Search results for: drug induced premature chromosome condensation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4860

Search results for: drug induced premature chromosome condensation

4440 Effectiveness of Group Therapy Based on Acceptance and Commitment on Self-Criticism and Coping Mechanism in People with Addiction

Authors: Mohamad Reza Khodabakhsh

Abstract:

Drug use and addiction are major biological, psychological, and social problems. In drug abuse treatment, it is important to pay attention to personality problems and coping methods of patients. Today, the third-wave treatments in psychotherapy emphasize people's awareness and acceptance of feelings and emotions, cognitions, and behaviors instead of challenging cognitions. For this reason, this research was conducted with the aim of investigating the effectiveness of group therapy based on acceptance and commitment to self-criticism and coping strategies of people with drug use disorder. This research was a quasi-experimental type of research (pre-test-post-test design with an unequal control group), and the statistical population of this research included all men with drug use disorder in Mashhad, 174 of whom among the 75 people eligible for this research, 30 of them were selected by available sampling method and randomly assigned to two experimental and control groups. In this research, Gilbert's self-criticism scale was used to measure self-criticism, and Andler and Barker's coping strategies questionnaire was used to measure coping strategies. Therapeutic intervention (treatment based on acceptance and commitment) was performed on the experimental group for eight sessions of 90 minutes, and then post-tests were taken from both groups, and multivariate analysis of covariance (MANCOVA) was used to analyze the data. The results showed that treatment based on acceptance and commitment significantly reduced self-criticism and improved coping strategies used by patients with drug use disorder (p>0.01). Therefore, treatment based on acceptance and commitment has been effective in reducing self-criticism and improving the coping strategies of patients with drug use disorder due to teaching clients to accept thoughts and conditions.

Keywords: treatment based on acceptance and commitment, self-criticism, coping strategies, addiction

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4439 Effects of Pharmaceutical Drugs on Fish (koi) Behaviour and Muscle Function

Authors: Gayathri Vijayakumar, Preethi Baskaran

Abstract:

The effluents that are let down by the industries mix with the water bodies and drastically affect the aquatic life, which leads to pollution and bio magnifications. Effluents mostly contain chemicals, heavy metals etc., and cause toxicity to the environment. The pharmaceutical industries too contribute. The by-products and other unwanted waste are discharged without any treatment; these causes DNA damage and affect behavior of aquatic life. The study was conducted on koi carp (Cyprinus carpio) the ornamental variety of common carp. A two week long study was conducted on them using common anti-depressant drug (Diazepam) in various concentrations. These drugs are known to cause behavioral damage and organ malfunctions (muscle twitch). The histopathological study conducted showed permanent muscle twitching and lesions in the fish samples studied. The sociability was also affected in the span of 14 days. Higher concentrations of this drug showed severe damage in the muscle structures. Thus, this drug can cause adverse effects on marine ecosystem and eventually cause bio magnification of drug by running through the food chain.

Keywords: pollution, toxicity, bio-magnifications, koi carp, muscle twitch, diazepam, histopathology

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4438 Calpain-Mediated, Cisplain-Induced Apoptosis in Breast Cancer Cells

Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

Abstract:

Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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4437 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

Abstract:

Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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4436 Drug Sensitivity Pattern of Organisms Causing Suppurative Otitis Media

Authors: Nagat M. Saeed, Mabruka S. Elashheb, Fatma M. Ben Rabaha, Aisha M Edrah

Abstract:

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

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

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4435 Improving the Aqueous Solubility of Taxol through Altering XLOGP3

Authors: Arianna Zhu, Thomas Bakupog

Abstract:

Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

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4434 Fabrication and Characterization of Transdermal Spray Using Film Forming Polymer

Authors: Paresh Patel, Harshit Patel

Abstract:

Superficial fungal skin infection is among the most common skin disease. The drug administration through skin has received attention due to several advantages: Avoidance of significant pre-systemic metabolism, drug levels within the therapeutic window, drugs with short biological half-lives, decreased side effects, the non-invasive character, and very high acceptance.

Keywords: transdermal spray, ketoconazole, Eudragit® RLPO, therapeutic window

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4433 Nano-emulsion/Nano-suspension as Precursors for Oral Dissolvable Film to Enhance Bioavalabilty for Poor-water Solubility Drugs

Authors: Yuan Yang, Mickey Lam

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Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

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4432 A New Cytoprotective Drug on the Basis of Cytisine: Phase I Clinical Trial Results

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

Abstract:

Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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4431 Neuroprotective Effect of Germinated Dolichos lablab on 6-Hydroxy Dopamine (6-OHDA) Induced Toxicity in SH-SY5Y Neuroblastoma Cell

Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

Abstract:

Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

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4430 Conjugated Chitosan-Carboxymethyl-5-Fluorouracil Nanoparticles for Skin Delivery

Authors: Mazita Mohd Diah, Anton V. Dolzhenko, Tin Wui Wong

Abstract:

Nanoparticles, being small with a large specific surface area, increase solubility, enhance bioavailability, improve controlled release and enable precision targeting of the entrapped compounds. In this study, chitosan as polymeric permeation enhancer was conjugated to a polar pro-drug, carboxymethyl-5-fluorouracil (CMFU) to increase the skin drug permeation. Chitosan-CMFU conjugate was synthesized using chemical conjugation process through succinate linker. It was then transformed into nanoparticles via spray drying method. The conjugation was elucidated using Fourier Transform Infrared and Proton Nuclear Magnetic Resonance techniques. The nanoparticle size, size distribution, zeta potential, drug content, skin permeation and retention profiles were characterized. The conjugation was denoted using 1H NMR by new peaks at signal δ = 4.184 ppm (singlet, 2H for CH2) and 7.676-7.688 ppm (doublet, 1H for C6) attributed to CMFU in chitosan-CMFU NMR spectrum. The nanoparticles had profiles of particle size: 93.97 ±35.11 nm, polydispersity index: 0.40 ± 0.14, zeta potential: +18.25 ±2.95 mV and drug content: 6.20 ± 1.98 % w/w. Almost 80 % w/w CMFU in the form of nanoparticles permeated through the skin in 24 hours and close to 50 % w/w permeation occurred in first 1-2 hours. Without conjugation to chitosan and nanoparticulation, less than 40 % w/w CMFU permeated through the skin in 24 hours. The skin drug retention likewise was higher with chitosan-CMFU nanoparticles (15.34 ± 5.82 % w/w) than CMFU (2.24 ± 0.57 % w/w). CMFU, through conjugation with chitosan permeation enhancer and processed in nanogeometry, had its skin permeation and retention degree promoted.

Keywords: carboxymethyl-5-fluorouracil, chitosan, conjugate, skin permeation, skin retention

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4429 DeepLig: A de-novo Computational Drug Design Approach to Generate Multi-Targeted Drugs

Authors: Anika Chebrolu

Abstract:

Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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4428 Tunable Control of Therapeutics Release from the Nanochannel Delivery System (nDS)

Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

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Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

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4427 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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4426 A Fast and Cost-Effective Method to Monitor Microplastics in Compost and Soiduration of Enterococcus Faecalis Penetration in Environmentally Exposed Root Canals Obturated With Lateral Condensation Technique

Authors: N. Thawornwisit, P. Pradoo, S. Nuypree, L. Jarukasetrporn, S. Jitpukdeebodintra

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Objective: The aim of this study was to evaluate the duration of the Enterococcus faecalis (E. faecalis) penetration into the gap between root canal wall and filling material at a 3 to 6 mm distance from the cementoenamel junction (CEJ) in the dislodged temporary filling, in vitro. Material and methods: Thirty-four single root canal mandibular premolars were divided into two experimental groups (N = 15) and one negative control (N = 4). Root canals were prepared and obturated with gutta-percha using lateral condensation technique, X-ray checked, and sterilized. Leakages were set up using the modified bacterial leakage model, and E. faecalis was used as a microbial marker. Leakages were evaluated at 3 and 7 days by culturing gutta-percha and dentine drilled from a 3-6 mm distance from CEJ. Broth turbidity was recorded and compared. Result: All four negative control and the 3-day experimental group showed no broth turbidity. For the 7-day experimental group, there was 33.3% leakage. Conclusion: Penetration of E. faecalis into the gap between root canal wall and filling material at a 3 to 6 mm distance from CEJ in the dislodged temporary filling were not found at three days. However, at seven days of exposure, bacteria could penetrate into the interface of the root canal and filling materials.

Keywords: coronal leakage, bacterial leakage model, enterococcus faecalis

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4425 Study on the Treatment of Waste Water Containing Nitrogen Heterocyclic Aromatic Hydrocarbons by Phenol-Induced Microbial Communities

Authors: Zhichao Li

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This project has treated the waste-water that contains the nitrogen heterocyclic aromatic hydrocarbons, by using the phenol-induced microbial communities. The treatment of nitrogen heterocyclic aromatic hydrocarbons is a difficult problem for coking waste-water treatment. Pyridine, quinoline and indole are three kinds of most common nitrogen heterocyclic compounds in the f, and treating these refractory organics biologically has always been a research focus. The phenol-degrading bacteria can be used in the enhanced biological treatment effectively, and has a good treatment effect. Therefore, using the phenol-induced microbial communities to treat the coking waste-water can remove multiple pollutants concurrently, and improve the treating efficiency of coking waste-water. Experiments have proved that the phenol-induced microbial communities can degrade the nitrogen heterocyclic ring aromatic hydrocarbon efficiently.

Keywords: phenol, nitrogen heterocyclic aromatic hydrocarbons, phenol-degrading bacteria, microbial communities, biological treatment technology

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4424 Carvedilol Ameliorates Potassium Dichromate-Induced Acute Renal Injury in Rats: Plausible Role of Inflammation and Apoptosis

Authors: Bidya Dhar Sahu, Meghana Koneru, R. Shyam Sunder, Ramakrishna Sistla

Abstract:

Environmental and occupational exposure to hexavalent chromium [Cr(VI)] via textile manufacture, metallurgy, spray paints, stainless steel industries, drinking water containing chromium are often known to cause acute renal injury in humans and animals. Nephrotoxicity is the major effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol using rat model of potassium dichromate (K2Cr2O7)-induced nephrotoxicity. Exploration of the underlying mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NF-κB (p65), restored antioxidant and mitochondrial respiratory enzyme activities and attenuated apoptosis related protein expressions in kidney tissues. The serum levels of TNF-α, the renal iNOS and myeloperoxidase activity were significantly decreased in carvedilol pre-treated K2Cr2O7-induced nephrotoxic rats. These results were further supported and confirmed by histological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against K2Cr2O7-induced nephrotoxicity in rats.

Keywords: apoptosis, carvedilol, inflammation, potassium dichromate-induced nephrotoxicity, applied pharmacology

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4423 Current Methods for Drug Property Prediction in the Real World

Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

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Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

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4422 Development of Site-Specific Colonic Drug Delivery System (Nanoparticles) of Chitosan Coated with pH Sensitive Polymer for the Management of Colonic Inflammation

Authors: Pooja Mongia Raj, Rakesh Raj, Alpana Ram

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Background: The use of multiparticulate drug delivery systems in preference to single unit dosage forms for colon targeting purposes dates back to 1985 when Hardy and co-workers showed that multiparticulate systems enabled the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. Methods: Site-specific colonic drug delivery system (nanoparticles) of 5-ASA were prepared and coated with pH sensitive polymer. Chitosan nanoparticles (CTNP) bearing 5-Amino salicylic acid (5-ASA) were prepared, by ionotropic gelation method. Nanoparticulate dosage form consisting of a hydrophobic core enteric coated with pH-dependent polymer Eudragit S-100 by solvent evaporation method, for the effective delivery of drug to the colon for treatment of ulcerative colitis. Results: The mean diameter of CTNP and ECTNP formulations were 159 and 661 nm, respectively. Also optimum value of polydispersity index was found to be 0.249 [count rate (kcps) was 251.2] and 0.170 [count rate (kcps) was 173.9] was obtained for both the formulations respectively. Conclusion: CTNP and Eudragit chitosan nanoparticles (ECTNP) was characterized for shape and surface morphology by scanning electron microscopy (SEM) appeared to be spherical in shape. The in vitro drug release was investigated using USP dissolution test apparatus in different simulated GIT fluids showed promising release. In vivo experiments are in further proceeding for fruitful results.

Keywords: colon targeting, nanoparticles, polymer, 5-amino salicylic acid, edragit

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4421 Is Presence of Psychotic Features Themselves Carry a Risk for Metabolic Syndrome?

Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

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Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

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4420 Factors Influencing Antipsychotic Drug Usage and Substitution among Nigerian Schizophrenic Patients

Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

Abstract:

Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

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4419 Protective Effect of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats

Authors: Aman Upaganlawar, Upasana Khairnar, Chandrashekhar Upasani

Abstract:

The present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride-induced spleen toxicity in rats. Male Wistar rats of either sex (200-250g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o), ascorbic acid (40 mg/kg/day, p.o), and combination of protocatechuic acid (20 mg/kg/day, p.o) and ascorbic acid (20 mg/kg/day, p.o) followed by aniline hydrochloride. At the end of treatment period, serum and tissue parameters were evaluated. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (Hemoglobin content, Red Blood Cells, White Blood Cells and Total iron content), tissue parameters (Lipid peroxidation, Reduced glutathione, Nitric oxide content) compared to control group. Histopathology of aniline hydrochloride-induced spleen showed significant damage compared to control rats. Treatment with Protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride-induced spleen toxicity. In conclusion Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride-induced splenic toxicity in rats.

Keywords: aniline, spleen toxicity, protocatechuic acid, ascorbic acid, antioxidants

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4418 Lipid-Coated Magnetic Nanoparticles for Frequency Triggered Drug Delivery

Authors: Yogita Patil-Sen

Abstract:

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.

Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)

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4417 The Spread of Drugs in Higher Education

Authors: Wantana Amatariyakul, Chumnong Amatariyakul

Abstract:

The research aims to examine the spread of drugs in higher education, especially amphetamine which is rapidly increasing in Thai society, its causes and effects, including the sociological perspective, in order to explain, prevent, control, and solve the problems. The students who participated in this research are regular students of Rajamangala University of Technology Isan, Khon Kaen Campus. The data were collected using questionnaires, group discussions, and in-depth interviews. The quantity data were analyzed using frequency, percentage, mean and standard deviation and using content analysis to analyzed quality data. The result of the study showed that the students had the results of examination on level of knowledge and understanding on drug abuse projected that the majority of sample group attained their knowledge on drug abuse respectively. Despite their uncertainty, the majority of samples presumed that amphetamine, marijuana and grathom (Mitragyna Speciosa Korth) would most likely be abused. The reason for first drug abuse is because they want to try and their friends convince them, as well as, they want to relax or solve the problems in life, respectively. The bad effects appearing to the drug addicts shows that their health deteriorates or worsens, as well as, they not only lose their money but also face with worse mental states. The reasons that respondents tried to avoid using drugs or refused drugs offered by friends were: not wanting to disappoint or upset their family members, fear of rejection by family members, afraid of being arrested by the police, afraid of losing their educational opportunity and ruining their future respectively. Students therefore defended themselves against drug addiction by refusing to try all drugs. Besides this, the knowledge about the danger and the harm of drugs persuaded them to stay away from drugs.

Keywords: drugs, higher education, drug addiction, spread of drugs

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4416 Study of Laser Induced Damage Threshold in HfO₂/SiO₂ Multilayer Films after β-Ray Irradiation

Authors: Meihua Fang, Tao Fei

Abstract:

Post-processing can effectively improve the resistance to laser damage in multilayer films used in a high power laser system. In this work, HfO₂/SiO₂ multilayer films are prepared by e-beam evaporation and then β-ray irradiation is employed as the post-processing method. The particle irradiation affects the laser induced damage threshold (LIDT), which includes defects, surface roughness, packing density, and residual stress. The residual stress that is relaxed during irradiation changes from compressive stress into tensile stress. Our results indicate that appropriate tensile stress can improve LIDT remarkably. In view of the fact that LIDT rises from 8 J/cm² to 12 J/cm², i.e., 50% increase, after the film has been irradiated by 2.2×10¹³/cm² β-ray, the particle irradiation can be used as a controllable and desirable post-processing method to improve the resistance to laser induced damage.

Keywords: β-ray irradiation, multilayer film, residual stress, laser-induced damage threshold

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4415 Modeling of Thermally Induced Acoustic Emission Memory Effects in Heterogeneous Rocks with Consideration for Fracture Develo

Authors: Vladimir A. Vinnikov

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The paper proposes a model of an inhomogeneous rock mass with initially random distribution of microcracks on mineral grain boundaries. It describes the behavior of cracks in a medium under the effect of thermal field, the medium heated instantaneously to a predetermined temperature. Crack growth occurs according to the concept of fracture mechanics provided that the stress intensity factor K exceeds the critical value of Kc. The modeling of thermally induced acoustic emission memory effects is based on the assumption that every event of crack nucleation or crack growth caused by heating is accompanied by a single acoustic emission event. Parameters of the thermally induced acoustic emission memory effect produced by cyclic heating and cooling (with the temperature amplitude increasing from cycle to cycle) were calculated for several rock texture types (massive, banded, and disseminated). The study substantiates the adaptation of the proposed model to humidity interference with the thermally induced acoustic emission memory effect. The influence of humidity on the thermally induced acoustic emission memory effect in quasi-homogeneous and banded rocks is estimated. It is shown that such modeling allows the structure and texture of rocks to be taken into account and the influence of interference factors on the distinctness of the thermally induced acoustic emission memory effect to be estimated. The numerical modeling can be used to obtain information about the thermal impacts on rocks in the past and determine the degree of rock disturbance by means of non-destructive testing.

Keywords: degree of rock disturbance, non-destructive testing, thermally induced acoustic emission memory effects, structure and texture of rocks

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4414 The Effect of Drug Prevention Programme Based On Cognitive-Behavioral Therapy (CBT) and Multidimensional Self Concept Module Towards Resiliency and Aggression Among At-Risk Youth in Malaysia

Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

Abstract:

This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

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4413 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats

Authors: Prerna Kalra, Surender Singh

Abstract:

Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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4412 Racism in Drug Policies: A Report on United States Legislation

Authors: Frederick Monyepao

Abstract:

Crack cocaine first appeared on the scene in the form of cocaine freebasing in the late 1970s. Stockbrokers, investment bankers, rock stars, Hollywood elites, and a few pro athletes were regular users of the substance. As criminogenic factors associated with substance abuse began to surface, congress passed new legislation. The laws led to the increase of health coverage insurances and the expansion of hospitals. By the mid-1980s, crack use spread into America's inner cities among impoverished African Americans and Latinos. While substance abuse increased among minority communities, legislation pertaining to substance abuse evolved. The prison industry also expanded the number of cells available. A qualitative approach was taken, drawing from a range secondary sources for contextual analysis. This paper traces out the continued marginalisation and racist undertones towards minorities as perpetuated by certain drug policies. It was discovered that the new legislation on crack was instrumental in the largest incarcerations the United States ever faced. Drug offenders increased in prisons eightfold from 1986 to 2000. The paper concludes that American drug control policies are consistently irrational and ineffective when measured by levels of substance use and abuse. On the contrary, these policies have been successful as agents of social control in maintaining the stratification patterns of racial/ethnic minorities and women. To move beyond prohibition, radical law and policy reform may require a change in narratives on substance use.

Keywords: crack, drug policy, minorities, racism, substance abuse

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4411 Preparation Non-Woven Nanofiber Structures for Uniform and Rapid Drug Releasing Applications Using an Electrospinning Process

Authors: Cho-Liang Chung

Abstract:

Uniform and rapid drug release are important for trauma dressing application. Low glass transition polymer system and non-woven nanofiber structures as the designs conduct rapid-release characteristics. In this study, polyvinylpyrrolidone, polysulfone, and polystyrene were dissolved in dimethylformamide to form precursor solution. These solutions were blended with vitamin C to form the electrospinning solutions. The non-woven nanofibers structures were successfully prepared using an electrospinning process. The following instruments were used to analyze the characteristics of non-woven nanofibers structures: Atomic force microscopy (AFM), Field Emission Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The AFM was used to scan the nanofibers. 3D Graphics were applied to explore the surface morphology of nanofibers. FE-SEM was used to explore the morphology of non-woven structures. XRD was used to identify crystal structures in the non-woven structures. The evolution of morphology of non-woven structures was changed dramatically in different durations, because of the moisture absorption and decreasing glass transition temperature; the non-woven nanofiber structures can be applied to uniform and rapid drug release for trauma dressing application.

Keywords: nanofibers, non-woven, electrospinning process, rapid drug releasing

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