فهرست مطالب

Advanced Pharmaceutical Bulletin
Volume:4 Issue: 1, Mar 2014

  • تاریخ انتشار: 1392/10/07
  • تعداد عناوین: 15
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  • Parisa Lotfinegad, Karim Shamsasenjan, Aliakbar Movassaghpour, Jafar Majidi, Behzad Baradaran Pages 5-13
    Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance.
    Keywords: Mesenchymal stem cells, Immunomodulation, Cell migration, Cell therapy
  • Abdul Aziz, Golam Sarwar Raju, Abhijit Das, Jamiuddin Ahmed, Mizanur Rahman Moghal Pages 15-19
    Purpose

    Crinum latifolium is a widely used plant in Asian folk and traditional medicine.In the present study, we have tried to find out the anthelmintic activity, total phenolic contents and cytotoxicity of the methanolic extract of the target plant.

    Methods

    Anthelmintic activity was assessed applying five different concentrations of the plant extract and recording the time of paralysis and death. Total phenolic contents were determined using Folin-Ciocaltu method, using Gallic acid as standard; while brine shrimp lethality test (BSLT) method was used to evaluate the cytotoxicity of the plant extract, where vincristine sulphate and DMSO was used as positive and negative control respectively.

    Result

    The lowest time for paralysis and death of worms, for test sample at highest concentration (50mg/ml), were found 24±0.45 and 46.4±0.60 min respectively, which gradually increased with the decrease of concentration. On the other hand, albendazole, which was used as standard, caused paralysis and death of worms at 56.2±0.20 min and 77.4±0.24 min respectively; whereas no mortality of the worms was observed, when distilled water was used as control. The crude methanolic extract exhibited lower amount of total phenolic content (17.50±2.64 mg/ml). In case of cytotoxicity measurement, the crude methanolic extract showed positive result (with LC50 15.652 μg/ml) compared to standard Vincristine sulphate (0.839 μg/ml); which indicated that the leaves of Crinum latifolium possess mild cytotoxic principles.

    Conclusion

    Therefore, further studies are suggested to evaluate the possible mechanism of action and the active compounds responsible for the biological activities of the plant extract.

    Keywords: Crinum latifolium (L.), Anthelmintic activity, Total phenolic content, Antioxidant activity, Cytotoxic activity, Amaryllidaceae
  • Reza Heidari, Hossein Babaei, Leila Roshangar, Mohammad Ali Eghbal Pages 21-28
    Purpose
    Methimazole is the most convenient drug used in the management of hyperthyroid patients. However, associated with its clinical use is hepatotoxicity as a life threatening adverse effect. The exact mechanism of methimazole-induced hepatotoxicity is still far from clear and no protective agent has been developed for this toxicity.
    Methods
    This study attempts to evaluate the hepatotoxicity induced by methimazole at different experimental conditions in a mice model. Methimazole-induced hepatotoxicity was investigated in different situations such as enzyme-induced and/or glutathione-depleted animals.
    Results
    Methimazole (100 mg/kg, i.p) administration caused hepatotoxicity as revealed by increase in serum alanine aminotransferase (ALT) activity as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in methimazole-treated mice. Combined administration of L-buthionine sulfoximine (BSO), as a glutathione depletory agent, caused a dramatic change in methimazole-induced hepatotoxicity characterized by hepatic necrosis and a severe elevation of serum ALT activity. Enzyme induction using phenobarbital and/or β-naphtoflavone beforehand, deteriorated methimazole-induced hepatotoxicity in mice. N-acetyl cysteine (300 mg/kg, i.p) administration effectively alleviated hepatotoxic effects of methimazole in both glutathione-depleted and/or enzyme-induced animals.
    Conclusion
    The severe hepatotoxic effects of methimazole in glutathione-depleted animals, reveals the crucial role of glutathione as a cellular defense mechanism against methimazole-induced hepatotoxicity. Furthermore, the more hepatotoxic properties of methimazole in enzyme-induced mice, indicates the role of reactive intermediates in the hepatotoxicity induced by this drug. The protective effects of N-acetylcysteine could be attributed to its radical/reactive metabolite scavenging, and/or antioxidant properties as well as glutathione replenishment activities
    Keywords: Enzyme induction, Glutathione, Hepatotoxicity, Methimazole, Mice, N, acetylcysteine
  • Ramlah Mohammad Ibrahim, Nurul Syima Hamdan, Maznah Ismail, Suraini Mohd Saini, Saiful Nizam Abd Rashid, Latiffah Abd Latiff, Rozi Mahmud Pages 29-33
    Purpose
    This study was conducted in menopausal women to determine the metabolic impact of Nigella sativa.
    Methods
    Thirty subjects who were menopausal women within the age limit of 45-60 were participated in this study and randomly allotted into two experimental groups. The treatment group was orally administered with N. sativa seeds powder in the form of capsules at a dose of 1g per day after breakfast for period of two months and compared to control group given placebo. Anthropometric and biochemical parameters were measured at baseline, 1st month, 2nd month and a month after treatment completed to determine their body weight, serum lipid profile and fasting blood glucose (FBG).
    Results
    The treatment group showed slight reduction with no significant difference in body weight changes of the respondents. However, significant (p<0.05) improvement was observed in total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and blood glucose (p<0.05).
    Conclusion
    These results suggested that treatment with N. sativa exert a protective effect by improving lipid profile and blood glucose which are in higher risk to be elevated during menopausal period.
    Keywords: Nigella sativa, Menopause, Metabolic syndrome, Hyperlipidemic, Hyperglycemia
  • Mahnaz Kesmati, Maysam Mard, Soltani, Lotfolah Khajehpour Pages 35-41
    Purpose
    A few studies have indicates that the sesame oil influences anxiety, but many reports show that β-1 adrenoceptors (ARs) of the basolateral amygdala (BLA) plays a pivotal role in this regard. Therefore, in this study the effect of acute injection of sesame oil on anxiety-like behavior in the presence and absence of the BLA β-1 ARs in the male Wistar rats were investigated.
    Methods
    Guide cannulas, for seven groups of rats, were implanted bilaterally into the BLA. Two weeks after the stereotaxic surgery, anxiety-like behaviors (the OAT%, OAE % and locomotor activity) were evaluated by Elevated Plus-Maze (EPM) for all groups. 3 groups received different volumes of sesame oil (i.p.) and they were compared with control group (received saline via i.p.), and the anxiogenic volume of sesame oil (1.5ml/kg) was determined. Then, 3 other groups received constant effective volume of sesame oil (1.5ml/kg) along with 3 different doses of betaxolol, selective β-1 ARs antagonist, intra BLA microinjection in order to be compared with sesame oil group (1.5 ml/kg).
    Results
    The acute injection of sesame oil with the volume dependent manner showed an anxiogenic effect with reduction of the OAT% and OAE% which the maximum effect of sesame oil was observed in the dose of 1.5mg/kg. Also, betaxolol with dose dependent manner attenuated the anxiogenic effects of sesame oil (1.5mg/kg), but this reduction could not remove the anxiety effects completely.
    Conclusion
    It seems that the sesame oil acute (i.p.) injection induces anxiety, and this effect is attenuated by inhibition of β-1ARs in the BLA.
    Keywords: Sesame oil_Anxiety_β 1 Adrenoceptors_Basolateral Amygdala_Elevated Plus_Maze
  • Mehdi Jahedi, Karim Shamsasenjan, Zohreh Sanaat, Mohamadreza Aliparasti, Shohreh Almasi, Mozhdeh Mohamadian, Babak Nejati, Amir Kamalifar, Ali Akbar Movassaghpour Pages 43-47
    Purpose
    The aim of this study was to evaluate the incidence of aberrant phenotypes and possible prognostic value in peripheral and bone marrow blood mononuclear cells of Iranian patients with AML.
    Methods
    56 cases of de novo AML (2010-2012) diagnosed by using an acute panel of monoclonal antibodies by multiparametric flowcytometry. Immunophenotyping was done on fresh bone marrow aspirate and/or peripheral blood samples using the acute panel of MoAbs is stained with Phycoerythrin (PE) /fluorescein isothiocyanate (FITC), Allophycocyanin (APC) and Peridinin-chlorophyll protein complex (perCP). We investigated Co-expression of lymphoid-associated markers CD2, CD3, CD7, CD 10, CD19, CD20 and CD22 in myeloblasts.
    Results
    Out of the 56 cases, 32 (57.1%) showed AP. CD7 was positive in 72.7% of cases in M1 and 28.5% in M2 but M3 and M4 cases lacked this marker. We detected CD2 in 58.35 of M1cases, 21.40% of M2 cases, 33.3 of M3 and 20% of M5; but M4 patients lacked this marker. The CBC analysis demonstrated a wide range of haemoglobin concentration, Platelet and WBC count which varied from normal to anaemia, thrombocytopenia to thrombocytosis and leukopenia to hyper leukocytosis.
    Conclusions
    Our findings showed that CD7 and CD2 were the most common aberrant marker in Iranian patients with AML. However, we are not find any significant correlation between aberrant phenotype changing and MRD in our population. Taken together, this findings help to provide new insights in to the investigation of other aberrant phenotypes that may play roles in diagnosis and therapeutic of AML.
    Keywords: Acute myeloid leukemia (AML), Aberrant Phenotypes (AP), CD markers
  • Nasser Ahmadiasl, Shokofeh Banaei, Alireza Alihemmati, Behzad Baradaran, Ehsan Azimian Pages 49-54
    Purpose
    Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure (ARF). The purpose of this study was to investigate the anti-inflammatory effect of erythropoietin (EPO) and melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats.
    Methods
    Male Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10mg/kg, i.p) and EPO (5000U/kg, i.p) were administered prior to ischemia. After 24 h reperfusion, blood samples were collected for the determination of total antioxidant capacity (TAC), malondialdehyde (MDA) and serum creatinine levels. Also, renal samples were taken for Immunohistochemical evaluation of Bcl2 and TNF-α (tumor necrosis factor-α) expression.
    Results
    Ischemia reperfusion increased creatinine, TAC, MDA levels and TNF-α expression, also, IR decreased Bcl2 expression. Treatment with EPO or MEL decreased creatinine, MDA levels, and increased TAC level. Also, MEL up-regulated Bcl2 expression and down-regulated TNF-α expression compared with EPO.
    Conclusion
    Treatment with EPO and MEL had a curative effect on renal IR injury. These results may indicate that MEL protects against inflammation and apoptosis better than EPO in renal IR injury.
    Keywords: Erythropoietin, Inflammation, Melatonin, Renal ischemia reperfusion
  • Negin Seyed, Gogani, Marveh Rahmati, Nosratollah Zarghami, Iraj Asvadi, Kermani, Mohammad Ali Hoseinpour, Feyzi, Mohammad Amin Moosavi Pages 55-60
    Purpose
    Despite significant improvements in treatment of chronic myelogenous leukemia (CML), the emergence of leukemic stem cell (LSC) concept questioned efficacy of current therapeutical protocols. Remaining issue on CML includes finding and targeting of the key genes responsible for self-renewal and proliferation of LSCs. Nucleostemin (NS) is a new protein localized in the nucleolus of most stem cells and tumor cells which regulates their self-renewal and cell cycle progression. The aim of this study was to investigate effects of NS knocking down in K562 cell line as an in vitro model of CML.
    Methods
    NS gene silencing was performed using a specific small interfering RNA (NS-siRNA). The gene expression level of NS was evaluated by RT-PCR. The viability and growth rate of K562 cells were determined by trypan blue exclusion test. Cell cycle distribution of the cells was analyzed by flow cytometry.
    Results
    Our results showed that NS knocking down inhibited proliferation and viability of K562 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G1 cell cycle arrest at short times of transfection (24 h) followed with apoptosis at longer times (48 and 72 h), suggest that post-G1 arrest apoptosis is occurred in K562 cells.
    Conclusion
    Overall, these results point to essential role of NS in K562 cells, thus, this gene might be considered as a promising target for treatment of CML.
    Keywords: Apoptosis, Cell cycle, Chronic myelogenous leukemia, K562, Nucleostemin, RNA interference
  • Davood Naziri, Masoud Hamidi, Salar Hassanzadeh, Vahideh Tarhriz, Bahram Maleki Zanjani, Hossein Nazemyieh, Mohamm Amin Hejazi, Mohammad Saeid Hejazi Pages 61-67
    Purpose
    Carotenoids are of great interest in many scientific disciplines because of their wide distribution, diverse functions and interesting properties. The present report describes a new natural source for carotenoid production.
    Methods
    Halorubrum sp., TBZ126, an extremely halophilic archaeon, was isolated from Urmia Lack following culture of water sample on marine agar medium and incubation at 30 °C. Then single colonies were cultivated in broth media. After that the cells were collected and carotenoids were extracted with acetone-methanol (7:3 v/v). The identification of carotenoids was performed by UV-VIS spectroscopy and confirmed by thin layer chromatography (TLC) in the presence of antimony pentachloride (SbCl5). The production profile was analyzed using liquid-chromatography mass spectroscopy (LC-MS) techniques. Phenotypic characteristics of the isolate were carried out and the 16S rRNA gene was amplified using polymerase chain reaction (PCR).
    Results
    LC-MS analytical results revealed that produced carotenoids are bacterioruberin, lycopene and β-carotene. Bacterioruberin was found to be the predominant produced carotenoid. 16S rRNA analysis showed that TBZ126 has 100% similarity with Halorubrum chaoviator Halo-G*T (AM048786).
    Conclusion
    Halorubrum sp. TBZ126, isolated from Urmia Lake has high capacity in the production of carotenoids. This extremely halophilic archaeon could be considered as a prokaryotic candidate for carotenoid production source for future studies.
    Keywords: Carotenoids, Halorubrum chaoviator, Bacterioruberin, Lycopene, β carotene
  • Emmanuel Ike Ugwuja Pages 69-74
    Purpose
    To determine the biochemical effects of energy drink alone or in combination with alcohol in normal albino rats.
    Methods
    Twenty male albino rats weighing 160-180g were assigned into groups A-E of four rats per group. Group A and B rats were given low and high doses of ED, respectively, groups C and D were administered low and high doses of EDmA, respectively while group E rats were given distilled water and served as control. The treatment lasted for 30 days after which the animals were killed and their blood collected for laboratory analyses using standard methods.
    Results
    There were no significant differences in body weight, packed cell volume and haemoglobin concentration with either administration of ED or EDmA in comparison to the control. Energy drink alone or EDmA has significant effects on total white blood cell count, plasma potassium, calcium, renal functions, liver enzymes and plasma triglycerides, with EDmA having more effects than ED alone, except for body weight where the energy drink alone has higher effect.
    Conclusion
    Consumption of energy drink alone or in combination with alcohol is associated with significant alterations in some biochemical parameters. Caution should be exercised while consuming either of them. Public health education is urgently needed to correct the wrong impression already formed by the unsuspecting consumers, especially the youths.
    Keywords: Energy drinks, Alcohol, Public health, Hypertension, Dyslipidaemia, Youths
  • Khaled Rashed, Monica Butnariu Pages 75-81
    Purpose
    The present study was carried out to evaluate antimicrobial and antioxidant activities from Eriobotrya japonica stems as well investigation of its chemical composition.
    Methods
    Methanol 80% extract of Eriobotrya japonica stems was tested for antimicrobial activity against bacterial and fungal strains and for antioxidant activity using oxygen radical absorbance capacity (ORAC) and the trolox equivalent antioxidant capacity (TEAC) assays and also total content of polyphenols with phytochemical analysis of the extract were determined.
    Results
    The results showed that the extract has a significant antimicrobial activity, it inhibited significantly the growth of Candida albicans suggesting that it can be used in the treatment of fungal infections, and it showed no effect on the other bacterial and fungal strains, the extract has a good antioxidant activity, it has shown high values of oxygen radical absorbance capacity and trolox equivalent antioxidant capacity, while it showed a low value of polyphenol content. Phytochemical analysis of the extract showed the presence of carbohydrates, terpenes, tannins and flavonoids, further phytochemical analysis resulted in the isolation and identification of three triterpenic acids, oleanolic, ursolic and corosolic acids and four flavonoids, naringenin, quercetin, kaempferol 3-O-β-glucoside and quercetin 3-O-α-rhamnoside.
    Conclusion
    These results may help to discover new chemical classes of natural antimicrobial antioxidant substances.
    Keywords: Eriobotrya japonica, tems, Antimicrobial, Antioxidant, Chemical constituents
  • Bohlool Habibi Asl, Haleh Vaez, Turan Imankhah, Samin Hamidi Pages 83-89
    Purpose
    Prescription of ketotifen as an effective antihistamine in asthma and allergic conditions is associated with side effect of weight gain. Caffeine is an agent which increases thermogenesis and improves energy expenditure and also effective in asthma. The aim of current study was to evaluate caffeine impact in reducing weight gain side effect of ketotifen.
    Methods
    Male mice at the weight limit of 20-30 g in 8 groups were randomly chosen and injected following drug dosages for 45 days intraperitoneally: control group (normal saline 10 ml/kg), three groups of ketotifen (4, 8, 16 mg/kg), three groups of caffeine (4, 8, 16 mg/kg) and one group of ketotifen (4 mg/kg) in combination with caffeine (4 mg/kg). Weight changes have been recorded and assessed every 3 days for 45 days.
    Results
    The results showed that in all dosages of the two drugs, significant weight loss occurred in comparison with the control group.
    Conclusion
    The effect of caffeine on weight loss according to our results, matches with human studies, while ketotifen contradictory to our assumption, resulted in weight loss which probably was related to the difference in metabolic pathways in mice and humans, or maybe the used doses of ketotifen in this study were insufficient to reduce TNF-α production or influence in serotonin release and be effective on appetite or weight gain.
    Keywords: Ketotifen, Caffeine, Appetite, Weight changes, Mice
  • Salman Asghari, Mahmoud Shekari Khaniani, Masood Darabi, Sima Mansoori Derakhshan Pages 91-95
    Purpose
    Stem cell factor (SCF) plays an important role in the survival, proliferation and differentiation of hematopoietic stem cells and progenitor cells. Potential therapeutic applications of SCF include hematopoietic stem cell mobilization, exvivo stem/progenitor cell expansion, gene therapy, and immunotherapy. Considering the cost and problem in accessibility of this product in Iran, clears the importance of indigenizing production of rhSCF. In the present work, we describe the construction of the soluble rhSCF expression vector in pET-26b (+) with periplasmic localization potential.
    Methods
    Following PCR amplification of human SCF ORF, it is cloned in pET-26b (+) vector in NcoI and XhoI sites. The recombinant construct was transformed into BL21 (DE3) Ecoli strains.
    Results
    The construction of recombinant vector was verified by colony PCR and sequence analysis of pET26b-hSCF vector. Sequence analyses proved that human SCF ORF has been inserted into NcoI and XhoI site with correct orientation downstream of strong T7 promotor and showed no nucleotide errors.
    Conclusion
    The SCF ORF was successfully cloned in pET-26b (+) expression vector and is ready for future production of SCF protein.
    Keywords: Human SCF, Cloning, pET, 26b(+)
  • Jahanbakhsh Samadikhah, Samad Ej Golzari, Babak Sabermarouf, Ida Karimzadeh, Parastou Tizro, Hadi Mohammad Khanli, Kamyar Ghabili Pages 97-100
    Purpose
    Atrial fibrillation (AF) is the most frequent arrhythmia that follows coronary artery bypass graft (CABG). Patients developing postoperative AF (POAF) have significantly higher mortality rates. The consistent prophylactic effectiveness of statins and vitamin C are well-accepted; however, no evaluation on combined therapy has been performed. We aimed at assessing the efficacy of combination therapy with statin and vitamin C in comparison with statin alone in the prevention of post CABG-AF.
    Methods
    In a randomized double blind clinical trial, 120 candidates of CABG were recruited in Tabriz Madani Educational Center in a 15-month period of time. Patients were randomized into two groups of 60 receiving oral atorvastatin (40mg) plus oral vitamin C (2g/d operation day and 1g/d for five consequent days) for intervention group and oral atorvastatin (40mg) for control group. Occurrence of post CABG AF was compared between the two groups.
    Results
    There were 60 patients, 43 males and 17 females with a mean age of 61.0±11.5 (29-78) years, in the intervention group and sixty patients, 39 males and 21 females with a mean age of 60.5±11.3 (39-81) years, in the control group. The post CABG AF occurred in 6 cases (10%) in the interventional group and 15 patients (25%) in the controls (P=0.03, odds ratio=0.33, 95% confidence interval 0.12-0.93).
    Conclusion
    Based on our findings, combination prophylaxis against post CABG AF with oral atorvastatin plus vitamin C is significantly more effective than single oral atorvastatin.
    Keywords: Atrial Fibrillation, Atorvastatin, Vitamin C, Coronary Artery Bypass Grafting