فهرست مطالب

Basic Medical Sciences - Volume:19 Issue:6, 2016
  • Volume:19 Issue:6, 2016
  • تاریخ انتشار: 1395/04/10
  • تعداد عناوین: 15
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  • Identification of Mycobacterium tuberculosis adherence-mediating components: a review of key methods to confirm adhesin function
    Saiyur Ramsugit, Manormoney Pillay* Pages 579-584
    Anti-adhesion therapy represents a potentially promising avenue for the treatment and prevention of tuberculosis in a post-antibiotic era. Adhesins are surface-exposed microbial structures or molecules that enable pathogenic organisms to adhere to host surfaces, a fundamental step towards host infection. Although several Mycobacterium tuberculosis adhesins have been identified, it is predicted that numerous additional adherence-mediating components contribute to the virulence and success of this pathogen. Significant further research to discern and characterize novel M. tuberculosis adhesins is, therefore, required to gain a holistic account of M. tuberculosis adhesion to the host. This would enable the identification of potential drug and vaccine targets for attenuating M. tuberculosis adherence and infectivity. Several methods have been successfully applied to the study and identification of M. tuberculosis adhesins. In this manuscript, we review these methods, which include adherence assays that utilize wild-type and gene knockout mutant strains, epitope masking and competitive inhibition analyses, extracellular matrix protein binding assays, microsphere adhesion assays, M. tuberculosis auto-aggregation assays, and in silico analyses.
    Keywords: Adhesin, Mycobacterium –, tuberculosis, Pathogenesis, Virulence factor
  • Adriana Bulboacă, Sorana D. Bolboacă, *, Habil SoimiŢ, A. Suciu Pages 585-593
    Objective
    The aim of this study was to investigate the effect of pre-treatment with curcumin on metabolic changes induced by two different pathophysiological mechanisms in rats (fructose diet and streptozotocin (STZ)-induced diabetes mellitus).
    Materials And Methods
    Five groups with 10 rats per group were investigated: control group (healthy rats), fructose diet groups without any pre-treatment (FD), fructose diet groups with curcumin pre-treatment (FDC), STZ-induced diabetes mellitus without any pre-treatment (SID) and STZ-induced diabetes mellitus with curcumin pre-treatment (SIDC). Systolic blood pressure, and several metabolic and oxidative stress parameters were assessed.
    Results
    Systolic blood pressure significantly increased in all groups compared with control group (P
    Conclusion
    The pre-treatment with curcumin in our experimental models significantly improved metabolic (total cholesterol, triglycerides, AST and ALT) as well as oxidative stress parameters (MDA, NOx, and Thiol) in both fructose diet and in STZ-induced diabetes in rats. These properties of curcumin may serve to improve the metabolic and oxidative stress conditions in patients with these pathological features.
    Keywords: Curcumin, Diabetes mellitus, Fructose, Metabolic syndrome Oxidative stress, Streptozotocin–induced diabetes
  • Fatemeh Damghani, Imanollah Bigdeli, Hossein Miladi, Gorji*, Atefeh Fadaei Pages 594-600
    Objective(s)
    This study evaluated the effect of swimming exercise during spontaneous methamphetamine (METH) withdrawal on the anxiety, depression, obsessive-compulsive disorder (OCD) and voluntary METH consumption in METH-dependent rats.
    Materials And Methods
    Male Wistar rats were repeatedly administered with bi-daily doses of METH (2 mg/kg, subcutaneous) over a period of 14 days. Exercised rats were submitted to swimming sessions (45 min/day, five days per week, for 14 days) during spontaneous METH-withdrawal. Then, all animals were tested for the assessment of anxiety by using the elevated plus-maze (EPM), the grooming behaviors (OCD), and depression using forced swimming test (FST) and voluntary METH consumption using a two-bottle choice (TBC) paradigm for the assessment of craving.
    Results
    The results showed that the swimmer METH-withdrawn rats exhibited an increase in EPM open arm time and entries and a reduction of immobility and grooming behaviors compared with the sedentary METH groups. Also, voluntary METH consumption was less in the swimmer METH-withdrawn rats than the sedentary METH groups throughout 5–8 days.
    Conclusion
    This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH.
    Keywords: Anxiety, Craving, Depression Methamphetamine, abstinance, Obsessive, compulsive disorder, Swimming
  • Ebrahim Faghihloo, Abolfazl Akbari, Fatemeh Adjaminezhad, Fard, Talat Mokhtari, Azad* Pages 601-607
    Objective(s)
    Valproic acid (VPA) has proven to be as one of the most promising useful drug with anticancer properties.In this study, we investigate the VPA effects on E-cadherin expression in HeLa, TC1, MKN45, and HCT116 cell lines. This study assesses the effects of VPA on human papillomavirus E7 expression in HPV positive cell lines.
    Materials And Methods
    Cell lines were treated by2 mmol/l VPA and expression of E-cadherin and E7 was analyzed by quantitative real-time PCR. Student’s t test and ANOVA were used to determine changes in expression levels.
    Results
    The results revealed that mean of E-cadherin expression is increased by VPA 1.8 times in HCT116 and MKN45 cell lines, also the mean of E-cadherin mRNA levels is up-regulated 2.9 times in HeLa and TC1 cell lines. So, E-cadherin augmentation induced by VPA in HeLa and TC-1, HPV positive cell lines, is higher than HPV negative cell lines MKN45 and HCT116. The mean of HPV E7 expression is decreased by VPA, 4.6 times in in HeLa and TC-1 cell lines.
    Conclusion
    This study demonstrates that re-expression of E-cadherin by VPA in HPV positive cell lines is more than HPV negative cell lines. Whereas, HPV E7 reduces the expression of E-cadherin, reduction of HPV E7 expression by VPA is related to more augmentation of E-cadherin in HPV positive cell lines. So, this study demonstrates that VPA has more anticancer properties in HPV positive cell lines, and could potentially be a promising candidate for cervical cancer treatment.
    Keywords: Cervical cancer, E, cadherin, HPV, Valproic acid
  • Maryam Ghadimkhani, Ehsan Saboory*, Shiva Roshan, Milani, Sedra Mohammdi, Yousef Rasmi Pages 608-614
    Objective(s)
    Febrile seizures (FS) are the most common type of convulsive events among children. Its prevalence has been estimated to be 2-5% in children between 3 months and 5 years old. Also, blood and CSF magnesium levels have been demonstrated to be reduced in children with FS. This study investigates the effect of MgSo4 pretreatment on the behaviors caused by hyperthermia (HT) and effect of these two on pentylen-tetrazol (PTZ)-induced seizure later in life.
    Materials And Methods
    Thirty two Wistar rats were assigned to 2 groups: saline-hyperthermia-pentylentetrazol (SHP) and magnesium-hyperthermia-pentylentetrazol (MHP). In both groups, HT was induced at the age of 18-19 days old. Before the HT, MHP group received MgSo4 and SHP group received normal saline intraperitoneally (IP). Behaviors of the rats were recorded during the HT. Then, in half of each group (n=8) at the age of 25-26 days old and in other half at the age of 78-79 days, seizure was induced by PTZ.
    Results
    The HT successfully caused convulsive behaviors in the rats and pretreatment with MgSo4 before HT attenuated HT-induced convulsive behaviors. PTZ-induced seizures a week later was more severe than those of 2 months later.
    Conclusion
    It can be concluded that pretreatment with MgSO4 inhibits HT-induced seizure and, in a long run, this intervention reduced PTZ-induced seizure later in life.
    Keywords: Hyperthermia, Later in life, MgSO4, PTZ, Seizure
  • Pages 615-623
    Objective(s)
    Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment.
    Materials And Methods
    Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored.
    Results
    In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P
    Conclusion
    In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria.
    Keywords: Captopril, Heart, Membrane fluidity, Mitochondria, Mitochondrial proton, translocating ATPases, Nifedipine
  • Hui Young Lee, Hyun, Jin Tae, Geum, Sil Cho, In Hye Kim, Jeong Hwi Cho, Joon Ha Park, Ji Hyeon Ahn, Bai Hui Chen, Bich, Na Shin, Moo, Ho Won, Chan Woo Park, Jun Hwi Cho, Jeong Yeol Seo, Jae, Chul Lee* Pages 624-631
    Objective(s)
    In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils.
    Materials And Methods
    IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given recovery times of 1 day, 2 days and 5 days and we examined change in c-myb immunoreactivity as well as neuronal damage/death in the hippocampus induced by a lethal transient ischemia.
    Results
    A lethal transient ischemia induced a significant loss of cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia, and this insult showed that c-myb immunoreactivity in cells of the SP of the CA1 region was significantly decreased at 2 days post-ischemia and disappeared at 5 days post-ischemia. However, IPC effectively prevented the neuronal loss in the SP and showed that c-myb immunoreactivity was constitutively maintained in the SP after a lethal transient ischemia.
    Conclusion
    Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult.
    Keywords: c, myb, Cells in stratum pyramidale, Delayed neuronal death, Ischemic preconditioning, Ischemia, reperfusion, Protection
  • Li Lin, Lijun Zhang, Liangzhu Yu, Lu Han, Wanli Ji, Hui Shen, Zhenwu Hu* Pages 632-637
    Objective(s)
    Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI.
    Materials And Methods
    Sprague-Dawley rats were randomly divided into two groups: control group and LPS group. ALI was induced by LPS intraperitoneal injection (3 mg/kg). The lung tissues were collected to measure lung injury score by histopathological evaluation, the protein expression of LC3-II and caspase-3 by Western blot, and microstructural changes by electron microscopy analysis.
    Results
    During ALI, lung cell death exhibited modifications in the death process at different stages of ALI. At early stages (1 hr and 2 hr) of ALI, the mode of lung cell death started with autophagy in LPS group and reached a peak at 2 hr. As ALI process progressed, apoptosis was gradually increased in the lung tissues and reached its maximal level at later stages (6 hr), while autophagy was time-dependently decreased.
    Conclusion
    These findings suggest that activated autophagy and apoptosis might play distinct roles at different stages of LPS-induced ALI. This information may enhance the understanding of lung pathophysiology at the cellular level during ALI and pulmonary infection, and thus help optimize the timing of innovating therapeutic approaches in future experiments with this model.
    Keywords: Acute lung injury, Apoptosis, Autophagy, Lipopolysaccharide
  • Parisa Nikpou, Daryoush Mohammad Nejad, Hajar Shafaei, Leila Roshangar, Nasser Samadi, Amir Mohammad Navali, Ali Reza Sadegpour, Dariush Shanehbandi, Jafar Soleimani Rad* Pages 638-645
    Objective(s)
    Three-dimensional biomimetic scaffolds have widespread applications in biomedical tissue engineering due to similarity of their nanofibrous architecture to native extracellular matrix. Co-culture system has stimulatory effect on chondrogenesis of adult mesenchymal stem cells. This work presents a co-culture strategy using human articular chondrons and adipose-derived stem cells (ASCs) from infrapatellar fat pad (IPFP) for cartilage tissue production.
    Materials And Methods
    Isolated stem cells were characterized by flowcytometry. Electrospun and polycaprolactone (PCL) scaffolds (900 nm fiber diameter) was obtained from Bon Yakhteh (Tehran- Iran) and human infrapatellar fat pad-derived stem cells (IPFP-ASCs) were seeded on them. IPFP- ASCs on scaffolds were co-cultured with articular chondrons using transwell. After 21 day, chondrogenic differentiation of stem cell was evaluated by determining the genes expression of collagen2, aggrecan and Indian hedgehog using real- time RT-PCR.
    Results
    Genes expression of collagen2, aggrecan by IPFP-ASCs did not alter significantly in comparison with control group. Howevers, expression of Indian hedgehog decreased significantly compared to control group (P˂ 0.05).
    Conclusion
    These findings indicate that chondrons obtained from osteoarthritic articular cartilage did not stimulate chondrogenic differentiation of IPFP-ASCs in co-culture.
    Keywords: Chondron, Co, culture, Nanofiber, Poly, e, caprolactone scaffold
  • Mahnaz Nouri, Shabnam Movassaghi, Alireza Foroumadi, Mansooreh Soleimani, Zahra Nadia Sharifi* Pages 646-652
    Objective(s)
    3, 4-methylenedioxymethamphetamine (MDMA) one of the methamphetamine derivatives that affect the reproductive system, has not been well understood. Many young people are consumers of drugs such as MDMA that can affect their reproductive capability. Apoptosis is the main mechanism for male infertility. Pentoxifylline (PTX) increases cAMP intracellularly and reduces tumor necrosis factor-α.
    This study aimed to investigate the protective effect of PTX administration in MDMA-induced apoptosis in testes of male Wistar rats.
    Materials And Methods
    Thirty male Wistar rats weighing 250–300 g were randomly divided into five groups: control group (without any intervention), group receiving 7.5 mg/kg MDMA three times every two hours for one day, first experimental group receiving 100 mg/kg PTX just at the time of third injection of MDMA, second experimental group receiving 100 mg/kg PTX a week before MDMA administration, and the vehicle group, which received MDMA놩抝. Two weeks later, testes were removed and prepared for H&E staining, TUNEL and Western blot techniques.
    Results
    There was a significant decrease of the score in the MDMA group compared with the control group. In first and second experimental groups, the quality of seminiferous epithelium was improved compared with the MDMA group. The number of TUNEL-positive cells/tubule increased in MDMA and vehicle groups, which is decreased by administration of PTX before MDMA. Expression of active caspase-3 significantly increased in MDMA group, which is significantly decreased by administration of PTX before MDMA.
    Conclusion
    PTX can significantly reduce the severity of lesions in the testes following administration of MDMA.
    Keywords: Apoptosis, Pentoxifylline, Testes, 3, 4, methylene, dioxymethamphetamine
  • Farhad Rahmanifar, Amin Tamadon, Davood Mehrabani*, Shahrokh Zare, Sorush Abasi, Saeideh Keshavarz, Mehdi Dianatpour, Zahra Khodabandeh, Iman Raze Ghian Jahromi, Omid Koohi, Hoseinabadi Pages 653-661
    Objective(s)
    Bone marrow-derived mesenchymal stem cells (BM-MSCs) potentials make them appropriate for cell therapy including ability of differentiation and release of anti-inflammatory cytokines and growth factors secreta. For treatment of azoospermia to induce proliferation and differentiation of germ cells, MSCs transplantation has been introduced. The aim of the present experimental case-control study was to histomorphometric evaluation of the germinal cells in seminiferous tubules of azoospermic rats before and after BM-MSCs allotransplantation.
    Materials And Methods
    In the present study, BM-MSCs were isolated from six male rats and confirmed. Their testes also served as intact negative controls. The recipient rats (n=6) were received two doses of 10 mg/kg of busulfan with 21 days interval to induce azoospermia. After cessation of spermatogenesis, the rats were allotransplanted with the BM-MSCs into efferent duct of right testes. Thirty-five days later, the right cell-treated testes were compared to left azoospermic ones.
    Results
    Histomorphometric analyses showed that the seminiferous tubules treated with BM-MSCs had normal morphology in comparison with azoospermic testes, which were without germinal layer. In most BM-MSCs-treated seminiferous tubules, spermatogenesis was observed.
    Conclusion
    The allotransplanted BM-MSCs could induce spermatogenesis in seminiferous tubules of azoospermic rats.
    Keywords: Azoospermia, Bone marrow mesenchymal, stem cell, Busulfan, Cell therapy, Rat
  • Zahra Tayarani, Najaran*, Maryam Akaberi, Mohsen Vatani, Seyed Ahmad Emami Pages 662-669
    Objective(s)
    Nepeta binaludensis Jamzad (Lamiaceae) has been used in folk medicine of Iran to cure various diseases. The plant is an endemic species to the country that has recently been identified in Razavi Khorasan province. To evaluate the antioxidant and anti-melanogenesis of N. binaludensis, in this study the inhibitory activity of different extracts of N. binaludensis in murine melanoma B16F10 cells is investigated.
    Materials And Methods
    The effects of petroleum ether, dichloromethane, ethyl acetate, and methanol extracts isolated from the plant on melanogenesis in B16 melanoma cells were investigated.To assess the inhibitory effects of this plant on melanogenesis, various assays were used including cytotoxicity, inhibition of mushroom tyrosinase and cellular tyrosinase, determination of melanin content, the effect of extracts on reactive oxygen species and western blot analysis of proteins involved in melanogenesis process.
    Results
    The content of melanin and the activity of tyrosinase were significantly reduced with different extracts of N. binaludensis in cells. Reactive oxygen species was also significantly decreased following the treatment of cell with the mentioned extracts, while a resazurin assay showed no cytotoxicity. Furthermore, we have found that the plant decreased the amount of tyrosinase and microphthalmia-associated transcription factor proteins, which verify the role of suppression of microphthalmia-associated transcription factor protein in melanogenesis inhibition.
    Conclusion
    Taken together the data indicate that N. binaludensis has inhibitory activity on melanin synthesis with no cytotoxic effects in B16 melanoma cells. Therefore, it merits future investigations to apply as whitening agent in hyperpigmentation.
    Keywords: Lamiaceae, Melanogenesis, Melanoma B16F10, Microphthalmia, associated, Nepeta binaludensis, Tyrosinase, Transcription factor
  • Liangrong Wang, Yuanlu Shan, Lei Chen, Bi Lin, Xiangqing Xiong, Lina Lin, Lida Jin* Pages 670-675
    Objective(s)
    Neutrophils play an important role in ischemia/reperfusion (IR) induced skeletal muscle injury. Microtubules are required for neutrophil activation in response to various stimuli. This study aimed to investigate the effects of colchicine, a microtubule-disrupting agent, on skeletal muscle IR injury in a rat hindlimb ischemia model.
    Materials And Methods
    Twenty-one Sprague-Dawley rats were randomly allocated into three groups: IR group, colchicine treated-IR (CO) group and sham operation (SM) group. Rats of both the IR and CO groups were subjected to 3 hr of ischemia by clamping the right femoral artery followed by 2 hr of reperfusion. Colchicine (1 mg/kg) was administrated intraperitoneally prior to hindlimb ischemia in the CO group. After 2 hr of reperfusion, we measured superoxide dismutase (SOD) and myeloperoxidase (MPO) activities, and malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the muscle samples. Plasma creatinine kinase (CK) and lactate dehydrogenase (LDH) levels were measured. We also evaluated the histological damage score and wet/dry weight (W/D) ratio.
    Results
    The histological damage score, W/D ratio, MPO activity, MDA, TNF-α and IL-1β levels in muscle tissues were significantly increased, SOD activity was decreased, and plasma CK and LDH levels were remarkably elevated in both the IR and CO groups compared to the SM group (P
    Conclusion
    Colchicine attenuates IR-induced skeletal muscle injury in rats.
    Keywords: Colchicine, Inflammation, Muscle, Reperfusion injury, Skeletal
  • Mitra Yousefpour*, Nima Naderi, Fereshteh Motamedi Pages 676-684
    Objective(s)
    Opioids and cannabinoids are two important compounds that have been shown to influence the activity of magnocellular neurons (MCNs) of supraoptic nucleus (SON). The interaction between opioidergic and cannabinoidergic systems in various structures of the brain and spinal cord is now well established, but not in the MCNs of SON.
    Materials And Methods
    In this study, whole cell patch clamp recording of neurons in rat brain slice was used to investigate the effect of acute morphine and cannabinoid administration on spontaneous inhibitory and excitatory spostsynaptic currents (sIPSCs and sEPSCs) in MCNs.
    Results
    Bath application of morphine produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency. In contrast, bath application of URB597 (fatty acid amide hydrolase (FAAH) inhibitor) produced a decrease in sEPSCs frequency but an increase in sIPSCs frequency. WIN55212-2 (cannabinoid receptor agonist) decreased both sIPSCs and sEPSCs frequencies of MCNs. Co-application of morphine and URB597 attenuated the effect of morphine on MCNs.
    Conclusion
    Taken together, these data indicated that at the cellular level, pharmacological augmentation of endocannabinoids could attenuate morphine effects on MCNs.
    Keywords: Cannabinoid, Morphine, sEPSC, sIPSC, Supraoptic nucleus
  • Aysel Kurt*, Levent Tumkaya, Suleyman Yuce, Hasan Turut, Medine Cumhur Cure, Ibrahim Sehitoglu, Yildiray Kalkan, Gokhan Pusuroglu, Erkan Cure Pages 685-691
    Objective(s)
    Carbon tetrachloride (CCl4) causes pulmonary toxicity. Infliximab (Ib) is a potent inhibitor of tumor necrosis factor-alpha (TNF-α). We aimed to investigate whether Ib has a protective effect on CCl4 induced lung injury.
    Materials And Methods
    Rats were divided into control, CCl4, and CCl4 groups. A single dose of 2 ml/kg CCI4 was administered to CCI4 group and a single dose of 7 mg/kg Ib was given to CCl4 group 24 hr before applying CCI4.
    Results
    TNF-α, malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels of the CCl4 group were markedly higher than both the control and CCl4 groups. The CCI4 group had lower histopathological injury than the CCl4 group.
    Conclusion
    Ib as a strong TNF-α blocker decreases the production of proinflammatory cytokines, MDA, and oxidative stress leading to a protective effect against CCl4 induced lung tissue injury.
    Keywords: Carbon tetrachloride, Infliximab, Nitric oxide, Pulmonary toxicity, Oxidative stress