Search results for: alveolar epithelium
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 160

Search results for: alveolar epithelium

130 Immunomodulation by Interleukin-10 Therapy in Mouse Airway Transplantation

Authors: Mohammaad Afzal Khan, Ghazi Abdulmalik Ashoor , Fatimah Alanazi, Talal Shamma, Abdullah Altuhami, Hala Abdalrahman Ahmed, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Microvascular injuries during inflammation are key causes of transplant malfunctioning and permanent failure, which play a major role in the development of chronic rejection of the transplanted organ. Inflammation-induced microvascular loss is a promising area to investigate the decisive roles of regulatory and effector responses. The present study was designed to investigate the impact of IL-10 on immunotolerance, in particular, the microenvironment of the allograft during rejection. Here, we investigated the effects of IL-10 blockade/ reconstitution and serially monitored regulatory T cells (Tregs), graft microvasculature, and airway epithelium in rejecting airway transplants. We demonstrated that the blocking/reconstitution of IL-10 significantly modulates CD4+FOXP3+ Tregs, microvasculature, and airway epithelium during rejection. Our findings further highlighted that blockade of IL-10 upregulated proinflammatory cytokines, IL-2, IL-1β, IFN-γ, IL-15, and IL-23, but suppressed IL-5 secretion during rejection; however, reconstitution of IL-10 significantly upregulated CD4+FOXP3+ Tregs, tissue oxygenation/blood flow and airway repair. Collectively, these findings demonstrate a potential reparative modulation of IL-10 during microvascular and epithelial repair, which could provide a vital therapeutic window to rejecting transplants in clinical practice.

Keywords: interleukin -10, regulatory T cells, allograft rejection, immunotolerance

Procedia PDF Downloads 149
129 The Morphological Changes of POV in Diabetic Patients and Its Correlation with Changes in Corneal Epithelium, Corneal Nerve, and the Fundus in Using Vivo Confocal Microscopy

Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

Abstract:

Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

Procedia PDF Downloads 40
128 Horizontal Bone Augmentation Using Two Membranes at Dehisced Implant Sites: A Randomized Clinical Study

Authors: Monika Bansal

Abstract:

Background: Placement of dental implant in narrow alveolar ridge is challenging to be treated. GBR procedure is currently most widely used to augment the deficient alveolar ridges and to treat the fenestration and dehiscence around dental implants. Thus, the objectives of the present study were to evaluate as well as compare the clinical performance of collagen membrane and titanium mesh for horizontal bone augmentation at dehisced implant sites. Methods and material: Total 12 single edentulous implant sites with buccal bone deficiency in 8 subjects were equally divided and treated simultaneously with either of the two membranes and DBBM(Bio-Oss) bone graft. Primary outcome measurements in terms of defect height and defect width were made using a calibrated plastic periodontal probe. Re-entry surgery was performed to remeasure the augmented site and to remove Ti-mesh at 6th month. Independent paired t-tests for the inter-group comparison and student-paired t-tests for the intra-group comparison were performed. The differences were considered to be significant at p ≤ 0.05. Results: Mean defect fill with respect to height and width was 3.50 ± 0.54 mm (87%) and 2.33 ± 0.51 mm (82%) for collagen membrane and 3.83 ± 0.75 mm (92%) and 2.50 ± 0.54 mm (88%) for Ti-mesh group respectively. Conclusions: Within the limitation of the study, it was concluded that mean defect height and width after 6 months were statistically significant within the group without significant difference between them, although defect resolution was better in Ti-mesh.

Keywords: collagen membrane, dehiscence, dental implant, horizontal bone, augmentation, ti-mesh

Procedia PDF Downloads 81
127 Exposure Assessment for Worker Exposed to Heavy Metals during Road Marking Operations

Authors: Yin-Hsuan Wu, Perng-Jy Tsai, Ying-Fang Wang, Shun-Hui Chung

Abstract:

The present study was conducted to characterize exposure concentrations, concentrations deposited on the different respiratory regions, and resultant health risks associated with heavy metal exposures for road marking workers. Road marking workers of three similar exposure groups (SEGs) were selected, including the paint pouring worker, marking worker, and preparing worker. Personal exposure samples were collected using an inhalable dust sampler (IOM), and the involved particle size distribution samples were estimated using an eight-stage Marple personal cascade impactor during five working days. In total, 25 IOM samples and 20 Marple samples were collected. All collected samples were analyzed for their heavy metal contents using the ICP/MS. The resultant heavy metal particle size distributions were also used to estimate the fractions of particle deposited on the head airways (Chead), tracheobronchial (Cthorac) and alveolar regions (Cresp) of the exposed workers. In addition, Pb and Cr were selected to estimate the incremental cancer risk, and Zn, Ti, and Mo were selected to estimate the corresponding non-cancer risk in the present study. Results show that three heavy metals, including Pb, Cr, and Ti, were found with the highest concentrations for the SEG of the paint pouring worker (=0.585±2.98, 0.307±1.71, 0.902±2.99 μg/m³, respectively). For the fraction of heavy metal particle deposited on the respiratory tract, both alveolar and head regions were found with the highest values (=23-43% and 39-61%, respectively). For both SEGs of the paint pouring and marking, 51% of Cr, 59-61% of Zn, and 48-51% of Ti were found to be deposited on the alveolar region, and 41-43% of Pb was deposited on the head region. Finally, the incremental cancer risk for the SEGs of the paint pouring, marking, and preparing were found as 1.08×10⁻⁵, 2.78×10⁻⁶, and 2.20×10⁻⁶, respectively. In addition, the estimated non-cancer risk for the above three SEGs was found to be consistently less than unity. In conclusion, though the estimated non-cancer risk was less than unity, all resultant incremental cancer risk was greater than 10⁻⁶ indicating the abatement of workers’ exposure is necessary. It is suggested that strategies, including placing on the molten kettle, substitution the currently used paints for less heavy metal containing paints, and wearing fume protecting personal protective equipment can be considered in the future from reducing the worker’s exposure aspect.

Keywords: health risk assessment, heavy metal, respiratory track deposition, road marking

Procedia PDF Downloads 138
126 3D Simulation of Orthodontic Tooth Movement in the Presence of Horizontal Bone Loss

Authors: Azin Zargham, Gholamreza Rouhi, Allahyar Geramy

Abstract:

One of the most prevalent types of alveolar bone loss is horizontal bone loss (HBL) in which the bone height around teeth is reduced homogenously. In the presence of HBL the magnitudes of forces during orthodontic treatment should be altered according to the degree of HBL, in a way that without further bone loss, desired tooth movement can be obtained. In order to investigate the appropriate orthodontic force system in the presence of HBL, a three-dimensional numerical model capable of the simulation of orthodontic tooth movement was developed. The main goal of this research was to evaluate the effect of different degrees of HBL on a long-term orthodontic tooth movement. Moreover, the effect of different force magnitudes on orthodontic tooth movement in the presence of HBL was studied. Five three-dimensional finite element models of a maxillary lateral incisor with 0 mm, 1.5 mm, 3 mm, 4.5 mm and 6 mm of HBL were constructed. The long-term orthodontic tooth tipping movements were attained during a 4-weeks period in an iterative process through the external remodeling of the alveolar bone based on strains in periodontal ligament as the bone remodeling mechanical stimulus. To obtain long-term orthodontic tooth movement in each iteration, first the strains in periodontal ligament under a 1-N tipping force were calculated using finite element analysis. Then, bone remodeling and the subsequent tooth movement were computed in a post-processing software using a custom written program. Incisal edge, cervical, and apical area displacement in the models with different alveolar bone heights (0, 1.5, 3, 4.5, 6 mm bone loss) in response to a 1-N tipping force were calculated. Maximum tooth displacement was found to be 2.65 mm at the top of the crown of the model with a 6 mm bone loss. Minimum tooth displacement was 0.45 mm at the cervical level of the model with a normal bone support. Tooth tipping degrees of models in response to different tipping force magnitudes were also calculated for models with different degrees of HBL. Degrees of tipping tooth movement increased as force level was increased. This increase was more prominent in the models with smaller degrees of HBL. By using finite element method and bone remodeling theories, this study indicated that in the presence of HBL, under the same load, long-term orthodontic tooth movement will increase. The simulation also revealed that even though tooth movement increases with increasing the force, this increase was only prominent in the models with smaller degrees of HBL, and tooth models with greater degrees of HBL will be less affected by the magnitude of an orthodontic force. Based on our results, the applied force magnitude must be reduced in proportion of degree of HBL.

Keywords: bone remodeling, finite element method, horizontal bone loss, orthodontic tooth movement.

Procedia PDF Downloads 317
125 Ultrastructural Changes Occur in Mice Lungs After Cessation to Exposure of Incense Smoke

Authors: Samar Rabah

Abstract:

Background: Incense woods are special kind of trees called Agarwood, which characterized by good smelling odors and many medical benefits. Incense smoke is heavily used in Saudi Arabia although comprehensive studies of its effects on health are limited. The present study demonstrated lung ultrastructure changes of mice after exposure and cessation to Incense smoke. Eighty mice are divided equally into four groups, three groups are exposed to different concentrations of Incense smoke (2, 4 and 6 gm) for three months, while the fourth group is control one. At the end of each month, lungs of five animals from each group are gathered, while the last five animals from each group are kept for another 60 days without exposure to the Incense smoke to allow for recovery. Results: Transmission electron microscope investigations of all exposed groups showed hypertrophy and hyperplasia in Clara Cells and some an enlargement of the macrophage to the point that it fills a large part of the alveolar lumen. Scanning electron microscope marks presence of mucus materials attached to the epithelial bronchioles. After prevention of exposure to the Incense smoke for 60 days, necrosis and degeneration in some cells of epithelial bronchioles, fibrosis of peribronchial, thickening in alveolar walls and aggregation of lymphoid cells were demonstrated. Conclusion: Based on the above findings and other related studies (not published), we conclude that exposure to Incense smoke causes harmful effects due to sever changes in pulmonary ultrastructure, such effects do not disappear even when Incense smoke inhalation was stopped. Therefore, we recommend that Incense smoke should use only in open places to reduce its harms.

Keywords: Incense smoke, lungs, ultrastructure of lungs, Agarwood

Procedia PDF Downloads 386
124 Effect of Inspiratory Muscle Training on Diaphragmatic Strength Following Coronary Revascularization

Authors: Abeer Ahmed Abdelhamed

Abstract:

Introduction: Postoperative pulmonary complications (PPCs) are the most common complications observed and managed after abdominal or cardiothoracic surgery. Hypoxemia, atelectasis, pleural effusion, or diaphragmatic dysfunction, are often a source of morbidity in cardiac surgery patients, and are more common in patients receiving unilateral or bilateral internal mammary artery (IMT) grafts than patients receiving saphenous vein (SV) grafts alone. Purpose: The aim of this work was to investigate the effect of Threshold load inspiratory muscle training on pulmonary gas exchange and maximum inspiratory pressure (MIP) in patient undergoing coronary revascularization. Subject: Thirty three male patients eligible for coronary revascularization were selected to participate in the study. Method: They were divided into two groups(17 patients in the intervention group and 16 patients in the control group), the interventional group received inspiratory muscle training at 30% of their maximum inspiratory pressure throughout the hospitalization period in addition to routine post operative care. Result: The results of this study showed a significant improvement on maximum inspiratory pressure(MIP), Arterial-alveolar pressure gradient (A-a gradient) and oxygen saturation in the intervention group. Conclusion: Inspiratory muscle training using threshold mode significantly improves maximum inspiratory pressure, pulmonary gas exchange tested by alveolar-arterial gradient and oxygen saturation in Patients undergoing coronary revascularization.

Keywords: coronary revascularization, inspiratory muscle training, maximum inspiratory pressure, pulmonary gas exchange

Procedia PDF Downloads 274
123 The Long-Term Effects of Immediate Implantation, Early Implantation and Delayed Implantation at Aesthetics Area

Authors: Xing Wang, Lin Feng, Xuan Zou, Hongchen liu

Abstract:

Immediate Implantation after tooth extraction is considered to be the ideal way to retain the alveolar bone, but some scholars believe the aesthetic effect in the Early Implantation case are more reliable. In this study, 89 patients were added to this retrospective study up to 5 years. Assessment indicators was including the survival of the implant (peri-implant infection, implant loosening, shedding, crowns and occlusal), aesthetics (color and fullness gums, papilla height, probing depth, X-ray alveolar crest height, the patient's own aesthetic satisfaction, doctors aesthetics score), repair defects around the implant (peri-implant bone changes in height and thickness, whether the use of autologous bone graft, whether to use absorption/repair manual nonabsorbable material), treatment time, cost and the use of antibiotics.The results demonstrated that there is no significant difference in long-term success rate of immediate implantation, early implantation and delayed implantation (p> 0.05). But the results indicated immediate implantation group could get get better aesthetic results after two years (p< 0.05), but may increase the risk of complications and failures (p< 0.05). High-risk indicators include gingival recession, labial bone wall damage, thin gingival biotypes, planting position and occlusal restoration bad and so on. No matter which type of implanting methods was selected, the extraction methods and bone defect amplification techniques are observed as a significant factors on aesthetic effect (p< 0.05).

Keywords: immediate implantation, long-term effects, aesthetics area, dental implants

Procedia PDF Downloads 330
122 Effects of Achillea millefolium L. Extract on Rat Spermatogenesis

Authors: Nasrin Takzaree, Gholamreza Hassanzadeh, Abbas Hadjiakhoondi, Mohammadreza Rouini

Abstract:

Introduction: Today herbal medicine are extensively used for various therapeutic reasons. Whereas Achillea millefolium L. comprises different chemical compounds it is used in classic and modern medicine for different purposes. Concerning the family planning as a principle matter, the idea of using specific herbal medicine is of great importance. Purpose: To investigate the effects of Achillea millefolium L. extract on fertility power and spermatogenesis process in male mature Wistar rats and the anti-fertility effects of this extract in male genital system. Material and methods: In this study 32 male mature Wistar rats were randomly divided in to 4 experimental groups. 1st experimental group included 8 rats receiving Achillea millefolium extract at the dose of 200 mg/kg intraperitoneally. Second and third groups received the extract the same at the doses of 400 and 800 mg/kg respectively. 4th group was considered as control group in which the parenteral distilled water was administered. after 20 days, rats were sacrificed and the spermatogenesis process was histologically examined. Results: In experimental groups receiving high doses of extract comparing with control group, thickness in seminiferous tubules basal membrane, decrease in germinal epithelium cells, congestion in testicular tissue, disarrangement in germinal epithelium cells as well as decrease in cellular condense were observed (p<0.001). Conclusion: Findings suggest that alcoholic extract of Achillea millefolium at high concentrations lead to the structural alterations and changes in spermatogenesis in testicular tissue.

Keywords: spermatogenesis, alcoholic extract of Achillea millefolium L., testis, Wistar rat

Procedia PDF Downloads 558
121 Histological Changes of Mice Lungs After Daily Exposure to Different Concentration of Incense Smoke

Authors: Samar Omar A. Rabah, Sahar Ragab El Hadad, Fatmah Albani

Abstract:

Since the discovery of Agarwood (Incense tree), many studies reported its characteristic effects and variable benefits, as either to produce Arabian Incense or as a traditional medicine against many diseases. Laboratory experiments were carried out on the effect of different concentrations of Incense smoke inhalation on the lung weight and tissue in female mice. This research derives its importance from the fact that Incense is heavily used in Saudi Arabia in the absence of thorough studies of its effects on health. Eighty animals are used in this study, and they are divided into four groups, each is 20 animals. Three groups are exposed to different concentrations (2, 4 and 6 gm) of Incense smoke daily for three months, and the fourth group is the control. At the end of each month, five animals from each group were dissected. Obtained data showed an increase but not significant in animal body and lung weight, this results return to natural increase as a result of normal growth of animals. Light microscope reveals some changes in the lung tissue, such as focal emphysema, rupture in the alveolar walls, hemorrhage, congestion, edema and few peri-bronchial lymphoid cells. After continuous exposure to Incense smoke focal necrosis and degradation are observed in some cells of epithelial bronchioles. Also, fibrosis of peri-bronchial, thickening in alveolar walls and aggregation of lymphoid cells are demonstrated in some lungs sections. according to the above manifestations it could be concluded that exposure to Incense smoke causes pulmonary harmful effects. Therefore, we can recommend that Incense smoke will be used only in open places to reduce its harms.

Keywords: incense smoke, lungs, histological changes of lungs, agarwood

Procedia PDF Downloads 466
120 Dealing with the Spaces: Ultra Conservative Approach from Childhood to Adulthood

Authors: Maryam Firouzmandi, Moosa Miri

Abstract:

Common reasons for early tooth loss are trauma, extraction due to caries or periodontal disease and congenital missing. The remaining space after tooth loss may cause functional and esthetic problems. Therefore restorative dentists should attempt to manage these spaces using conservative methods. The goal is to restore the lost esthetic and function, prevent phonetic, self-esteem and personality problems and tongue habits. Preserving alveolar bone is also of great importance during the growth stage. Purpose: When deciding about the management of the missing tooth, space implants are contradicted until the completion of dentoalveolar development. Even in adulthood, due to systemic or periodontal problems or biological and economic issues, the implant might not be indicated. In this article, the alternative conservative restorative methods of space maintenance are going to be discussed. Essix retainers are made chair-side as easy as forming a custom bleaching tray with some modifications. They are esthetically acceptable and not expensive. These temporaries provide support for the lips but could not be used during function. Mini-screw-supported temporaries are another option for maintaining the space, especially after orthodontic treatment when there is a time lag between the termination of orthodontic treatment and definitive restoration. Two techniques will be presented for this kind of restoration: Denture tooth pontic or a composite crown. The benefits are alveolar bone preservation, Physiologic pressure on the alveolar ridge to increase its density and even can be retained until the completion of the definitive treatment. Bonded fixed partial denture includes Maryland bridge, fiber-reinforced composite bridge, resin-bonded bridge, and ceramic bonded bridge. These types of bridges are recommended to be used after a pubertal growth spurt and a recent meta-analysis considered their clinical success similar to conventional FDPs and implant-supported crowns. However, they have several advantages that are going to be discussed by presenting some clinical examples. Practical instruction on how to construct an FRC bridge and a novel chair-side Maryland bridge will be given by means of clinical cases. Clinical relevance: minimally invasive options should always be considered and destruction of healthy enamel and dentin during the preparation phase should be avoided as much as possible.

Keywords: tooth missing, fiber-reinforced composite, Maryland, Essix retainers, screw-retained restoration

Procedia PDF Downloads 172
119 Characteristics of the Particle Size Distribution and Exposure Concentrations of Nanoparticles Generated from the Laser Metal Deposition Process

Authors: Yu-Hsuan Liu, Ying-Fang Wang

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The objectives of the present study are to characterize nanoparticles generated from the laser metal deposition (LMD) process and to estimate particle concentrations deposited in the head (H), that the tracheobronchial (TB) and alveolar (A) regions, respectively. The studied LMD chamber (3.6m × 3.8m × 2.9m) is installed with a robot laser metal deposition machine. Direct-reading instrument of a scanning mobility particle sizer (SMPS, Model 3082, TSI Inc., St. Paul, MN, USA) was used to conduct static sampling inside the chamber for nanoparticle number concentration and particle size distribution measurements. The SMPS obtained particle number concentration at every 3 minutes, the diameter of the SMPS ranged from 11~372 nm when the aerosol and sheath flow rates were set at 0.6 and 6 L / min, respectively. The resultant size distributions were used to predict depositions of nanoparticles at the H, TB, and A regions of the respiratory tract using the UK National Radiological Protection Board’s (NRPB’s) LUDEP Software. Result that the number concentrations of nanoparticles in indoor background and LMD chamber were 4.8×10³ and 4.3×10⁵ # / cm³, respectively. However, the nanoparticles emitted from the LMD process was in the form of the uni-modal with number median diameter (NMD) and geometric standard deviation (GSD) as 142nm and 1.86, respectively. The fractions of the nanoparticles deposited on the alveolar region (A: 69.8%) were higher than the other two regions of the head region (H: 10.9%), tracheobronchial region (TB: 19.3%). This study conducted static sampling to measure the nanoparticles in the LMD process, and the results show that the fraction of particles deposited on the A region was higher than the other two regions. Therefore, applying the characteristics of nanoparticles emitted from LMD process could be provided valuable scientific-based evidence for exposure assessments in the future.

Keywords: exposure assessment, laser metal deposition process, nanoparticle, respiratory region

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118 Correlation between Cephalometric Measurements and Visual Perception of Facial Profile in Skeletal Type II Patients

Authors: Choki, Supatchai Boonpratham, Suwannee Luppanapornlarp

Abstract:

The objective of this study was to find a correlation between cephalometric measurements and visual perception of facial profile in skeletal type II patients. In this study, 250 lateral cephalograms of female patients from age, 20 to 22 years were analyzed. The profile outlines of all the samples were hand traced and transformed into silhouettes by the principal investigator. Profile ratings were done by 9 orthodontists on Visual Analogue Scale from score one to ten (increasing level of convexity). 37 hard issue and soft tissue cephalometric measurements were analyzed by the principal investigator. All the measurements were repeated after 2 weeks interval for error assessment. At last, the rankings of visual perceptions were correlated with cephalometric measurements using Spearman correlation coefficient (P < 0.05). The results show that the increase in facial convexity was correlated with higher values of ANB (A point, nasion and B point), AF-BF (distance from A point to B point in mm), L1-NB (distance from lower incisor to NB line in mm), anterior maxillary alveolar height, posterior maxillary alveolar height, overjet, H angle hard tissue, H angle soft tissue and lower lip to E plane (absolute correlation values from 0.277 to 0.711). In contrast, the increase in facial convexity was correlated with lower values of Pg. to N perpendicular and Pg. to NB (mm) (absolute correlation value -0.302 and -0.294 respectively). From the soft tissue measurements, H angles had a higher correlation with visual perception than facial contour angle, nasolabial angle, and lower lip to E plane. In conclusion, the findings of this study indicated that the correlation of cephalometric measurements with visual perception was less than expected. Only 29% of cephalometric measurements had a significant correlation with visual perception. Therefore, diagnosis based solely on cephalometric analysis can result in failure to meet the patient’s esthetic expectation.

Keywords: cephalometric measurements, facial profile, skeletal type II, visual perception

Procedia PDF Downloads 114
117 Airborne Pollutants and Lung Surfactant: Biophysical Impacts of Surface Oxidation Reactions

Authors: Sahana Selladurai, Christine DeWolf

Abstract:

Lung surfactant comprises a lipid-protein film that coats the alveolar surface and serves to prevent alveolar collapse upon repeated breathing cycles. Exposure of lung surfactant to high concentrations of airborne pollutants, for example tropospheric ozone in smog, can chemically modify the lipid and protein components. These chemical changes can impact the film functionality by decreasing the film’s collapse pressure (minimum surface tension attainable), altering it is mechanical and flow properties and modifying lipid reservoir formation essential for re-spreading of the film during the inhalation process. In this study, we use Langmuir monolayers spread at the air-water interface as model membranes where the compression and expansion of the film mimics the breathing cycle. The impact of ozone exposure on model lung surfactant films is measured using a Langmuir film balance, Brewster angle microscopy and a pendant drop tensiometer as a function of film and sub-phase composition. The oxidized films are analyzed using mass spectrometry where lipid and protein oxidation products are observed. Oxidation is shown to reduce surface activity, alter line tension (and film morphology) and in some cases visibly reduce the viscoelastic properties of the film when compared to controls. These reductions in functionality of the films are highly dependent on film and sub-phase composition, where for example, the effect of oxidation is more pronounced when using a physiologically relevant buffer as opposed to water as the sub-phase. These findings can lead to a better understanding on the impact of continuous exposure to high levels of ozone on the mechanical process of breathing, as well as understanding the roles of certain lung surfactant components in this process.

Keywords: lung surfactant, oxidation, ozone, viscoelasticity

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116 The Investigation of Effect of Alpha Lipoic Acid against Damage on Neonatal Rat Lung to Maternal Tobacco Smoke Exposure

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

Abstract:

This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

Procedia PDF Downloads 183
115 The Correlation between Clostridium Difficile Infection and Bronchial Lung Cancer Occurrence

Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

Abstract:

Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

Procedia PDF Downloads 199
114 Influence of Smoking on Fine And Ultrafine Air Pollution Pm in Their Pulmonary Genetic and Epigenetic Toxicity

Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

Abstract:

In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

Procedia PDF Downloads 320
113 Development of the Squamate Egg Tooth on the Basis of Grass Snake Natrix natrix Studies

Authors: Mateusz Hermyt, Pawel Kaczmarek, Weronika Rupik

Abstract:

The egg tooth is a crucial structure during hatching of lizards and snakes. In contrast to birds, turtles, crocodiles, and monotremes, egg tooth of squamate reptiles is a true tooth sharing common features of structure and development with all the other teeth of vertebrates. The egg tooth; however, due to its function, exhibits structural differences in relation to regular teeth. External morphology seems to be important in the context of phylogenetic relationships within Squamata but up to date, there is scarce information concerning structure and development of the egg tooth at the submicroscopical level. In presented studies detailed analysis of the egg tooth development in grass snake has been performed with the usage of light (including fluorescent), transmission and scanning electron microscopy. Grass snake embryo’s heads have been used in our studies. Grass snake is common snake species occurring in most of Europe including Poland. The grass snake is characterized by the presence of single unpaired egg tooth (as in most squamates) in contrast to geckos and dibamids possessing paired egg teeth. Studies show changes occurring on the external morphology, tissue and cellular levels of differentiating egg tooth. The egg tooth during its development changes its curvature. Initially, faces directly downward and in the course of its differentiation, it gradually changes to rostro-ventral orientation. Additionally, it forms conical dentinal protrusions on the sides. Histological analysis showed that egg tooth development occurs in similar steps in relation to regular teeth. It undergoes initiation, bud, cap and bell morphological stages. Analyses focused on describing morphological changes in hard tissues (mainly dentin and predentin) of egg tooth and in cells which enamel organ consists of. It included: outer enamel epithelium, stratum intermedium, inner enamel epithelium, odontoblasts, and cells of dental pulp. All specimens used in the study were captured according to the Polish regulations concerning the protection of wild species. Permission was granted by the Local Ethics Commission in Katowice (41/2010; 87/2015) and the Regional Directorate for Environmental Protection in Katowice (WPN.6401.257.2015.DC).

Keywords: hatching, organogenesis, reptile, Squamata

Procedia PDF Downloads 155
112 SockGEL/PLUG: Injectable Nano-Scaled Hydrogel Platforms for Oral and Maxillofacial Interventional Application

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 84
111 Aquaporin-1 as a Differential Marker in Toxicant-Induced Lung Injury

Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

Abstract:

Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

Procedia PDF Downloads 152
110 A 3d Intestine-On-Chip Model Allows Colonization with Commensal Bacteria to Study Host-Microbiota Interaction

Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

Abstract:

The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

Procedia PDF Downloads 106
109 A Minimally Invasive Approach Using Bio-Miniatures Implant System for Full Arch Rehabilitation

Authors: Omid Allan

Abstract:

The advent of ultra-narrow diameter implants initially offered an alternative to wider conventional implants. However, their design limitations have restricted their applicability primarily to overdentures and cement-retained fixed prostheses, often with unpredictable long-term outcomes. The introduction of the new Miniature Implants has revolutionized the field of implant dentistry, leading to a more streamlined approach. The utilization of Miniature Implants has emerged as a promising alternative to the traditional approach that entails the traumatic sequential bone drilling procedures and the use of conventional implants for full and partial arch restorations. The innovative "BioMiniatures Implant System serves as a groundbreaking bridge connecting mini implants with standard implant systems. This system allows practitioners to harness the advantages of ultra-small implants, enabling minimally invasive insertion and facilitating the application of fixed screw-retained prostheses, which were only available to conventional wider implant systems. This approach streamlines full and partial arch rehabilitation with minimal or even no bone drilling, significantly reducing surgical risks and complications for clinicians while minimizing patient morbidity. The ultra-narrow diameter and self-advancing features of these implants eliminate the need for invasive and technically complex procedures such as bone augmentation and guided bone regeneration (GBR), particularly in cases involving thin alveolar ridges. Furthermore, the absence of a microcap between the implant and abutment eliminates the potential for micro-leakage and micro-pumping effects, effectively mitigating the risk of marginal bone loss and future peri-implantitis. The cumulative experience of restoring over 50 full and partial arch edentulous cases with this system has yielded an outstanding success rate exceeding 97%. The long-term success with a stable marginal bone level in the study firmly establishes these implants as a dependable alternative to conventional implants, especially for full arch rehabilitation cases. Full arch rehabilitation with these implants holds the promise of providing a simplified solution for edentulous patients who typically present with atrophic narrow alveolar ridges, eliminating the need for extensive GBR and bone augmentation to restore their dentition with fixed prostheses.

Keywords: mini-implant, biominiatures, miniature implants, minimally invasive dentistry, full arch rehabilitation

Procedia PDF Downloads 44
108 Calcium Release- Activated Calcium Channels as a Target in Treatment of Allergic Asthma

Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

Abstract:

Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

Procedia PDF Downloads 497
107 iPSC-derived MSC Mediated Immunosuppression during Mouse Airway Transplantation

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

Procedia PDF Downloads 131
106 Studies on the Histomorphometry of the Digestive Tract and Associated Digestive Glands in Ostrich (Struthio camelus) with Gender and Progressing Age in Pakistan

Authors: Zaima Umar, Anas S. Qureshi, Adeel Sarfraz, Saqib Umar, Talha Umar, Muhammad Usman

Abstract:

Ostrich has been a good source of food and income for people across the world. To get a better understanding of health and health-related problems, the knowledge of its digestive system is of utmost importance. The present study was conducted to determine the morphological and histometrical variations in the digestive system and associated glands of ostrich (Struthio camelus) as regard to the gender and progressive age. A total of 40 apparently healthy ostriches of both genders and two progressive age groups; young one (less than two year, group A); and adult (2-15 years, group B) in equal number were used in this study. Digestive organs including tongue, esophagus, proventriculus, gizzard, small and large intestines and associated glands like liver and pancreas were collected immediately after slaughtering the birds. The organs of the digestive system and associated glands of each group were studied grossly and histologically. Grossly colour, shape consistency, weight and various dimensions (length, width, and circumference) of organs of the digestive tract and associated glands were recorded. The mean (± SEM) of all gross anatomical parameters in group A were significantly (p ≤ 0.01) different from that of group B. For microscopic studies, 1-2 cm tissue samples of organs of the digestive system and associated glands were taken. The tissue was marked and fixed in the neutral buffer formaldehyde solution for histological studies. After fixation, the sections of 5-7 µm were cut and stained by haematoxylin and eosin stain. All the layers (epithelium, lamina propria, lamina muscularis, submucosa and tunica muscularis) were measured (µm) with the help of automated computer software Image J®. The results of this study provide valuable information on the gender and age-related histological and histometrical variations in the digestive organs of ostrich (Struthio camelus). The microscopic studies of different parts of the digestive system revealed highly significant differences (p ≤ 0.01) among the two groups. The esophagus was lined by non-keratinized stratified squamous epithelium. The duodenum, jejunum, and ileum showed similar histological structures. Statistical analysis revealed significant (p ≤ 0.05) increase in the thickness of different tunics of the gastrointestinal tract in adult birds (up to 15 years) as compared with young ones (less than two years). Therefore, it can be concluded that there is a gradual but consistent growth in the observed digestive organs mimicking that of other poultry species and may be helpful in determining the growth pattern in this bird. However, there is a need to record the changes at closer time intervals.

Keywords: ostrich, digestive system, histomorphometry, grossly

Procedia PDF Downloads 119
105 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure

Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

Abstract:

Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: autophagy, cell death, digestive system, ultrastructure

Procedia PDF Downloads 208
104 “SockGEL/PLUG” Injectable Smart/Intelligent and Bio-Inspired Sol-Gel Nanomaterials for Simple and Complex Oro-Dental and Cranio-Maxillo-Facial Interventional Applications

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 42
103 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 484
102 Effect of Different Local Anesthetic Agents on Physiological Parameters and Vital Signs during Extraction in Children

Authors: Rasha F. Sharaf

Abstract:

Administration of local anesthesia for a child is considered a painful procedure, which affects his vital signs, physiological parameters, and his further attitude in the dental clinic. During the extraction of mandibular molars, the nerve block technique is the most commonly used for the administration of local anesthesia; however, this technique requires deep penetration of the needle, which causes pain and discomfort for the child. Therefore, the inferior alveolar nerve block technique can be substituted with an infiltration technique which is not painful if a potent anesthetic solutions will be used. In the current study, the effect of Articaine 4% will be compared to Mepivacaine 2%, and their influence on the vital signs of the child, as well as their ability to control pain during extraction, will be assessed.

Keywords: anesthesia, articaine, pain control, extraction

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101 Post-Hatching Development of the Cloacal Bursa in Chicken

Authors: Fatimah A. Alhomaid

Abstract:

A total of 40 one day-old LSL chicks (Lohman Selected Loghorn) were used in this study. In 20 days-old chicks, the bursa was formed of mucosa, musculosa and serosa. Its lamina propria was lymphoid in nature. After hatching, the bursa continued to grow and became fully developed at the 30th day post- hatching. It appeared as a blind sac. Its lumen was occupied by 12-13 mucosal folds. Each fold was lined by tall columnar or pseudo- stratified columnar epithelium. Its core was made of lamina propria infiltrated by a large number of lymphoid follicles. Most follicles possessed an outer corona surrounding a germinal center. At the age of 6 weeks physiological regression of the bursa was observed. The lymphoid follicles were decreased in size, the lymphocytes were depleted and the interfollicular stroma became obvious, thicker and more fibrous. Fibrosis of the lymphoid follicles was frequently seen in some sections at the age of 30 weeks.

Keywords: Bursa of fabricius, lymphocytes, cloacal Bursa

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