Cytotoxic effect of Iranian vipera lebetina snake venom on HUVEC cells

Envenomation 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 carried out to evaluate the direct toxicity effect of V. lebetina crude venom on Human Umbilical Vein Endothelial Cells [HUVECs]. The effect of V. lebetina snake venom on HUVECs growth inhibition was determined by MTT assay and neutral red uptake assay. The integrity of cell membrane through LDH release was measured with the Cytotoxicity Detection Kit. Morphological changes of endothelial cells were also evaluated using a phase contrast microscope. In MTT assay, crude venom showed a cytotoxic effect on endothelial cells which was confirmed by the effect observed with neutral red assay. Also, crude venom caused changes in the integrity of cell membrane by LDH release. The morphological alterations enhanced in high concentration results in total cells number reduced. V. lebetina venom showed potential direct cytotoxic effects on human endothelial cells in a manner of concentration-dependent inhibition

FTIR microspectroscopy reveals chemical changes in mice fetus following phenobarbital administration

Phenobarbital 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 [120 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 microm] of normal and Phenobarbital treated fetus brains and livers were used for FTIR measurement in the wave number region of 400- 4000 cm. The results were shown by 2 derivatization of spectra and also subtracting from control spectra. In liver, the intensity at 1054 cm, 1155 cm, 1353 cm, 1453cm,1645 cm, 1622 cm, 2944 cm, 2913 cm and 2845 cm were shifted and increased. In the brain, the intensity at 879 cm, 911 cm, 955 cm, 1223 cm, 1256 cm, 1304 cm, 1360 cm, 1453 cm, 1529 cm, 1636 cm, 2845 cm, 2915 cm and 2950 cm were increased and shifted. The most important changes of the fetus brain tissue are on the beta structure of proteins due to the amide I bands at 1636 cm, 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

Immunomodulatory effects of bee venom in human synovial fibroblast cell line

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-1 beta 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 micro g/mL and 10 micro g/mL, respectively. Our results showed that interleukin-1 beta mRNA level was significantly up-regulated by CSC treatments in LPS-stimulated synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1 beta 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

FTIR-microspectroscopy detection of metronidazole teratogenic effects on mice fetus

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 [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. Serial sectioning [10 micro m] 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

Effects of odontobuthus doriae scorpion venom on mouse sciatic nerve

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 [micro]g/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[degree]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

Silo effect a prominence factor to decrease efficiency of pharmaceutical industry

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

Partial fractionation of venoms from two Iranian vipers, echis carinatus and cerastes persicus fieldi and evaluation of their antiplatelet activity

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 micro M]-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

Developing a suitable model for supplier selection based on supply chain risks: an empirical study from Iranian pharmaceutical companies

The supply chain represents the critical link between the development of new product and the market in pharmaceutical industry. Over the years, improvements made in supply chain operations have focused largely on ways to reduce cost and gain efficiencies in scale. In addition, powerful regulatory and market forces have provided new incentives for pharmaceutical firms to basically rethink the way they produce and distribute products, and also to re-imagine the role of the supply chain in driving strategic growth, brand differentiation and economic value in the health continuum. The purpose of this paper is to formulate basic factors involved in risk analysis of pharmaceutical industry, and also determine the effective factors involved in suppliers selection and their priorities. This paper is based on the results of literature review, experts' opinion acquisition, statistical analysis and also using MADM models on data gathered from distributed questionnaires. The model consists of the following steps and components: first factors involved in to supply chain risks are determined. Based on them a framework is considered. According the result of statistical analysis and MADM models the risk factors are formulated. The paper determines the main components and influenceial factors involving in the supply chain risks. Results showed that delivery risk can make an important contribution to mitigate the risk of pharmaceutical industry

Effects of teucrium polium ethyl acetate extract on serum, liver and muscle triglyceride content of sucrose-induced insulin resistance in rat

Possessing putative hypolipidemic effects, Teucrium polium [TP] have been traditionally used as a medicinal plant in Iran. The aim of the present study was to investigate this effect on the sucrose-induced insulin resistance male rat model. Thirty Wistar male rats weighting 180 +/- 20 g were divided into five groups of six each. Four groups were given sucrose 50% in drinking water for 10 weeks. In 8th week of treatment, three groups of them were randomly selected and treated with Teucrium polium [T. polium] ethyl acetate extract [50, 100 and 200 mg/Kg for two weeks]. Control animals were fed using normal rat chow. After ten weeks, blood samples were collected from the heart. Blood Glucose, insulin, leptin, lipid content and fasting insulin resistance index [FIRI] as well as liver and muscle glycogen and lipid contents were determined. Final data were analyzed by ANOVA and post-hoc Tukey's test. Liver glycogen contents and blood levels of glucose and insulin were significantly increased in high sucrose [HS] group compared with control group. A significant decrease was observed in blood glucose and insulin levels, FIRI, serum total lipid, triglyceride and VLDL-c as well as the liver triglyceride level, muscle and liver glycogen contents in 100 and 200 mg/Kg of TP-treated groups compared with HS group. Leptin level was significantly decreased in 50 and 100 mg/Kg groups compared with HS group. The treatment with T. polium ethyl acetate extract [TP-EAE] induced a dose-dependent reduction in serum, liver and muscle triglyceride [TG] and liver glycogen content levels, as well as serum insulin. These effects may be attributed, in part, to the hypolipidemic effect of TP flavonoids; otherwise, the hepatoprotective and antioxidant activity of TP-EAE may improve the liver function and reverse harmful sucrose effects

Cytotoxic effects of two Iranian scorpions odontobuthusdoriae and bothutus saulcyi on five human cultured cell lines and fractions of toxic venom

Scorpion venom toxicity is of major concern due to its influence on human activities and public health. We investigated the in-vitro process of cell death caused by two Iranian scorpions Odontobuthus doriae and Bothutus salceyi venom on human cell lines. The aim of this study was to provide further information about triggering cell death and suggestion of methods for the elimination of unwanted cells such as tumor cells. The cytotoxicity and apoptosis induced by effect of scorpion venoms on five established eukaryotic cell lines are analyzed on different human cell lines. All cultured cell lines were incubated with varying doses of scorpion venom for 24 h at 37°C. Control culture was treated with an equal amount of SFM. The percentage of cell survival was measured using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium [MTT] colorimetric assay. Our data demonstrated that Bothutus saulcyi, does not show cytotoxic effect on any of the used cell lines. Odontobuthus doriae, however, has resulted a dose dependent cytotoxic effect with maximum at 1 ug/mL on 1321N1 glioma like cell line. Then the cytotoxic venom of O. doriae was fractionated using Sephadex G50 gel chromatography. The toxic fractions on mouse used to Cytotoxicity assay on 1321 N1 cell line and data demonstrated that, the fraction F3 showed a dose dependent Cytotoxicity assay. Further studies to explode the mode of action of these venoms are recommended and purification of the toxic fraction should be done

pharmacological effects of odonthobuthus doriae scorpion venom and its extracted fractions on neuro-muscular transmission

The effect of Odonthobuthos doriae [O.d] scorpion venom at 0/3, 1 and 3, 10 microg/ml concentrations were investigated on nerve-muscle transmission, using the Twitch tension technique. A concentration of 0.3 microg/ml caused a small change in the twitch height in response to indirect muscle stimulation, but higher concentrations [1, 3, 10 microg/ml] caused a transient augmentation in twitch response followed by a large contracture in the chick biventer cervices [CBC] preparation. This effect could be defined as a complex action of the venom, predominately presynaptic, in which its' effects on postjunctional synapses is also maintained. In order to find out which bioactive fraction could explain the venom effects, the soluble crude venom was partially separated by the gel filtration method, using a Sephadex G50 column, and four fractions were separated. Two of the four purified fractions [O.d F[3], O.d F[4]] were characterized as toxic and their LD[50] values were lower than the crude venom. Unlike the O.d Fj and O.d F[2] fractions, O.d F[3] and O.d F[4] fractions caused a significant block in the twitch and contracture, in comparison to the control sample. in conclusion, fractions O.d F[3] and O.d F[4] are supposed to be as the biological active components of the O.d. venom

In vitro assessment of bee venom effects on matrix metalloproteinase activity and interferon production

Controversial immunomodulatory properties of bee venom [BV] have provided an appropriate field for more investigation. The aim of present research was to verify the effects of honeybee venom on matrix metalloproteinase activity and interferon production as well as cell proliferation in monocyte and fibroblast cell lines. The monocyte and fibroblast cell lines [K562, HT-1080, WEHI-164] were used in order to assess proliferative response, interferon-1 production and matrix metalloproteinase-2 [MMP-2] activity. Australian BV [ABV] and Iranian BV [IBV] preparations at concentrations of 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, and 1microg/ml were added to each overnight cultured cells. In time course study, cells were treated each with ABV and IBV. In all cases supernatants were collected 24 hours after treatment. A sample of the each medium was used for zymography and interferons assay. Nontreated cells were used as controls. The production of IFN-alpha and IFN-beta in supernatant of cell cultures was assessed using enzyme linked immunoassay procedure. MMP-2 activity, as an inflammatory index, was evaluated using zymoanalysis method. The results of this study showed that, there were no significant difference between two sources of honey bee venoms when they were added to an identical cell line, whereas, the responses of various cell lines against bee venom were different. The increasing amounts of bee venom to human monocyte cell line [K562] revealed a significant increase in proliferative response. Our findings showed that the bee venom had no influence on IFN-alpha production in cell culture media, whereas, adding the BV to K562 cell line could significantly increase the production level of IFN-beta only on day 8 post-treatment. In addition the effect of bee venom on MMP-2 activity in both cell culture media, WEHI-164 and K562 was similar. The stimulatory effect of bee venom on MMP-2 activity occurred at low doses. In contrast, its inhibitory effect was seen at high concentrations. It is concluded that, honeybee venom affects on MMP-2 activity and interferon beta production as well as cell proliferation in a time and dose-dependent manner