Search results for: drug administration
2389 Subacute Toxicity Study of Total Alkaloids of Seeds of Peganum harmala in Female Rat
Authors: Mahdeb Nadia, Ghadjati Nadhra, Bettihi Sara, Daamouche Z. El Youm, Bouzidi Abdelouahab
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The effects of subacute administration of total alkaloids of seeds Peganum harmala were studied in female Albino-Wistar rats. After intraperitoneal administration of dose 50 mg/kg for 10 days and 40 mg/kg for 7 days of total alkaloids to the seeds of Peganum harmala (animal treatment lasted 17 days), there were remarkable changes in general appearance and deaths occurred in experimental group. After 17 days a significant reduction was observed in the surviving animals treated with total alkaloid seeds.The Red Blood Cells (RBC), Hematocrit (HCT), Hemoglobin (HGB) and White blood cells (WBCs), show significant reduction in the treated groups. There were no statistical differences in Glutamic-Oxaloacetic Transaminase (GOT), Glutamic-pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP), total protein, glucose and creatinine observed between groups. However the urea was significantly higher in the treated female rats than the control group. Histological examination of liver showed no histopathological changes. Alkaloids of Peganum harmala showed significant toxicity in female rats.Keywords: Peganum harmala, rat, liver, kidney, alkaloids, toxicity
Procedia PDF Downloads 4392388 Cardioprotective Effect of Oleanolic Acid and Urosolic Acid against Doxorubicin-Induced Cardiotoxicity in Rats
Authors: Sameer N. Goyal, Chandragauda R. Patil
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Oleanolic acid (3/3-hydroxy-olea-12-en-28-oic acid) and its isomer, Ursolic acid (38-hydroxy-urs-12-en-28-oic acid) are triterpenoids compounds which exist widely in plant kingdom in the free acid form or as glycosidic triterpenoids saponins. The aim of the study is to evaluate intravenously administered oleanolic acid and ursolic acid in doxorubicin induced cardiotoxicity. Cardiotoxicity was induced in albino wistar rat with single intravenous injection of doxorubicin at dose of 67.75mg/kg i.v for 48 hrs at 12 hrs interval following doxorubicin administration in the same model cardioprotective effect of amifostine (90 mg/kg i.v, single dose prior 30 min before doxorubicin administration) was evaluated as standard treatment. Induction of cardiotoxicity was confirmed by rise in cardiac markers in serum such as CK–MB, LDH and also by electrocardiographically. The doxorubicin treated group significantly increased in QT interval, serum CK-MB, serum LDH, SGOT, SGPT and antioxidant parameter. Both the treatment group showed significant protective effect on Hemodynamic, electrocardiographic, biochemical, and antioxidant parameters. The oleanolic acid showed slight protective effect in histological lesions in doxorubicin induced cardiotoxicity. Hence, the results indicate that Oleanolic acid has more cardioprotective potential than ursolic acid against doxorubicin induced cardiotoxicity in rats.Keywords: cardioprotection, doxorubicin, oleanolic acid, ursolic acid
Procedia PDF Downloads 5272387 Psychosocial Challenges of Multi-Drug Resistant Tuberculosis (MDR-TB) Patients at St. Peter TB Specialized Hospital in Addis Ababa
Authors: Tamrat Girma Biru
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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy
Procedia PDF Downloads 3912386 Protective Effect of the Histamine H3 Receptor Antagonist DL77 in Behavioral Cognitive Deficits Associated with Schizophrenia
Authors: B. Sadek, N. Khan, D. Łażewska, K. Kieć-Kononowicz
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The effects of the non-imidazole histamine H3 receptor (H3R) antagonist DL77 in passive avoidance paradigm (PAP) and novel object recognition (NOR) task in MK801-induced cognitive deficits associated with schizophrenia (CDS) in adult male rats, and applying donepezil (DOZ) as a reference drug were investigated. The results show that acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly improved MK801-induced (0.1 mg/kg, i.p.) memory deficits in PAP. The ameliorating activity of DL77 (5 mg/kg, i.p.) in MK801-induced deficits was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10 mg/kg, i.p.) or with the antimuscarinic antagonist scopolamine (SCO, 0.1 mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10 mg/kg, i.p.). Moreover, the memory enhancing effect of DL77 (5 mg/kg, i.p.) in MK801-induced memory deficits in PAP was strongly reversed when rats were pretreated with a combination of ZOL (10 mg/kg, i.p.) and SCO (1.0 mg/kg, i.p.). Furthermore, the significant ameliorative effect of DL77 (5 mg/kg, i.p.) on MK801-induced long-term memory (LTM) impairment in NOR test was comparable to the DOZ-provided memory-enhancing effect, and was abrogated when animals were pretreated with the histamine H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to provide procognitive effect on MK801-induced short-term memory (STM) impairment in NOR test. In addition, DL77 (5 mg/kg) did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM), demonstrating that improved performances with DL77 (5 mg/kg) in PAP or NOR are unrelated to changes in emotional responding or spontaneous locomotor activity. These results provide evidence for the potential of H3Rs for the treatment of neurodegenerative disorders related to impaired memory function, e.g. CDS.Keywords: histamine H3 receptor, antagonist, learning, memory impairment, passive avoidance paradigm, novel object recognition
Procedia PDF Downloads 2032385 Towards a Biologically Relevant Tumor-on-a-Chip: Multiplex Microfluidic Platform to Study Breast Cancer Drug Response
Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle
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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip
Procedia PDF Downloads 2642384 Public Governance in Brazil: The Perception of Professionals and Counselors of the Courts of Auditors on Transparency, Responsiveness and Accountability of Public Policies
Authors: Paulino Varela Tavares, Ana Lucia Romao
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Public governance represents an articulated arrangement, dynamic and interactive, present in the exercise of authority aimed at strengthening the decision-making procedure in public administration with transparency, accountability, responsiveness and capable of to emerge control and social empowerment, to pursue and achieve the objectives efficiently and with the effectiveness desired for the collectivity, respecting the laws and provide social, institutional and economic equity in society. In this context, using a multidimensional approach with the application of a questionnaire with four questions directed to twenty Counselors of the Courts of Auditors of the States (Brazil) and twenty professionals (liberals, teachers, and specialists) of the public administration in Brazil, preliminary results indicate that 70% believe that the level of transparency in public policies is low; 40% say that the government makes accountability because it is required by law, but, other instruments must be developed to force the government to account for all accounts with society; 75% say that government responsiveness is very limited because of the lack of long term planning, which is greatly affected by party political issues in Brazil. Therefore, the results, as yet, point out that Brazilian society has a huge challenge regarding the transparency, accountability, and responsiveness of governments in relation to their public policies.Keywords: accountability, public governance, responsiveness, transparency
Procedia PDF Downloads 1542383 Hepatitis B, Hepatitis C and HIV Infections and Associated Risk Factors among Substance Abusers in Mekelle Substance Users Treatment and Rehabilitation Centers, Tigrai, Northern Ethiopia
Authors: Tadele Araya, Tsehaye Asmelash, Girmatsion Fiseha
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Background: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) constitute serious healthcare problems worldwide. Blood-borne pathogens HBV, HCV and HIV are commonly associated with infections among substance or Injection Drug Users (IDUs). The objective of this study was to determine the prevalence of HBV, HCV, and HIV infections among substance users in Mekelle Substance users Treatment and Rehabilitation Centers. Methods: A cross-sectional study design was used from Dec 2020 to Sep / 2021 to conduct the study. A total of 600 substance users were included. Data regarding the socio-demographic, clinical and sexual behaviors of the substance users were collected using a structured questionnaire. For laboratory analysis, 5-10 ml of venous blood was taken from the substance users. The laboratory analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) at Mekelle University, Department of Medical Microbiology and Immunology Research Laboratory. The Data was analyzed using SPSS and Epi-data. The association of variables with HBV, HCV and HIV infections was determined using multivariate analysis and a P value < 0.05 was considered statistically significant. Result: The overall prevalence rate of HBV, HCV and HIV infections were 10%, 6.6%, and 7.5%, respectively. The mean age of the study participants was 28.12 ± 6.9. A higher prevalence of HBV infection was seen in participants who were users of drug injections and in those who were infected with HIV. HCV was comparatively higher in those who had a previous history of unsafe surgical procedures than their counterparts. Homeless participants were highly exposed to HCV and HIV infections than their counterparts. The HBV/HIV Co-infection prevalence was 3.5%. Those doing unprotected sexual practices [P= 0.03], Injection Drug users [P= 0.03], those who had an HBV-infected person in their family [P=0.02], infected with HIV [P= 0.025] were statistically associated with HBV infection. HCV was significantly associated with Substance users and previous history of unsafe surgical procedures [p=0.03, p=0.04), respectively. HIV was significantly associated with unprotected sexual practices and being homeless [p=0.045, p=0.05) respectively. Conclusion-The highly prevalent viral infection was HBV compared to others. There was a High prevalence of HBV/HIV co-infection. The presence of HBV-infected persons in a family, unprotected sexual practices and sharing of needles for drug injection were the risk factors associated with HBV, HIV, and HCV. Continuous health education and screening of the viral infection coupled with medical and psychological treatment is mandatory for the prevention and control of the infections.Keywords: hepatitis b virus, hepatitis c virus, HIV, substance users
Procedia PDF Downloads 852382 Novel Solid Lipid Nanoparticles for Oral Delivery of Oxyresveratrol: Effect of the Formulation Parameters on the Physicochemical Properties and in vitro Release
Authors: Yaowaporn Sangsen, Kittisak Likhitwitayawuid, Boonchoo Sritularak, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee
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Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.Keywords: solid lipid nanoparticles, physicochemical properties, in vitro drug release, oxyresveratrol
Procedia PDF Downloads 3972381 Intestacy and Business Continuity among Entrepreneurs in Ondo State, Nigeria
Authors: Igbekoyi Olusola Esther, Olurankinse Felix
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This paper examined the factors that militate against Will writing among entrepreneurs in Ondo State Nigeria and the effect of intestate death on business continuity after the exit of the entrepreneurs. The paper was written with a view to providing information on the reasons why intestate death is common among entrepreneurs in Ondo State and the effects on continuity of business after death of the initial owners. Data were obtained from primary source through the administration of questionnaires to entrepreneurs drawn from 50 registered manufacturing companies. These companies have been in existence for a minimum of 10 years with minimum staff strength of 20 workers each. These companies were selected using the purposive random sampling technique in order to capture firms that meet the requirements of this paper. Data obtained were analyzed using descriptive statistics, chi-square and regression analysis. The findings of the paper revealed that administration of Will, traditional beliefs, Will execution procedures, age and non- admissibility of Wills in court are the major factors that militates against Will writing among entrepreneurs in Ondo State. It was also discovered that chaos and instability in business, reduction in sales and productivity, poor succession planning, polygamous nature of marriages, difficulty in sourcing for funds and gender preference are joint predictors of business continuity in event intestate death which is evident in the result where R2 =.954;(F 6, 26)= 89.644; (P < 0.01). The individual beta co-efficient, t- statistics and significance of each variable revealed that gender preference (.735; 7.031; .000) and poor succession plan (.402; 2.840; .009) have significant positive effect on business continuity; while reduction in sales and productivity (-.059; -.335; .740) and difficulty in sourcing for funds (-.217; -1.367; .188) have negative effect; other variables also have positive relationship but they are not significant. It is therefore concluded that business continuity after the exit of the entrepreneur is highly dependent on the rebuilding of confidence on Wills administration in ondo state Nigeria, proper succession planning and elimination of gender preferences.Keywords: intestacy, business continuity, entrepreneurs, will, succession planning
Procedia PDF Downloads 3292380 Between Buddha and Tsar: Kalmyk Buddhist Sangha in Late Russian Empire
Authors: Elzyata Kuberlinova
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This study explores how the Kalmyk Buddhist sangha responded to the Russian empire’s administrative integration and how the Buddhist clerical institutions were shaped in the process of interaction with representatives of the predominantly Orthodox state. The eighteenth-nineteenth century Russian imperial regime adhered to a religion-centred framework to govern its diverse subjects. Within this framework, any form of religious authority was considered a useful tool in the imperial quest for legibility. As such, rather than imposing religious homogeneity, the Russian administration engineered a framework of religious toleration and integrated the non-Orthodox clerical institutions in the empire’s administration. In its attempt to govern the large body of Kalmyk Buddhist sangha, the Russian government had to incorporate the sangha into the imperial institutional establishment. To this end, the Russian government founded the Lamaist Spiritual Governing Board in 1834, which became a part of the civil administration, where the Kalmyk Buddhist affairs were managed under the supervision of the Russian secular authorities. In 1847 the Lamaist Spiritual Board was abolished and Buddhist religious authority was transferred to the Lama of the Kalmyk people. From 1847 until the end of the empire in 1917 the Lama was the manager and intermediary figure between the Russian authorities and the Kalmyks where religious affairs were concerned. Substantial evidence collected in archives in Elista, Astrakhan, Stavropol and St.Petersburg show that despite being on the government’s payroll, first the Lamaist Spiritual Governing Board and later on the Lama did not always serve the interests of the state, and did not always comply with the Russian authorities’ orders. Although being incorporated into the state administrative system the Lama often found ways to manoeuvre the web of the Russian imperial bureaucracy in order to achieve his own goals. The Lama often used ‘every-day forms of resistance’ such as feigned misinterpretation, evasion, false compliance, feigned ignorance, and sabotage in order to resist without directly confronting or challenging the state orders.Keywords: Buddhist Sangha, intermediary, Kalmyks, Lama, legibility, resistance, reform, Russian empire
Procedia PDF Downloads 2222379 A Study Concerning Foreign Worker Migration in Thailand
Authors: Napatsorn Suput-Anyaporn
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This paper aimed to investigate multilateral relationships across the factors which included labor shortage, trade union, turnover rate of employee, labor law and regulation, and effectiveness of foreign worker administration in the scope of foreign workers in the industrial manufacturing sector of Thailand. The research employed both quantitative and qualitative approaches, in which foreign workers from Myanmar, Laos and Cambodia in the industrial manufacturing sector in selected areas of Thailand were sampled for the quantitative data collection, and persons in the chief executive management and the supervisor levels, and persons in the academic area in relation with foreign workers were selected as the sample for the qualitative data collection method. Thus, a questionnaire, in-depth interview and focus group were utilized as tools in this research paper. The discussion placed an emphasis on the fact that Thailand should design more effective law and regulations for the foreign workers administration and management in response to preparing for the coming ASEAN Economic Community with the declaration of the free- flow labor movement policy.Keywords: industrial manufacturing sector, labor law and regulation, labor shortage, migrant worker, trade union, turnover rate of employee
Procedia PDF Downloads 4122378 Optimization of the Administration of Intravenous Medication by Reduction of the Residual Volume, Taking User-Friendliness, Cost Efficiency, and Safety into Account
Authors: A. Poukens, I. Sluyts, A. Krings, J. Swartenbroekx, D. Geeroms, J. Poukens
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Introduction and Objectives: It has been known for many years that with the administration of intravenous medication, a rather significant part of the planned to be administered infusion solution, the residual volume ( the volume that remains in the IV line and or infusion bag), does not reach the patient and is wasted. This could possibly result in under dosage and diminished therapeutic effect. Despite the important impact on the patient, the reduction of residual volume lacks attention. An optimized and clearly stated protocol concerning the reduction of residual volume in an IV line is necessary for each hospital. As described in my Master’s thesis, acquiring the degree of Master in Hospital Pharmacy, administration of intravenous medication can be optimized by reduction of the residual volume. Herewith effectiveness, user-friendliness, cost efficiency and safety were taken into account. Material and Methods: By usage of a literature study and an online questionnaire sent out to all Flemish hospitals and hospitals in the Netherlands (province Limburg), current flush methods could be mapped out. In laboratory research, possible flush methods aiming to reduce the residual volume were measured. Furthermore, a self-developed experimental method to reduce the residual volume was added to the study. The current flush methods and the self-developed experimental method were compared to each other based on cost efficiency, user-friendliness and safety. Results: There is a major difference between the Flemish and the hospitals in the Netherlands (Province Limburg) concerning the approach and method of flushing IV lines after administration of intravenous medication. The residual volumes were measured and laboratory research showed that if flushing was done minimally 1-time equivalent to the residual volume, 95 percent of glucose would be flushed through. Based on the comparison, it became clear that flushing by use of a pre-filled syringe would be the most cost-efficient, user-friendly and safest method. According to laboratory research, the self-developed experimental method is feasible and has the advantage that the remaining fraction of the medication can be administered to the patient in unchanged concentration without dilution. Furthermore, this technique can be applied regardless of the level of the residual volume. Conclusion and Recommendations: It is recommendable to revise the current infusion systems and flushing methods in most hospitals. Aside from education of the hospital staff and alignment on a uniform substantiated protocol, an optimized and clear policy on the reduction of residual volume is necessary for each hospital. It is recommended to flush all IV lines with rinsing fluid with at least the equivalent volume of the residual volume. Further laboratory and clinical research for the self-developed experimental method are needed before this method can be implemented clinically in a broader setting.Keywords: intravenous medication, infusion therapy, IV flushing, residual volume
Procedia PDF Downloads 1352377 The Jurisprudential Evolution of Corruption Offenses in Spain: Before and after the Economic Crisis
Authors: Marta Fernandez Cabrera
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The period of economic boom generated by the housing bubble created a climate of social indifference to the problem of corruption. This resulted in the persecution and conviction for these criminal offenses being low. After the economic recession, social awareness about the problem of corruption has increased. This has led to the Spanish citizenship requiring the public authorities to try to end the problem in the most effective way possible. In order to respond to the continuous social demands that require an exemplary punishment, the legislator has made changes in crimes against the public administration in the Spanish Criminal Code. However, from the point of view of criminal law, the social change has not served to modify only the law, but also the jurisprudence. After the recession, judges are punishing more severely these conducts than in the past. Before the crisis, it was usual for criminal judges to divert relevant behavior to other areas of the legal system such as administrative law and acquit in the criminal field. Criminal judges have considered that administrative law already has mechanisms that can effectively deal with this type of behavior in order to respect the principle of subsidiarity or ultima ratio. It has also been usual for criminal judges to acquit civil servants due to the absence of requirements unrelated to the applicable offense. For example, they have required an economic damage to the public administration when the offense in the criminal code does not require it. Nevertheless, for some years, these arguments have either partially disappeared or considerably transformed. Since 2010, a jurisprudential stream has been consolidated that aims to provide a more severe response to corruption than it had received until now. This change of opinion, together with greater prosecution of these behaviors by judges and prosecutors, has led to a significant increase in the number of individuals convicted of corruption crimes. This paper has two objectives. The first one is to show that even though judges apply the law impartially, they are flexible to social changes. The second one is to identify the erroneous arguments the courts have used up until now. To carry out the present paper, it has been done a detailed analysis of the judgments of the supreme court before and after the year 2010. Therefore, the jurisprudential analysis is complemented with the statistical data on corruption available.Keywords: corruption, public administration, social perception, ultima ratio principle
Procedia PDF Downloads 1462376 Identifying Reforms Required in Construction Contracts from Resolved Disputed Cases
Authors: K. C. Iyer, Yogita Manan Bindal, Sumit Kumar Bakshi
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The construction industry is plagued with disputes and litigation in India with many stalled projects seeking dispute resolution. This has an adverse effect on the performance and overall project delivery and impacts future investments within the industry. While construction industry is the major driver of growth, there has not been major reforms in the government construction contracts. The study is aimed at identifying the proactive means of dispute avoidance, focusing on reforms required within the construction contracts, by studying 49 arbitration awards of construction disputes. The claims presented in the awards are aggregated to study the causes linked to the contract document and are referred against the prospective recommendation and practices as surveyed from literature review of research papers. Within contract administration, record keeping has been a major concern as they are required by the parties to substantiate the claims or the counterclaims and therefore are essential in any dispute redressal process. The study also observes that the right judgment is inhibited when the record keeping is improper and due to lack of coherence between documents, the dispute resolution period is also prolonged. The finding of the research will be relevant to industry practitioners in contract drafting with a view to avoid disputes.Keywords: construction contract, contract administration, contract management, dispute avoidance
Procedia PDF Downloads 2652375 Molecular Mechanism on Inflammation and Antioxidant Role of Pterocarpus Marsupiumin in Experimental Hyperglycaemia
Authors: Leelavinothan Pari , Ayyasamy Rathinam
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Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines
Procedia PDF Downloads 3762374 Solubility and Dissolution Enhancement of Poorly Soluble Drugs Using Biosericin
Authors: Namdeo Jadhav, Nitin Salunkhe
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Currently, sericin is being treated as waste of sericulture industry, especially at reeling process. Looking at prospective physicochemical properties, an attempt has been made to explore pharmaceutical applications of sericin waste in fabrication of medicated solid dispersions. Solid dispersions (SDs) of poorly soluble drugs (Lornoxicam, Meloxicam & Felodipine) were prepared by spray drying, solvent evaporation, ball milling and physical kneading in mass ratio of drug: sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3 w/w) and were investigated by solubility, ATR-FTIR, XRD and DSC, micromeritics and tablettability, surface morphology and in-vitro dissolution. It has been observed that sericin improves solubility of drugs by 8 to 10 times compared to pure drugs. The presence of hydrogen bonding between drugs and sericin was confirmed from the ATR-FTIR spectra. Amongst these methods, spray dried (1:2 w/w) SDs showed fully amorphous state representing molecularly distributed drug as confirmed from XRD and DSC study. Spray dried meloxicam SDs showed better compressibility and compactibility. The microphotograph of spray dried batches of lornoxicam (SDLX) and meloxicam SDs (SDMX) showed bowl shaped, and bowl plus spherical particles respectively, while spray dried felodipine SDs (SDFL) showed spherical shape. The SDLX, SDMX and SDFL (1:2 w/w) displayed better dissolution performance than other methods. Conclusively, hydrophilic matrix of sericin can be used to deliver poor water soluble drugs and its aerodynamic shape may show a great potential for various drug deliveries. If established as pharmaceutical excipient, sericin holds a potential to revolutionise economics of pharmaceutical industry, and sericulture farming, especially of Asian countries.Keywords: biosericin, poorly soluble drugs, solid dispersion, solubility and dissolution improvement
Procedia PDF Downloads 2552373 An Activatable Prodrug for the Treatment of Metastatic Tumors
Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim
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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence
Procedia PDF Downloads 4532372 Comparative in silico and in vitro Study of N-(1-Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent
Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal
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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.Keywords: Doxorubicin, auto dock, in silco, in vitro
Procedia PDF Downloads 4192371 Data Security and Privacy Challenges in Cloud Computing
Authors: Amir Rashid
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Cloud Computing frameworks empower organizations to cut expenses by outsourcing computation resources on-request. As of now, customers of Cloud service providers have no methods for confirming the privacy and ownership of their information and data. To address this issue we propose the platform of a trusted cloud computing program (TCCP). TCCP empowers Infrastructure as a Service (IaaS) suppliers, for example, Amazon EC2 to give a shout box execution condition that ensures secret execution of visitor virtual machines. Also, it permits clients to bear witness to the IaaS supplier and decide if the administration is secure before they dispatch their virtual machines. This paper proposes a Trusted Cloud Computing Platform (TCCP) for guaranteeing the privacy and trustworthiness of computed data that are outsourced to IaaS service providers. The TCCP gives the deliberation of a shut box execution condition for a client's VM, ensuring that no cloud supplier's authorized manager can examine or mess up with its data. Furthermore, before launching the VM, the TCCP permits a client to dependably and remotely acknowledge that the provider at backend is running a confided in TCCP. This capacity extends the verification of whole administration, and hence permits a client to confirm the data operation in secure mode.Keywords: cloud security, IaaS, cloud data privacy and integrity, hybrid cloud
Procedia PDF Downloads 2992370 Iron-Metal-Organic Frameworks: Potential Application as Theranostics for Inhalable Therapy of Tuberculosis
Authors: Gabriela Wyszogrodzka, Przemyslaw Dorozynski, Barbara Gil, Maciej Strzempek, Bartosz Marszalek, Piotr Kulinowski, Wladyslaw Piotr Weglarz, Elzbieta Menaszek
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MOFs (Metal-Organic Frameworks) belong to a new group of porous materials with a hybrid organic-inorganic construction. Their structure is a network consisting of metal cations or clusters (acting as metallic centers, nodes) and the organic linkers between nodes. The interest in MOFs is primarily associated with the use of their well-developed surface and large porous. Possibility to build MOFs of biocompatible components let to use them as potential drug carriers. Furthermore, forming MOFs structure from cations possessing paramagnetic properties (e.g. iron cations) allows to use them as MRI (Magnetic Resonance Imaging) contrast agents. The concept of formation of particles that combine the ability to transfer active substance with imaging properties has been called theranostic (from words combination therapy and diagnostics). By building MOF structure from iron cations it is possible to use them as theranostic agents and monitoring the distribution of the active substance after administration in real time. In the study iron-MOF: Fe-MIL-101-NH2 was chosen, consisting of iron cluster in nodes of the structure and amino-terephthalic acid as a linker. The aim of the study was to investigate the possibility of applying Fe-MIL-101-NH2 as inhalable theranostic particulate system for the first-line anti-tuberculosis antibiotic – isoniazid. The drug content incorporated into Fe-MIL-101-NH2 was evaluated by dissolution study using spectrophotometric method. Results showed isoniazid encapsulation efficiency – ca. 12.5% wt. Possibility of Fe-MIL-101-NH2 application as the MRI contrast agent was demonstrated by magnetic resonance tomography. FeMIL-101-NH2 effectively shortening T1 and T2 relaxation times (increasing R1 and R2 relaxation rates) linearly with the concentrations of suspended material. Images obtained using multi-echo magnetic resonance imaging sequence revealed possibility to use FeMIL-101-NH2 as positive and negative contrasts depending on applied repetition time. MOFs micronization via ultrasound was evaluated by XRD, nitrogen adsorption, FTIR, SEM imaging and did not influence their crystal shape and size. Ultrasonication let to break the aggregates and achieve very homogeneously looking SEM images. MOFs cytotoxicity was evaluated in in vitro test with a highly sensitive resazurin based reagent PrestoBlue™ on L929 fibroblast cell line. After 24h no inhibition of cell proliferation was observed. All results proved potential possibility of application of ironMOFs as an isoniazid carrier and as MRI contrast agent in inhalatory treatment of tuberculosis. Acknowledgments: Authors gratefully acknowledge the National Science Center Poland for providing financial support, grant no 2014/15/B/ST5/04498.Keywords: imaging agents, metal-organic frameworks, theranostics, tuberculosis
Procedia PDF Downloads 2512369 A Machine Learning-Based Model to Screen Antituberculosis Compound Targeted against LprG Lipoprotein of Mycobacterium tuberculosis
Authors: Syed Asif Hassan, Syed Atif Hassan
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Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction
Procedia PDF Downloads 3912368 Governance and Public Policy: The Perception of Civil Society Participation in Brazil and South Africa
Authors: Paulino V. Tavares, Ana L. Romao
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Public governance, in general, is essential to qualify and educate, pedagogically, the decision-making process of the government in relation to the management of resources and the provision of public services, with transparency and active participation of individuals and citizens for the development of a more democratic environment, besides stimulating control and social empowerment, aiming at the development of the collectivity. In this context, the participation of society in the elaboration, execution, and control of public policies is prominent to strengthen public governance itself. With this, using a multidimensional approach with the application of two questionnaires to a universe of twenty Counselors of the Courts of Auditors (Brazil), twenty professionals of public administration (Brazil), twenty Government/Provincial Counselors (South Africa), and twenty South African professionals of public administration, the preliminary results indicate that the participation of civil society, for both countries, is very low in the elaboration, execution, and control of public policies. At the same time, about 70% of the answers obtained indicate, on average, three possible paths to increase the participation of civil society. With this, it is delineated that developing new horizons to strengthen both public policies how social participation is necessary, but, for both, it is important that governments and civil society, in their respective countries, have an awareness of the effective importance of this interaction.Keywords: Brazil, civil society, participation, South Africa
Procedia PDF Downloads 1442367 Formulation and Evaluation of Glimepiride (GMP)-Solid Nanodispersion and Nanodispersed Tablets
Authors: Ahmed. Abdel Bary, Omneya. Khowessah, Mojahed. al-jamrah
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Introduction: The major challenge with the design of oral dosage forms lies with their poor bioavailability. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability. The aim of this study was to develop solid nanodispersed tablet formulation of Glimepiride for the enhancement of the solubility and bioavailability. Methodology: Solid nanodispersions of Glimepiride (GMP) were prepared using two different ratios of 2 different carriers, namely; PEG6000, pluronic F127, and by adopting two different techniques, namely; solvent evaporation technique and fusion technique. A full factorial design of 2 3 was adopted to investigate the influence of formulation variables on the prepared nanodispersion properties. The best chosen formula of nanodispersed powder was formulated into tablets by direct compression. The Differential Scanning Calorimetry (DSC) analysis and Fourier Transform Infra-Red (FTIR) analysis were conducted for the thermal behavior and surface structure characterization, respectively. The zeta potential and particle size analysis of the prepared glimepiride nanodispersions was determined. The prepared solid nanodispersions and solid nanodispersed tablets of GMP were evaluated in terms of pre-compression and post-compression parameters, respectively. Results: The DSC and FTIR studies revealed that there was no interaction between GMP and all the excipients used. Based on the resulted values of different pre-compression parameters, the prepared solid nanodispersions powder blends showed poor to excellent flow properties. The resulted values of the other evaluated pre-compression parameters of the prepared solid nanodispersion were within the limits of pharmacopoeia. The drug content of the prepared nanodispersions ranged from 89.6 ± 0.3 % to 99.9± 0.5% with particle size ranged from 111.5 nm to 492.3 nm and the resulted zeta potential (ζ ) values of the prepared GMP-solid nanodispersion formulae (F1-F8) ranged from -8.28±3.62 mV to -78±11.4 mV. The in-vitro dissolution studies of the prepared solid nanodispersed tablets of GMP concluded that GMP- pluronic F127 combinations (F8), exhibited the best extent of drug release, compared to other formulations, and to the marketed product. One way ANOVA for the percent of drug released from the prepared GMP-nanodispersion formulae (F1- F8) after 20 and 60 minutes showed significant differences between the percent of drug released from different GMP-nanodispersed tablet formulae (F1- F8), (P<0.05). Conclusion: Preparation of glimepiride as nanodispersed particles proven to be a promising tool for enhancing the poor solubility of glimepiride.Keywords: glimepiride, solid Nanodispersion, nanodispersed tablets, poorly water soluble drugs
Procedia PDF Downloads 4882366 When Messages Cause Distraction from Advertising: An Eye-Tracking Study
Authors: Nilamadhab Mohanty
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It is essential to use message formats that make communication understandable and correct. It is because; the information format can influence consumer decision on the purchase of a product. This study combines information from qualitative inquiry, media trend analysis, eye tracking experiment, and questionnaire data to examine the impact of specific message format and consumer perceived risk on attention to the information and risk retention. We investigated the influence of message framing (goal framing, attribute framing, and mix framing) on consumer memory, study time, and decisional uncertainty while deciding on the purchase of drugs. Furthermore, we explored the impact of consumer perceived risk (associated with the use of the drug, i.e., RISK-AB and perceived risk associated with the non-use of the drug, i.e., RISK-EB) on message format preference. The study used eye-tracking methods to understand the differences in message processing. Findings of the study suggest that the message format influences information processing, and participants' risk perception impacts message format preference. Eye tracking can be used to understand the format differences and design effective advertisements.Keywords: message framing, consumer perceived risk, advertising, eye tracking
Procedia PDF Downloads 1222365 The Suitability of Agile Practices in Healthcare Industry with Regard to Healthcare Regulations
Authors: Mahmood Alsaadi, Alexei Lisitsa
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Nowadays, medical devices rely completely on software whether as whole software or as embedded software, therefore, the organization that develops medical device software can benefit from adopting agile practices. Using agile practices in healthcare software development industries would bring benefits such as producing a product of a high-quality with low cost and in short period. However, medical device software development companies faced challenges in adopting agile practices. These due to the gaps that exist between agile practices and the requirements of healthcare regulations such as documentation, traceability, and formality. This research paper will conduct a study to investigate the adoption rate of agile practice in medical device software development, and they will extract and outline the requirements of healthcare regulations such as Food and Drug Administration (FDA), Health Insurance Portability and Accountability Act (HIPAA), and Medical Device Directive (MDD) that affect directly or indirectly on software development life cycle. Moreover, this research paper will evaluate the suitability of using agile practices in healthcare industries by analyzing the most popular agile practices such as eXtream Programming (XP), Scrum, and Feature-Driven Development (FDD) from healthcare industry point of view and in comparison with the requirements of healthcare regulations. Finally, the authors propose an agile mixture model that consists of different practices from different agile methods. As result, the adoption rate of agile practices in healthcare industries still low and agile practices should enhance with regard to requirements of the healthcare regulations in order to be used in healthcare software development organizations. Therefore, the proposed agile mixture model may assist in minimizing the gaps existing between healthcare regulations and agile practices and increase the adoption rate in the healthcare industry. As this research paper part of the ongoing project, an evaluation of agile mixture model will be conducted in the near future.Keywords: adoption of agile, agile gaps, agile mixture model, agile practices, healthcare regulations
Procedia PDF Downloads 2362364 Biogenic Amines Production during RAS Cheese Ripening
Authors: Amr Amer
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Cheeses are among those high-protein-containing foodstuffs in which enzymatic and microbial activities cause the formation of biogenic amines from amino acids decarboxylation. The amount of biogenic amines in cheese may act as a useful indicator of the hygienic quality of the product. In other words, their presence in cheese is related to its spoilage and safety. Formation of biogenic amines during Ras cheese (Egyptian hard cheese) ripening was investigated for 4 months. Three batches of Ras cheese were manufactured using Egyptian traditional method. From each batch, Samples were collected at 1, 7, 15, 30, 60, 90 and 120 days after cheese manufacture. The concentrations of biogenic amines (Tyramine, Histamine, Cadaverine and Tryptamine) were analyzed by high performance liquid chromatography (HPLC). There was a significant increased (P<0.05) in Tyramine levels from 4.34± 0.07 mg|100g in the first day of storage till reached 88.77± 0.14 mg|100g at a 120-day of storage. Also, Histamine and Cadaverine levels had the same increased pattern of Tyramine reaching 64.94± 0.10 and 28.28± 0.08 mg|100g in a 120- day of storage, respectively. While, there was a fluctuation in the concentration of Tryptamine level during ripening period as it decreased from 3.24± 0.06 to 2.66± 0.11 mg|100g at 60-day of storage then reached 5.38±0.08 mg|100g in a 120- day of storage. Biogenic amines can be formed in cheese during production and storage: many variables, as pH, salt concentration, bacterial activity as well as moisture, storage temperature and ripening time, play a relevant role in their formation. Comparing the obtained results with the recommended standard by Food and Drug Administration "FDA" (2001), High levels of biogenic amines in various Ras cheeses consumed in Egypt exceeded the permissible value (10 mg%) which seemed to pose a threat to public health. In this study, presence of high concentrations of biogenic amines (Tyramine, Histamine, cadaverine and Tryptamine) in Egyptian Ras cheeses reflects the bad hygienic conditions under which they produced and stored. Accordingly, the levels of biogenic amines in different cheeses should be come in accordance with the safe permissible limit recommended by FDA to ensure human safety.Keywords: Ras cheese, biogenic amines, tyramine, histamine, cadaverine
Procedia PDF Downloads 4362363 Jail Reentry in Rural America: A Quasi-Experimental Examination of a Rural Behavioral Health Reentry Program
Authors: Debra L. Stanley, Gabriela Wasileski
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Offenders face many challenges as they transition from being incarcerated to the community, ranging from housing and employment needs to long standing problems with addictions and mental health issues. A lack of appropriate behavioral health services in the more remote parts of the United States has led to a significant illegal substance abuse problem, housing instability, and unaddressed mental health and trauma issues. High rates of poverty and unemployment exacerbate the growing behavioral health issues, drug overdoses, co-occurring disorders, and crime that are so prevalent across rural communities. This study examines the challenges of rural jail reentry faced by offenders in a treatment capacity. The client-centered evidence-based program is uniquely designed to provide continuity of care that focuses on issues which affect rural communities. Prior to release from jail, individuals go through comprehensive assessment screenings to measure mental health and substance use disorder as well as trauma and prior crime victimization histories; the assessments help to target client-specific services. The quasi-experimental research design tracks clients throughout their recovery and reintegration into the community. Individuals in a rural program often do not have the benefit of easy access or peer mentoring that is so often found in urban recovery programs. Therefore, much of the support is provided through telehealth and e-services. The goal of this study is to explore the nature of rural reentry programs and measures of recidivism, drug overdoses, and other behavioral health needs and successful reentry to include stable housing and employment.Keywords: jail reentry, rehabilitation, behavioral health, drug abuse, recidivism
Procedia PDF Downloads 952362 Inhibition of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium Tuberculosis Using High Throughput Virtual Screening and Molecular Dynamics Studies
Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper
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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics
Procedia PDF Downloads 1792361 Free Radical Scavenging Activity and Total Phenolic Assessment of Drug Repurposed Medicinal Plant Metabolites: Promising Tools against Post COVID-19 Syndromes and Non-Communicable Diseases in Botswana
Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane
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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes
Procedia PDF Downloads 1272360 Fabrication and Characterization of Folic Acid-Grafted-Thiomer Enveloped Liposomes for Enhanced Oral Bioavailability of Docetaxel
Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman
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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability
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