Search results for: stem cell therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5876

Search results for: stem cell therapy

4466 Solid-State Luminescence of Fluorenone Grafted onto Cellulose Aldehyde Backbone Using Different Organic Amine Spacers

Authors: Isam M. Arafa, Mazin Y. Shatnawi, Yaser A. Yousef, Batool Zaid Al-Momani

Abstract:

The present work describes the preparation, characterization, and luminescence of a series of fluorenone (FL) based luminophores grafted onto modified cellulose microfibers. The FL is condensed onto cellulose aldehyde using three diamine spacers (H₂N-NH₂, H₂N(CH₂)₂NH₂ and H₂N(CH₂)₃NH₂) to afford Cell=Spacer=FL. The obtained products were characterized by spectroscopic (FT-IR, UV–Vis), thermal gravimetric analysis (TGA), and microscopic (Optical, SEM) techniques. The UV-Vis spectra of the FL=N(CH₂)ₓNH₂ (x = 0, 2, 3) moieties show that they are transparent in the 375- 800 nm region while they exhibit intense absorption band below 350 nm attributed to n-π* and π-π* transitions. The solid-state photoluminescence (PLs-s) of the cold-pressed pellets of the FL=N(CH₂)ₓNH₂ and Cell=Spacer=FL placed in a quartz cuvette show strong emission in the 500-550 nm region upon irradiation with Xe lamp light (λex = 320 nm). The PLs-s green emission of the grafted Cell=Spacer=FL was evaluated relative to that of the FL-based precursor. These grafted conjugated products have the potential to be used as analyte sensors for typical nitroaromatics/aromatic amines and be further extended to immunoassay studies for aromatic amino acids such as phenylalanine and histidine.

Keywords: luminescence, cellulose, fluorenone, grafting, solid state

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4465 Influence of Pretreatment Magnetic Resonance Imaging on Local Therapy Decisions in Intermediate-Risk Prostate Cancer Patients

Authors: Christian Skowronski, Andrew Shanholtzer, Brent Yelton, Muayad Almahariq, Daniel J. Krauss

Abstract:

Prostate cancer has the third highest incidence rate and is the second leading cause of cancer death for men in the United States. Of the diagnostic tools available for intermediate-risk prostate cancer, magnetic resonance imaging (MRI) provides superior soft tissue delineation serving as a valuable tool for both diagnosis and treatment planning. Currently, there is minimal data regarding the practical utility of MRI for evaluation of intermediate-risk prostate cancer. As such, the National Comprehensive Cancer Network’s guidelines indicate MRI as optional in intermediate-risk prostate cancer evaluation. This project aims to elucidate whether MRI affects radiation treatment decisions for intermediate-risk prostate cancer. This was a retrospective study evaluating 210 patients with intermediate-risk prostate cancer, treated with definitive radiotherapy at our institution between 2019-2020. NCCN risk stratification criteria were used to define intermediate-risk prostate cancer. Patients were divided into two groups: those with pretreatment prostate MRI, and those without pretreatment prostate MRI. We compared the use of external beam radiotherapy, brachytherapy alone, brachytherapy boost, and androgen depravation therapy between the two groups. Inverse probability of treatment weighting was used to match the two groups for age, comorbidity index, American Urologic Association symptoms index, pretreatment PSA, grade group, and percent core involvement on prostate biopsy. Wilcoxon Rank Sum and Chi-squared tests were used to compare continuous and categorical variables. Of the patients who met the study’s eligibility criteria, 133 had a prostate MRI and 77 did not. Following propensity matching, there were no differences between baseline characteristics between the two groups. There were no statistically significant differences in treatments pursued between the two groups: 42% vs 47% were treated with brachytherapy alone, 40% vs 42% were treated with external beam radiotherapy alone, 18% vs 12% were treated with external beam radiotherapy with a brachytherapy boost, and 24% vs 17% received androgen deprivation therapy in the non-MRI and MRI groups, respectively. This analysis suggests that pretreatment MRI does not significantly impact radiation therapy or androgen deprivation therapy decisions in patients with intermediate-risk prostate cancer. Obtaining a pretreatment prostate MRI should be used judiciously and pursued only to answer a specific question, for which the answer is likely to impact treatment decision. Further follow up is needed to correlate MRI findings with their impacts on specific oncologic outcomes.

Keywords: magnetic resonance imaging, prostate cancer, definitive radiotherapy, gleason score 7

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4464 Periodontal Disease or Cement Disease: New Frontier in the Treatment of Periodontal Disease in Dogs

Authors: C. Gallottini, W. Di Mari, A. Amaddeo, K. Barbaro, A. Dolci, G. Dolci, L. Gallottini, G. Barraco, S. Eramo

Abstract:

A group of 10 dogs (group A) with Periodontal Disease in the third stage, were subjected to regenerative therapy of periodontal tissues, by use of nano hydroxy apatite (NHA). These animals induced by general anesthesia, where treated by ultrasonic scaling, root planning, and at the end by a mucogingival flap in which it was applied NHA. The flap was closed and sutured with simple steps. Another group of 10 dogs (group B), control group, was treated only by scaling and root planning. No patient was subjected to antibiotic therapy. After three months, a check was made by inspection of the oral cavity, radiography and bone biopsy at the alveolar level. Group A showed a total restitutio ad integrum of the periodontal structures, and in group B still mild gingivitis in 70% of cases and 30% of the state remains unchanged. Numerous experimental studies both in animals and humans have documented that the grafts of porous hydroxyapatite are rapidly invaded by fibrovascular tissue which is subsequently converted into mature lamellar bone tissue by activating osteoblast. Since we acted on the removal of necrotic cementum and rehabilitating the root tissue by polishing without intervention in the ligament but only on anatomical functional interface of cement-blasts, we can connect the positive evolution of the clinical-only component of the cement that could represent this perspective, the only reason that Periodontal Disease become a Cement Disease, while all other clinical elements as nothing more than a clinical pathological accompanying.

Keywords: nanoidroxiaphatite, parodontal disease, cement disease, regenerative therapy

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4463 Acceptance and Commitment Therapy as a Treatment for Alcohol Use Disorders in South Korea

Authors: Kim Eunha

Abstract:

This study examined a group-based intervention for alcohol use disorders based on the principles of acceptance and commitment therapy (ACT) in patients (N=22; 63.7% female; M = 38.2 years old; 100% South Korean) in a residential alcohol addiction treatment program. Patients were randomly assigned to either ACT group (receiving the ACT intervention) or control group (receiving treatment as usual). The ACT intervention consisted of four 2-hr group sessions scheduled during two weeks. The first session focused on the negative effects of suppression and avoidance, and a rationale for defusion and acceptance using several of the well-known ACT metaphors (e.g., Two Scales Metaphor, Man in the Hole). The second session taught defusion and acceptance skills through such exercises as mindfulness, cutting a sour fruit, naming one’s thoughts, and physicalizing. The third session included another mindfulness exercise and encouraged the participants to identify their values and set up life goals. The last session included more discussion on values and life goals, especially related to family and intimacy. The effects of the interventions were assessed using intent-to-treat analyses. The ACT interventions resulted in smaller immediate gains in motivation to stay sober and reductions in depression, anxiety, and experiential avoidance. In addition, at a 2-month follow up, those who attended the ACT group reported a lower average level of alcohol consumption and higher treatment attendance compared to the control group. These preliminary findings suggest that additional treatment and testing of ACT for alcohol use disorders will be crucial.

Keywords: acceptance and commitment therapy, alcohol use disorders, defusion, values

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4462 Colocalization Analysis to Understand Yttrium Uptake in Saxifraga paniculata Using Complementary Imaging Technics

Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose

Abstract:

Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.

Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium

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4461 Biogeography Based CO2 and Cost Optimization of RC Cantilever Retaining Walls

Authors: Ibrahim Aydogdu, Alper Akin

Abstract:

In this study, the development of minimizing the cost and the CO2 emission of the RC retaining wall design has been performed by Biogeography Based Optimization (BBO) algorithm. This has been achieved by developing computer programs utilizing BBO algorithm which minimize the cost and the CO2 emission of the RC retaining walls. Objective functions of the optimization problem are defined as the minimized cost, the CO2 emission and weighted aggregate of the cost and the CO2 functions of the RC retaining walls. In the formulation of the optimum design problem, the height and thickness of the stem, the length of the toe projection, the thickness of the stem at base level, the length and thickness of the base, the depth and thickness of the key, the distance from the toe to the key, the number and diameter of the reinforcement bars are treated as design variables. In the formulation of the optimization problem, flexural and shear strength constraints and minimum/maximum limitations for the reinforcement bar areas are derived from American Concrete Institute (ACI 318-14) design code. Moreover, the development length conditions for suitable detailing of reinforcement are treated as a constraint. The obtained optimum designs must satisfy the factor of safety for failure modes (overturning, sliding and bearing), strength, serviceability and other required limitations to attain practically acceptable shapes. To demonstrate the efficiency and robustness of the presented BBO algorithm, the optimum design example for retaining walls is presented and the results are compared to the previously obtained results available in the literature.

Keywords: bio geography, meta-heuristic search, optimization, retaining wall

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4460 Management of Renal Malignancies with IVC Thrombus: Our Experience

Authors: Sujeet Poudyal

Abstract:

Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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4459 The Biochemical and Radiographic Evaluation of the Non-Metastatic Bone Disease in Patients with Renal Cell Carcinoma Undergoing Hemodialysis

Authors: Aliakbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi

Abstract:

Background: Bones are commonly affected by renal cell carcinoma (RCC) (primarily or secondary), and this condition causes bone fragility. The aim of this study was to evaluate the diagnostic value of noninvasive methods for the diagnosis of ROD in RCC patients on hemodialysis (HD) in northern Iran. Methods: In this cross-sectional study, 50 RCC patients with ESRD referred to dialysis units in northern Iran during 2021-2024 were randomly selected and investigated. The biochemical and radiographic evaluation of ROD and its subtypes was performed, and then all patients underwent bone biopsy and histopathological study, and finally, the diagnostic value of the noninvasive methods was assessed. Results: The mean age of patients was 58.9 ± 11.7 years, and 27 cases (54.0%) were female. 38 (76.0%) of RCC patients with ESRD had ROD, and 12 patients (24.0%) had no evidence of bone disorders. The sensitivity, specificity, positive and predictive values and accuracy of the noninvasive methods for the diagnosis of ROD were 92%, 82%, 95%, 75% and 90%, respectively. Conclusion: This study showed that the frequency of ROD in RCC patients with ESRD in northern Iran was high and the biochemical and radiographic markers have a high diagnostic value for ROD as well as histopathological assessment.

Keywords: renal cell carcinoma, renal osteodystrophy, hemodialysis, non-metastatic

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4458 Non-Steroidal Microtubule Disrupting Analogues Induce Programmed Cell Death in Breast and Lung Cancer Cell Lines

Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

Abstract:

A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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4457 Blood Clot Emulsification via Ultrasonic Thrombolysis Device

Authors: Sun Tao, Lou Liang, Tan Xing Haw Marvin, Gu Yuandong Alex

Abstract:

Patients with blood clots in their brains can experience problems with their vision or speech, seizures and general weakness. To treat blood clots, clinicians presently have two options. The first involves drug therapy to thin the blood and thus reduce the clot. The second choice is to invasively remove the clot using a plastic tube called a catheter. Both approaches carry a high risk of bleeding, and invasive procedures, such as catheter intervention, can also damage the blood vessel wall and cause infection. Ultrasonic treatment as a potential alternative therapy to break down clots is attracting growing interests due to the reduced adverse effects. To demonstrate the concept, in this investigation a microfabricated ultrasonic device was electrically packaged with printed circuit board to treat healthy human blood. The red blood cells could be broken down after 3-hour ultrasonic treatment.

Keywords: microfabrication, blood clot, ultrasonic thrombolysis device, ultrasonic device

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4456 Preventing the Septic Shock in an Oncological Patient with Febrile Neutropenia Submitted to Chemotherapy: The Nurse's Responsibility

Authors: Hugo Reis, Isabel Rabiais

Abstract:

The main purpose of the present study is to understand the nurse’s responsibility in preventing the septic shock in an oncological patient with febrile neutropenia submitted to chemotherapy. In order to do it, an integrative review of literature has been conducted. In the research done in many databases, it was concluded that only 7 out of 5202 articles compiled the entire inclusion standard present in the strict protocol of research, being this made up by all different methodologies. On the research done in the 7 articles it has resulted 8 text macro-units associated to different nursing interventions: ‘Health Education’; ‘Prophylactic Therapy Administration’; ‘Scales Utilization’; ‘Patient Evaluation’; ‘Environment Control’; ‘Performance of Diagnostic Auxiliary Exams’; ‘Protocol Enforcement/Procedure Guidelines’; ‘Antibiotic Therapy Administration’. Concerning the prevalence/result’s division there can be identified many conclusions: the macro-units ‘Patient Evaluation’, ‘Performance of Diagnostic Auxiliary Exams’, and ‘Antibiotic Therapy Administration’ present themselves to be the most prevalent in the research – 6 in 7 occurrences (approximately 85.7%). Next, the macro-unit ‘Protocol Enforcement/Procedure Guidelines’ presents itself as an important expression unit – being part of 5 out of the 7 analyzed studies (approximately 71.4%). The macro-unit ‘Health Education’, seems to be in the same way, an important expression unit – 4 out of the 7 (or approximately 57%). The macro-unit ‘Scales Utilization’, represents a minor part in the research done – it’s in only 2 out of the 7 cases (approximately 28.6%). On the other hand, the macro-units ‘Prophylactic Therapy Administration’ and ‘Environment Control’ are the two categories with fewer results in the research - 1 out of the 7 cases, the same as approximately 14.3% of the research results. Every research done to the macro-unit ‘Antibiotic Therapy Administration’ agreed to refer that the intervention should be strictly done, in a period of time less than one hour after diagnosing the fever, with the purpose of controlling the quick spread of infection – minimizing its seriousness. Identifying these interventions contributes, concluding that, to adopt strategies in order to prevent the phenomenon that represents a daily scenario responsible for the cost´s increase in health institutions, being at the same time responsible for the high morbidity rates and mortality increase associated with this specific group of patients.

Keywords: febrile neutropenia, oncology nursing, patient, septic shock

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4455 Clinician's Perspective of Common Factors of Change in Family Therapy: A Cross-National Exploration

Authors: Hassan Karimi, Fred Piercy, Ruoxi Chen, Ana L. Jaramillo-Sierra, Wei-Ning Chang, Manjushree Palit, Catherine Martosudarmo, Angelito Antonio

Abstract:

Background: The two psychotherapy camps, the randomized clinical trials (RCTs) and the common factors model, have competitively claimed specific explanations for therapy effectiveness. Recently, scholars called for empirical evidence to show the role of common factors in therapeutic outcome in marriage and family therapy. Purpose: This cross-national study aims to explore how clinicians, across different nations and theoretical orientations, attribute the contribution of common factors to therapy outcome. Method: A brief common factors questionnaire (CFQ-with a Cronbach’s Alpha, 0.77) was developed and administered in seven nations. A series of statistical analyses (paired-samples t-test, independent sample t-test, ANOVA) were conducted: to compare clinicians perceived contribution of total common factors versus model-specific factors, to compare each pair of common factors’ categories, and to compare clinicians from collectivistic nations versus clinicians from individualistic nation. Results: Clinicians across seven nations attributed 86% to common factors versus 14% to model-specific factors. Clinicians attributed 34% of therapeutic change to client’s factors, 26% to therapist’s factors, 26% to relationship factors, and 14% to model-specific techniques. The ANOVA test indicated each of the three categories of common factors (client 34%, therapist 26%, relationship 26%) showed higher contribution in therapeutic outcome than the category of model specific factors (techniques 14%). Clinicians with psychology degree attributed more contribution to model-specific factors than clinicians with MFT and counseling degrees who attributed more contribution to client factors. Clinicians from collectivistic nations attributed larger contributions to therapist’s factors (M=28.96, SD=12.75) than the US clinicians (M=23.22, SD=7.73). The US clinicians attributed a larger contribution to client’s factors (M=39.02, SD=1504) than clinicians from the collectivistic nations (M=28.71, SD=15.74). Conclusion: The findings indicate clinicians across the globe attributed more than two thirds of therapeutic change to CFs, which emphasize the training of the common factors model in the field. CFs, like model-specific factors, vary in their contribution to therapy outcome in relation to specific client, therapist, problem, treatment model, and sociocultural context. Sociocultural expectations and norms should be considered as a context in which both CFs and model-specific factors function toward therapeutic goals. Clinicians need to foster a cultural competency specifically regarding the divergent ways that CFs can be activated due to specific sociocultural values.

Keywords: common factors, model-specific factors, cross-national survey, therapist cultural competency, enhancing therapist efficacy

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4454 Comparison of Water Equivalent Ratio of Several Dosimetric Materials in Proton Therapy Using Monte Carlo Simulations and Experimental Data

Authors: M. R. Akbari , H. Yousefnia, E. Mirrezaei

Abstract:

Range uncertainties of protons are currently a topic of interest in proton therapy. Two of the parameters that are often used to specify proton range are water equivalent thickness (WET) and water equivalent ratio (WER). Since WER values for a specific material is nearly constant at different proton energies, it is a more useful parameter to compare. In this study, WER values were calculated for different proton energies in polymethyl methacrylate (PMMA), polystyrene (PS) and aluminum (Al) using FLUKA and TRIM codes. The results were compared with analytical, experimental and simulated SEICS code data obtained from the literature. In FLUKA simulation, a cylindrical phantom, 1000 mm in height and 300 mm in diameter, filled with the studied materials was simulated. A typical mono-energetic proton pencil beam in a wide range of incident energies usually applied in proton therapy (50 MeV to 225 MeV) impinges normally on the phantom. In order to obtain the WER values for the considered materials, cylindrical detectors, 1 mm in height and 20 mm in diameter, were also simulated along the beam trajectory in the phantom. In TRIM calculations, type of projectile, energy and angle of incidence, type of target material and thickness should be defined. The mode of 'detailed calculation with full damage cascades' was selected for proton transport in the target material. The biggest difference in WER values between the codes was 3.19%, 1.9% and 0.67% for Al, PMMA and PS, respectively. In Al and PMMA, the biggest difference between each code and experimental data was 1.08%, 1.26%, 2.55%, 0.94%, 0.77% and 0.95% for SEICS, FLUKA and SRIM, respectively. FLUKA and SEICS had the greatest agreement (≤0.77% difference in PMMA and ≤1.08% difference in Al, respectively) with the available experimental data in this study. It is concluded that, FLUKA and TRIM codes have capability for Bragg curves simulation and WER values calculation in the studied materials. They can also predict Bragg peak location and range of proton beams with acceptable accuracy.

Keywords: water equivalent ratio, dosimetric materials, proton therapy, Monte Carlo simulations

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4453 Pattern of Anisometropia, Management and Outcome of Anisometropic Amblyopia

Authors: Husain Rajib, T. H. Sheikh, D. G. Jewel

Abstract:

Background: Amblyopia is a frequent cause of monocular blindness in children. It can be unilateral or bilateral reduction of best corrected visual acuity associated with decrement in visual processing, accomodation, motility, spatial perception or spatial projection. Anisometropia is an important risk factor for amblyopia that develops when unequal refractive error causes the image to be blurred in the critical developmental period and central inhibition of the visual signal originating from the affected eye associated with significant visual problems including anisokonia, strabismus, and reduced stereopsis. Methods: It is a prospective hospital based study of newly diagnosed of amblyopia seen at the pediatric clinic of Chittagong Eye Infirmary & Training Complex. There were 50 anisometropic amblyopia subjects were examined & questionnaire was piloted. Included were all patients diagnosed with refractive amblyopia between 3 to 13 years, without previous amblyopia treatment, and whose parents were interested to participate in the study. Patients diagnosed with strabismic amblyopia were excluded. Patients were first corrected with the best correction for a month. When the VA in the amblyopic eye did not improve over month, then occlusion treatment was started. Occlusion was done daily for 6-8 hours (full time) together with vision therapy. The occlusion was carried out for 3 months. Results: In this study about 8% subjects had anisometropia from myopia, 18% from hyperopia, 74% from astigmatism. The initial mean visual acuity was 0.74 ± 0.39 Log MAR and after intervention of amblyopia therapy with active vision therapy mean visual acuity was 0.34 ± 0.26 Log MAR. About 94% of subjects were improving at least two lines. The depth of amblyopia associated with type of anisometropic refractive error and magnitude of Anisometropia (p<0.005). By doing this study 10% mild amblyopia, 64% moderate and 26% severe amblyopia were found. Binocular function also decreases with magnitude of Anisometropia. Conclusion: Anisometropic amblyopia is a most important factor in pediatric age group because it can lead to visual impairment. Occlusion therapy with at least one instructed hour of active visual activity practiced out of school hours was effective in anisometropic amblyopes who were diagnosed at the age of 8 years and older, and the patients complied well with the treatment.

Keywords: refractive error, anisometropia, amblyopia, strabismic amblyopia

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4452 Intracellular Sphingosine-1-Phosphate Receptor 3 Contributes to Lung Tumor Cell Proliferation

Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

Abstract:

Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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4451 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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4450 Combined Proteomic and Metabolomic Analysis Approaches to Investigate the Modification in the Proteome and Metabolome of in vitro Models Treated with Gold Nanoparticles (AuNPs)

Authors: H. Chassaigne, S. Gioria, J. Lobo Vicente, D. Carpi, P. Barboro, G. Tomasi, A. Kinsner-Ovaskainen, F. Rossi

Abstract:

Emerging approaches in the area of exposure to nanomaterials and assessment of human health effects combine the use of in vitro systems and analytical techniques to study the perturbation of the proteome and/or the metabolome. We investigated the modification in the cytoplasmic compartment of the Balb/3T3 cell line exposed to gold nanoparticles. On one hand, the proteomic approach is quite standardized even if it requires precautions when dealing with in vitro systems. On the other hand, metabolomic analysis is challenging due to the chemical diversity of cellular metabolites that complicate data elaboration and interpretation. Differentially expressed proteins were found to cover a range of functions including stress response, cell metabolism, cell growth and cytoskeleton organization. In addition, de-regulated metabolites were annotated using the HMDB database. The "omics" fields hold huge promises in the interaction of nanoparticles with biological systems. The combination of proteomics and metabolomics data is possible however challenging.

Keywords: data processing, gold nanoparticles, in vitro systems, metabolomics, proteomics

Procedia PDF Downloads 507
4449 Demographic Assessment and Evaluation of Degree of Lipid Control in High Risk Indian Dyslipidemia Patients

Authors: Abhijit Trailokya

Abstract:

Background: Cardiovascular diseases (CVD’s) are the major cause of morbidity and mortality in both developed and developing countries. Many clinical trials have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, reduces the incidence of coronary and cerebrovascular events across a broad spectrum of patients at risk. Guidelines for the management of patients at risk have been established in Europe and North America. The guidelines have advocated progressively lower LDL-C targets and more aggressive use of statin therapy. In Indian patients, comprehensive data on dyslipidemia management and its treatment outcomes are inadequate. There is lack of information on existing treatment patterns, the patient’s profile being treated, and factors that determine treatment success or failure in achieving desired goals. Purpose: The present study was planned to determine the lipid control status in high-risk dyslipidemic patients treated with lipid-lowering therapy in India. Methods: This cross-sectional, non-interventional, single visit program was conducted across 483 sites in India where male and female patients with high-risk dyslipidemia aged 18 to 65 years who had visited for a routine health check-up to their respective physician at hospital or a healthcare center. Percentage of high-risk dyslipidemic patients achieving adequate LDL-C level (< 70 mg/dL) on lipid-lowering therapy and the association of lipid parameters with patient characteristics, comorbid conditions, and lipid lowering drugs were analysed. Results: 3089 patients were enrolled in the study; of which 64% were males. LDL-C data was available for 95.2% of the patients; only 7.7% of these patients achieved LDL-C levels < 70 mg/dL on lipid-lowering therapy, which may be due to inability to follow therapeutic plans, poor compliance, or inadequate counselling by physician. The physician’s lack of awareness about recent treatment guidelines also might contribute to patients’ poor adherence, not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style and the cost of medication. Statin was the most commonly used anti-dyslipidemic drug across population. The higher proportion of patients had the comorbid condition of CVD and diabetes mellitus across all dyslipidemic patients. Conclusion: As per the European Society of Cardiology guidelines the ideal LDL-C levels in high risk dyslipidemic patients should be less than 70%. In the present study, 7.7% of the patients achieved LDL-C levels < 70 mg/dL on lipid lowering therapy which is very less. Most of high risk dyslipidemic patients in India are on suboptimal dosage of statin. So more aggressive and high dosage statin therapy may be required to achieve target LDLC levels in high risk Indian dyslipidemic patients.

Keywords: cardiovascular disease, diabetes mellitus, dyslipidemia, LDL-C, lipid lowering drug, statins

Procedia PDF Downloads 205
4448 Early Metastatic Cancer: A Review of Its Management and Outcomes

Authors: Diwei Lin, Amanda Jia Hui Tan

Abstract:

In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability or injury. Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchiectomy followed by chemotherapy. Even then, the prognosis is extremely poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases.

Keywords: testicular cancer, choriocarcinoma, cryptorchidism, chemotherapy, metastatic testicular cancer

Procedia PDF Downloads 368
4447 Examining the Relationship Between Depression and Drug and Alcohol Use in Iran

Authors: Masoumeh Kazemi

Abstract:

Depression is one of the most common mental disorders that damage mental health. In addition to mental distress, mental health damage affects other dimensions of human health, including physical and social health. According to the national study of diseases and injuries in Iran, the third health problem of the country is depression. The purpose of this study was to measure the level of depression in people referred to Karaj psychiatric treatment centers, and to investigate the relationship between depression and drug and alcohol consumption. The statistical population included 5000 people. Morgan table was used to determine the sample size. The research questions sought to identify the relationship between depression and factors such as drug and alcohol use, employment and marital status, and gender. Beck standard questionnaire was used to collect complete information. Cronbach's alpha coefficient was used to confirm the reliability of the questionnaire. To test research hypotheses, non-parametric methods of correlation coefficient, Spearman's rank, Mann-Whitney and Kruskal-Wallis tests were used. The results of using SPSS statistical software showed that there is a direct relationship between depression and drug and alcohol use. Also, the rate of depression was higher in women, widows and unemployed people. Finally, by conducting the present study, it is suggested that people use the following treatments in combination for effective recovery: 1. Cognitive Behavioral Therapy (CBT) 2. Interpersonal Therapy (IPT) 3. Treatment with appropriate medication 4. Special light therapy 5. Electric shock treatment (in acute and exceptional cases) 6. Self-help

Keywords: alcohol, depression, drug, Iran

Procedia PDF Downloads 62
4446 Dexamethasone: Impact on Testicular Activity

Authors: Sadi-Guettaf Hassiba, Hadj-Bekkouche Fatima

Abstract:

Dexamethasone (Dex) is a synthetic glucocorticoid that is used in therapy. However prolonged treatments with high doses are often required. This causes side effects that interfere with the activity of several endocrine systems, including the gonadotropic axis. The aim of our study is to determine the effect of Dex on testicular function in prepubertal Wistar rats. Newborn Wistar rats are submitted to intraperitoneal injection of Dex (1μg of Dex dissolved in NaCl 0.9% / 5g bw) for 20 days and then sacrificed at the age of 40days. A control group received NaCl 0.9%. The rat is weighed daily. The plasmatic levels of testosterone, LH and FSH were measured by radioimmunoassay. A histo-morphometric study was performed on sections of testis. Treated groups showed a significant decrease in body weight (p < 0.05), testis weight (p < 0.05) and plasma levels of testosterone (p < 0.05), of LH (P < .05) and FSH (p> 0.05). There is a reduction of seminiferous tubules average diameter and also of the seminiferous epithelium thickness with an increasing of lumen tubular. The diameter of the Leydig cells and Sertoli cell nucleus is also significantly reduced. Spermatogenesis is blocked at the stage round spermatid unlike witnesses or elongated spermatid stage is found. These results suggest that Dex administered during neonatal life influences testicular activity in the long term.

Keywords: dexamethasone, FSH, LH, rat, testis, testosterone

Procedia PDF Downloads 275
4445 Microbioreactor System for Cell Behavior Analysis Focused on Nerve Tissue Engineering

Authors: Yusser Olguín, Diego Benavente, Fernando Dorta, Nicole Orellana, Cristian Acevedo

Abstract:

One of the greatest challenges of tissue engineering is the generation of materials in which the highest possible number of conditions can be incorporated to stimulate the proliferation and differentiation of cells, which will be transformed together with the material into new functional tissue. In this sense, considering the properties of microfluidics and its relationship with cellular micro-environments, the possibility of controlling flow patterns and the ability to design diverse patterns in the chips, a microfluidic cell culture system can be established as a means for the evaluation of the effect of different parameters in a controlled and precise manner. Specifically in relation to the study and development of alternatives in peripheral nervous tissue engineering, it is necessary to consider different physical and chemical neurotrophic stimuli that promote cell growth and differentiation. Chemical stimuli include certain vitamins, glucocorticoids, gangliosides, and growth factors, while physical stimuli include topological stimuli, mechanical forces of the cellular environment and electrical stimulation. In this context, the present investigation shows the results of cell stimulation in a microbioreactor using electrical and chemical stimuli, where the differentiation of PC12 cells as a neuronal model is evidenced by neurite expression, dependent on the stimuli and their combination. The results were analysed with a multi-factor statistical approach, showing several relationships and dependencies between different parameters. Chip design, operating parameters and concentrations of neurotrophic chemical factors were found to be preponderant, based on the characteristics of the electrical stimuli.

Keywords: microfluidics, nerve tissue engineering, microbioreactor, electrical stimuli

Procedia PDF Downloads 91
4444 CYP2D6*4 Allele Frequency and Extrapyramidal Side Effects during Haloperidol Therapy Among Russians and Tatars: A Pilot Study

Authors: Irina S. Burashnikova, Dmitriy A. Sychev, Ruslan Y. Kazakov

Abstract:

Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. CYP2D6*4 polymorphism frequency varies among different ethnic groups. We studied CYP2D6*4 polymorphism frequency in Tatar and Russian schizophrenic patients and association of CYP2D6*4 polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. Results: Heterozygous CYP2D6*4 allele carrier frequency among Tatars was lower (23.8% vs 32.4% in Russians), but the differences did not reach statistical significance. CYP2D6*4 allele frequency among Tatars was also lower (11.9% vs 24.3% in Russians), but the difference was not quite significant (p=0.0592). Average daily haloperidol dose in the group without EPD was significantly higher than in the group with EPD (11.35±4.6 vs 13.87±3.3 mg, p=0.0252), but average daily haloperidol dose/weight ratios in the compared groups had no significant differences. Statistically significant association between EPD development and heterozygous CYP2D6*1/*4 genotype and CYP2D6*4 allele carrier frequency was revealed among all schizophrenic patients and among those of Tatar nationality. Further well designed pharmacogenetic studies in different Russian regions are needed to improve psychotropic therapy safety and to establish evidence-based indications for pharmacogenetic testing in clinical practice.

Keywords: antipsychotic, CYP2D6 polymorphism, ethnic differences of CYP2D6*4 allele frequency, extrapyramidal side effects/disorder, schizophrenia, pharmacogenetics, Russians, Tatars

Procedia PDF Downloads 326
4443 Integrating Non-Psychoactive Phytocannabinoids and Their Cyclodextrin Inclusion Complexes into the Treatment of Glioblastoma

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

Abstract:

Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

Procedia PDF Downloads 185
4442 Unexplored Anti-HCV Potential of Lichen rangiferinus: An in Vitro Study over Virus Cultures

Authors: Ila Shukla, Lubna Azmi, Shyam Sunder Gupta, C. V. Rao

Abstract:

Treatments against Hepatitis-C virus (HCV) are already available, but the current high cost of such treatments limit them to wealthy patients only. Hence our current study is aimed at the rectification of HCV infection by using Lichen rangiferinus (LRE) extract in in vitro cultures. Anti-HCV activity of the given extract was evaluated using the virus grown in cell culture (HCVcc). Two control inhibitors, erlotinib and telaprevir, were systematically included in each experiment. At the end of the incubation period, we evaluated cell viability and viral replication. The LRE inhibited the growth of HCV in a dose dependent manner.

Keywords: Erlotinib, Hepatitis C, Lichen rangiferinus, Telaprevir

Procedia PDF Downloads 339
4441 Antitumor Activity of Gold Nanorods against Mammary Gland and Skin Carcinoma in Dogs and Cats

Authors: Abdoon A.S., El Ashkar E.A., Kandil O.M., Wael H. Eisa, Shaban A.M., Khaled H.M., El Ashkar M.R., El Shaer M., Hussein H., Shaalan A.H., El Sayed M.

Abstract:

Cancer is a major obstacle to human health and development worldwide. Conventional strategies for cancer intervention include surgery, chemotherapy, and radiation therapy. Recently, plasmon photothermal therapy (PPTT) was introduced as a promising treatment for the management of cancer and several non-cancerous diseases that are generally characterized by overgrowth of abnormal cells. The present work was conducted to evaluate the cytotoxic efficacy and toxicity of gold nanorods (AuNRs) in dogs and cats suffering from spontaneous mammary gland. AuNRs was injected intratumoral (IT, n=10, dose of 75 p.p.m/kg body weight) or by using spray method after surgical removal of cancer tissue (n=2) in dogs and cats. Then exposed to laser light after 60 min. Treated animals were observed every 2 days and the morphological changes in tumor size and shape were recorded. Blood samples were collected before and after treatment for checking CBC, liver and kidney functions. Results revealed that AuNRs successfully treat mammary gland tumor in dogs and cats (adenocarcinoma type 1 to IV). AuNRs induced sloughing of carcinogenic tissue within 5 to 15 days. AuNRs have no toxic effect on blood profile and the toxicity studies still under evaluation. Conclusion, AuNRs can be used for treatment of mammary gland carcinoma in dogs and cats.

Keywords: pet animals, mammary gland tumor, AuNRs, photothermal therapy, toxicity studies

Procedia PDF Downloads 385
4440 Preparation of Polymer-Stabilized Magnetic Iron Oxide as Selective Drug Nanocarriers to Human Acute Myeloid Leukemia

Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

Procedia PDF Downloads 233
4439 Detection of Lymphedema after Breast Cancer in Yucatecan Women

Authors: Olais A. Ingrid, Peraza G. Leydi, Estrella C. Damaris

Abstract:

Breast cancer is the most common among women worldwide; the different treatments can bring sequels that directly affect the quality of life, such as lymphedema. The objective was to determine if there is presence of lymphedema secondary to breast cancer in Yucatecan women. It was an observational, analytical, cross-sectional study, 92 women were included who met the following criteria: women with surgical treatment for unilateral: breast cancer, aged between 25 and 65 years old, minimum 6 weeks after unilateral breast surgery and have completed any type of chemotherapy or adjuvant radiotherapy treatment for breast cancer. The evaluation was through indirect measurement volume by circometry to determine the presence of lymphedema. 23% of women had lymphedema grade I. It related to the presence of some of the symptoms like stiffness, swelling, decreased range of motion and feeling of heaviness in the arm of the operated side of the breast. It is important to determine the presence of lymphedema to perform physical therapy treatment.

Keywords: breast cancer, lymphedema, physical therapy, Yucatan

Procedia PDF Downloads 354
4438 Critical Role of Lipid Rafts in Influenza a Virus Binding to Host Cell

Authors: Dileep Kumar Verma, Sunil Kumar Lal

Abstract:

Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

Procedia PDF Downloads 368
4437 Obsessive-Compulsive Disorder: Development of Demand-Controlled Deep Brain Stimulation with Methods from Stochastic Phase Resetting

Authors: Mahdi Akhbardeh

Abstract:

Synchronization of neuronal firing is a hallmark of several neurological diseases. Recently, stimulation techniques have been developed which make it possible to desynchronize oscillatory neuronal activity in a mild and effective way, without suppressing the neurons' firing. As yet, these techniques are being used to establish demand-controlled deep brain stimulation (DBS) techniques for the therapy of movement disorders like severe Parkinson's disease or essential tremor. We here present a first conceptualization suggesting that the nucleus accumbens is a promising target for the standard, that is, permanent high-frequency, DBS in patients with severe and chronic obsessive-compulsive disorder (OCD). In addition, we explain how demand-controlled DBS techniques may be applied to the therapy of OCD in those cases that are refractory to behavioral therapies and pharmacological treatment.

Keywords: stereotactic neurosurgery, deep brain stimulation, obsessive-compulsive disorder, phase resetting

Procedia PDF Downloads 514