significant decrease in particle size upon storage, suggesting 'anti-Ostwald' ripening effect. AmpB-loaded NLC formulation showed %EE of 94.3 ± 0.02 % and incorporation of chitosan increased the %EE significantly, to 99.3 ± 0.15 %. This suggests that the addition of chitosan renders stability to the NLC formulation, interacting with the anionic segment of the NLC and preventing the drug leakage. AmpB in both NLC and ChiAmpB NLC showed polyaggregation which is the non-toxic conformation. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic pH (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.

Keywords: Amphotericin B, mucoadhesion, nanostructured lipid carriers, oral delivery

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Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

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Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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Authors: Ria Ghosh, Soumendra Singh, Dipanjan Mukherjee, Susmita Mondal, Monojit Das, Uttam Pal, Aniruddha Adhikari, Aman Bhushan, Surajit Bose, Siddharth Sankar Bhattacharyya, Debasish Pal, Tanusri Saha-Dasgupta, Maitree Bhattacharyya, Debasis Bhattacharyya, Asim Kumar Mallick, Ranjan Das, Samir Kumar Pal

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Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k1 ~652 s 1. However, no significant release of encapsulated TB at micellar concentration was observed within the experimental time frame. This originated from the higher binding affinity of TB towards the nano-cavity of SDS at micellar concentration which does not allow the delivery of TB from the nano-cavity of SDS micelles to DNA. Thus, molecular recognition controls the extent of DNA recognition by TB which in turn modulates the rate of delivery of TB from SDS in a concentration-dependent manner.

Keywords: DNA, drug delivery, micelle, pre-micelle, SDS, toluidine blue

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Authors: Xiaohan Gu

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China is perceived as one of the most politically corrupt countries in the world. The 2021 Transparency International Corruption Perceptions Index China (RPC) ranks the country in 66th place out of 180 countries in the Index, where the 180 countries are perceived to have the most corrupt public sector. This paper proposes a theory on the impact of corruption on the consumption of luxury goods. We test the theory and evaluate the effectiveness of China’s anti-corruption campaign in 2012 by conducting a difference-in-differences analysis of product-city-level alcohol and cigarette consumption from 2013 to 2022. We find that the campaign increased sales of middle-end baijiu and cigarettes but decreased sales of luxury baijiu and cigarettes, contrasting with the trend for low-end products. This substitution pattern may be attributable to decreased public spending on luxury goods. This substitution pattern is moderated by officials’ wages and anti-corruption efforts, which supports the theoretical predictions.

Keywords: substitution effect, baijiu, corruption, anti-corruption, chinese political connection

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Authors: Saleh Mobasseri, Mohammad Mobasseri

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The article refers to the history of the rise of brake system and described it’s importance in passenger’s lives. The disc brake system performance and ABS are also compared with each other by the kinetic and kinematic analysis of the braking system,and evaluate the impact of each parameters is checked on the vehicle stopping distance. Anti−lock braking system (ABS) is one of the most important features that affect on vehicle safety and for this reason much efforts have been made to improve this system. The objectives of the anti−lock system (ABS) are as follows: Preventing the wheels from locking, achieving maximum technical momentum in terms of braking,stability,reducing stopping distances. In this paper,we study the comparative of ABS brake and disc brake.

Keywords: anti−lock braking System (ABS), stopping distances, booster, car stability, force exerted on the brake pedal

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Authors: Venoos Iman, Suzita Mohd Noor, Syam Mohan, Mohamad Ibrahim Noordin

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Girinimbine, a carbazole alkaloid was isolated from the stem bark and root of Murraya koenigii and its structure and purity was identified by HPLC and LC-MS. Here we report that Girinimbine strongly inhibit angiogenesis activity both in vitro and in vivo. MTT result showed that girinimbine inhibits cell proliferation of the HUVECS cell line in vitro. Result of endothelial cell invasion, migration, tube formation and wound healing assays also demonstrated significant time and does dependent inhibition by girinimbine. Moreover, girinibine mediates its anti-angiogenic activity through up- and down-regulation of angiogenic and anti-aniogenic proteins. Furthermore, anti-angiogenic potential of girinimbine was evidenced in vivo on zebrafish model. Girinimbine inhibited neo-vessels formation in zebrafish embryos during 24 hours exposure time. Together, these results demonstrated for the first time that girinimbine could effectively suppress angiogenesis and strongly suggest that it might be a novel angiogenesis inhibitor.

Keywords: anti-angiogenic, carbazole alkaloid, girinimbine, zebrafish

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Authors: Linda Chularojmontri, Seewaboon Sireeratawong, Suvara Wattanapitayakul

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Terminalia arjuna Roxb. (family Combretaceae) is commonly known as ‘Sa maw thet’ in Thai. The fruit is used in traditional medicine as natural mild laxatives, carminative and expectorant. Aim of the study: This research aims to study the anti-inflammatory, analgesic and antipyretic activities of Terminalia arjuna extract by using animal models in comparison to the reference drugs. Materials and Methods: The anti-inflammatory study was conducted by two experimental animal models namely ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema. The study of analgesic activity used two methods of pain induction including acetic acid and heat-induced pain. In addition, the antipyretic activity study was performed by induced hyperthermia with yeast. Results: The results showed that the oral administration of Terminalia arjuna extract possessed acute anti-inflammatory effect in carrageenan-induced paw edema. Terminalia arjuna extract showed the analgesic activity in acetic acid-induced writhing response and heat-induced pain. This indicates its peripheral effect by inhibiting the biosynthesis and/or release of some pain mediators and some mechanism through Central nervous system. Moreover, Terminalia arjuna extract at the dose of 1000 and 1500 mg/kg body weight showed the antipyretic activity, which might be because of the inhibition of prostaglandins. Conclusion: The findings of this study indicated that the Terminalia arjuna extract possesses the anti-inflammatory, analgesic and antipyretic activities in animals.

Keywords: analgesic activity, anti-inflammatory activity, antipyretic activity, Terminalia arjuna extract

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Authors: Surya R. Niraula, Devendra B Chhetry, Girish K. Singh, S. Nagesh, Frederick A. Connell

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Background: Although random sampling is generally considered to be the gold standard for population-based research, the majority of drug abuse research is based on non-random sampling despite the well-known limitations of this kind of sampling. Method: We compared the statistical properties of two surveys of drug abuse in the same community: one using snowball sampling of drug users who then identified “friend controls” and the other using a random sample of non-drug users (controls) who then identified “friend cases.” Models to predict drug abuse based on risk factors were developed for each data set using conditional logistic regression. We compared the precision of each model using bootstrapping method and the predictive properties of each model using receiver operating characteristics (ROC) curves. Results: Analysis of 100 random bootstrap samples drawn from the snowball-sample data set showed a wide variation in the standard errors of the beta coefficients of the predictive model, none of which achieved statistical significance. One the other hand, bootstrap analysis of the random-sample data set showed less variation, and did not change the significance of the predictors at the 5% level when compared to the non-bootstrap analysis. Comparison of the area under the ROC curves using the model derived from the random-sample data set was similar when fitted to either data set (0.93, for random-sample data vs. 0.91 for snowball-sample data, p=0.35); however, when the model derived from the snowball-sample data set was fitted to each of the data sets, the areas under the curve were significantly different (0.98 vs. 0.83, p < .001). Conclusion: The proposed method of random sampling of controls appears to be superior from a statistical perspective to snowball sampling and may represent a viable alternative to snowball sampling.

Keywords: drug abuse, matched case-control study, non-probability sampling, probability sampling

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Authors: S. Bouameur, S. Chirani

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The aim of this study was to evaluate the potential use of EthylCellulose in the preparation of microspheres as a Drug Delivery System for sustained release of phenobarbital. The microspheres were prepared by solvent evaporation technique using ethylcellulose as polymer matrix with a ratio 1:2, dichloromethane as solvent and Polyvinyl alcohol 1% as processing medium to solidify the microspheres. Size, shape, drug loading capacity and entrapement efficiency were studied.

Keywords: phenobarbital, microspheres, ethylcellulose, polyvinylacohol

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

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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Authors: Fatma M. Benrabha

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The aim of the study was to determine the type and pattern of antibiotic susceptibility of the pathogenic microorganisms causing chronic suppurative otitis media (CSOM), which could lead to better therapeutic decisions and consequently avoidance of appearance of resistance to specific antibiotics. Most frequently isolated agents were Pseudomonas aeruginosa 28.5%; followed by Staphylococcus aureus 18.2%; proteus mirabilis 13.9%; Providencia stuartti 6.7%; Bacteroides melaninogenicus, Aspergillus sp., candida sp., 4.2% each; and other microorganisms were represented in 3-0.2%. Drug sensitivities pattern of Pseudomonas aeruginosa showed that ciprofloxacin was active against the majority of isolates (93.9%) followed by ceftazidime 86.2%, amikacin 76.2% and gentamicin 40.8%. However, Staphylococcus aureus isolates were resistant to penicillin 72.7%, erythromycin 28.6%, cephalothin 18.2%, cloxacillin 8.3% and ciprofloxacin was active against 96.2% of isolates. The resistance pattern of proteus mirabilis were 55.6% to ampicillin, 47.1% to carbencillin, 29.4% to cephalothin, 14.3% to gentamicin and 4.8% to amikacin while 100% were sensitive to ciprofloxacin. We conclude that ciprofloxacin is the best drug of choice in treatment of CSOM caused by the common microorganisms.

Keywords: otitis media, chronic suppurative otitis media (CSOM), microorganism, drug sensitivity

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Authors: Reena K., Mamatha H. G., Somshekarayya, P. Kumar

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Objectives: The annual proficiency testing of intermediate reference laboratories is conducted by the National Reference Laboratory (NRL) to assess the efficiency of the laboratories to correctly identify Mycobacterium tuberculosis and to determine its drug susceptibility pattern. The proficiency testing results from 2013 to 2017 were analyzed to determine laboratories that were consistent in reporting quality results and those that had difficulty in doing so. Methods: A panel of twenty cultures were sent out to each of these laboratories. The laboratories were expected to grow the cultures in their own laboratories, set up drug susceptibly testing by all the methods they were certified for and report the results within the stipulated time period. The turnaround time for reporting results, specificity, sensitivity positive and negative predictive values and efficiency of the laboratory in identifying the cultures were analyzed. Results: Most of the laboratories had reported their results within the stipulated time period. However, there was enormous delay in reporting results from few of the laboratories. This was mainly due to improper functioning of the biosafety level III laboratory. Only 40% of the laboratories had 100% efficiency in solid culture using Lowenstein Jensen medium. This was expected as a solid culture, and drug susceptibility testing is not used for diagnosing drug resistance. Rapid molecular methods such as Line probe assay and Genexpert are used to determine drug resistance. Automated liquid culture system such as the Mycobacterial growth indicator tube is used to determine prognosis of the patient while on treatment. It was observed that 90% of the laboratories had achieved 100% in the liquid culture method. Almost all laboratories had achieved 100% efficiency in the line probe assay method which is the method of choice for determining drug-resistant tuberculosis. Conclusion: Since the liquid culture and line probe assay technologies are routinely used for the detection of drug-resistant tuberculosis the laboratories exhibited higher level of efficiency as compared to solid culture and drug susceptibility testing which are rarely used. The infrastructure of the laboratory should be maintained properly so that samples can be processed safely and results could be declared on time.

Keywords: annual proficiency testing, drug susceptibility testing, intermediate reference laboratory, national reference laboratory

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Authors: Bayu Rizky Pratama, Hardiansyah Nur Sahaya

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Riau Province is the worst emitter for forest burning which causes the huge scale of externality such as declining of forest habitat, health disease, and climate change impact. Indonesia forum of budget transparency for Riau Province (FITRA) reported the length of forest burning reached about 186.069 hectares which is 7,13% of total national forest burning disaster, consisted of 107.000 hectares of peatland and the rest 79.069 hectares of mineral land. Anti-fire group, a voluntary group next to the forest, to help in protecting the forest burning and heavily smoke residual has been established but unfortunately the implementation still far from expectation. This research will emphasize on (1) how the anti-fire group contribute to fire hazard tackling; (2) the identification of SWOT analysis to enhance the group benefit; and (3) government policy implication to maximize the role of Anti-fire group and reduce the case of forest burning as well as heavily smoke which can raise climate change impact. As the observation found some weakness from SWOT identification such as (1) lack of education and training; (2) facility in extinguishing the fire damage; (3) law for economic incentive; (4) communication and field experience; (5) also the reporting the fire case.

Keywords: anti-fire group, forest burning impact, SWOT, climate change mitigation

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Authors: Alaa Hamed Salama, Rehab Nabil Shamma

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Introduction: Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to review the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly (ethylene oxide)-poly (propylene oxide) for the more effective encapsulation of Lornoxicam (LX) as a hydrophobic model drug. Methods: The co-micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic® PE/P84, and Synperonic® PE/F127 and the hydrophobic poloxamine counterpart (Tetronic® T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results: Results showed a sharp solubility increase from 0.46 mg/ml up to more than 4.34 mg/ml, representing about 136-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size. The optimized formulation was characterized by 1HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. Conclusion: LX-loaded polymeric nanomicellar formulation was fabricated allowing easy application of the drug in the form of clear eye drops that do not cause blurred vision or discomfort, thus achieving high patient compliance.

Keywords: confocal laser scanning microscopy, Histopathological studies, Lornoxicam, micellar solubilization

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Authors: Shivankar Agrawal, Indira Sarangthem

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Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major causes of healthcare-associated and community-onset infections worldwide. Hence the search for non-toxic natural compounds having antibacterial activity has intensified for future drug development. The exploration of less studied niches of Earth can highly increase the possibility to discover novel bioactive compounds. Therefore, in this study, the cultivable fraction of fungi from the sediments of natural hot springs has been studied to mine potential fungal candidates with antibacterial activity against the human pathogen Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. We isolated diverse strains of thermophilic fungi from a collection of samples from sediment. Following a standard method, we isolated a promising thermophilic fungus strain IBSD19, identified as Acrophialophora levis, possessing the potential to produce an anti-Staphylococcus aureus agent. The growth conditions were optimized and scaled to fermentation, and its produced extract was subjected to chemical extraction. The ethyl acetate fraction was found to display significant activity against Staphylococcus aureus and MRSA with a minimum inhibitory concentration (MIC) of 0.5 mg/ml and 4 mg/ml, respectively. The cell membrane integrity assay and SEM suggested that the fungal metabolites cause bacteria clustering and further lysis of the cell.

Keywords: antibacterial activity, antioxidant, fungi, Staphylococcus aureus, MRSA, thermophiles

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Authors: Mohammad Khosravi, Ali Kiani, Behroz Dastar, Parvin Showrang

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Review was carried out on important anti-nutritional compounds of livestock and poultry foods and the effect of radiation usage. Nowadays, with advancement in technology, different methods have been considered for the optimum usage of nutrients in livestock and poultry foods. Steaming, extruding, pelleting, and the use of chemicals are the most common and popular methods in food processing. Use of radiation in food processing researches in the livestock and poultry industry is currently highly regarded. Ionizing (electrons, gamma) and non-ionizing beams (microwave and infrared) are the most useable rays in animal food processing. In recent researches, these beams have been used to remove and reduce the anti-nutritional factors and microbial contamination and improve the digestibility of nutrients in poultry and livestock food. The evidence presented will help researchers to recognize techniques of relevance to them. Simplification of some of these techniques, especially in developing countries, must be addressed so that they can be used more widely.

Keywords: antitrypsin, gamma anti-nutritional components, phytic acid, radiation

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Authors: Rifa’ah Mahmudah Bulu’

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MRSA is an important nosocomial pathogen in the world. Therefore, the prevention and effort to control MRSA is still very important to conduct. One of the preventions of MRSA, which have been reported by several studies, is Cefriaxone and Ethanol Extract of Ant Plant. This research is an experimental test to determine the potency of MRSA’s anti-bacterial with Cefriaxone (30 μg) and Ethanol Extract of Ant Plant (13 mg/ml) based on inhibition zone on LAB (Lempeng Agar Biasa). The size of inhibition zone that is formed on Cefriaxone is adjusted with CSLI criteria, which ≥ 21 mm of inhibition zone is called sensitive; ≤13 mm is called resistance and between 14-20 mm is called intermediate. This research is conducted three times. Comparative test between Cefriaxone and Ethanol Extract of Ant Plant is analyzed by Maan Whitney’s statistic method. The Result of Cefriaxone anti-bacterial potency shows the variety of inhibition zone. Cefriaxone forms approximately 16,5-20 mm with average 18,22mm of inhibition zone that make Cefriaxone’s criteria to MRSA’s inhibition is intermediate. Anti-bacterial potency of Ethanol Extract of Ant Plant is about 0,5-2 mm with average 1,17 mm of inhibition zone that prove MRSA is sensitive to Ant Plant. The conclusion of this research shows that Cefriaxone is intermediate to MRSA’s inhibition, while MRSA is sensitive to Ethanol Extract of Ant Plant, which at the end; it creates different potency of anti-bacterial between Cefriaxone and Ethanol Extract of Ant Plant.

Keywords: MRSA, cefriaxone, ant plant, CSLI, mann whitney

Procedia PDF Downloads 367