Search results for: pituitary tumours

Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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Authors: Gerard Bray, Derek Mao, Arya Bahadori, Sachinka Ranasinghe

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The EAU currently recommends partial nephrectomy as the preferred management for localised cT1 renal tumours, irrespective of surgical approach. With the advent of robotic assisted partial nephrectomy, there is growing evidence that warm ischaemia time may be reduced compared to the traditional laparoscopic approach. There is still no clear differences between the two approaches with regards to other peri-operative and oncological outcomes. Current limitations in the field denote the lack of single surgeon series to compare the two approaches as other studies often include multiple operators of different experience levels. To the best of our knowledge, this study is the first single surgeon series comparing peri-operative outcomes of robotic assisted and laparoscopic PN. The current study aims to reduce intra-operator bias while maintaining an adequate sample size to assess the differences in outcomes between the two approaches. We retrospectively compared patient demographics, peri-operative outcomes, and renal function derangements of all partial nephrectomies undertaken by a single surgeon with experience in both laparoscopic and robotic surgery. Warm ischaemia time, length of stay, and acute renal function deterioration were all significantly reduced with robotic partial nephrectomy, compared to laparoscopic nephrectomy. This study highlights the benefits of robotic partial nephrectomy. Further prospective studies with larger sample sizes would be valuable additions to the current literature.

Keywords: partial nephrectomy, robotic assisted partial nephrectomy, warm ischaemia time, peri-operative outcomes

Procedia PDF Downloads 109

Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

Procedia PDF Downloads 277

Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Muhammad Badruzzaman, Alif Hasan, Md. Shahjahan

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Propiconazole is a triazole fungicide extensively used in agriculture which can harm to non-target organisms in aquatic environment through runoff. Chronic exposure to environmental pesticides turn to behavioral impairment in vertebrates including teleosts. However, the potential effect of this fungicide on neurobehavioral impairment and release from it in vertebrates has not been fully explored. In this work, we examined the role of melatonin to rescue fungicide induced neurobehavioral and reproductive alternation and its connection with changes in dopaminergic activity in the brain of Mystus cavasius. After fish were exposed to water containing propiconazole at 0, 0.1, 5, and 250 µg/L for 3 days, significant increases of DA, 3,4-dihydroxyphenylacetic acid (DOPAC; a DA metabolite), and their ratio (DOPAC/DA) were observed in whole brain at 250 µg/L concentration. When fish were treated with propiconazole at 250 µg/L for 3 days, there was a significant elevation of DA, DOPAC and DOPAC/DA in diencephalon and pituitary, and only DA in the telencephalon, compared with control fish. Besides, it induced a reduction in extracellular serotonin and had an anxiolytic-like effect, supported by a decrease in cortisol production. Increased locomotor activity, anxiety and aggressiveness, decreased gonadosomatic index with few vitellogenic oocytes in ovaries after propiconazole treatment. When fish were treated with melatonin, D1 (SCH-23390) or D2 (Haloperidol) dopamine receptor antagonists and combined of melatonin and D1/D2 receptor antagonist and was observed melatonin + D2 receptor antagonist rescued fungicide induced all behavioral changes in fish. These results indicate that propiconazole increases locomotor activity, anxiety and aggressiveness and decreases reproductive activity, which was rescued by combined treatment of melatonin and dopamine receptor antagonist.

Keywords: behavior, catfish, dopamine, fungicide, melatonin

Procedia PDF Downloads 86

Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

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Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin

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Authors: Samarpreet Singh, Gerald Giesbrecht

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Both c-section and antibiotic exposure are linked to gut microbiota imbalance in infants. Such disturbance is associated with the Hypothalamic-Pituitary-Adrenal (HPA) axis function. However, the literature only has contradicting evidence for the association between c-sections and the HPA axis. Therefore, this study aims to test if the mode of delivery and antibiotics exposure is associated with the HPA axis. Also, whether exposure to both interacts with the HPA-axis. It was hypothesized that associations and interactions would be observed. Secondary data analysis was used for this co-relational study. Data for the mode of delivery and antibiotics exposure variables were documented from hospital records or self-questionnaires. In addition, cortisol levels (Area under the curve with respect to increasing (AUCi) and Area under the curve with respect to ground (AUCg)) were based on saliva collected from three months old during the infant’s visit to the lab and after drawing blood. One-way and between-subject ANOVA analyses were run on data. No significant association between delivery mode and infant cortisol level was found, AUCi and AUCg, p > .05. Only the infant’s AUCg was found to be significantly higher if there were antibiotics exposure at delivery (p = .001) or their mothers were exposed during pregnancy (p < .05). Infants born by c-section and exposed to antibiotics at three months had higher AUCi than those born vaginally, p < .02. These results imply that antibiotic exposure before three months is associated with an infant’s stress response. The association might increase if antibiotic exposure occurs three months after a c-section birth. However, more robust and causal evidence in future studies is needed, given a variable group’s statistically weak sample size. Nevertheless, the results of this study still highlight the unintended consequences of antibiotic exposure during delivery and pregnancy.

Keywords: HPA-axis, antibiotics, c-section, gut-microbiota, development, stress

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Authors: L. Lamola, E. Manolas, A. Krause

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Background: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. Methods: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited, and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. Results: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. Conclusions: According to the literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however, we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population.

Keywords: Africa, genetics, germline-variants, paediatric-cancer

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Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

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Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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Authors: Mihai-Ionut Firescu, Mark A. P. Carson

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We present a case of inferior vena cava agenesis (IVCA) associated with bilateral deep venous thrombosis (DVT) in a patient with Beckwith-Wiedemann syndrome (BWS). In adult patients with BWS presenting with bilateral lower limb oedema, specific aetiological factors should be considered. These include cardiomyopathy and intraabdominal tumours. Congenital malformations of the IVC, through causing relative venous stasis, can lead to lower limb oedema either directly or indirectly by favouring lower limb venous thromboembolism; however, they are yet to be reported as an associated feature of BWS. Given its life-threatening potential, the prompt initiation of treatment for bilateral DVT is paramount. In BWS patients, however, this can prove more complicated. Due to overgrowth, the above-average birth weight can continue throughout childhood. In this case, the patient’s weight reached 170 kg, impacting on anticoagulation choice, as direct oral anticoagulants have a limited evidence base in patients with a body mass above 120 kg. Furthermore, the presence of IVCA leads to a long-term increased venous thrombosis risk. Therefore, patients with IVCA and bilateral DVT warrant specialist consideration and may benefit from multidisciplinary team management, with hematology and vascular surgery input. Conclusion: Here, we showcased a rare cause for bilateral lower limb oedema, respectively bilateral deep venous thrombosis complicating IVCA in a patient with Beckwith-Wiedemann syndrome. The importance of this case lies in its novelty, as the association between IVC agenesis and BWS has not yet been described. Furthermore, the treatment of DVT in such situations requires special consideration, taking into account the patient’s weight and the presence of a significant, predisposing vascular abnormality.

Keywords: Beckwith-Wiedemann syndrome, bilateral deep venous thrombosis, inferior vena cava agenesis, venous thromboembolism

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Authors: Sekena H. Abd El-Aziem, Heba A. M. Abd El-Kader, Sally S. Alam, Othman E. Othman

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Growth hormone (GH) is an anabolic hormone synthesized and secreted by the somatotroph cells of the anterior lobe of the pituitary gland in a circadian and pulsatile manner, the pattern of which plays an important role in postnatal longitudinal growth and development, tissue growth, lactation, reproduction as well as protein, lipid and carbohydrate metabolism. The aim of this study was to detect the genetic polymorphism of GH gene in five camel breeds reared in Egypt; Sudany, Somali, Mowaled, Maghrabi and Falahy, using PCR-RFLP technique. Also this work aimed to identify the single nucleotide polymorphism between different genotypes detected in these camel breeds. The amplified fragment of camel GH at 613-bp was digested with the restriction enzyme MspI and the result revealed the presence of three different genotypes; CC, CT and TT in tested breeds and significant differences were recorded in the genotype frequencies between these camel breeds. The result showed that the Maghrabi breed that is classified as a dual purpose camels had higher frequency for allele C (0.75) than those in the other tested four breeds. The sequence analysis declared the presence of a SNP (C→T) at position 264 in the amplified fragment which is responsible for the destruction of the restriction site C^CGG and consequently the appearance of two different alleles C and T. The nucleotide sequences of camel GH alleles T and C were submitted to nucleotide sequences database NCBI/Bankit/GenBank and have accession numbers: KP143517 and KP143518, respectively. It is concluded that only one SNP C→T was detected in GH gene among the five tested camel breeds reared in Egypt and this nucleotide substitution can be used as a marker for the genetic biodiversity between camel breeds reared in Egypt. Also, due to the possible association between allele C and higher growth rate, we can used it in MAS for camels and enter the camels possess this allele in breeding program as a way for enhancement of growth trait in camel breeds reared in Egypt.

Keywords: camel breeds in Egypt, GH, PCR-RFLP, SNPs

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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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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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Authors: Rakan Hassan M. Alzahrani, Ziyad Alzahrani, Bader Bashrahil, Abdulrahman Elyasi, Abdullah a Ghaddaf, Rayan Alzahrani, Mohammed Alkathlan, Nawaf Alghamdi, Dakheelallah Almutairi

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Background: Corticosteroid irrigations, which regularly involve the off-label use of budesonide mixed with normal saline in high volume Sino-nasal irrigations, have been more commonly used in the management of post-operative chronic rhinosinusitis (CRS). Objective: This article attempted to measure the efficacy of post-operative budesonide nasal irrigation compared to normal saline-alone nasal irrigation in the management of chronic rhinosinusitis (CRS) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: The databases PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched by two independent authors. Only RCTs comparing budesonide irrigation to normal saline alone irrigation for CRS with or without polyposis after functional endoscopic sinus surgery (FESS) were eligible. A random effect analysis model of the reported CRS-related quality of life (QOL) measures and the objective endoscopic assessment scales of the disease was done. Results: Only 6 RCTs met the eligibility criteria, with a total number of participants of 356. Compared to normal saline irrigation, budesonide nasal irrigation showed statically significant improvements in both the CRS-related quality of life (QOL) and the endoscopic findings (MD= -4.22 confidence interval [CI]: -5.63, -2.82 [P < 0.00001]), (SMD= -0.50 confidence interval [CI]: -0.93, -0.06 [P < 0.03]) respectively. Conclusion: Both intervention arms showed improvements in CRS-related QOL and endoscopic findings in post-FESS chronic rhinosinusitis with or without polyposis. However, budesonide irrigation seems to have a slight edge over conventional normal saline irrigation with no reported serious side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression.

Keywords: Budesonide, chronic rhinosinusitis, corticosteroids, nasal irrigation, normal saline

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Authors: Junaid Mahmood Alam

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Revalidating and harmonizing clinical chemistry analytical principles and optimizing methods through quality control programs and assessments is the preeminent means to attain optimal outcome within the clinical laboratory services. Present study reports revalidation of our existing IFCC regularized analytical methods, particularly hepatic and thyroid function tests, by optimization of precision analyses and processing through external and internal quality assessments and regression determination. Parametric components of hepatic (Bilirubin ALT, γGT, ALP), cardiac (LDH, AST, Trop I) and thyroid/pituitary (T3, T4, TSH, FT3, FT4) function tests were used to validate analytical techniques on automated chemistry and immunological analyzers namely Hitachi 912, Cobas 6000 e601, Cobas c501, Cobas e411 with UV kinetic, colorimetric dry chemistry principles and Electro-Chemiluminescence immunoassay (ECLi) techniques. Process of validation and revalidation was completed with evaluating and assessing the precision analyzed Preci-control data of various instruments plotting against each other with regression analyses R2. Results showed that: Revalidation and optimization of respective parameters that were accredited through CAP, CLSI and NEQAPP assessments depicted 99.0% to 99.8% optimization, in addition to the methodology and instruments used for analyses. Regression R2 analysis of BilT was 0.996, whereas that of ALT, ALP, γGT, LDH, AST, Trop I, T3, T4, TSH, FT3, and FT4 exhibited R2 0.998, 0.997, 0.993, 0.967, 0.970, 0.980, 0.976, 0.996, 0.997, 0.997, and R2 0.990, respectively. This confirmed marked harmonization of analytical methods and instrumentations thus revalidating optimized precision standardization as per IFCC recommended guidelines. It is concluded that practices of revalidating and harmonizing the existing or any new services should be followed by all clinical laboratories, especially those associated with tertiary care hospital. This is will ensure deliverance of standardized, proficiency tested, optimized services for prompt and better patient care that will guarantee maximum patients’ confidence.

Keywords: revalidation, standardized, IFCC, CAP, harmonized

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: Elisabeth Louise Ndjengue Mindang, Charline Florence Awounfack, Derek Tantoh Ndinteh, Rui W. M. Krause, Dieudonne Njamen

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The evolution of human fertility over the last 50 years has shown considerable problems due to a growing number of couples that find it difficult to procreate without medical assistance. In Africa, this inability to conceive affect 30 to 40% of couples. A number of contaminants in the environment are thought to contribute significantly to the observed infertility epidemic. Methods: On this basis, the impact of 40-days unique oral administration (between 9 and 10 am) of potassium sorbate (at of 12.5, 45, and 78 mg/kg BW doses) was evaluated on sexual maturation and hematologic parameters on immature Wistar rats (21-22 days of age). At the end of the treatment, animals were sacrificed. Vaginal opening was evaluated before the sacrifice. After the sacrifice, relative weight of reproductive organs, pituitary gonadotrophin level (LH and FSH), and sexuals steroids (estrogen and progesterone), cholesterol level in ovaries, folliculogenesis, and some hematological parameters were evaluated. Results: Compared to the control group, no significant variation was observed in the body weight of the animals treated with patassium sorbate. On the other hand, potassium sorbate, a significantly lower percentage (25%) of vaginal-opening in these rats, was observed from day 46 of age (p <0.01); likewise, a significant decrease was observed on the relative weight of the ovaries (p <0.01), number of primary follicles (p <0.01), and a significant increase of follicle number (p <0.001) at 78 mg/kg BW have been obseved. Potassium sorbate always decreased the number of white blood cells (p <0.05). Taken together, these results confirm the disturbing effects on the endocrine system, causing a decrease in fertility by increasing the number of follicles in atresia. A deleterious effect on the immune system was also observed. Overall, these results validate at least in part the global observations on the growing decline in fertility in populationsfeeding increasingly on industrial processed foods.

Keywords: potassium sorbate, early puberty, folliculogenesis, endocrine disruptor, immatur wistar rat

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Authors: Einat Peles, Anat Sason, Ariel Claman, Gabriel Barkay, Miriam Adelson

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Individuals with opioid addiction are characterized as suffering from stress responses disturbance, including the hypothalamic-pituitary-adrenal (HPA) axis, and autonomic nervous system function. HPA axis is known to be stabilized during methadone maintenance treatment (MMT). Mindfulness (present-oriented, nonjudgmental awareness of cognitions, emotions, perceptions, and habitual behavioral reactions in daily life) counteracts stress. To our knowledge, the relation between perceived stress and mindfulness trait among MMT patients has never been studied. To measure indices of mindfulness and their relation to perceived stress among MMT patients, a cross-sectional random sample of current MMT patients was performed using questionnaires for perceived stress (PSS) and mindfulness trait (FFMQ- yields a total score and individual scores for five internally consistent mindfulness factors: Observing, Describing, Acting with awareness and consciousness, Non-judging the inner experience, Non-reactivity to the inner experience). Two additional groups were studied to serve as reference groups; Medical students that are known to suffer from stress, and Axis II psychiatric diagnosis patients that are known to characterized with poor mindfulness trait. Results: Groups included 41 MMT patients, 27 Axis II patients and 36 medical students. High perceived stressed (PSS≥18) defined among 61% of the MMT patients and 50% of the medical students. Highest mindfulness score observed among non-stressed MMT patients (153.5±17.2) followed by the groups of stressed MMT and non-stressed student (128.9±17.0 and 130.5±13.3 respectively), with the lowest score among stressed students (116.3±17.9) (multivariate analyses, corrected model p (F=14.3) < 0.0005, p (group) < 0.0005, p (stress) < 0.0005, p (interaction) =0.2). Linear inverse correlations were found between perceived stress score and mindfulness score among MMT patients (R=-0.65, p < 0.0005) and students (R=-0.51, p=0.002). Axis II patients had the lowest mindfulness score (103.4±25.3). Conclusion: High prevalence of high perceived stressed which characterized with poor mindfulness trait observed in both MMT patients and medical students, two different population groups. The effectiveness of mindfulness treatment in reducing stress and improve mindfulness trait should be evaluated to improve rehabilitation of MMT patients, and students success.

Keywords: mindfulness, stress, methadone maintenance treatment, medical students

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

Abstract:

Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

Abstract:

Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Reham Hajomer, Ikram Elsiddig, Amna Hamad

Abstract:

Lepidium sativum (Garden Cress) belonging to Brassicaceae family is an annual herb locally known as El-rshad. In Ayurveda it is an important medicinal plant, traditionally used for the treatment of jaundice, liver problems, spleen diseases, gastrointestinal disorders, menstrual problems, fracture, arthritis, inflammatory conditions and for treatment of hypothyroidism. Hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones (Triiodithyronine T3 and Thyroxine T4) which are commonly caused by iodine deficiency. It’s divided into primary and secondary hypothyroidism, the primary caused by failure of thyroid function and secondary due to the failure of adequate thyroid-stimulating hormone (TSH) secretion from the pituitary gland or thyroid -releasing hormone (TRH) from the hypothalamus. The disease is most common in women over age 60. The objective regarding this study is to know whether Lepidium sativum would affect the level of thyroid hormones. The extract was prepared with 96% ethanol using Soxhlet apparatus. The anti-hypothyroidism activity was tested by using thirty male Wistar rats weighing (100-140 g) were used in the experiment. They were grouping into five groups, Group 1: Normal group= Administered only distilled water. Then 10 mg/kg Propylthiouracil was added to the drinking water of all other groups to induce hypothyroidism. Group 2: Negative control without any treatment; Group 3: Test group= treated with oral administration of 500mg/kg extract; Group 4: treated with oral administration of 250mg/kg of the extract; Group 5: Standard group (positive control) = treated with intraperitoneal Levothyroxine. All rats were incubated for 20 days at animal house with room temperature of proper ventilation provided with standard diet. The result show that the Lepidium sativum extract was found to increases the T3 and T4 in the propylthiouracil induced rats with values (0.29 ng/dl T3 and 0.57 U T4) for the 500mg/kg and (0.27 ng/dl T3 and 0.517 U T4) for the 250mg/kg in comparison with standard with values (0.241 ng/dl T3 and 0.516 U T4) so that Lepidium sativum can be stimulatory to thyroid function and possess significant anti-hypothyroidism effect with p-values ranges from (0.000006*-0.893472). In conclusion, from results obtained, Lepidium sativum plant extract was found to posses anti-hypothyroidism effects so its act as an agent that stimulates thyroid hormone secretion.

Keywords: anti-hypothyroidism, extract, lepidium, sativum

Procedia PDF Downloads 161

Authors: Ana Bermudez de Castro Muela, Xiomara Santos Salas, Silvia Cayon Somacarrera

Abstract:

The aim of this review is to explain what is the intracranial hypotension and its main causes, and also to approach to the diagnostic management in the different clinical situations, understanding radiological findings, and physiopathological substrate. An approach to the diagnostic management is presented: what are the guidelines to follow, the different tests available, and the typical findings. We review the myelo-CT and myelo-RM studies in patients with suspected CSF fistula or hypotension of unknown cause during the last 10 years in three centers. Signs of intracranial hypotension (subdural hygromas/hematomas, pachymeningeal enhancement, venous sinus engorgement, pituitary hyperemia, and lowering of the brain) that are evident in baseline CT and MRI are also sought. The intracranial hypotension is defined as a lower opening pressure of 6 cmH₂O. It is a relatively rare disorder with an annual incidence of 5 per 100.000, with a female to male ratio 2:1. The clinical features it’s an orthostatic headache, which is defined as development or aggravation of headache when patients move from a supine to an upright position and disappear or typically relieve after lay down. The etiology is a decrease in the amount of cerebrospinal fluid (CSF), usually by loss of it, either spontaneous or secondary (post-traumatic, post-surgical, systemic disease, post-lumbar puncture etc.) and rhinorrhea and/or otorrhea may exist. The pathophysiological mechanisms of hypotension and CSF hypertension are interrelated, as a situation of hypertension may lead to hypotension secondary to spontaneous CSF leakage. The diagnostic management of intracranial hypotension in our center includes, in the case of being spontaneous and without rhinorrhea and/or otorrhea and according to necessity, a range of available tests, which will be performed from less to more complex: cerebral CT, cerebral MRI and spine without contrast and CT/MRI with intrathecal contrast. If we are in a situation of intracranial hypotension with the presence of rhinorrhea/otorrhea, a sample can be obtained for the detection of b2-transferrin, which is found in the CSF physiologically, as well as sinus CT and cerebral MRI including constructive interference steady state (CISS) sequences. If necessary, cisternography studies are performed to locate the exact point of leakage. It is important to emphasize the significance of myelo-CT / MRI to establish the diagnosis and location of CSF leak, which is indispensable for therapeutic planning (whether surgical or not) in patients with more than one lesion or doubts in the baseline tests.

Keywords: cerebrospinal fluid, neuroradiology brain, magnetic resonance imaging, fistula

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Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

Abstract:

Changes in behaviour and physiology are the most important responses of marine life to anthropogenic impacts such as climate change and over-fishing. Behavioural changes (such as a shift in distribution or changes in phenology) can ensure that a species remains in an environment suited for its optimal physiological performance. However, if marine life is unable to shift their distribution, they are reliant on physiological adaptation (either by broadening their metabolic curves to tolerate a range of stressors or by shifting their metabolic curves to maximize their performance at extreme stressors). However, since there are links between fish physiology and behaviour, changes to either of these traits may have reciprocal interactions. This paper reviews the current knowledge of the links between the behaviour and physiology of fishes, discusses these in the context of exploitation and climate change, and makes recommendations for future research needs. The review revealed that our understanding of the links between fish behaviour and physiology is rudimentary. However, both are hypothesized to be linked to stress responses along the hypothalamic pituitary axis. The link between physiological capacity and behaviour is particularly important as both determine the response of an individual to a changing climate and are under selection by fisheries. While it appears that all types of capture fisheries are likely to reduce the adaptive potential of fished populations to climate stressors, angling, which is primarily associated with recreational fishing, may induce fission of natural populations by removing individuals with bold behavioural traits and potentially the physiological traits required to facilitate behavioural change. Future research should focus on assessing how the links between physiological capacity and behaviour influence catchability, the response to climate change drivers, and post-release recovery. The plasticity of phenotypic traits should be examined under a range of stressors of differing intensity in several species and life history stages. Future studies should also assess plasticity (fission or fusion) in the phenotypic structuring of social hierarchy and how this influences habitat selection. Ultimately, to fully understand how physiology is influenced by the selective processes driven by fisheries, long-term monitoring of the physiological and behavioural structure of fished populations, their fitness, and catch rates are required.

Keywords: climate change, metabolic shifts, over-fishing, phenotypic plasticity, stress response

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Authors: C. Romero, R. Ortega, P. Sánchez-Camacho, P. Aguilar, V. Segur, J. Ruiz, G. Gutiérrez

Abstract:

Introduction: Breast cancer is a leading cause of death in CLM. (2.8% of all deaths in women and 13,8% of deaths from tumors in womens). It is the most tumor incidence in CLM region with 26.1% from all tumours, except nonmelanoma skin (Cancer Incidence in Five Continents, Volume X, IARC). Cancer registries are a good information source to estimate cancer incidence, however the data are usually available with a lag which makes difficult their use for health managers. By contrast, mortality and survival statistics have less delay. In order to serve for resource planning and responding to this problem, a method is presented to estimate the incidence of mortality and survival data. Objectives: To estimate the incidence of breast cancer by age group in CLM in the period 1991-2013. Comparing the data obtained from the model with current incidence data. Sources: Annual number of women by single ages (National Statistics Institute). Annual number of deaths by all causes and breast cancer. (Mortality Registry CLM). The Breast cancer relative survival probability. (EUROCARE, Spanish registries data). Methods: A Weibull Parametric survival model from EUROCARE data is obtained. From the model of survival, the population and population data, Mortality and Incidence Analysis MODel (MIAMOD) regression model is obtained to estimate the incidence of cancer by age (1991-2013). Results: The resulting model is: Ix,t = Logit [const + age1*x + age2*x2 + coh1*(t – x) + coh2*(t-x)2] Where: Ix,t is the incidence at age x in the period (year) t; the value of the parameter estimates is: const (constant term in the model) = -7.03; age1 = 3.31; age2 = -1.10; coh1 = 0.61 and coh2 = -0.12. It is estimated that in 1991 were diagnosed in CLM 662 cases of breast cancer (81.51 per 100,000 women). An estimated 1,152 cases (112.41 per 100,000 women) were diagnosed in 2013, representing an increase of 40.7% in gross incidence rate (1.9% per year). The annual average increases in incidence by age were: 2.07% in women aged 25-44 years, 1.01% (45-54 years), 1.11% (55-64 years) and 1.24% (65-74 years). Cancer registries in Spain that send data to IARC declared 2003-2007 the average annual incidence rate of 98.6 cases per 100,000 women. Our model can obtain an incidence of 100.7 cases per 100,000 women. Conclusions: A sharp and steady increase in the incidence of breast cancer in the period 1991-2013 is observed. The increase was seen in all age groups considered, although it seems more pronounced in young women (25-44 years). With this method you can get a good estimation of the incidence.

Keywords: breast cancer, incidence, cancer registries, castilla-la mancha

Procedia PDF Downloads 286

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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Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

Abstract:

Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

Abstract:

The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

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Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

Abstract:

Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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