Search results for: hereditary breast-ovarian cancer syndrome
Commenced in January 2007
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Edition: International
Paper Count: 2908

Search results for: hereditary breast-ovarian cancer syndrome

1168 Place of Radiotherapy in the Treatment of Intracranial Meningiomas: Experience of the Cancer Center Emir Abdelkader of Oran Algeria

Authors: Taleb L., Benarbia M., Boutira F. M., Allam H., Boukerche A.

Abstract:

Introduction and purpose of the study: Meningiomas are the most common non-glial intracranial tumors in adults, accounting for approximately 30% of all central nervous system tumors. The aim of our study is to determine the epidemiological, clinical, therapeutic, and evolutionary characteristics of a cohort of patients with intracranial meningioma treated with radiotherapy at the Emir Abdelkader Cancer Center in Oran. Material and methods: This is a retrospective study of 44 patients during the period from 2014 to 2020. The overall survival and relapse-free survival curves were calculated using the Kaplan-Meier method. Results and statistical analysis: The median age of the patients was 49 years [21-76 years] with a clear female predominance (sex ratio=2.4). The average diagnostic delay was seven months [2 to 24 months], the circumstances of the discovery of which were dominated by headaches in 54.5% of cases (n=24), visual disturbances in 40.9% (n=18), and motor disorders in 15.9% (n=7). The seat of the tumor was essentially at the level of the base of the skull in 52.3% of patients (n=23), including 29.5% (n=13) at the level of the cavernous sinus, 27.3% (n=12) at the parasagittal level and 20.5% (n=9) at the convexity. The diagnosis was confirmed surgically in 36 patients (81.8%) whose anatomopathological study returned in favor of grades I, II, and III in respectively 40.9%, 29.5%, and 11.4% of the cases. Radiotherapy was indicated postoperatively in 45.5% of patients (n=20), exclusive in 27.3% (n=12) and after tumor recurrence in 27.3% of cases (n=18). The irradiation doses delivered were as follows: 50 Gy (20.5%), 54 Gy (65.9%), and 60 Gy (13.6%). With a median follow-up of 69 months, the probabilities of relapse-free survival and overall survival at three years are 93.2% and 95.4%, respectively, whereas they are 71.2% and 80.7% at five years. Conclusion: Meningiomas are common primary brain tumors. Most often benign but can also progress aggressively. Their treatment is essentially surgical, but radiotherapy retains its place in specific situations, allowing good tumor control and overall survival.

Keywords: diagnosis, meningioma, surgery, radiotherapy, survival

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1167 Oral Antibiotics in Trans-Rectal Prostate Biopsy and Its Efficacy to Reduce Infectious Complications: Systematic Review

Authors: Mohand Yaghi, O. Kehinde

Abstract:

Background: For the diagnosis of prostate cancer Trans-rectal prostate biopsy (TRPB) is used commonly, the procedure is associated with infective complications. There is evidence that antibiotics (ABx) decrease infective events after TRPB, but different regimens are used. Aim: To systematically review different regimens of prophylactic oral antibiotics in TRPB. Design: Medline, Embase, Clinical trials site, and Cochrane library were searched, experts were consulted about relevant studies. Randomized clinical trials (RCT) conducted in the last twenty years, which investigated different oral antibiotic regimens in TRPB, and compared their efficacy to reduce infectious complications were analyzed. Measurements: Primary outcomes were bacteriuria, urinary tract infection (UTI), fever, bacteremia, sepsis. Secondary outcomes were hospitalization rate, and the prevalence of ABx-resistant bacteria. Results: Nine trials were eligible with 3012 patients. Antibiotics prevented bacteriuria (3.5% vs. 9.88%), UTI (4.46% vs. 9.75%), and hospitalization (0.21% vs. 2.13%) significantly in comparison with placebo or no treatment. No significant difference was found in all outcomes of the review between the single dose regimen and the 3 days. The single dose regimen was as effective as the multiple dose except in Bacteriuria (6.75% vs. 3.25%), and the prevalence of ABx-resistant bacteria (1.57% vs. 0.27%). Quinolones reduced only UTI significantly in comparison with other antibiotics. Lastly, Ciprofloxacin is the best Quinolone to prevent UTI, and hospitalization. Conclusion: it is essential to prescribe prophylactic Antibiotics in TRPB. No conclusive evidence could be claimed about the superiority of the multiple or the 3 days regimens to the single dose regimen. Unexpectedly, ABx-resistant bacteria was identified more often in the single dose cohorts.

Keywords: infection, prostate cancer, sepsis, TRPB

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1166 Optimization of Rehabilitation in Scapolohumeral Periarthrosis Using Botulinum Toxin

Authors: M. A. Akulov, V. O. Zaharov, A. A. Tomskij

Abstract:

Introduction: Scapulohumeral periarthrosis, resulting as a reaction to mechanical injury of shoulder tendons and muscles, is associated with high incidence of temporal and permanent disability. There is a strong need for investigation of treatment of that patient group. Severe pain leads to limitation of movements range, which result in secondary alterations of joint capsule and ligamentous apparatus. Muscle tension and edema, swelling of fascial and fibrous structures result in nerve and vascular compression in intramuscular and osseo-muscular-fibrous spaces. Botulinum toxin injection leads to decrease of muscle tone, increase of movements range and associated pain alleviation. Study aim: Optimization of rehabilitation process in scapolohumeral periarthrosis using Xeomin. Patients and methods: 40 patients aged 37-56 years with scapulohumeral periarthrosis were evaluated. Patients were divided into two groups according to treatment regimen. The first (main) group included 21 patients, receiving intramuscular Xeomin 150-200 U in the area of brachio-scapular joint and trigger points (inducing motion range limitation and pain). Treatment procedures were combined with physical therapy and osteopathic procedures. The second (control) group included 19 patients, receiving conventional physical therapy and osteopathic procedures. The evaluation and efficacy comparison was carried out using McGill pain questionnaire, Clinical Global Impression scale (CGI), and patient-reported increase of brachio-scapular joint movement range and pain decrease at 1, 3 and 6 months of treatment. Results. The study demonstrated a significant improvement in the main group after one month of treatment, which persisted during months of treatment. At baseline, rank pain index on McGill pain questionnaire was 18,4±4,9 and 17,8±5,1 in the main and control group, respectively (p > 0,05). At 1 month of treatment we observed a significant decrease of pain syndrome (no pain or modest pain) and increase of movement range in angular degrees in the main group (р < 0,05). In the control group significant improvements were observed only on the 3 month of treatment (р < 0,05), but at 6 months of treatment the improvement in pain syndrome and motion range in brachio-scapular joint was significantly smaller, than in the main group. Rank pain index on McGill pain scale was 5,2±1,8 in the main group compared to 12,0±2,6 in the control group (р < 0,05). At 6 months of treatment patients in the first group reported a significant/highly significant improvement of general health on CGI, whereas in the second group most patients reported a minimal improvement. We observed a sustained and persistent improvement of motion range in brachio-scapular joint in the main group. Conclusion: Xeomin injections as a part of rehabilitation process in scapulohumeral periarthrosis lead to reduced time and increased quality of rehabilitation.

Keywords: botulinum toxin, rehabilitation, scapulohumeral periarthrosis

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1165 A 3D Cell-Based Biosensor for Real-Time and Non-Invasive Monitoring of 3D Cell Viability and Drug Screening

Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang

Abstract:

In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.

Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems

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1164 A Review of Current Practices in Tattooing of Colonic Lesion at Endoscopy

Authors: Dhanashree Moghe, Roberta Bullingham, Rizwan Ahmed, Tarun Singhal

Abstract:

Aim: The NHS Bowel Screening Programme recommends the use of endoscopic tattooing for suspected malignant lesions that later require surgical or endoscopic localisation, using local protocols as guidance. This is in accordance with guidance from the BSG (The British Society of Gastroenterologists). We used a well-recognised local protocol as a standard to audit current tattooing practice in a large district general hospital with no current local guidelines. Method: A retrospective quantitative analysis of 50 patients who underwent segmental colonic resection for cancer over a 6-month period in 2021. We reviewed historic electronic endoscopy reports recording relevant data on tattoo indication and placement. Secondly, we carried out an anonymous survey of 16 independent lower GI endoscopists on self-reported details of their practice. Results: In our study, 28 patients (56%) had a tattoo placed at the time of their colonoscopy. Of these, only 53% (n=15) had the tattoo distal to the lesion, with the measured distance of the tattoo from the lesion only being documented in 8 reports. Only seven patients (25%) had a circumferential (4 quadrant) placement of the tattoo. 13 patients had lesions either in the caecum or rectum, locations deemed unnecessary as per BSG guidelines. Of the survey responses collected, there were four different protocols being used to guide practice. Only 50% of respondents placed tattoos at the correct distance from the lesion, and 83% placed the correct number of tattoos. Conclusion: There is a lack of standardisation of practices in colonic tattooing demonstrated in our study with incomplete compliance to our standard. The inadequate documentation of tattoo location can contribute to confusion and inaccuracy in the intraoperative localisation of lesions. This has the potential to increase operation length and morbidity. There is a need to standardise both technique and documentation in colonoscopic tattooing practice.

Keywords: colorectal cancer, endoscopic tattooing, colonoscopy, NHS BSCP

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1163 Study on Co-Relation of Prostate Specific Antigen with Metastatic Bone Disease in Prostate Cancer on Skeletal Scintigraphy

Authors: Muhammad Waleed Asfandyar, Akhtar Ahmed, Syed Adib-ul-Hasan Rizvi

Abstract:

Objective: To evaluate the ability of serum concentration of prostate specific antigen between two cutting points considering it as a predictor of skeletal metastasis on bone scintigraphy in men with prostate cancer. Settings: This study was carried out in department of Nuclear Medicine at Sindh Institute of Urology and Transplantation (SIUT) Karachi, Pakistan. Materials and Method: From August 2013 to November 2013, forty two (42) consecutive patients with prostate cancer who underwent technetium-99m methylene diphosphonate (Tc-99mMDP) whole body bone scintigraphy were prospectively analyzed. The information was collected from the scintigraphic database at a Nuclear medicine department Sindh institute of urology and transplantation Karachi Pakistan. Patients who did not have a serum PSA concentration available within 1 month before or after the time of performing the Tc-99m MDP whole body bone scintigraphy were excluded from this study. A whole body bone scintigraphy scan (from the toes to top of the head) was performed using a whole-body Moving gamma camera technique (anterior and posterior) 2–4 hours after intravenous injection of 20 mCi of Tc-99m MDP. In addition, all patients necessarily have a pathological report available. Bony metastases were determined from the bone scan studies and no further correlation with histopathology or other imaging modalities were performed. To preserve patient confidentiality, direct patient identifiers were not collected. In all the patients, Prostate specific antigen values and skeletal scintigraphy were evaluated. Results: The mean age, mean PSA, and incidence of bone metastasis on bone scintigraphy were 68.35 years, 370.51 ng/mL and 19/42 (45.23%) respectively. According to PSA levels, patients were divided into 5 groups < 10ng/mL (10/42), 10-20 ng/mL (5/42), 20-50 ng/mL (2/42), 50-100 (3/42), 100- 500ng/mL (3/42) and more than 500ng/mL (0/42) presenting negative bone scan. The incidence of positive bone scan (%) for bone metastasis for each group were O1 patient (5.26%), 0%, 03 patients (15.78%), 01 patient (5.26%), 04 patients (21.05%), and 10 patients (52.63%) respectively. From the 42 patients 19 (45.23%) presented positive scintigraphic examination for the presence of bone metastasis. 1 patient presented bone metastasis on bone scintigraphy having PSA level less than 10ng/mL, and in only 1 patient (5.26%) with bone metastasis PSA concentration was less than 20 ng/mL. therefore, when the cutting point adopted for PSA serum concentration was 10ng/mL, a negative predictive value for bone metastasis was 95% with sensitivity rates 94.74% and the positive predictive value and specificities of the method were 56.53% and 43.48% respectively. When the cutting point of PSA serum concentration was 20ng/mL the observed results for Positive predictive value and specificity were (78.27% and 65.22% respectively) whereas negative predictive value and sensitivity stood (100% and 95%) respectively. Conclusion: Results of our study allow us to conclude that serum PSA concentration of higher than 20ng/mL was the most accurate cutting point than a serum concentration of PSA higher than 10ng/mL to predict metastasis in radionuclide bone scintigraphy. In this way, unnecessary cost can be avoided, since a considerable part of prostate adenocarcinomas present low serum PSA levels less than 20 ng/mL and for these cases radionuclide bone scintigraphy could be unnecessary.

Keywords: bone scan, cut off value, prostate specific antigen value, scintigraphy

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1162 Aberrant Acetylation/Methylation of Homeobox (HOX) Family Genes in Cumulus Cells of Infertile Women with Polycystic Ovary Syndrome (PCOS)

Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

Abstract:

Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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1161 A New and Simple Method of Plotting Binocular Single Vision Field (BSVF) using the Cervical Range of Motion - CROM - Device

Authors: Mihir Kothari, Heena Khan, Vivek Rathod

Abstract:

Assessment of binocular single vision field (BSVF) is traditionally done using a Goldmann perimeter. The measurement of BSVF is important for the management of incomitant strabismus, viz. orbital fractures, thyroid orbitopathy, oculomotor cranial nerve palsies, Duane syndrome etc. In this paper, we describe a new technique for measuring BSVF using a CROM device. Goldmann perimeter is very bulky and expensive (Euro 5000.00 or more) instrument which is 'almost' obsolete from the contemporary ophthalmology practice. Whereas, CROM can be easily made in the DIY (do it yourself) manner for the fraction of the price of the perimeter (only Euro 15.00). Moreover, CROM is useful for the accurate measurement of ocular torticollis vis. nystagmus, paralytic or incomitant squint etc, and it is highly portable.

Keywords: binocular single vision, perimetry, cervical rgen of motion, visual field, binocular single vision field

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1160 Dosimetric Comparison of Conventional Optimization Methods with Inverse Planning Simulated Annealing Technique

Authors: Shraddha Srivastava, N. K. Painuly, S. P. Mishra, Navin Singh, Muhsin Punchankandy, Kirti Srivastava, M. L. B. Bhatt

Abstract:

Various optimization methods used in interstitial brachytherapy are based on dwell positions and dwell weights alteration to produce dose distribution based on the implant geometry. Since these optimization schemes are not anatomy based, they could lead to deviations from the desired plan. This study was henceforth carried out to compare anatomy-based Inverse Planning Simulated Annealing (IPSA) optimization technique with graphical and geometrical optimization methods in interstitial high dose rate brachytherapy planning of cervical carcinoma. Six patients with 12 CT data sets of MUPIT implants in HDR brachytherapy of cervical cancer were prospectively studied. HR-CTV and organs at risk (OARs) were contoured in Oncentra treatment planning system (TPS) using GYN GEC-ESTRO guidelines on cervical carcinoma. Three sets of plans were generated for each fraction using IPSA, graphical optimization (GrOPT) and geometrical optimization (GOPT) methods. All patients were treated to a dose of 20 Gy in 2 fractions. The main objective was to cover at least 95% of HR-CTV with 100% of the prescribed dose (V100 ≥ 95% of HR-CTV). IPSA, GrOPT, and GOPT based plans were compared in terms of target coverage, OAR doses, homogeneity index (HI) and conformity index (COIN) using dose-volume histogram (DVH). Target volume coverage (mean V100) was found to be 93.980.87%, 91.341.02% and 85.052.84% for IPSA, GrOPT and GOPT plans respectively. Mean D90 (minimum dose received by 90% of HR-CTV) values for IPSA, GrOPT and GOPT plans were 10.19 ± 1.07 Gy, 10.17 ± 0.12 Gy and 7.99 ± 1.0 Gy respectively, while D100 (minimum dose received by 100% volume of HR-CTV) for IPSA, GrOPT and GOPT plans was 6.55 ± 0.85 Gy, 6.55 ± 0.65 Gy, 4.73 ± 0.14 Gy respectively. IPSA plans resulted in lower doses to the bladder (D₂

Keywords: cervical cancer, HDR brachytherapy, IPSA, MUPIT

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1159 Apoptosis Inducing Potential of Onosma Bracteata Wall. in Mg-63 Human Osteosarcoma Cells via cdk2/Cyclin E Pathway

Authors: Ajay Kumar, Satwinderjeet Kaur

Abstract:

Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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1158 Development of an Electrochemical Aptasensor for the Detection of Human Osteopontin Protein

Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

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The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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1157 Green Synthesis of Nicotine Analogues via Cycloaddition Reactions

Authors: Agnieszka Fryźlewicz, Jowita Kras, Mikołaj Sadowski, Agnieszka Łapczuk-Krygier, Agnieszka Kącka-Zych Radomir Jasiński

Abstract:

Nicotines are a group of compounds containing conjugated pyridine and pyrrolidine molecular segments. They are widely applied in medicine, pharmacy, and agriculture. Namely as researched treatment of Alzheimer, depression, Parkinson's, Tourette syndrome, general nervous and mental disorders. Furthermore, nicotine itself is used as a stimulant, animal repellent and was widely applied as an insecticide. In our work, we obtained nicotine analogues with possible applications in agriculture. The synthesis employed [3+2] cycloaddition (32CA) reactions, occurring between pirydyl-functionalised nitrones and conjugated nitroalkenes, that allowed us to fully regio- and stereoselectively obtain product. Moreover, cycloaddition reaction realizes rapidly in mild conditions with the full atomic economy, thus fitting into “green chemistry” trends.

Keywords: nicotine, isoxazolidine, 1-3-dipolar cycloaddition, green chemistry, biological and pharmacological activity

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1156 Circadian-Clock Controlled Drug Transport Across Blood-Cerebrospinal Fluid Barrier

Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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1155 Preparation, Characterisation, and Measurement of the in vitro Cytotoxicity of Mesoporous Silica Nanoparticles Loaded with Cytotoxic Pt(II) Oxadiazoline Complexes

Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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1154 Prostatic Cyst in Suprapubic Ultrasound Examination

Authors: Angelis P. Barlampas, Ghita Bianca-Andreea

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A case of a prostatic midline cyst is presented, which was found during a routine general ultrasound examination in an otherwise healthy young man. The incidence of prostatic cysts discovered in suprapubic ultrasound examination has constantly been rising over the previous decades. Despite the fact that the majority of them are benign, a significant amount is related to symptoms, such as pain, dysuria, infertility, and even cancer. The wide use of ultrasound examination and the increasing availability of high-resolution ultrasound systems have rendered new diagnostic challenges. Once upon a time a suprapubic ultrasound was only useful for measuring only the size and the dimensions of the prostatic gland. It did not have the ability to analyze and resolve structures such as cystic or solid nodules. The current machine equipment has managed to depict the imaging characteristics of lesions with high acuity that compares of an intrarectal ultrasound. But the last one is a specialized examination, which demands expertise and good knowledge. Maybe the time has come for the general radiologist and, especially the one who uses suprapubic ultrasound, to pay more attention to the examination of the prostate gland and to take advantage of the superb abilities and the high resolution of the new ultrasound systems. That is exactly, what this case is emphasizing. The incidental discovery of prostatic cysts, and the relatively little available literature about managing them turns them into an interesting theme for exploring and studying. The prostatic cysts are further divided into midline and paramidline cysts, with the first being usually utricle cysts. A more precise categorization is as follows: A midline cystic lesion usually regards a Mullerian duct cyst, a prostatic utricle cyst, an ejaculatory duct cyst, a prostatic cystadenoma, a ductus deferens cyst, and a TURP. On the other hand, a lateral cystic lesion usually refers to a cystic degeneration of benign prostatic hyperplasia, a prostatic retention cyst, a seminal vesicle cyst, diverticular prostatitis, a prostatic abscess, cavitatory prostatitis from chronic prostatitis, a parasitic prostatic cyst, a cystic prostatic carcinoma, e.t.c.

Keywords: prostatic cyst, radiology, benign prostatic lesions, prostatic cancer, suprapubic prostatic ultrasound

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1153 Heart Failure Identification and Progression by Classifying Cardiac Patients

Authors: Muhammad Saqlain, Nazar Abbas Saqib, Muazzam A. Khan

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Heart Failure (HF) has become the major health problem in our society. The prevalence of HF has increased as the patient’s ages and it is the major cause of the high mortality rate in adults. A successful identification and progression of HF can be helpful to reduce the individual and social burden from this syndrome. In this study, we use a real data set of cardiac patients to propose a classification model for the identification and progression of HF. The data set has divided into three age groups, namely young, adult, and old and then each age group have further classified into four classes according to patient’s current physical condition. Contemporary Data Mining classification algorithms have been applied to each individual class of every age group to identify the HF. Decision Tree (DT) gives the highest accuracy of 90% and outperform all other algorithms. Our model accurately diagnoses different stages of HF for each age group and it can be very useful for the early prediction of HF.

Keywords: decision tree, heart failure, data mining, classification model

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1152 Detection of JC Virus DNA and T-Ag Expression in a Subpopulation of Tunisian Colorectal Carcinomas

Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

Abstract:

Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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1151 Dermoscopy Compliance: Improving Melanoma Detection Pathways Through Quality Improvement

Authors: Max Butler

Abstract:

Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.

Keywords: melanoma, dermoscopy, plastic surgery, quality improvement

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1150 Pattern Of Polymorphism SLC22A1 Gene In Children With Diabetes Mellitus Type 2

Authors: Elly Usman, S. Dante, Diah Purnamasari

Abstract:

Type 2 diabetes mellitus ( T2DM ) is a syndrome characterized by a state of increased blood sugar levels due to chronic disorders of insulin secretion by pancreatic beta cells and insulin action or a combination of both. The organic cation transporter 1, encoded by the SLC22A1 gene, responsible for the uptake of the antihyperglycemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene was associated with the glucose - lowering effect of metformin. Method case study research design. Samples are children with type 2 diabetes mellitus who meet the inclusion criteria. The results proportions SLC22A1 gene polymorphisms in children with diabetes mellitus type 2 amounted to 52.04 % at position 400T/C, there is one heterozygous and one at position 595T/C Conclusion The presence of SLC22A1 gene polymorphisms in children with diabetes mellitus type 2.

Keywords: diabetes Mellitus type 2, metformin, organic cation transporter 1, pharmacogenomics

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1149 Powder Assisted Sheet Forming to Fabricate Ti Capsule Magnetic Hyperthermia Implant

Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

Abstract:

To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

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1148 Procalcitonin and Other Biomarkers in Sepsis Patients: A Prospective Study

Authors: Neda Valizadeh, Soudabeh Shafiee Ardestani, Arvin Najafi

Abstract:

Objectives: The aim of this study is to evaluate the association of mid-regional pro-atrial natriuretic peptide (MRproANP), procalcitonin (PCT), proendothelin-1 (proET-1) levels with sepsis severity in Emergency ward patients. Materials and Methods: We assessed the predictive value of MRproANP, PCT, copeptin, and proET-1 in early sepsis among patients referring to the emergency ward with a suspected sepsis. Results-132 patients were enrolled in this study. 45 (34%) patients had a final diagnosis of sepsis. A higher percentage of patients with definite sepsis had systemic inflammatory response syndrome (SIRS) criteria at initial visit in comparison with no-sepsis patients (P<0.05) and were admitted to the hospital (P<0.05). PCT levels were higher in sepsis patients [P<0.05]. There was no significant differences for MRproANP or proET-1 in sepsis patients (P=0.47). Conclusion: A combination of SIRS criteria and PCT levels is beneficial for the early sepsis diagnosis in emergency ward patients with a suspicious infection disease.

Keywords: emergency, prolactin, sepsis, biomarkers

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1147 Choosing Mountains Over the Beach: Evaluating the Effect of Altitude on Covid Brain Severity and Treatment

Authors: Kennedy Zinn, Chris Anderson

Abstract:

Chronic Covid syndrome (CCS) is a condition in which individuals who test positive for Covid-19 experience persistent symptoms after recovering from the virus. CCS affects every organ system, including the central nervous system. Neurological “long-haul” symptoms last from a few weeks to several months and include brain fog, chronic fatigue, dyspnea, mood dysregulation, and headaches. Data suggest that 10-30% of individuals testing positive for Covid-19 develop CCS. Current literature indicates a decreased quality of life in persistent symptoms. CCS is a pervasive and pernicious COVID-19 sequelae. More research is needed to understand risk factors, impact, and possible interventions. Research frequently cites cytokine storming as noteworthy etiology in CCS. Cytokine storming is a malfunctional immune response and facilitates multidimensional interconnected physiological responses. The most prominent responses include abnormal blood flow, hypoxia/hypoxemia, inflammation, and endothelial damage. Neurological impairments and pathogenesis in CCS parallel that of traumatic brain injury (TBI). Both exhibit impairments in memory, cognition, mood, sustained attention, and chronic fatigue. Evidence suggests abnormal blood flow, inflammation, and hypoxemia as shared causal factors. Cytokine storming is also typical in mTBI. The shared characteristics in symptoms and etiology suggest potential parallel routes of investigation that allow for better understanding of CCS. Research on the effect of altitude in mTBI varies. Literature finds decreased rates of concussions at higher altitudes. Other studies suggest that at a higher altitude, pre-existing mTBI symptoms are exacerbated. This may mean that in CCS, the geographical location where individuals live and the location where individuals experienced acute Covid-19 symptoms may influence the severity and risk of developing CCS. It also suggests that clinics which treat mTBI patients could also provide benefits for those with CCS. This study aims to examine the relationships between altitude and CCS as a risk factor and investigate the longevity and severity of symptoms in different altitudes. Existing patient data from a concussion clinic using fMRI scans and self-reported symptoms will be used for approximately 30 individuals with CCS symptoms. The association between acclimated altitude and CCS severity will be analyzed. Patients will be classified into low, medium, and high altitude groups and compared for differences on fMRI severity scores and self-reported measures. It is anticipated that individuals living in lower altitudes are at higher risk of developing more severe neuropsychological symptoms in CCS. It is also anticipated that a treatment approach for mTBI will also be beneficial to those with CCS.

Keywords: altitude, chronic covid syndrome, concussion, covid brain, EPIC treatment, fMRI, traumatic brain injury

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1146 Water Quality, Risk, Management and Distribution in Abeokuta, Ogun State

Authors: Ayedun Hassan, Ayadi Odunayo Peter

Abstract:

The ancient city of Abeokuta has been supplied with pipe borne water since 1911, yet, a continuous increase in population and unplanned city expansion makes water a very precious and scarce commodity. The government reserved areas (GRA’s) are well planned, and public water supply is available; however, the sub-urban areas consist of scattered structures with individuals trying to source water by digging wells and boreholes. The geology of the city consists of basement rock which makes digging wells and boreholes very difficult. The present study was conducted to assess the risk arising from the consumption of toxic elements in the groundwater of Abeokuta, Ogun State, Nigeria. Forty-five groundwater samples were collected from nine different areas of Abeokuta and analyzed for physicochemical parameters and toxic elements. The physicochemical parameters were determined using standard methods, while the toxic elements were determined using Inductively Coupled Plasma-Mass Spectrometer (ICP/MS). Ninety-six percent (96%) of the water sample has pH < 6.5, and 11% has conductivity > 250 µSCm⁻¹ limits in drinking water as recommended by WHO. Seven percent (7%) of the samples have Pb concentration >10 µgL⁻¹ while 75% have Al concentration >200 µgL⁻¹ recommended by WHO. The order for risk of cancer from different area of Abeokuta are Cd²⁺ > As³⁺ > Pb²⁺ > Cr⁶⁺ for Funaab, Camp and Obantoko; As³⁺ > Cd²⁺ > Pb²⁺ > Cr⁶⁺ for Ita Osin, Isale Igbein, Ake and Itoku; Cd²⁺ >As > Cr⁶⁺ > Pb²⁺ for Totoro; Pb²⁺ > Cd²⁺ > As³⁺ > Cr⁶⁺ for Idiaba. The order of non-cancer hazard index (HI) calculated for groundwater of Abeokuta City are Cd²⁺ > As³⁺ > Mn²⁺ > Pb²⁺ > Ni²⁺ and were all greater than one, which implies susceptibility to other illnesses. The sources of these elements are the rock and inappropriate waste disposal method, which leached the elements into the groundwater. A combination of sources from food will accumulate these elements in the human body system. Treatment to remove Al and Pb is necessary, while the method of water distribution should be reviewed to ensure access to potable water by the residents.

Keywords: Abeokuta, groundwater, Nigeria, risk

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1145 Destruction of Colon Cells by Nanocontainers of Ferromagnetic

Authors: Lukasz Szymanski, Zbigniew Kolacinski, Grzegorz Raniszewski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza, Karolina Przybylowska-Sygut, Ireneusz Majsterek, Zbigniew Kaminski, Justyna Fraczyk, Malgorzata Walczak, Beata Kolasinska, Adam Bednarek, Joanna Konka

Abstract:

The aim of this work is to investigate the influence of electromagnetic field from the range of radio frequencies on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon - ferromagnetic nanocontainers (FNCs) includes: The synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Pristine ferromagnetic carbon nanotubes are not suitable for application in medicine and biotechnology. Appropriate functionalization of ferromagnetic carbon nanotubes allows to receiving materials useful in medicine. Finally, a product contains folic acids on the surface of FNCs. The folic acid is a ligand of folate receptors – α which is overexpressed on the surface of epithelial tumours cells. It is expected that folic acids will be recognized and selectively bound by receptors presented on the surface of tumour cells. In our research, FNCs were covalently functionalized in a multi-step procedure. Ferromagnetic carbon nanotubes were oxidated using different oxidative agents. For this purpose, strong acids such as HNO3, or mixture HNO3 and H2SO4 were used. Reactive carbonyl and carboxyl groups were formed on the open sides and at the defects on the sidewalls of FNCs. These groups allow further modification of FNCs as a reaction of amidation, reaction of introduction appropriate linkers which separate solid surface of FNCs and ligand (folic acid). In our studies, amino acid and peptide have been applied as ligands. The last step of chemical modification was reaction-condensation with folic acid. In all reaction as coupling reagents were used derivatives of 1,3,5-triazine. The first trials in the device for hyperthermal RF generator have been done. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz. Obtained functionalized nanoparticles enabled to reach the temperature of denaturation tumor cells in given frequencies.

Keywords: cancer colon cells, carbon nanotubes, hyperthermia, ligands

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1144 Concentrations of Leptin, C-Peptide and Insulin in Cord Blood as Fetal Origins of Insulin Resistance and Their Effect on the Birth Weight of the Newborn

Authors: R. P. Hewawasam, M. H. A. D. de Silva, M. A. G. Iresha

Abstract:

Obesity is associated with an increased risk of developing insulin resistance. Insulin resistance often progresses to type-2 diabetes mellitus and is linked to a wide variety of other pathophysiological features including hypertension, hyperlipidemia, atherosclerosis (metabolic syndrome) and polycystic ovarian syndrome. Macrosomia is common in infants born to not only women with gestational diabetes mellitus but also non-diabetic obese women. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age (LGA) are more likely to be obese in childhood. It is also established from previous studies that Asian populations have higher percentage body fat at a lower body mass index compared to Caucasians. High leptin levels in cord blood have been reported to correlate with fetal adiposity at birth. Previous studies have also shown that cord blood C-peptide and insulin levels are significantly and positively correlated with birth weight. Therefore, the objective of this preliminary study was to determine the relationship between parameters of fetal insulin resistance such as leptin, C-peptide and insulin and the birth weight of the newborn in a study population in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns and the concentration of insulin, leptin, and C-peptide were measured by ELISA technique. Birth weight, length, occipital frontal, chest, hip and calf circumferences of newborns were measured and characteristics of the mother such as age, height, weight before pregnancy and weight gain were collected. The relationship between insulin, leptin, C-peptide, and anthropometrics were assessed by Pearson’s correlation while the Mann-Whitney U test was used to assess the differences in cord blood leptin, C-peptide, and insulin levels between groups. A significant difference (p < 0.001) was observed between the insulin levels of infants born LGA (18.73 ± 0.64 µlU/ml) and AGA (13.08 ± 0.43 µlU/ml). Consistently, A significant increase in concentration (p < 0.001) was observed in C-peptide levels of infants born LGA (9.32 ± 0.77 ng/ml) compared to AGA (5.44 ± 0.19 ng/ml). Cord blood leptin concentration of LGA infants (12.67 ng/mL ± 1.62) was significantly higher (p < 0.001) compared to the AGA infants (7.10 ng/mL ± 0.97). Significant positive correlations (p < 0.05) were observed among cord leptin levels and the birth weight, pre-pregnancy maternal weight and BMI between the infants of AGA and LGA. Consistently, a significant positive correlation (p < 0.05) was observed between the birth weight and the C peptide concentration. Significantly high concentrations of leptin, C-peptide and insulin levels in the cord blood of LGA infants suggest that they may be involved in regulating fetal growth. Although previous studies suggest comparatively high levels of body fat in the Asian population, values obtained in this study are not significantly different from values previously reported from Caucasian populations. According to this preliminary study, maternal pre-pregnancy BMI and weight may contribute as significant indicators of cord blood parameters of insulin resistance and possibly the birth weight of the newborn.

Keywords: large for gestational age, leptin, C-peptide, insulin

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1143 Triple Case Phantom Tumor of Lungs

Authors: Angelis P. Barlampas

Abstract:

Introduction: The term phantom lung mass describes the ovoid collection of fluid within the interlobular fissure, which initially creates the impression of a mass. The problem of correct differential diagnosis is great, especially in plain radiography. A case is presented with three nodular pulmonary foci, the shape, location, and density of which, as well as the presence of chronic loculated pleural effusions, suggest the presence of multiple phantom tumors of the lung. Purpose: The aim of this paper is to draw the attention of non-experienced and non-specialized physicians to the existence of benign findings that mimic pathological conditions and vice versa. The careful study of a radiological examination and the comparison with previous exams or further control protect against quick wrong conclusions. Methods: A hospitalized patient underwent a non-contrast CT scan of the chest as part of the general control of her situation. Results: Computed tomography revealed pleural effusions, some of them loculated, increased cardiothoracic index, as well as the presence of three nodular foci, one in the left lung and two in the right with a maximum density of up to 18 Hounsfield units and a mean diameter of approximately five centimeters. Two of them are located in the characteristical anatomical position of the major interlobular fissure. The third one is located in the area of the right lower lobe’s posterior basal part, and it presents the same characteristics as the previous ones and is likely to be a loculated fluid collection, within an auxiliary interlobular fissure or a cyst, in the context of the patient's more general pleural entrapments and loculations. The differential diagnosis of nodular foci based on their imaging characteristics includes the following: a) rare metastatic foci with low density (liposarcoma, mucous tumors of the digestive or genital system, necrotic metastatic foci, metastatic renal cancer, etc.), b) necrotic multiple primary lung tumor locations (squamous epithelial cancer, etc. ), c) hamartomas of the lung, d) fibrotic tumors of the interlobular fissures, e) lipoid pneumonia, f) fluid concentrations within the interlobular fissures, g) lipoma of the lung, h) myelolipomas of the lung. Conclusions: The collection of fluid within the interlobular fissure of the lung can give the false impression of a lung mass, particularly on plain chest radiography. In the case of computed tomography, the ability to measure the density of a lesion, combined with the provided high anatomical details of the location and characteristics of the lesion, can lead relatively easily to the correct diagnosis. In cases of doubt or image artifacts, comparison with previous or subsequent examinations can resolve any disagreements, while in rare cases, intravenous contrast may be necessary.

Keywords: phantom mass, chest CT, pleural effusion, cancer

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1142 Evaluation of Naringenin Role in Inhibiton of Lung Tumor Progression in Mice

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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1141 Meniere's Disease and its Prevalence, Symptoms, Risk Factors and Associated Treatment Solutions for this Disease

Authors: Amirreza Razzaghipour Sorkhab

Abstract:

One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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1140 Restless Leg Syndrome as the Presenting Symptom of Neuroendocrine Tumor

Authors: Mustafa Cam, Nedim Ongun, Ufuk Kutluana

Abstract:

Introduction: Restless LegsSyndrome (RLS) is a common, under-recognized disorder disrupts sleep and diminishes quality of life (1). The most common conditions highly associated with RLS include renalfailure, iron and folic acid deficiency, peripheral neuropathy, pregnancy, celiacdisease, Crohn’sdiseaseandrarelymalignancy (2).Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficientanemic populations is unknown (2). We report here a case of RLS due to iron deficiency in the setting of neuroendocrinetumor. Report of Case: A 35 year-old man was referred to our clinic with general weakness, weight loss (10 kg in 2 months)and 2-month history of uncomfortable sensations in his legs with urge to move, partially relieved by movement. The symptoms were presented very day, worsening in the evening; the discomfort forced the patient to getup and walk around at night. RLS was severe, with a score of 22 at the International RLS ratingscale. The patient had no past medical history. The patient underwent a complete set of blood analyses and the following ab normal values were found (normal limitswithinbrackets): hemoglobin 9.9 g/dl (14-18), MCV 70 fL (80-94), ferritin 3,5 ng/mL (13-150). Brain and spinemagnetic resonance imaging was normal. The patient consultated with gastroenterology clinic and gastointestinal systemendoscopy was performed for theetiology of the iron deficiency anemia. After the gastricbiopsy, results allowed us to reach the diagnosis of neuroen docrine tumor and the patient referred to oncology clinic. Discussion: The first important consideration from this case report is that the patient was referred to our clinic because of his severe RLS symptoms dramatically reducing his quality of life. However, our clinical study clearly demonstrated that RLS was not the primary disease. Considering the information available for this patient, we believe that the most likely possibility is that RLS was secondary to iron deficiency, a very well-known and established cause of RLS in theliterature (3,4). Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation that most commonly originate in the lungs and gastrointestinal tract (5). NETs vary widely in their clinical presentation; symptoms are often nonspecific and can be mistaken for those of other more common conditions (6). 50% of patients with reported disease stage have either regional or distant metastases at diagnosis (7). Accurate and earlier NET diagnosis is the first step in shortening the time to optimal care and improved outcomes for patients (8). The most important message from this case report is that RLS symptoms can sometimes be thesign of a life-threatening condition. Conclusion: Careful and complete collection of clinical and laboratory data should be carried out in RLS patients. Inparticular, if RLS onset coincides with weight loss and iron deficieny anemia, gastricendos copy should be performed. It is known about that malignancy is a rare etiology in RLS patients and to our knowledge; it is the first case with neuro endocrine tumor presenting with RLS.

Keywords: neurology, neuroendocrine tumor, restless legs syndrome, sleep

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1139 Carriage of 675 4G/5G Polymorphism in PAI-1 Gene and Its Association with Early Pregnancy Losses in Patients with Polycystic Ovary Syndrome

Authors: R. Komsa-Penkova, G. Golemanov, G. Georgieva, K. Popovski, N. Slavov, P. Ivanov, K. Kovacheva, S. Rathee, E. Konova, A. Blajev

Abstract:

Leptin and PAI-1 are important cytokines and may play a role in the regulation of PCOS development. PCOS is frequently associated with obesity, high BMI index and consequently with increased risk of metabolic disorders. The aim of the present study was to evaluate PAI-1 levels, genetic influence of the carriage of 675 4G/5G polymorphism in PAI-1 gene and leptin as a marker of obesity in the development of PCOS. Methods: Genotyping in 84 patients with PCOS and PCO and 100 healthy control subjects to detect single nucleotide deletion 675 G in the promoter of PAI-1 gene. The present study provides evidence that SNP 4G in the PAI-1 gene is associated with early pregnancy losses in patients with polycystosis. Further to this, there is a correlation between leptin levels, PAI-1 levels and BMI in the patients with PCOS, which confirms the role of obesity as a risk factor for PCOS.

Keywords: carriage of 675 4G/5G polymorphism, PCOS, early pregnancy losses, PAI-1 gene

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