Search results for: pericardial adipose tissue

Authors: Georgeta Voicu, Cristina Daniela Ghitulica, Andreia Cucuruz, Cristina Busuioc

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In the field of tissue engineering, the compositional and microstructural features of the employed materials play an important role, with implications on the mechanical and biological behaviour of the medical devices. In this context, the development of apatite - natural biopolymer composites represents a choice of many scientific groups. Thus, hydroxyapatite powders were synthesized by a wet method, namely co-precipitation, starting from high purity reagents (CaO, MgO, and H3PO4). Moreover, the substitution of calcium with magnesium have been approached, in the 5 - 10 wt.% range. Afterward, the phosphate powders were integrated in two types of composites with chitosan, different from morphological point of view. First, 3D porous scaffolds were obtained by a freeze-drying procedure. Second, uniform, compact films were achieved by film casting. The influence of chitosan molecular weight (low, medium and high), as well as apatite powder to polymer ratio (1:1 and 1:2) on the morphological properties, were analysed in detail. In conclusion, the reported biocomposites, prepared by a straightforward route are suitable for bone substitution or repairing applications.

Keywords: bone reconstruction, chitosan, composite scaffolds, hydroxyapatite

Procedia PDF Downloads 322

Authors: Jing Zhang, Yvonne Reinwald, Nick Poulson, Alicia El Haj, Chung See, Mike Somekh, Melissa Mather

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Biomedical imaging of native tissue using light offers the potential to obtain excellent structural and functional information in a non-invasive manner with good temporal resolution. Image contrast can be derived from intrinsic absorption, fluorescence, or scatter, or through the use of extrinsic contrast. A major challenge in applying optical microscopy to in vivo tissue imaging is the effects of light attenuation which limits light penetration depth and achievable imaging resolution. Recently Selective Plane Illumination Microscopy (SPIM) has been used to map the 3D distribution of fluorophores dispersed in biological structures. In this approach, a focused sheet of light is used to illuminate the sample from the side to excite fluorophores within the sample of interest. Images are formed based on detection of fluorescence emission orthogonal to the illumination axis. By scanning the sample along the detection axis and acquiring a stack of images, 3D volumes can be obtained. The combination of rapid image acquisition speeds with the low photon dose to samples optical sectioning provides SPIM is an attractive approach for imaging biological samples in 3D. To date all implementations of SPIM rely on the use of fluorescence reporters be that endogenous or exogenous. This approach has the disadvantage that in the case of exogenous probes the specimens are altered from their native stage rendering them unsuitable for in vivo studies and in general fluorescence emission is weak and transient. Here we present for the first time to our knowledge a label-free implementation of SPIM that has downstream applications in the clinical setting. The experimental set up used in this work incorporates both label-free and fluorescent illumination arms in addition to a high specification camera that can be partitioned for simultaneous imaging of both fluorescent emission and scattered light from intrinsic sources of optical contrast in the sample being studied. This work first involved calibration of the imaging system and validation of the label-free method with well characterised fluorescent microbeads embedded in agarose gel. 3D constructs of mammalian cells cultured in agarose gel with varying cell concentrations were then imaged. A time course study to track cell proliferation in the 3D construct was also carried out and finally a native tissue sample was imaged. For each sample multiple images were obtained by scanning the sample along the axis of detection and 3D maps reconstructed. The results obtained validated label-free SPIM as a viable approach for imaging cells in a 3D gel construct and native tissue. This technique has the potential use in a near-patient environment that can provide results quickly and be implemented in an easy to use manner to provide more information with improved spatial resolution and depth penetration than current approaches.

Keywords: bioimaging, optics, selective plane illumination microscopy, tissue imaging

Procedia PDF Downloads 247

Authors: Ahmed Auda, Manjree Agarwala, Giles Hardya, Yonglin Rena

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Botrytis cinerea is a major pest for many plants. It can attack a wide range of plant parts. It can attack buds, flowers, and leaves, stems, and fruit. However, B. cinerea can be mixed with other diseases that cause the same damage. There are many species of botrytis and more than one different strains of each. Botrytis might infect the foliage of nursery stock stored through winter in damp conditions. There are no known resistant plants. Botrytis must have nutrients or food source before it infests the plant. Nutrients leaking from wounded plant parts or dying tissue like old flower petals give the required nutrients. From this food, the fungus becomes more attackers and invades healthy tissue. Dark to light brown rot forms in the ill tissue. High humidity conditions support the growth of this fungus. However, we suppose that selection pressure can act on the morphological and neurophysiologic filter properties of the receiver and on both the biochemical and the physiological regulation of the signal. Communication is implied when signal and receiver evolves toward more and more specific matching, culminating. In other hand, receivers respond to portions of a body odor bouquet which is released to the environment not as an (intentional) signal but as an unavoidable consequence of metabolic activity or tissue damage. Each year Botrytis species can cause considerable economic losses to plant crops. Even with the application of strict quarantine and control measures, these fungi can still find their way into crops and cause the imposition of onerous restrictions on exports. Blueberry fruit mould caused by a fungal infection usually results in major losses during post-harvest storage. Therefore, the management of infection in early stages of disease development is necessary to minimize losses. The overall purpose of this study will develop sensitive, cheap, quick and robust diagnostic techniques for the detection of B. cinerea in blueberry. The specific aim was designed to investigate the performance of volatile organic compounds (VOCs) in the detection and discrimination of blueberry fruits infected by fungal pathogens with an emphasis on Botrytis in the early storage stage of post-harvest.

Keywords: botrytis cinerea, blueberry, GC/MS, VOCs

Procedia PDF Downloads 241

Authors: Waleed Aly Sayed Ahmed, Eman Kishk, Tahani Shams

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Aim: To study the effects of co-administration of phosphodiesterase-5 inhibitor (PDE-5) and sodium selenite against the damage induced by ovarian ischemia-reperfusion in rats. Materials and Methods: A total of forty-two sexually mature, virgin, female rats were divided randomly into six groups of seven each: sham group (C), ischemia group (I), ischemia/reperfusion group (I/R), ischemia/reperfusion plus 1.4mg/kg sildenafil (I/R+S) group, ischemia/reperfusion plus 0.2mg/kg selenium (I/R+Se) group and ischemia/reperfusion plus combination of sildenafil and selenium (I/R+S+Se) group. In ischemia group (I), rats were exposed to ischemia for 3 hours (h). In ischemia/reperfusion group (I/R), rats were exposed to ischemia for 3 h followed by 6 h of reperfusion. Treated groups received 1.4mg/kg sildenafil or 0.2 mg/kg selenium or both 30 min before reperfusion. Both ovaries were surgically removed carefully. One ovary was examined for histopathological changes and the other was subject to biochemical analysis including malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx). Results: Assessment of ovarian tissue damage using a scoring system showed marked vascular congestion, interstitial edema, leukocyte infiltration, hemorrhage, and follicular degeneration in ischemia and ischemia/reperfusion groups. Tissue damage score for I, IR and all treated groups were significantly higher than those of the sham group (p<0.001), while tissue damage score decreased significantly in I/R+S and I/R+Se groups compared to I/R group (p<0.05), and notably, the difference was highly significant in I/R+S+Se group (p<0.001). There was significant increase in MDA levels and reduction in activities of CAT and GPx in I/R group compared to the sham group (p < 0.05). In I/R+S and I/R+Se groups, MDA was significantly decreased compared to the I/R group (p<0.05) and the difference was highly significant with co-administration of sildenafil and selenium (p<0.001). CAT and GPx were higher in all treated groups compared to I/R group (p<0.05). Conclusion: The co-administration of sildenafil citrate and selenium are highly protective against damage induced by ovarian ischemia/reperfusion in rats.

Keywords: phosphodiesterase-5 inhibitor, sildenafil, antioxidant, selenium, ovarian ischemia

Procedia PDF Downloads 312

Authors: Waseem Al Talalwah, Shorok Al Dorazi, Roger Soames

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Persistent sciatic artery is a rare anatomical vascular variation resulting from a lack of regression of the embryonic dorsal axial artery. The axial artery is the main artery supplying the lower limb during development in the first trimester. The current research includes 206 sciatic artery cases in 171 patients between 1864 and 2012. It aims to identify the risk factor of sciatic artery aneurysm in congenital limb anomalies. Sciatic artery aneurysm was diagnosed incidentally in amniotic band syndrome (ABS) existing with no congenital anomaly in 0.7% or with double knee in 0.7%, with the tibia in 0.7% and with hemihypertrophy or soft tissue hypertrophy in 1.4%. Therefore, the current study indicates a relationship the same gene responsible for the congenital limb deformities may be responsible for non-regression of the sciatic artery. Furthermore, pediatricians should refer cases of congenital limb anomalies for vascular evaluation prior to corrective surgical intervention.

Keywords: amniotic band syndrome, congenital limb deformities, double knee, sciatic artery, sciatic artery aneurysm , soft tissue hypertrophy

Procedia PDF Downloads 376

Authors: Lucian Mocan

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We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

Procedia PDF Downloads 368

Authors: Reza Khoshnood, Zahra Khoshnood, Ali Hajinajaf, Farzad Fahim, Behdokht Hajinajaf, Farhad Fahim

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In 2013, 24 fish samples were taken from two fishery regions in Bandar-Abbas and Bandar-Lengeh, the fishing grounds north of Hormoz Strait (Persian Gulf) near the Iranian coastline. The two flat fishes were oriental sole (Euryglossa orientalis) and deep flounder (Psettodes erumei). Using the ROPME method (MOOPAM) for chemical digestion, Cd concentration was measured with a nonflame atomic absorption spectrophotometry technique. The average concentration of Cd in the edible muscle tissue of deep flounder was measured in Bandar-Abbas and was found to be 0.15±.06 µg g-1. It was 0.1±.05 µg.g-1 in Bandar-Lengeh. The corresponding values for oriental sole were 0.2±0.13 and 0.13±0.11 µg.g-1. The average concentration of Cd in the liver tissue of deep flounder in Bandar-Abbas was 0.22±.05 µg g-1 and that in Bandar-Lengeh was 0.2±0.04 µg.g-1. The values for oriental sole were 0.31±0.09 and 0.24±0.13 µg g-1 in Bandar-Abbas and Bandar-Lengeh, respectively.

Keywords: trace metal, Euryglossa orientalis, Psettodes erumei, Persian Gulf

Procedia PDF Downloads 669

Authors: Lyudmila V. Ignatova, Yelena V. Brazhnikova, Togzhan D. Mukasheva, Ramza Zh. Berzhanova, Anel A. Omirbekova

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Endophytic microorganisms are presented in plants of different families growing in the foothills and piedmont plains of Trans-Ili Alatau. It was found that the maximum number of endophytic micromycetes is typical to the Fabaceae family. The number of microscopic fungi in the roots reached (145.9±5.9)×103 CFU/g of plant tissue; yeasts - (79.8±3.5)×102 CFU/g of plant tissue. Basically, endophytic microscopic fungi are typical for underground parts of plants. In contrast, yeasts more infected aboveground parts of plants. Small amount of micromycetes is typical to inflorescence and fruits. Antagonistic activity of selected micromycetes against Fusarium graminearum, Cladosporium sp., Phytophtora infestans and Botrytis cinerea phytopathogens was detected. Strains with a broad, narrow and limited range of action were identified. For further investigations Rh2 and T7 strains were selected, they are characterized by a broad spectrum of fungicidal activity and they formed the large inhibition zones against phytopathogens. Active antagonists are attributed to the Rhodotorula mucilaginosa and Beauveria bassiana species.

Keywords: endophytic micromycetes, fungicidal activity, prevalence, plants

Procedia PDF Downloads 320

Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Rajnish Gupta, R. S. Gupta

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Present research was aimed to investigate antidiabetic and antioxidant status of Lupeol in streptozotocin induced diabetes. Rats were divided into following groups mainly: control, diabetic, normal group as well as diabetic treated with Lupeol at 25 and 35 mg/kg b.wt./day for 21 days, diabetic group treated with glibenclamide. Tissue (pancreas, kidney and liver) as well as serum biochemical parameters were analysed for any abnormal behavior. Lupeol administration reduced diabetes onset with significant improvement in serum insulin level also strengthened by increase in β-Cell counts. A significant decrease was observed in serum glucose level. Furthermore, Lupeol treatment increased the antioxidant enzymes, glycolytic enzymes and also protein levels with a decrease in the level of thiobarbituric acid-reactive oxygen species and gluconeogenic enzymes. Present study proves that Lupeol administration significantly reinstated serum and tissue biochemical parameters and thus strengthening its antidiabetic potential.

Keywords: oxidative stress, pterostilbene, thiobarbituric acid, reactive oxygen species

Procedia PDF Downloads 470

Authors: Ali Mirtaghavi, Andy Baldwin, Rajendarn Muthuraj, Jack Luo

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Recent advances in biomaterials have led to utilizing biopolymers to develop 3D scaffolds in tissue regeneration. One of the major challenges of designing biomaterials for 3D scaffolds is to mimic the building blocks similar to the extracellular matrix (ECM) of the native tissues. Biopolymer based aerogels obtained by freeze-drying have shown to provide structural similarities to the ECM owing to their 3D format and a highly porous structure with interconnected pores, similar to the ECM. Gelatin (GEL) is known to be a promising biomaterial with inherent regenerative characteristics owing to its chemical similarities to the ECM in native tissue, biocompatibility abundance, cost-effectiveness and accessible functional groups, which makes it facile for chemical modifications with other biomaterials to form biocomposites. Despite such advantages, gelatin offers poor mechanical properties, sensitive enzymatic degradation and high viscosity at room temperature which limits its application and encourages its use to develop biocomposites. Hydrophilic biomass-based cellulose nanofibrous (CNF) has been explored to use as suspension for biocomposite aerogels for the development of 3D porous structures with excellent mechanical properties, biocompatibility and slow enzymatic degradation. In this work, CNF biocomposite aerogels with various ratios of CNF:GEL) (90:10, 70:30 and 50:50) were prepared by freeze-drying technique, and their properties were investigated in terms of physicochemical, mechanical and biological characteristics. Epichlorohydrin (EPH) was used to investigate the effect of chemical crosslinking on the molecular interaction of CNF: GEL, and its effects on physicochemical, mechanical and biological properties of the biocomposite aerogels. Ultimately, chemical crosslinking helped to improve the mechanical resilience of the resulting aerogels. Amongst all the CNF-GEL composites, the crosslinked CNF: GEL (70:30) biocomposite was found to be favourable for cell attachment and viability. It possessed highly porous structure (porosity of ~93%) with pore sizes ranging from 16-110 µm, adequate mechanical properties (compression modulus of ~47 kPa) and optimal biocompatibility both in-vitro and in-vivo, as well as controlled enzymatic biodegradation, high water penetration, which could be considered a suitable option for wound healing application. In-vivo experiments showed improvement on inflammation and foreign giant body cell reaction for the crosslinked CNF: GEL (70:30) compared to the other samples. This could be due to the superior interaction of CNF with gelatin through chemical crosslinking, resulting in more optimal in-vivo improvement. In-vitro cell culture investigation on human dermal fibroblasts showed satisfactory 3D cell attachment over time. Overall, it has been observed that the developed CNF: GEL aerogel can be considered as a potential scaffold for soft tissue regeneration application.

Keywords: 3D scaffolds, aerogels, Biocomposites , tissue engineering

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Authors: Hilal T. Sasmazel, Seda Surucu

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Skin tissue engineering is a promising field for the treatment of skin defects using scaffolds. This approach involves the use of living cells and biomaterials to restore, maintain, or regenerate tissues and organs in the body by providing; (i) larger surface area for cell attachment, (ii) proper porosity for cell colonization and cell to cell interaction, and (iii) 3-dimensionality at macroscopic scale. Recent studies on this area mainly focus on fabrication of scaffolds that can closely mimic the natural extracellular matrix (ECM) for creation of tissue specific niche-like environment at the subcellular scale. Scaffolds designed as ECM-like architectures incorporating into the host with minimal scarring/pain and facilitate angiogenesis. This study is related to combining of synthetic PCL and natural chitosan polymers to form 3D PCL/Chitosan core-shell structures for skin tissue engineering applications. Amongst the polymers used in tissue engineering, natural polymer chitosan and synthetic polymer poly(ε-caprolactone) (PCL) are widely preferred in the literature. Chitosan has been among researchers for a very long time because of its superior biocompatibility and structural resemblance to the glycosaminoglycan of bone tissue. However, the low mechanical flexibility and limited biodegradability properties reveals the necessity of using this polymer in a composite structure. On the other hand, PCL is a versatile polymer due to its low melting point (60°C), ease of processability, degradability with non-enzymatic processes (hydrolysis) and good mechanical properties. Nevertheless, there are also several disadvantages of PCL such as its hydrophobic structure, limited bio-interaction and susceptibility to bacterial biodegradation. Therefore, it became crucial to use both of these polymers together as a hybrid material in order to overcome the disadvantages of both polymers and combine advantages of those. The scaffolds here were fabricated by using electrospinning technique and the characterizations of the samples were done by contact angle (CA) measurements, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-Ray Photoelectron spectroscopy (XPS). Additionally, gas permeability test, mechanical test, thickness measurement and PBS absorption and shrinkage tests were performed for all type of scaffolds (PCL, chitosan and PCL/chitosan core-shell). By using ImageJ launcher software program (USA) from SEM photographs the average inter-fiber diameter values were calculated as 0.717±0.198 µm for PCL, 0.660±0.070 µm for chitosan and 0.412±0.339 µm for PCL/chitosan core-shell structures. Additionally, the average inter-fiber pore size values exhibited decrease of 66.91% and 61.90% for the PCL and chitosan structures respectively, compare to PCL/chitosan core-shell structures. TEM images proved that homogenous and continuous bead free core-shell fibers were obtained. XPS analysis of the PCL/chitosan core-shell structures exhibited the characteristic peaks of PCL and chitosan polymers. Measured average gas permeability value of produced PCL/chitosan core-shell structure was determined 2315±3.4 g.m-2.day-1. In the future, cell-material interactions of those developed PCL/chitosan core-shell structures will be carried out with L929 ATCC CCL-1 mouse fibroblast cell line. Standard MTT assay and microscopic imaging methods will be used for the investigation of the cell attachment, proliferation and growth capacities of the developed materials.

Keywords: chitosan, coaxial electrospinning, core-shell, PCL, tissue scaffold

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Authors: Smita Shenoy, Amoolya Gowda, Tara Shanbhag, Krishnananda Prabhu, Venumadhav Nelluri

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The study was undertaken to assess the effect of ethanolic extract of Michelia champaca on excision wound healing in diabetic wistar rats. Excision wound was made in five groups of rats after inducing diabetes with streptozotocin in four groups. Paraffin was applied to wounds in nondiabetic and diabetic control and 2.5%, 5%, 10% ointment of extract to wounds in three diabetic test groups. Monitoring of wound contraction rate, the period of epithelization and histopathological examination of granulation tissue was done. There was a significant (p < 0.05) decrease in the period of epithelization and a significant increase in the wound contraction rate on day 12 and 16 in rats treated with 5% and 10% ointment as compared to diabetic rats. There was a better organization of collagen fibers in the granulation tissue of wounds treated with 10% ointment. The higher dose of ethanolic extract of Michelia champaca promoted wound healing in diabetic Wistar rats.

Keywords: Michelia champaca, excision wound, contraction, epithelization

Procedia PDF Downloads 359

Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

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High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

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Authors: Kumalo F. I., Malimabe M. A., Gumede T. P., Mosoabisane M. F. T.

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This study investigates the fabrication and characterization of bio-nanocomposites consisting of poly (butylene succinate) (PBS) and poly (ԑ-caprolactone) (PCL), reinforced with cellulose extracted from Eucomis autumnalis, a medicinal plant. Bio-nanocomposite films were prepared using the solvent casting method, with cellulose content ranging from 1 to 3 wt%. During the solution casting method, 15 ml of chloroform was used to dissolve an overall mass of 0.5g of each polymer as well as the combination of their bio-nanocomposites. Comprehensive analysis was conducted using FTIR, SEM, TEM, DSC, TGA, and XRD to assess morphological, thermal, and structural properties. Mechanical properties were not investigated due to the thin nature of the films. The results indicated significant improvements in the thermal stability and morphological properties with increasing cellulose content, showcasing the potential of these materials for tissue engineering applications. The use of cellulose extracted from a medicinal plant highlights the potential for sustainable and biocompatible materials in biomedical applications.

Keywords: bio-nanocomposites, poly (butylene succinate), poly(ԑ-caprolactone), Eucomis autumnalis, medicinal plant

Procedia PDF Downloads 51

Authors: Neda Sinaei, Davood Zare, Mehrdad Azin

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Polyhydroxyalkanoates (PHAs) are biocompatible and biodegradable polymers produced by a wide range of bacterial strains. These biopolymers are significantly studied for drug delivery and tissue engineering applications because of their fascinating physicochemical properties. Polyhydroxybutyrate (PHB) scaffold that has been extracted from a novel bacteria using oil wastewater was selected to study. Some physical parameters affecting scaffold properties such as PHB concentration, solvent evaporation speed, and ultrasonic time were investigated. Scanning electron microscopy was used to evaluate the porosity. Afterward, the biocompatibility of PHB scaffold was assessed. Initial results showed the highly porous PHB scaffold structure with a variety of pore sizes. Subsequent results indicated that more unique pore sizes can be obtained by optimizing physical factors. It would be noticed that the morphology of the pore structure was accordingly affected by ultrasonic time. Hence, In vitro cell viability tests on the PHB scaffold using human foreskin fibroblasts revealed strong cell attachment and proliferation supports. Therefore, it can be concluded that the cost-effective PHB scaffold has the potential using as a biomaterial cell adhesion substrate in therapeutic applications.

Keywords: Polyhydroxybutyrate, biocompatible, scaffold, porous, tissue engineering

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Authors: Viktoriia Burkina, Vladimir Zlabek, Galia Zamaratskaia

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Cytochromes P450 (CYP) are important family of enzymes in Phase I metabolism. Environmental pollutants often act as inducers of the gene expression and activities CYP1A1 and CYP3A-like isoforms in fish. The activities are generally measured in the fish liver or gills, and less is known about tissue distribution of expression. In present study, the CYP1A1 and CYP3A-like activities were measured in rainbow trout liver, gill, intestine, heart, brain and gonads. The activities of CYP1A1 and CYP3A-like proteins were estimated as the rates of 7-ethoxyresorufin-O-deethylation (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation (BFCOD), respectively. The CYP1A1 and CYP3A-like activities were detectable in all investigated fish tissues, with the highest activity in hepatic tissue followed by heart > brain > gill > intestine > gonads. To confirm the presence of CYP1A1 in different tissues, EROD activity was measured in presence of the selective inhibitors ellipticine (CYP1A1), ketoconazole (CYP3A), 8-methoxypsoralen (human CYP2A) and diallyl sulphide (CYP2E1). It was found that ellipticine, ketoconazole and 8-methoxypsoralen inhibited hepatic EROD activity by 88-98%. Ellipticine inhibited gill, intestine, and gonad EROD activity by 50%. In conclusion, EROD and BFCOD activities were detected in rainbow trout liver, gill, intestine, heart, brain and gonads. Further studies are needed to fully identify all CYP450 isoforms responsible for these activities. Acknowledgement: The study was financially supported by the Ministry of Education, Youth and Sports of the Czech Republic - projects „CENAKVA “(No. CZ.1.05/2.1.00/01.0024), “CENAKVA Center Development “(No. CZ.1.05/2.1.00/19.0380), “CENAKVA II “(No. LO1205 under the NPU I program), and "Development of USB - International mobility (No. CZ.02.2.69/0.0/0.0/16_027/0008364).

Keywords: BFCOD, EROD, fish, phase I metabolism, selective inhibitors

Procedia PDF Downloads 151

Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan

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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.

Keywords: breast cancer, expression, leptin, leptin receptors

Procedia PDF Downloads 139

Authors: Nishanth Venugopal Menon, Chuah Yon Jin, Samantha Phey, Wu Yingnan, Zhang Ying, Vincent Chan, Kang Yuejun

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Cell Migration is a vital phenomenon that the cells undergo in various physiological processes like wound healing, disease progression, embryogenesis, etc. Cell migration depends primarily on the chemical and physical cues available in the cellular environment. The chemical cue involves the chemokines secreted and gradients generated in the environment while physical cues indicate the impact of matrix properties like nanotopography and stiffness on the cells. Mesenchymal Stem Cells (MSCs) have been shown to have a role wound healing in vivo and its migration to the site of the wound has been shown to have a therapeutic effect. In the field of stem cell based tissue regeneration of bones and cartilage, one approach has been to introduce scaffold laden with MSCs into the site of injury to enable tissue regeneration. In this work, we have studied the combinatorial impact of the substrate physical properties on MSC migration. A microfluidic in vitro model was created to perform the migration studies. The microfluidic model used is a three compartment device consisting of two cell seeding compartments and one migration compartment. Four different PDMS substrates with varying substrate roughness, stiffness and hydrophobicity were created. Its surface roughness and stiffness was measured using Atomic Force Microscopy (AFM) while its hydrphobicity was measured from the water contact angle using an optical tensiometer. These PDMS substrates are sealed to the microfluidic chip following which the MSCs are seeded and the cell migration is studied over the period of a week. Cell migration was quantified using fluorescence imaging of the cytoskeleton (F-actin) to find out the area covered by the cells inside the migration compartment. The impact of adhesion proteins on cell migration was also quantified using a real-time polymerase chain reaction (qRT PCR). These results suggested that the optimal substrate for cell migration would be one with an intermediate level of roughness, stiffness and hydrophobicity. A higher or lower value of these properties affected cell migration negatively. These observations have helped us in understanding that different substrate properties need to be considered in tandem, especially while designing scaffolds for tissue regeneration as cell migration is normally impacted by the combinatorial impact of the matrix. These observations may lead us to scaffold optimization in future tissue regeneration applications.

Keywords: cell migration, microfluidics, in vitro model, stem cell migration, scaffold, substrate properties

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Authors: Nalan Kaya, D. Ozlem Dabak, Gonca Ozan, Elif Erdem, Enver Ozan

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One of the common causes of cardiovascular disease (CVD) is smoking. Moreover, tobacco smoke decreases the amount of oxygen that the blood can carry and increases the tendency for blood clots. Ellagic acid is a powerful antioxidant found especially in red fruits. It was shown to block atherosclerotic process suppressing oxidative stress and inflammation. The aim of this study was to examine the protective effects of ellagic acid against oxidative damage on heart tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Heart tissues and blood samples were taken. Histological and biochemical analyzes were performed. Vascular congestion, hyperemic areas, inflammatory cell infiltration and increased connective tissue in the perivascular area were observed in tobacco smoke and tobacco smoke + corn oil groups. Increased connective tissue in the perivascular area, hemorrhage and inflammatory cell infiltration were decreased in tobacco smoke + EA group. Group-II GSH level was not changed (significantly), CAT, SOD, GPx activities were significantly higher than group-I. Compared to group-II, group-IV GSH, SOD, CAT, GPx activities were increased, and MDA level was decreased significantly. Group-II and Group-III levels were similar. The results indicate that ellagic acid could protect the heart tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, heart, rat, tobacco smoke

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Authors: Maryam Tajadod

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The treatment of cancer is one of the main challenges of nuclear medicine; while cancer begins in an organ, such as the breast or prostate, it spreads to the bone, resulting in metastatic bone. In the treatment of cancer with radiotherapy, the determination of the involved tissues’ dose is one of the important steps in the treatment protocol. Comparing absorbed doses for Lu-177 and Ra-223 and Ac-225 in the bone marrow and soft tissue of bone phantom with evaluating energetic emitted particles of these radionuclides is the important aim of this research. By the use of MCNPX computer code, a model for bone phantom was designed and the values of absorbed dose for Ra-223 and Ac-225, which are Alpha emitters & Lu-177, which is a beta emitter, were calculated. As a result of research, in comparing gamma radiation for three radionuclides, Lu-177 released the highest dose in the bone marrow and Ra-223 achieved the lowest level. On the other hand, the result showed that although the figures of absorbed dose for Ra and Ac in the bone marrow are near to each other, Ra spread more energy in cortical bone. Moreover, The alpha component of the Ra-223 and Ac-225 have very little effect on bone marrow and soft tissue than a beta component of the lu-177 and it leaves the highest absorbed dose in the bone where the source is located.

Keywords: bone metastases, lutetium-177, radium-223, actinium-225, absorbed dose

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Authors: Tomohiko Utsuki, Kyoka Sato

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In emergency medicine, it is recognized that brain resuscitation is very important for the reduction of mortality rate and neurological sequelae. Especially, the control of brain temperature (BT), intracranial pressure (ICP), and cerebral blood flow (CBF) are most required for stabilizing brain’s physiological state in the treatment for such as brain injury, stroke, and encephalopathy. However, the manual control of BT, ICP, and CBF frequently requires the decision and operation of medical staff, relevant to medication and the setting of therapeutic apparatus. Thus, the integration and the automation of the control of those is very effective for not only improving therapeutic effect but also reducing staff burden and medical cost. For realizing such integration and automation, a mathematical model of brain physiological state is necessary as the controlled object in simulations, because the performance test of a prototype of the control system using patients is not ethically allowed. A model of cerebral blood circulation has already been constructed, which is the most basic part of brain physiological state. Also, a migration model of extracellular fluid in brain has been constructed, however the condition that the total volume of intracranial cavity is almost changeless due to the hardness of cranial bone has not been considered in that model. Therefore, in this research, the dynamic migration model of extracellular fluid in brain was constructed on the consideration of the changelessness of intracranial cavity’s total volume. This model is connectable to the cerebral blood circulation model. The constructed model consists of fourteen compartments, twelve of which corresponds to perfused area of bilateral anterior, middle and posterior cerebral arteries, the others corresponds to cerebral ventricles and subarachnoid space. This model enable to calculate the migration of tissue fluid from capillaries to gray matter and white matter, the flow of tissue fluid between compartments, the production and absorption of cerebrospinal fluid at choroid plexus and arachnoid granulation, and the production of metabolic water. Further, the volume, the colloid concentration, and the tissue pressure of/in each compartment are also calculable by solving 40-dimensional non-linear simultaneous differential equations. In this research, the obtained model was analyzed for its validation under the four condition of a normal adult, an adult with higher cerebral capillary pressure, an adult with lower cerebral capillary pressure, and an adult with lower colloid concentration in cerebral capillary. In the result, calculated fluid flow, tissue volume, colloid concentration, and tissue pressure were all converged to suitable value for the set condition within 60 minutes at a maximum. Also, because these results were not conflict with prior knowledge, it is certain that the model can enough represent physiological state of brain under such limited conditions at least. One of next challenges is to integrate this model and the already constructed cerebral blood circulation model. This modification enable to simulate CBF and ICP more precisely due to calculating the effect of blood pressure change to extracellular fluid migration and that of ICP change to CBF.

Keywords: dynamic model, cerebral extracellular migration, brain resuscitation, automatic control

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Authors: Amir Moslehi, Gholamreza Raisali

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Microdosimetric detectors based on multiple-thick gas electron multiplier (multiple-THGEM) configurations are being used in various fields of radiation protection and dosimetry. In the present work, microdosimetric response of these detectors to fast neutrons has been investigated by Monte Carlo method. Three similar microdosimeters made of A-150 and rexolite as the wall materials are designed; the first based on single-THGEM, the second based on double-THGEM and the third is based on triple-THGEM. Sensitive volume of the three microdosimeters is a right cylinder of 5 mm height and diameter which is filled with the propane-based tissue-equivalent (TE) gas. The TE gas with 0.11 atm pressure at the room temperature simulates 1 µm of tissue. Lineal energy distributions for several neutron energies from 10 keV to 14 MeV including 241Am-Be neutrons are calculated by the Geant4 simulation toolkit. Also, mean quality factor and dose-equivalent value for any neutron energy has been determined by these distributions. Obtained data derived from the three microdosimeters are in agreement. Therefore, we conclude that the multiple-THGEM structures present similar microdosimetric responses to fast neutrons.

Keywords: fast neutrons, geant4, multiple-thick gas electron multiplier, microdosimeter

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Authors: Mayada Mazher, Ahmed Moustafa, Ahmed Abdellatif

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Background: Autophagy is a eukaryotic, highly conserved catabolic process implicated in many pathophysiologies such as wound healing. Autophagy-associated genes serve as a scaffolding platform for signal transduction of macrophage polarization during the inflammatory phase of wound healing and tissue repair process. In the current study, we report a model for the interplay between autophagy-associated genes and macrophages polarization associated genes. Methods: In silico analysis was performed on 249 autophagy-related genes retrieved from the public autophagy database and gene expression data retrieved from Gene Expression Omnibus (GEO); GSE81922 and GSE69607 microarray data macrophages polarization 199 DEGS. An integrated protein-protein interaction network was constructed for autophagy and macrophage gene sets. The gene sets were then used for GO terms pathway enrichment analysis. Common transcription factors for autophagy and macrophages' polarization were identified. Finally, microRNAs enriched in both autophagy and macrophages were predicated. Results: In silico prediction of common transcription factors in DEGs macrophages and autophagy gene sets revealed a new role for the transcription factors, HOMEZ, GABPA, ELK1 and REL, that commonly regulate macrophages associated genes: IL6,IL1M, IL1B, NOS1, SOC3 and autophagy-related genes: Atg12, Rictor, Rb1cc1, Gaparab1, Atg16l1. Conclusions: Autophagy and macrophages' polarization are interdependent cellular processes, and both autophagy-related proteins and macrophages' polarization related proteins coordinate in tissue remodelling via transcription factors and microRNAs regulatory network. The current work highlights a potential new role for transcription factors HOMEZ, GABPA, ELK1 and REL in wound healing.

Keywords: autophagy related proteins, integrated network analysis, macrophages polarization M1 and M2, tissue remodelling

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Authors: Ahsan Khan, Nazish Shah, Muhammad Salman

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The present study deals with the toxicological effects of copper, lead and chromium on brain and liver tissues of grass carp (Ctenopharyngodon idella). The average length of experimental fish was 8.5 ± 5.5 cm and weighed 9.5 ± 6.5 g. Grass carp was exposed to lethal concentration (LC₁₅) of copper, lead and chromium for 24, 48, 72 and 96 hours respectively. (LC₁₅) for copper was 1.5, 1.4, 1.2 and 1mgL⁻¹. Similarly, LC₁₅ of lead was 250, 235, 225 and 216mgL⁻¹ while (LC₁₅) for chromium was 25.5, 22.5, 20 and 18mgL⁻¹ respectively. During the time of exposure against various doses of heavy metals the grass carp showed some behavioral changes. In the initial stages of experiment, the rapid movements and gulping of air were observed. Several times the fish tried to jump to scat from the toxic median. In addition, the accumulation of heavy metals in different tissues of grass carp particularly in liver and brain tissues were observed. Lead was highly accumulated in brain tissue after the exposure of fish for 24 and 48 hours, while highly accumulated in liver tissues after the exposure of fish for 72 and 96 hours. Chromium was highly accumulated in the liver tissues after the exposure of fish for 24 hours while its accumulation was found highly in the brain tissues after the exposure of fish for 48, 72 and 96 hours. Similarly, accumulation of copper concentration was found highly in brain tissues after the exposure of 48 and 96 hours while its accumulation was high in liver tissues after the exposure of 24 and 72 hours. Comparatively maximum accumulation of lead was found in brain and liver tissues of grass carp followed by chromium and copper. Furthermore, accumulation of these metals caused many abnormalities like gliosis, destruction of cell, change in cell shape and shrinkage of cells in brain tissue while in liver tissues aggregation in hepatocytes, widen space between cells and also destruction of cell was observed. These experiments and observations can be useful to monitor the aquatic pollution and quality of aquatic environment system.

Keywords: brain, grass carp, liver, lethal concentration, toxicity

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

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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

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Authors: Balakrishna Valluru, Ruth Suckling

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A 16 year old male was found collapsed on the road following stab injuries to the chest and abdomen and was transported to the emergency department by ambulance. On arrival in the emergency department the patient was breathless and appeared pale. He was maintaining his airway with spontaneous breathing and had a heart rate of 122 beats per minute with a blood pressure of 83/63 mmHg. He was resuscitated initially with three units of packed red cells. Clinical examination identified three incisional wounds each measuring 2 cm. These were in the left para-sternal region, right infra-scapular region and left upper quadrant of the abdomen. The chest wound over the left parasternal area at the level of 4tth intercostal space was bleeding intermittently on leaning forwards and was relieving his breathlessness intermittently. CT imaging was performed to characterize his injuries and determine his management. CT scan of chest and abdomen showed moderate size haemopericardium with left sided haemopneumothorax. The patient underwent urgent surgical repair of the left ventricle and left anterior descending artery. He recovered without complications and was discharged from the hospital. This case highlights the fact that the potential to develop a life threatening cardiac tamponade was mitigated by the left parasternal stab wound. This injury fortuitously provided a pericardial window through which the bleeding from the injured left ventricle and left anterior descending artery could drain into the left hemithorax providing an opportunity for timely surgical intervention to repair the cardiac injuries.

Keywords: stab, incisional, haemo-pericardium, haemo-pneumothorax

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Authors: L. C. Prasanna, Antony Sylvan D’Souza, Kumar M. R. Bhat

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Although life as a conjoined twin would seem intolerable, there has recently been an increased interest in this subject because of the increasing number of cases where attempts have been made to separate them surgically. We have reviewed articles on cardiovascular anomalies in conjoined twins and presenting rarest anomaly in dicephalus parapagus fetus having two heads attached to one body from the neck or upper chest downwards, with a pair of limbs and a set of reproductive organs. Both the twins shared a common thoracic cavity with a single sternum. When the thoracic cavity was opened, a common anterior mediastinum was found. On opening the pericardium, two separate, closely apposed hearts were exposed. The two cardia are placed side by side. The left heart was slightly larger than the right and were joined at the atrial levels. Four atrial appendages were present, two for each twin. The atrial complex was a common chamber posterior to the ventricles. A single large tributary which could be taken as inferior vena cava drains into the common atrial chamber. In this case, the heart could not be assigned to either twin and therefore, it is referred to as the shared heart within a common pericardial sac. The right and left descending thoracic aorta have joined with each other just above the diaphragm to form a common descending thoracic aorta which has an opening in the diaphragm to be continued as common abdominal aorta which has a normal branching pattern. Upon an interior dissection, it is observed that the two atria have a wide communication which could be a wide patent foramen ovale and this common atrial cavity has a communication with a remnant of a possible common sinus venosus.

Keywords: atrium, congenital anomaly, conjoined twin, sinus venosus

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Authors: A. S. Lunev, A. A. Larenkov, O. E. Klementyeva, G. E. Kodina

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Background and aims: 68Ga-citrate is one of prospective radiopharmaceutical for PET-imaging of inflammation and infection. 68Ga-citrate is 67Ga-citrate analogue using since 1970s for SPECT-imaging. There's known rebinding reaction occurs past Ga-citrate injection and gallium (similar iron Fe3+) binds with blood transferrin. Then radiolabeled protein complex is delivered to pathological foci (inflammation/infection sites). But excessive gallium bindings with transferrin are cause of slow blood clearance, long accumulation time in foci (24-72 h) and exception of application possibility of the short-lived gallium-68 (T½ = 68 min). Injection of additional chemical agents (e.g. Fe3+ compounds) competing with radioactive gallium to the blood transferrin joining (blocking of its metal binding capacity) is one of the ways to solve formulated problem. This phenomenon can be used for correction of 68Ga-citrate pharmacokinetics for increasing of the blood clearance and accumulation in foci. The aim of real studying is research of effect of stable Fe-citrate on 68Ga-citrate tissue distribution. Materials and methods: 68Ga-citrate without/with extra injection of stable Fe-citrate (III) was injected nonlinear mice with inflammation models (aseptic soft tissue inflammation, lung infection, osteomyelitis). PET/X-RAY Genisys4 (Sofie Bioscience, USA) was used for non-invasive PET imaging (for 30, 60, 120 min past injection 68Ga-citrate) with subsequent reconstruction of imaging and their analysis (value of clearance, distribution volume). Scanning time is 10 min. Results and conclusions: I. v. injection of stable Fe-citrate blocks the metal-binding capability of transferrin serum and allows decreasing gallium-68 radioactivity in blood significantly and increasing accumulation in inflammation (3-5 time). It allows receiving more informative PET-images of inflammation early (for 30-60 min after injection). Pharmacokinetic parameters prove it. Noted there is no statistically significant difference between 68Ga-citrate accumulation for different inflammation model because PET imaging is indication of pathological processes and is not their identification.

Keywords: 68Ga-citrate, Fe-citrate, PET imaging, mice, inflammation, infection

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Authors: Alpana Meena

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Background: Tuberculosis is one of the major causes of death in south-east nations. Anti-TB–induced hepatotoxicity (AIH) is associated with a mortality of 6%–12%. The risk is increased when the drugs are combined. Reintroduction of anti-tuberculosis drugs in patients with AIH has never been studied systematically. The present study was planned to see the clinical profile of patients of AIH and the response to reintroduction of therapy. Methods: The trial was conducted in the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, on 32 patients with extra-pulmonary tuberculosis who developed AIH. Patients were randomly allocated into 3 groups. In group 1- Isoniazid (INH) and Rifampicin (RIF) were given at full dosages (weight calculated) from day 1. In group 2- RIF was given at maximum dosage from day 1 and INH at maximum dosage from day 8. In group 3- INH was given at maximum dosage from day 1 and RIF at maximum dosage from day 8. Pyrazinamide was added when above regimens were tolerated. Results: The mean age of presentation was 29.37±13.497 years. The incidence was found to be highest in patients with tubercular meningitis (41%) followed by abdominal, pericardial, disseminated, spinal, and lymph nodes. The mean latent period for development of AIH was 7.84 days ± 6.149 days and the median normalization days for LFT’s was 8.81 ± 4.22 days (3-21). In the study, 21% patients had recurrence of AIH with majority of patients having tolerated the reintroduction of drugs. Pyrazinamide was introduced after establishing isoniazid and rifampicin safety, thus emphasizing the role of gradual reintroduction of ATT to avoid the combined effects of hepatotoxicity. Conclusion: To conclude, the recurrence rate of hepatotoxicity was not statistically significant between the three groups studied (p > 0.05), and thus all 3 hepatotoxic drugs can be reintroduced safely in patients developing AIH.

Keywords: anti-tubercular therapy induced hepatotoxicity, extra-pulmonary tuberculosis, reintroduction regimens, risk factors

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