Search results for: corticosterone hormone
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 271

Search results for: corticosterone hormone

91 New Off-Line SPE-GC-MS/MS Method for Determination of Mineral Oil Saturated Hydrocarbons/Mineral Oil Hydrocarbons in Animal Feed, Foods, Infant Formula and Vegetable Oils

Authors: Ovanes Chakoyan

Abstract:

MOH (mineral oil hydrocarbons), which consist of mineral oil saturated hydrocarbons(MOSH) and mineral oil aromatic hydrocarbons(MOAH), are present in various products such as vegetable oils, animal feed, foods, and infant formula. Contamination of foods with mineral oil hydrocarbons, particularly mineral oil aromatic hydrocarbons(MOAH), exhibiting carcinogenic, mutagenic, and hormone-disruptive effects. Identifying toxic substances among the many thousands comprising mineral oils in food samples is a difficult analytical challenge. A method based on an offline-solid phase extraction approach coupled with gas chromatography-triple quadrupole(GC-MS/MS) was developed for the determination of MOSH/MOAH in various products such as vegetable oils, animal feed, foods, and infant formula. A glass solid phase extraction cartridge loaded with 7 g of activated silica gel impregnated with 10 % silver nitrate for removal of olefins and lipids. The MOSH/MOAH fractions were eluated with hexane and hexane: dichloromethane : toluene, respectively. Each eluate was concentrated to 50 µl in toluene and injected on splitless mode into GC-MS/MS. Accuracy of the method was estimated as measurement of recovery of spiked oil samples at 2.0, 15.0, and 30.0 mg kg -1, and recoveries varied from 85 to 105 %. The method was applied to the different types of samples (sunflower meal, chocolate ships, santa milk chocolate, biscuits, infant milk, cornflakes, refined sunflower oil, crude sunflower oil), detecting MOSH up to 56 mg/kg and MOAH up to 5 mg/kg. The limit of quantification(LOQ) of the proposed method was estimated at 0.5 mg/kg and 0.3 mg/kg for MOSH and MOAH, respectively.

Keywords: MOSH, MOAH, GC-MS/MS, foods, solid phase extraction

Procedia PDF Downloads 51
90 Modulation of Alternative Respiration Pathyway under Salt Stress in Exogenous Estrogen-Treated Maize Seedlings

Authors: Farideh K. Khosroushahi, Serkan Erdal, Mucip Geni̇şel

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Soil salinity is one of the major abiotic stress factors that restricts arable land and reduces crop productivity worldwide. High salt concentration adversely affects plant growth and development inducing water deficit, ionic toxicity, nutrient imbalance, and lead to oxidative stress. Although the stimulating role of mammalian sex hormones on various biological and biochemical processes under normal and stress condition have been proven, there is no study regarding with these hormone's effect on modulation of the alternative respiration pathway and AOX gene expression. In this study, changes in alternative respiration pathway in leaves of maize seedlings under salinity and the possible modulating effect of estrogen on these changes were investigated. Maize seedlings were grown in a hydroponic media for 11 days and then were exposed to salt stress for 3 days after being sprayed estrogen. The data obtained from oxygen consumption revealed that salt stress elevated cellular respiration value in the leaves. In addition, a marked increase was observed at alternative respiration level in salt-stressed seedlings. Compared to salt application alone, supplementation with estrogen resulted in a significant rise in alternative oxidase (AOX) activities. Similarly, while salt stress caused to rise in expressions of AOX gene compared to control seedlings, estrogen application resulted in further activation of these genes’ expression compared to stressed-seedlings alone. These data revealed that mitigating role of estrogen against the detrimental effects of salt stress is linked to modulation of alternative respiration pathway.

Keywords: alternative oxidase, estrogen, Ssalt stress, AOX, maize

Procedia PDF Downloads 185
89 Role of Zinc in Catch-Up Growth of Low-Birth Weight Neonates

Authors: M. A. Abdel-Wahed, Nayera Elmorsi Hassan, Safaa Shafik Imam, Ola G. El-Farghali, Khadija M. Alian

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Low-birth-weight is a challenging public health problem. Aim: to clarify role of zinc on enhancing catch-up growth of low-birth-weight and find out a proposed relationship between zinc effect on growth and the main growth hormone mediator, IGF-1. Methods: Study is a double-blind-randomized-placebo-controlled trial conducted on low-birth-weight-neonates delivered at Ain Shams University Maternity Hospital. It comprised 200 Low-birth-weight-neonates selected from those admitted to NICU. Neonates were randomly allocated into one of the following two groups: group I: low-birth-weight; AGA or SGA on oral zinc therapy at dose of 10 mg/day; group II: Low-birth-weight; AGA or SGA on placebo. Anthropometric measurements were taken including birth weight, length; head, waist, chest, mid-upper arm circumferences, triceps and sub-scapular skin-fold thicknesses. Results: At 12-month-old follow-up visit, mean weight, length; head (HC), waist, chest, mid-upper arm circumferences and triceps; also, infant’s proportions had values ≥ 10th percentile for weight, length and HC were significantly higher among infants of group I when compared to those of group II. Oral zinc therapy was associated with 24.88%, 25.98% and 19.6% higher proportion of values ≥ 10th percentile regarding weight, length and HC at 12-month-old visit, respectively [NNT = 4, 4 and 5, respectively]. Median IGF-1 levels measured at 6 months were significantly higher in group I compared to group II (median (range): 90 (19 – 130) ng/ml vs. 74 (21 – 130) ng/ml, respectively, p=0.023). Conclusion: Oral zinc therapy in low-birth-weight neonates was associated with significantly more catch-up growth at 12-months-old and significantly higher serum IGF-1 at 6-month-old.

Keywords: low-birth-weight, zinc, catch-up growth, neonates

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88 Anti-Prostate Cancer Effect of GV-1001, a Novel Gonadotropin-Releasing Hormone Receptor Ligand

Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

Procedia PDF Downloads 331
87 Green Synthesis of Silver Nanoparticles with Aqueous Extract of Moringa oleifera Lam Leaves and Its Ameliorative Effect on Benign Prostatic Hyperplasia in Wistar Rat

Authors: Rotimi Larayetana, Yahaya Abdulrazaq, Oladunni O. Falola, Abayomi Ajayi

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The aim of this study was to perform green synthesis of silver nanoparticles (AgNPs) with the aqueous extract of Moringa oleifera Lam (M oleifera) leaves and determine its effects on benign prostatic hyperplasia in Wistar rats. Silver nitrate (AgNO₃) solution was reduced using the aqueous extract of Moringa oleifera Lam leaves, the resultant biogenic AgNPs were characterized by Fourier transformed infrared spectrophotometric, SEM, TEM and X-ray diffraction analysis. Animal experiments involved thirty (30) adult male Wistar rats randomly divided into five groups (A to E; n ₌ 5). Group A received only subcutaneous injection of olive oil daily while the other groups got 3 mg/kg/daily of testosterone propionate (TP) subcutaneously plus 50 mg/kg/daily of AgNPs intraperitoneally (B), 3 mg/kg/daily of TP plus 25 mg/kg/daily of AgNPs (C), 3 mg/kg/daily of TP only (D) and 25 mg/kg/daily of AgNPs only (E). The animals were sacrificed after 14 days, and the prostate gland, liver, and kidney were processed for histological analysis. Phytochemical screening and GC-MS analysis were performed to determine the composition of the M oleifera extract used. Biogenic AgNPs with an average diameter of 23 nm were synthesized. Biogenic AgNPs ameliorated hormone-induced prostate enlargement, and the inhibition of prostatic hypertrophy could be due to the presence of a significant amount of plant fatty acids and phytosterols in the aqueous extract of M oleifera extract. However, the administration of biogenic AgNPs at higher doses impacted negatively on the cytoarchitecture of the liver. Green synthesis of AgNPs with the aqueous extract of Moringa oleifera might be beneficial for the treatment of BPH.

Keywords: benign prostatic hyperplasia, biogenic synthesis, Moringa oleifera, silver nanoparticles, testosterone

Procedia PDF Downloads 52
86 The Effect of Melatonin on Acute Liver Injury: Implication to Shift Work Related Sleep Deprivation

Authors: Bing-Fang Lee, Srinivasan Periasamy, Ming-Yie Liu

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Shift work sleep disorder is a common problem in industrialized world. It is a type of circadian rhythmic sleep disorders characterized by insomnia and sleep deprivation. Lack of sleep in workers may lead to poor health conditions such as hepatic dysfunction. Melatonin is a hormone secreted by the pineal gland to alleviate insomnia. Moreover, it is a powerful antioxidant and may prevent acute liver injury. Therefore, workers take in melatonin to deal with sleep-related health is an important issue. The aim of this study was to investigate the effect of melatonin on an acute hepatic injury model sinusoidal obstruction syndrome (SOS) in mice. Male C57BL/6 mice were injected with a single dose (500 mg/kg) of monocrotaline (MCT) to induce SOS. Melatonin (1, 3, 10 and 30 mg/kg) was injected 1 h before MCT treatment. After 24 h of MCT treatment, mice were sacrificed. The blood and liver were collected. Organ damage was evaluated by serum biochemistry, hematology analyzer, and histological examination. Low doses of melatonin (1 and 3 mg/kg) had no protective effect on SOS. However, high doses (10 and 30 mg/kg) exacerbated SOS. In addition, it not only increased serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and extended liver damage indicated by histological examination but also decreased platelet levels, lymphocyte ratio, and glutathione level; it had no effect on malondialdehyde and nitric oxide level in SOS mice. To conclude, melatonin may exacerbate MCT-induced SOS in mice. Furthermore, melatonin might have a synergistic action with SOS. Usage of melatonin for insomnia by people working in long shift must be cautioned; it might cause acute hepatic injury.

Keywords: acute liver injury, melatonin, shift work, sleep deprivation

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85 Modulation of Tamoxifen-Induced Cytotoxicity in Breast Cancer Cell Lines by 3-Bromopyruvate

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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84 Indoleamines (Serotonin & Melatonin) in Edible Plants: Its Influence on Human Health

Authors: G. A. Ravishankar, A. Ramakrishna

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Melatonin (MEL) and Serotonin (SER), also known as [5-Hydroxytryptamine (5-HT)] are reported to be in a range of plant types which are edible. Their occurrence in plants species appears to be ubiquitous. Their presence in high quantities in plants assumes significance owing to their physiological effects upon consumption by human beings. MEL is a well known animal hormone mainly released by the pineal gland known to influence circadian rhythm, sleep, apart from immune enhancement. Similarly, SER is a neurotransmitter that regulates mood, sleep and anxiety in mammals. It is implicated in memory, behavioral changes, scavenging reactive oxygen species, antipsychotic, etc. Similarly Role of SER and MEL in plant morphogenesis, and various physiological processes through intense research is beginning to unfold. These molecules are in common foods viz banana, pineapple, plum, nuts, milk, grape wine. N- Feruloyl serotonin and p-coumaroyl serotonin found in certain seeds are found to possess antioxidant, anti-inflammatory, antitumor, antibacterial, and anti-stress potential apart from reducing depression and anxiety. MEL is found in Mediterranean diets, nuts, cherries, tomato berries, and olive products. Consumption of foods rich in MEL is known to increase blood MEL levels which have been implicated in protective effect against cardiovascular damage, cancer initiation and growth. MEL is also found in wines, green tea, beer, olive oil etc. Moreover, presence of SER and MEL in Coffee beans (green and roasted beans) and decoction has been reported us. In this communication we report the occurrence of indole amines in edible plants and their implications in human health.

Keywords: serotonin, melatonin, edible plants, neurotransmitters, physiological effects

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83 Evaluation of Gene Expression after in Vitro Differentiation of Human Bone Marrow-Derived Stem Cells to Insulin-Producing Cells

Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

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Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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82 Seed Quality Aspects of Nightshade (Solanum Nigrum) as Influenced by Gibberellins (GA3) on Seed

Authors: Muga Moses

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Plant growth regulators are actively involved in the growth and yield of plants. However, limited information is available on the combined effect of gibberellic acid (GA3) on growth attributes and yield of African nightshade. This experiment will be designed to fill this gap by studying the performance of African nightshade under the application of hormones. Gibberellic acid is a plant growth hormone that promotes cell expansion and division. A greenhouse and laboratory experiment will be conducted at the University of Sussex biotechnology greenhouse and Agriculture laboratory using a growth chamber to study the effect of GA3 on the growth and development attributes of African nightshade. The experiment consists of three replications and 5 treatments and is laid out in a randomized complete block design consisting of various concentrations of GA3. 0ppm, 50ppm, 100ppm, 150ppm and 200ppm. local farmer seed was grown in plastic pots, 6 seeds then hardening off to remain with four plants per pot at the greenhouse to attain purity of germplasm, proper management until maturity of berries then harvesting and squeezing to get seeds, paper dry on the sun for 7 days. In a laboratory, place 5 Whatman filter paper on glass petri-dish subject to different concentrations of stock solution, count 50 certified and clean, healthy seeds, then arrange on the moist filter paper and mark respectively. Spray with the stock solution twice a day and protrusion of radicle termed as germination count and discard to increase the accuracy of precision. Data will be collected on the application of GA3 to compare synergistic effects on the growth, yield, and nutrient contents on African nightshade.

Keywords: African nightshade, growth, yield, shoot, gibberellins

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81 Role of Pro-Inflammatory and Regulatory Cytokines in Pathogenesis of Graves’ Disease in Association with Autoantibody Thyroid and Regulatory FoxP3 T-Cells

Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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80 Annual Audit for the Year 2021 for Patients with Hyperparathyroidism: Not as Rare an Entity as We Believe

Authors: Antarip Bhattacharya, Dhritiman Maitra

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Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia due to autonomous production of parathormone (PTH) and the third most common endocrine disorder. Upto 2% of postmenopausal women could have this condition. Primary hyperparathyroidism is characterized by hypercalcemia with a high or insufficiently suppressed level of parathyroid hormone and is caused by a solitary parathyroid adenoma in 85-90% of patients. PHPT may also be caused by parathyroid hyperplasia (involving multiple glands) or parathyroid carcinoma. Associated morbidities and sequelae include decreased bone mineral density, fractures, kidney stones, hypertension, cardiac comorbidities and psychiatric disorder which entail huge costs for treatment. In the year 2021, by virtue of running a Breast and Endocrine Surgery clinic in a Tier 1 city at a tertiary care hospital, the opportunity to be associated with patients of hyperparathyroidism came our way. Here, we shall describe the spectrum of clinical presentations and customisation of treatment for parathyroid diseases with reference to the above patients. A retrospective analysis of the data of all patients presenting with symptoms of parathyroid diseases was made and classified according to the cause. 13 patients had presented with symptoms of hyperparathyroidism and each case presented with unique symptoms and necessitated detailed evaluation. The treatment or surgery offered to each patient was tailored to his/her individual disease and led to favourable outcomes. Diseases affecting parathyroid are not as rare as we believe. Each case merits detailed clinical evaluation, investigations and tailoring of suitable treatment with regard to medical management and extent of surgery. Intra-operative frozen section/iOPTH monitoring are really useful adjuncts for intra-operative decision making.

Keywords: hyperparathyroidism, parathyroid adenoma, parathyroid surgery, PTH

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79 In vitro Study on Characterization and Viability of Vero Cell Lines after Supplementation with Porcine Follicular Fluid Proteins in Culture Medium

Authors: Mayuva Youngsabanant, Suphaphorn Rabiab, Hatairuk Tungkasen, Nongnuch Gumlungpat, Mayuree Pumipaiboon

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The porcine follicular fluid proteins (pFF) of healthy small size ovarian follicles (1-3 mm in diameters) of Large White pig ovaries were collected by sterile technique. They were used for testing the effect on cell viability and characterization of Vero cell lines using MTT assay. Two hundred microliter of round shape Vero cell lines were culture in 96 well plates with DMEM for 24 h. After that, they were attachment to substrate and some changed into fibroblast shape and spread over the surface after culture for 48 h. Then, Vero cell lines were treated with pFF at concentration of 2, 4, 20, 40, 200, 400, 500, and 600 µg proteins/mL for 24 h. Yields of the best results were analyzed by using one-way ANOVA. MTT assay reviewed an increasing in percentage of viability of Vero cell lines indicated that at concentration of 400-600 µg proteins/mL showed higher percentage of viability (115.64 ± 6.95, 106.91 ± 5.27 and 116.73 ± 20.15) than control group. They were significantly different from the control group (p < 0.05) but lower than the positive control group (DMEM with 10% heat treated fetal bovine serum). Cell lines showed normal character in fibroblast elongate shape after treated with pFF except in high concentration of pFF. This result implies that pFF of small size ovarian follicle at concentration of 400-600 µg proteins/mL could be optimized concentration for using as a supplement in Vero cell line culture medium to promote cell viability instead of growth hormone from fetal bovine serum. This merit could be applied in other cell biotechnology researches. Acknowledgements: This work was funded by a grant from Silpakorn University and Faculty of Science, Silpakorn University, Thailand.

Keywords: cell viability, porcine follicular fluid, MTT assay, Vero cell line

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78 The Effect of Malaria Parasitaemia on Serum Reproductive Hormonal Levels of Asymptomatic HIV Subjects in Nauth Nnewi, South Eastern Nigeria

Authors: Ezeugwunne Ifeoma Priscilla, Charles Chinedum Onyenekwe, Joseph Eberendu Ahaneku, Rosemary Adanma Analike, Adesuwa Peace Eidangbe

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This study was designed to assess the effect of malaria parasitaemia on serum reproductive hormone levels of asymptomatic HIV adult subjects. A total of 271 participants aged between 17 and 58 ears were conveniently recruited. 135 asymptomatic HIV-infected subjects participated in the study; 67 of them had malaria parasitaemia. 136 HIV seropositive control subjects, 68 of them had malaria parasitaemia. Blood samples were collected from the participants for the determination of HIV status by immunoassay and immunochromatography. Enzyme-linked immunosorbent assay (ELISA) was used to assay for serum LH, FSH, Estrogen, testosterone, progesterone, prolactin, and PSA levels, CD4+T cell counts by Cyflow method, thick and thin films determination of malaria parasitaemia count and density by WHO. Student's t-tests and ANOVA were used to compare means. P<0.05 was considered statistically significant. The results showed significant differences in serum levels of LH, FSH, PSA, estrogen, progesterone, and testosterone amongst the groups at P<0.05, respectively. The serum levels of LH, FSH, and PSA were significantly higher in malaria-infected asymptomatic HIV subjects than in asymptomatic HIV subjects with malaria parasitaemia (P<0.05 in each case). Also, the serum levels of LH, FSH, PSA, estrogen, and progesterone were significantly higher in malaria-infected asymptomatic HIV subjects compared with malaria-infected HIV seronegative subjects (P<0.05, respectively). The mean MP counts and MP density were significantly higher in asymptomatic HIV subjects compared to HIV seronegative subjects (P<0.05, in each case). The mean serum levels of testosterone were significantly lower in both malaria-infected and malaria uninfected HIV seronegative subjects (P<0.05, in each case). In conclusion, Malaria and HIV co-infection might increase the burden of hypogonadism as well as primary testicular failure, hyperprogesteronaemia, elevated levels of estrogen, and PSA in adult males asymptomatic HIV subjects.

Keywords: malaria parasitaemia, HIV, CD4, reproductive hormones

Procedia PDF Downloads 107
77 In Ovo Injection of N-Carbamylglutamate Improves Growth Performance, Muscle Fiber Development, and Meat Quality in Broiler Chickens

Authors: Wang Yuan-hao, Habtamu Ayalew, Jing Wang, Shugeng Wu, Kai Qiu, Guanghai Qi, Haijun Zhang

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N-carbamylglutamate (NCG) has emerged as a promising candidate for regulating endogenous arginine synthesis, thereby promoting desirable growth, carcass traits, and muscle development in broilers. Thus, this study aimed to investigate the effects of NCG in ovo feeding on the growth performance, growth hormones, and meat quality of Ross 308 breeder broilers. A total of 1680 embryo eggs were equally allocated into three treatment groups: non punctured control (NC), saline-injected control (SC; 100μL/egg), and N-carbamylglutamate injected group (NCG; 2 mg/egg). The treatment solution was injected into the amniotic cavity of the embryo at 17.5 days of incubation (DOI). For the subsequent 42 days of post hatch experimental sampling, a total of 360 broiler chicks with 6 replications per treatment and 15 chicks per replication were used. Chickens in the NCG group showed significantly higher (P<0.05) body weight gain (BWG) and final body weight (FBW) at both 21 and 42 days after hatch (DAH), while feed conversion efficiency (FCE) was significantly improved (P<0.05) at 42 DAH. The weight and percentage of drums at 21 DAH and the weight and percentage of breast muscle at 42 DAH were significantly higher (P<0.05) in the NCG group. In addition, insulin (INS), growth hormone (GH), and testosterone (T) levels were significantly higher (P<0.05) in the NCG groups at 21 and 42 DAH. Furthermore, triiodothyronine (T3) and tetraiodothyronine (T4) levels were significantly higher (P<0.05) in the NCG treatment group. Interestingly, meat color values were also significantly higher (P<0.05) in the NCG group at 24 hrs postmortem. Collectively, these findings show that 2 mg NCG in ovo injection improves the growth performance and meat quality of broilers; even the effects extend into the market age of the chickens.

Keywords: N-carbamylglutamate, broiler, in ovo injection, growth performance, meat quality

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76 Preparation of Flurbiprofen Derivative for Enhanced Brain Penetration

Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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75 Quantitative Detection of the Conformational Transitions between Open and Closed Forms of Cytochrome P450 Oxidoreductase (CYPOR) at the Membrane Surface in Different Functional States

Authors: Sara Arafeh, Kovriguine Evguine

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Cytochromes P450 are enzymes that require a supply of electrons to catalyze the synthesis of steroid hormones, fatty acids, and prostaglandin hormone. Cytochrome P450 Oxidoreductase (CYPOR), a membrane bound enzyme, provides these electrons in its open conformation. CYPOR has two cytosolic domains (FAD domain and FMN domain) and an N-terminal in the membrane. In its open conformation, electrons flow from NADPH, FAD, and finally to FMN where cytochrome P450 picks up these electrons. In the closed conformation, cytochrome P450 does not bind to the FMN domain to take the electrons. It was found that when the cytosolic domains are isolated, CYPOR could not bind to cytochrome P450. This suggested that the membrane environment is important for CYPOR function. This project takes the initiative to better understand the dynamics of CYPOR in its full length. Here, we determine the distance between specific sites in the FAD and FMN binding domains in CYPOR by Forster Resonance Energy Transfer (FRET) and Ultrafast TA spectroscopy with and without NADPH. The approach to determine these distances will rely on labeling these sites with red and infrared fluorophores. Mimic membrane attachment is done by inserting CYPOR in lipid nanodiscs. By determining the distances between the donor-acceptor sites in these domains, we can observe the open/closed conformations upon reducing CYPOR in the presence and absence of cytochrome P450. Such study is important to better understand CYPOR mechanism of action in various endosomal membranes including hepatic CYPOR which is vital in plasma cholesterol homeostasis. By investigating the conformational cycles of CYPOR, we can synthesize drugs that would be more efficient in affecting the steroid hormonal levels and metabolism of toxins catalyzed by Cytochrome P450.

Keywords: conformational cycle of CYPOR, cytochrome P450, cytochrome P450 oxidoreductase, FAD domain, FMN domain, FRET, Ultrafast TA Spectroscopy

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74 Microbial Electrochemical Remediation System: Integrating Wastewater Treatment with Simultaneous Power Generation

Authors: Monika Sogani, Zainab Syed, Adrian C. Fisher

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Pollution of estrogenic compounds has caught the attention of researchers as the slight increase of estrogens in the water bodies has a significant impact on the aquatic system. They belong to a class of endocrine disrupting compounds (EDCs) and are able to mimic hormones or interfere with the action of endogenous hormones. The microbial electrochemical remediation system (MERS) is employed here for exploiting an electrophototrophic bacterium for evaluating the capacity of biodegradation of ethinylestradiol hormone (EE2) under anaerobic conditions with power generation. MERS using electro-phototrophic bacterium offers a tailored solution of wastewater treatment in a developing country like India which has a huge solar potential. It is a clean energy generating technology as they require only sunlight, water, nutrients, and carbon dioxide to operate. Its main feature that makes it superior over other technologies is that the main fuel for this MERS is sunlight which is indefinitely present. When grown in light with organic compounds, these photosynthetic bacteria generate ATP by cyclic photophosphorylation and use carbon compounds to make cell biomass (photoheterotrophic growth). These cells showed EE2 degradation and were able to generate hydrogen as part of the process of nitrogen fixation. The two designs of MERS were studied, and a maximum of 88.45% decrease in EE2 was seen in a total period of 14 days in the better design. This research provides a better insight into microbial electricity generation and self-sustaining wastewater treatment facilities. Such new models of waste treatment aiming waste to energy generation needs to be followed and implemented for building a resource efficient and sustainable economy.

Keywords: endocrine disrupting compounds, ethinylestradiol, microbial electrochemical remediation systems, wastewater treatment

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73 Evaluation of a Chitin Synthesis Inhibitor Novaluron in the Shrimp Palaemon Adspersus: Impact on Ecdysteroids and Chitin Contents

Authors: Hinda Berghiche, Hamida Benradia, Noureddine Soltani

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Pesticides are widely used in crop production and are known to induce a major contamination of ecosystems especially in aquatic environments. The leaching of a large amount of pollutants derived from agricultural activities (fertilizers, pesticides) might contaminate rivers which diverse into the likes and estuarine and coastal environments affecting several organisms such as crustacean species. In this context, there is searched for new selective insecticides with minimal toxic effects on the environment and human health such as growth insect regulators (GIRs). The current study aimed to examine the impact of novaluron (CE 20%), a potent benzoylphenylurea derivative insecticide on mosquito larvae, against non-target shrimp, Palaemon adspersus (Decapoda, Palaemonidae). The compound was tested at two concentrations (0.91 mg/L and 4.30 mg/L) corresponding respectively to the LC50 and LC90 determined against fourth-instar larvae of Culiseta longiareolata (Diptera, Culicidae). The molting hormone titer was determined in the haemolymph by an enzyme-immunoassay, while chitin was measured in peripheral integument at different stages during the molting cycle. Under normal conditions, the haemolymphatic ecdysteroid concentrations increased during the molting cycle to reach peak at stage D. In the treated series, we note absence of the peak at stage D and an increase at stages B, C and D as compared to the controls. Concerning the chitin amounts, we observe an increase from stage A to stage C followed by a decrease at stage D. Exposition of shrimps to novaluron resulted in a significant decrease of values at all molting stages with a dose-response effect. Thus, the insecticide can present secondary effects on this non-target arthropod species.

Keywords: toxicology, novaluron, crustacean, palaemon adspersus, ecdysteroids, cuticle, chitin

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72 The Role of Surgery to Remove the Primary Tumor in Patients with Metastatic Breast Cancer

Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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71 Hesperidin through Acting on Proliferating Cell Nuclear Antigen and Follicle Stimulating Hormone Receptor Expression Decreased Ovarian Toxicity Induced by Malathion

Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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70 Breast Cancer: The Potential of miRNA for Diagnosis and Treatment

Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

Procedia PDF Downloads 63
69 Plant Mediated RNAi Approach to Knock Down Ecdysone Receptor Gene of Colorado Potato Beetle

Authors: Tahira Hussain, Ilhom Rahamkulov, Muhammad Aasim, Ugur Pirlak, Emre Aksoy, Mehmet Emin Caliskan, Allah Bakhsh

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RNA interference (RNAi) has proved its usefulness in functional genomic research on insects recently and is considered potential strategy in crop improvement for the control of insect pests. The different insect pests incur significant losses to potato yield worldwide, Colorado Potato Beetle (CPB) being most notorious one. The present study focuses to knock down highly specific 20-hydroxyecdysone hormone-receptor complex interaction by using RNAi approach to silence Ecdysone receptor (EcR) gene of CPB in transgenic potato plants expressing dsRNA of EcR gene. The partial cDNA of Ecdysone receptor gene of CPB was amplified using specific primers in sense and anti-sense orientation and cloned in pRNAi-GG vector flanked by an intronic sequence (pdk). Leaf and internodal explants of Lady Olympia, Agria and Granola cultivars of potato were infected with Agrobacterium strain LBA4404 harboring plasmid pRNAi-CPB, pRNAi-GFP (used as control). Neomycin phosphotransferase (nptII) gene was used as a plant selectable marker at a concentration of 100 mg L⁻¹. The primary transformants obtained have shown proper integration of T-DNA in plant genome by standard molecular analysis like polymerase chain reaction (PCR), real-time PCR, Sothern blot. The transgenic plants developed out of these cultivars are being evaluated for their efficacy against larvae as well adults of CPB. The transgenic lines are expected to inhibit expression of EcR protein gene, hindering their molting process, hence leading to increased potato yield.

Keywords: plant mediated RNAi, molecular strategy, ecdysone receptor, insect metamorphosis

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68 Tackling Food Waste Challenge with Nanotechnology: Controllable Ripening via Metal Organic Framework

Authors: Boce Zhang, Yaguang Luo

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Ripening of climacteric fruits, such as bananas and avocados, are usually initiated days prior to the retail marketing. However, upon the onset of irreversible ripening, they undergo rapid spoilage if not consumed within a narrow climacteric time window. Controlled ripening of climacteric fruits is a critical step to provide consumers with high-quality products while reducing postharvest losses and food waste. There is a high demand for technologies that can retard the ripening process or enable accelerated ripening immediately before consumption. In this work, metal−organic framework (MOF) was developed as a solid porous matrix to encapsulate gaseous hormone, including ethylene, for subsequent application. The feasibility of the on-demand stimulated ripening of bananas and avocados is also evaluated. MOF was synthesized and loaded with ethylene gas. The MOF−ethylene was placed inside sealed containers with preclimacteric bananas and avocados and stored at 16 °C. The fruits were treated for 24-48 hours, and evaluated for ripening progress. Results indicate that MOF−ethylene treatment significantly accelerated the ripening-related changes of color and textural properties in treated bananas and avocados. The average ripening period for both avocados and bananas were reduced in half by using this method. No significant differences of quality characteristics at respective ripening stages were observed between produce ripened via MOF-ethylene versus exogenously supplied ethylene gas or endogenously produced ethylene. Solid MOF matrices could have multiple advantages compared to existing systems, including easy to transport and safe to use by minimally trained produce handlers and consumers. We envision that this technology can help tackle food waste challenges at the critical retail and consumer stages in the food supply chain.

Keywords: climacteric produce, controllable ripening, food waste challenge, metal organic framework

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67 Early Hypothyroidism after Radiotherapy for Nasopharyngeal Carcinoma

Authors: Nejla Fourati, Zied Fessi, Fatma Dhouib, Wicem Siala, Leila Farhat, Afef Khanfir, Wafa Mnejja, Jamel Daoud

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Purpose: Radiation induced hypothyroidism in nasopharyngeal cancer (NPC) ranged from 15% to 55%. In reported data, it is considered as a common late complication of definitive radiation and is mainly observed 2 years after the end of treatment. The aim of this study was to evaluate the incidence of early hypothyroidism within 6 months after radiotherapy. Patients and methods: From June 2017 to February 2020, 35 patients treated with concurrent chemo-radiotherapy (CCR) for NPC were included in this prospective study. Median age was 49 years [23-68] with a sex ratio of 2.88. All patients received intensity modulated radiotherapy (IMRT) at a dose of 69.96 Gy in 33 daily fractions with weekly cisplatin (40mg/m²) chemotherapy. Thyroid stimulating hormone (TSH) and Free Thyroxine 4 (FT4) dosage was performed before the start of radiotherapy and 6 months after. Different dosimetric parameters for the thyroid gland were reported: the volume (cc); the mean dose (Dmean) and the %age of volume receiving more than 45 Gy (V45Gy). Wilcoxon Test was used to compare these different parameters between patients with or without hypothyroidism. Results: At baseline, 5 patients (14.3%) had hypothyroidism and were excluded from the analysis. For the remaining 30 patients, 9 patients (30%) developed a hypothyroidism 6 months after the end of radiotherapy. The median thyroid volume was 10.3 cc [4.6-23]. The median Dmean and V45Gy were 48.3 Gy [43.15-55.4] and 74.8 [38.2-97.9] respectively. No significant difference was noted for all studied parameters. Conclusion: Early hypothyroidism occurring within 6 months after CCR for NPC seems to be a common complication (30%) that should be screened. Good patient monitoring with regular dosage of TSH and FT4 makes it possible to treat hypothyroidism in asymptomatic phase. This would be correlated with an improvement in the quality of life of these patients. The results of our study do not show a correlation between the thyroid doses and the occurrence of hypothyroidism. This is probably related to the high doses received by the thyroid in our series. These findings encourage more optimization to limit thyroid doses and then the risk of radiation-induced hypothyroidism

Keywords: nasopharyngeal carcinoma, hypothyroidism, early complication, thyroid dose

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66 Multi-Disciplinary Rehabilitation in Osmotic Demyelination Syndrome: A Case Report

Authors: Wei Qu, Cassandra Agius, Nikki Varvazovsky, Angela Meade

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The goals of the case study are to address the importance of early diagnosis of osmotic demyelination syndrome (ODS) and to analyse the types, duration, and intensities of the rehabilitation program to promote neurological and functional recovery. It can be associated with biphasic course of disease and severe neurological and neuropsychiatric symptoms. Although a few treatment modalities, such as plasmapheresis, immunoglobulin therapy, steroid, and thyrotrophin-releasing hormone, have been suggested, there is no effective treatment for ODS. The overall prognosis of established ODS is generally poor. A high proportion of patients have a severe permanent disability, which has led to social, economic, and emotional burdens to carers and societies. In this case, a 69-year-old retired pensioner with chronic alcoholism was admitted to the hospital with a reduced level of consciousness and tonic-clonic seizure. He had severe hyponatraemia (serum sodium 118 mmol/L) and hypokalemia (serum potassium 2.8 mmol/L). He was treated with anticonvulsants, 150ml 3% hypertonic saline over one hour, and 40 mmol potassium chloride over one hour, and his sodium was increased by 11 mmol/L in the first 24 hours. However, he had worsened neurological symptoms with quadriplegia, dysphagia, anarthria, and confusion, and the radiological features suggested the diagnosis of ODS. He had minimal neurological recovery during the first four weeks of hospital admission. He was treated with seven weeks of a multi-disciplinary intensive rehabilitation program. On discharge, he had made a significant cognitive and functional recovery and could mobilize independently without a walking aid. In conclusion, ODS can still occur despite correcting sodium following the current clinical guidelines. Patients with severe neurological deficits in the context of osmotic demyelination syndrome would benefit from intensive rehabilitation to facilitate their functional improvement and to promote their quality of life.

Keywords: osmotic demyelination syndrome, hyponatremia, central pontine and extrapontine myelinolysis, rehabilitation

Procedia PDF Downloads 62
65 Challenges in the Management of Her2 Neu Positive Breast Cancer Patients: Real World Data from India

Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala

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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.

Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab

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64 Correlation of Leptin with Clinico-Pathological Features of Breast Cancer

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

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

Keywords: breast cancer, expression, leptin, leptin receptors

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63 Exercise Intensity Increasing Appetite, Energy, Intake Energy Expenditure, and Fat Oxidation in Sedentary Overweight Individuals

Authors: Ghalia Shamlan, M. Denise Robertson, Adam Collins

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Appetite control (i.e. control of energy intake) is important for weight maintenance. Exercise contributes to the most variable component of energy expenditure (EE) but its impact is beyond the energy cost of exercise including physiological, behavioural, and appetite effects. Exercise is known to acutely influence effect appetite but evidence as to the independent effect of intensity is lacking. This study investigated the role of exercise intensity on appetite, energy intake (EI), appetite related hormone, fat utilisation and subjective measures of appetite. One hour after a standardised breakfast, 10 sedentary overweight volunteers. Subjects undertook either 8 repeated 60 second bouts of cycling at 95% VO2max (high intensity) or 30 minutes of continuous cycling, at a fixed cadence, equivalent to 50% of the participant’s VO2max (low intensity) in a randomised crossover design. Glucose, NEFA, glucagon-like peptide-1 (GLP-1) were measured fasted, postprandial, and pre and post-exercise. Satiety was assessed subjectively throughout the study using visual analogue scales (VAS). Ad libitum intake of a pasta meal was measured at the end (3-h post-breakfast). Interestingly, there was not significant difference in EE fat oxidation between HI and LI post-exercise. Also, no significant effect of high intensity (HI) was observed on the ad libitum meal, 24h and 48h EI post-exercise. However the mean 24h EI was 3000 KJ lower following HI than low intensity (LI). Despite, no significant differences in hunger score, glucose, NEFA and GLP-1 between both intensities were observed. However, NEFA and GLP-1 plasma level were higher until 30 min post LI. In conclusion, the similarity of EE and oxidation outcomes could give overweight individuals an option to choose between intensities. However, HI could help to reduce EI. There are mechanisms and consequences of exercise in short and long-term appetite control; however, these mechanisms warrant further explanation. These results support the need for future research in to the role of in regulation energy balance, especially for obese people.

Keywords: appetite, exercise, food intake, energy expenditure

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62 Development of a Robust Protein Classifier to Predict EMT Status of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Tumors

Authors: ZhenlinJu, Christopher P. Vellano, RehanAkbani, Yiling Lu, Gordon B. Mills

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The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal characteristics, such as profound disruption of cell-cell junctions, loss of apical-basolateral polarity, and extensive reorganization of the actin cytoskeleton to induce cell motility and invasion. A hallmark of EMT is its capacity to promote metastasis, which is due in part to activation of several transcription factors and subsequent downregulation of E-cadherin. Unfortunately, current approaches have yet to uncover robust protein marker sets that can classify tumors as possessing strong EMT signatures. In this study, we utilize reverse phase protein array (RPPA) data and consensus clustering methods to successfully classify a subset of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumors into an EMT protein signaling group (EMT group). The overall survival (OS) of patients in the EMT group is significantly worse than those in the other Hormone and PI3K/AKT signaling groups. In addition to a shrinkage and selection method for linear regression (LASSO), we applied training/test set and Monte Carlo resampling approaches to identify a set of protein markers that predicts the EMT status of CESC tumors. We fit a logistic model to these protein markers and developed a classifier, which was fixed in the training set and validated in the testing set. The classifier robustly predicted the EMT status of the testing set with an area under the curve (AUC) of 0.975 by Receiver Operating Characteristic (ROC) analysis. This method not only identifies a core set of proteins underlying an EMT signature in cervical cancer patients, but also provides a tool to examine protein predictors that drive molecular subtypes in other diseases.

Keywords: consensus clustering, TCGA CESC, Silhouette, Monte Carlo LASSO

Procedia PDF Downloads 437