Search results for: normalized glandular dose
Commenced in January 2007
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Edition: International
Paper Count: 1772

Search results for: normalized glandular dose

362 Study of Radiation Response in Lactobacillus Species

Authors: Kanika Arora, Madhu Bala

Abstract:

The small intestine epithelium is highly sensitive and major targets of ionizing radiation. Radiation causes gastrointestinal toxicity either by direct deposition of energy or indirectly (inflammation or bystander effects) generating free radicals and reactive oxygen species. Oxidative stress generated as a result of radiation causes active inflammation within the intestinal mucosa leading to structural and functional impairment of gut epithelial barrier. As a result, there is a loss of tolerance to normal dietary antigens and commensal flora together with exaggerated response to pathogens. Dysbiosis may therefore thought to play a role in radiation enteropathy and can contribute towards radiation induced bowel toxicity. Lactobacilli residing in the gut shares a long conjoined evolutionary history with their hosts and by doing so these organisms have developed an intimate and complex symbiotic relationships. The objective behind this study was to look for the strains with varying resistance to ionizing radiation and to see whether the niche of the bacteria is playing any role in radiation resistance property of bacteria. In this study, we have isolated the Lactobacillus spp. from probiotic preparation and murine gastrointestinal tract, both of which were supposed to be the important source for its isolation. Biochemical characterization did not show a significant difference in the properties, while a significant preference was observed in carbohydrate utilization capacity by the isolates. Effect of ionizing radiations induced by Co60 gamma radiation (10 Gy) on lactobacilli cells was investigated. A cellular survival curve versus absorbed doses was determined. Radiation resistance studies showed that the response of isolates towards cobalt-60 gamma radiation differs from each other and significant decrease in survival was observed in a dose-dependent manner. Thus the present study revealed that the property of radioresistance in Lactobacillus depends upon the source from where they have been isolated.

Keywords: dysbiosis, lactobacillus, mitigation, radiation

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361 A Pilot Study of Influences of Scan Speed on Image Quality for Digital Tomosynthesis

Authors: Li-Ting Huang, Yu-Hsiang Shen, Cing-Ciao Ke, Sheng-Pin Tseng, Fan-Pin Tseng, Yu-Ching Ni, Chia-Yu Lin

Abstract:

Chest radiography is the most common technique for the diagnosis and follow-up of pulmonary diseases. However, the lesions superimposed with normal structures are difficult to be detected in chest radiography. Chest tomosynthesis is a relatively new technique to obtain 3D section images from a set of low-dose projections acquired over a limited angular range. However, there are some limitations with chest tomosynthesis. Patients undergoing tomosynthesis have to be able to hold their breath firmly for 10 seconds. A digital tomosynthesis system with advanced reconstruction algorithm and high-stability motion mechanism was developed by our research group. The potential for the system to perform a bidirectional chest scan within 10 seconds is expected. The purpose of this study is to realize the influences of the scan speed on the image quality for our digital tomosynthesis system. The major factors that lead image blurring are the motion of the X-ray source and the patient. For the fore one, an experiment of imaging a chest phantom with three different scan speeds, which are 6 cm/s, 8 cm/s, and 15 cm/s, was proceeded to understand the scan speed influences on the image quality. For the rear factor, a normal SD (Sprague-Dawley) rat was imaged with it alive and sacrificed to assess the impact on the image quality due to breath motion. In both experiments, the profile of the ROIs (region of interest) and the CNRs (contrast-to-noise ratio) of the ROIs to the normal tissue of the reconstructed images was examined to realize the degradations of the qualities of the images. The preliminary results show that no obvious degradation of the image quality was observed with increasing scan speed, possibly due to the advanced designs for the hardware and software of the system. It implies that higher speed (15 cm/s) than that of the commercialized tomosynthesis system (12 cm/s) for the proposed system is achieved, and therefore a complete chest scan within 10 seconds is expected.

Keywords: chest radiography, digital tomosynthesis, image quality, scan speed

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360 Consumer Health Risk Assessment from Some Heavy Metal Bioaccumulation in Common Carp (Cyprinus Carpio) from Lake Koka, Ethiopia

Authors: Mathewos Temesgen, Lemi Geleta

Abstract:

Lake Koka is one of the Ethiopian Central Rift Valleys lakes, where the absorbance of domestic, agricultural, and industrial waste from the nearby industrial and agro-industrial activities is very common. The aim of this research was to assess the heavy metal bioaccumulation in edible parts of common carp (Cyprinus carpio) in Lake Koka and the health risks associated with the dietary intake of the fish. Three sampling sites were selected randomly for primary data collection. Physicochemical parameters (pH, Total Dissolved Solids, Dissolved Oxygen and Electrical Conductivity) were measured in-situ. Four heavy metals (Cd, Cr, Pb, and Zn) in water and bio-accumulation in the edible parts of the fish were analyzed with flame atomic absorption spectrometry. The mean values of TDS, EC, DO and pH of the lake water were 458.1 mg/L, 905.7 µ s/cm, 7.36 mg/L, and 7.9, respectively. The mean concentrations of Zn, Cr, and Cd in the edible part of fish were also 0.18 mg/kg, ND-0.24 mg/kg, and ND-0.03 mg/kg, respectively. Pb was, however, not identified. The amount of Cr in the examined fish muscle was above the level set by FAO, and the accumulation of the metals showed marked differences between sampling sites (p<0.05). The concentrations of Cd, Pb and were below the maximum permissible limit. The results also indicated that Cr has a high transfer factor value and Zn has the lowest. The carcinogenic hazard ratio values were below the threshold value (<1) for the edible parts of fish. The estimated weekly intake of heavy metals from fish muscles ranked as Cr>Zn>Cd, but the values were lower than the Reference Dose limit for metals. The carcinogenic risk values indicated a low health risk due to the intake of individual metals from fish. Furthermore, the hazard index of the edible part of fish was less than unity. Generally, the water quality is not a risk for the survival and reproduction of fish, and the heavy metal contents in the edible parts of fish exhibited low carcinogenic risk through the food chain.

Keywords: bio-accumulation, cyprinus carpio, hazard index, heavy metals, Lake Koka

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359 Traumatic Brain Injury Induced Lipid Profiling of Lipids in Mice Serum Using UHPLC-Q-TOF-MS

Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

Abstract:

Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

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358 Prospective Cohort Study on Sequential Use of Catheter with Misoprostol vs Misoprostol Alone for Second Trimester Medical Abortion

Authors: Hanna Teklu Gebregziabher

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Background: A variety of techniques for medical termination of second-trimester pregnancy can be used, but there is no consensus about which is the best. Even though most evidence suggests the combined use of intracervical Foley catheter and vaginal misoprostol is safe, effective, and acceptable method for termination of second-trimester pregnancy, which is comparable to mifepristone-misoprostol combination regimen with lower cost and no additional maternal risks. The use of mifepristone and misoprostol alone with no other procedure is still the most common procedure in different institutions for 2nd-trimester pregnancy. Methods: A cross-sectional comparative prospective study design is employed on women who were admitted for 2nd-trimester medical abortion and medical abortion failed or if there was no change in cervical status after 24 hours of 1st dose of misoprostol. The study was conducted at St. Paulose Hospital Millennium Medical College. A sample of 44 participants in each arm was necessary to give a two-tailed test, a type 1 error of 5%, 80% statistical power, and a 1:1 ratio among groups. Thus, a total of 94 cases, 47 from each arm, were recruited. Data was entered and cleaned by using Epi-info and analyzed using SPSS version 29.0 statistical software and was presented in descriptive and tabular forms. Different variables were cross-tabulated and compared for significant differences and statistical analysis using the chi-square test and independent t-test, to conclude. Result: There was a significant difference between the two groups on induction to expulsion time and number of doses used. The mean ± SD of induction to expulsion time for those used misoprostol alone was 48.09 ± 11.86 and those who used trans-cervical catheter sequentially with misoprostol were 36.7 ±6.772. Conclusion: The use of a trans-cervical Foley catheter in conjunction with misoprostol in a sequential manner is a more effective, safe, and easily accessible procedure. In addition, the cost of utilizing the catheter is less compared to the cost of misoprostol and is readily available. As a good substitute, we advised using Trans-cervical Catether even for medical abortions performed in the second trimester.

Keywords: second trimester, medical abortion, catheter, misoprostol

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357 Evaluation of Anti-Arthritic Activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb in Freund's Complete Adjuvant Induced Arthritic Rat Model

Authors: Akshada Amit Koparde, Candrakant S. Magdum

Abstract:

Objective: To investigate the anti-arthritic activity of chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb in adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). Methods: Forty two healthy albino rats were selected and randomly divided into six groups. Freund’s complete adjuvant (FCA) was used to induce arthritis and then treated with chloroform extract, isolate 1 and dichloromethane extract, isolate 2 for 28 days. The various parameters like paw volume, haematological parameters (RBC, WBC, Hb and ESR), were studied. Structural elucidation of active constituents isolate 1 and isolate 2 from Eulophia ochreata Lindl and Zingiber cassumunar Roxb will be done using GCMS and H1NMR. Results: In FCA induced arthritic rats, there was significant increase in rat paw volume whereas chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb treated groups showed strong significant reduction in paw volume. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with extracts at the dose of 200 mg/kg. Further histopathological studies revealed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb by preventing cartilage and bone destruction of the arthritic joints of AA rats. Conclusion: Extracts and isolates of Eulophia ochreata Lindl and Zingiber cassumunar Roxb have shown anti-arthritic activity. Decrease in paw volume and normalization of haematological abnormalities in adjuvant induced arthritic rats is significantly seen in the experiment. Further histopathological studies confirmed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb.

Keywords: arthritis, Eulophia ochreata Lindl, Freund's complete adjuvant, paw volume, Zingiber cassumunar Roxb

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356 Effects of Anti-FGL2 Monoclonal Antibody SPF89 on Vascular Inflammation

Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang

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Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).

Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells

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355 Synergistic Effects of Chrysin-Curcumin Loaded in PLGA-PEG Nanoparticles on Inhibiting Breast Cancer Cell Line Growth

Authors: N. Zarghami, M. Mohammadinejad, A. Akbarzadeh, Y. Pilehvar-Soltanahmadi, F. Zarghami

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Breast cancer is known to be the most common cancer in women. Cyclin D1 is a proto-oncogene and over expression of cyclin D1 is directly associated with tumorgenesis. Cyclin D1 is overexpressed in more than 50% of breast cancer cases. Curcumin is derived from turmeric (curcuma longa) and chrysin is a component that could be extracted from many plants and honey. These two plants derived compounds are believed to assist in inhibition of the cancer cells growth and reducing cyclin D1 expression. In this work, the hypothesis is to combine curcumin and chrysin in order to analyze the potential synergistic effect in inhibition of cell proliferation and down regulation of cyclin D1. In addition, use of PLGA-PEG to improve bioavailability of pure curcumin and chrysin, while reinforcing the potential effect of this combination. PLGA-PEG nanoparticles were synthesized and characterized with FT-IR and 1HNMR methods. Although morphological features were analyzed by SEM. Afterward curcumin and chrysin were encapsulated with synthesized PLGA-PEG and MTT-assay was performed to measure cytotoxicity effect of these plant constitutes. T-47D cells were treated with proper concentration of these constituents and Real-time PCR was carried out to evaluate cyclin D1 expression levels. Curcumin, chrysin and combination of curcumin –chrysin in intact and nano-capsulated form affected T-47D cells in time and dose dependent manner and the combination of these compounds had synergistic effects. Real-time PCR results, revealed that curcumin, chrysin and combination of curcumin-chrysin in pure and encapsulated form inhibited cyclin D1 expression. Compared to pure components, different concentrations of nano-curcumin, nano chrysin and nano-combination caused further decline in cyclin D12 expression by 5-11%, 8-22% and 6-18% respectively. Our results demonstrated that, combination of chrysin-curcumin had synergistic effect and nano capsulated form of this component had grater inhibition on cyclin D1 expression.

Keywords: breast cancer, cyclin D1, curcumin, chrysin, nanoparticles

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354 Cucurbita pepo L. Attenuates Diabetic Neuropathy by Targeting Oxidative Stress in STZ-Nicotinamide Induced Diabetic Rats

Authors: Navpreet Kaur, Randhir Singh

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Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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353 The Effect of Metformin in Combination with Dexamethasone on the CXCR4 Level in Multiple Myeloma Cell Line

Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

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Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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352 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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351 Kinetics of Inhibition of Xanthine Oxidase by Lycium Arabicum and Its Protective Effect against Oxonate-Induced Hyperuricemia and Renal Dysfunction in Mice

Authors: Naouel Boussoualim, Hayat Trabsa, Imane Krache, Seddik Khennouf, Noureddine Charef, Lekhmici Arrar, Abderrahmane Baghiani

Abstract:

Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects. Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin, and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight. Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract. Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.

Keywords: lycium arabicum, uric acid, creatinine, superoxide, phenolic compounds, flavonoids, hyperuricemia

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350 Comparison of GIS-Based Soil Erosion Susceptibility Models Using Support Vector Machine, Binary Logistic Regression and Artificial Neural Network in the Southwest Amazon Region

Authors: Elaine Lima Da Fonseca, Eliomar Pereira Da Silva Filho

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The modeling of areas susceptible to soil loss by hydro erosive processes consists of a simplified instrument of reality with the purpose of predicting future behaviors from the observation and interaction of a set of geoenvironmental factors. The models of potential areas for soil loss will be obtained through binary logistic regression, artificial neural networks, and support vector machines. The choice of the municipality of Colorado do Oeste in the south of the western Amazon is due to soil degradation due to anthropogenic activities, such as agriculture, road construction, overgrazing, deforestation, and environmental and socioeconomic configurations. Initially, a soil erosion inventory map constructed through various field investigations will be designed, including the use of remotely piloted aircraft, orbital imagery, and the PLANAFLORO/RO database. 100 sampling units with the presence of erosion will be selected based on the assumptions indicated in the literature, and, to complement the dichotomous analysis, 100 units with no erosion will be randomly designated. The next step will be the selection of the predictive parameters that exert, jointly, directly, or indirectly, some influence on the mechanism of occurrence of soil erosion events. The chosen predictors are altitude, declivity, aspect or orientation of the slope, curvature of the slope, composite topographic index, flow power index, lineament density, normalized difference vegetation index, drainage density, lithology, soil type, erosivity, and ground surface temperature. After evaluating the relative contribution of each predictor variable, the erosion susceptibility model will be applied to the municipality of Colorado do Oeste - Rondônia through the SPSS Statistic 26 software. Evaluation of the model will occur through the determination of the values of the R² of Cox & Snell and the R² of Nagelkerke, Hosmer and Lemeshow Test, Log Likelihood Value, and Wald Test, in addition to analysis of the Confounding Matrix, ROC Curve and Accumulated Gain according to the model specification. The validation of the synthesis map resulting from both models of the potential risk of soil erosion will occur by means of Kappa indices, accuracy, and sensitivity, as well as by field verification of the classes of susceptibility to erosion using drone photogrammetry. Thus, it is expected to obtain the mapping of the following classes of susceptibility to erosion very low, low, moderate, very high, and high, which may constitute a screening tool to identify areas where more detailed investigations need to be carried out, applying more efficient social resources.

Keywords: modeling, susceptibility to erosion, artificial intelligence, Amazon

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349 Formulation of Famotidine Solid Lipid Nanoparticles (SLN): Preparation, Evaluation and Release Study

Authors: Rachmat Mauludin, Nurmazidah

Abstract:

Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

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348 Comparative Evaluation of Pentazocine and Tramadol as Pre-Emptive Analgesics for Ovariohysterectomy in Female Dogs

Authors: Venkatgiri, Ranganath, L. Nagaraja, B. N. Sagar Pandav, S. M. Usturge, D. Dilipkumar, B. V. Shivprakash, B. Bhagwanthappa, D. Jahangir

Abstract:

A comparative evaluation of Tramadol and Pentazocine as a pre-emptive analgesic in clinical cases of female dogs undergoing ovariohysterectomy was undertaken during this study. During the study, the following parameters were assessed viz., Rectal temperature (ᵒF), Respiratory rate (breaths/min) and Heart rate (beats/min). Hematological and biochemical parameters viz., total erythrocyte count (TEC) (millions/cmm), hemoglobin (g %), otal leucocytes count (TLC) (thousands/cmm), differential leucocytes count (DLC) (%), serum creatinine (mg/dl), plasma protein (mg/dl), blood glucose (mg/dl) was estimated before the surgery and after administration of general anaesthesia and immediate postoperative periods of 0, 12 and 24 hr respectively. Mean Total Pain Score (MTPS) includes measurement of parameters like posture, vocalization, activity level, response to palpation and agitation at different intervals was calculated before surgery and after administration of general anesthesia and post-operative periods of 1, 2, 4, 6, 12hrs and 24 hrs respectively. Mean Total Pain Score (MTPS) was given for each parameter (Posture, Vocalization, Activity Level, Response to Palpation and Agitation) like 0,1,2,3. (maximum score will be given was 4.). Results were revealed in all three groups including control group. There were significant minor alterations in physiological, hematological and biochemical parameters. MTPS (mean total pain score) were revealed and found a significant alteration when compared with control group. In conclusion, Tramadol found to be a better analgesic and had up to 8hrs of analgesic effect and Pentazocine is superior in post-operative pain management when compared to Tramadol because this group of dogs experienced less surgical stress, consumed less anesthetic dose, they recovered early, and they had less MTPS score.

Keywords: dog, pentazocine, tramadol, ovariohysterectomy

Procedia PDF Downloads 149
347 Existential Affordances and Psychopathology: A Gibsonian Analysis of Dissociative Identity Disorder

Authors: S. Alina Wang

Abstract:

A Gibsonian approach is used to understand the existential dimensions of the human ecological niche. Then, this existential-Gibsonian framework is applied to rethinking Hacking’s historical analysis of multiple personality disorder. This research culminates in a generalized account of psychiatric illness from an enactivist lens. In conclusion, reflections on the implications of this account on approaches to psychiatric treatment are mentioned. J.J. Gibson’s theory of affordances centered on affordances of sensorimotor varieties, which guide basic behaviors relative to organisms’ vital needs and physiological capacities (1979). Later theorists, notably Neisser (1988) and Rietveld (2014), expanded on the theory of affordances to account for uniquely human activities relative to the emotional, intersubjective, cultural, and narrative aspects of the human ecological niche. This research shows that these affordances are structured by what Haugeland (1998) calls existential commitments, which draws on Heidegger’s notion of dasein (1927) and Merleau-Ponty’s account of existential freedom (1945). These commitments organize the existential affordances that fill an individual’s environment and guide their thoughts, emotions, and behaviors. This system of a priori existential commitments and a posteriori affordances is called existential enactivism. For humans, affordances do not only elicit motor responses and appear as objects with instrumental significance. Affordances also, and possibly primarily, determine so-called affective and cognitive activities and structure the wide range of kinds (e.g., instrumental, aesthetic, ethical) of significances of objects found in the world. Then existential enactivism is applied to understanding the psychiatric phenomenon of multiple personality disorder (precursor of the current diagnosis of dissociative identity disorder). A reinterpretation of Hacking’s (1998) insights into the history of this particular disorder and his generalizations on the constructed nature of most psychiatric illness is taken on. Enactivist approaches sensitive to existential phenomenology can provide a deeper understanding of these matters. Conceptualizing psychiatric illness as strictly a disorder in the head (whether parsed as a disorder of brain chemicals or meaning-making capacities encoded in psychological modules) is incomplete. Rather, psychiatric illness must also be understood as a disorder in the world, or in the interconnected networks of existential affordances that regulate one’s emotional, intersubjective, and narrative capacities. All of this suggests that an adequate account of psychiatric illness must involve (1) the affordances that are the sources of existential hindrance, (2) the existential commitments structuring these affordances, and (3) the conditions of these existential commitments. Approaches to treatment of psychiatric illness would be more effective by centering on the interruption of normalized behaviors corresponding to affordances targeted as sources of hindrance, the development of new existential commitments, and the practice of new behaviors that erect affordances relative to these reformed commitments.

Keywords: affordance, enaction, phenomenology, psychiatry, psychopathology

Procedia PDF Downloads 117
346 Association between Levels of Volatile Organic Compound Metabolites and Cigarette Smoking-Related Urothelial Carcinoma

Authors: Chi-Jung Chung, Chao-Hsiang Chang, Chiu-Shong Liu, Sheng-Wei Li, Mu-Chi Chung, Ting-Jie Wen, Hui-Ling Lee

Abstract:

Cigarette smoke contains volatile organic compounds (VOCs), such as acrylamide, 1,3-butadiene, and benzene. This study aimed to explore the associations between the urinary levels of cotinine and VOC metabolites and the risk of urothelial carcinoma (UC). A hospital-based case–control study involving two groups matched on the basis of age ( ± 3 years) and gender was designed. UC was clinically diagnosed through urological examinations and pathologically verified. Smoking-related information was collected through questionnaires and face-to-face interviews with all study participants. Urine samples were collected for the analysis of the urinary levels of VOC metabolites, cotinine, and 8-hydroxydeoxygua- nosine (8-OHdG), which was selected as a proxy of oxidative stress. Multiple logistic regressions were applied to estimate the risk of UC. The urinary cotinine and 8-OHdG levels of the UC group were higher than those of the control group. The urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N- acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S- (4- hydroxy-2-buten-1-yl)-Lcysteine-3, trans, trans-muconic acid (t,t- MA), and S-phenylmercapturic acid (SPMA) increased as the urinary levels of cotinine increased. Relevant dose-response relationships between the risk of UC risk and the urinary levels of AAMA , t,t-MA, SPMA, and 8-OHdG were found after adjusting for potential risk factors. The UC risk of participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG were 3.5–6-fold higher than those of other participants. Increased urinary levels of VOC metabolites were associated with smoking-related UC risk. The development of UC should be explored in large-scale in vitro or in vivo studies with the repeated measurement of VOC metabolites.

Keywords: volatile organic compound, urothelial carcinoma, cotinine, 8-hydroxydeoxyguanosine

Procedia PDF Downloads 125
345 Effect of an Oral Dose of M. elsdenii NCIMB 41125 on Lower Digestive Tract, Bacteria Count and Rumen Fermentation in Holstein Calves

Authors: M. C. Muya, L. J. Erasmus

Abstract:

Twenty four new born male Holstein calves were divided into two treatments groups and used to evaluate the effects of M. elsdenii NCIMB 41125. The first groups were dosed with 50 ml containing 108 CFU/mL of M. elsdenii NCIMB 41125 (Me) and the control calves were not dosed. Within each of the two treatments groups, calves were divided into three treatment groups (Not dosed: 7 d, 14 d and 21 d vs dosed Me 7 d, Me14 and Me21 d (treatments), each groups contained 4 calves within which two calves were euthanized at 24 h and two calves at 72 h. Calves entered the trial until euthanize at whether 24 or 72 H after dosing time. After receiving colostrum for 3 consecutive days after birth, calves were fed whole milk and had free access to a commercial calf starter pellet and fresh water. Fecal grab samples were taken from each calf in duplicate +24 h or +72 h relative to dosing. Immediately after euthanizing, the digestive tract was harvested, and duplicate rumen and colon digesta samples collected for VFA’s determination and DNA extraction for bacteria count using 16s RNA PCR probe technique. Independent two t-test was performed to compare mean volatile fatty acids. Mixed-effects linear regressions were performed to establish relationships between: 1) M. elsdenii and Me, and between VFA’s and Me using SAS (2009). M. elsdenii NCIMB 41125 was detected in the faeces, colon and rumen of dosed calves at both +24H and +72H and ranged from 1.6 x 106 to 4.9 x 109 cfu/ml, indicating its potential to colonize in the digestive tract of calves. There was a strong positive relationship (R²=0.96; P < 0.0001) between M. elsdenii NCIMB 41125 and M. elsdenii population (cfu/ml) in the rumen, suggesting that the increase in M. elsdenii was due to increased M. elsdenii NCIMB 41125. An increase in butyrate was observed from +24 h to +72 h when calves were dosed on both d 7 and 14. Results showed that Me presented a positive relationship with butyrate (P < 0.001, R² = 0.43) and a concomitant negative relationship with acetate (P = 0.017, R² = -0.33). These results suggest that dosing pre-weaned dairy calves with M. elsdenii NCIMB 41125 has the potential to alter ruminal VFA production through increasing proportions of butyrate at the expense of propionate.

Keywords: calves, megasphaera elsdenii, rumen fermentation, bacteria

Procedia PDF Downloads 376
344 Analysis of Expression of SP and NOS in the Porcine Nodose Ganglion (NG) Sensory Neurons Supplying Prepyloric Stomach Region after Intragastric Hydrochloric Acid Infusion

Authors: Liliana Rytel, Jarosław Całka

Abstract:

One of the diseases that are very common health problem of modern man is the stomach hyperacidity. It is well known that this pathological state, during which gastric glands secrete too much of hydrochloric acid can be caused due to various factors such as stress, eating habits, alcohol, smoking and some, especially anti-inflammatory drugs. Moreover, hyperacidity is recognized as one of factors leading to development of peptic ulcer disease. Therefore, we analyzed expression of substance P (SP) and neuronal isoform of nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric infusion of hydrochloric acid. The study was performed on 8 immature gilts of the Large White Polish breed. All animals were injected retrograde marker Fast Blue (FB) into the anterior prepyloric stomach wall. After injections of FB, pigs were divided into two groups: control (group C; n = 4) and experimental (HCL group, n = 4) and after convalescence period of 23 days, animals of HCL group were subjected to renewed anaesthesia. Then, 0.25 M aqueous solution of hydrochloric acid with a dose of 5 ml/kg body weight was administered intragastrically with use of a stomach tube. On 28th day, all control and HCL pigs were euthanized and bilateral reght (rNG) and left (lNG) were collected. Cryostat sections were processed for double immunofluorescence using anibodies against SP and NOS. Immunofluorescence staining in the even-numbered ganglia nodes showed the presence of FB-positive cells expressing SP (45,9 ± 3,38% in rNG and 60,4 ± 1,71% in lNG), and nNOS (34,9 ± 6,83% in rNG and 49,9 ± 9,32% in lNG). In HCL group increased expression of both SP (54,8 ± 5,34% in rNG and 56,9 ± 3,28 % in lNG) as well as nNOS (54,9 ± 4,45% in rNG and 52,5 ± 2,17 % in lNG) in FB+ perikaria was found. The acquired results suggest that SP and nNOS are neurotransmitters and/ or neuromodulators participating in the sensory regulation of the prepyloric region of porcine stomach function as well as their potential role in development of the stomach inflamatory state.

Keywords: nNOS, nodose ganglion, pig, SP

Procedia PDF Downloads 286
343 Study of Biological Denitrification using Heterotrophic Bacteria and Natural Source of Carbon

Authors: Benbelkacem Ouerdia

Abstract:

Heterotrophic denitrification has been proven to be one of the most feasible processes for removing nitrate from wastewater and drinking water. In this process, heterotrophic bacteria use organic carbon for both growth and as an electron source. Underground water pollution by nitrates become alarming in Algeria. A survey carried out revealed that the nitrate concentration is in continual increase. Studies in some region revealed contamination exceeding the recommended permissible dose which is 50 mg/L. Worrying values in the regions of Mascara, Ouled saber, El Eulma, Bouira and Algiers are respectively 72 mg/L, 75 mg/L, 97 mg/L, 102 mg/L, and 158 mg/L. High concentration of nitrate in drinking water is associated with serious health risks. Research on nitrate removal technologies from municipal water supplies is increasing because of nitrate contamination. Biological denitrification enables the transformation of oxidized nitrogen compounds by a wide spectrum of heterotrophic bacteria into harmless nitrogen gas with accompanying carbon removal. Globally, denitrification is commonly employed in biological nitrogen removal processes to enhance water quality The study investigated the valorization of a vegetable residue as a carbon source (dates nodes) in water treatment using the denitrification process. Throughout the study, the effect of inoculums addition, pH, and initial concentration of nitrates was also investigated. In this research, a natural organic substance: dates nodes were investigated as a carbon source in the biological denitrification of drinking water. This material acts as a solid substrate and bio-film carrier. The experiments were carried out in batch processes. Complete denitrification was achieved varied between 80 and 100% according to the type of process used. It was found that the nitrate removal rate based on our results, we concluded that the removal of organic matter and nitrogen compounds depended mainly on the initial concentration of nitrate. The effluent pH was mainly affected by the C/N ratio, where a decrease increases pH.

Keywords: biofilm, carbon source, dates nodes, heterotrophic denitrification, nitrate, nitrite

Procedia PDF Downloads 465
342 Methods for Early Detection of Invasive Plant Species: A Case Study of Hueston Woods State Nature Preserve

Authors: Suzanne Zazycki, Bamidele Osamika, Heather Craska, Kaelyn Conaway, Reena Murphy, Stephanie Spence

Abstract:

Invasive Plant Species (IPS) are an important component of effective preservation and conservation of natural lands management. IPS are non-native plants which can aggressively encroach upon native species and pose a significant threat to the ecology, public health, and social welfare of a community. The presence of IPS in U.S. nature preserves has caused economic costs, which has estimated to exceed $26 billion a year. While different methods have been identified to control IPS, few methods have been recognized for early detection of IPS. This study examined identified methods for early detection of IPS in Hueston Woods State Nature Preserve. Mixed methods research design was adopted in this four-phased study. The first phase entailed data gathering, the phase described the characteristics and qualities of IPS and the importance of early detection (ED). The second phase explored ED methods, Geographic Information Systems (GIS) and Citizen Science were discovered as ED methods for IPS. The third phase of the study involved the creation of hotspot maps to identify likely areas for IPS growth. While the fourth phase involved testing and evaluating mobile applications that can support the efforts of citizen scientists in IPS detection. Literature reviews were conducted on IPS and ED methods, and four regional experts from ODNR and Miami University were interviewed. A questionnaire was used to gather information about ED methods used across the state. The findings revealed that geospatial methods, including Unmanned Aerial Vehicles (UAVs), Multispectral Satellites (MSS), and Normalized Difference Vegetation Index (NDVI), are not feasible for early detection of IPS, as they require GIS expertise, are still an emerging technology, and are not suitable for every habitat for the ED of IPS. Therefore, Other ED methods options were explored, which include predicting areas where IPS will grow, which can be done through monitoring areas that are like the species’ native habitat. Through literature review and interviews, IPS are known to grow in frequently disturbed areas such as along trails, shorelines, and streambanks. The research team called these areas “hotspots” and created maps of these hotspots specifically for HW NP to support and narrow the efforts of citizen scientists and staff in the ED of IPS. The results further showed that utilizing citizen scientists in the ED of IPS is feasible, especially through single day events or passive monitoring challenges. The study concluded that the creation of hotspot maps to direct the efforts of citizen scientists are effective for the early detection of IPS. Several recommendations were made, among which is the creation of hotspot maps to narrow the ED efforts as citizen scientists continues to work in the preserves and utilize citizen science volunteers to identify and record emerging IPS.

Keywords: early detection, hueston woods state nature preserve, invasive plant species, hotspots

Procedia PDF Downloads 79
341 Valorization of Dates Nodes as a Carbon Source Using Biological Denitrification

Authors: Ouerdia Benbelkacem Belouanas

Abstract:

Heterotrophic denitrification has been proven to be one of the most feasible processes for removing nitrate from waste water and drinking water. In this process, heterotrophic bacteria use organic carbon for both growth and as an electron source. Underground water pollution by nitrates become alarming in Algeria. A survey carried out revealed that the nitrate concentration is in continual increase. Studies in some region revealed contamination exceeding the recommended permissible dose which is 50 mg/L. Worrying values in the regions of Mascara, Ouled saber, El Eulma, Bouira and Algiers are respectively 72 mg/L, 75 mg/L, 97 mg/L, 102 mg/L, and 158 mg/L. High concentration of nitrate in drinking water is associated with serious health risks. Research on nitrate removal technologies from municipal water supplies is increasing because of nitrate contamination. Biological denitrification enables transformation of oxidized nitrogen compounds by a wide spectrum of heterotrophic bacteria into harmless nitrogen gas with accompanying carbon removal. Globally, denitrification is commonly employed in biological nitrogen removal processes to enhance water quality. The study investigated the valorization of a vegetable residue as a carbon source (dates nodes) in water treatment using the denitrification process. Throughout the study, the effect of inoculums addition, pH, and initial concentration of nitrates was also investigated. In this research, a natural organic substance: dates nodes were investigated as a carbon source in the biological denitrification of drinking water. This material acts as a solid substrate and bio-film carrier. The experiments were carried out in batch processes. Complete denitrification was achieved varied between 80 and 100% according to the type of process used. It was found that the nitrate removal rate based on our results, we concluded that the removal of organic matter and nitrogen compounds depended mainly on initial concentration of nitrate. The effluent pH was mainly affected by the C/N ratio, where a decrease increases pH.

Keywords: biofilm, carbon source, dates nodes, heterotrophic denitrification, nitrate, nitrite

Procedia PDF Downloads 396
340 Proliferative Effect of Some Calcium Channel Blockers on the Human Embryonic Kidney Cell Line

Authors: Lukman Ahmad Jamil, Heather M. Wallace

Abstract:

Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

Procedia PDF Downloads 180
339 Hypoglycemic and Hypolipidemic Effects of Aqueous Flower Extract from Nyctanthes arbor-tristis L.

Authors: Brahmanage S. Rangika, Dinithi C. Peiris

Abstract:

Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

Procedia PDF Downloads 353
338 Seismic Response of Reinforced Concrete Buildings: Field Challenges and Simplified Code Formulas

Authors: Michel Soto Chalhoub

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Building code-related literature provides recommendations on normalizing approaches to the calculation of the dynamic properties of structures. Most building codes make a distinction among types of structural systems, construction material, and configuration through a numerical coefficient in the expression for the fundamental period. The period is then used in normalized response spectra to compute base shear. The typical parameter used in simplified code formulas for the fundamental period is overall building height raised to a power determined from analytical and experimental results. However, reinforced concrete buildings which constitute the majority of built space in less developed countries pose additional challenges to the ones built with homogeneous material such as steel, or with concrete under stricter quality control. In the present paper, the particularities of reinforced concrete buildings are explored and related to current methods of equivalent static analysis. A comparative study is presented between the Uniform Building Code, commonly used for buildings within and outside the USA, and data from the Middle East used to model 151 reinforced concrete buildings of varying number of bays, number of floors, overall building height, and individual story height. The fundamental period was calculated using eigenvalue matrix computation. The results were also used in a separate regression analysis where the computed period serves as dependent variable, while five building properties serve as independent variables. The statistical analysis shed light on important parameters that simplified code formulas need to account for including individual story height, overall building height, floor plan, number of bays, and concrete properties. Such inclusions are important for reinforced concrete buildings of special conditions due to the level of concrete damage, aging, or materials quality control during construction. Overall results of the present analysis show that simplified code formulas for fundamental period and base shear may be applied but they require revisions to account for multiple parameters. The conclusion above is confirmed by the analytical model where fundamental periods were computed using numerical techniques and eigenvalue solutions. This recommendation is particularly relevant to code upgrades in less developed countries where it is customary to adopt, and mildly adapt international codes. We also note the necessity of further research using empirical data from buildings in Lebanon that were subjected to severe damage due to impulse loading or accelerated aging. However, we excluded this study from the present paper and left it for future research as it has its own peculiarities and requires a different type of analysis.

Keywords: seismic behaviour, reinforced concrete, simplified code formulas, equivalent static analysis, base shear, response spectra

Procedia PDF Downloads 211
337 Computer Aide Discrimination of Benign and Malignant Thyroid Nodules by Ultrasound Imaging

Authors: Akbar Gharbali, Ali Abbasian Ardekani, Afshin Mohammadi

Abstract:

Introduction: Thyroid nodules have an incidence of 33-68% in the general population. More than 5-15% of these nodules are malignant. Early detection and treatment of thyroid nodules increase the cure rate and provide optimal treatment. Between the medical imaging methods, Ultrasound is the chosen imaging technique for assessment of thyroid nodules. The confirming of the diagnosis usually demands repeated fine-needle aspiration biopsy (FNAB). So, current management has morbidity and non-zero mortality. Objective: To explore diagnostic potential of automatic texture analysis (TA) methods in differentiation benign and malignant thyroid nodules by ultrasound imaging in order to help for reliable diagnosis and monitoring of the thyroid nodules in their early stages with no need biopsy. Material and Methods: The thyroid US image database consists of 70 patients (26 benign and 44 malignant) which were reported by Radiologist and proven by the biopsy. Two slices per patient were loaded in Mazda Software version 4.6 for automatic texture analysis. Regions of interests (ROIs) were defined within the abnormal part of the thyroid nodules ultrasound images. Gray levels within an ROI normalized according to three normalization schemes: N1: default or original gray levels, N2: +/- 3 Sigma or dynamic intensity limited to µ+/- 3σ, and N3: present intensity limited to 1% - 99%. Up to 270 multiscale texture features parameters per ROIs per each normalization schemes were computed from well-known statistical methods employed in Mazda software. From the statistical point of view, all calculated texture features parameters are not useful for texture analysis. So, the features based on maximum Fisher coefficient and the minimum probability of classification error and average correlation coefficients (POE+ACC) eliminated to 10 best and most effective features per normalization schemes. We analyze this feature under two standardization states (standard (S) and non-standard (NS)) with Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA) and Non-Linear Discriminant Analysis (NDA). The 1NN classifier was performed to distinguish between benign and malignant tumors. The confusion matrix and Receiver operating characteristic (ROC) curve analysis were used for the formulation of more reliable criteria of the performance of employed texture analysis methods. Results: The results demonstrated the influence of the normalization schemes and reduction methods on the effectiveness of the obtained features as a descriptor on discrimination power and classification results. The selected subset features under 1%-99% normalization, POE+ACC reduction and NDA texture analysis yielded a high discrimination performance with the area under the ROC curve (Az) of 0.9722, in distinguishing Benign from Malignant Thyroid Nodules which correspond to sensitivity of 94.45%, specificity of 100%, and accuracy of 97.14%. Conclusions: Our results indicate computer-aided diagnosis is a reliable method, and can provide useful information to help radiologists in the detection and classification of benign and malignant thyroid nodules.

Keywords: ultrasound imaging, thyroid nodules, computer aided diagnosis, texture analysis, PCA, LDA, NDA

Procedia PDF Downloads 261
336 Silica Nanoparticles Induced Oxidative Stress and Inflammation in MRC-5 Human Lung Fibroblasts

Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

Abstract:

Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

Procedia PDF Downloads 127
335 Impact of a Structured Antimicrobial Stewardship Program in a North-East Italian Hospital

Authors: Antonio Marco Miotti, Antonella Ruffatto, Giampaola Basso, Antonio Madia, Giulia Zavatta, Emanuela Salvatico, Emanuela Zilli

Abstract:

A National Action Plan to fight antimicrobial resistance was launched in Italy in 2017. In order to reduce inappropriate exposure to antibiotics and infections from multi-drug resistant bacteria, it is essential to set up a structured system of surveillance and monitoring of the implementation of National Action Plan standards, including antimicrobial consumption, with a special focus on quinolones, third generation cephalosporins and carbapenems. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Pharmaceutical Service to the Hospital of Cittadella, ULSS 6 Euganea – Health Trust (District of Padua) for the years 2019 (before the pandemic), 2020 and 2021 for all classes of antibiotics. Multidisciplinary meetings have been organized monthly by the local Antimicrobial Stewardship Group. Between 2019 and 2021, an increase in the consumption of carbapenems in the Intensive Care Unit (from 12.2 to 18.2 DDD, + 49.2%) and a decrease in Medical wards (from 5.3 to 2.6 DDD, - 50.9%) was reported; a decrease in the consumption of quinolones in Intensive Care Unit (from 17.2 to 10.8 DDD, - 37.2%), Medical wards (from 10.5 to 6.6 DDD, - 37.1%) and Surgical wards (from 10.2 to 9.3 DDD, - 8.8%) was highlighted; an increase in the consumption of third generation cephalosporins in Medical wards (from 18.1 to 22.6 DDD, + 24,1%) was reported. Finally, after an increase in the consumption of macrolides between 2020 and 2019, in 2021, a decrease was reported in the Intensive Care Unit (DDD: 8.0 in 2019, 18.0 in 2020, 6.4 in 2021) and Medical wards (DDD: 9.0 in 2019, 13.7 in 2020, 10.9 in 2021). Constant monitoring of antimicrobial consumption and timely identifying of warning situations that may need a specific intervention are the cornerstone of Antimicrobial Stewardship programs, together with analysing data on bacterial resistance rates and infections from multi-drug resistant bacteria.

Keywords: carbapenems, quinolones, antimicrobial, stewardship

Procedia PDF Downloads 132
334 Investigating Clarity Ultrasound Transperineal Ultrasound Imaging as a Method of Localising the Prostate, Compared to Cone Beam Computed Tomography with Fiducials

Authors: Harley Stephens

Abstract:

Although fiducial marker insertion is regarded as the ‘gold standard’ in terms of image guided radiotherapy (IGRT), its application must be considered carefully as the procedure can be invasive, time-consuming, and reliant on consultant expertise. Precision of the fiducials is dependent on these markers remaining in the same location and on the prostate not changing shape during the course treatment. To facilitate the acquirement of non-ionising IGRT and intra-fractional prostate tracking, Clarity TPUS was developed as an alternative imaging system. The main benefits of Clarity TPUS are that it is non-invasive, non-ionising and cost-effective. Other studies have compared fiducials to transabdominal ultrasound, which has since been proven to not be as accurate as trans-perineal imaging, as included in this study. CBCT fiducial translations and Clarity TPUS translations for 120 images as part of the PACE-C prostate SABR trial were retrospectively evaluated by three imaging specialists. Differences were analysed using correlation and Bland-Altman plots. Inter-observer matches agreed within 3mm 88.3 % of the time in left/right direction, 86.7 % of the time in in superior/inferior direction, and 91.7% of the time in ant/post direction. They agreed within 5mm more than 98.3 % of the time in all directions. The intra-class correlation co-efficient was calculated for each direction to show agreement between imaging specialist for inter-observer variability. Each was 0.95 or above, with 1 indicating perfect reliability. Agreement between observers was slightly higher for CBCT and fiducials at 98.7% agreement within 5 mm, compared to clarity TPUS where 96.7% agreement was seen within 5mm. Clarity TPUS has the benefit of no additional dose and intra-fractional monitoring, and results show a good correlation between the different modalities. Inter-observer variability is to be considered, and further research with a larger population would be of benefit.

Keywords: oncology, prostate radiotherapy, image guided radiotherapy, IGRT

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333 Protective Effect of Bexarotene, a Selective RXRα Agonist, against Hypotension Associated with Inflammation and Tissue Injury Linked to Decreased Circulating iNOS Levels in A Rat Model of Septic Shock

Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

Abstract:

We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

Procedia PDF Downloads 296