Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms

<p>Abstract</p> <p>Background</p> <p>Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI) tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (<it>OXT</it>) and its receptor (<it>OXTR</it>) genes in patients with GI complaints without visible organic abnormalities.</p> <p>Methods</p> <p>Genetic variants in the <it>OXT </it>promoter region, and in the <it>OXTR </it>gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS), 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235) genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the <it>OXT </it>gene (rs6133010 A>G) and 4 related to the <it>OXTR </it>gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T) were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays.</p> <p>Results</p> <p>There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G <it>OXT </it>promoter A/G genotype tended to be more common in the 154 non-persistent (27.3%) subjects than in the 254 lactase persistant (18.1%) subjects and in the healthy controls (19.4%) (p = 0.08). When direct comparing, the A/G genotype was less common in the <it>OXT </it>promoter region in controls (p = 0.09) and in subjects with lactase persistence (p = 0.03) compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the <it>OXT </it>promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%).</p> <p>No significant differences in frequencies of the investigated <it>OXTR </it>SNPs were noted in this study.</p> <p>Conclusion</p> <p>The results suggest that polymorphism in the promoter region of the <it>OXT </it>gene is most common in subjects with lactase non-persistence. This polymorphism may not be related to GI symptoms, as it is related to lactase non-persistence also in healthy controls.</p

Palmitic Acid-Induced Toxicity Reduction Due to Production of Triacylglycerol in Cardiac Muscle Cells by Linoleic Acid

BACKGROUND AND OBJECTIVE: Lipotoxicity-induced cardiovascular diseases are increasing significantly in human populations. The effect of linoleic acid in reducing lipotoxicity of cardiac muscle cells was investigated in this study. METHODS: In this empirical study, ventricular muscle cells from the hearts of five adult rats were cultured in 24-well plates. They were randomly treated in four groups including one control group (0.5 mM bovine serum albumin (BSA)) and three treatment groups treated with palmitic acid (0.5 mM), linoleic acid (0.25 mM) and a combination of linoleic acid and palmitic acid (0.25 mM + 0.5 mM). Wells in each row of plates were dedicated to one group. Level of cellular triacylglycerol, cellular diacylglycerol, DNA Fragmentation and survival rate was evaluated 24 and 48 hours after culturing. Each two wells belonging to each group were used to evaluate every factor and all the steps were repeated three times. FINDINGS: Compared with palmitic acid treatment alone, adding linoleic acid to palmitic acid decreased the level of DNA Fragmentation by 4.65% and 6.15% (p0.05). It also increased the level of cellular triacylglycerol by 40% and 44% (p<0.03) and increased cellular survival by 6.25% and 10.52% (p<0.01), respectively 24 and 48 hours after cultivation. CONCLUSION: Results of the study revealed that linoleic acid reduces the palmitic acid-induced toxicity by producing triacylglycero

Cytotoxic effect of ICD-85 (venom-derived peptides) on MDA-MB-231 cell line

Since 1987, when chemopreventive testing programs began, more than 1,000 agents and agent combinations have been selected and evaluated in preclinical studies of chemopreventive activity against various types of cancers. In the present study we aimed to provide quantitative and qualitative characterization of biological and pharmacological activities of ICD-85 on MDA-MB-231 cell line (a highly invasive breast cancer cell line) in order to gain a better understanding of the cytotoxic and apoptotic effects of this compound. For this study, the MDA-MB-231 cell line was used and the effect of ICD-85 was assayed by measuring the activity of the cytosolic enzyme lactate dehydrogenase (LDH), released into the culture medium after membrane damage. Morphological alterations of cells were investigated in the control group and cells incubated with ICD-85 as cytotoxic agent. Results showed, in the test group, that cells incubated with 16 µg/mL of ICD-85 had decreased cytoplasmic branching. Some cells were had ruptured and lost the continuity of their surrounding membranes while some had shrunk. Cells incubated with higher doses (above16 µg/mL) showed similar changes towards cellular normality with more severity. Results obtained from the ICD-85 stability test reveal that the effect of ICD-85 on MDA-MB-231 cell line in culture medium is stable throughout the incubation time period (24 hours). It appears that ICD-85 at higher concentrations acts at the membrane level, which allows the passage of ions down the concentration gradient, resulting in osmotic changes in organelles followed by several unidentified mechanisms leading to cell death. At lower concentrations, it appears that ICD-85 can prevent cell growth by another mechanism, which may be one of the causes for apoptosis in the cell line

Effects of Chronic Exposure to Lead Acetate on the Reactions to Painful Stimuli in Mice

Introduction: Influences of lead on functions of many organ systems are known, but less experimental studies has been done on influences over the behavior, including pain sensation. This study was carried out to reveal possible changes in the onset and intensity of reactions to painful stimuli in mice, after long-term exposure to lead acetate. Methods: In this experimental study, 24 adult male albino mice were divided randomly into 3 groups of 8 each. Control group received fresh water ad lib and 2 treated groups received drinking water contaminated by either 5 ppm or 500 ppm of LA for 90 consecutive days. On the day of 91, nociceptive were performed using a hot plate and formalin, to evaluate onset and intensity of&nbsp; reaction in response to the thermal and chemical pain, respectively. At the end, the animals were euthanized and blood samples were collected for determination of cortisol levels using an ELISA assay. Results: The animals exposed to LA showed a delay in reaction to painful stimuli induced by thermal stimulus by 52% and 59% with low and high doses, respectively. Thermal pain intensity of reactions to was declined by 63% with LA 5 ppm and by 82% with LA 500 ppm (P<0.05). Delayed reaction to chemical stimulus was also prominent in treated groups up to 68% and the pain intensity was declined by 80%, but they were not statistically significant. Blood cortisol levels remained almost unchanged. Conclusion: Delayed reaction to painful stimuli after chronic LA exposure may be considered as a complication which weaken the alarming role of the pain. Further studies regarding the mechanism of action and the extent of the importance of these effects are warranted

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

Mohammad Amrollahi-Sharifabadi,1 Mohammad Kazem Koohi,1 Ehsan Zayerzadeh,2 Mohammad Hassan Hablolvarid,3 Jalal Hassan,1 Alexander M Seifalian4 1Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran; 2Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute, Karaj, Iran; 3Department of Pathology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran; 4NanoRegMed Ltd, Nanotechnology and Regenerative Medicine Commercialization Centre, The London BioScience Innovation Centre, London, UK Background: Graphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge.Methods: This study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3&ndash;6 layers, lateral dimension=5&ndash;10 &micro;m, and thickness=0.8&ndash;2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations.Results: The results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum.Conclusion: In conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs. Keywords: graphene oxide, nanoplatelets, toxicity, preclinical, rat, histopathology, nanotechnolog