Search results for: interferon gamma release assay
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2807

Search results for: interferon gamma release assay

2387 Bioactive Substances-Loaded Water-in-Oil/Oil-in-Water Emulsions for Dietary Supplementation in the Elderly

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

Abstract:

Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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2386 Second Order Statistics of Dynamic Response of Structures Using Gamma Distributed Damping Parameters

Authors: Badreddine Chemali, Boualem Tiliouine

Abstract:

This article presents the main results of a numerical investigation on the uncertainty of dynamic response of structures with statistically correlated random damping Gamma distributed. A computational method based on a Linear Statistical Model (LSM) is implemented to predict second order statistics for the response of a typical industrial building structure. The significance of random damping with correlated parameters and its implications on the sensitivity of structural peak response in the neighborhood of a resonant frequency are discussed in light of considerable ranges of damping uncertainties and correlation coefficients. The results are compared to those generated using Monte Carlo simulation techniques. The numerical results obtained show the importance of damping uncertainty and statistical correlation of damping coefficients when obtaining accurate probabilistic estimates of dynamic response of structures. Furthermore, the effectiveness of the LSM model to efficiently predict uncertainty propagation for structural dynamic problems with correlated damping parameters is demonstrated.

Keywords: correlated random damping, linear statistical model, Monte Carlo simulation, uncertainty of dynamic response

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2385 Best Combination of Design Parameters for Buildings with Buckling-Restrained Braces

Authors: Ángel de J. López-Pérez, Sonia E. Ruiz, Vanessa A. Segovia

Abstract:

Buildings vulnerability due to seismic activity has been highly studied since the middle of last century. As a solution to the structural and non-structural damage caused by intense ground motions, several seismic energy dissipating devices, such as buckling-restrained braces (BRB), have been proposed. BRB have shown to be effective in concentrating a large portion of the energy transmitted to the structure by the seismic ground motion. A design approach for buildings with BRB elements, which is based on a seismic Displacement-Based formulation, has recently been proposed by the coauthors in this paper. It is a practical and easy design method which simplifies the work of structural engineers. The method is used here for the design of the structure-BRB damper system. The objective of the present study is to extend and apply a methodology to find the best combination of design parameters on multiple-degree-of-freedom (MDOF) structural frame – BRB systems, taking into account simultaneously: 1) initial costs and 2) an adequate engineering demand parameter. The design parameters considered here are: the stiffness ratio (α = Kframe/Ktotal), and the strength ratio (γ = Vdamper/Vtotal); where K represents structural stiffness and V structural strength; and the subscripts "frame", "damper" and "total" represent: the structure without dampers, the BRB dampers and the total frame-damper system, respectively. The selection of the best combination of design parameters α and γ is based on an initial costs analysis and on the structural dynamic response of the structural frame-damper system. The methodology is applied to a 12-story 5-bay steel building with BRB, which is located on the intermediate soil of Mexico City. It is found the best combination of design parameters α and γ for the building with BRB under study.

Keywords: best combination of design parameters, BRB, buildings with energy dissipating devices, buckling-restrained braces, initial costs

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2384 Gamma Irradiated Sodium Alginate and Phosphorus Fertilizer Enhances Seed Trigonelline Content, Biochemical Parameters and Yield Attributes of Fenugreek (Trigonella foenum-graecum L.)

Authors: Tariq Ahmad Dar, Moinuddin, M. Masroor A. Khan

Abstract:

There is considerable need in enhancing the content and yield of active constituents of medicinal plants keeping in view their massive demand worldwide. Different strategies have been employed to enhance the active constituents of medicinal plants and the use of phytohormones has been proved effective in this regard. Gamma-irradiated Sodium alginate (ISA) is known to elicit an array of plant defense responses and biological activities in plants. Considering the medicinal importance, a pot experiment was conducted to explore the effect of ISA and phosphorus on growth, yield and quality of fenugreek (Trigonella foenum-graecum L.). ISA spray treatments (0, 40, 80 and 120 mg L-1) were applied alone and in combination with 40 kg P ha-1 (P40). Crop performance was assessed in terms of plant growth characteristics, physiological attributes, seed yield and the content of seed trigonelline. Of the ten-treatments, P40 + 80 mg L−1 of ISA proved the best. The results showed that foliar spray of ISA alone or in combination with P40 augmented the plant vegetative growth, enzymatic activities, trigonelline content, trigonelline yield and economic yield of fenugreek. Application of 80 mg L−1 of ISA applied with P40 gave the best results for almost all the parameters studied compared to control or to 80 mg L−1 of ISA applied alone. This treatment increased the total content of chlorophyll, carotenoids, leaf -N, -P and -K and trigonelline compared to the control by 24.85 and 27.40%, 15 and 23.52%, 18.70 and 16.84%, 15.88 and 18.92%, 12 and 14.44%, at 60 and 90 DAS respectively. The combined application of 80 mg L−1 of ISA along with P40 resulted in the maximum increase in seed yield, trigonelline content and trigonelline yield by146, 34 and 232.41%, respectively, over the control. Gel permeation chromatography revealed the formation of low molecular weight fractions in ISA samples, containing even less than 20,000 molecular weight oligomers, which might be responsible for plant growth promotion in this study. Trigonelline content was determined by reverse phase high performance liquid chromatography (HPLC) with C-18 column.

Keywords: gamma-irradiated sodium alginate, phosphorus, gel permeation chromatography, HPLC, trigonelline content, yield

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2383 Transdermal Medicated- Layered Extended-Release Patches for Co-delivery of Carbamazepine and Pyridoxine

Authors: Sarah K. Amer, Walaa Alaa

Abstract:

Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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2382 Investigation of Cytotoxic Compounds in Ethyl Acetate and Chloroform Extracts of Nigella sativa Seeds by Sulforhodamine-B Assay-Guided Fractionation

Authors: Harshani Uggallage, Kapila D. Dissanayaka

Abstract:

A Sulforhodamine-B assay-guided fractionation on Nigella sativa seeds was conducted to determine the presence of cytotoxic compounds against human hepatoma (HepG2) cells. Initially, a freeze-dried sample of Nigella sativa seeds was sequentially extracted into solvents of increasing polarities. Crude extracts from the sequential extraction of Nigella sativa seeds in chloroform and ethyl acetate showed the highest cytotoxicity. The combined mixture of these two extracts was subjected to bioassay guided fractionation using a modified Kupchan method of partitioning, followed by Sephadex® LH-20 chromatography. This chromatographic separation process resulted in a column fraction with a convincing IC50 (half-maximal inhibitory concentration) value of 13.07µg/ml, which is considerable for developing therapeutic drug leads against human hepatoma. Reversed phase High-Performance Liquid Chromatography (HPLC) was finally conducted for the same column fraction, and the result indicates the presence of one or several main cytotoxic compounds against human HepG2 cells.

Keywords: cytotoxic compounds, half-maximal inhibitory concentration, high-performance liquid chromatography, human HepG2 cells, nigella sativa seeds, Sulforhodamine-B assay

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2381 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

Abstract:

The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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2380 The Use of Beneficial Microorganisms from Diverse Environments for the Management of Aflatoxin in Maize

Authors: Mathias Twizeyimana, Urmila Adhikari, Julius P. Sserumaga, David Ingham

Abstract:

The management of aflatoxins (naturally occurring toxins produced by certain fungi, most importantly Aspergillus flavus and A. parasiticus) relies mostly on the use of best cultural practices and, in some cases, the use of the biological control consisting of atoxigenic strains inhibiting the toxigenic strains through competition resulting in considerable toxin reduction. At AgBiome, we have built a core collection of over 100,000 fully sequenced microbes from diverse environments and employ both the microbes and their sequences in the discovery of new biological products for disease and pest control. The most common approach to finding beneficial microbes consists of isolating microorganisms from samples collected from diverse environments, selecting antagonistic strains through empirical screening, studying modes of action, and stabilization through the formulation of selected microbial isolates. A total of 608 diverse bacterial strains were screened using a high-throughput assay (48-well assay) to identify strains that inhibit toxigenic A. flavus growth on maize kernels. Active strains in 48-well assay had their pathogen inhibiting activity confirmed using the Flask Assay and were concurrently tested for their ability to reduce the aflatoxin content in maize grains. Strains with best growth inhibition and reduction of aflatoxin were tested in the greenhouse and field trials. From the field trials, three bacterial strains, AFS000009 (Pseudomonas chlororaphis), AFS032321 (Bacillus subtilis), AFS024683 (Bacillus velezensis), had aflatoxin concentrations (ppb) values that were significantly lower than those of inoculated control. The identification of biological products with high efficacy in inhibiting pathogen growth and eventually reducing the aflatoxin content will provide a valuable alternative to control strategies used in aflatoxin contamination management.

Keywords: aflatoxin, microorganism bacteria, biocontrol, beneficial microbes

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2379 Theta-Phase Gamma-Amplitude Coupling as a Neurophysiological Marker in Neuroleptic-Naive Schizophrenia

Authors: Jun Won Kim

Abstract:

Objective: Theta-phase gamma-amplitude coupling (TGC) was used as a novel evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. However, to our best knowledge, no studies have reported the diagnostic utility of the TGC in the resting-state electroencephalographic (EEG) of neuroleptic-naive patients with schizophrenia compared to healthy controls. Thus, the purpose of this EEG study was to understand the underlying mechanisms in patients with schizophrenia by comparing the TGC at rest between two groups and to evaluate the diagnostic utility of TGC. Method: The subjects included 90 patients with schizophrenia and 90 healthy controls. All patients were diagnosed with schizophrenia according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) by two independent psychiatrists using semi-structured clinical interviews. Because patients were either drug-naïve (first episode) or had not been taking psychoactive drugs for one month before the study, we could exclude the influence of medications. Five frequency bands were defined for spectral analyses: delta (1–4 Hz), theta (4–8 Hz), slow alpha (8–10 Hz), fast alpha (10–13.5 Hz), beta (13.5–30 Hz), and gamma (30-80 Hz). The spectral power of the EEG data was calculated with fast Fourier Transformation using the 'spectrogram.m' function of the signal processing toolbox in Matlab. An analysis of covariance (ANCOVA) was performed to compare the TGC results between the groups, which were adjusted using a Bonferroni correction (P < 0.05/19 = 0.0026). Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of the TGC data for schizophrenia diagnosis. Results: The patients with schizophrenia showed a significant increase in the resting-state TGC at all electrodes. The delta, theta, slow alpha, fast alpha, and beta powers showed low accuracies of 62.2%, 58.4%, 56.9%, 60.9%, and 59.0%, respectively, in discriminating the patients with schizophrenia from the healthy controls. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, displaying an overall classification accuracy of 92.5%. Conclusion: As TGC includes phase, which contains information about neuronal interactions from the EEG recording, TGC is expected to be useful for understanding the mechanisms the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The resting-state TGC value was increased in the patients with schizophrenia compared to that in the healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Further research exploring the association between TGC and medical or psychiatric conditions that may confound EEG signals will help clarify the potential utility of TGC.

Keywords: quantitative electroencephalography (QEEG), theta-phase gamma-amplitude coupling (TGC), schizophrenia, diagnostic utility

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2378 Lipid Nanoparticles for Spironolactone Delivery: Physicochemical Characteristics, Stability and Invitro Release

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

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2377 Reforms in China's Vaccine Administration: Vulnerabilities, Legislative Progresses and the Systemic View of Vaccine Administration Law

Authors: Lin Tang, Xiaoxia Guo, Lingling Zhang

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Recent vaccine scandals overshadowed China’s accomplishment of public health, triggering discussions on the causes of vaccine incidents. Through legal interpretation of selected vaccine incidents and analysis of systemic vulnerabilities in vaccine circulation and lot release, a panoramic review of legislative progresses in the vaccine administration sheds the light on this debate. In essence, it is the combination of the lagging legal system and the absence of information technology infrastructure in the process of vaccine administration reform that has led to the recurrence of vaccine incidents. These findings have significant implications for further improvement of vaccine administration and China’s participation in global healthcare.

Keywords: legislation, lot release, public health, reform, vaccine administration, vaccine circulation

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2376 Cratoxy Formosum (Jack) Dyer Leaf Extract-Induced Human Breast and Liver Cancer Cells Death

Authors: Benjaporn Buranrat, Nootchanat Mairuae

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Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.

Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death

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2375 Morphological Characteristics and Bioreactivity of Inhalable Particles during the Temple Fair in Kaifeng

Authors: Qiao Yushuang, Shao Longyi

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This paper presents the result of plasmid assay of inhalable particulates PM10 and PM2.5 that were collected during the period of the 11th Hanyuan temple fair of ancestor worship in Kaifeng City. By use of a high-resolution Field Emission Scanning Electron Microscopy (FESEM) and image analysis (IA) technology, the morphological characteristics and Particle Size Distribution (PSD) of each were analyzed and the Bioreactivity of PM10 was evaluated by using plasmid DNA assay. The result shows that, as the dominant component of the samples taken in the urban area of Kaifeng City, the mineral particles, compared with the other components including the soot aggregates, coal ash, and unidentified particles, have a much greater amount and volume. The mineral particles exhibited a decentralized quantity - size distribution, whose presence could be available among the particles sizing 2.5μm or smaller. In contrast, the volume-size distribution of mineral particles is scattered in a relatively narrow range of between1μm and 2.5μm. According to the plasmid assay the TD50 (toxic dose of PM causing 50% of plasmid damage, expressed in μg/ml) of water-soluble PM10 and whole fraction of Kaifeng airborne PM10 was measured respectively at 220-208μg/ml and 300-400μg/ml versus 160μg/ml and 190μg/ml for PM2.5. It can be seen that the whole fraction of airborne particles caused more oxidative damage than the water-soluble fractions, and the PM2.5 has a greater oxidative capacity than the PM10.

Keywords: inhalable particulates (PM10 and PM2.5), morphological features, bioreactivity, Kaifeng

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2374 Ethnopharmacological Analysis of Fermented Herbal Concoctions

Authors: Ishmael Ntlhamu

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In Limpopo Province, the use of herbal concoctions is becoming very popular. These concoctions are claimed to be capable of treating ulcers, diabetes, certain STDs, blood cleansing, and many more types of diseases. The aim of this study was to evaluate the phytochemical composition, evaluate the pharmacological effects and consumption safety in herbal concoctions to treat various kinds of ailments in Limpopo. The concoctions were extracted with 80% acetone. Microorganisms in the concoctions were identified using the Vitek 2 compact system. Qualitative phytochemical analysis was determined using standard chemical tests and thin layer chromatography (TLC). Total polyphenol content was quantified. Antioxidant activity was quantified using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay and ferric reducing power. Antimicrobial activities were determined using a broth micro-dilution assay and bioautography. Cell viability assay was used to determine the cytotoxicity. Results showed that concoctions had antioxidant activity. Presence of different phytoconstituents was observed. Isolated microorganisms were identified as Burkholderia pseudomallei, Staphylococcus vitulimus, Enterococcus columbae, Kocuria kristanae, Staphylococcus intermedius, Cryptococcus laurenti. and Burkholderia pseudomallei (highly pathogenic). Therefore, phytochemicals prove that the concoctions can heal as the antimicrobial tests also displayed activity. Moreover, the concoctions did not exhibit cytotoxic effects. However, contaminants raise concerns, not only for consumer safety but also the quality of herbal concoctions available as part of the traditional medicinal practice in Limpopo.

Keywords: antimicrobials, concoctions, cytotoxicity, phytochemicals

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2373 Ammonia Release during Photocopying Operations

Authors: Kiurski S. Jelena, Kecić S. Vesna, Oros B. Ivana, Ranogajec G. Jonjaua

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The paper represents the dependence of ammonia concentration on microclimate parameters and photocopying shop circulation. The concentration of ammonia was determined during 8-hours working time over five days including three sampling points of a photocopying shop in Novi Sad, Serbia. The obtained results pointed out that the room temperature possesses the highest impact on ammonia release. The obtained ammonia concentration was in the range of 1.53 to 0.42ppm and decreased with the temperature decreasing from 24.6 to 20.7 °C. As the detected concentrations were within the permissible levels of The Occupational Safety and Health Administration, The National Institute for Occupational Safety and The Health and Official Gazette of Republic of Serbia, in the range of 35 to 200ppm, there was no danger to the employee’s health in the photocopying shop.

Keywords: ammonia, emission, indoor environment, photocopying procedure

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2372 Biodegradable Cross-Linked Composite Hydrogels Enriched with Small Molecule for Osteochondral Regeneration

Authors: Elena I. Oprita, Oana Craciunescu, Rodica Tatia, Teodora Ciucan, Reka Barabas, Orsolya Raduly, Anca Oancea

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Healing of osteochondral defects requires repair of the damaged articular cartilage, the underlying subchondral bone and the interface between these tissues (the functional calcified layer). For this purpose, developing a single monophasic scaffold that can regenerate two specific lineages (cartilage and bone) becomes a challenge. The aim of this work was to develop variants of biodegradable cross-linked composite hydrogel based on natural polypeptides (gelatin), polysaccharides components (chondroitin-4-sulphate and hyaluronic acid), in a ratio of 2:0.08:0.02 (w/w/w) and mixed with Si-hydroxyapatite (Si-Hap), in two ratios of 1:1 and 2:1 (w/w). Si-Hap was synthesized and characterized as a better alternative to conventional Hap. Subsequently, both composite hydrogel variants were cross-linked with (N, N-(3-dimethylaminopropyl)-N-ethyl carbodiimide (EDC) and enriched with a small bioactive molecule (icariin). The small molecule icariin (Ica) (C33H40O15) is the main active constituent (flavonoid) of Herba epimedium used in traditional Chinese medicine to cure bone- and cartilage-related disorders. Ica enhances osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), facilitates matrix calcification and increases the specific extracellular matrix (ECM) components synthesis by chondrocytes. Afterward, the composite hydrogels were characterized for their physicochemical properties in terms of the enzymatic biodegradation in the presence of type I collagenase and trypsin, the swelling capacity and the degree of crosslinking (TNBS assay). The cumulative release of Ica and real-time concentration were quantified at predetermined periods of time, according to the standard curve of standard Ica, after hydrogels incubation in saline buffer at physiological parameters. The obtained cross-linked composite hydrogels enriched with small-molecule Ica were also characterized for morphology by scanning electron microscopy (SEM). Their cytocompatibility was evaluated according to EN ISO 10993-5:2009 standard for medical device testing. Thus, analyses regarding cell viability (Live/Dead assay), cell proliferation (Neutral Red assay) and cell adhesion to composite hydrogels (SEM) were performed using NCTC clone L929 cell line. The final results showed that both cross-linked composite hydrogel variants enriched with Ica presented optimal physicochemical, structural and biological properties to be used as a natural scaffold able to repair osteochondral defects. The data did not reveal any toxicity of composite hydrogels in NCTC stabilized cell lines within the tested range of concentrations. Moreover, cells were capable of spreading and proliferating on both composite hydrogel surfaces. In conclusion, the designed biodegradable cross-linked composites enriched with Si and Ica are recommended for further testing as natural temporary scaffolds, which can allow cell migration and synthesis of new extracellular matrix within osteochondral defects.

Keywords: composites, gelatin, osteochondral defect, small molecule

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2371 Microfiber Release During Laundry Under Different Rinsing Parameters

Authors: Fulya Asena Uluç, Ehsan Tuzcuoğlu, Songül Bayraktar, Burak Koca, Alper Gürarslan

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Microplastics are contaminants that are widely distributed in the environment with a detrimental ecological effect. Besides this, recent research has proved the existence of microplastics in human blood and organs. Microplastics in the environment can be divided into two main categories: primary and secondary microplastics. Primary microplastics are plastics that are released into the environment as microscopic particles. On the other hand, secondary microplastics are the smaller particles that are shed as a result of the consumption of synthetic materials in textile products as well as other products. Textiles are the main source of microplastic contamination in aquatic ecosystems. Laundry of synthetic textiles (34.8%) accounts for an average annual discharge of 3.2 million tons of primary microplastics into the environment. Recently, microfiber shedding from laundry research has gained traction. However, no comprehensive study was conducted from the standpoint of rinsing parameters during laundry to analyze microfiber shedding. The purpose of the present study is to quantify microfiber shedding from fabric under different rinsing conditions and determine the effective rinsing parameters on microfiber release in a laundry environment. In this regard, a parametric study is carried out to investigate the key factors affecting the microfiber release from a front-load washing machine. These parameters are the amount of water used during the rinsing step and the spinning speed at the end of the washing cycle. Minitab statistical program is used to create a design of the experiment (DOE) and analyze the experimental results. Tests are repeated twice and besides the controlled parameters, other washing parameters are kept constant in the washing algorithm. At the end of each cycle, released microfibers are collected via a custom-made filtration system and weighted with precision balance. The results showed that by increasing the water amount during the rinsing step, the amount of microplastic released from the washing machine increased drastically. Also, the parametric study revealed that increasing the spinning speed results in an increase in the microfiber release from textiles.

Keywords: front load, laundry, microfiber, microfiber release, microfiber shedding, microplastic, pollution, rinsing parameters, sustainability, washing parameters, washing machine

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2370 Management and Evaluation of the Importance of Porous Media in Biomedical Engineering as Associated with Magnetic Resonance Imaging Besides Drug Delivery

Authors: Fateme Nokhodchi Bonab

Abstract:

Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

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2369 Development and in vitro Characterization of Loteprednol Etabonate-Loaded Polymeric Nanoparticles for Ocular Delivery

Authors: Abhishek Kumar Sah, Preeti K. Suresh

Abstract:

Effective drug delivery to the eye is a massive challenge, due to complicated physiological ocular barriers, rapid washout by tear and nasolachrymal drainage. Thus, most of the conventional ophthalmic formulations face the problem of low ocular bioavailability. Ophthalmic drug therapy can be improved by enhancing the precorneal drug retention along with improved drug penetration. The aim of the present investigation was to develop and evaluate a biodegradable polymer poly (D, L-lactide-co-glycolide) (PLGA) coated nanoparticulate carrier of loteprednol etabonate. PLGA nanoparticles were prepared by modified emulsification/solvent diffusion method using high-speed homogenizer followed by sonication. The nanoparticles were characterized for various parameters such as particle size, zeta potential, polydispersity index, X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), in vitro drug release profile and stability. The prepared nanocarriers displayed mean particle size in the range of 271.7 to 424.4 nm, with zeta potential less than –10 mV. In vitro release in simulated tear fluid (STF) nanocarrier showed an extended release profile of loteprednol etabonate. TEM confirmed the spherical morphology and smooth surface of the particles. All the prepared formulations were found to be stable at varying temperatures.

Keywords: drug delivery, ocular delivery, polymeric nanoparticles, loteprednol etabonate

Procedia PDF Downloads 551
2368 Overall Function and Symptom Impact of Self-Applied Myofascial Release in Adult Patients With Fibromyalgia. A Seven-Week Pilot Study

Authors: Domenica Tambasco, Riina Bray, Sophia Jaworski, Gillian Grant, Celeste Corkery

Abstract:

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and reduced function. Management of symptoms include medications, physical treatments and mindfulness therapies. Myofascial Release is a modality that has been successfully applied in var-ious musculoskeletal conditions. However, to the author’s best knowledge, it is not yet recog-nized as a self-management therapy option in Fibromyalgia. In this study, we investigated whether Self-applied Myofascial Release (SMR) is associated with overall improved function and symptoms in Fibromyalgia. Methods: Eligible adult patients with a confirmed diagnosis of Fibromyalgia at Women’s College Hospital were recruited to SMR. Sessions ran for 1 hour once a week for 7 weeks, led by the same two Physiotherapists knowledgeable in this physical treat-ment modality. The main outcome measure was an overall impact score for function and symp-toms based on the validated assessment tool for Fibromyalgia, the Revised Fibromyalgia Impact Questionnaire (FIQR), measured pre and post-intervention. Both descriptive and analytical methods were applied and reported. Results: We analyzed results using a paired t-test to deter-mine if there was a statistically significant difference in mean FIQR scores between initial (pre-intervention) and final (post-intervention) scores. A clinically significant difference in FIQR was defined as a reduction in score by 10 or more points. Conclusions: Our pilot study showed that SMR appeared to be a safe and effective intervention for our Fibromyalgia participants and the overall impact on function and symptoms occurred in only 7 weeks. Further studies with larger sample sizes comparing SMR to other physical treatment modalities (such as stretching) in an RCT are recommended.

Keywords: fibromyalgia, myofascial release, physical therapy, FIQR

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2367 The Long-Term Leaching Behaviour of 137Cs, 60Co and 152Eu Radionuclides Incorporated in Mortar Matrices Made from Natural Aggregates and Recycled Aggregates

Authors: R. Deju, M. Mincu, D. Gurau

Abstract:

During the interim storage or final disposal of low level waste, migration/diffusion of radionuclides can occur when the waste comes in contact with water. The long-term leaching behaviour into surrounding fluid (demineralized water) of 137Cs, 60Co and 152Eu radionuclides, artificially incorporated in mortar matrices made from natural aggregates (river sand) and recycled radioactive concrete was studied. Results presented in this work are obtained in two years of mortar testing and will be used for the safety increasing in the storage of low level radioactive waste. The study involved the influence of curing time, type and size distribution of the aggregates on leaching behaviour. The mortar samples were immersed in distilled water for 30 days. The leached activity of the mortar samples was measured on samples from the immersing water and analyzed through a gamma-ray spectrometry method using an HPGe detector with a GESPECOR code for efficiency evaluation. The long-term leaching behaviour of the radionuclides was evaluated from the leaching data calculating the apparent diffusion coefficient.

Keywords: gamma spectrometry, leaching behavior, reuse and recycling of radioactive concrete, waste management

Procedia PDF Downloads 248
2366 Low Resistivity Pay Identification in Carbonate Reservoirs of Yadavaran Oilfield

Authors: Mohammad Mardi

Abstract:

Generally, the resistivity is high in oil layer and low in water layer. Yet there are intervals of oil-bearing zones showing low resistivity, high porosity, and low resistance. In the typical example, well A (depth: 4341.5-4372.0m), both Spectral Gamma Ray (SGR) and Corrected Gamma Ray (CGR) are relatively low; porosity varies from 12-22%. Above 4360 meters, the reservoir shows the conventional positive difference between deep and shallow resistivity with high resistance; below 4360m, the reservoir shows a negative difference with low resistance, especially at depths of 4362.4 meters and 4371 meters, deep resistivity is only 2Ω.m, and the CAST-V imaging map shows that there are low resistance substances contained in the pores or matrix in the reservoirs of this interval. The rock slice analysis data shows that the pyrite volume is 2-3% in the interval 4369.08m-4371.55m. A comprehensive analysis on the volume of shale (Vsh), porosity, invasion features of resistivity, mud logging, and mineral volume indicates that the possible causes for the negative difference between deep and shallow resistivities with relatively low resistance are erosional pores, caves, micritic texture and the presence of pyrite. Full-bore Drill Stem Test (DST) verified 4991.09 bbl/d in this interval. To identify and thoroughly characterize low resistivity intervals coring, Nuclear Magnetic Resonance (NMR) logging and further geological evaluation are needed.

Keywords: low resistivity pay, carbonates petrophysics, microporosity, porosity

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2365 Enhanced Cell Adhesion on PMMA by Radio Frequency Oxygen Plasma Treatment

Authors: Fatemeh Rezaei, Babak Shokri

Abstract:

In this study, PMMA films are modified by oxygen plasma treatment for biomedical applications. The plasma generator is capacitively coupled radio frequency (13.56 MHz) power source. The oxygen pressure and gas flow rate are kept constant at 40 mTorr and 30 sccm, respectively and samples are treated for 2 minutes. Hydrophilicity and biocompatibility of PMMA films are studied before and after treatments in different applied powers (10-80 W). In order to monitor the plasma process, the optical emission spectroscopy is used. The wettability and cellular response of samples are investigated by water contact angle (WCA) analysis and MTT assay, respectively. Also, surface free energy (SFE) variations are studied based on the contact angle measurements of three liquids. It is found that RF oxygen plasma treatment enhances the biocompatibility and also hydrophilicity of PMMA films.

Keywords: cellular response, hydrophilicity, MTT assay, PMMA, RF plasma

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2364 The Effects of Grape Waste Bioactive Compounds on the Immune Response and Oxidative Stress in Pig Kidney

Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

Abstract:

Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

Procedia PDF Downloads 298
2363 Determination of the Toxicity of a Lunar Dust Simulant on Human Alveolar Epithelial Cells and Macrophages in vitro

Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

Abstract:

Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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2362 The Cell Viability Study of Extracts of Bark, Flowers, Leaves and Seeds of Indian Dhak Tree, Flame of Forest

Authors: Madhavi S. Apte, Milind Bhitre

Abstract:

In pharmaceutical research and new drug development, medicinal plants have important roles. Similarly, Indian dhak tree belonging to family Fabaceae has been widely used in the traditional Indian medical system of ‘Ayurveda’ for the treatment of a variety of ailments. Hence the cell viability study was undertaken to evaluate and compare the activity of extracts of various parts like flower, bark, leaf, seed by conducting MTT assay method along with other pharmacognostical studies. The methanolic extracts of bark, flowers, leaves, and seeds were used for the study. The cell viability MTT assay was performed using the standard operating procedures. The extracts were dissolved in DMSO and serially diluted with complete medium to get the concentrations range of test concentration. DMSO concentration was kept < 0.1% in all the samples. HUVEC cells maintained in appropriate conditions were seeded in 96 well plates and treated with different concentrations of the test samples and incubated at 37°C, 5% CO₂ for 96 hours. MTT reagent was added to the wells and incubated for 4 hours; the dark blue formazan product formed by the cells was dissolved in DMSO under a safety cabinet and read at 550nm. Percentage inhibitions were calculated and plotted with the concentrations used to calculate the IC50 values. The bark, flower, leaves and seed extracts have shown the cytotoxicity activity and can be further studied for antiangiogenesis activity.

Keywords: pharmacognosy, Cell viability, MTT assay, anti-angiogenesis

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2361 The Concentration of Selected Cosmogenic and Anthropogenic Radionuclides in the Ground Layer of the Atmosphere (Polar and Mid-Latitudes Regions)

Authors: A. Burakowska, M. Piotrowski, M. Kubicki, H. Trzaskowska, R. Sosnowiec, B. Myslek-Laurikainen

Abstract:

The most important source of atmospheric radioactivity are radionuclides generated as a result of the impact of primary and secondary cosmic radiation, with the nuclei of nitrogen oxygen and carbon in the upper troposphere and lower stratosphere. This creates about thirty radioisotopes of more than twenty elements. For organisms, the four of them are most important: ³H, ⁷Be, ²²Na, ¹⁴C. The natural radionuclides, which are present in Earth crust, also settle on dust and particles of water vapor. By this means, the derivatives of uranium and thorium, and long-life 40K get into the air. ¹³⁷Cs is the most widespread isotope, that is implemented by humans into the environment. To determine the concentration of radionuclides in the atmosphere, high volume air samplers were used, where the aerosol collection took place on a special filter fabric (Petrianov filter tissue FPP-15-1.5). In 2002 the high volume air sampler AZA-1000 was installed at the Polish Polar Observatory of the Polish Academy of Science in Hornsund, Spitsbergen (77°00’N, 15°33’E), designed to operate in all weather conditions of the cold polar region. Since 1991 (with short breaks) the ASS-500 air sampler has been working, which is located in Swider at the Kalinowski Geophysical Observatory of Geophysics Institute of the Polish Academy of Science (52°07’N, 21°15’E). The following results of radionuclides concentrations were obtained from both stations using gamma spectroscopy analysis: ⁷Be, ¹³⁷Cs, ¹³⁴Cs, ²¹⁰Pb, ⁴⁰K. For gamma spectroscopy analysis HPGe (High Purity Germanium) detector were used. These data were compared with each other. The preliminary results gave evidence that radioactivity measured in aerosols is not proportional to the amount of dust for both studied regions. Furthermore, the results indicate annual variability (seasonal fluctuations) as well as a decrease in the average activity of ⁷Be with increasing latitude. The content of ⁷Be in surface air also indicates the relationship with solar activity cycles.

Keywords: aerosols, air filters, atmospheric beryllium, environmental radionuclides, gamma spectroscopy, mid-latitude regions radionuclides, polar regions radionuclides, solar cycles

Procedia PDF Downloads 141
2360 Encapsulation of Venlafaxine-Dowex® Resinate: A Once Daily Multiple Unit Formulation

Authors: Salwa Mohamed Salah Eldin, Howida Kamal Ibrahim

Abstract:

Introduction: Major depressive disorder affects high proportion of the world’s population presenting cost load in health care. Extended release venlafaxine is more convenient and could reduce discontinuation syndrome. The once daily dosing also reduces the potential for adverse events such as nausea due to reduced Cmax. Venlafaxine is an effective first-line agent in the treatment of depression. A once daily formulation was designed to enhance patient compliance. Complexing with a resin was suggested to improve loading of the water soluble drug. The formulated systems were thoroughly evaluated in vitro to prove superiority to previous trials and were compared to the commercial extended release product in experimental animals. Materials and Methods: Venlafaxine-resinates were prepared using Dowex®50WX4-400 and Dowex®50WX8-100 at drug to resin weight ratio of 1: 1. The prepared resinates were evaluated for their drug content, particle shape and surface properties and in vitro release profile in gradient pH. The release kinetics and mechanism were evaluated. Venlafaxine-Dowex® resinates were encapsulated using O/W solvent evaporation technique. Poly-ε-caprolactone, Poly(D, L-lactide-co-glycolide) ester, Poly(D, L-lactide) ester and Eudragit®RS100 were used as coating polymers alone and in combination. Drug-resinate microcapsules were evaluated for morphology, entrapment efficiency and in-vitro release profile. The selected formula was tested in rabbits using a randomized, single-dose, 2-way crossover study against Effexor-XR tablets under fasting condition. Results and Discussion: The equilibrium time was 30 min for Dowex®50WX4-400 and 90 min for Dowex®50WX8-100. The percentage drug loaded was 93.96 and 83.56% for both resins, respectively. Both drug-Dowex® resintes were efficient in sustaining venlafaxine release in comparison to the free drug (up to 8h.). Dowex®50WX4-400 based venlafaxine-resinate was selected for further encapsulation to optimize the release profile for once daily dosing and to lower the burst effect. The selected formula (coated with a mixture of Eudragit RS and PLGA in a ratio of 50/50) was chosen by applying a group of mathematical equations according to targeted values. It recorded the minimum burst effect, the maximum MDT (Mean dissolution time) and a Q24h (percentage drug released after 24 hours) between 95 and 100%. The 90% confidence intervals for the test/reference mean ratio of the log-transformed data of AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfies the bioequivalence criteria. Conclusion: The optimized formula could be a promising extended release form of the water soluble, short half lived venlafaxine. Being a multiple unit formulation, it lowers the probability of dose dumping and reduces the inter-subject variability in absorption.

Keywords: biodegradable polymers, cation-exchange resin, microencapsulation, venlafaxine hcl

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2359 Synthesis of [1-(Substituted-Sulfonyl)-Piperidin-4-yl]-(2,4-Difluoro-Phenyl)-Methanone Oximes and Their Biological Activity

Authors: L. Mallesha, C. S. Karthik, P. Mallu

Abstract:

A series of new [1-(substituted-benzoyl)-piperidin-4-yl]-(2,4-difluoro-phenyl)-methanone oxime derivatives, 3(a-f) were synthesized and characterized by different spectral studies. All compounds were evaluated for their in vitro antibacterial activity against bacterial strains. These compounds were screened for their antioxidant activity by DPPH• and Fe2+ chelating assay. Antiproliferative effects were evaluated using the MTT assay method against two human cancer cell lines and one astrocytoma brain tumor cell line. Compound 3b exhibited moderate antibacterial activity when compared with other compounds. All the compounds showed antioxidant activity, where compound 3f was the best radical scavenger and Fe2+ ion scavenger. Compounds, 3b, and 3d showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Piperidine, antibacterial, antioxidant, antiproliferative

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2358 Targeted Delivery of Sustained Release Polymeric Nanoparticles for Cancer Therapy

Authors: Jamboor K. Vishwanatha

Abstract:

Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.

Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin

Procedia PDF Downloads 325