Search results for: vitamin D receptor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 823

Search results for: vitamin D receptor

703 Vitamin D Supplementation Potentiates the Clinical Benefits of Metformin and Pioglitazone in Indian Women with Polycystic Ovary Syndrome

Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

Abstract:

Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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702 The Association of Estrogen Receptor Alpha Xbai Gg Genotype and Severe Preeclampsia

Authors: Saeedeh Salimi, Farzaneh Farajian- Mashhadi, Ehsan Tabatabaei, Mahnaz Shahrakipoor, Minoo Yaghmaei, Mojgan Mokhtari

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Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore ERα gene could be a possible candidate for preeclampsia(PE) susceptibility. In the current study, we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: One hundred ninety-two pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by PCR-RFLP method. Results: The frequency of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; P = 0.02) and in severe PE compared to normotensive women [OR= 1.8(1.1-3), P=0.02] after adjusting for age, ethnicity and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.

Keywords: estrogen receptor-α, polymorphism, gene, preeclampsia

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701 Effect of Convective Dryness Combined with Osmotic Dehydration, Blanching, Microwave and Ultrasonic Treatment on Bioactive Compounds and Rehydration Capacity of Dried Plums

Authors: Elena Corina Popescu, Magda Gabriela Bratu

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Increasing interest in keeping bioactive compounds (anthocyanins, vitamin C) and dried fruit quality has motivated the researchers to investigate new combined drying technologies. The aim of this study was to evaluate the effects of convective dryness combined with osmotic dehydration, blanching, microwave treatment and ultrasonic treatment on the quality of dried plums. Osmotic dehydration was achieved by maintaining plums for 1 h in sucrose solution (300Brix). For microwave treatment, the plums were kept at 400 W for 80 sec. For ultrasonic treatment, plums were immersed in distilled water and sonicated for 30 minutes at 40 kHz and 200 W. The blanching consists of immersing plums in hot water at 90°C for 20 seconds and cooling them rapidly. Conventional drying was carried out at 70°C for 630 minutes. Drying curves, drying rate, anthocyanin and vitamin C stability, acidity variation (expressed as malic acid), reducing sugar content, and rehydration capacity of dried plums were analyzed. Blanching led to the largest amount of evaporated water. Blanched plums have had 13.36% less water than sonicated ones. The lowest anthocyanal loss of 34.5% was obtained in osmotically dehydrated plums, and 2.93% vitamin C is found in the plums sonicated. There were no significant differences in regards acidity and reducing sugar. The plums blanched before drying have had a high capacity of rehydration.

Keywords: anthocyanin, dried plums, pretreatments, vitamin C

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700 Regulation of RON-Receptor Tyrosine Kinase Functions by Epstein-Barr-Virus (EBV) Nuclear Antigen 3C

Authors: Roshika Tyagi, Shuvomoy Banerjee

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Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

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699 Serum 25-Hydroxyvitamin D Levels and Depression in Persons with Human Immunodeficiency Virus Infection: A Cross-Sectional and Prospective Study

Authors: Kalpana Poudel-Tandukar

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Background: Human Immunodeficiency Virus (HIV) infection has been frequently associated with vitamin D deficiency and depression. Vitamin D deficiency increases the risk of depression in people without HIV. We assessed the cross-sectional and prospective associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and depression in a HIV-positive people. Methods: A survey was conducted among 316 HIV-positive people aged 20-60 years residing in Kathmandu, Nepal for a cross-sectional association at baseline, and among 184 participants without depressive symptoms at baseline who responded to both baseline (2010) and follow-up (2011) surveys for prospective association. The competitive protein-binding assay was used to measure 25(OH)D levels and the Beck Depression Inventory-Ia method was used to measure depression, with cut off score 20 or higher. Relationships were assessed using multiple logistic regression analysis with adjustment of potential confounders. Results: The proportion of participants with 25(OH)D level of <20ng/mL, 20-30ng/mL, and >30ng/mL were 83.2%, 15.5%, and 1.3%, respectively. Only four participants with 25(OH)D level of >30ng/mL were excluded in the further analysis. The mean 25(OH)D level in men and women were 15.0ng/mL and 14.4ng/mL, respectively. Twenty six percent of participants (men:23%; women:29%) were depressed. Participants with 25(OH)D level of < 20 ng/mL had a 1.4 fold higher odds of depression in a cross-sectional and 1.3 fold higher odds of depression after 18 months of baseline compared to those with 25(OH)D level of 20-30ng/mL (p=0.40 and p=0.78, respectively). Conclusion: Vitamin D may not have significant impact against depression among HIV-positive people with 25(OH)D level below normal ( > 30ng/mL).

Keywords: depression, HIV, Nepal, vitamin D

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698 Comparative Study of Amyloidogenic Potential of AgNO3 and Freund's Adjuvant (AF) with That of Vitamin Free Casein, on Spatio-Temporal Pattern of Experimental Amyloidosis in Mice

Authors: Alireza Javed, Keivan Jamshidi

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Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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697 Differential Expression of Arc in the Mesocorticolimbic System Is Involved in Drug and Natural Rewarding Behavior in Rats

Authors: Yuhua Wang, Mu Li, Jinggen Liu

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Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

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696 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

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695 Quantitative on Fatty Acid Profiles, Lipid Contents and Fat-Soluble Vitamin A of Freshwater Fish Species in Tonle Sap Lake, Cambodia

Authors: Sengly Sroy, Elodie Arnaud, Adrien Servent, Sokneang In, Sylvie Avallone

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In Cambodia, fish plays an important role for local community in term of food habits, preference and contribution to several nutritional intakes. Consumed on a daily basis, fishes and their derivatives products are good sources of proteins, essential fatty acids and fat-soluble vitamins. They mainly obtain from the Tonle Sap Lake but, during the last decade, the fish population decreased drastically due to climate change and human activities as well. Contamination by agricultural residues and heavy metals were identified. However, fishes are currently used in several nutrition programs for children and pregnant women to improve their nutritional status. The aim of our work was to characterize the nutritional profile and contamination of 10 fish species consumed near the Tonle Sap Lake with a special attention to fatty acid and fat-soluble vitamin profiles. Fish samples were analyzed for their nutritional profiles (AOAC methods for macronutrients and micronutrients), their lipid content (Folch modified method), their Fatty acid (FAME method), their vitamin A (HPLC) and their heavy metals (ICP-MS). The total lipid contents ranged from 1.43 to 10.00% according to fish species. Lipid profile was mainly dominated by saturated fat (from 47.95 to 57.32%) but some fish species were particularly rich in ω-3 and ω-6 especially eicosapentaenoic acid EPA (3.05%) and docosahexaenoic acid DHA (2.82%). The more the fishes were fats, the more they contained vitamin A, DHA and EPA. Vitamin A is particularly abundant in small fishes (250.10 μg RE/100 g) compare to big ones (13.77 μg RE/100 g) because they are consumed as a whole with their organs (liver) and head. However, the contents of heavy metal in some species are higher than the maximum permitted level (MPL) from codex alimentarius, especially Mn. The results obtained provided important information on the most interesting fish in term of human nutrition and the potential risk of contaminants. The fatty acids are important for child development and pregnant women. These data are useful for supply chain stakeholders and the people in charge of nutrition program.

Keywords: fat-soluble vitamin, fatty acid, freshwater fish, lipid content, Tonle Sap Lake

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694 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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693 Trastuzumab Decorated Bioadhesive Nanoparticles for Targeted Breast Cancer Therapy

Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

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Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

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692 Immunohistochemical Expression of β-catenin and Epidermal Growth Factor Receptor in Adamantinomatous Craniopharyngioma

Authors: Ghada Esheba, Fatimah Alturkistani, Arwa Obaid, Ahdab Bashehab, Moayad Alturkistani

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Introduction: Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the sellar/parasellar region. CPs have been classified histopathologically, genetically, clinically and prognostically into two distinctive subtypes: adamantinomatous and papillary variants. Aim: To examine the pattern of expression of both the β-catenin and epidermal growth factor receptor (EGFR) in surgically resected samples of adamantinomatous CP, and to asses for the possibility of using anti-EGFR in the management of ACP patients. Materials and methods: β-catenin and EGFR immunostaining was performed on paraffin-embedded tissue sections of 18 ACP cases. Result: 17 out of 18 cases (94%) of ACP exhibited strong nuclear/cytoplasmic expression of β-catenin, 15 (83%) of APC cases were positive for EGFR. Conclusion: Nuclear accumulation of β-catenin is a diagnostic hallmark of ACP. EGFR positivity in most cases of ACP could qualify the use of anti-EGFR therapy. 

Keywords: craniopharyngioma, adamantinomatous, papillary, epidermal growth factor receptor, B-catenin

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691 Physiological Response of Water-Restricted Xhosa Goats Supplemented with Vitamin C

Authors: O.F. Akinmoladun, F.N. Fon, C.T. Mpendulo, O. Okoh

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The sustainability of livestock production is under threat as a result of water scarcity, fluctuating precipitation, and high environmental temperature. These combined stressors have impacted negatively on general animal production and welfare, necessitating a very reliable and cost-effective management practices, especially in arid and water-limited regions of the world. Instead of the above, this study was designed to investigate the growth performance and physiological response of water-restricted Xhosa ear-lobe goats fed diets supplemented with single or multiple vitamin C (VC) during summer. The total forty-eight goats used for the experiment were balanced for body weight and randomly assigned to the seven treatment groups (seven goats/treatment): GI (W100%); GII (W70%); GIII (W50%); GIV (W70%+3g/day VC); GV ((W50% +3g/day VC); GVI (W70%+3g/d VC+extra 5g on every eight-day); GVII (W50%+3g/d VC+extra 5g on every eight-day). The design was a complete randomized design and VC was administered per os. At the end of the 75-day feeding trial, GIII (W50%) animals were the most affected (P<0.05) and the effect was more pronounced in their body condition scores (BCs). Weight loss and depression in feed intake due to water restriction (P<0.05) were attenuated by VC treated groups (GIV-GVII). Changes in body thermal gradient (BTG) and rectal temperature (RcT) were similar (P>0.05) across the various experimental groups. The attenuation effect of VC was significant in responses to respiratory rate (RR) and cortisol. Supplementation of VC (either single or multiple) did not significantly (P>0.05) improve water restriction effect on body condition scores (BCs) and FAMACHA©. The current study found out that Xhosa ear lobe goats can adapt to the prevailing bioclimatic changes and limited water intake. However, supplementation of vitamin C can be beneficial at modulating these stressful stimuli. Continuous consistencies in the outcome of vitamin C on water-stressed animals can help validate recommendations especially to farmers in the arid and water-limited regions across the globe.

Keywords: vitamin C, Xhosa ear-lobe, thermotolerance, water stress

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690 Protection against Sodium Arsenate Induced Fetal Toxicity in Albino Mice by Vitamin C and E

Authors: Fariha Qureshi, Mohammad Tahir

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Epidemiological evidences indicated that arsenic contamination in drinking water increased the incidence of spontaneous abortion, stillbirth and premature babies in pregnant women. This study was designed to investigate the protective role of vitamin C&E against sodium arsenate induced fetal toxicity in albino mice. Twenty-four pregnant albino mice of BALB/c strain were randomly divided into 4 groups having 6 animals in each. Group A1 served as control and was injected with 0.1ml/kg/day distilled water I/P for 18 days. Groups A2,A3 & A4 received single I/P injection of sodium arsenate 35mg/kg on 8th gestational day, whereas groups A3 and A4 were also given Vitamin C and E by I/P injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8th GD and continued for the rest of the pregnancy period. The early implantation sites, fetal resorptions, weight of live fetuses and crown rump length were recorded. Gross morphological examination was carried out for malformations. Fetal kidneys were extracted for histological and micrometric analysis. Group A2 exhibited an increased incidence of abortion, fetal resorptions, significant decrease in number of litter and fetal weight; the difference of means was statistically significant among the groups (p<0.000). In group A2 fetal kidneys presented glomerulonephritis with acute tubular necrotic changes and interstitial fibrosis. Groups A3&A4 showed statistically significant improvement in these parameters. The results revealed the antioxidant potential of Vitamin C and E in protecting against arsenic induced fetal toxicity in mice.

Keywords: fetal toxicity, fetal resorptions, interstitial fibrosis, tocopherol

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689 The Incidence of Acetylcholine Receptor Antibody Positive Myasthenia Gravis in South Africa

Authors: Mombaur Busisiwe, Lesosky Maia, Liebenberg Lisa, Heckmann Jeannine

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Introduction: To assess age- and gender-specific incidence rates (IR) of acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG) in South Africa, and geographical variation in incidence. Methods: IRs were calculated from positive AChR antibody laboratory data between 2011 and 2012, using 2011 population census data. Results:890 individuals were seropositive, for an annual IR of 8.5 per million. Age-standardized IR for early- (< 50) and late-onset (≥ 50) MG were 4.1 and 24 per million, respectively, and for juveniles, 4.3 per million. The IR between provinces ranged from 1 to 19 per million. Conclusions: In this Southern hemisphere African population, the overall IR and peak IR (in older men) for seropositive MG is comparable to that in Europe and North America, arguing against environmental factors. However, IRs may be higher among children with African genetic ancestry. Geographical variation in incidence underscores the importance of outreach programs for regions with limited resources.

Keywords: incidence rates (IR), acetylcholine receptor (AChR), myasthenia gravis (MG), South Africa

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688 Serum 25-Hydroxyvitamin D Levels in Korean Breast Cancer Patients

Authors: Sung Yong Kim, Byung Joo Song

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Background: Circulating 25-hydroxyvitamin D (25(OH)D) levels has been considered to be inversely related to breast cancer development, recurrence risk, and mortality. Mean vitamin D levels in Korean population is lower than western countries due to higher incidence of lactose intolerance and lower exposure to sunlight. The purpose of this study was to assess incidence of 25(OH)D deficiency at diagnosis and after adjuvant chemotherapy and to investigate the correlation serum 25(OH)D levels with clinicopathologic features. Methods: From December 2011 to October 2012, 280 breast cancer patients seen at a single tertiary cancer center were enrolled. Serum 25(OH)D was measured at the time of surgery and after completion of adjuvant chemotherapy. Statistical analyses used chi-square test, Fisher's exact test, t-test, and ANOVA. Results: Mean serum 25(OH)D was 18.5 ng/ml. The 25(OH)D levels were deficient (<20 ng/ml) in 190 patients (67.9%), insufficient (20-29 ng/ml) in 51 patients(18.2%), and sufficient (30-150 ng/ml) in 39 patients(13.9%). A notable decrease in 25(OH)D concentration was observed(p<0.001) after chemotherapy but was not related to chemotherapy regimens. It was found significant lower 25(OH)D levels at winter season(from October to March, p=0.030). Subjects with invasive carcinoma (IDC or ILC) had significantly lower circulating levels of 25(OH)D than those with ductal carcinoma in situ(DCIS) (p=0.010). Patients with larger tumor size tends to have lower serum 25(OH)D but there were no statistical significance. Conclusions: Most of the breast cancer patients showed deficient or insufficient serum 25(OH)D concentration. Incidence of vitamin D deficiency was higher in invasive carcinoma than DCIS. Serum 25(OH)D levels were decreased after chemotherapy. Consideration should be given to the supplement of vitamin D to those patients.

Keywords: breast neoplasms, vitamin D, Korean population, breast cancer

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687 Ageing Gingiva: A New Hope for Autologous Stem Cell Therapy

Authors: Ankush M. Dewle, Suditi Bhattacharya, Prachi R. Abhang, Savita Datar, Ajay J. Jog, Rupesh K. Srivastava, Geetanjali Tomar

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Objectives: The aim of this study was to investigate the quality of mesenchymal stem cells (MSCs) obtained from ageing gingival tissues, in order to suggest their potential role in autologous stem cell therapy for old individuals. Methods: MSCs were isolated from gingival tissues of young (18-45 years) and old (above 45 years) donors by enzymatic digestion. MSCs were analysed for cfu-f, surface marker expression by flow-cytometry and multilineage differentiation potential. The angiogenic potential was compared in a chick embryo yolk sac membrane model. The aging and differentiation markers including SA-β-galactosidase and p21 respectively were analysed by staining and flow-cytometry analysis. Additionally, osteogenic markers such as glucocorticoid receptor (GR), vitamin D receptor (VDR) were measured by flow-cytometry and RT-qPCR was performed for quantification of osteogenic gene expression. Alizarin Red S and alkaline phosphatase (ALP) activity were also quantitated. Results: Gingival MSCs (GMSCs) from both the age groups were similar in their morphology and displayed cfu-f. They had similar expression of MSC surface markers and p21, comparable rate of proliferation and differentiated to all the four lineages. GMSCs from young donors had a higher adipogenic differentiation potential as compared to the old GMSCs. Moreover, these cells did not display a significant difference in ALP activity probably due to comparable expression of GR, VDR, and osteogenic genes. Conclusions: Ageing of GMSCs occurs at a much slower rate than stem cells from other sources. Thus we suggest GMSCs as an excellent candidate for autologous stem cell therapy in degenerative diseases of elderly individuals. Clinical Significance: GMSCs could help overcome the setbacks in clinical implementation of autologous stem cell therapy for regenerative medicine in all age group of patient.

Keywords: bone regeneration, cell therapy, senescence, stem cell

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686 The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review

Authors: James Pietris

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Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent.1This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Keywords: glaucoma, nicotinamide, vitamin B3, optic neuropathy

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685 Importance of Macromineral Ratios and Products in Association with Vitamin D in Pediatric Obesity Including Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

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Metabolisms of macrominerals, those of calcium, phosphorus and magnesium, are closely associated with the metabolism of vitamin D. Particularly magnesium, the second most abundant intracellular cation, is related to biochemical and metabolic processes in the body, such as those of carbohydrates, proteins and lipids. The status of each mineral was investigated in obesity to some extent. Their products and ratios may possibly give much more detailed information about the matter. The aim of this study is to investigate possible relations between each macromineral and some obesity-related parameters. This study was performed on 235 children, whose ages were between 06-18 years. Aside from anthropometric measurements, hematological analyses were performed. TANITA body composition monitor using bioelectrical impedance analysis technology was used to establish some obesity-related parameters including basal metabolic rate (BMR), total fat, mineral and muscle masses. World Health Organization body mass index (BMI) percentiles for age and sex were used to constitute the groups. The values above 99th percentile were defined as morbid obesity. Those between 95th and 99th percentiles were included into the obese group. The overweight group comprised of children whose percentiles were between 95 and 85. Children between the 85th and 15th percentiles were defined as normal. Metabolic syndrome (MetS) components (waist circumference, fasting blood glucose, triacylglycerol, high density lipoprotein cholesterol, systolic pressure, diastolic pressure) were determined. High performance liquid chromatography was used to determine Vitamin D status by measuring 25-hydroxy cholecalciferol (25-hydroxy vitamin D3, 25(OH)D). Vitamin D values above 30.0 ng/ml were accepted as sufficient. SPSS statistical package program was used for the evaluation of data. The statistical significance degree was accepted as p < 0.05. The important points were the correlations found between vitamin D and magnesium as well as phosphorus (p < 0.05) that existed in the group with normal BMI values. These correlations were lost in the other groups. The ratio of phosphorus to magnesium was even much more highly correlated with vitamin D (p < 0.001). The negative correlation between magnesium and total fat mass (p < 0.01) was confined to the MetS group showing the inverse relationship between magnesium levels and obesity degree. In this group, calcium*magnesium product exhibited the highest correlation with total fat mass (p < 0.001) among all groups. Only in the MetS group was a negative correlation found between BMR and calcium*magnesium product (p < 0.05). In conclusion, magnesium is located at the center of attraction concerning its relationships with vitamin D, fat mass and MetS. The ratios and products derived from macrominerals including magnesium have pointed out stronger associations other than each element alone. Final considerations have shown that unique correlations of magnesium as well as calcium*magnesium product with total fat mass have drawn attention particularly in the MetS group, possibly due to the derangements in some basic elements of carbohydrate as well as lipid metabolism.

Keywords: macrominerals, metabolic syndrome, pediatric obesity, vitamin D

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684 The Impact of Maternal Micronutrient Levels on Risk of Offspring Neural Tube Defects in Egypt

Authors: Eman M. El-Sayed, Sahar A. Abdelaziz, Maha M. Saber Abd El Latif

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Neural tube defects (NTD) are important causes of infant mortality. Poor nutrition was essential factor for central nervous system deformation. Mothers gave NTD offspring had abnormal serum levels of micronutrients. The present research was designed to study the effect of maternal micronutrient levels and oxidative stress on the incidence of NTD in offspring. The study included forty mothers; twenty of them of 30.9+7.28 years had conceived fetuses with NTD were considered as cases; and twenty mothers of 28.2 + 7.82 years with healthy neonates. We determined serum vitamin B12 and folic acid by using radioimmunoassays. Also, serum zinc was assessed using atomic absorption spectrophotometry. While serum copper and iron were measured colorimetrically and serum ceruloplasmin was analyzed by radialimmunodiffusion. Cases showed significantly lower levels of folic acid, vitamin B12 and zinc (P< 0.0005, 0.01, 0.01 respectively) than that of the control. Concentrations of copper, ceruloplasmin, and iron were markedly increased in cases as compared to controls (P < 0.01, 0.01, and 0.05 respectively). In conclusion, the current study clearly indicated the etiology of NTD cannot be explained with one strict etiologic mechanism, on the contrary, an interaction among maternal nutritional factors and oxidative stress would explain these anomalies. Vitamin B12, folic acid, and zinc supplementations should be considered for further decrease in the occurrence of NTD. Preventing excess iron during pregnancy favors better pregnancy outcomes.

Keywords: ceruloplasmin, copper, folic acid, iron, neural tube defects, oxidative stress, vitamin b12, zinc

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683 Effect of Long-Term Boron Exposure on Liver Structure of Adult Male Albino Rats and a Possible Role of Vitamin C

Authors: Ola Abdel-Tawab Hussein

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Background: Boron is a naturally occurring agent and an essential trace element of human, animals and higher plants. It is released in the form of boric acid (BA) that is water soluble and biolologically available. Its largest uses are in glass, detergents, agriculture, leather tanning industries, cosmetics, photographic materials, soaps and cleaners. Human consume daily few milligrams in the water, fruits and vegetables. High doses of boron had been recorded to be developmental and reproductive toxin in animals(Only few studies on human had investigated the health effects associated with exposure to boron. Vitamin C is a major water soluble non-enzymatic antioxidant, acts to overcome the oxidative stress. Aim of the work: However , the liver is exposed to toxic substances that are absorbed, degraded or conjugated there were little information exists about the effects of boron that it would specifically have in the liver tissue of experimental rats. So the present work aimed to study the effects of long-term boron ingestion on histological structural of the liver of adult male albino rats and to evaluate the protective role of vitamin C against induced changes. Material and Methods: 30 adult male albino rats were divided into 3 equal groups; Group I: control, Group II: recieved drinking water containing 55x10-6 gm boron/liter for 90 days and Group III: recieved vitamin C (200mg/Kg.B.W) orally concomitant with boron for the same period. liver specimens were processed for light and electron microscopic(TEM) study. Results: Examination of the liver sections of group II revealed foci of severe dilatation and congestion of central and portal veins with mononuclear cellular infiltration and hepatocellular vacuolation. Increased collagen deposition specially around the portal areas. Marked electrolucent areas in the cytoplasm, heterochromatic nuclei and destroyed organelles of the hepatocytes. Apoptotic cells were observed and decreased lipid content of ito cells. In Group III the co administration of vitamin C improved most of the structural changes of the hepatocytes, Ito cells, increased binucleated cells and decreased collagen fibers deposition. Conclusion: Thus, the long term exposure to boron, induced histological changes on the structure of liver. The co administration of vitamin C improved most of these structural changes.

Keywords: boron, liver, vitamin C, rats

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682 Dietary Habit and Anthropometric Status in Hypertensive Patients Compared to Normotensive Participants in the North of Iran

Authors: Marjan Mahdavi-Roshan, Arsalan Salari, Mahbobeh Gholipour

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Hypertension is one of the important reasons of morbidity and mortality in countries, including Iran. It has been shown that hypertension is a consequence of the interaction of genetics and environment. Nutrients have important roles in the controlling of blood pressure. We assessed dietary habit and anthropometric status in patients with hypertension in the north of Iran, and that have special dietary habit and according to their culture. This study was conducted on 127 patients with newly recognized hypertension and the 120 normotensive participants. Anthropometric status was measured and demographic characteristics, and medical condition were collected by valid questionnaires and dietary habit assessment was assessed with 3-day food recall (two weekdays and one weekend). The mean age of participants was 58 ± 6.7 years. The mean level of energy intake, saturated fat, vitamin D, potassium, zinc, dietary fiber, vitamin C, calcium, phosphorus, copper and magnesium was significantly lower in the hypertensive group compared to the control (p < 0.05). After adjusting for energy intake, positive association was observe between hypertension and some dietary nutrients including; Cholesterol [OR: 1.1, P: 0.001, B: 0.06], fiber [OR: 1.6, P: 0.001, B: 1.8], vitamin D [OR: 2.6, P: 0.006, B: 0.9] and zinc [OR: 1.4, P: 0.006, B: 0.3] intake. Logistic regression analysis showed that there was not significant association between hypertension, weight and waist circumference. In our study, the mean intake of some nutrients was lower in the hypertensive individuals compared to the normotensive individual. Health training about suitable dietary habits and easier access to vitamin D supplementation in patients with hypertension are cost-effective tools to improve outcomes in Iran.

Keywords: hypertension, north of Iran, dietary intake, weight

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681 The Effect of Probiotic and Vitamin B Complex Supplementation on Interferon-γ and Interleukin-10 Levels in Patients with TB Infection during Intensive Phase Therapy

Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

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Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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680 Relation between Biochemical Parameters and Bone Density in Postmenopausal Women with Osteoporosis

Authors: Shokouh Momeni, Mohammad Reza Salamat, Ali Asghar Rastegari

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Background: Osteoporosis is the most prevalent metabolic bone disease in postmenopausal women associated with reduced bone mass and increased bone fracture. Measuring bone density in the lumbar spine and hip is a reliable measure of bone mass and can therefore specify the risk of fracture. Dual-energy X-ray absorptiometry(DXA) is an accurate non-invasive system measuring the bone density, with low margin of error and no complications. The present study aimed to investigate the relationship between biochemical parameters with bone density in postmenopausal women. Materials and methods: This cross-sectional study was conducted on 87 postmenopausal women referred to osteoporosis centers in Isfahan. Bone density was measured in the spine and hip area using DXA system. Serum levels of calcium, phosphorus, alkaline phosphatase and magnesium were measured by autoanalyzer and serum levels of vitamin D were measured by high-performance liquid chromatography(HPLC). Results: The mean parameters of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium did not show a significant difference between the two groups(P-value>0.05). In the control group, the relationship between alkaline phosphatase and BMC and BA in the spine was significant with a correlation coefficient of -0.402 and 0.258, respectively(P-value<0.05) and BMD and T-score in the femoral neck area showed a direct and significant relationship with phosphorus(Correlation=0.368; P-value=0.038). There was a significant relationship between the Z-score with calcium(Correlation=0.358; P-value=0.044). Conclusion: There was no significant relationship between the values ​​of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium parameters and bone density (spine and hip) in postmenopaus

Keywords: osteoporosis, menopause, bone mineral density, vitamin d, calcium, magnesium, alkaline phosphatase, phosphorus

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679 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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678 Nutritional Potentials of Two Nigerian Green Leafy Vegetables

Authors: Philippa C. Ojimelukwe, Felix C. Okpalanma, Emmanuel A. Mazi

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The carotenoid content, vitamins (ascorbic acid, riboflavin, thiamin, niacin and vitamin K) and mineral contents (K, Ca, Mg, Zn and Fe) of raw, cooked (moist heat treatment) and stored Gnetum africanum and Pterocarpus mildbraedii leaves were investigated in the present research. Raw G. africanum contained higher total carotenoids (246.93µg/g edible portion) than P. mildbraedii (83.53µg/g edible portion) However, moist heat treatment significantly improved the total carotenoid content of P. mildbraedii. The carotenoid profiles of P. mildbraedii and G. africanum showed improved contents of beta cryptoxanthin , 9-cis, 11-cis and 13 cis beta carotenes due to moist heat treatment. Lutein contents of the two green leafy vegetables were quite high in raw, heat treated and stored samples. The two green leafy vegetables were good sources of vitamin K (118-120 µg). Moist heat treatment significantly (p < 0.05) increased the mineral contents of P.mildbraedii and G. africanum. The vitamin contents were reduced. Storage at ambient temperature (30oC) in the dark led to good retention of the minerals but not the vitamins.

Keywords: Gnetum africanum, Pterocarpus mildbraedii, carotenoid profile, vitamins, minerals

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677 Etiologies of Megaloblastic Anemia in a Pediatric Hospital

Authors: Atitallah Sofien, Bouyahia Olfa, Mohsen S., Boussetta Khadija, Khemiri Monia, Fitouri Zohra, Boukthir Samir

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Introduction: Megaloblastic anemia (MA) is rare in children. The diversity of its etiologies can lead to misdiagnosis and may, therefore, delay the treatment. The aim of this study was to describe the epidemiological and etiological characteristics of children followed for MA at the Tunis children's hospital. Methodology: This is a retrospective study over a period of 25 years of all cases of MA in children in the Children's Hospital of Tunis. The diagnosis of MA was confirmed by myelogram in all patients. Results: We collected 29 observations, with an incidence of 1.2 cases/year and a sex ratio of 1. Sixty percent of the children were aged between 3 months and 2 years. The consultation time was between 15 and 30 days in a third of the patients. The clinical examination showed hypotrophy in 13% of cases, hepatosplenomegaly in 6% of cases, neurological or neurosensory damage in 23% of cases, and cardiac damage in 10% of children. MA was associated with thrombocytopenia in 65% of cases and leukoneutropenia in 24% of cases. One in 5 children had pancytopenia. The etiologies were mainly thiamine deficiency, Immerslund disease (20%), nutritional deficiency (13%), and Biermer anemia (13%). One of the patients presented an MA revealing visceral leishmaniasis. The outcome under vitamin B12, the dose of which was adapted to each etiology, was favorable for all patients. Conclusion: MA is rare in children with multiple etiologies that are mainly dominated by hereditary conditions and nutritional deficiencies, mainly in vitamin B12. The association with visceral leishmaniasis seems to be a particularity in our country not reported in the literature.

Keywords: megaloblastic anemia, children, vitamin B12, anemia

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676 Considerations in Pregnancy Followed by Obesity Surgery

Authors: Maryam Nazari, Atefeh Ghanbari, Saghar Noorinia

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Obesity, as an abnormal or excessive accumulation of fat, is caused by genetic, behavioral and environmental factors. Recently, obesity surgeries, such as bariatric surgery, as the last measure to control obesity, have attracted experts and society, especially women, attention, so knowing the possible complications of this major surgery and their control in reproductive age is of particular importance due to its effects on pregnancy outcomes. Bariatric surgery reduces the risk of diabetes and high blood pressure associated with pregnancy, premature birth, macrosomia, stillbirth and dumping syndrome. Although in the first months after surgery, nausea and vomiting caused by changes in intra-abdominal pressure are associated with an increased risk of malabsorption of micronutrients such as folic acid, iron, vitamin B1, D, calcium, selenium and phosphorus and finally, fetal growth disorder. Moreover, serum levels of micronutrients such as vitamin D, calcium, and iron in mothers who used to have bariatric surgery and their babies have been shown to be lower than in mothers without a history of bariatric surgery. Moreover, vitamin A deficiency is shown to be more widespread in pregnancies after bariatric surgery, which leads to visual problems in newborns and premature delivery. However, complications such as the duration of hospitalization of newborns in the NICU, disease rate in the first 28 days of life and congenital anomalies are not significantly different in babies born to mothers undergoing bariatric surgery compared to the control group. In spite of the vast advantages following obesity surgeries, due to the catabolic conditions and severe weight loss followed by such major intervention and the probability of nutrients malnutrition in a pregnant woman and her baby, after having surgery, at least 12 to 18 months should be considered to get pregnant as a recovery period. In addition, taking essential supplements before and at least 6 months after this approach is recommended.

Keywords: bariatric surgery, pregnancy, malnutrition, vitamin and mineral deficiency

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675 Design and Synthesis of Some Oxadiazole Bearing Benzimidazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors

Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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674 25 (OH)D3 Level and Obesity Type, and Its Effect on Renal Excretory Function in Patients with a Functioning Transplant

Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba, Marek Jan Kuzniewski

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Introduction: Vitamin D3 has a proven pleiotropic effect, not only responsible for calcium and phosphate management, but also influencing normal functioning of the whole body. Aim: Evaluation of vitamin D3 resources and its effect on a nutritional status, obesity type and glomerular filtration in kidney transplant recipients. Methods: Group of 152 (81 women and 71 men, average age 47.8 ± 11.6 years) patients with a functioning renal transplant their body composition was assessed using the bioimpendance method (BIA) and anthropometric measurements more than 3 months after the transplant. The nutritional status and the obesity type were determined with the Waist to Height Ratio (WHtR) and the Waist to Hip Ratio (WHR). 25- Hydroxyvitamin D3 (25 (OH)D3) was determined, together with its correlation with the obesity type and the glomerular filtration rate (eGFR) calculated with the MDRD formula. Results: The mean 25 (OH)D3 level was 20.4 ng/ml. 30ng/ml was considered as a minimum correct level 22,7% of patients from the study group were classified to be a correct body weight, 56,7% of participants had an android type and 20,6% had a gynoid type. Significant correlation was observed between 25 (OH)D3 deficiency and abdominal obesity (p < 0.005) in patients. Furthermore, a statistically significant relationship was demonstrated between the 25 (OH)D3 levels and eGFR in patients after a kidney transplant. Patients with an android body type had lower eGFR versus those with the gynoid body type (p=0.004). Conclusions: Correct diet in patients after a kidney transplant determines minimum recommended serum levels of vitamin D3. Excessive fatty tissue, low levels of 25 (OH)D3), may be a predictor for android obesity and renal injury; therefore, correct diet and pharmacological management together with physical activities adapted to the physical fitness level of a patient are necessary.

Keywords: kidney transplantation, glomerular filtration rate, obesity, vitamin D3

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