hossein vatanpour
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The Iranian Echis Carinatus (IEC) venom is an exclusive natural source of bio-substances for a wide range of purposes in the blood coagulation cascade. The present study for the first time was aimed to assess novel pro-coagulant, anti-coagulant and anti-platelet proteins, named EC1.5 (a), EC5.1 (b) and EC4 (a) from Iranian Echis Carinatus (IEC) venom.These peptides were purified by multi-step chromatography methods. Hematological properties were measured using activated clotting tests, platelet aggregation studies, and hemorrhage assessment. Subsequently, these proteins were identified through both their intact molecular mass and peptide mass fingerprint (PMF) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Multiple sequence alignments were performed by ClustalW, Bioedit software. Molegro Data Modeller (MDM) 3.0 software was used to predict the putative tertiary structure of proteins.EC1.5 (a), a single-band protein with a molecular mass of 66 and 55 kDa, was observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a reduced and non-reduced state, respectively. Based on the Mascot results, we considered that EC1.5 (a) is a metalloproteinase of group ΙΙ which exhibited potent pro-coagulant activity. It is predicted that the EC1.5 (a) with hemorrhagic activity, potentially is a metalloproteinase/disintegrin region that constitutes the disintegrin-like domains. Our findings demonstrate that the disintegrin domain of EC1.5 (a) lacks platelet aggregation inhibitory activity. On the contrary, this factor shows the property of a platelet aggregation inducer. Also, the EC5.1 (b) was observed as a single-band protein with a molecular mass of 7.5 kDa. EC5.1 (b) showed both anti-coagulant and anti-platelet properties. Additionally, the structure of the EC5.1 (b) fraction is expected to be similar to that of phospholipase A2, while EC4 (a) structure is potentially very similar to that of Echistatin with 5 kDa molecular mass. We introduce the predicted structure of P-II snake venom metalloproteinase/ disintegrin domains, phospholipase A2 and Echistatin-like fractions. Further research is therefore needed to determine the complete structure of these novel fractions and elucidate their mechanism of action and future therapeutic applications of cardiovascular and homeostasis disorders.Keywords: Disintegrin, Hemorrhagic metalloproteinases, Platelet aggregation inducer, Phospholipase A2, MALDI TOF, MS
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Health dietary supplements compared to prescription drugs are different in deciding to consume and the end user is the main decision maker. Packaging plays the most important role in product marketing and branding in the nutritional supplement industry. Packaging shape and color can impact a decision to buy as well as identify what type of item it is and whom it is made for. Packaging factors such as color and shape are important in clinical and marketing aspects. Many types of research on the effect of packaging on psychology or marketing aims have been investigated. This study aimed to evaluate consumers' preferences for color and shape in oral solid dosage forms (OSDF) by eye-tracking technique. Eye movements are directly correlated to feelings, attention, learning, and reminding of an advertisement or product. This study tried to find consumer preferences by considering eye movements. This study includes two parts: evaluating the independent impact of color and the independent impact of shape on drowning the participants' attention by tracking the eyes. Thirty participants (15 men and 15 women, aged 20 to 50) with normal and full-color vision participated in the experiment. Images with a neutral (grey) background including 8 colors for each tablet form were made based on previous studies. Images with a neutral (grey) background including 8 shapes for each color were made. Shapes were selected based on the most current shapes used in the pharmaceutical industry. The images were shown to participants and their eye movements were collected by eye tracking device (TobiiT60). The descriptive data analysis indicated that white is the most favored color among the sampling population with a mean vision time of 2252 milliseconds. On the other hand, the pink color was selected as the least favored. For shapes, descriptive analysis of data indicated that the hard gelatin capsules are the most favored dosage form among the sampling population with a mean vision time of 1238 milliseconds. On the other hand, pearl 1 was selected as the least favored compared to other shapes with a mean vision time of 992 milliseconds. Based on the results of this research, the preferable form of general dietary supplement is small and white totally. The results indicated that white color is the most favored color and pink color is the least favored one. In addition, the hard capsule was selected as the most favored dosage form while the pearl was selected as the least favored one. No significant difference between men and women groups was observed. This may be important for pharmaceuticals to produce medicines with the most preferences for both clinical and marketing aspects. Color is the most preferred characteristic with the perception that color is related to the therapeutic indication of supplements. Shape and size can affect preferences regarding the compliance of patients.
Keywords: Visual Aspects, Consumer Preferences, Food Supplements, Eye-Tracking, Neuromarketing -
Epilepsy, as a neurological disease, can be defined as frequent seizure attacks. Further, it affects many other aspects of patients’ mental activities, such as learning and memory. Scorpion venoms have gained notice as compounds with potential antiepileptic properties. Among them, Buthotus schach (BS) is one of the Iranian scorpions studied by Aboutorabi et al., who fractionated, characterized, and tested this compound using electrophysiological techniques in brain slices (patch-clamp recording). In the present study, the fraction obtained from gel electrophoresis was investigated through behavioral and electrophysiological assays. At first, ventricular cannulation was performed in rats, and then the active fraction (i.e., F3), carbamazepine, and the vehicle were microinjected into the brain before seizure induction by the subcutaneous (SC) injection of pentylenetetrazol (PTZ). Seizure behaviors were scaled according to Racine stages. Memory and learning were evaluated using the Y-maze and passive avoidance tests. Other groups entered evoked field potential recording after microinjection and seizure induction. Population spike (PS) and field excitatory postsynaptic potential (fEPSP) were measured. The F3 fraction could prevent the fifth stage and postpone the third stage of seizure compared to the control (carbamazepine) group. There was no significant improvement in memory and learning in the group treated with the F3 fraction. Also, PS amplitude increased significantly, and long-term potentiation was successfully formed after the high-frequency stimulation of the performant pathway. Our results support the antiepileptic effects of the F3 fraction of BS venom, evidenced by behavioral and electrophysiological studies. However, the effects of this fraction on memory and learning were not in the same direction, suggesting the involvement of two different pathways.
Keywords: Epilepsy, Scorpion, Memory, Learning, Synaptic, Plasticity, Field, Recording, Acute, Seizure -
Biolmpacts, Volume:12 Issue: 5, Sep 2022, PP 431 -438Introduction
Acute kidney injury (AKI) may have a negative effect on mitochondrial hemostasis and bioenergetics as well as coenzyme Q10 (CoQ10) content. PGC-1α, AMPK, sirtuin 1 (Sirt1), and Sirt3, as the key metabolic regulators under nutritional stress, stimulate energy production via mitochondrial biogenesis during AKI. However, no report is available on the relationship between CoQ10 level and nutrient sensors in the pathophysiology of AKI caused by Hemiscorpius lepturus scorpion envenomation.
MethodsThree doses of venoms (1, 5, and 10 mg/kg) were administered by subcutaneous (SC) injection to male albino mice. The animals were sacrificed 1 day or 7 days after administration of venom and their kidneys were collected to analyze gene expression involved in AKI, nutrient sensors, and apoptosis signaling activation by real-time polymerase chain reaction (PCR) and the measurement of CoQ10 level using the High-performance liquid chromatography (HPLC) method.
ResultsThe data indicated a significant decrease in CoQ10 level after the administration of venom in 5 and 10 mg/kg. In addition, 1 day after the treatment, a significant over-expression of Sirt1 (5 and 10 mg/kg) was observed compared with normal mice. Overexpression of Sirt3 occurred 1 day and 7 days after treatment only at the dose of 5.0 mg/kg of venom. Furthermore, over-expression of AMPK as an important mitochondrial energetic sensor happened 1 day and 7 days after the injection of venom (5 mg/kg) (P<0.01). The significant increase in the gene expression of caspase-9 and 3 after the injection of venom (5 and 10 mg/kg) confirmed the role of cell death signaling.
ConclusionThe venom-induced energy-sensing pathways have a key role in gene expression of PGC-1α, AMPK, Sirt3, and CoQ10 content after venom-induced AKI.
Keywords: Acute kidney injury, Coenzyme Q10, Sirtuin 3, Sirtuin 1, 5' AMP-activated protein kinase, envenomation -
The pharmaceutical industry's performance in the global economy has been affected by the growing competition associated with globalization, economic liberalization, and the trade-related aspect of the intellectual property rights (TRIPS) agreement. To maintain performance, organizations need to consider strategic foresight (SF) and organizational resilience (OR) to anticipate future trends and survive crises. By proposing a conceptual framework, this study examines the relationship between organizational resilience, strategic foresight, competitive advantage (CA), and firm performance (FP). A conceptual framework was developed to assess the hypotheses in the pharmaceutical industry. Then, partial least squares structural equation modeling (PLS-SEM) was applied to investigate the relationships quantitatively. The results of structural equation modeling (SEM) based on the data generated from 202 completed questionnaires by the pharmaceutical companies in Iran demonstrate that OR, SF, and CA have significant positive impacts on FP. Moreover, CA partially mediates the relationship between OR and FP and also between SF and FP. The findings of this study enrich the existing literature by demonstrating that early detection of environmental change and resilient manner assist Iranian pharmaceutical firms to survive if joining the WTO. This is the first study that examines the direct and indirect effect of OR and SF on the FP, considering the mediating impact of CA. This investigation attempts to address the mechanisms through which OR and SF affect organizational performance, especially in the pharmaceutical industry.Keywords: Organizational resilience, Strategic foresight, pharmaceutical companies, Firm performance, Competitive advantage
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IntroductionIt is a long time that natural toxin research is conducted to unlock the medical potential of toxins. Although venoms-toxins cause pathophysiological conditions, they may be effective to treat several diseases. Since toxins including scorpion toxins target voltage-gated ion channels, they may have profound effects on excitable cells. Therefore, elucidating the cellular and electrophysiological impacts of toxins, particularly scorpion toxins would be helpful in future drug development opportunities.MethodsIntracellular recording was made from F1 cells of Helix aspersa in the presence of calcium Ringer solution in which Na+ and K+ channels were blocked. Then, the modulation of channel function in the presence of extracellular application of F4 and F6 toxins and kaliotoxin (KTX; 50 nM and 1 μM) was examined by assessing the electrophysiological characteristics of calcium spikes.ResultsThe two active toxin fractions, similar to KTX, a known Ca2+-activated K+ channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca2+ spikes. Therefore, it might be inferred that these two new fractions induce neuronal hyperexcitability possibly, in part, by blocking calcium-activated potassium channel current. However, this supposition requires further investigation using voltage clamping technique.ConclusionThese toxin fractions may act as blocker of calcium-activated potassium channels.Keywords: Scorpion Venom, Intracellular recording, Calcium spike, Buthotus schach
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Bothutous Schach (BS) scorpion venom consists of several polypeptides that could modulate ion channels. In this study, the effects of BS crude venom on passive and active electrophysiological properties of rat neurons in supraoptic nucleus (SON) of hypothalamus was investigated using whole-cell patch clamp technique. The results showed that bath application of BS venom produced significant change in passive properties of SON neurons, namely a decrease in resting membrane potential and an increase in input resistance of the cells. Also, significant change in active properties of SON neurons was shown after bath application of BS venom; including a decrease in the number of evoked action potential along with an increase in half width and decay time of action potential and a significant decrease in afterhyperpolarization amplitude. Finally, a decreased latency to the first spike accompanied by a lower current threshold to elicit the first spike was shown compared with the values before venom application. These effects are possibly through blocking different ion channels including potassium channels. Further experiments using different fractions of the venom is required to specify venom effects on various ion channels.Keywords: Buthotus schach, Ion channels, Whole-cell patch clamp, Scorpion venom
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The influence of company reputation, or what is often referred to as corporate reputation on branding strategy and producing intangible asset for different industries has been researched in western countries, but there is a gap for the generalizability of findings to countries out of the United State and Europe . To establish the western researchers external validity of theories in other countries and to obtain a better understanding of the influences of branding and company reputation on pharmaceutical business markets, the researchers applied this study for Iran, a country in the Middle East. The obtained results using SEM (by P.L.S. 2.0 software ) showed good relationship between value creation and brand differentiation (β = 0.360 and t-value = 3.167), between corporate communication and brand differentiation (β = 0.022 and t-value = 3.668) and between strategic resources and brand differentiation (β = 0.289 and t-value = 2.247 ). This study is a pioneering attempt in Iran to measure the impact of corporate reputation on brand differentiation strategy.Keywords: Corporate Reputation, Value Creation, Strategic Resource, Corporate Communication, Brand, Brand Differentiation
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The impact of corporate reputation uses, including value creation, corporate communication and strategic resources on branding strategies such as segmentation and producing intangible assets for different industries is investigated in western countries in the past few years, but there is a gap for the generalizability of findings to countries out of the United Estates and Europe. To establish the western researcher’s external validity of theories in other countries and to obtain a better understanding of the influences of branding and corporate reputation in pharmaceutical business markets, the researchers applied this study for Iran, as a country in the Middle East . The obtained results using SEM ( by P.L.S. 2.0 software ) showed a weak relation between value creation and brand segmentation (β = 0.307 and t-value = 1.806) and no significant relation between corporate communication and strategic resources with brand segmentation (β = 0.199 and t-value = 1.301) and (β = 0.246 and t-value = 1.465 ). Based on these findings; and previous researches in this field, it seems that pharmaceutical managers and marketers need to change their thoughts and practices regarding segmentation and reputation.This study is a pioneering attempt in Iran to evaluate the impact of corporate reputation on brand segmentation strategy.
Keywords: Corporate Reputation, Value creation, Strategic Resource, Corporate Communication, brand, Brand Segmentation -
مقدمه و اهدافپر عرق کردنی اولیه (Primary hyperhidrosis) یک اختلال عملکردی با علت ناشناخته و برآمده از تحریک بیش از حد اعصاب سمپاتیک تحریک کننده غدد عرق است. در سالهای اخیر مطالعات زیادی برای بررسی اثر بخشی جریان های گوناگون برروی پرعرق کردنی کف دست صورت گرفته که یکی از این روش ها استفاده از جریان مستقیم پالس دار است که بدلیل کاهش خطر سوختگی و شوک الکتریکی، جلوگیری از پلاریته و نداشتن آزار حسی مورد توجه محققان قرارگرفته است. هدف از انجام این مطالعه مقایسه اثر بخشی و پایایی یونتوفروزیس آب لوله کشی با جریان مستقیم پیوسته و جریان مستقیم پالس دار بر پر عرق کردنی اولیه کف دست می باشد.مواد و روش هادر این مطالعه تعداد 20 فرد داوطلب گرفتار به پرعرق کردنی اولیه کف دست با دامنه سنی 18 الی 45 سال مورد مطالعه قرار گرفتند. شرکت کننده ها بطور تصادفی به دو گروه مداخله ای تحت درمان با هر دو جریان مستقیم پیوسته و جریان مستقیم پالس دار قرار گرفتند. تست گرویمتری برای اندازه گیری میزان عرق کردن در شروع درمان، جلسه چهارم وهشتم درمان وهفته های 4، 8 و 12 پس از پایان درمان استفاده شد. کیفیت زندگی شرکت کننده ها با استفاده از پرسشنامه DLQI در شروع درمان و پیگیری های بعدی ارزیابی شد.یافته هامیزان عرق کردن بطور معناداری در طول 8 جلسه درمان در هر دو گروه مداخله کاهش یافت. کیفیت زندگی در هر دو گروه نیز بهبود یافت(01/0< P).نتیجه گیرییافته های بدست آمده از این مطالعه نشان می دهد که هر دو جریان مستقیم پیوسته و پالس دار در درمان هایپرهیدروزیس کف دست موثر است اما استفاده از یونتوفروزیس آب لوله کشی با جریان مستقیم پالس دار نسبت به جریان مستقیم پیوسته دارای پیامدهای جانبی کمتری می باشد.کلید واژگان: یونتوفورزیس, پرعرق کردنی اولیه, جریان مستقیم پیوسته, جریان مستقیم پالس دار, دستBackground And AimsPrimary Hyperhidrosis (PHH) is a functional disorder of idiopathic etiology caused by overstimulation of the sympathetic nervous system stimulating the sweat glands. In the recent years, many studies have evaluated the effectiveness of the palmar hyperhidrosis; one of these methods is the use of pulsed direct current which has been of interest to researchers due to its effect on prevention and reduction of the risk of burns and electrical shock, polarity, and discomfort. The aim of the present study was to compare the efficacy and long-lasting effect of tap water iontophoresis in continous direct and pulsed direct currents on primary hyperhidrosis of hand.Materials And MethodA total of 20 participants, aged 18-45, volunteerd and were diagnosed with the primary palmar hyperhidrosis. Participants were randomly assigned into two intervention groups treated by either ontophoresis of the tap water with DC or with pulsed DC. Gravimetric method was also applied to measure the sweating rate at the baseline, 4 days, 1 week, 4 weeks, 8 weeks, and 12 weeks after the treatment. Participants quality of life was also assessed using the DLQI at baseline and all follow-up time points.ResultsSweating rate significantly reduced during the eight treatment sessions in both intervention groups.The quality of life, too, improved in both intervention groups (PConclusionThe findings of the present study suggest that both continuous and pulsed direct current is effective in the treatment of palmar hyperhidrosis, but Iontophoresis with pulsed direct current has less side effects.Keywords: Iontophoresis, Hyperhidrosis, Pulsed direct current, Direct current, Hand
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Buthotus schach is one of the dangers scorpion in Iran that belong to the Buthidae family. Toxins are existing in venom scorpion, modulate the ion channels by blocking or opening the pore of the channel or by altering the voltage gating and useful as pharmacological tools. In the present study, we investigated the effect of venom and its obtained fractions by gel filtrations on electrophysiological properties of magnocellular supraoptic of hypothalamus by using whole cell patch clamp. In our result were shown, scorpion crude venom and its fraction effect on Na gated voltage channels. A significant decrease was revealed in amplitude firing, in venom various concentration and some of the venom fraction. Also a significant increase was shown in half width and rise time 10% to 90% actions potential firing. Previous evidence was revealed change in electrophysiological properties such as amplitude and rise time 10% to 90%, related to sodium gated voltage channels. Sodium channels toxins existed on scorpion venom caused modulate on sodium channels. In order to access bioactive components, six fractions were collected by gel chromatography techniques. After bath application of fraction, four components were found F2, F3, F4 and F6. Also F2 and F3 component show the same effects than venom on electrophysiological properties of magnocellular supraoptic than venom.Keywords: Buthotus schach, Voltage Gated Na Channels, Scorpion Toxin, Whole-Cell Patch Clamp, Current Clamp, Gel Filteration
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Cancer is the leading cause of death worldwide. Current anticancer drugs involve various toxic side effects; efforts are ongoing to develop new anticancer agents especially from the screening of natural compounds. Present study investigated cytotoxic effects and mode of cell death induced by the Caspian cobra venom in some human cancer cell lines.
Cytotoxic effects of snake venom toxins (SVT) were investigated via monitoring of morphological changes, MTT, trypan blue exclusion and LDH release assays. Mechanism of cell death was determined by AO/EtBr double staining, caspase-3 activity assay, flow cytometric analysis of apoptosis and mitochondrial membrane potential measurement.
In morphological analysis, apoptotic alterations related to apoptosis such as cytoplasmic blebbing, chromatin condensation and irregularity in shape were seen. IC50 of SVT in HepG2, MCF7and DU145 cell lines were 26.59, 28.85 and 21.17µg/ml, respectively and significantly different from the MDCK normal cell line (IC50=47.1 µg/ml). AO/EtBr double staining showed the best apoptotic/necrotic ratio at 15 µg/ml after 48 h. LDH release showed no significant differences between 10 µg/ml SVT and cisplatin. Flowcytometric analysis confirms mitochondrial membrane potential loss and more than 95% apoptotic cell death at 15 µg/ml. Caspase-3 was significantly activated at doses higher than 2.5 μg/ml with a maximal activity at 10 μg/ml.
Results from this study demonstrate that SVT induces mitochondrial and caspase-3 dependent apoptosis in cancer cell lines with minimum effects on studied normal cell. This potential might candidate this venom as a suitable choice for cancer treatmentKeywords: Snake, Venom, Aapoptosis, Cytotoxicity, Cancer -
BackgroundOpioid drugs are the most effective drugs for the treatment of moderate to severe pain. Rates of opioid use are influenced by a variety of factors. The aim of this study was to determine the pattern of use of parenteral opioid drugs in hospitalized patients in a referral teaching hospital.MethodsIn a retrospective study, required data were extracted from medical records of adult patients who had received any parenteral opioid analgesic in the 6-month period from March 2013 to September 2013. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) system method was used for evaluation of opioid analgesic use in patients.ResultsThe overall usage of parenteral opioid analgesics was 730.51 DDDs with meperidine (Pethidine) having the most amounts of use (588.69 DDDs and 33.23 DDDs/100 bed-days). Overall, the male surgery ward and emergency department had the most amounts of use based on the number of DDDs (445.8 DDDs) and per 100 bed-days (1046 DDDs/100 bed-days), respectively. Methadone use was most in the infectious diseases ward.ConclusionThe trend of parenteral opioid analgesics consumption is increasing in this hospital. Therefore, better adherence to pain treatment guidelines by medical staff is necessary for rational use of these drugs.Keywords: Drug Utilization Evaluation, Parenteral Opioid Drugs, Hospitalized Patients
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FTIR Microspectroscopy Reveals Chemical Changes in Mice Fetus Following Phenobarbital AdministrationPhenobarbital is a phenobarbiturate used as a sedative, anticonvulsant, or hypnotic with the doses prescribed and can cause teratogenic effects. The goal of this study was to examine an alternative method for the recognition of the mechanism or the bimolecular potential changes in mice fetus caused by Phenobarbital using FTIR micro spectroscopy. The mice were injected with Phenobarbital (120mg/kg) on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Sections (10µm) of normal and Phenobarbital treated fetus brains and livers were used for FTIR measurement in the wave number region of 400- 4000 cm-1. The results were shown by 2ndderivativization of spectra & also subtraction from control spectra. In liver, the intensity at 1054 cm-1, 1155 cm-1, 1353 cm-1, 1453cm-1,1645 cm-1, 1622 cm-1, 2944 cm-1, 2913 cm-1 and 2845 cm-1 were shifted and increased. In the brain, the intensity at 879 cm-1, 911 cm-1, 955 cm-1, 1223 cm-1, 1256 cm-1, 1304 cm-1, 1360 cm-1, 1453 cm-1, 1529 cm-1, 1636 cm-1, 2845 cm-1, 2915 cm-1& 2950 cm-1 were increased and shifted. The most important changes of the fetus brain tissue are on the β structure of proteins due to the amide I bands at 1636 cm-1, while extensive effects on the DNA structure were obvious for the Phenobarbital treated liver tissues. As a conclusion, FTIR spectroscopy might well be assumed as a potentially powerful teratogenic measurement instrument with a unique ability to identify the modified bimolecular structures.Keywords: FTIR, Microspectroscopy, Phenobarbital, Teratogenic, mice fetus
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ObjectiveEnvenomation by heamotoxic snakes constituted a critical health occurrence in the world. Bleeding is the most sever consequence following snake bite with viperid and crothalid snakes. It is believed that the degradation of vascular membrane caused hemorrhage; in contrast, some suggested that direct cytotoxicity has role in endothelial cell disturbances. This study was to evaluate the direct toxicity effect of V.Lebetina crude venom on Human Umbilical Vein Endothelial Cells (HUVECs).MethodsThe effect of V. lebetina snake venom on growth inhibition of HUVECs was determined by MTT assay and neutral red uptake test. The integrity of cell membrane through LDH release was measured with the Cytotoxicity Detection Kit. Morphological changes of endothelial cells also were evaluated using a phase contrast microscope.Resultcrude venom induced a concentration dependent inhibition on HUVECs with an IC50 value of 11.77 μg/ml after 24 h of incubation at MTT assay and 10.52 μg/ml at neutral red uptake test. In MTT assay, V. Lebetina crude venom showed a cytotoxic effect on endothelial cells which was confirmed by the effect observed with neutral red assay. Also, crude venom caused disturbances in the integrity of cell membrane by LDH release. The morphological alterations enhanced in high concentration and finally total cells number reduced.ConclusionV. Lebetina venom showed potential direct cytotoxic effects on human endothelial cells in a manner of concentration dependent inhibition.Keywords: Snake venom, Cytotoxicity effect, HUVEC, Hemorrhage, V. Lebetina
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As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smoke-induced inflammatory response in fibroblast-like synoviocytes (FLS). Cytotoxicity of cigarette smoke condensate (CSC) and bee venom were determined by the tetrazolium (MTT) method in cultured synovial fibroblastes. The expression of interleukin-1β and sirtuin1 mRNA were analyzed by SYBR green real-time quantitative PCR. Differences between the mean values of treated and untreated groups were assessed by student t-test. Based on MTT assay, CSC and BV did not exert any significant cytotoxic effects up to 40 µg/mL and 10 µg/mL, respectively. Our results showed that interleukin-1β mRNA level was significantly up-regulated by CSC treatments in LPS-stimulated synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1β and Sirt1 were up-regulated even in lower concentrations of BV and attenuated at higher concentrations. Also, BV attenuated the CSC-induced and LPS-induced inflammatory responses in synovial fibroblasts. Our results support the epidemiological studies indicating pro-inflammatory effects of CSC and anti-inflammatory effects of BV on FLS cell line.Keywords: Bee Venom, Cigarette, Cytokine, Sirt1, Fibroblast, like Synoviocytes
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سابقه و هدفدرک چگونگی اثرات سلولی و الکتروفیزیولوژیک سموم، از جمله سموم عقرب، می تواند گامی در جهت تولید داروهای جدید باشد. (Buthotusschach (BS یکی از خطرناک ترین عقرب های نواحی گرمسیر ایران است. هدف مطالعه حاضر، بررسی اثرات الکتروفیزیولوژیک دو جزء فعال استخراج شده از سم عقرب(Buthotusschach (BS برشکل پتانسیل عمل نورون F1حلزون باغی بود.روش بررسیثبت داخل سلولی از جسم سلولی نورون های F1حلزون باغی در حضور و عدم حضور دو جزء فعال F6 وF4 جدا شده از سم عقرب BS در دو غلظت مختلف50 نانومولار و 1 میکرو مولار انجام شد.یافته هادر شرایط کنترل، پتانسیل استراحت غشای نورون ها 43.11±0.33- میلی ولت، دامنه پتانسیل عمل 39/0±34/49 میلی ولت و فاصله زمانی رسیدن پتانسیل عمل به قله خود17.02±0.32 میلی ثانیه بود. در حالی که افزودن جزء F4 به مایع خارج سلولی، اثر دوگانه بصورت وابسته به ولتاژ روی پتانسیل استراحت غشا داشت، به طوری که درغلظت 50 نانومولار موجب هیپرپلاریزاسیون پتانسیل استراحت غشا شد (48.81±0.54- میلی ولت؛ 0/001>P)، اما دوز 1میکرومولار آن پتانسیل غشا را به سمت ولتاژهای دپلاریزه شیفت داد (40.35±0.25 - میلی ولت؛ 0/001>P). دامنه پتانسیل عمل تنها تحت تاثیر دوز پایین کاهش معنی داری یافت (45.38±0.46 میلی ولت؛ 0/001>P). مدت زمان لازم برای رسیدن به قله بطور معنی داری (0/001>P) تحت تاثیر هردو غلظت افزایش پیدا کرد. حال آنکه افزودن جزءF6 موجب دپلاریزاسیون پتانسیل استراحت غشا شد. محلول رینگر حاوی جزءF6 با غلظت 50 نانومولار هم چنین باعث افزایش دامنه (52.27±0.39 میلی ولت؛ 001/0>P) و مدت زمان رسیدن به قله پتانسیل عمل (28.04±0.92 میلی ثانیه؛ 0/001>P) شد، در حالی که غلظت بالاتر محلول هیچ اثر معنی داری روی این پارامترها نداشت.نتیجه گیریاجزائ جدید جدا شده از سم عقرب Buthotusschach به ویژه در غلظت پایین باعث تغییر ویژگی های پتانسیل شد که با توجه به نقش کانالهای سدیمی در دامنه و زمان رسیدن به قله پتانسیل عمل به نظر می رسد این اجزا از طریق تاثیر بر کانا ل-های سدیمی موجب تغییرات ذکر می شود.
کلید واژگان: سم عقرب, ثبت داخل سلولی, پتانسیل عمل, Buthotus schachBackgroundUnderstanding the electrophysiological effects of toxins, may facilitate new drugs discovery. Buthotusschach (BS) has been shown to be one of the most dangerous scorpions in tropical part of Iran. Present study was aimed to investigate the electrophysiological effects of two active fractions (F4 and F6) isolated from BS scorpion toxin on action potential (AP) characteristics of snail neurons.Materials And MethodsIntracellular recording was made from F1 cells of Helix aspersa in the presence and absence of extracellular application of F4 and F6fractions (50nM and1µM) isolated from BS scorpion venom.ResultsIn control condition, the resting membrane of neurons (RMP) -43.11±0.33 mV,the AP amplitude was 49.34±0.39mV and the time to peak of AP was 17.02±0.32 ms. While addition of F4 fraction to the bathing solution had a dual effects on membrane potential in a voltage dependent manner. Therefore,it caused membrane hyperpolarization at 50nM (-48.81±0.54 mV; p<0.001), but its 1µM concentration shifted the membrane potential towards depolarized voltages (-40.35±0.25 mV; p<0.001).The amplitude of AP was significantly decreased only by low dose of F4 fraction (45.38±0.46mV; p<0.001).The time to peak was significantly (p≤0.001) increased by both concentrations of F4 fraction. While F6 fraction made the RMP more depolarized. In addition, Ringer containing 50nM of F6 fraction led to a significant increase in the amplitude (52.27±0.39 mV; p<0.001) and the time to peak of AP (28.04±0.92 ms, p<0.001),whereas at higher concentration had no significant effect on these parameters.ConclusionF4 and F6 fractions caused changes in the AP characteristics, which based on the role of sodium channels in the amplitude and the time to peak it seems these fractions possibly changes the aforementioned parameters through effects on sodium channels.Keywords: Scorpion toxin, Intracellular recording, Action potential, Buthotusschach -
Miconazole is an imidazole antifungal agent, commonly applied topically to the skin or mucous membranes. The aim of this study was to examine the alternative method for gaining mechanism or the bimolecular changes caused by the possible teratogenic effects of Miconazole on mice fetus brain tissue using FTIR-Microspectroscopy. The mice were injected with Miconazole (60 mg/Kg) on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Sections (10 μm) of control and Miconazole treated fetus brain tissue were used for FTIR measurement in the mid- infrared region. The results were shown by spectra 2nd derivative and also subtracting from control spectra. A lower intensity in the lipid (2800–3000 cm-1) and amid I (1600–1800 cm-1) regions of Miconazole treated mice fetus brain tissue was observed compared to the control mice fetus brain tissue. No major spectral shifting was observed at amide I band, amide II band and nucleic acid regions. As a conclusion, FTIR-Microspectroscopy can be a useful tool for teratogenic measurement with a unique ability to identify the modified bimolecular structures in mice fetus tissues.
Keywords: Antimicrobial, Linezolid, MIC, 1, 3-oxazolone-5-one, FT-IR, 1H-NMR -
Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. There are controversy aspects about its teratogenicity. A teratogenic agent can alter morphology or subsequent function of the fetus. The aim of this study was to examine an alternative method for the recognition of the mechanism or the bimolecular potential changes in mice fetus caused by Metronidazole using FTIR micro spectroscopy. The mice were injected with metronidazole (60mg/kg) on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Serial sectioning (10µm) of normal and metronidazole-treated brains and livers were used for FTIR measurement in the wave number region of 600- 3600 cm-1.The results showed that there were some variations between the fetus of normal and treated brain and liver. The band intensities in fetus brain and liver of test animals were reduced and shifted at 707 cm-1, 1155 cm-1, 1054 cm-1,, 1256 cm-1 and 1219 cm-1, 1453 cm-1 and 1525 cm-1, 1622 cm-1, 1645 cm-1 and 2944 cm-1,while the band intensities were increased and shifted at 879 cm-1, 810 cm-1, 1223 cm-1, 1256 cm-1 1360 cm-1, 1723 cm-1. It was concluded that most of variations in brain and liver of Metronidazole treated fetuses are in amid bands, nucleic acid and carbohydrate related bands. Based on these findings FTIR spectroscopy can be a useful tool for bio diagnostic.Keywords: FTIR, Microspectroscopy, Metronidazole, Teratogenic, mice fetus, Bio, spectroscopy
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Temporary paralysis is a rare manifestation of envenoming following the yellow Iranian scorpion, Odontobuthus doriae (O. doriae). Thus, to elucidate the underlying mechanism, we investigated the neurotoxic effect of venom in the sciatic nerve, the possible mechanism in a mice model. The neurotoxicity and temperature effects in the venom-induced neurotoxicity were examined using the mouse sciatic nerve and mouse phrenic nerve-hemidiaphragm (MHD) preparations. O. doriae venom (1 µg/mL) caused changes in the perineural waveform associated with nerve terminal action potentials. Venom affected on both negative and positive components of the waveform which is known as a compound action potential. The time-response relationship of venom-induced depression of resting membrane potential (RMP) was significant (p < 0.05). No significant difference in augmentation was seen in room temperature in comparison with 37°C. In conclusion, although there was no evidence that the venom had any specific curarizing action at the neuromuscular junction, the results suggest that the venom exerts its neuromuscular transmission on the sciatic nerve through potassium and sodium ionic-currents. Furthermore, the influence of temperature on neurotoxicity was ineffective on blockade of the neuromuscular transmission in-vitro.Keywords: Mouse, Sciatic nerve, Odontobuthus doriae, Venom, Iranian scorpion
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To be sure, all the industries try to be involved in globalization with a constant trend to find out ways to increase productivity across different functions within an organization to maintain competitive advantage world. Pharmaceutical industries are not exceptional and further are based on fragmentation. So these kind of companies need to cope with several barriers such as silo mentality that may affect efficiency of their business activity. Due to eliminate a part of resources such as raw materials, new molecule developed, financial and human resources and so on, companies can gradually loss their competitive potentials in the market and increase their expenses.Furthermore, to avoid any business disturbances in financially connected companies due to silo effect, they should arrange their management to integrated organization form. Otherwise, actions taken by one business member of the chain can influence the profitability of all the other members in the chain. That is why recently supply chain has generated much interest in many business units.In this paper, it has been tried to investigate the different aspects of silo effect which can affect integrate supply chain.Finally, a fluent communication, high level of information exchange, fragmentation management, cross-functional control in a supply chain management format are needed to reduce or control silo effect within entire chain of the holding company by Supply chain management.Keywords: Silo, Fragmented, Pharmaceutical, Integration, Supply, Management
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For the time being our pharmacy curriculum is in Iran mostly based on lecturing methods as instructional strategies. In this method of education a great deal of declarative knowledge as well as a large number of students could be covered at the same time. Indeed based on the job description of a pharmacist, pharmacy graduates should work in a relevant field in pharmacy retail, in order to be able to solve any health related problems, rather than having merely declarative knowledge. Colleges of pharmacy can utilize problem based learning (PBL) to aid anticipated learning outcomes and practice competencies of entry level pharmacists. Problem-based learning is an effective approach to enhance cognitive strategies and long-term memory as well. In this method pharmacists will be involved in expanded patient care responsibilities which require graduates to possess enhanced communication skills, greater problem-solving capabilities, effective critical thinking abilities and decision making skills. Moreover, PBL has the potential to integrate the basic sciences with clinical practice too. However, to achieve the PBL method of learning, curriculum modification and various instructional strategies will have to be considered to facilitate the learning outcomes needed for the practice of pharmaceutical care. Fortunately, already a number of pharmacy courses includeing, over the counter (OTC) medicines, pharmacotherapeutics, pharmacy administration, toxicology, pharmacy practice, pharmacology, clinical pharmacy and some other advanced courses, lend themselves to the PBL instructions. However, the use of the PBL learning method may in some basic courses such as pharmaceutical sciences, biochemistry, medicinal chemistry and so on face difficulties. For such courses is there an other option close to PBL is called the problem-solving model. The differenc between then is that is in PBL the specific situation is defined as the problem and student should analyse the situation and provide a solution, whereas in the problem solving metod for student better understanding problems have been designed for students to solve together and find answers to them. Hence basic sciences in pharmacy education are best taught by conventional curriculum and problem solving method and advanced courses could be taught using the PBL model. In order to succeed, we need to change the pharmacy curriculum, by integrating the knowledge with practice. Conditions needed to make integration possible are as follows: 1) a well- developed national health policy; 2) a plan for the development and coordination of human resources for health; 3) a discussion and decision committee to review the curriculum; and 4) organization to consider financial aspects, compensation, maintenance of quality of the services and academic standards. Apart from the face that PBL strategy is valuable in helping students to learn team collaboration, listening, and participating in interdisciplinary discussion, students will be able to clarify for themselves the abilities they bring to a health care team. This will help them to obey their job responsibility as a good consultant for physicians, nurses, patients, and other health care professionals. PBL is directing the learning strategy to: keep the students engaged in active learning, hold students responsible for the entire knowledge base that applies to different courses of pharmacy, use a facilitator of knowledge (tutor) rather than presenter of knowledge, and design a variety of clinical scenarios that can be extended into chronic followed-up care and treatment. To achieve this situation it is highly recommended to revise pharmacy curriculum and develop methods of teaching and learning.Keywords: PBL
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Platelet aggregation inhibitory effect and anticoagulant properties of fractions separated from the venoms of Cerastes persicus fieldi and Echis carinatus were investigated. The partial fractionation was performed on a Sephadex G-100 column. Two fractions separated from Cerastes persicus fieldi showed anti platelet aggregation activity on ADP (200 µM)-induced platelet aggregation (ca 80% inhibition). Attempts to measure the antiplatelet aggregation activity of crude Echis carinatus venom and its fractions were not successful due to the protein coagulation of the plasma samples after the addition of venom. Anticoagulant activities of venoms were also evaluated. Total venom of Echis carinatus showed anti coagulant activity in PT test, while its fractions showed procoagulant activity.Keywords: Anticoagulant, Antiplatelet aggregation, Snake venom, Echis carinatus, Cerastes persicus fieldi, Gel filtration
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