Search results for: mice

Authors: Horia Păunescu

Abstract:

Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was „blinded” to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests. Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: Antidepressant, depressant, forced swim, NSAIDs.

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

Abstract:

Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: 177Lu, DOTATOC, adenocarcinoma, breast cancer, BALB/c mice.

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Authors: A.S. Sikarwar, S. Ambu, T .H. Wong

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Snake bite cases in Malaysia most often involve the species Naja-naja and Calloselasma rhodostoma. In keeping with the need for a rapid snake venom detection kit in a clinical setting, plate and dot-ELISA test for the venoms of Naja-naja sumatrana, Calloselasma rhodostoma and the cobra venom fraction V antigen was developed. Polyclonal antibodies were raised and further used to prepare the reagents for the dot-ELISA test kit which was tested in mice, rabbit and virtual human models. The newly developed dot- ELISA kit was able to detect a minimum venom concentration of 244ng/ml with cross reactivity of one antibody type. The dot-ELISA system was sensitive and specific for all three snake venom types in all tested animal models. The lowest minimum venom concentration detectable was in the rabbit model, 244ng/ml of the cobra venom fraction V antigen. The highest minimum venom concentration was in mice, 1953ng/ml against a multitude of venoms. The developed dot-ELISA system for the detection of three snake venom types was successful with a sensitivity of 95.8% and specificity of 97.9%.

Keywords: ELISA, Venom, SVDK, Naja-naja sumatrana , Calloselasma rhodostoma.

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Authors: Titin Andri Wihastuti, Djanggan Sargowo

Abstract:

NFκB is a transcription factor regulating many function of the vessel wall. In the normal condition , NFκB is revealed diffuse cytoplasmic expressionsuggesting that the system is inactive. The presence of activation NFκB provide a potential pathway for the rapid transcriptional of a variety of genes encoding cytokines, growth factors, adhesion molecules and procoagulatory factors. It is likely to play an important role in chronic inflamatory disease involved atherosclerosis. There are many stimuli with the potential to active NFκB, including hyperlipidemia. We used 24 mice which was divided in 6 groups. The HFD given by et libitum procedure during 2, 4, and 6 months. The parameters in this study were the amount of NFKB activation ,H2O2 as ROS and VCAM-1 as a product of NFKB activation. H2O2 colorimetryc assay performed directly using Anti Rat H2O2 ELISA Kit. The NFKB and VCAM-1 detection obtained from aorta mice, measured by ELISA kit and imunohistochemistry. There was a significant difference activation of H2O2, NFKB and VCAM-1 level at induce HFD after 2, 4 and 6 months. It suggest that HFD induce ROS formation and increase the activation of NFKB as one of atherosclerosis marker that caused by hyperlipidemia as classical atheroschlerosis risk factor.

Keywords: High Fat Diet, NFKB, H2O2, atherosclerosis

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Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin

Abstract:

Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.

Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease.

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Authors: Hai Xu, Yiwei Wang, Xi Bao, Bihua Deng, Pengcheng Li, Yu Lu

Abstract:

T7 phage could be used as a perfect vector for peptides expression and haptens presentation. T7-3GnRH recombinant phage was constructed by inserting three copies of Gonadotrophin Releasing Hormone (GnRH) gene into the multiple cloning site of T7 Select 415-1b phage genome. The positive T7-3GnRH phage was selected by using polymerase chain reaction amplification, and the p10B-3GnRH fusion protein was verified by SDS-PAGE and Western-blotting assay. T7-3GnRH vaccine was made and immunized with 10¹⁰ pfu in 0.2 ml per dose in mice. Blood samples were collected at an interval in weeks, and anti-GnRH antibody and testosterone concentrations were detected by ELISA and radioimmunoassay, respectively. The results show that T7-3GnRH phage particles confer a high immunogenicity to the GnRH-derived epitope. Moreover, the T7-3GnRH vaccine induced higher level of anti-GnRH antibody than ImproVac^®. However, the testosterone concentrations in both immunized groups were at a similar level, and the testis developments were significantly inhibited compared to controls. These findings demonstrated that the anti-GnRH antibody could neutralize the endogenous GnRH to down regulate testosterone level and limit testis development, highlighting the potential value of T7-3GnRH in the immunocastration vaccine research.

Keywords: Gonadotrophin releasing hormone, GnRH, immunocastration, T7 phage, phage vaccine.

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Authors: Chan-Jung Liang, Shu-Huei Wang, Pei-Jhen Wu, Jaw-Shiun Tsai, Chau-Chung Wu, Yuh-Lien Chen

Abstract:

Heme oxygenase-1 (HO-1), an enzyme degrading heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to heme release. In the present study, the effects of TNF-a on the expression of heme oxygenase-1 (HO-1) in human aortic endothelial cells (HAECs) as well as the related mechanisms were investigated. 10 ng/mL TNF-α treatment significantly increased HO-1 expression after 6h, then a further increase at 12h and declined at 24h. Treatment with 2 ng/mL of TNF-a after 12 h resulted in a significant increase in HO-1 expression, which peaked at 10 ng/mL, then declined at 20 ng/mL. TNF-α induced HO-1 expression and then HO-1 expression reduced  vascular cell adhesion molecule-1 (VCAM-1) expression. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen-activated protein kinases (MAPKs) demonstrated TNF-α-induced ERK1/2, JNK, and p38 phosphorylation. The increase in HO-1 expression in response to TNF-α treatment was affected by pretreatment with SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), not with PD98059 (an ERK1/2 inhibitor). The expression of HO-1 was stronger in aortas of TNF-α-treated apo-E deficient mice when compared with control mice. These results suggest that low dose of TNF-α treatment notably induced HO-1 expression was mediated through JNK/p38 phosphorylation and may have a protective potential in cardiovascular diseases and inflammatory response through the regulation of HO-1 expression.

Keywords: Heme oxygenase-1 inflammation, endothelial cells, mitogen-activated protein kinases (MAPKs).

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Authors: Dike H. Ogbuagu, Etsede J. Oritsematosan

Abstract:

This work investigated possible inductions of CaC₂, often misused by fruit vendors to stimulate artificial ripening, on mammalian sperm morphology and viability. Thirty isogenic strains of male albino mice, Mus musculus (age≈ 8weeks; weight= 32.52.0g) were acclimatized (ambient temperature 28.0±1.0°C) for 2 weeks and fed standard growers mash and water ad libutum. They were later exposed to graded toxicant concentrations (w/w) of 2.5000, 1.2500, 0.6250, and 0.3125% in 4 cages. A control cage was also established. After 5 weeks, 3 animals from each cage were sacrificed by cervical dislocation and the cauda epididymis excised. Sperm morphology and viability were determined by microscopic procedures. The ANOVA, means plots, Student’s t-test and variation plots were used to analyze data. The common abnormalities observed included Double Head, Pin Head, Knobbed Head, No Tail and With Hook. The higher toxicant concentrations induced significantly lower body weights [F_(829.899) ˃ F_crit(4.19)] and more abnormalities [F_(26.52) ˃ F_crit(4.00)] at P˂0.05. Sperm cells in the control setup were significantly more viable than those in the 0.625% (t=0.005) and 2.500% toxicant doses (t=0.018) at the 95% confidence limit. CaC₂ appeared to induced morphological abnormalities and reduced viability in sperm cells of M. musculus.

Keywords: Artificial ripening, Calcium carbide, fruit vendors, sperm morphology, sperm viability.

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Authors: S. M. M. Syairah, M. H. Rajikin, A-R. Sharaniza

Abstract:

Several embryonic cellular mechanism including cell cycle, growth and apoptosis are regulated by phosphatidylinositol-3- kinase (PI3K)/Akt signaling pathway. The goal of present study is to determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol (δ-TCT) on the regulations of PI3K/Akt genes in murine morula. Twenty four 6-8 week old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) received tocopherol stripped corn oil, G2 was given 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity) and G4 received 60 mg/kg/day α-TOC. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. About fifty morulas from each group were used in the gene expression analyses using Affymetrix QuantiGene Plex 2.0 Assay. Present data showed a significant increase (p<0.05) in the average number (mean + SEM) of morula produced in G2 (27.32 + 0.23), G3 (25.42 + 0.21) and G4 (27.21 + 0.34) compared to control group (G1 – 14.61 + 0.25). This is parallel with the high expression of PDK1 gene with increase of 2.75-fold (G2), 3.07-fold (G3) and 3.59-fold (G4) compared to G1. From the present data, it can be concluded that supplementation with δ-TCT(s) and α-TOC induced high expression of PDK1 in G2-G4 which enhanced the PI3K/Akt signaling activity, resulting in the increased number of morula.

Keywords: Embryonic development, morula, nicotine, vitamin E.

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Authors: M. G. Tadros, S. M. Ezzat, M. M. Salama, M. A. Farag

Abstract:

In this study, the in vitro anticholinesterase activity of
the volatile oils of both O. basilicum and O. africanum was
investigated and both samples showed significant activity. The major
constituents of the two oils were isolated using several column
chromatographies. Linalool, 1,8-cineol and eugenol were isolated
from the volatile oil of O. basilicum and camphor was isolated from
the volatile oil of O. africanum. The anticholinesterase activities of
the isolated compounds were also evaluated where 1,8-cineol showed
the highest inhibitory activity followed by camphor. To confirm these
activities, learning and memory enhancing effects were tested in
mice. Memory impairment was induced by scopolamine, a
cholinergic muscarinic receptor antagonist. Anti-amnesic effects of
both volatile oils and their terpenoids were investigated by the
passive avoidance task in mice. We also examined their effects on
brain acetylcholinesterase activity. Results showed that scopolamineinduced
cognitive dysfunction was significantly attenuated by
administration of the volatile oils and their terpenoids, eugenol and
camphor, in the passive avoidance task and inhibited brain
acetylcholinesterase activity. These results suggest that O. basilicum
and O. africanum volatile oils can be good candidates for further
studies on Alzheimer’s disease via their acetylcholinesterase
inhibitory actions.

Keywords: Acetylcholinesterase, Ocimum africanum, Ocimum basilicum, passive avoidance.

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Authors: Sansani Rungrattawatchai

Abstract:

The White Kwao (Pueraria mirifica), a potent phytoestrogenic medicinal plant, has long been use in Thailand as a traditional folkmedicine. However, no scientific information of the direct effect of White Kwao on the development of mammalian embryo was available. Therefore, the purpose of this study was to investigate the effect of White Kwao extract on the in vitro development and implantation rate of mouse embryos. This study was designed into two experiments. In the first experiment, the two-cell stage mouse embryos were collected from the oviduct of superovulated mature female mice, and randomly cultured in three different media, the M16, M16 supplemented with 0.52μg esthinylestradiol-17β, and M16 supplemented with 10 mg/ml White Kwao extract. The culture was incubated in CO2 incubator at 37 oC . After the embryos were cultivated, the developments of embryos were observed every 24 hours for 5 days. The development rate of embryos from the two-cell stage to blastocyst stage in the media was with White Kwao was significantly higher (p<0.05) than those of the control group (68.50% versus 43.50%) but did not differ from the positive control group (68.50% versus 57.66%). In the second experiment, hatched blastocysts, which obtained from three different media, were differently labeled the nuclei with two polynucleotide-specific fluorochromes, the propidium iodide (PI) and the bisbenzimide. The results showed that the number of trophectoderm cells in the blastocysts that cultivated in the media with White Kwao did not significantly differ from the control (80.00 versus 70 cells) and the positive control group (80.00 versus 112.50 cells). The average number of inner cell mass in the White Kwao treated group did not significantly differ from the control group (20.50 versus 16.00 cells) and the positive control group (20.50 versus 20.50 cells). The total cell number including the trophectoderm and the inner cell mass of the individual hatched blastocyst was evaluated. The cell number in the blastocysts obtained from the media with the White Kwao did not significantly differ from the control (94.25 + 9.50 versus 92.33 + 4.05) and the positive control group (94.25 + 9.50 versus 110.33 + 9.16). The results demonstrated that the White Kwao treatment group did have a stimulating effect on the in vitro development of mouse embryos. The exact mechanism that White Kwao stimulated mouse embryo development is not known. The suspect mechanism may in a manner similar to the mechanism that of estrogen stimulated the development of the mouse embryos. Futher studies are needed to transfer the blastocyst into the endometrium of pseudopreagnancy mice to evaluate the effect of White Kwao on implantation

Keywords: White Kwao (Pueraria mirifica), blastocyst.

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Authors: Nelly К. Akhmatova, Оlga V. Lebedinskaya, Ancha V. Baranova, Еlena А. Lebedinskaya, Ekaterina V. Sorokina, Elvin А. Akhmatov, Аnatoliy P. Godovalov, Stanislav G. Markushin

Abstract:

An influence of intranasal combined injection of live cold-adapted influenza vaccine with chitosan derivatives as adjuvants on the subpopulation structure of mononuclear leukocytes of mouse spleen which reflects the orientation of the immune response was studied. It is found that the inclusion of chitosan preparations promotes activation of cellular-level of immune response.

Keywords: Immunophenotype, chitosan, cold-adapted vaccine, intranasal injection.

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Authors: Archana Mukherjee, Aruna Korde, Sudipta Chakraborty, H. D. Sarma, Grace Samuel, M. R. A. Pillai

Abstract:

Radiolabeled cyclic RGD peptides targeting integrin αvβ3 are reported as promising agents for the early diagnosis of metastatic tumors. With an aim to improve tumor uptake and retention of the peptide, cyclic RGD peptide dimer E[c (RGDfK)] 2 (E = Glutamic acid, f = phenyl alanine, K = lysine) coupled to the bifunctional chelator DOTA was custom synthesized and radiolabelled with 68Ga. Radiolabelling of cyclic RGD peptide dimer with 68Ga was carried out using HEPES buffer and biological evaluation of the complex was done in nude mice bearing HT29 tumors.

Keywords: 68Ga peptides, Angiogenesis imaging, Cyclic RGD peptides, PET Imaging.

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Authors: A. G. Abdellatif, H. M.Gargoum, A. A. Debani, M. Bengleil, S. Alshalmani, N. El Zuki, O. El Fitouri

Abstract:

In this study the administration of 660 mg/kg of the ethanolic extract of the Alhagigraecorum (Camel Thorn)to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl₄) or acetaminophen as compared to animals receiving CCl₄ or acetaminophen alone. Histopatological investigation also confirmed that, camel thorn extract protects liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand the cardiac toxicity produced by adriamycine was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with unexpected increase in the cardiac toxicity –induced by adriamycin in rodents.

Keywords: Acetaminophen, Adriamycin, Alhagi graecorum, Carbon tetrachloride.

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Authors: Liansheng Ren, Xihua Yang, Guoping Wang, Hong Zhang, Lili Zhao, Zhenguo Mi

Abstract:

The inhibition effect of brazilin to human bladder tumor cell line T24 in vitro and in vivo was studied. The results of the in vitro experiments showed that brazilin has strong inhibition activity on the target cells. The inhibition ratio of 100 μg/mL brazilin and 100 μg/mL mitomycin to the target cells was 90.90 % and 63.24 % respectively, which showed that brazilin has higher inhibition activity than mitomycin under the same concentration. Brazilin could induce cell apoptosis in T24 cells. Significant antitumor activity of brazilin was also showed in the animals experiments. The life extention rate of 200 mg/mL, 300 mg/kg, and 400 mg/kg brazilin intraperitoneally injected into Balb/c-nu-nu nude mice that with human bladder cancer were 51.50 %, 56.90 %, and 58.42 %（P<0.05）. Our study showed that brazilin has significant inhibitory effect on human bladder tumor cell.

Keywords: bladder cancer, brazilin, inhibition, T24 cell line

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Authors: Yulia Irnidayanti, Win Darmanto, Agus Abadi

Abstract:

research goal was to determine the expression levels cDNA of brain embrio at gestation days 10 (GD-10). The Electroforesis DNA results showed that GAPDH, Fibronectin1, Ncam1, Tenascin, Vimentin, Neurofilament heavy, Neurofilament medium and Neurofilament low were 447 bp, 462 bp, 293 bp. 416 bp, 327 bp, 301 bp, 398 bp and 289 bp. Result of real-time RT-PCR on brain Embryo at gestation days 10 showed that the expression of copy gen Fibronectin 36 copies, Ncam 21,708 copies; Tenascin 24,505 copies; Vimentin 538,554 copies; Neurofilament heavy 2,419 copies; Neurofilament medium 92,928 copies; Neurofilament low 125,809 copies. Vimentin expressed gene copies is very high compared with other gene copies. This condition are caused by Vimentin, that contribute to proliferate of brain development. The vimentin role to cell proliferation of brain.

Keywords: GAPDH, Fibronectin, Ncam, Tenascin, vimentin, Neurofilamen heavy, Neurofilament medium, Neurofilamen low.

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Authors: Deepak Mohan, Sushma Sharma

Abstract:

Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: Arthritis, diclofenac, histoarchitecture, sinusoidal.

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Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: Anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde.

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Authors: Hadi Hasanzadeh, Manijhe Mokhtari-Dizaji, S.Zahra Bathaie, Zuhair M. Hassan, Hamid R. Miri, Mahbobe Alamolhoda, Vahid Nilchiani, Hamid Goudarzi

Abstract:

The nanosized polymeric micelles release the drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. In this study, adult female Balb/C mice were transplanted with spontaneous breast adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg doxorubicin in one of three forms: free doxorubicin, micellar doxorubicin without sonication and micellar doxorubicin with sonication. To increase cavitation yield, the tumor region was sonicated with low level dual frequency of 3 MHz and 28 kHz. The animals were sacrificed 24 h after injection, and their tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The drug content in their tumor, heart, spleen, liver, kidneys and plasma was determined using tissue fluorimetry. The results show that in the group that received micellar doxorubicin with sonication, the drug concentration in the tumor tissue was nine and three times higher than in the free doxorubicin group and the micellar doxorubicin without sonication group, respectively. In the micellar doxorubicin with sonication group, the drug concentration in other tissues was lower than other groups (p<0.05). We conclude that dual frequency sonication improves drug release from micelles and increases the drug uptake by tumors due to sonoporation.

Keywords: Nanomicelles, Dual frequency ultrasound, Drug delivery

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Authors: Mouse, cardiac myocytes, computer simulation, action potential.

Abstract:

Heterogeneous repolarization causes dispersion of the T-wave and has been linked to arrhythmogenesis. Such heterogeneities appear due to differential expression of ionic currents in different regions of the heart, both in healthy and diseased animals and humans. Mice are important animals for the study of heart diseases because of the ability to create transgenic animals. We used our previously reported model of mouse ventricular myocytes to develop 2D mouse ventricular tissue model consisting of 14,000 cells (apical or septal ventricular myocytes) and to study the stability of action potential propagation and Ca2+ dynamics. The 2D tissue model was implemented as a FORTRAN program code for highperformance multiprocessor computers that runs on 36 processors. Our tissue model is able to simulate heterogeneities not only in action potential repolarization, but also heterogeneities in intracellular Ca2+ transients. The multicellular model reproduced experimentally observed velocities of action potential propagation and demonstrated the importance of incorporation of realistic Ca2+ dynamics for action potential propagation. The simulations show that relatively sharp gradients of repolarization are predicted to exist in 2D mouse tissue models, and they are primarily determined by the cellular properties of ventricular myocytes. Abrupt local gradients of channel expression can cause alternans at longer pacing basic cycle lengths than gradual changes, and development of alternans depends on the site of stimulation.

Keywords: Mouse, cardiac myocytes, computer simulation, action potential

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Authors: S. Nasri, G. H. Amin, A. Azimi

Abstract:

The use of herbs to treat disease is accompanied with the history of human life. This research is aimed to study the anti-inflammatory and antinociceptive effects of hydroalcoholic extract of aerial parts of "Tanacetum balsamita balsamita". In the experimental studies 144 male mice are used. In the inflammatory test, animals were divided into six groups: Control, positive control (receiving Dexamethason at dose of 15mg/kg), and four experimental groups receiving Tanacetum balsamita balsamita hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. Xylene was used to induce inflammation. Formalin was used to study the nociceptive effects. Animals were divided into six groups: control group, positive control group (receiving morphine) and four experimental groups receiving Tanacetum balsamita balsamita (Tb.) hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. I.p. injection of drugs or normal saline was performed 30 minutes before test. The data were analyzed by using one way Variance analysis and Tukey post test. Aerial parts of Tanacetum balsamita balsamita hydroalcoholic extract decreased significantly inflammatory at dose of 200mg/kg (P<0/001) and caused a significant decrease and alleviated the nociception in both first and second phases at doses of 200mg/kg (p<0/001) and 100mg/kg (P<0/05). Tanacetum balsamita balsamita extract has the anti-inflammatory and anti-nociceptive effects which seems to be related with flavonoids especially Quercetin.

Keywords: Inflammation, nociception, Hydroalcoholic extract, aerial parts of Tanacetum balsamita balsamita L.

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Authors: Funmilola O. Omoya, Abdul O. Momoh

Abstract:

Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plantbased anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: Anti-malaria, Curative, Plant-based anti-malaria agents.

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

Abstract:

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

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

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Authors: Asma Meziti, Hicham Meziti, Kaouthar Boudiaf, Benboubetra Mustapha, Hemama Bouriche.

Abstract:

Nigella sativa L. is an aromatic plant belonging to the family Ranunculaceae. It has been used traditionally, especially in the middle East and India, for the treatment of asthma, cough, bronchitis, headache, rheumatism, fever, influenza and eczema. Several biological activities have been reported in Nigella sativa seeds, including antioxidant. In this context we tried to estimate the antioxidant activity of various extracts prepared from Nigella sativa seeds, methanolic extract (ME), chloroformic extract (CE), hexanic extract (HE : fixed oil), ethyl acetate extract (EAE) water extract (WE). The Folin-Ciocalteu assay showed that CE and EAE contained high level of phenolic compounds 81.31 and 72.43μg GAE/mg of extract respectively. Similarly, the CE and EAE exhibited the highest DPPH radical scavenging activity, with IC50 values of 106.56μg/ml and 121.62μg/ml respectively. In addition, CE and HE showed the most scavenging activity against superoxide radical generated in the PMS-NADH-NBT system with respective IC50 values of 361.86 μg/ml and 371.80 μg/ml, which is comparable to the activity of the standard antioxidant BHT (344.59 μg/ml). Ferrous ion chelating capacity assay showed that WE, EAE and ME are the most active with 40.57, 39.70 and 22.02 mg EDTA-E/g of extract. The inhibition of linoleic acid/ß-carotene coupled oxidation was estimated by ßcarotene bleaching assay, this showed a highest relative antioxidant activity with CE and EAE (69.82% of inhibition). The antioxidant activities of the methanolic extract and the fixed oil are confirmed by an in vivo assay in mice, the daily oral administration of methanolic extract (500 and 800 mg/kg/day) and fixed oil (2 and 4 ml/kg/day) during 21 days, resulted in a significant enhancement of the blood total antioxidant capacity (measured by KRL test) and the plasmatic antioxidant capacity towards DPPH radical.

Keywords: Antioxidant Capacity, Chelating, Phenolic Compounds, Nigella Sativa, Scavenger

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Authors: Yanling Li, Linying Ji, Zita Oravecz, Timothy R. Brick, Michael D. Hunter, Sy-Miin Chow

Abstract:

Assessing several individuals intensively over time yields intensive longitudinal data (ILD). Even though ILD provide rich information, they also bring other data analytic challenges. One of these is the increased occurrence of missingness with increased study length, possibly under non-ignorable missingness scenarios. Multiple imputation (MI) handles missing data by creating several imputed data sets, and pooling the estimation results across imputed data sets to yield final estimates for inferential purposes. In this article, we introduce dynr.mi(), a function in the R package, Dynamic Modeling in R (dynr). The package dynr provides a suite of fast and accessible functions for estimating and visualizing the results from fitting linear and nonlinear dynamic systems models in discrete as well as continuous time. By integrating the estimation functions in dynr and the MI procedures available from the R package, Multivariate Imputation by Chained Equations (MICE), the dynr.mi() routine is designed to handle possibly non-ignorable missingness in the dependent variables and/or covariates in a user-specified dynamic systems model via MI, with convergence diagnostic check. We utilized dynr.mi() to examine, in the context of a vector autoregressive model, the relationships among individuals’ ambulatory physiological measures, and self-report affect valence and arousal. The results from MI were compared to those from listwise deletion of entries with missingness in the covariates. When we determined the number of iterations based on the convergence diagnostics available from dynr.mi(), differences in the statistical significance of the covariate parameters were observed between the listwise deletion and MI approaches. These results underscore the importance of considering diagnostic information in the implementation of MI procedures.

Keywords: Dynamic modeling, missing data, multiple imputation, physiological measures.

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Authors: E. Happ, A. Albert Tóth

Abstract:

The aim of the research is to investigate the forms of the demands of leisure tourism in a West-Hungarian industrial city, Győr. Today, Győr is still a traditional industrial city, its industry is mainly based on vehicle industry, but the role of tourism is increasing in the life of the city as well. Because of the industrial nature and the strong economy of the city, the ratio of business tourists is high. It can be stated that MICE tourism is dominating in Győr. Developments of the last decade can help the city with new tourism products to increase the leisure tourism. The new types of tourism – besides business tourism – can help the providers to increase the occupancy rates and the demand at the weekends. The research demonstrates the theoretical background of the topic, and it shows the present situation of the tourism in Győr with secondary data. The secondary research contains statistical data from the Hungarian Statistical Office and the city council, and it is based on the providers’ data. The next part of the paper shows the potential types of leisure tourism with the help of primary research. The primary research contains the results of an online questionnaire with a sample of 1000 potential customers. It is completed with 10 in-depth interviews with tourism experts, who explained their opinions about the opportunities of leisure tourism in Győr from the providers’ side. The online questionnaire was filled out in spring 2017 by customers, who have already stayed in Győr or plan to visit the city. At the same time in-depth interviews were made with hotel managers, head of touristic institutions and employees at the council. Based on the research it can be stated that the touristic supply of Győr allows the increase of the leisure tourism ratio in the city. Primarily, the cultural and health tourism show potential development, but the supply side of touristic services can be developed in order to increase the number of guest nights. The tourism marketing needs to be strengthened in the city, and a distinctive marketing activity - from other cities - is needed as well. To conclude, although Győr is an industrial city, it has a transforming industrial part, and tourism is also strongly present in its economy. Besides the leading role of business tourism, different types of leisure tourism have the opportunity to take place in the city.

Keywords: Business Tourism, Győr, industrial city, leisure tourism, touristic demand.

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