Search results for: drug abuse

Authors: M. S. Deshpande, Snehal D. Bomble

Abstract:

Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH), and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Worldwide, the number of TB cases has continued to increase, but the incidence rate has decreased since 2003. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB, and HIV-TB co-infections. There is an unmet medical need to discover newer synthetic molecules and new generation of potent drugs for the treatment of tuberculosis which will shorten the time of treatment, be potent and safe while effective facing resistant strains and non-replicative, latent forms, reduce adverse side effect and not interfere in the antiretroviral therapy. This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emergence of tuberculosis.

Keywords: tuberculosis, mycobacterium, multi-drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB

Procedia PDF Downloads 348

Authors: Polycarp A. Igbojekwe, Chizoba Amajuoyi, Peterson Nwokorie

Abstract:

The main purpose of this study was to carry out a survey of customer’s aggression towards hotel workers and make contributions on the prevalence and rationale behind customer’s aggression. Data for the study were gathered with a four-point Likert type rating scale. Samples were drawn from frontline hotel employees, managers and customers of twelve (12) hotels selected from three zones of Imo State. Data analyses were conducted using simple percentage, descriptive statistics; and Z-test statistical technique was used to test hypotheses. Among other factors, service failure and verbal abuse by service providers and poor quality product compared to price were identified by customers as the three major factors that can lead to customer aggression. Frontline employees indentified verbal abuse as the most common mode of aggression and that customer aggression causes emotional disturbance in them. The study also revealed that customer aggression is more prevalent in the 1&2 star hotels than it is in 3-5 star hotels. Most of the hotels have not institutionalized systematic approaches needed to effectively face the challenges of customer aggression, thus, customer aggression has become a common feature in the industry. Frontline jobs demand high emotional input. Therefore, we recommend that frontline employees should be given emotional support by their managers and also trained on how to cope with emotional disturbance.

Keywords: customer aggression, emotional disturbance, employee well-being, service failure, verbal abuse

Procedia PDF Downloads 249

Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

Abstract:

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

Procedia PDF Downloads 283

Authors: Gedefaye Nibret Mihretie

Abstract:

Background: Transactional sex is casual sex between two people to receive material incentives in exchange for sexual favors. Transactional sex is associated with negative consequences, which increase the risk of sexually transmitted diseases, including HIV/AIDS, unintended pregnancy, unsafe abortion, and physiological trauma. Many primary studies in Sub-Saharan Africa have been conducted to assess the prevalence and associated factors of transactional sex among women. These studies had great discrepancies and inconsistent results. Hence, this systematic review and meta-analysis aimed to synthesize the pooled prevalence of the practice of transactional sex among women and its associated factors in Sub-Saharan Africa. Method: Cross-sectional studies were systematically searched from March 6, 2022, to April 24, 2022, using PubMed, Google Scholar, HINARI, Cochrane Library, and grey literature. The pooled prevalence of transactional sex and associated factors was estimated using DerSemonial-Laird Random Effect Model. Stata (version 16.0) was used to analyze the data. The I-squared statistic was used to assess the studies' heterogeneity. A funnel plot and Egger's test were used to check for publication bias. A subgroup analysis was performed to minimize the underline heterogeneity depending on the study years, source of data, sample sizes and geographical location. Results: Four thousand one hundred thirty articles were extracted from various databases. The final thirty-two studies were included in this systematic review, including 108,075 participants. The pooled prevalence of transactional sex among women in Sub-Saharan Africa was 12.55%, with a confidence interval of 9.59% to 15.52%. Educational status (OR = .48, 95%CI, 0.27, 0.69) was the protective factors of transactional sex whereas, alcohol use (OR = 1.85, 95% CI: 1.19, 2.52), early sex debut (OR = 2.57, 95%CI, 1.17, 3.98), substance abuse (OR = 4.21, 95% CI: 2.05, 6.37), having history of sexual experience abuse (OR = 4.08, 95% CI: 1.38, 6.78), physical violence abuse (OR = 6.59, 95% CI: 1.17, 12.02), and sexual violence abuse (OR = 3.56, 95% CI: 1.15, 8.27) were the risk factors of transactional sex. Conclusion: The prevalence of transactional sex among women in Sub-Saharan Africa was high. Educational status, alcohol use, substance abuse, early sex debut, having a history of sexual experiences, physical violence, and sexual violence were predictors of transaction sex. Governmental and other stakeholders are designed to reduce alcohol utilization, provide health information about the negative consequences of early sex debut, substance abuse, and reduce sexual violence, ensuring gender equality through mass media, which should be included in state policy.

Keywords: women’s health, child health, reproductive health, midwifery

Procedia PDF Downloads 63

Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev

Abstract:

Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.

Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse

Procedia PDF Downloads 243

Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

Abstract:

Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

Procedia PDF Downloads 260

Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

Abstract:

Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

Procedia PDF Downloads 284

Authors: Delband Yekta Moazami

Abstract:

Background: For proper care and treatment of HIV patients and drug users, the medical staff and physicians must have a correct and positive attitude and knowledge towards such patients. We aimed to assess the attitudes in a sample of health care workers (HCW) working in different hospitals and clinics and medical students in Georgia towards HIV infected people and drug users in Tbilisi. Method: We conducted a cross-sectional study to assess attitudes of health care workers towards people living with HIV and drug users in hospitals and clinics in Tbilisi. The study was carried out from 1st of May 2020 till 30th of September 2020. Data were collected using a self-administered structured online questionnaire. With this tool we evaluated four facets of attitudes: Discrimination, Acceptance of HIV/AIDS patients, Acceptance of drug users and Fear. All data were imported and analyzed with the software SPSS 22 for windows. Results: In total data was collected from168 respondents, that among them 107 (65%) were women and majority of the participants were medical doctors. Women had more acceptance attitudes rather than men towards drug abusers. We found significant differences regarding expressing negative attitudes among HCW who were more than 50 years old comparing with other age groups in all four aspects. Medical doctors expressed more acceptances towards people with HIV and drug users comparing two other groups. Also our study revealed that the group with working experience 21 years and more, showed more discriminatory attitudes comparing other groups. Conclusion: Based on our study findings, there are significant differences regarding respondent’s attitudes based on gender, medical specialty and working experience in health care system. People struggling with HIV and drug use need nonjudgmental and positive behaviors from health care workers and physicians in order to help them for harm reduction and receiving appropriate treatment.

Keywords: hiv, addiction, attitudes, healthcare workers

Procedia PDF Downloads 48

Authors: Iman I. Salama, Samia M. Sami, Somaia I. Salama, Zeinab N. Said, Thanaa M. Rabah, Aida M. Abdel-Mohsin

Abstract:

This is a national community-based project to evaluate the effectiveness of HBV vaccination program in prevention of infection. HBV markers were tested in the sera of 3600 vaccinated children. Infected children were followed up for 1 year. Prevalence of HBV infection was 0.39 % (0.28% positive for anti-HBc, 0.03% positive for HBsAg and 0.08% positive for both). One year later, 50% of positive anti-HBc children turned negative with sustained positivity for positive HBsAg cases. HBV infection was significantly higher at age above 9 years (0.6%) compared to 0.2% at age 3-9 years and 0% at younger age (P < 0.05). Logistic analysis revealed that predictors for HBV infection were history of blood transfusion, regular medical injection, and family history of either HBV infection or drug abuse (adjusted odds ratios 6.2, 5.6, 7.6 & 19.1 respectively). HBV vaccination program produced adequate protection. Adherence to infection control measures and safe blood transfusion are recommended.

Keywords: HBV infection, HBV vaccine, children, Egypt

Procedia PDF Downloads 393

Authors: Vadim Makarov, Stewart T.Cole

Abstract:

PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

Procedia PDF Downloads 131

Authors: A. Hilsana, Vinay U. Rao, M. Sudhakar

Abstract:

Even though a number of non-steroidal anti-inflammatory drugs (NSAIDS) are available with different chemistries, they share a common solubility characteristic that is they are relatively more soluble in alkaline environment and practically insoluble in acidic environment. This work deals with developing a wax matrix drug delivery platform for controlled delivery of three model NSAIDS, Diclofenac sodium (DNa), Mefenamic acid (MA) and Naproxen (NPX) using the melt granulation technique. The aim of developing the platform was to have a general understanding on how an erodible matrix system modulates drug delivery rate and extent and how it can be optimized to give a delivery system which shall release the drug as per a common target product profile (TPP). Commonly used waxes like Cetostearyl alcohol and stearic acid were used singly an in combination to achieve a TPP of not 15 to 35% in 1 hour and not less than 80% Q in 24 hours. Full factorial design of experiments was followed for optimization of the formulation.

Keywords: NSAIDs, controlled delivery, target product profile, melt granulation

Procedia PDF Downloads 300

Authors: Friday G. Okibe, Edit B. Agbaji, Victor O. Ajibola, Christain C. Onoyima

Abstract:

Controlled drug delivery systems reduce dose-dependent toxicity associated with potent drugs, including anticancer drugs. In this research, hydroxyapatite (HA) and hydroxyapatite-sodium alginate nanocomposites (HASA) were successfully prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The FTIR result showed absorption peaks characteristics of pure hydroxyapatite (HA), and also confirmed the chemical interaction between hydroxyapatite and sodium alginate in the formation of the composite. Image analysis from SEM revealed nano-sized hydroxyapatite and hydroxyapatite-sodium alginate nanocomposites with irregular morphologies. Particle size increased with the formation of the nanocomposites relative to pure hydroxyapatite, with no significant change in particles morphologies. Drug loading and in-vitro drug release study were carried out using synthetic body fluid as the release medium, at pH 7.4 and 37 °C and under perfect sink conditions. The result shows that drug loading is highest for pure hydroxyapatite and decreased with increasing quantity of sodium alginate. However, the release study revealed that HASA-5%wt and HASA-20%wt presented better release profile than pure hydroxyapatite, while HASA-33%wt and HASA-50%wt have poor release profiles. This shows that Methotrexate-loaded hydroxyapatite-sodium alginate if prepared under optimal conditions is a potential carrier for effective delivery of Methotrexate.

Keywords: drug-delivery, hydroxyapatite, methotrexate, nanocomposites, sodium alginate

Procedia PDF Downloads 237

Authors: Gajera Lalit, Shah Pranav, Shah Shailesh

Abstract:

Venlafaxine hydrochloride has a short elimination half-life of 5 ± 2 hr, and absorption window in the upper part of gastrointestinal tract. The conventional tablets need to be administered two to three times a day and possess an oral bioavailability of 45%. The purpose of this study was to formulate gastroretentive effervescent floating tablets of Venlafaxine HCl. Different grades of HPMC namely K15M, K4M, K100M and E15LV were employed as swelling polymers whereas sodium bicarbonate was employed as gas generating agent. The direct compression method was employed for the formulation of tablets. The tablets were evaluated in terms of hardness, friability, weight variation, drug content, water uptake, in-vitro floating behavior and in-vitro drug release study. All the formulations exhibited very short floating lag time of < 1 min and total floating time of 12 hr. Formulation L3 containing 25 mg and 75 mg of HPMC E15 LV and HPMC K15M respectively exhibited complete drug release within 12 hrs.

Keywords: venlafaxine HCl, hydroxyl propyl methylcellulose, floating gastro retentive tablets, in-vitro drug release, non-fickian diffusion

Procedia PDF Downloads 503

Authors: G. Melo, J. Felix, S. Maciel, C. Fernandes, W. Rodrigues

Abstract:

In Brazilian public policy, the Centres of Reference for Social Assistance (CRAS in Portuguese) are part of the Unified Social Assistance System (SUAS in Portuguese). SUAS is responsible for addressing spontaneous or currently active cases that are brought forth from other services in the social assistance network. The following case was reviewed by CRAS’s team in Recife, Brazil, after a complaint of child abuse was filed against the mother of a 7-year-old girl by the girl’s aunt. The girl is the daughter of an incestuous relationship between her mother and her older brother. The complaint was registered by service staff and five interventions were subsequently carried out on behalf of the child. These interventions provided a secure place for dialogue with both the child and her family and allowed for an investigation of the abuse to proceed. They took place in the child’s school as well as her aunt’s residence. At school, the child (with her classmates) watched a video and listened to a song about the prevention of child abuse. This was followed up with a second intervention to determine any signs of Post-Traumatic Stress Disorder (PTSD), by having the child play with the mobile app ‘My Angela’. Books on the themes of family and fear were also read to the child on different occasions at her school – after every intervention she was asked to draw something related to fear and her concept of a family. After the interventions and discussing the case as a team, we reached several conclusions: 1) The child did not appear to show any symptoms of PTSD; 2) She normally fantasized about her future and life story; 3) She did not allow herself to be touched by strangers with whom she lacks a close relationship (such as classmates or her teacher); 4) Through her drawings, she reproduced the conversations she had had with the staff; 5) She habitually covered her drawings when asked questions about the abuse. In this particular clinical case, we want to highlight that the role of the Psychologist’s intervention at CRAS is to attempt to resolve the issue promptly (and not to develop a prolonged clinical study based on traditional methods), by making use of the available tools from the social assistance network, and by making referrals to the relevant authorities, such as the Public Ministry, so that final protective actions can be taken and enforced. In this case, the Guardian Council of the Brazilian Public Ministry was asked to transfer the custody of the child to her uncle. The mother of the child was sent to a CAPS (Centre for Psychosocial Care), having been diagnosed with psychopathology. The child would then participate in NGO programs that allow for a gradual reduction of social exposure to her mother before being transferred to her uncle’s custody in Sao Paulo.

Keywords: child abuse, intervention, social psychology, violence

Procedia PDF Downloads 289

Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

Procedia PDF Downloads 269

Authors: Farzad Khajavi, Farzaneh Jalilfar, Faranak Jafari, Leila Shokrani

Abstract:

Formulation of Ranolazine in the form of extended-release tablet in 500 mg dosage form was performed using Eudragit L100-55 as a retarding agent. Drug-release profiles were investigated in comparison with the reference Ranexa extended-release 500 mg tablet. F₂ and f₁ were calculated as 64.16 and 8.53, respectively. According to Peppas equation, the release of drug is controlled by diffusion (n=0.5). The tablets were put into accelerated stability conditions (40 °C, 75% humidity) for 3 and 6 months. The dissolution release profiles and other physical and chemical characteristics of the tablets confirmed the robustness and stability of formulation in this condition.

Keywords: drug release, extended-release tablet, ranolazine, stability

Procedia PDF Downloads 119

Authors: Ida Madieha Abdul Ghani Azmi, Heng Gee Lim, Adlan Abdul Razak, Nasaruddin Abdul Rahman

Abstract:

The objective of competition law is to maximise consumer welfare through the regulation of anti-competitive behaviour that results in the distortion of the market. Intellectual property law also seeks to enhance consumer welfare in the long run by encouraging the development of useful devices and processes. Nevertheless, in some circumstances, the IP owners behave in such a way that makes it difficult for rival companies to sell substitute products and technology in the market. Intellectual property owners may also reach a dominant position in the market such that they are able to dictate unfair terms and conditions on other market players. Among the two major categories of anti-competitive behavior is the use of horizontal and vertical agreement to constrain effective competition and abuse of dominant position. As a result, many countries have regulated the conduct of the IP owners that are considered as anti-competitive including the US, Canada, and Singapore. This paper visits the proposed IP Guidelines recently drafted by the Malaysian Competition Commission and investigates to what extent it resolves most of the anti-competitive behavior of the IP owners. The paper concludes by suggesting some of the rules that could be prescribed by the Competition Commission in order to maintain the relevancy of competition law as the main check against the abuse of rights by the intellectual property owners.

Keywords: abuse of dominant position, consumer welfare, intellectual property rights, vertical and horizontal agreements

Procedia PDF Downloads 191

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

Abstract:

Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

Procedia PDF Downloads 55

Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

Abstract:

Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

Procedia PDF Downloads 52

Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

Procedia PDF Downloads 80

Authors: H. R. Kelidari, M. Saeedi, J. Akbari, K. Morteza-Semnani, H. Valizadeh

Abstract:

Spironolactoe (SP) a synthetic steroid diuretic is a poorly water-soluble drug with a low and variable oral bioavailability. Regarding to the good solubility of SP in lipid materials, SP loaded Solid lipid nanoparticles (SP-SLNs) and nanostructured lipid carrier (SP-SLNs) were thus prepared in this work for accelerating dissolution of this drug. The SP loaded NLC with stearic acid (SA) as solid lipid and different Oleic Acid (OA) as liquid lipid content and SLN without OA were prepared by probe ultrasonication method. With increasing the percentage of OA from 0 to 30 wt% in SLN/NLC, the average size and zeta potential of nanoparticles felled down and entrapment efficiency (EE %) rose dramatically. The obtained micrograph particles showed pronounced spherical shape. Differential Scanning Calorimeter (DSC) measurements indicated that the presence of OA reduced the melting temperature and melting enthalpy of solid lipid in NLC structure. The results reflected good long-term stability of the nanoparticles and the measurements show that the particle size remains lower in NLC compare to SLN formulations, 6 months after production. Dissolution of SP-SLN and SP-NLC was about 5.1 and 7.2 times faster than raw drugs in 120 min respectively. These results indicated that the SP loaded NLC containing 70:30 solid lipid to liquid lipid ratio is a suitable carrier of SP with improved drug EE and steady drug release properties.

Keywords: drug release, lipid nanoparticles, spironolactone, stability

Procedia PDF Downloads 301

Authors: Sean Hall

Abstract:

Nanosystems for drug delivery are not new; as medicines evolve, so too does the desire to deliver a more targeted, patient-compliant medicine. Though, historically the widespread use of nanosystems for drug delivery has been fouled by non-replicability, scalability, toxicity issues, and economics. Examples include steps of manufacture and thus cost to manufacture, toxicity for nanoparticle scaffolding, autoimmune response, and considerable technical expertise for small non-commercial yields. This, unfortunately, demonstrates the not-so-obvious chasm between science and drug formulation for regulatory approval. Regardless there is a general and global desire to improve the delivery of medicines, reduce potential side effect profiles, promote increased patient compliance, and increase and/or speed public access to medicine availability. In this paper, the author will discuss NanoCelle®, a nano-delivery platform that specifically addresses degradation and solubility issues that expands from fundamental micellar preparations. NanoCelle® has been deployed in several Australian listed medicines and is in use of several drug candidates across small molecules, with research endeavors now extending into large molecules. The author will discuss several research initiatives as they relate to NanoCelle® to demonstrate similarities seen in various drug substances; these examples will include both in vitro and in vivo work.

Keywords: NanoCelle®, micellar, degradation, solubility, toxicity

Procedia PDF Downloads 152

Authors: S. V. Patil, P. S. Dounde, S. S. Patil

Abstract:

Emulgels have emerged as one of the most interesting topical delivery system as it has dual release control system that is gel and emulsion. The major objective behind this formulation is delivery of hydrophobic drugs to systemic circulation via skin. In fact presence of a gelling agent in water phase converts a classical emulsion in to emulgel. The emulgel for dermatological use has several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, water-soluble, longer shelf life, bio-friendly, transparent and pleasing appearance. Various penetration enhancers can potentiate the effect. So this can be used as better topical drug delivery systems over present conventional systems available in market. Piroxicam is a non-steroidal anti-inflammatory drug that has major problems when administered orally; it is an insoluble drug and has irritant effect on gastro intestinal tract lead to ulceration and bleeding. The aim of this study was to overcoming these problems through preparation of topical emulgel of this drug. Emulgel of Piroxicam was prepared using Carbopol 940 along with mentha oil and clove oil as permeation enhancer. The prepared emulgel were evaluated for their physical appearance, pH determination, viscosity, spreadability, in vitro drug release, ex vivo permeation studies. All the prepared formulations showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. The emulgel was found to be stable with respect to physical appearance, pH, rheological properties and drug content at all temperature and conditions for three month.

Keywords: emulgel, piroxicam, menthe oil, clove oil

Procedia PDF Downloads 431

Authors: Maria Elisabete Costa Ferreira

Abstract:

Domestic violence is a serious social issue in which victims are mostly women. Domestic violence develops in cycles, starting with the building of tension, passing through the incident of abuse and ending with reconciliation, also known as honeymoon. As time goes by, the shorter these phases become, and the greater and more severe the attacks, rarely leading to the death of the victim of abuse. Sometimes, the victim stops the abuse by killing the aggressor, usually after the immediate aggression has taken place. This poses an important obstacle to the claim of self-defense by the victim of domestic violence pending trial for the homicide of her long-time abuser. The main problem with self-defense claims in such cases is that the law requires the act of aggression to be present or imminent (imminent threat or immediate danger) so that it permits the victim to take her defense into her own hands. If the episode of aggression has already taken place, this general requirement for the admissibility of self-defense is not satisfied. This paper sheds new light on the concept of the actuality of the aggression, understanding that, since domestic violence is a permanent offense, for as long as the victim stays under the domain of the aggressor, imminent threat will be present, allowing the self-defense claim of a woman who kills her abuser in such circumstances to be admissible. An actualist interpretation of the requirement of the necessity of the means used in self-defense will be satisfied when evaluated from the subjective perspective of the intimate partner victim. Necessity will be satisfied if it is reasonable for the victim to perceive the use of lethal force as the only means to release herself from the abuser.

Keywords: domestic violence, homicide, self-defense, imminent threat, necessity of lethal force

Procedia PDF Downloads 27

Authors: Yuhua Wang, Mu Li, Jinggen Liu

Abstract:

Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

Procedia PDF Downloads 354

Authors: Debalke Dale, Bezabh Geneta, Yohannes Amene, Yordanos Bergene, Mohammed Yimam

Abstract:

Background: A drug therapy problem (DTP) is an event or circumstance that involves drug therapies that actually or potentially interfere with the desired outcome and requires professional judgment to resolve. Heart failure is an emerging worldwide threat whose prevalence and health loss burden constantly increase, especially in the young and in low-to-middle-income countries. There is a lack of population-based incidence and prevalence of heart failure (HF) studies in sub-Saharan African countries, including Ethiopia. Objective: The aim of this study was designed to assess drug therapy problems and associated factors among patients with HF in the medical ward of Arba Minch General Hospital(AGH), Ethiopia, from June 5 to August 20, 2022. Methods: A retrospective cross-sectional study was conducted among 180 patients with HF who were admitted to the medical ward of AGH. Data were collected from patients' cards by using questionnaires. The data were categorized and analyzed by using SPSS version 25.0 software, and data were presented in tables and words based on the nature of the data. Result: Out of the total, 85 (57.6%) were females, and 113 (75.3%) patients were aged over fifty years. Of the 150 study participants, 86 (57.3%) patients had at least one DTP identified, and a total of 116 DTPs were identified, which is 0.77 DTPs per patient. The most common types of DTP were unnecessary drug therapy (32%), followed by the need for additional drug therapy (36%), and dose too low (15%). Patients who used polypharmacy were 5.86 (AOR) times more likely to develop DTPs than those who did not (95% CI = 1.625–16.536, P = 0.005), and patients with more co-morbid conditions developed 3.68 (AOR) times more DTPs than those who had fewer co-morbidities (95% CI = 1.28–10.5, P = 0.015). Conclusion: The results of this study indicated that drug therapy problems were common among medical ward patients with heart failure. These problems are adversely affecting the treatment outcomes of patients, so it requires the special attention of healthcare professionals to optimize them.

Keywords: heart failure, drug therapy problems, Arba Minch general hospital, Ethiopia

Procedia PDF Downloads 71

Authors: Humraaz Kaja, Kofi Mensah, Frasia Oosthuizen

Abstract:

Background and Aim: Vilazodone was approved in 2011 as an antidepressant to treat the major depressive disorder. As a relatively new drug, it is not clear if all adverse effects have been identified. The aim of this study was to review the adverse effects reported to the WHO Programme for International Drug Monitoring (PIDM) in order to add to the knowledge about the safety profile and adverse effects caused by vilazodone. Method: Data on adverse effects reported for vilazodone was obtained from the database VigiAccess managed by PIDM. Data was extracted from VigiAccess using Excel® and analyzed using descriptive statistics. The data collected was compared to the patient information leaflet (PIL) of Viibryd® and the FDA documents to determine adverse drug reactions reported post-marketing. Results: A total of 9708 adverse events had been recorded on VigiAccess, of which 6054 were not recorded on the PIL and the FDA approval document. Most of the reports were received from the Americas and were for adult women aged 45-64 years (24%, n=1059). The highest number of adverse events reported were for psychiatric events (19%; n=1889), followed by gastro-intestinal effects (18%; n=1839). Specific psychiatric disorders recorded included anxiety (316), depression (208), hallucination (168) and agitation (142). The systematic review confirmed several psychiatric adverse effects associated with the use of vilazodone. The findings of this study suggested that these common psychiatric adverse effects associated with the use of vilazodone were not known during the time of FDA approval of the drug and is not currently recorded in the patient information leaflet (PIL). Conclusions: In summary, this study found several adverse drug reactions not recorded in documents emanating from clinical trials pre-marketing. This highlights the importance of continued post-marketing surveillance of a drug, as well as the need for further studies on the psychiatric adverse events associated with vilazodone in order to improve the safety profile.

Keywords: adverse drug reactions, pharmacovigilance, post-marketing surveillance, vilazodone

Procedia PDF Downloads 84

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

Abstract:

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

Procedia PDF Downloads 51

Authors: Chuan Yin

Abstract:

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

Procedia PDF Downloads 348

Authors: Raj Kumar, Prem Felix Siril

Abstract:

The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

Procedia PDF Downloads 284