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Sample records for cobra naja naja

  1. Neutralization of cobra venom by cocktail antiserum against venom proteins of cobra (Naja naja naja).

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanaiyan, G; Vimal, S; Madan, N; Sundar Raj, N; Mohammed Yusuf Bilal, S; Nazeer Basha, A; Farook, M A; Sahul Hameed, A S; Sridevi, G

    2014-01-01

    Naja naja venom was characterized by its immunochemical properties and electrophoretic pattern which revealed eight protein bands (14 kDa, 24 kDa, 29 kDa, 45 kDa, 48 kDa, 65 kDa, 72 kDa and 99 kDa) by SDS-PAGE in reducing condition after staining with Coomassie Brilliant Blue. The results showed that Naja venom presented high lethal activity. Whole venom antiserum or individual venom protein antiserum (14 kDa, 29 kDa, 65 kDa, 72 kDa and 99 kDa) of venom could recognize N. naja venom by Western blotting and ELISA, and N. naja venom presented antibody titer when assayed by ELISA. The neutralization tests showed that the polyvalent antiserum neutralized lethal activities by both in vivo and in vitro studies using mice and Vero cells. The antiserum could neutralize the lethal activities in in-vivo and antivenom administered after injection of cobra venom through intraperitoneal route in mice. The cocktail antiserum also could neutralize the cytotoxic activities in Vero cell line by MTT and Neutral red assays. The results of the present study suggest that cocktail antiserum neutralizes the lethal activities in both in vitro and in vivo models using the antiserum against cobra venom and its individual venom proteins serum produced in rabbits. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  2. The multiplicity of cardiotoxins from Naja naja atra (Taiwan cobra) venom.

    PubMed

    Chang, L S; Huang, H B; Lin, S R

    2000-08-01

    Four novel cardiotoxins were isolated from Naja naja atra (Taiwan cobra) venom by successive separation on a SP-Sephadex C-25 column and a reverse phase column. Amino acid sequences of the cardiotoxins were determined by Edman degradation and carboxypeptidase digestion. It shows that these cardiotoxins comprise 60 amino acid residues. Comparative analyses on the amino acid sequences of cardiotoxins from the venoms of N. naja atra and other Naja species indicated that amino acid substitutions of cardiotoxin isoforms frequently occurred at positions 7-11, 27-32 and 45-47. The hypervariable segments encoded by the second and third exon of cardiotoxin genes are located at or near the tips of loop structure of cardiotoxin molecules. These results, together with the suggestions that the residues at the tips of cardiotoxins' loop structure were involved in the manifestation of the biological activities of cardiotoxins, reflect that the preferential mutations may contribute to alterations in the function of cardiotoxin molecules. Analysis on the secondary structure of pre-mRNAs of N. naja atra cardiotoxin 4 gene and N. naja sputatrix cardiotoxin 3 gene has shown that the hypervariable regions of the exon 2 pertain to form intra-exon pairings and are not involved in the formation of intron-exon pairings. Since the pairings of splice sites and gene architecture were supposed to be associated with intron-exon recognition, it is likely that the preferred loci of mutations occurring with the evolution of cardiotoxin genes would not affect the processing of cardiotoxin precursors.

  3. Hematology and serum biochemistry of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa).

    PubMed

    Muliya, Sanath Krishna; Bhat, Mudraje Narayana

    2016-08-01

    To study the hematology and serum biochemistry parameters of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa) and to evaluate the differences in the same between captive and wild populations. Animals were categorized into four groups, viz., wild Indian spectacled cobra (n=10), wild Indian rat snakes (n=10), captive Indian spectacled cobra (n=10), and captive Indian rat snake (n=10). The snakes were restrained with restraint tubes, and 2 ml of blood was collected from either heart or ventral coccygeal vein. Hematological examinations were performed manually and serum biochemistry assays were performed on semi-automated clinical chemistry analyzer. The values of total erythrocyte count, packed cell volume, and hemoglobin were slightly low in captive spectacled cobras and captive rat snakes compared to wild ones, whereas total leukocyte count was found to be slightly high in wild spectacled cobras compared to captive ones. All the recorded values of biochemical and electrolyte analytes were found to be well within expected range for snakes except for total protein and chloride levels in both the species which was slightly above the expected range. The hematology and serum biochemistry intervals of the two most common Indian snakes are presented here. The data will be useful in routine health evaluations and aiding in better medical management of the species studied. Since this study is the first to report complete hematologic and blood biochemical ranges for the study species, observations made here can also be used as referral intervals for future use.

  4. Acquired factor VIII deficiency after consuming the dried gallbladder of a cobra, Naja naja

    PubMed Central

    Kim, Hyun Ju; Lee, Won Sik; Lee, Young Jin; Jun, Hyun Soo; Seo, Su-Kil

    2010-01-01

    Acquired factor VIII deficiency is very rare, often fatal. It is associated with pregnancy, autoimmune diseases, malignancy, and drugs, although no underlying cause is found in 50%. A 49-year-old male was referred with right shoulder bruising. The coagulation test showed a prolonged activated partial thromboplastin time. The factor VIII level was less than 1%, and the factor VIII inhibitor antibody titer was 246 Bethesda units/mL. The findings were compatible with acquired factor VIII deficiency. He had consumed the dried gallbladder of a cobra, Naja naja, for two weeks, it contained venom. After the initial treatment with factor VIII, he did not take supplemental coagulation factor VIII. The patient was readmitted with left forearm swelling. He lost consciousness suddenly and brain computed tomography (CT) revealed a subdural hematoma. Despite administering recombinant factor VII, his bleeding was not controlled and he died. PMID:21120211

  5. Systemic pathological effects induced by cobra (Naja naja) venom from geographically distinct origins of Indian peninsula.

    PubMed

    Shashidharamurthy, R; Mahadeswaraswamy, Y H; Ragupathi, L; Vishwanath, B S; Kemparaju, K

    2010-11-01

    Indian cobra (Naja naja) venom from different geographical locations varied in its composition and biochemical, pharmacological and immunological properties. Recently it has been shown that the variation in composition of venom from different geographical origin of Indian peninsula is due to the quantitative difference in the same components and also the presence of different biochemical entities with respect to their origin. This disparity in venom composition may be due to several environmental factors. However, very little is known about the systemic effects on vital organs caused by the venom due to regional variation. In the present investigation, the venom samples procured from eastern, western and southern regions were compared for histopathological effects on skeletal muscle and some vital organs (heart, lungs, liver and kidney) in the mouse model. All the three venom samples damaged vital organs such as cardiac muscle, gastrocnemius muscle, liver, lungs and kidneys; however, the extent of damage varied greatly. Eastern venom predominantly damaged cardiac muscle and kidney, western venom injured the liver and the southern venom affected the lung. In addition, the eastern venom caused the recruitment of a flux of inflammatory cells in the skeletal muscle unlike southern and western venom samples. These results suggest the diversity of target-specific toxins in all the three regional venoms. Thus, the study explores the possible variations in the pathological effects of cobra (Naja naja) venom samples on vital organs due to geographical distribution in the Indian subcontinent. It also emphasizes the importance of intra-specific variation of venom samples for the production of efficacious and region-specific therapeutic antivenom. Copyright © 2009. Published by Elsevier GmbH.

  6. Screening of plants containing Naja naja siamensis cobra venom inhibitory activity using modified ELISA technique.

    PubMed

    Daduang, Sakda; Sattayasai, Nison; Sattayasai, Jintana; Tophrom, Pattara; Thammathaworn, Achra; Chaveerach, Arunrat; Konkchaiyaphum, Monruedee

    2005-06-15

    Enzyme-linked immunosorbent assay (ELISA) has been modified for screening plants with antagonistic activity to Naja naja siamensis cobra venom. Aqueous extracts from plants were investigated for their inhibitory effects on the binding of anti-cobra venom antibody to antigen, cobra venom, fixed onto 96-well microtiter plates. Ingredients in extracts were allowed to react with immobilized venom before the subsequent addition of antivenom antibody. Venom components affected by exposure to the extracts, unable to interact with their specific antibody, were predicted to be unable to bind to their native destinations or natural receptors. Curcuma cf. zedoaria, an old Thai medicinal plant, showed clear inhibitory activity in the ELISA test. Neurotoxin and protein degradative enzymes, major components in venom, were identified as targets of this extract in Western immunoblotting analysis. Ingredients in the extract showed high affinity to the toxin in competition assay by immunoprecipitation. The extract attenuated toxin activity by extending contraction time of diaphragm muscle after envenomation and had a potency to protect cellular proteins from venom degradative enzymes. Curcuma parviflora, with less activity in ELISA, exhibited acceptable results in two experiments but negative results in two experiments, whereas Curcuma longa, having low activity in the ELISA test, never showed any favorable results. Screening of 36 samples could classify plants into an inhibition range of 0 to 86%. This modified ELISA is recommended as a preliminary screening method for inhibitors with a large number of samples.

  7. Hematology and serum biochemistry of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa)

    PubMed Central

    Muliya, Sanath Krishna; Bhat, Mudraje Narayana

    2016-01-01

    Aim: To study the hematology and serum biochemistry parameters of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa) and to evaluate the differences in the same between captive and wild populations. Materials and Methods: Animals were categorized into four groups, viz., wild Indian spectacled cobra (n=10), wild Indian rat snakes (n=10), captive Indian spectacled cobra (n=10), and captive Indian rat snake (n=10). The snakes were restrained with restraint tubes, and 2 ml of blood was collected from either heart or ventral coccygeal vein. Hematological examinations were performed manually and serum biochemistry assays were performed on semi-automated clinical chemistry analyzer. Results: The values of total erythrocyte count, packed cell volume, and hemoglobin were slightly low in captive spectacled cobras and captive rat snakes compared to wild ones, whereas total leukocyte count was found to be slightly high in wild spectacled cobras compared to captive ones. All the recorded values of biochemical and electrolyte analytes were found to be well within expected range for snakes except for total protein and chloride levels in both the species which was slightly above the expected range. Conclusion: The hematology and serum biochemistry intervals of the two most common Indian snakes are presented here. The data will be useful in routine health evaluations and aiding in better medical management of the species studied. Since this study is the first to report complete hematologic and blood biochemical ranges for the study species, observations made here can also be used as referral intervals for future use. PMID:27651683

  8. Hematology and plasma biochemistry of wild-caught Indian cobra Naja naja (Linnaeus, 1758)

    PubMed Central

    2014-01-01

    Background Hematology and plasma biochemistry parameters are useful in the assessment and management of snake physiological status. Although reference ranges are readily available for many snake species, they are lacking for most venomous ophidians. We determined hematology and plasma biochemistry reference ranges for the wild-caught Indian cobra, Naja naja. Results Blood samples, taken from the ventral tail vein, were assessed for erythrocyte count, total leukocyte count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, considering the sex of snakes. Results revealed the erythrocyte numbers (male, 390000 ± 12503.33/mm3 and female, 347500 ± 7505.55/mm3), shapes and the centrally located oval nuclei. Leukocytes were round, circular or disk-shaped, and the mean size was larger in male than female snakes. The maximum number of leukocytes was found to be 11700 ± 100/mm3 in male and 12100 ± 200/mm3 in female snakes, and mean values of differential leukocyte count differed statistically between male and female snakes. The total leukocyte levels were found to be higher in female snakes, but the levels of hemoglobin, hematocrit, and MCV values were higher in male snakes. However, the MCH and MCHC values remained higher in female snakes throughout the study period. Mean protein and cholesterol contents differed significantly between male (45.32 ± 1.76 and 3.76 ± 0.06 mg/mL) and female (12.47 ± 0.82 and 4.72 ± 0.2 mg/mL) snakes. Conclusions In conclusion, monitoring snake hematological and biochemical parameters can serve as a means to evaluate the physiological and health status of N. naja populations, which may be a useful indicator of their environmental status. PMID:24735569

  9. Venom analysis of long-term captive Pakistan cobra (Naja naja) populations.

    PubMed

    Modahl, Cassandra M; Doley, Robin; Kini, R Manjunatha

    2010-01-01

    Venom production facilities keep established colonies of captive snakes to obtain venom for research and antiserum production. Due to strict regulations of importation, some of these colonies are formed with only a small number of initial animals and consist of closely related individuals (sometimes siblings). To understand the effect of long-term captivity on the venom composition and its impact on antiserum production, we analyzed 15 long-term captive Naja naja (Pakistan) originating from two separate venom production colonies using liquid chromatography-mass spectrometry and electrophoresis. The chromatogram produced from each individual cobra venom was found to be different. When the protein molecular masses of the peaks were identified, it was found that all the venoms consisted of the same protein composition, but the concentration of the proteins were different. Although three-finger toxins and phospholipase A(2) enzymes are the major toxic components present in these venoms, there was a clear difference in the amounts of each individual isoform. Such variation may affect the ability of antivenoms in neutralizing the toxic components of the wild type venom.

  10. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities.

    PubMed

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-04-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials.

  11. DOSE -RESPONSE RELATIONSHIP OF CRUDE COBRA VENOM (NAJA JANA) IN THE DOG

    DTIC Science & Technology

    The study was conducted to determine the dose - response effects of crude cobra venom (Naja naja) in the anesthetized dog. It was concluded that the LD50 is about 0.105 mg/kg, and the LD99 is 0.148 mg/kg.

  12. Gamma irradiation of Egyptian Cobra (Naja haje) Venom.

    PubMed

    Shaban, E A; Ahmed, A A; Ayobe, M H

    1996-01-01

    The aim of the present study was to prepare an effective and safe toxoid for the Egyptian Cobra (Naja haje) Venom by gamma irradiation. The effects of gamma irradiation (0.1-10 M rad) on the toxicity, as well as the antigen antibody complex formation reactivity was described. It appears from the results that the lethality of Naja haje venom irradiated in the dry form was not affected up to a dose of 10 M rad (100 KGy). On the other hand, the venom irradiated in the aqueous solution form showed a decrease in its lethality, and this was proportionately related to the dose of irradiation, while the ability of the venom antigens to react with its corresponding antibodies was retained up to irradiation dose of 5 M rad. The results of double immunodiffusion of non irradiated and the different dose levels of gamma irradiated venom (0.1-5 M rad) against a commercial Egyptian polyvalent antivenin, all showed similar patterns, the four visible lines obtained in the immunodiffusion reactions were identical and joined smoothly at the corners, indicating that there was no change in antigenic reactivity with antibodies determinants.

  13. Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

    PubMed Central

    Wong, Kin Ying; Tan, Choo Hock; Tan, Nget Hong

    2016-01-01

    Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography–mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03–0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs. PMID:27022154

  14. Antihaemorrhagic potentials of Fagonia cretica against Naja naja karachiensis (black Pakistan cobra) venom.

    PubMed

    Razi, Muhammad Tahir; Asad, Muhammad Hassham Hassan Bin; Khan, Taous; Chaudhary, Muhammad Zabta; Ansari, Muhammad Tayyab; Arshad, Muhammad Anwar; Saqib, Qazi Najam-us

    2011-12-01

    Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens' eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite.

  15. The Protective Effects of Cobra Venom from Naja naja atra on Acute and Chronic Nephropathy.

    PubMed

    Wang, Shu-Zhi; He, He; Han, Rong; Zhu, Jia-Li; Kou, Jian-Qun; Ding, Xiao-Lan; Qin, Zheng-Hong

    2013-01-01

    This study investigated the effects of Naja naja atra venom (NNAV) on acute and chronic nephropathy in rats. Rats received 6 mg/kg adriamycin (ADR) once to evoke the chronic nephropathy or 8 ml/kg 50% v/v glycerol to produce acute renal failure (ARF). The NNAV was given orally once a day starting five days prior to ADR or glycerol injection and continued to the end of experiments. The animals were placed in metabolic cages for 24 h for urine collection for urinary protein determination. The kidney function-related biochemical changes and index of oxidative stress were determined with automatic biochemistry analyzer or colorimetric enzyme assay kits. The pathomorphological changes were observed using light and transmission electron microcopies. The levels of inflammatory cytokines and NF- κ B activation were determined using ELISA kits, Western blot analysis, or immunofluorescence. The results showed that NNAV relieved ADR-induced chronic nephropathy and glycerol-triggered acute renal failure syndromes including proteinuria, hypoalbuminemia, hyperlipidemia, serum electrolyte unbalance, renal oxidative stress, and pathological damages. NNAV reduced kidney levels of TNF- α and IL-1 β , but it increased the levels of I κ B- α and inhibited NF- κ B p65 nuclear localization. These findings suggest that NNAV may be a valuable therapeutic drug for acute and chronic kidney diseases.

  16. Cross-Reactivity against Naja sumatrana (Black Spitting Cobra) Envenoming from the Haffkine Antivenom in a Mouse Model

    PubMed Central

    Lim, Francis; Earnest, Arul; Gopalakrishnakone, Ponnampalam

    2013-01-01

    Naja sumatrana is the dominant cobra species in Malaysia, Singapore, Borneo, and Sumatra, and it does not have specific antivenom. The Haffkine antivenom has been advocated instead. This study aims to determine the efficacy of this antivenom against Naja sumatrana envenoming using a mouse model. Methods. Male Swiss albino mice were used. Intravenous LD50 was first determined separately for Naja naja and Naja sumatrana venom. ED50 was determined by preincubating antivenom with each venom at 2.5 LD50 before administering the mixture into the tail vein. Validation was carried out using a challenge test. Each mouse received 111 µg of Naja sumatrana venom intramuscularly followed by intraperitoneal administration of dilute Haffkine antivenom. Survival was recorded 24 hours after envenoming. Results. The LD50 of Naja naja venom was 78.13 µg, standard error (SE) 13.3 µg. The ED50 of the Haffkine antivenom against Naja naja venom was 45.9 mg, SE 7.5 mg. The LD50 and ED50 of Naja sumatrana venom were 55.5 µg, SE 12.0 µg; and 73.9 mg, SE 12.0 mg, respectively. The intra-peritoneal ED50 against 111 µg intramuscular Naja sumatrana venom was 136.95 mg, SE 36.74 mg. Conclusion. The Haffkine polyvalent antivenom exhibited cross-neutralisation against Naja sumatrana venom when used at a higher dose. PMID:23997967

  17. Naja naja oxiana Cobra Venom Cytotoxins CTI and CTII Disrupt Mitochondrial Membrane Integrity: Implications for Basic Three-Fingered Cytotoxins

    PubMed Central

    Gasanov, Sardar E.; Shrivastava, Indira H.; Israilov, Firuz S.; Kim, Aleksandr A.; Rylova, Kamila A.; Zhang, Boris; Dagda, Ruben K.

    2015-01-01

    Cobra venom cytotoxins are basic three-fingered, amphipathic, non-enzymatic proteins that constitute a major fraction of cobra venom. While cytotoxins cause mitochondrial dysfunction in different cell types, the mechanisms by which cytotoxins bind to mitochondria remain unknown. We analyzed the abilities of CTI and CTII, S-type and P-type cytotoxins from Naja naja oxiana respectively, to associate with isolated mitochondrial fractions or with model membranes that simulate the mitochondrial lipid environment by using a myriad of biophysical techniques. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy data suggest that both cytotoxins bind to isolated mitochondrial fractions and promote the formation of aberrant non-bilayer structures. We then hypothesized that CTI and CTII bind to cardiolipin (CL) to disrupt mitochondrial membranes. Collectively, 31P-NMR, electron paramagnetic resonance (EPR), proton NMR (1H-NMR), deuterium NMR (2H-NMR) spectroscopy, differential scanning calorimetry, and erythrosine phosphorescence assays suggest that CTI and CTII bind to CL to generate non-bilayer structures and promote the permeabilization, dehydration and fusion of large unilamellar phosphatidylcholine (PC) liposomes enriched with CL. On the other hand, CTII but not CTI caused biophysical alterations of large unilamellar PC liposomes enriched with phosphatidylserine (PS). Mechanistically, single molecule docking simulations identified putative CL, PS and PC binding sites in CTI and CTII. While the predicted binding sites for PS and PC share a high number of interactive amino acid residues in CTI and CTII, the CL biding sites in CTII and CTI are more divergent as it contains additional interactive amino acid residues. Overall, our data suggest that cytotoxins physically associate with mitochondrial membranes by binding to CL to disrupt mitochondrial structural integrity. PMID:26091109

  18. Anti arthritic and anti inflammatory activity of a cytotoxic protein NN-32 from Indian spectacle cobra (Naja naja) venom in male albino rats.

    PubMed

    Gomes, Antony; Datta, Poulami; Das, Tanaya; Biswas, Ajoy Kumar; Gomes, Aparna

    2014-11-01

    The anti arthritic and anti inflammatory activity of NN-32, a cytotoxic protein from Indian spectacle cobra snake (Naja naja) venom has been studied in Freund's complete adjuvant (FCA) induced arthritis and carrageenan induced anti inflammatory model. NN-32 treatment showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats. NN-32 treatment recovered carrageenan induced inflammation as compared to control group of rats. The findings showed that the cytotoxic protein NN-32 shares anti arthritic and anti inflammatory activity and thus NN-32 may target complex pathophysiological processes like cancer- arthritis-inflammation.

  19. The Antimicrobial Activity of an Acidic Phospholipase A₂ (NN-XIa-PLA₂) from the Venom of Naja naja naja (Indian Cobra).

    PubMed

    Sudarshan, S; Dhananjaya, B L

    2015-08-01

    Microbial resistance against antibiotics is considered as a potentially serious threat to public health. Therefore, there is much interest in developing new molecules with novel modes of action. In this study, when antimicrobial potential of an acidic protein-NN-XIa-PLA2 (Naja naja venom phospholipase A2 fraction-XIa) of N. naja venom was evaluated, it demonstrated potent bactericidal action against the human pathogenic strains. It inhibited more significantly, the gram-positive bacteria, when compared to gram-negative bacteria. The minimum inhibitory concentration (MIC) values ranged from 17 to 20 μg/ml. It was interesting to observe that the NN-XIa-PLA2 showed comparable antibacterial activity to the standard antibiotics used. It was found that there was a strong correlation between phospholipase A2 (PLA2) activities, hemolytic, and antimicrobial activity. Further, it is found that in the presence of p-bromophenacyl bromide (p-BPB), there is a significant decrease in enzymatic activity and associated antimicrobial activities, suggesting that a strong correlation exists between catalytic activity and antimicrobial effects, which thereby destabilize the membrane bilayer. However, other mechanisms cannot be completely ruled out. Thus, these studies encourage further in-depth study on molecular mechanisms of antibacterial properties and thereby help in development of this protein into a possible therapeutic lead molecule for treating bacterial infections.

  20. Coagulopathies in Naja naja karachiensis (black Pakistan cobra) bites and its effect on coagulation tests upon storage of platelet-poor plasma.

    PubMed

    Asad, Muhammad Hassham Hassan Bin; Razi, Muhammad Tahir; Khan, Taous; Najam-Us-saqib, Qazi; Murtaza, Ghulam; Hussain, Muhammad Shahzad; Hussain, Muhammad Sikandar; Karim, Sabiha; Hussain, Izhar

    2012-01-01

    The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet-poor plasma, activated partial thromboplastin time (aPTT), prothrombin time (PT) / international normalized ratio (INR), thrombin time (TT) and to evaluate its effect on clotting time upon storage of plasma for a specific time period with possible mechanism responsible for that. Prolongation of PT / INR, aPTT and TT was observed when different concentrations of venom were introduced due to degeneration of fibrinogen. Preservation of plasma for three months further prolong clotting time for coagulation tests, however, difference of PT and TT results were not very prominent as compared to aPTT. Minute concentrations of cobra venom and short as well as long storage of platelet-poor plasma badly affects the INR ratio.

  1. Comparison of the primary structures, cytotoxicities, and affinities to phospholipids of five kinds of cytotoxins from the venom of Indian cobra, Naja naja.

    PubMed

    Suzuki-Matsubara, Mieko; Athauda, Senarath B P; Suzuki, Yoshiyuki; Matsubara, Kazumi; Moriyama, Akihiko

    2016-01-01

    The molecular mechanism underlying the hemolytic and cytolytic processes of cobra cytotoxins (CTXs) is not yet fully elucidated. To examine this, we analyzed the amino acid sequences, hemolytic and cytotoxic activities, and affinities to phospholipids of the five major CTXs purified from the venom of Indian cobra, Naja naja. CTX2, CTX7, and CTX8 belonged to S-type, and CTX9 and CTX10 to P-type. Comparisons of CTX7 with CTX8 and CTX9 with CTX10 revealed similar primary structures and hemolytic and cytolytic activities. CTX2, whose primary structure was rather different from the others, showed several times weaker hemolytic and cytolytic biological activities than the others. The comparison of CTX2 with CTX7 suggested the importance of Lys30 in loop II for the strong hemolytic and cytolytic activities of S-type CTXs. Cloning of 12 CTX cDNAs from the Naja naja venom cDNA library revealed that 18 out of 23 substitutions found in CTX cDNAs were nonsynonymous. This clearly indicated the accelerated evolution of CTX genes. Multiple sequence alignment of 51 kinds of CTX cDNAs and calculations of nonsynonymous and synonymous substitutions indicated that the codons coding the three loops' regions, which may interact with the hydrophobic tails of phospholipids, have undergone an accelerated evolution. In contrast, the codons coding for amino acid residues considered to participate in the recognition and binding of the hydrophilic head groups of phospholipids, eight Cys residues, and those likely stabilizing β core structure, were all conserved.

  2. Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry.

    PubMed

    Malih, Ibtissam; Ahmad rusmili, Muhamad Rusdi; Tee, Ting Yee; Saile, Rachid; Ghalim, Noreddine; Othman, Iekhsan

    2014-01-16

    The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity. Naja haje legionis is one of the medically important snakes implicated in the pathogenesis of snake bite in Morocco. The absence of information about venom composition and clinical manifestations of envenomation by this cobra represents an obstacle for the management of this environmental disease in the country. The elucidation of Moroccan cobra venom composition will provide a reasonable guidance for clinician to understand the pathophysiological conditions associated with cobra envenomation and the elaboration of better management strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Comparison of sea snake (Hydrophiidae) neurotoxin to cobra (Naja) neurotoxin.

    PubMed

    Komori, Yumiko; Nagamizu, Masaya; Uchiya, Kei-Ichi; Nikai, Toshiaki; Tu, Anthony T

    2009-12-01

    Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone.

  4. Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra).

    PubMed

    Yap, Michelle Khai Khun; Fung, Shin Yee; Tan, Kae Yi; Tan, Nget Hong

    2014-05-01

    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. The Development of the Skull of the Egyptian Cobra Naja h. haje (Squamata: Serpentes: Elapidae)

    PubMed Central

    Khannoon, Eraqi R.; Evans, Susan E.

    2015-01-01

    Background The study of craniofacial development is important in understanding the ontogenetic processes behind morphological diversity. A complete morphological description of the embryonic skull development of the Egyptian cobra, Naja h. haje, is lacking and there has been little comparative discussion of skull development either among elapid snakes or between them and other snakes. Methodology/Principal Findings We present a description of skull development through a full sequence of developmental stages of the Egyptian cobra, and compare it to other snakes. Associated soft tissues of the head are noted where relevant. The first visible ossification centres are in the supratemporal, prearticular and surangular, with slight ossification visible in parts of the maxilla, prefrontal, and dentary. Epiotic centres of ossification are present in the supraoccipital, and the body of the supraoccipital forms from the tectum posterior not the tectum synoticum. The venom glands are visible as distinct bodies as early at stage 5 and enlarge later to extend from the otic capsule to the maxilla level with the anterior margin of the eye. The gland becomes more prominent shortly before hatching, concomitant with the development of the fangs. The tongue shows incipient forking at stage 5, and becomes fully bifid at stage 6. Conclusions/Significance We present the first detailed staging series of cranial development for the Egyptian cobra, Naja h. haje. This is one of the first studies since the classical works of G. de Beer and W. Parker that provides a detailed description of cranial development in an advanced snake species. It allows us to correct errors and misinterpretations in previous accounts which were based on a small sample of specimens of uncertain age. Our results highlight potentially significant variation in supraoccipital formation among squamates and the need for further research in this area. PMID:25860015

  6. The phylogeny of cobras inferred from mitochondrial DNA sequences: evolution of venom spitting and the phylogeography of the African spitting cobras (Serpentes: Elapidae: Naja nigricollis complex).

    PubMed

    Wüster, Wolfgang; Crookes, Steven; Ineich, Ivan; Mané, Youssouph; Pook, Catharine E; Trape, Jean-François; Broadley, Donald G

    2007-11-01

    We use phylogenetic analysis of 1333 bp of mitochondrial DNA sequence to investigate the phylogeny and historical biogeography of the cobra-like elapid snakes, with special reference to the evolution of spitting and the phylogeography of the African spitting cobras, a radiation widespread in open vegetational formations throughout sub-Saharan Africa. Our results suggest that spitting adaptations appear to have evolved three times in cobras, but alternative scenarios cannot be rejected. The Asiatic Naja are monophyletic and originate from a single colonization of Asia from Africa. The radiation of the African spitting Naja appears to date back to the early Miocene and many speciation events in the group predate the Pliocene expansion of grasslands and the radiation of large grazing mammals in Africa. The cladogenic events in this complex appear to have been triggered by both ecological changes and tectonic events associated with the formation and expansion of the African Rift Valley. Taxonomically, our data confirm the inclusion of Boulengerina and Paranaja within Naja, and reveal a clade of African rainforest cobras including N. melanoleuca, Paranaja multifasciata and Boulengerina that constitutes the sister clade of the African open-formation non-spitting cobras. Naja nigricollis is polyphyletic, and we therefore recognize N. nigricincta as a separate species, more closely related to N. ashei and N. mossambica than to N. nigricollis.

  7. Improved method for the isolation, characterization and examination of neuromuscular and toxic properties of selected polypeptide fractions from the crude venom of the Taiwan cobra Naja naja atra.

    PubMed

    Ständker, L; Harvey, A L; Fürst, S; Mathes, I; Forssmann, W G; Escalona de Motta, G; Béress, L

    2012-09-15

    An improved chromatographic method was developed to isolate and purify polypeptides and proteins from the crude venom of the Taiwan cobra Naja naja atra. The procedure devised is simple, easy to reproduce, and enables large scale isolation of almost all polypeptides and proteins in this cobra venom. Six pure polypeptide fractions of the venom were isolated and characterized using gel filtration on Sephadex G50 (medium), ion exchange chromatography on SP-Sephadex C25, desalting on Sephadex G25 (fine) and preparative HPLC on a RPC 18 column. The neuromuscular activity of these fractions was tested on the chick biventer cervicis nerve-muscle preparation and their toxicity (LD(50)) was determined after i.v. administration in mice. Their antinociceptive activity was tested in the mouse abdominal test by i.v. application. Two of these polypeptide samples had major physiological effects: one acted as a cardiotoxin causing reversible myocardial contractures with no effect on muscle twitches elicited by nerve stimulation (NS); another was a neurotoxin that blocked muscle contractions in response to NS and exogenously added acetylcholine. The cardiotoxic fraction was identified as CTX I, a well-known cardiotoxin present in this venom, and the neurotoxin was identified as neurotoxin-α with an LD50 in mice of 0.075 mg/kg.

  8. An analysis of venom ontogeny and prey-specific toxicity in the Monocled Cobra (Naja kaouthia).

    PubMed

    Modahl, Cassandra M; Mukherjee, Ashis K; Mackessy, Stephen P

    2016-09-01

    Venoms of snakes of the family Elapidae (cobras, kraits, mambas, and relatives) are predominantly composed of numerous phospholipases A2 (PLA2s) and three-finger toxins (3FTxs), some of which are lethal while others are not significantly toxic. Currently, the only identified prey-specific toxins are several nonconventional 3FTxs, and given the large diversity of 3FTxs within Monocled Cobra (Naja kaouthia) venom, it was hypothesized that several 3FTxs, previously found to be non-toxic or weakly toxic 3FTxs in murine models, could potentially be toxic towards non-murine prey. Additionally, it was hypothesized that ontogenetic dietary shifts will be correlated with observable changes in specific 3FTx isoform abundance. Adult and juvenile N. kaouthia venom composition was investigated using ion-exchange FPLC, 1D and 2D SDS-PAGE, mass spectrometry, and various enzymatic and LD50 assays. Alpha-cobratoxin (α-elapitoxin) was the only significantly toxic (LD50 < 1 μg/g) 3FTx found in N. kaouthia venom and was equally toxic toward both lizard and mouse models. The abundance and diversity of 3FTxs and most enzyme activities did not vary between adult and juvenile cobra venoms; however, total venom PLA2 activity and specific PLA2 isoforms did vary, with juveniles lacking several of the least acidic PLA2s, and these differences could have both biological (related to predation) and clinical (antivenom efficacy) implications. Nevertheless, the ubiquitous presence of α-cobratoxin in both adult and juvenile cobra venoms, with high toxicity toward both reptiles and mammals, represents a venom compositional strategy wherein a single potent toxin effectively immobilizes a variety of prey types encountered across life history stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Tsukamurella serpentis sp. nov., isolated from the oral cavity of Chinese cobras (Naja atra).

    PubMed

    Tang, Ying; Teng, Jade L L; Cheung, Candy L W; Ngan, Antonio H Y; Huang, Yi; Wong, Samson S Y; Yip, Eric K T; Ng, Kenneth H L; Que, Tak-Lun; Lau, Susanna K P; Woo, Patrick C Y

    2016-09-01

    Two bacterial strains, HKU54T and HKU55, were isolated from the oral cavity of two Chinese cobras (Naja atra) in Hong Kong. 16S rRNA gene sequence analysis revealed 100 % sequence identity between HKU54T and HKU55, and the two strains shared 99.0 % sequence identities with Tsukamurella inchonensis ATCC 700082T. The two strains had unique biochemical profiles distinguishable from closely related species of the genus Tsukamurella. DNA-DNA hybridization confirmed that they belonged to the same species (≥92.1±7.9 % DNA-DNA relatedness) but were distinct from all other known species of the genus Tsukamurella (≤52.6±5.3 % DNA-DNA relatedness). Chemotaxonomic and morphological analyses of the two strains also demonstrated results consistent with their classification in the genus Tsukamurella. The DNA G+C contents of strains HKU54T and HKU55 were 69.2±1.5 mol% and 69.2±1.3 mol% (mean±sd; n=3) respectively. A novel species, Tsukamurella serpentis sp. nov., is proposed to accommodate strains HKU54T and HKU55, with HKU54T (=JCM 31017T=DSM 100915T) designated as the type strain.

  10. Weak neurotoxin from Naja kaouthia cobra venom affects haemodynamic regulation by acting on acetylcholine receptors.

    PubMed

    Ogay, Alexey Ya; Rzhevsky, Dmitry I; Murashev, Arkady N; Tsetlin, Victor I; Utkin, Yuri N

    2005-01-01

    Recent in vitro studies of weak neurotoxins from snake venoms have demonstrated their ability to interact with both muscle-type and neuronal alpha7 nicotinic acetylcholine receptors (nAChR). However, the biological activity in vivo of weak neurotoxins remains largely unknown. We have studied the influence of weak neurotoxin (WTX) from the venom of cobra Naja kaouthia on arterial blood pressure (BP) and heart rate (HR) in rats and mice. It was found that intravenous injection of WTX induced a dose-dependent decrease in BP and an increase in HR in both species, the rats being more sensitive to WTX. Application of WTX following blockade of nAChRs or muscarinic acetylcholine receptors (mAChR) by hexamethonium or atropine, respectively, showed that both nAChRs and mAChRs are involved in the haemodynamic effects of WTX. Blockade of either nAChRs or mAChRs affected WTX action differently in rats and mice, thus reflecting interspecies differences in haemodynamic regulation.

  11. Purification and characterization of an anticoagulant phospholipase A(2) from Indian monocled cobra (Naja kaouthia) venom.

    PubMed

    Doley, Robin; Mukherjee, Ashis Kumar

    2003-01-01

    An anticoagulant, non-toxic phospholipase A(2) was isolated from the venom of Indian monocled cobra (Naja kaouthia) by a combination of ion-exchange chromatography on CM-Sephadex C-50 and gel filtration on Sephadex G-50. This purified protein named NK-PLA(2)-I, had a subunit molecular mass of 13.6 kDa and migrated as a dimer under non-reduced condition in SDS-PAGE. NK-PLA(2)-I was a highly thermostable protein requiring basic pH optima for its catalytic activity and showed preferential hydrolysis of phosphotidylcholine. This protein exhibited higher anticoagulant, indirect hemolysis, liver and heart tissue damaging activity but exerted less toxicity, direct hemolysis, edema and lung tissue damaging activity as compared to whole venom. Treatment of NK-PLA(2)-I with rho-BPB, TPCK, PMSF, antivenom and heating had almost equal effect on PLA(2), and other pharmacological properties except in vitro tissue damaging activity. Current investigation provides a fairly good indication that NK-PLA(2)-I induces various pharmacological effects by mechanisms, which are either dependent or independent of its catalytic activity.

  12. Unique features of myogenesis in Egyptian cobra (Naja haje) (Squamata: Serpentes: Elapidae).

    PubMed

    Khannoon, Eraqi R; Rupik, Weronika; Lewandowski, Damian; Dubińska-Magiera, Magda; Swadźba, Elwira; Daczewska, Małgorzata

    2016-03-01

    During early stages of myotomal myogenesis, the myotome of Egyptian cobra (Naja haje) is composed of homogenous populations of mononucleated primary myotubes. At later developmental phase, primary myotubes are accompanied by closely adhering mononucleated cells. Based on localization and morphology, we assume that mononucleated cells share features with satellite cells involved in muscle growth. An indirect morphological evidence of the fusion of mononucleated cells with myotubes is the presence of numerous vesicles in the subsarcolemmal region of myotubes adjacent to mononucleated cell. As differentiation proceeded, secondary muscle fibres appeared with considerably smaller diameter as compared to primary muscle fibre. Studies on N. haje myotomal myogenesis revealed some unique features of muscle differentiation. TEM analysis showed in the N. haje myotomes two classes of muscle fibres. The first class was characterized by typical for fast muscle fibres regular distribution of myofibrils which fill the whole volume of muscle fibre sarcoplasm. White muscle fibres in studied species were a prominent group of muscles in the myotome. The second class showed tightly paced myofibrils surrounding the centrally located nucleus accompanied by numerous vesicles of different diameter. The sarcoplasm of these cells was characterized by numerous lipid droplets. Based on morphological features, we believe that muscle capable of lipid storage belong to slow muscle fibres and the presence of lipid droplets in the sarcoplasm of these muscles during myogenesis might be a crucial adaptive mechanisms for subsequent hibernation in adults. This phenomenon was, for the first time, described in studies on N. haje myogenesis.

  13. Paraspecific neutralization of the venom of African species of cobra by an equine antiserum against Naja melanoleuca: a comparative study.

    PubMed

    Casasola, Andrea; Ramos-Cerrillo, Blanca; de Roodt, Adolfo R; Carbajal Saucedo, Alejandro; Chippaux, Jean-Philippe; Alagón, Alejandro; Stock, Roberto P

    2009-05-01

    Venoms of snakes belonging to the same Genera tend to share biochemical, toxinological and antigenic characteristics. Accordingly, paraspecific neutralization of venom lethality by experimental antisera and commercial antivenoms has been reported. We studied the spectrum of neutralization of lethality of an experimental monovalent equine antiserum against the strongly neurotoxic African forest cobra (Naja melanoleuca) when tested against venoms of most species of African Naja, both neuro and cytotoxic as described by some authors. We report a comparison of the median lethal doses (LD50) of the venoms and the paraspecific median effective doses (ED50) of the antiserum calculated using three methods: Spearman-Kärber and Probit (currently recommended by the World Health Organization), and non-linear regression. An ample--but not complete--spectrum of paraspecific neutralization of lethality was observed against both spitting and non-spitting species of African Naja with a clearly more efficient neutralization of the more potent venoms, the implications of which are discussed. The median lethal and effective doses calculated by the three methods are remarkably consistent and may warrant consideration of non-linear regression methods for the calculation of venom lethality and antivenom potency by venom/antivenom researchers and producers.

  14. [Fibrinogen/fibrin-specific enzymes from copperhead (Agkistrodon halys halys) and cobra (Naja oxiana eichwald) snake venoms].

    PubMed

    Yunusova, E S; Sadykov, E S; Sultanalieva, N M; Shkinev, A V

    2016-03-01

    Ability of fractions of cobra's (Naja oxiana Eichwald) and copperhead snake's (Agkistrodon halys halys) venoms to hydrolyze fibrinogen/fibrin was studied. In cobra's snake a component with molecular mass of nearly 60 kDa was found to hydrolyze a-chain of fibrinogen but failed to hydrolyze casein/azocasein and fibrin. A fibrinogen-specific metalloproteinase, the enzyme was inhibited by EDTA. Cobra's venom reduced the mass of donor's fresh blood clots. The copperhead snake's venom and the fractions obtained by gel-filtration (HW-50) and ion exchange chromatography (DEAE-650) were found to hydrolyze casein/azocasein, a- and b-chains of fibrinogen/fibrin and donor's blood clots. The results from the study of the venom and proteolytically active fractions are the evidence for a thrombolytic potential in a copperhead snake's venom.

  15. Comparative study of the cytolytic activity of snake venoms from African spitting cobras (Naja spp., Elapidae) and its neutralization by a polyspecific antivenom.

    PubMed

    Méndez, Ileana; Gutiérrez, José María; Angulo, Yamileth; Calvete, Juan J; Lomonte, Bruno

    2011-11-01

    Venoms of several Naja species found in Sub-Saharan Africa, and commonly known as "spitting cobras", induce a predominantly cytotoxic pattern of envenomings that may evolve into tissue necrosis and gangrene. Cytotoxic components of their venoms have been identified as members of the three-finger toxin and phospholipase A(2) protein families. In this study, an in vitro assay using the myogenic cell line C2C12, was utilized to compare the cytolytic activities of venoms from five species of spitting cobras: Naja nigricollis, Naja katiensis, Naja pallida, Naja nubiae, and Naja mossambica. These venoms were strongly cytotoxic, causing a 50% effect at ~1.5 μg/well (15 μg/ml), except for N. katiensis venom, which required nearly twice this amount. Using the cell-based assay, the ability of an equine polyspecific antivenom (EchiTab-Plus-ICP) to neutralize cytotoxicity was assessed. The antivenom completely inhibited the cytotoxic activity of all five venoms, although high antivenom/venom ratios were needed. Neutralization curves displayed the following decreasing order of efficiency: N. nubiae > N. pallida > N. mossambica > N. nigricollis > N. katiensis. Results indicate that neutralizing antibodies toward toxins responsible for this particular effect are present in the antivenom, albeit in low titers. Fucoidan, a natural sulfated polysaccharide known to inhibit the toxic effects of some basic snake venom components, was unable to reduce cytotoxicity of Naja venoms. Results emphasize the need of enhancing the immunogenicity of low molecular mass toxins during antivenom production, as well as to search for useful toxin inhibitors which could complement antivenom therapy.

  16. The protective effects of Mucuna pruriens seed extract against histopathological changes induced by Malayan cobra (Naja sputatrix) venom in rats.

    PubMed

    Fung, S Y; Tan, N H; Liew, S H; Sim, S M; Aguiyi, J C

    2009-04-01

    Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.

  17. Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom.

    PubMed

    Das, Tanaya; Bhattacharya, Shamik; Biswas, Archita; Gupta, Shubho Das; Gomes, Antony; Gomes, Aparna

    2013-04-01

    A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.

  18. Anticancer Activity a of Caspian Cobra (Naja naja oxiana) snake Venom in Human Cancer Cell Lines Via Induction of Apoptosis

    PubMed Central

    Ebrahim, Karim; Vatanpour, Hossein; Zare, Abbas; Shirazi, Farshad H.; Nakhjavani, Mryam

    2016-01-01

    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 treatment PMID:28228809

  19. Cloning and characterization of cDNAs encoding three isoforms of phospholipase A2 in Malayan spitting cobra (Naja naja sputatrix) venom.

    PubMed

    Armugam, A; Earnest, L; Chung, M C; Gopalakrishnakone, P; Tan, C H; Tan, N H; Jeyaseelan, K

    1997-01-01

    cDNAs encoding three phospholipase A2 (PLA2) isoforms in Naja naja sputatrix were cloned and characterized. One of them encoded an acidic PLA2 (APLA) while the others encoded neutral PLA2 (NPLA-1 and NPLA-2). The specific characteristics of APLA and NPLA were attributed to mutations at nt139 and nt328 from G to C and G to A, respectively, resulting in amino acid substitutions from Asp20 and 83 in APLA to His20 and Asn83 in NPLA. Amino acid sequencing of purified protein also showed the presence of this Asp20 and His20 in APLA and NPLA, respectively. The cDNA encoding one of the PLA2 (NAJPLA-2A), when expressed in Escherichia coli, yielded a protein that exhibited PLA2 activity.

  20. Salmonella serovar distribution in cobras (Naja kaouthia), snake-food species, and farm workers at Queen Saovabha Snake Park, Thailand.

    PubMed

    Prapasarakul, Nuvee; Pulsrikarn, Chaiwat; Vasaruchapong, Taksa; Lekcharoen, Pisin; Chanchaithong, Pattrarat; Lugsomya, Kittitat; Keschumras, Nitiwadee; Thanomsuksinchai, Natthakarn; Tanchiangsai, Kanittha; Tummaruk, Padet

    2012-03-01

    The purpose of the current study was to investigate the prevalence and serovar distribution of Salmonella isolates in cobras and their environment at a snake park. A total of 166 fecal or intestinal samples were examined, comprising 39 samples from captive cobras (Naja kaouthia), 70 from recently wild-caught cobras, 19 from wild-caught cobras that had been kept on the farm for over 3 months, 18 from mice (Mus musculus), 12 from frogs (Hoplobatrachus rugulosus), and 8 from farm workers. Specific serological identification was performed, and pulsed-field gel electrophoresis (PFGE) was utilized for DNA analysis. Out of all snakes (n = 128), 20 of the 30 animals used for snake food and 3 of the 8 samples from personnel were positive for Salmonella spp. There were 228 Salmonella isolates, with a total of 29 serovars from subspecies I and IIIb, composed of 24 serovars from cobras and 5 from the other sources. Salmonella Amsterdam was predominant in captive-born and captive cobras, followed by S. Poona and S. Bareilly, respectively (P < 0.05). Salmonella I 4,[5],12:i:- was the sole serovar detected from the mice, while 3 serovars including Ramatgan, I 4,[5],12:e,h:-, and rough strain were detected only from frogs (P < 0.001). Salmonella Derby was only detected in workers. On the basis of the PFGE results, evidence of movement of isolates between human beings and snakes, and between snakes and frogs, was found for S. Poona and S. Wandsworth, respectively. The study suggests that Salmonella spp. act as true residents in the intestinal tract of cobras with high risk of environmental contamination through fecal shedding.

  1. Comparison of proteomic profiles of the venoms of two of the 'Big Four' snakes of India, the Indian cobra (Naja naja) and the common krait (Bungarus caeruleus), and analyses of their toxins.

    PubMed

    Choudhury, Manisha; McCleary, Ryan J R; Kesherwani, Manish; Kini, R Manjunatha; Velmurugan, Devadasan

    2017-09-01

    Snake venoms are mixtures of biologically-active proteins and peptides, and several studies have described the characteristics of some of these toxins. However, complete proteomic profiling of the venoms of many snake species has not yet been done. The Indian cobra (Naja naja) and common krait (Bungarus caeruleus) are elapid snake species that are among the 'Big Four' responsible for the majority of human snake envenomation cases in India. As understanding the composition and complexity of venoms is necessary for successful treatment of envenomation in humans, we utilized three different proteomic profiling approaches to characterize these venoms: i) one-dimensional SDS-PAGE coupled with in-gel tryptic digestion and electrospray tandem mass spectrometry (ESI-LC-MS/MS) of individual protein bands; ii) in-solution tryptic digestion of crude venoms coupled with ESI-LC-MS/MS; and iii) separation by gel-filtration chromatography coupled with tryptic digestion and ESI-LC-MS/MS of separated fractions. From the generated data, 81 and 46 different proteins were identified from N. naja and B. caeruleus venoms, respectively, belonging to fifteen different protein families. Venoms from both species were found to contain a variety of phospholipases A2 and three-finger toxins, whereas relatively higher numbers of snake venom metalloproteinases were found in N. naja compared to B. caeruleus venom. The analyses also identified less represented venom proteins including L-amino acid oxidases, cysteine-rich secretory proteins, 5'-nucleotidases and venom nerve growth factors. Further, Kunitz-type serine protease inhibitors, cobra venom factors, phosphodiesterases, vespryns and aminopeptidases were identified in the N. naja venom, while acetylcholinesterases and hyaluronidases were found in the B. caeruleus venom. We further analyzed protein coverage (Lys/Arg rich and poor regions as well as potential glycosylation sites) using in-house software. These studies expand our

  2. Development of a polymerase chain reaction to distinguish monocellate cobra (Naja khouthia) bites from other common Thai snake species, using both venom extracts and bite-site swabs.

    PubMed

    Suntrarachun, S; Pakmanee, N; Tirawatnapong, T; Chanhome, L; Sitprija, V

    2001-07-01

    A PCR technique was used in this study to identify and distinguish monocellate cobra snake bites using snake venoms and swab specimens from snake bite-sites in mice from bites by other common Thai snakes. The sequences of nucleotide primers were selected for the cobrotoxin-encoding gene from the Chinese cobra (Naja atra) since the sequences of monocellate cobra (Naja kaouthia) venom are still unknown. However, the 113-bp fragment of cDNA of the cobrotoxin-encoding gene was detected in the monocellate cobra venom using RT-PCR. This gene was not found in the venoms of Ophiophagus hannah (king cobra), Bungarus fasciatus (banded krait), Daboia russelii siamensis (Siamese Russell's Viper, and Calloselasma rhodostoma (Malayan pit viper). Moreover, direct PCR could detect a 665-bp fragment of the cobrotoxin-encoding gene in the monocellate cobra venom but not the other snake venoms. Likewise, this gene was only observed in swab specimens from cobra snake bite-sites in mice. This is the first report demonstrating the ability of PCR to detect the cobrotoxin-encoding gene from snake venoms and swab specimens. Further studies are required for identification of this and other snakes from the bite-sites on human skin.

  3. Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2015-04-29

    Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness. Biogeographical variations were observed in the venom proteome of monocled cobra (Naja kaouthia) from Malaysia, Thailand and Vietnam. The Thai N. kaouthia venom is particularly rich in long neurotoxins, while the Malaysian and Vietnamese specimens were predominated with cytotoxins. The differentially expressed toxin profile accounts for the discrepancy in the lethal dose of the venom from different populations. Commercially available Thai antivenoms (monovalent and polyvalent) were able to neutralize the three venoms at different effective doses, hence supporting their uses in the three regions. While dose adjustment according to

  4. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins.

    PubMed

    Laustsen, Andreas H; Gutiérrez, José María; Lohse, Brian; Rasmussen, Arne R; Fernández, Julián; Milbo, Christina; Lomonte, Bruno

    2015-06-01

    The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38 different proteins that were either identified or assigned to families. Estimation of relative protein abundances revealed that venom is dominated by three-finger toxins (77.5%; including 24.3% cytotoxins and 53.2% neurotoxins) and phospholipases A2 (13.5%). It also contains lower proportions of components belonging to nerve growth factor, ohanin/vespryn, cysteine-rich secretory protein, C-type lectin/lectin-like, nucleotidase, phosphodiesterase, metalloproteinase, l-amino acid oxidase, cobra venom factor, and cytidyltransferase protein families. Small amounts of three nucleosides were also evidenced: adenosine, guanosine, and inosine. The most relevant lethal components, categorized by means of a 'toxicity score', were α-neurotoxins, followed by cytotoxins/cardiotoxins. IgGs isolated from a person who had repeatedly self-immunized with a variety of snake venoms were immunoprofiled by ELISA against all venom fractions. Stronger responses against larger toxins, but lower against the most critical α-neurotoxins were obtained. As expected, no neutralization potential against N. kaouthia venom was therefore detected. Combined, our results display a high level of venom complexity, unveil the most relevant toxins to be neutralized, and provide prospects of discovering human IgGs with toxin neutralizing abilities through use of phage display screening. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Isolation and characterization of microsatellite loci in the Chinese Cobra Naja atra (Elapidae).

    PubMed

    Lin, Long-Hui; Mao, Lu-Xi; Luo, Xia; Qu, Yan-Fu; Ji, Xiang

    2011-01-01

    We characterize thirteen polymorphic microsatellite loci isolated from Naja atra genomic libraries, which were enriched for AC-motif microsatellites. The thirteen loci were screened on a group of 48 individuals from two populations, one in Yong'an and the other in Ganzhou. These markers revealed a relatively high degree of genetic diversity (4-12 alleles per locus) and heterozygosity (Ho ranged from 0.213-0.854 and He ranged from 0.301-0.838). Tests for departure from Hardy-Weinberg equilibrium and for linkage disequilibrium were conducted for each of the two populations separately. After sequential Bonferroni correction, none of the 13 loci showed significant departures from Hardy-Weinberg equilibrium. Hierarchical analysis of molecular variance indicated that a small but significant (P < 0.001) proportion (16.0%) of the total variation in the microsatellite DNA data were attributable to differences among populations, indicating geographical structuring and restricted gene flow. It could be attributable to the Wuyi mountains in the area having a sufficiently isolating effect to significantly reduce gene flow. Our microsatellite data also showed a low N(m) (1.31) value in the two populations from mainland China. Thus, the Yong'an and Ganzhou populations could be treated as distinct evolutionarily significant units (ESUs). The high level of polymorphism revealed by these microsatellite markers will be useful for the study of gene flow, population structure and evolutionary history of N. atra.

  6. Protective activity of medicinal plants and their isolated compounds against the toxic effects from the venom of Naja (cobra) species.

    PubMed

    Shabbir, Arham; Shahzad, Muhammad; Masci, Paul; Gobe, Glenda C

    2014-11-18

    Various medicinal plants have protective properties against the toxicities of the venom of cobra snake (Naja species). They may be used as local first aid for the treatment of snakebite victims, and can significantly inhibit lethality, cardio-, neuro-, nephro- and myotoxicity, hemorrhage, and respiratory paralysis induced by the cobra snake venom. The plants or their extracts may also complement the benefits of conventional anti-serum treatment. This review provides information on the protective, anti-venom, properties of medicinal plants against snakebites from cobras. In addition, it identifies knowledge gaps and suggests further research opportunities. The literature was searched using databases including Google Scholar, PubMed, ScienceDirect, Scopus and Web of Science. The searches were limited to peer-reviewed journals written in English with the exception of some books and a few articles in foreign languages. The plants possess neutralization properties against different cobra venom enzymes, such as hyaluronidase, acetylcholinesterase, phospholipase A2 and plasma proteases. Different active constituents that show promising activity against the effects of cobra venom include lupeol acetate, β-sitosterol, stigmasterol, rediocides A and G, quercertin, aristolochic acid, and curcumin, as well as the broad chemical groups of tannins, glycoproteins, and flavones. The medicinal plants can increase snakebite victim survival time, decrease the severity of toxic signs, enhance diaphragm muscle contraction, block antibody attachment to venom, and inhibit protein destruction. In particular, the cardiovascular system is protected, with inhibition of blood pressure decline and depressed atrial contractility and rate, and prevention of damage to heart and vessels. The designs of experimental studies that show benefits, or otherwise, of use of medicinal plants have some limitations: deficiency in identification and isolation of active constituents responsible for

  7. Venomics of Naja sputatrix, the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization.

    PubMed

    Tan, Nget Hong; Wong, Kin Ying; Tan, Choo Hock

    2017-03-22

    The venom proteome of Naja sputatrix (Javan spitting cobra) was elucidated through reverse-phase HPLC, nano-ESI-LCMS/MS and data mining. A total of 97 distinct protein forms belonging to 14 families were identified. The most abundant proteins are the three-finger toxins (3FTXs, 64.22%) and phospholipase A2 (PLA2, 31.24%), followed by nerve growth factors (1.82%), snake venom metalloproteinase (1.33%) and several proteins of lower abundance (<1%) including a variety of venom enzymes. At subproteome, the 3FTx is dominated by cytotoxins (48.08%), while short neurotoxins (7.89%) predominate over the long neurotoxins (0.48%) among other neurotoxins of lesser toxicity (muscarinic toxin-like proteins, 5.51% and weak neurotoxins, 2.26%). The major SNTX, CTX and PLA2 toxins were isolated with intravenous median lethal doses determined as 0.13, 1.06 and 0.50μg/g in mice, respectively. SABU, the Indonesia manufactured homologous tri-specific antivenom could neutralize the CTX and PLA2 fraction with moderate potency (potency=0.14-0.16mg toxin per ml antivenom). The SNTX, however, was very poorly neutralized with a potency level of 0.034mg/ml, indicating SNTX as the main limiting factor in antivenom neutralization. The finding helps elucidate the inferior efficacy of SABU reported in neutralizing N. sputatrix venom, and supports the call for antivenom improvement.

  8. The Phylogeographical Pattern and Conservation of the Chinese Cobra (Naja atra) across Its Range Based on Mitochondrial Control Region Sequences

    PubMed Central

    Lin, Long-Hui; Hua, Lei; Qu, Yan-Fu; Gao, Jian-Fang; Ji, Xiang

    2014-01-01

    The vulnerable Chinese cobra (Naja atra) ranges from southeastern China south of the Yangtze River to northern Vietnam and Laos. Large mountain ranges and water bodies may influence the pattern of genetic diversity of this species. We sequenced the mitochondrial DNA control region (1029 bp) using 285 individuals collected from 23 localities across the species' range and obtained 18 sequences unique to Taiwan from GenBank for phylogenetic and population analysis. Two distinct clades were identified, one including haplotypes from the two westernmost localities (Hekou and Miyi) and the other including haplotypes from all sampling sites except Miyi. A strong population structure was found (Φst = 0.76, P<0.0001) with high haplotype diversity (h = 1.00) and low nucleotide diversity (π = 0.0049). The Luoxiao and Nanling Mountains act as historical geographical barriers limiting gene exchange. In the haplotype network there were two “star” clusters. Haplotypes from populations east of the Luoxiao Mountains were represented within one cluster and haplotypes from populations west of the mountain range within the other, with haplotypes from populations south of the Nanling Mountains in between. Lineage sorting between mainland and island populations is incomplete. It remains unknown as to how much adaptive differentiation there is between population groups or within each group. We caution against long-distance transfers within any group, especially when environmental differences are apparent. PMID:25184236

  9. Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom.

    PubMed

    Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C

    2012-01-01

    Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.

  10. Region-specific neutralization of Indian cobra (Naja naja) venom by polyclonal antibody raised against the eastern regional venom: A comparative study of the venoms from three different geographical distributions.

    PubMed

    Shashidharamurthy, R; Kemparaju, K

    2007-01-01

    Indian cobra (Naja naja) venoms from different geographical locations vary in their composition, biochemical, and pharmacological properties. Venom samples from eastern, western and southern India are compared in this study. The venom from eastern region was found to be the most lethal of the three regional venoms. Monovalent antivenom (NNEV-IgG) prepared against the eastern venom was found to cross-react with the other two regional venoms. NNEV-IgG at an Ag:Ab ratio of 1:25 completely neutralized the lethality of eastern venom. At this ratio, it did not neutralize the other two venoms, but the survival time of experimental mice was extended significantly. Commercially available polyvalent antivenom neutralized the lethality of western venom at an Ag:Ab ratio of 1:60 and increased the survival time of experimental mice injected with eastern and southern venoms marginally. Further, NNEV-IgG neutralized the tested pharmacological and enzymatic activities of all the three venom samples dose dependently, with neutralization potency varying with the geographic origin of the tested venoms. Thus, the present study demonstrates the diversity in the immunological properties of venom from different geographical regions and underscores the importance of developing region-specific antivenoms for therapeutic purpose.

  11. Structure of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-peptide with phospholipase A2 from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution.

    PubMed

    Mirza, Zeenat; Pillai, Vikram Gopalakrishna; Zhong, Wei-Zhu

    2014-03-10

    Alzheimer's disease (AD) is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ) are the prime player of AD's neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2) in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer's Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS) of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB) Code: 3JQ5). This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ-Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD.

  12. Activity of cytotoxin P4 from the venom of the cobra snake Naja nigricollis on gram-positive bacteria and eukaryotic cell lines.

    PubMed

    Möllmann, U; Gutsche, W; Maltz, L; Ovadia, M

    1997-05-01

    The cytotoxin P4 from the venom of the cobra snake Naja nigricollis was examined for activity against aerobic gram-positive and gram-negative bacteria, yeasts, fungi and eucaryotic cell lines by determination of minimal inhibitory concentrations (MIC) and IC50 values, respectively. Cytotoxin P4 exhibits antimicrobial activity against Bacillus subtilis, Micrococcus flavus and Sarcina lutea. Targets in gram-negative bacteria and fungi apparently were not reached. Toxicity against eucaryotic cells is in a narrow range between lethal and tolerable concentrations.

  13. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Sim, Si Mui; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Pathogenesis of dermonecrosis induced by venom of the spitting cobra, Naja nigricollis: An experimental study in mice.

    PubMed

    Rivel, Mario; Solano, Daniela; Herrera, María; Vargas, Mariángela; Villalta, Mauren; Segura, Álvaro; Arias, Ana Silvia; León, Guillermo; Gutiérrez, José María

    2016-09-01

    The pathogenesis of dermonecrosis induced by the venom of the African spitting cobra Naja nigricollis was investigated in a mouse model. Intradermal injection of venom induced a macroscopic necrotic lesion. Histological examination revealed early edema of the dermis, followed by blistering, loss of skin appendages and reduction in cellularity. By 24 h, necrosis of the dermis was evident, sections of epidermis were lost, and a fibrinoid hyaline material filled the damaged areas. Abundant inflammatory infiltrate was present in the hypodermis and basal dermis, and there was an increment in the expression of matrix metalloproteinases (MMPs). Thrombi were observed in blood vessels. Abundant cells were present in the dermis by 7 days. By 14 and 28 days, re-epithelization had occurred, collagen was widespread in the dermis, and few skin appendages were present. The RP-HPLC fractions that reproduced the necrotic activity were composed of low molecular mass cytotoxins of the three-finger toxin family and, to a lesser extent, of phospholipases A2 (PLA2). Inhibition of PLA2 of venom by p-bromophenacyl bromide did not reduce the area of necrosis, but modified the appearance of necrotic regions. Depletion of neutrophils and inhibition of venom metalloproteinases and tissue MMPs did not affect dermonecrosis. IgG and F(ab')2 antivenoms were effective in the neutralization of dermonecrosis when incubated with venom prior to injection. However, when antivenoms were administered immediately after venom injection, dermonecrosis was reduced only to a partial extent, underscoring the difficulties in neutralizing this effect with antivenoms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: inhibition of anticoagulant activity by low molecular weight heparin.

    PubMed

    Dutta, Sumita; Gogoi, Debananda; Mukherjee, Ashis K

    2015-03-01

    In the present study, anticoagulant and platelet modulating activities of an acidic phospholipase A2 (NnPLA2-I) purified from Indian cobra Naja naja venom was investigated. The NnPLA2-I displayed a mass of 15.2 kDa and 14,186.0 Da when analyzed by SDS-PAGE and MALDI-TOF-MS, respectively. Peptide mass fingerprinting analysis of the NnPLA2-I showed its significant similarity with phospholipase A2 enzymes purified from cobra venom. BLAST analysis of one tryptic peptide sequence of NnPLA2-I demonstrated putative conserved domains of the PLA2-like superfamily. The Km and Vmax values of NnPLA2-I toward hydrolysis of its most preferred substrate-phosphotidylcholine (PC)-were determined to be 0.72 mM and 29.3 μmol min(-1) mg(-1), respectively. The anticoagulant activity of NnPLA2-I was found to be higher than the anticoagulant activity of heparin/AT-III or warfarin. The histidine modifying reagent, monovalent and polyvalent antivenom differentially inhibited the catalytic and anticoagulant activities of NnPLA2-I. Low molecular weight heparin did not inhibit the catalytic and platelet deaggregation activity of NnPLA2-I, albeit its anticoagulant activity was significantly reduced. The NnPLA2-I showed a non-enzymatic, mixed inhibition of thrombin with a Ki value of 9.3 nM. Heparin significantly decreased, with an IC50 value of 15.23 mIU, the thrombin inhibitory activity of NnPLA2-I. The NnPLA2-I uniquely increased the amidolytic activity of FXa without influencing its prothrombin activating property. NnPLA2-I showed dose-dependent deaggregation of platelet rich plasma (PRP) and inhibited the collagen and thrombin-induced aggregation of PRP. However, deaggregation of washed platelets by NnPLA2-I demonstrated in presence of PC or platelet poor plasma. Alkylation of histidine residue of NnPLA2-I resulted in 95% and 21% reduction of its platelet deaggregation and platelet binding properties, respectively. NnPLA2-I did not show cytotoxicity against human glioblastoma U87MG cells

  16. Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca.

    PubMed

    Lauridsen, Line P; Laustsen, Andreas H; Lomonte, Bruno; Gutiérrez, José María

    2017-01-06

    A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1wt%), which includes post-synaptically acting α-neurotoxins. Phospholipases A2 (PLA2) were the second most abundant group of proteins (12.9wt%), followed by metalloproteinases (SVMPs) (9.7wt%), cysteine-rich secretory proteins (CRISPs) (7.6wt%), and Kunitz-type serine proteinase inhibitors (3.8wt%). A number of additional protein families comprised each <3wt% of venom proteins. A toxicity screening of the fractions, using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53mg/kg. Three polyspecific antivenoms manufactured in South Africa and India were tested for their immunoreactivity against crude venom and fractions of N. melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom, the South African antivenom showing a higher titer against the neurotoxin-containing fractions. This toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant targets to be neutralized.

  17. Changes in the arterial blood pressure, heart rate and normal ECG parameters of rat after envenomation with Egyptian cobra (Naja haje) venom.

    PubMed

    Omran, M A; Abdel-Nabi, I M

    1997-06-01

    1. The effect of Egyptian cobra (Naja haje) venom on the normal electrical activity of the cardiac muscles (ECG) and arterial blood pressure of envenomated rats were investigated in this study. 2. Rats were divided into three groups. The first group was injected im with saline and considered as control group. Rats of the second and third groups were injected IM with 0.02 micrograms and 0.04 micrograms cobra venom/gim b.wt, respectively. 3. Mean blood pressure (MBP), heart rate (HR) and four different ECG parameters (PR and QT intervals, R and T wave amplitudes) were measured over 1 h following envenomation. 4. The low dose (0.02 micrograms/g) of N. haje venom caused hypotension accompanied by an increase in the HR, whereas hypertension and bradycardia developed after injection of the high dose (0.04 micrograms/g) of venom. 5. There was a decrease in the P-R interval after administration of the low dose and prolongation of it after the high dose. The Q-T interval and R-wave amplitude were significantly increased after injection of both doses. T-wave amplitude was significantly elevated only after injection of the high dose. 6. The present results indicate that the Egyptian cobra (N. haje) venom significantly alters the arterial blood pressure and ECG parameters of envenomated rats. The suggests that impairment of the electrical activity of cardiac muscle may be one of the reasons why victims of cobra bite die.

  18. Protein Characterization of Javan Cobra (Naja sputatrix) Venom Following Sun Exposure and Photo-Oxidation Treatment

    NASA Astrophysics Data System (ADS)

    Sulistiyani; Biki, R. S.; Andrianto, D.

    2017-03-01

    Snake venom has always been known for its toxicity that can cause fatality, however, it is also one of the important biological resources to be used for disease treatment. In Indonesia, snake venom previously expose under the sun has been used for alternative treatment of some diseases such as dengue fever, atherosclerosis, cancer, and diabetes. There has been very little scientific evidence on the use of snake venom of Indonesia origin as well as its protein characteristic. Thus, the objective of this research is to characterize the protein content and the specific activity of the venom of Javan Cobra (N.sputatrix) when treated with sun exposure in comparison with photo-oxidation by ultraviolet. Qualitative analysis of protein contents was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). The L-amino acid oxidase activity (LAAO) and the phospholipase A2 (PLA2) activities were determined using spectrophotometry. The venom’s protein was separated into 5 main protein bands with molecular weight ranging from 14 to 108 kDa. A time course study showed that the venom lost 91% of its LAAO activity and 96% of PLA2 activity after 6 hours of sun exposure. UV photo-oxidation carried out for 3 hours decreased 91% of LAAO activity, and almost diminished all of PLA2 activity (99.8%). These findings suggest that the exposure of N. sputatrix venom under the sun and UV photo-oxidation decreased its toxicity as shown by the significant reduction of the enzymes activity, but did not affect the protein’s integrity. Therefore, these approaches produced N.sputatrix venom with less toxicity but still withheld other characters of intact proteins.

  19. Molecular modeling of NK-CT1, from Indian monocellate cobra (Naja kaouthia) and its docking interaction with human DNA topoisomerase II alpha

    PubMed Central

    Bandopadhyay, Pathikrit; Halder, Soma; Sarkar, Mrinmoy; Kumar Bhunia, Sujay; Dey, Sananda; Gomes, Antony; Giri, Biplab

    2016-01-01

    A 6.76 kDa molecular weight cardio and cytotoxic protein of 60 amino acids in length called NK-CT1, was purified from the venom of Indian monocellate cobra (Naja kaouthia) by ion-exchange chromatography and HPLC as described in our earlier report. Therefore it is of interest to utlize the sequence of NK-CT1 for further functional inference using molecular modeling and docking. Thus homology model of NK-CT1 is described in this report. The anti-proliferative activity of the protein, binding with human DNA topoisomerase-II alpha was demonstrated using docking data with AUTODOCK and AUTODOCK MGL tools. Data shows that M26, V27 and S28 of NK-CT1 is in close contact with the nucleotides of the oligonucleotide, bound with topoisomerase-II alpha complex. PMID:28149043

  20. Antivenom activity of triterpenoid (C34H68O2) from Leucas aspera Linn. against Naja naja naja venom induced toxicity: antioxidant and histological study in mice.

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Thomas, John; Balachander, V; Babu, V Sarath; Bilal, S Mohammed Yusuf; Majeed, S Abdul; Madan, N; Raj, N Sundar; Vimal, S; Nambi, K S N; Hameed, A S Sahul

    2014-04-01

    The isolated and identified triterpenoid, 1-hydroxytetratriacontane-4-one (C34H68O2), obtained from the methanolic leaf extract of Leucas aspera Linn. was explored for the first time for antisnake venom activity. The plant (L. aspera Linn.) extract significantly antagonized the spectacled cobra (Naja naja naja) venom induced lethal activity in a mouse model. It was compared with commercial antiserum obtained from King Institute of Preventive Medicine (Chennai, Tamil Nadu, India). N. naja naja venom induced a significant decrease in antioxidant superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH and glutathione-S-transferase activities and increased lipid peroxidase (LPO) activity in different organs such as heart, liver, kidney and lungs. The histological changes following the antivenom treatment were also evaluated in all these organs. There were significant alterations in the histology. Triterpenoid from methanol extract of L. aspera Linn. at a dose level of 75 mg per mouse significantly attenuated (neutralized) the venom-induced antioxidant status and also the LPO activity in different organs.

  1. The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom.

    PubMed

    Cherdchu, C; Poopyruchpong, N; Adchariyasucha, R; Ratanabanangkoon, K

    1977-06-01

    Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be "snakebite antidote" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom.

  2. Long-lasting convulsant effect on the cerebral cortex of Naja naja venom

    PubMed Central

    Bhargava, V. K.; Horton, R. W.; Meldrum, B. S.

    1970-01-01

    1. A neurotoxic fraction has been prepared from Indian cobra venom (Naja naja) by column chromatography on CM Sephadex. 2. When assayed for lethality in mice, or for neuromuscular blocking potency in the rat phrenic nerve-diaphragm preparation, this fraction was 2·4-2·9 times as potent as whole venom. 3. Application of either whole venom (0·5-1·0 mg/ml) or the neurotoxic fraction (0·25-1·0 mg/ml) to the exposed cerebral cortex of the rat led to the appearance in the somatosensory evoked potential of abnormal negative waves, resembling in amplitude and latency those produced by the cortical application of strychnine or curare. 4. This effect differed from that produced by strychnine or curare in that after washing off the toxin the abnormal responses persisted for as long as the experiment continued (8-9 hours). PMID:5425281

  3. Immunological cross-reactivity and neutralization of the principal toxins of Naja sumatrana and related cobra venoms by a Thai polyvalent antivenom (Neuro Polyvalent Snake Antivenom).

    PubMed

    Leong, Poh Kuan; Fung, Shin Yee; Tan, Choo Hock; Sim, Si Mui; Tan, Nget Hong

    2015-09-01

    The low potency of cobra antivenom has been an area of concern in immunotherapy for cobra envenomation. This study sought to investigate factors limiting the neutralizing potency of cobra antivenom, using a murine model. We examined the immunological reactivity and neutralizing potency of a Thai polyvalent antivenom against the principal toxins of Naja sumatrana (Equatorial spitting cobra) venom and two related Asiatic cobra venom α-neurotoxins. The antivenom possesses moderate neutralizing potency against phospholipases A2 (P, potency of 0.98mg/mL) and moderately weak neutralizing potency against long-chain α-neurotoxins (0.26-0.42mg/mL) but was only weakly effective in neutralizing the short-chain α-neurotoxins and cardiotoxins (0.05-0.08mg/mL). The poor neutralizing potency of the antivenom on the low molecular mass short-chain neurotoxins and cardiotoxins is presumably the main limiting factor of the efficacy of the cobra antivenom. Our results also showed that phospholipase A2, which exhibited the highest ELISA reactivity and avidity, was most effectively neutralized, whereas N. sumatrana short-chain neurotoxin, which exhibited the lowest ELISA reactivity and avidity, was least effectively neutralized by the antivenom. These observations suggest that low immunoreactivity (low ELISA reactivity and avidity) is one of the reasons for poor neutralization of the cobra venom low molecular mass toxins. Nevertheless, the overall results show that there is a lack of congruence between the immunological reactivity of the toxins toward antivenom and the effectiveness of toxin neutralization by the antivenom, indicating that there are other factors that also contribute to the weak neutralization capacity of the antivenom. Several suggestions have been put forward to overcome the low efficacy of the cobra antivenom. The use of a 'proper-mix' formulation of cobra venoms as immunogen, whereby the immunogen mixture used for hyperimmunization contains a mix of various types

  4. Effects of topical heparin, antivenom, tetracycline and dexamethasone treatment in corneal injury resulting from the venom of the black spitting cobra (Naja sumatrana), in a rabbit model.

    PubMed

    Cham, Gregory; Pan, James Chuan-Hsin; Lim, Francis; Earnest, Arul; Gopalakrishnakone, P

    2006-01-01

    The Naja sumatrana cobra can spit venom in defense and may result in permanent blindness. The study sought to determine the efficacy of topical heparin, Haffkine antivenom, tetracycline and dexamethasone. Male New Zealand White Rabbits were used. Pooled venom was frozen at -30 degrees C. 0.05 mL of 20 times dilute venom was introduced into the conjunctiva, in groups of three rabbits randomly. Heparin at 5000 IU/mL, Haffkine antivenom or saline control was administered repeatedly on each rabbit's eye over 158 minutes, after a specified delay. In other groups, 1% tetracycline, 0.1% dexamethasone or a placebo ointment was applied and repeated at 24 and 48 hours. All the rabbits were assessed after 24, 48, 72 hours, one and two weeks by an ophthalmologist blinded to the treatment arms. Following ocular envenomation, there was immediate blepharospasm, lacrimal secretions, redness and chemosis; more intense in the normal saline group. The Roper-Hall grades improved, corneas re-epithelialized and inflammation quietened in the heparin and antivenom-treated rabbit eyes compared to controls. Scarring appeared from the first week, but ameliorated in the heparin and antivenom groups. Heparin treatment remained efficacious up to four minutes delay. The tetracycline, dexamethasone and placebo groups had worsening Roper-Hall trends, greater corneal epithelial loss, inflammation and scarring. Combined heparin-tetracycline therapy was as efficacious with heparin alone. Topical heparin or antivenom therapy significantly improved overall outcomes in rabbit corneas exposed to Naja sumatrana venom, compared to tetracycline, dexamethasone and controls. Heparin treatment remains efficacious up to 4 minutes delay.

  5. Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats.

    PubMed

    Abdel Moneim, Ahmed E; Ortiz, Francisco; Leonardo-Mendonça, Roberto C; Vergano-Villodres, Roberto; Guerrero-Martínez, Jose Antonio; López, Luis C; Acuña-Castroviejo, Darío; Escames, Germaine

    2015-03-01

    Naja haje envenomation is one of the leading causes of death due to snakebite. Antiserum therapy sometimes fails to provide enough protection against venom toxicity. In this study, we investigated the protective effects of melatonin against N. haje venom in rats. The animals were injected with venom (0.25mg/kg) and/or melatonin (10mg/kg) and compared with vehicle-treated rats. There was oxidative/nitrosative damage and apoptosis in the liver, heart, and kidneys of venom-injected rats. Melatonin counteracted the increased lipoperoxidation and nitric oxide, prevented decreased glutathione peroxidase and reductase activity, reduced the glutathione disulfide/glutathione (GSSG/GSH) ratio, and maintained the GSH pool. Furthermore, melatonin administration was associated with a reduction of apoptosis, which was increased in venom-injected rats. Overall, these results suggest that melatonin mitigates oxidative/nitrosative stress in venom-induced cardio-hepato-renal injury in rats. Our results suggest that melatonin treatment may ameliorate some of the effects of N. haje envenomation. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, Clinical Features of Envenoming and Management of 70 Identified Cases

    PubMed Central

    Faiz, M. A.; Ahsan, M. F.; Ghose, A.; Rahman, M. R.; Amin, R.; Hossain, M.; Tareq, M. N. U.; Jalil, M. A.; Kuch, U.; Theakston, R. D. G.; Warrell, D. A.; Harris, J. B.

    2017-01-01

    We describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May–July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities. PMID:28138054

  7. The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

    PubMed

    Yap, Michelle Khai Khun; Tan, Nget Hong; Sim, Si Mui; Fung, Shin Yee; Tan, Choo Hock

    2015-10-01

    The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

  8. Proteomic characterization of two snake venoms: Naja naja atra and Agkistrodon halys

    PubMed Central

    Li, Shuting; Wang, Jingqiang; Zhang, Xumin; Ren, Yan; Wang, Ning; Zhao, Kang; Chen, Xishu; Zhao, Caifeng; Li, Xiaolei; Shao, Jianmin; Yin, Jianning; West, Matthew B.; Xu, Ningzhi; Liu, Siqi

    2004-01-01

    Snake venom is a complex mixture of proteins and peptides, and a number of studies have described the biological properties of several venomous proteins. Nevertheless, a complete proteomic profile of venom from any of the many species of snake is not available. Proteomics now makes it possible to globally identify proteins from a complex mixture. To assess the venom proteomic profiles from Naja naja atra and Agkistrodon halys, snakes common to southern China, we used a combination strategy, which included the following four different approaches: (i) shotgun digestion plus HPLC with ion-trap tandem MS, (ii) one-dimensional SDS/PAGE plus HPLC with tandem MS, (iii) gel filtration plus HPLC with tandem MS and (iv) gel filtration and 2DE (two-dimensional gel electrophoresis) plus MALDI–TOF (matrix-assisted laser desorption ionization–time-of-flight) MS. In the present paper, we report the novel identification of 124 and 74 proteins and peptides in cobra and viper venom respectively. Functional analysis based upon toxin categories reveals that, as expected, cobra venom has a high abundance of cardio- and neurotoxins, whereas viper venom contains a significant amount of haemotoxins and metalloproteinases. Although approx. 80% of gel spots from 2DE displayed high-quality MALDI-TOF-MS spectra, only 50% of these spots were confirmed to be venom proteins, which is more than likely to be a result of incomplete protein databases. Interestingly, these data suggest that post-translational modification may be a significant characteristic of venomous proteins. PMID:15285721

  9. Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

    PubMed Central

    Chanhome, Lawan; Tan, Nget Hong

    2017-01-01

    Background The monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology. Methods The transcriptomes were sequenced on the Illumina HiSeq platform, assembled and followed by transcript clustering and annotations for gene expression and function. Pairwise or multiple sequence alignments were conducted on the toxin genes expressed. Substitution rates were studied for the major toxins co-expressed in NK-M and NK-T. Results and discussion The toxin transcripts showed high redundancy (41–82% of the total mRNA expression) and comprised 23 gene families expressed in NK-M and NK-T, respectively (22 gene families were co-expressed). Among the venom genes, three-finger toxins (3FTxs) predominated in the expression, with multiple sequences noted. Comparative analysis and selection study revealed that 3FTxs are genetically conserved between the geographical specimens whilst demonstrating distinct differential expression patterns, implying gene up-regulation for selected principal toxins, or alternatively, enhanced transcript degradation or lack of transcription of certain traits. One of the striking features that elucidates the inter-geographical venom variation is the up-regulation of α-neurotoxins (constitutes ∼80.0% of toxin’s fragments per kilobase of exon model per million mapped reads (FPKM)), particularly the long-chain α-elapitoxin-Nk2a (48.3%) in NK-T but only 1.7% was noted in NK-M. Instead, short neurotoxin isoforms were up-regulated in NK-M (46.4%). Another distinct transcriptional pattern observed is the

  10. Naja atra snakebite in Taiwan.

    PubMed

    Mao, Yan-Chiao; Liu, Po-Yu; Chiang, Liao-Chun; Lai, Chih-Sheng; Lai, Kuo-Lung; Ho, Cheng-Hsuan; Wang, Te-Huo; Yang, Chen-Chang

    2017-08-23

    Naja atra snakebite is uncommon in Taiwan and causes distinct effects on its victims. Although the Taiwan government produces its own specific antivenom, little information on the management of N. atra snakebite is available. We retrospectively evaluated 183 patients admitted to two medical centers. Of these, 45 were identified as definite cases of N. atra snakebite, 86 as suspected cases, and 52 as clinical cases. Demographic data, symptomatology, and management were compared between these case groups. Symptomatology and management were similar in the three groups. Among the 183 patients, 10 (5.5%) were asymptomatic and nine (4.9%) had transient and partial ptosis or body weakness. The principal effects were local tissue swelling and pain in 173 patients (94.5%), followed by clinically suspected wound infection in 148 (80.9%), skin necrosis in 120 (65.6%), necrotizing soft tissue infection in 77 (42.1%), fever in 59 (32.2%), and gastrointestinal effects in 53 (29%). The median total dose of specific antivenom needed to treat N. atra envenoming was 10 vials. In the envenomed patients, debridement was required in 74 patients (42.8%), fasciotomy/fasciectomy in 46 (26.6%), and finger or toe amputation in seven (4%). The first operation was performed at a median of 3.5 days after the bite. Based on these typical manifestations, clinical diagnosis of N. atra snakebites may be feasible and practical. In contrast to other snakes of Elapidae family, N. atra bite did not cause serious neurological effects. Early surgical consultation should be obtained because half of the patients underwent surgery due to infectious complications. Acute compartment syndrome was the surgical indication in rare cases; however, overestimation of the incidence may have occurred. This syndrome should be confirmed by serial intracompartmental pressure monitoring instead of only physical examination, and a sufficient dose of antivenom should be given prior to surgical decompression.

  11. A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom.

    PubMed

    Sintiprungrat, Kitisak; Watcharatanyatip, Kamolwan; Senevirathne, W D S T; Chaisuriya, Papada; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Ratanabanangkoon, Kavi

    2016-01-30

    Naja naja (Indian cobra) from Sri Lanka and India is the WHO Category 1 medically important snakes in both countries. Some antivenom produced against Indian N. naja (NNi) were less effective against Sri Lankan N. naja (NNsl). Proteomes of NNi and NNsl venoms were studied by RP-HPLC, SDS-PAGE and LC/MS/MS. Six protein families were identified in both venoms with the most abundant were the 3 finger toxins (3FTs) where cytotoxins (CTX) subtype predominated, followed by phospholipase A2, cysteine-rich venom protein, snake venom metalloproteases, venom growth factors, and protease inhibitors. Qualitative and quantitative differences in the venomics profiles were observed. Some proteins were isolated from either NNi or NNsl venom. Postsynaptic neurotoxins (NTX) were identified for the first time in NNsl venom. Thus, there are geographic intra-specific variations of venom composition of the two N. naja. The relative abundance of CTX and NTX explained well the clinical manifestations of these venoms. Antivenomics study of an Indian antivenom (Vins) showed the antibodies effectively bound all venom toxins from both snakes but more avidly to the Indian venom proteins. The lower antibody affinity towards the 'heterologous' venom was the likely cause of poor efficacy of the Indian antivenom used to treat NNsl envenoming.

  12. Delineating residues for haemolytic activities of snake venom cardiotoxin 1 from Naja naja as probed by molecular dynamics simulations and in vitro validations.

    PubMed

    Gorai, Biswajit; Sivaraman, Thirunavukkarasu

    2017-02-01

    Cardiotoxins (CTXs) are single polypeptide chain consisting of 59-62 amino acids with four disulfide bridges and globular proteins of simple β-sheet folds. The CTXs are one of principal toxic components causing haemolysis and damaging various cells and belong to three-finger toxin (TFT) superfamily of snake venoms. However, there is no natural or synthetic small molecular inhibitor to the protein toxins to date. In the present study, modes of interaction of cardiotoxin 1 (CTX1) from Indian cobra (Naja naja) with heterogeneous erythrocyte membrane (EM) model system have been extensively examined by using all-atom molecular dynamics (MD) simulations in near physiological conditions and comprehensive analyses of the MD data revealed two distinct principal regions ('head groove' and 'loop groove') of the protein toxin for establishing structural interactions with the EM system. Moreover, combined analyses of data from high-throughput virtual screening of NCI small molecular database, in vitro haemolytic assays for top-hits of the chemical compounds against crude venom of Naja naja and as well CTXs purified from the venom and pharmacokinetic examinations on the chemical compounds retarding haemolytic activities of CTXs suggested that Etidronic acid and Zoledronic acid are promising prototypic chemical inhibitors to CTXs of snake venoms.

  13. Purification, partial characterization, crystallization and preliminary X-ray diffraction of a novel cardiotoxin-like basic protein from Naja naja atra (South Anhui) venom

    SciTech Connect

    Rong, Hui; Li, Yan; Lou, Xiao-hua; Zhang, Xio; Gao, Yong-xiang; Teng, Mai-kun Niu, Li-wen

    2007-02-01

    A novel cardiotoxin-like basic protein from Naja naja atra was crystallized and diffraction data were collected to 2.35 Å resolution. A novel cardiotoxin-like basic protein was isolated from the venom of the Chinese cobra (Naja naja atra) from the south of Anhui in China. The protein inhibits the expression of vascular endothelial growth factor and basic fibroblast growth factor in human lung cancer cell line H1299 and induces the haemolysis of rabbit erythrocytes under low-lecithin conditions. After a two-step chromatographic purification, the resultant 7 kDa protein was crystallized by the hanging-drop vapour-diffusion method at room temperature. A complete data set was collected to 2.35 Å resolution using an in-house X-ray diffraction system. The crystal belongs to space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 43.2, c = 147.9 Å. There are two molecules in the crystallographic asymmetric unit.

  14. Two-dimensional 1H-NMR study of the spatial structure of neurotoxin II from Naja naja oxiana.

    PubMed

    Golovanov, A P; Lomize, A L; Arseniev, A S; Utkin, Y N; Tsetlin, V I

    1993-05-01

    The spatial structure of neurotoxin II from the venom of the central Asian cobra Naja naja oxiana was determined by two-dimensional 1H-NMR techniques and computational analysis. Nearly complete proton resonance assignments for 61 amino acid residues have been made using two-dimensional (2D) homonuclear total correlated spectroscopy, 2D homonuclear double-quantum-filtered correlated spectroscopy and 2D homonuclear NOE spectroscopy (NOESY) experiments. The cross-peak volumes in NOESY spectra spin-spin coupling constants of vicinal protons NH-C alpha H and C alpha H-C beta H and the observation of slow deuterium exchange of amide protons were used to define local structure and a set of constraints for distance geometry program DIANA. The average root-mean-square deviations are 53 pm for backbone heavy atoms and 118 pm for all heavy atoms of 19 final neurotoxin II conformations. The spatial structure is characterized by a short double-stranded (residues 1-5 and 13-17) and a triple-stranded (residues 22-30, 33-41 and 50-54) antiparallel beta-sheets.

  15. Assessment of the neutralizing potency of antisera raised against native and γ-irradiated Naja nigricollis (black-necked spitting cobra) venom in rabbits, concerning its cardiotoxic effect.

    PubMed

    Abdou, F; Denshary, E E; Shaaban, E; Mohamed, M

    2017-01-01

    The present study was designed to prepare a specific safe antiserum for Naja nigricollis using γ-irradiated (1.5KGy and3KGy) venoms. Rabbits were used for active immunization using irradiated venoms (1.5 and 3 kGy) as a toxoid, mice were used for determination of LD50 post immunization and the rats were used for neutralization of the cardiotoxic effect of venom. Results of the immunodiffusion test indicated that the sera of rabbits raised against non-irradiated, 1.5- and 3-kGy γ-irradiated venom, had the same results of precipitin bands. A significant inhibition of phospholipase A2 activities was obtained when neutralized with native, γ-irradiated (1.5KGy and3KGy) venoms. On the other hand, preincubation of the venom ½ LD50 (0.154 mg/kg i.p.) with each antiserum (non-irradiated or irradiated venom) at 37°C for 1 h in a ratio (1:4) produced a significant reduction in the values of creatine kinase and creatine kinase isoenzyme-MB. However, significant elevation in aspartate aminotransferase level and no change in lactate dehydrogenase level were observed. So the results of this study indicated that the irradiated venom treatment reduces the cardiotoxic effect of venom in immunized immunization animals for preparing vaccines.

  16. Neutralisation of lethality, myotoxicity and toxic enzymes of Naja kaouthia venom by Mimosa pudica root extracts.

    PubMed

    Mahanta, M; Mukherjee, A K

    2001-04-01

    Aqueous and alcoholic extracts of dried roots of Mimosa pudica were tested for their inhibitory activity on lethality, myotoxicity and toxic enzymes of Naja kaouthia venom. The aqueous extract, particularly the normal water extract, displayed a significant inhibitory effect on the lethality, myotoxicity and tested enzyme activities of venom compared with alcoholic extracts. The present finding suggests that aqueous extracts of M. pudica root possess compound(s), which inhibit the activity of cobra venom.

  17. Differential hydrolysis of erythrocyte and mitochondrial membrane phospholipids by two phospholipase A2 isoenzymes (NK-PLA2-I and NK-PLA2-II) from the venom of the Indian monocled cobra Naja kaouthia.

    PubMed

    Doley, Robin; King, Glenn F; Mukherjee, Ashis K

    2004-05-01

    We previously demonstrated that venom from the Indian monocled cobra Naja kaouthia is a rich source of phospholipase A2 enzymes, and we purified and characterized a major PLA2 isoenzyme (NK-PLA2-I) from N. kaouthia venom. In the present study, we report the purification and biochemical characterization of a second PLA2 isoenzyme (NK-PLA2-II) from the same venom. A comparison of the membrane phospholipid hydrolysis patterns by these two PLA2s has revealed that they cause significantly more damage to mitochondrial membranes (NK-PLA2-I > NK-PLA2-II) as compared to erythrocyte membranes due to more efficient binding of the enzymes to mitochondrial membranes. Fatty acid release patterns by these PLA2s from the membrane phospholipid PC-pools indicate that NK-PLA2-I does not discriminate between saturated and unsaturated fatty acids whereas NK-PLA2-II shows a preference for unsaturated fatty acids during the initial phase of attack. The current investigation provides new insight into the molecular arrangement of NK-PLA2-sensitive domains in erythrocyte and mitochondrial membranes and highlights the contribution of polar, but uncharged, amino acids such as serine and cysteine in NK-PLA2 induced membrane damage.

  18. Antibacterial Activity of Isolated Immunodominant Proteins of Naja Naja (Oxiana) Venom

    PubMed Central

    talebi mehrdar, Mahboobeh; madani, Rasool; hajihosseini, Reza; moradi bidhendi, Soheila

    2017-01-01

    The aim of this study is to investigate antibacterial effects of immunodominant proteins isolated from the venom of Naja Naja Oxiana snake against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. The innate immune system is an important line of defense against bacterial diseases. Antibacterial peptides and proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial diseases and the potential of being converted into new therapeutic agents. Identification of immunodominant proteins of the venom of Naja Naja Oxiana snake was performed by SDS-PAGE and western blot analysis. Identified proteins were isolated directly from preparative gel electrophoresis by Electro-elution. In the next step, antibacterial effects of immunodominant proteins were tested against several strains of clinical isolates, including S.aureus, B.subtilis (Gram-positive bacteria) P.aeruginosa and E.coli (Gram-negative bacteria) using broth microdilution and disc-diffusion assays. In order to compare the results of the disc-diffusion assay, antibacterial effects of several antibiotics (Gentamicin, Ampicillin, Penicillin, Amoxicillin and Ciprofloxacin) were also examined using the same conditions. Results showed that immunodominant proteins of (14, and 65kDa) with high immunogenicity were very effective in inhibiting the growth of two Gram-positive bacteria (S.aureus, B.sub) that were tested. However, they were only moderately effective in inhibiting the growth of the two tested Gram-negative bacteria (P.aeruginosa and E.coli). However, immunodominant proteins of 22 kDa and 32kDa with high immunogenicity, showed slight effectiveness in inhibiting the growth of two; the Gram-positive and Gram-negative bacteria that were tested. To the best of our knowledge, these immunodominant proteins are novel antigens for potent antimicrobial effects against two gram-positive bacteria (S.aureus, B.subtilis ) and less

  19. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    PubMed Central

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  20. Pre-clinical assessment of the effectiveness of modified polyvalent antivenom in the neutralization of Naja naja venom toxicity.

    PubMed

    Kadali, Renu; Kadiyala, Gopi; Gurunathan, Jayaraman

    2016-11-01

    The potency of conventional antivenom (AV) conjugated to soy protein nanoparticles (NPs) (C-AV) was compared with the free AV in neutralizing the systemic toxicity of Naja naja venom. The effective dose (ED50 ) of AV and C-AV to neutralize the venom-induced toxicity in mice was found to be 19.89 and 9.50 mg, respectively. The histopathological examination of heart, liver, and kidney indicated that the systemic toxicity induced by the venom was effectively neutralized by lower concentrations of C-AV than compared with AV. In addition, C-AV was found to be more effective in neutralizing the edema forming activity of N. naja venom compared with the AV. Thus, the results of this study indicate that the potency of commercially available AV could be improved by conjugating it to soy protein NPs.

  1. Naja naja karachiensis Envenomation: Biochemical Parameters for Cardiac, Liver, and Renal Damage along with Their Neutralization by Medicinal Plants

    PubMed Central

    Asad, Muhammad Hassham Hassan Bin; Ubaid, Muhammad; Durr-e-Sabih; Sajjad, Ashif; Mehmood, Rubada; Mahmood, Qaisar; Ansari, Muhammad Muzzmil; Karim, Sabiha; Mehmood, Zahid; Hussain, Izhar

    2014-01-01

    Naja naja karachiensis envenomation was found to hit more drastically heart, liver, and kidneys. 400 μg/kg of venom-raised moderate serum levels of ALT (72 ± 4.70 U/L, 0.1 > P > 0.05), AST (157 ± 24.24 U/L, 0.1 > P > 0.05), urea (42 ± 3.08 mg/dL, 0.05 > P > 0.02), creatinine (1.74 ± 0.03 mg/dL, 0.01 > P > 0.001), CK-MB (21 ± 1.5 U/L, 0.05 > P > 0.02), and LDH (2064 ± 15.98 U/L, P < 0.001) were injected in experimental rabbits. However, lethality was enhanced with 800 μg/kg of venom in terms of significant release of ALT (86 ± 5.0 U/L, 0.05 > P > 0.02), AST (251 ± 18.2 U/L, 0.01 > P > 0.001), urea (57.6 ± 3.84 mg/dL, 0.02 > P > 0.01), creatinine (2.1 ± 0.10 mg/dL, 0.02 > P > 0.01), CK-MB (77 ± 11.22 U/L, 0.05 > P > 0.02), and LDH (2562 ± 25.14 U/L, P ≪ 0.001). Among twenty-eight tested medicinal plant extracts, only Stenolobium stans (L.) Seem was found the best antivenom (P > 0.5) compared to the efficacy of standard antidote (ALT = 52.5 ± 3.51 U/L, AST = 69.5 ± 18.55 U/L, urea = 31.5 ± 0.50 mg/dL, creatinine = 1.08 ± 0.02 mg/dL, CK-MB = 09 ± 0.85 U/L, and LDH = 763 ± 6.01 U/L). Other plant extracts were proved less beneficial and partly neutralized the toxicities posed by cobra venom. However, it is essential in future to isolate and characterize bioactive compound(s) from Stenolobium stans (L.) Seem extract to overcome the complications of snake bite. PMID:24877153

  2. Naja naja karachiensis envenomation: biochemical parameters for cardiac, liver, and renal damage along with their neutralization by medicinal plants.

    PubMed

    Asad, Muhammad Hassham Hassan Bin; Murtaza, Ghulam; Ubaid, Muhammad; Durr-e-Sabih; Sajjad, Ashif; Mehmood, Rubada; Mahmood, Qaisar; Ansari, Muhammad Muzzmil; Karim, Sabiha; Mehmood, Zahid; Hussain, Izhar

    2014-01-01

    Naja naja karachiensis envenomation was found to hit more drastically heart, liver, and kidneys. 400 μg/kg of venom-raised moderate serum levels of ALT (72 ± 4.70 U/L, 0.1 > P > 0.05), AST (157 ± 24.24 U/L, 0.1 > P > 0.05), urea (42 ± 3.08 mg/dL, 0.05 > P > 0.02), creatinine (1.74 ± 0.03 mg/dL, 0.01 > P > 0.001), CK-MB (21 ± 1.5 U/L, 0.05 > P > 0.02), and LDH (2064 ± 15.98 U/L, P < 0.001) were injected in experimental rabbits. However, lethality was enhanced with 800 μg/kg of venom in terms of significant release of ALT (86 ± 5.0 U/L, 0.05 > P > 0.02), AST (251 ± 18.2 U/L, 0.01 > P > 0.001), urea (57.6 ± 3.84 mg/dL, 0.02 > P > 0.01), creatinine (2.1 ± 0.10 mg/dL, 0.02 > P > 0.01), CK-MB (77 ± 11.22 U/L, 0.05 > P > 0.02), and LDH (2562 ± 25.14 U/L, P ≪ 0.001). Among twenty-eight tested medicinal plant extracts, only Stenolobium stans (L.) Seem was found the best antivenom (P > 0.5) compared to the efficacy of standard antidote (ALT = 52.5 ± 3.51 U/L, AST = 69.5 ± 18.55 U/L, urea = 31.5 ± 0.50 mg/dL, creatinine = 1.08 ± 0.02 mg/dL, CK-MB = 09 ± 0.85 U/L, and LDH = 763 ± 6.01 U/L). Other plant extracts were proved less beneficial and partly neutralized the toxicities posed by cobra venom. However, it is essential in future to isolate and characterize bioactive compound(s) from Stenolobium stans (L.) Seem extract to overcome the complications of snake bite.

  3. Late Quaternary records of Najas spp. (Najadaceae) from the southwestern Baltic region.

    PubMed

    Bennike, O; Jensen, J B.; Lemke, W

    2001-04-01

    Seeds of the submerged vascular plants Najas marina, Najas minor and Najas flexilis are reported from submarine Holocene deposits from the southwestern part of the Baltic Sea, and we also report on a find of Najas minor from an Eemian deposit in Jutland, which is the first record of this species from the Eemian of Denmark. The common and widespread occurrence of especially the southern extralimital N. minor is indicative of higher than present summer temperatures during the period from 10300 to 8000cal.yearsBP.

  4. Elapid snake venom analyses show the specificity of the peptide composition at the level of genera Naja and Notechis.

    PubMed

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-02-28

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms-that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes.

  5. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    PubMed Central

    Zhu, Kou-Zhu; Liu, Yan-Li; Gu, Jin-Hua; Qin, Zheng-Hong

    2013-01-01

    To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV) in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg), the native NNAV (untreated with heat; 90 μg/kg), and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg) were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA) rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg) significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis. PMID:23634171

  6. Venom ophthalmia from Naja mossambica in KwaZulu Natal, South Africa: a reminder to all that for ocular chemical injury, dilution is the solution.

    PubMed

    Hoffman, Jeremy

    2015-10-01

    Venom ophthalmia caused by venoms of spitting elapids such as the Mozambique Spitting Cobra (Naja mossambica) is seen in regions where people live in close proximity to elapids, such as in the KwaZulu Natal region of South Africa. We report such a case in a 43-year-old woman who presented to Mosvold Hospital, a district hospital in South Africa. Clinical features and best practice management of venom ophthalmia will be discussed.

  7. Biodistribution and kinetic studies of technetium-99m labeled Naja naja karachiensis venom via gamma scintigraphic and SPECT images.

    PubMed

    Bin-Asad, Muhammad Hassham-Hassan; e-Sabih, Durr; Ahmad, Israr; Choudhry, Bashir Ahmad; Murtaza, Ghulam; Hussain, Izhar

    2015-07-01

    Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 µg stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 µg, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), skin (0.45% activity/g), intestines (0.35% activity/g), skeleton muscles (0.3% activity/g), brain (0.14% activity/g) and stomach (0.05% activity/g) are included. After 24 hours of injection, poisoned blood of rabbits was almost cleared from venom. Gamma scintigraphic images (up to 2 hours) along with bio distribution suggest that kidneys are main organs of excretion in rabbits. Elimination started immediately after administration of venom however, possible sites for metabolism of venom are liver and lungs. More accumulation of venom in heart compared to brain suggests its higher affinity (thus possible higher toxicity) to cardiac muscles as compared to brain tissues.

  8. Modulated mechanism of phosphatidylserine on the catalytic activity of Naja naja atra phospholipase A2 and Notechis scutatus scutatus notexin.

    PubMed

    Chiou, Yi-Ling; Lin, Shinne-Ren; Hu, Wan-Ping; Chang, Long-Sen

    2014-12-15

    Phosphatidylserine (PS) externalization is a hallmark for apoptotic death of cells. Previous studies showed that Naja naja atra phospholipase A2 (NnaPLA2) and Notechis scutatus scutatus notexin induced apoptosis of human cancer cells. However, NnaPLA2 and notexin did not markedly disrupt the integrity of cellular membrane as evidenced by membrane permeability of propidium iodide. These findings reflected that the ability of NnaPLA2 and notexin to hydrolyze membrane phospholipids may be affected by PS externalization. To address that question, this study investigated the membrane-interacted mode and catalytic activity of NnaPLA2 and notexin toward outer leaflet (phosphatidylcholine/sphingomyelin/cholesterol, PC/SM/Chol) and inner leaflet (phosphatidylserine/phosphatidylethanolamine/cholesterol, PS/PE/Chol) of plasma membrane-mimicking vesicles. PS incorporation promoted enzymatic activity of NnaPLA2 and notexin on PC and PC/SM vesicles, but suppressed NnaPLA2 and notexin activity on PC/SM/Chol and PE/Chol vesicles. PS incorporation increased the membrane fluidity of PC vesicles but reduced membrane fluidity of PC/SM, PC/SM/Chol and PE/Chol vesicles. PS increased the phospholipid order of all the tested vesicles. Moreover, PS incorporation did not greatly alter the binding affinity of notexin and NnaPLA2 with phospholipid vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that membrane-bound mode of notexin and NnaPLA2 varied with the targeted membrane compositions. The fine structure of catalytic site in NnaPLA2 and notexin in all the tested vesicles showed different changes. Collectively, the present data suggest that membrane-inserted PS modulates PLA2 interfacial activity via its effects on membrane structure and membrane-bound mode of NnaPLA2 and notexin, and membrane compositions determine the effect of PS on PLA2 activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Ophidascaris wangi sp. n. and O. najae (Gedoelst, 1916) (Ascaridida: Ascaridoidea) from snakes in China.

    PubMed

    Li, Liang; Guo, Yan-Ning; Li, Jian; Zhang, Lu-Ping

    2014-12-01

    Ophidascaris wangi sp. n. collected from the king rat snake Elaphe carinata (Günther) (Serpentes: Colubridae) in China is described using both light and scanning electron microscopy. The new species differs from its congeners in the presence of narrow lateral alae originating a short distance posterior to the base of the ventrolateral lips, its relatively long oesophagus (3.57-4.54 mm long, representing 6.6-7.6% of body length), its short spicules (1.89-2.14 mm long, representing 3.9-4.3% of body length), the number and arrangement of caudal papillae (49-57 pairs in total, arranged as follows: 43-51 pairs precloacal, 2 pairs joined paracloacal and 4 pairs postcloacal), the presence of a particular papilliform medioventral, postcloacal ornamentation and the morphology of the eggs and tip of the female tail. In addition, Ophidascaris najae (Gedoelst, 1916), collected from the king cobra Ophiophagus hannah Cantor (Serpentes: Elapidae) in China, is also redescribed. The morphology of the cervical papillae, labial denticles and phasmids of the female is described for the first time.

  10. Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms.

    PubMed

    Jin, Yang; Lu, Qiumin; Zhou, Xingding; Zhu, Shaowen; Li, Rui; Wang, Wanyu; Xiong, Yuliang

    2003-10-01

    Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes.

  11. Phytogeography of Najas gracillima (Hydrocharitaceae) in North America and its cryptic introduction to California.

    PubMed

    Les, Donald H; Peredo, Elena L; Benoit, Lori K; Tippery, Nicholas P; King, Ursula M; Sheldon, Sallie P

    2013-09-01

    The discontinuous North American distribution of Najas gracillima has not been explained satisfactorily. Influences of extirpation, nonindigenous introduction, and postglacial migration on its distribution were evaluated using field, fossil, morphological, and molecular data. Najas is a major waterfowl food, and appropriate conservation measures rely on accurate characterization of populations as indigenous or imperiled. • Seed lengths of N. gracillima from native Korean populations, a nonindigenous Italian population, and North American populations were compared using digital image analysis. DNA sequence analyses from these regions provided nine nrITS genotypes and eight cpDNA haplotypes. • Najas gracillima seeds from Eurasia and California are shorter than those from eastern North America. Nuclear and chloroplast DNA sequences of N. gracillima from Korea and Italy were identical to California material but differed from native eastern North American plants. Eastern North American specimens of N. gracillima at localities above the last glacial maximum boundary were identical or similar genetically to material from the northeastern United States and Atlantic Coastal Plain and Piedmont but divergent from plants of the Interior Highlands-Mississippi Embayment region. • In California, N. gracillima is nonindigenous and introduced from Asia. In eastern North America, populations that colonized deglaciated areas were derived primarily from refugia in the Atlantic Coastal Plain and Piedmont. Genetic data indicate initial postglacial migration to northeastern North America, with subsequent westward dispersal into the Upper Great Lakes. These results differentiate potentially invasive California populations from seriously imperiled indigenous eastern North American populations.

  12. Hierarchical structure and mechanical properties of snake (Naja atra) and turtle (Ocadia sinensis) eggshells.

    PubMed

    Chang, Yin; Chen, Po-Yu

    2016-02-01

    After hundreds of million years of evolution, natural armors have evolved in various organisms, and has manifested in diverse forms such as eggshells, abalone shells, alligator osteoderms, turtle shells, and fish scales. Eggshells serve as multifunctional shields for successful embryogenesis, such as protection, moisture control and thermal regulation. Unlike calcareous avian eggshells which are brittle and hard, reptilians have leathery eggshells that are tough and flexible. Reptilian eggshells can withstand collision damages when laid in holes and dropped onto each other, and reduce abrasion caused by buried sand. In this study, we investigate structure and mechanical properties of eggshells of Taiwan cobra snake (Naja atra) and Chinese striped-neck turtle (Ocadia sinensis). From Acid Fuchsin Orange G (AFOG) staining and ATR-FTIR examination, we found that both eggshells are mainly composed of keratin. The mechanical properties of demineralized snake and turtle eggshells were evaluated by tensile and fracture tests and show distinctly difference. Turtle eggshells are relatively stiff and rigid, while snake eggshells behave as elastomers, which are highly extensible and reversible. The exceptional deformability (110-230% tensile strain) and toughness of snake eggshells are contributed by the wavy and random arrangement of keratin fibers as well as collagen layers. Multi-scale toughening mechanisms of snake eggshells were observed and elucidated, including crack deflection and twisting, fibers reorientation, sliding and bridging, inter-laminar shear effect, as well as the α-β phase transition of keratin. Inspirations from the structural and mechanical designs of reptilian eggshells may lead to the synthesis of tough, extensible, lightweight composites which could be further applied in the flexible devices, packaging and bio-medical fields. Amniotic eggshells serve as multifunctional shields for successful embryogenesis. The avian eggshells have been extensively

  13. Prophylactic effect of Mucuna pruriens Linn (velvet bean) seed extract against experimental Naja sputatrix envenomation: gene expression studies.

    PubMed

    Fung, Shin Yee; Sim, Si Mui; Kandiah; Jeyaseelan; Armugam, Arunmozhiarasi; Aguiyi, John Chinyere; Tan, Nget Hong

    2014-09-01

    Mucuna pruriens is widely used in traditional medicine for treatments of various diseases. In certain region of Nigeria, the seed is used as oral prophylactics for snakebite. Rats pretreated with the aqueous extract from M. pruriens seed (MPE) were protected against the lethal effects of Naja sputatrix (Javan spitting cobra) venom [Tan et al., J Ethnopharmacol, 123 (2009) 356]. The pretreatment also protected against venom-induced histopathological changes in rat heart. To contribute to the understanding of the mechanism of cardio-protective action, the present study examined the effects of MPE-pretreatment on gene expression profile of rat heart as well as effect of MPE-pretreatment on N. sputatrix venom-induced gene expression alterations in rat heart. The gene expression profiles were examined by microarray analysis and verified by real time PCR. The results showed that pretreatment with MPE caused 50 genes in the rat heart substantially up-regulated of which 19 were related to immune responses, 7 were related to energy production and metabolism. The up-regulation of genes related to energy metabolism probably plays a role in maintaining the viability of the heart. Four other genes that were up-regulated (alpha synuclein, natriuretic peptide precursor, calsequestrin and triadin) were involved in the maintenance of homeostasis of the heart or maintaining its viability, thereby contributing to the direct protective action. The results demonstrated that protective effect of MPE pretreatment against snake venom poisoning may involve a direct action on the heart.

  14. Biochemical and biological characterization of Naja kaouthia venom from North-East India and its neutralization by polyvalent antivenom

    PubMed Central

    Das, Diganta; Urs, Nanjaraj; Hiremath, Vilas; Vishwanath, Bannikuppe Sannanaik; Doley, Robin

    2013-01-01

    This study describes biochemical and biological properties of Naja kaouthia (Indian monocled cobra) venom of North-East India. The LD50 of the crude venom was found to be 0.148mg/kg and neurotoxicitic symptoms like paralysis of lower limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed. The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed weak proteolytic and low direct hemolytic activities. It did not exhibit any hemorrhage when injected intradermally to mice. Anticoagulant activity was prominent when recalcification, prothrombin and activated partial thrombinplastin time were tested on platelet poor plasma. Rotem analysis of whole citrated blood in presence of venom showed delay in coagulation time and clot formation time. Fibrinogen of whole citrated blood was depleted by venom when analyzed in Sonoclot. Crude venom at 10µg and after 16hr of incubation was found to degrade α chain of fibrinogen. Neutralization study showed that Indian polyvalent antivenom could neutralize some of the biochemical and biological activities as well as its fibrinogenolytic activity. PMID:24349704

  15. Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja atra) and evolution of toxin genes

    PubMed Central

    2011-01-01

    Background Kraits (genus Bungarus) and cobras (genus Naja) are two representative toxic genera of elapids in the old world. Although they are closely related genera and both of their venoms are very toxic, the compositions of their venoms are very different. To unveil their detailed venoms and their evolutionary patterns, we constructed venom gland cDNA libraries and genomic bacterial artificial chromosome (BAC) libraries for Bungarus multicinctus and Naja atra, respectively. We sequenced about 1500 cDNA clones for each of the venom cDNA libraries and screened BAC libraries of the two snakes by blot analysis using four kinds of toxin probes; i.e., three-finger toxin (3FTx), phospholipase A2 (PLA2), kunitz-type protease inhibitor (Kunitz), and natriuretic peptide (NP). Results In total, 1092 valid expressed sequences tags (ESTs) for B. multicinctus and 1166 ESTs for N. atra were generated. About 70% of these ESTs can be annotated as snake toxin transcripts. 3FTx (64.5%) and β bungarotoxin (25.1%) comprise the main toxin classes in B. multicinctus, while 3FTx (95.8%) is the dominant toxin in N. atra. We also observed several less abundant venom families in B. multicinctus and N. atra, such as PLA2, C-type lectins, and Kunitz. Peculiarly a cluster of NP precursors with tandem NPs was detected in B. multicinctus. A total of 71 positive toxin BAC clones in B. multicinctus and N. atra were identified using four kinds of toxin probes (3FTx, PLA2, Kunitz, and NP), among which 39 3FTx-postive BACs were sequenced to reveal gene structures of 3FTx toxin genes. Conclusions Based on the toxin ESTs and 3FTx gene sequences, the major components of B. multicinctus venom transcriptome are neurotoxins, including long chain alpha neurotoxins (α-ntx) and the recently originated β bungarotoxin, whereas the N. atra venom transcriptome mainly contains 3FTxs with cytotoxicity and neurotoxicity (short chain α-ntx). The data also revealed that tandem duplications contributed the most to

  16. Primary structures of cardiotoxin analogues II and IV from the venom of Naja jaja atra.

    PubMed

    Kaneda, N; Sasaki, T; Hayashi, K

    1977-03-28

    Cardiotoxin analogues II and IV were isolated from the venom of Naja naja atra by gel filtration on Sephadex G-50 followed by CM-cellulose chromatography. The venom contains at least four cardiotoxin analogues that account for about 54% of the weight of the lyophilized crude venom. These four cardiotoxin analogues, named cardiotoxin analogues I, II, III, and IV, show strong cytotoxicity to Yoshida sarcoma cells but the lethal toxicity is one-order less. These toxins contain 60 amino acid residues in a single peptide chain. Cardiotoxin analogue IV differs from cardiotoxin analogue II only by the presence of arginine in place of a leucine residue at position 1. A comparison of the amino acid sequences of these toxins with that of cobrotoxin, a neurotoxin containing 62 amino acid residues obtained from the same snake venom, shows that about 20 amino acid residues, including 8 half cystine residues, are identical, assuming 3 residues deletion and 2 residues insertion in the cardiotoxin molecule.

  17. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2016-03-26

    Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89-6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61-2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity.

  18. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms

    PubMed Central

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89–6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61–2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity. PMID:27023606

  19. Proteomic characterization and comparison of venoms from two elapid snakes (Bungarus multicinctus and Naja atra) from China.

    PubMed

    Shan, Lin-Lin; Gao, Jian-Fang; Zhang, Yan-Xia; Shen, Shan-Shan; He, Ying; Wang, Jin; Ma, Xiao-Mei; Ji, Xiang

    2016-04-14

    Bungarus multicinctus (many-banded krait) and Naja atra (Chinese cobra) are widely distributed and medically important venomous snakes in China; however, their venom proteomic profiles have not been fully compared. Here, we fractionated crude venoms and analyzed them using a combination of proteomic techniques. Three-finger toxins (3-FTx) and phospholipase A2 (PLA2) were most abundant in both species, respectively accounting for 32.6% and 66.4% of total B. multicinctus venom, and 84.3% and 12.2% of total N. atra venom. Venoms from these two species contained one common protein family and six less abundant species-specific protein families. The proteomic profiles of B. multicinctus and N. atra venoms and analysis of toxicological activity in mice suggested that 3-FTx and PLA2 are the major contributors to clinical symptoms caused by envenomation. The venoms differed in enzymatic activity, likely the result of inter-specific variation in the amount of related venom components. Antivenomics assessment revealed that a small number of venom components (3-FTxs and PLA2s in B. multicinctus, and 3-FTxs in N. atra) could not be immunocaptured completely, suggesting that we should pay attention to enhancing the immune response of these components in designing commercial antivenoms for B. multicinctus and N. atra. The proteomic profiles of venoms from two medically important snake species - B. multicinctus and N. atra - have been explored. Quantitative and qualitative differences are evident in both venoms when proteomic profiles and transcriptomic results are compared; this is a reminder that combined approaches are needed to explore the precise composition of snake venom. Two protein families (3-FTx and PLA2) of high abundance in these snake venoms are major players in the biochemical and pharmacological effects of envenomation. Elucidation of the proteomic profiles of these snake venoms is helpful in understanding composition-function relationships and will facilitate the

  20. Spectroscopic investigations on the binding of persimmon tannin to phospholipase A 2 from Chinese cobra ( Naja naja atra)

    NASA Astrophysics Data System (ADS)

    Yang, Jie; Zhong, Li; Zou, Bo; Tian, Yan; Xu, Shu-fen; Yao, Ping; Li, Chun-mei

    2012-01-01

    To understand the anti-venom mechanism of persimmon tannin, the interaction between persimmon tannin (PT) and phospholipase A 2 (PLA 2) under physiological conditions was investigated by fluorescence quenching technique in combination with Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra techniques. The results revealed that gradual fluorescence quenching was observed by titration of PLA 2 (2.0 μM) with increasing concentrations of PT (from 0 to 2.025 μM), and the type of quenching was found to be a static quenching process. Stern-Volmer plots were not linear but had an intersection at CPT ≈ 1.0 μM, indicating that PT binded to more than one class of sites on PLA 2. The binding sites calculated on basis of Scatchard plots were about 2, supporting this result. The enthalpy change (Δ H) and entropy change (Δ S) of the binding sites were -17.44 kJ/mol and 59.90 kJ/mol·, separately, suggesting that hydrophobic interaction played a main role in the binding. In addition, synchronous fluorescence, FT-IR and CD spectra showed that dramatic conformational changes in PLA 2 were induced by its interaction with PT.

  1. Effects of temperature on decomposition of a potential nuisance species: the submerged aquatic macrophyte Egeria najas Planchon (Hydrocharitaceae).

    PubMed

    Carvalho, P; Thomaz, S M; Bini, L M

    2005-02-01

    Decomposition of aquatic plants is influenced by several biotic and abiotic factors. Among them, temperature plays an important role. Despite the increasing number of studies describing the effects of temperature on the decomposition of aquatic macrophytes, little attention has been given to the decay of submerged macrophytes. In this paper, we assessed the effect of temperature on weight loss and chemical composition of detritus of the submerged aquatic macrophyte Egeria najas Planchon (Hydrocharitaceae). Fresh plant material was maintained at 17 degrees C and 27 degrees C, in the dark, in incubation chambers. The overall decay process was best described by a linear model, with rates of 0.014 day(-1) (R2= 94%) and 0.045 day(-1) (R2= 96%) obtained at 17 degrees C and 27 degrees C, respectively. The analysis of covariance (ANCOVA) indicated a significant difference between the decomposition rates at the two temperatures. The rapid breakdown of E. najas detritus, indicated by the decay coefficient, may be explained by its low content of resistant compounds such as cellulose and lignin. The variables analyzed in this study (pH, electrical conductivity, dissolved oxygen in the water and organic matter, total nitrogen and total phosphorus concentration in detritus) showed accentuated responses at 27 degrees C. It is likely that the higher temperature increased microbial activity and, therefore, oxygen consumption in the water, consequently affecting the pH and the rate of ion and nutrient liberation into the aquatic ecosystem. Due to the rapid decomposition of E. najas at high temperatures, a small exportation is expected of this species from its stands to distant regions in tropical reservoirs, where it is considered a potential nuisance species.

  2. Antisnake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis

    PubMed Central

    Hasson, S. S.; Al-Jabri, A. A.; Sallam, T. A.; Al-Balushi, M. S.; Mothana, R. A. A.

    2010-01-01

    The objective of the study is to investigate whether the Hibiscus aethiopicus L. plant has neutralization activity against venoms of two clinically important snakes. The H. aethiopicus was dried and extracted with water. Different assays were performed to evaluate the plant's acute toxicity and its anti-snake venom activities. The results showed that H. aethiopicus extract alone had no effect on the viability of C2C12 muscle cells, but significantly (P < .05) protected muscle cells against the toxic effects of E. ocellatus venom at 55, 150, and 300 μg/mL. The maximum protective effect of the extract was exhibited at 75 μg/mL. The extract significantly (P < .001) inhibited the cytotoxic effects of E. ocellatus venom at 300 μg/mL. All rabbits (n = 10) and guinea pigs (n = 10) were alive after the two weeks of given the lethal dosage 16 g/Kg of the H. aethiopicus extract herbal solution. No abnormal behaviour was observed of both groups of animals. All guinea pigs (n = 3) treated with venoms alone (5 mg/kg) died. However, all guinea pigs (n = 21) treated with venom (5 mg/kg) and the extract (400 to 1000 mg/kg) survived. Guinea pigs (n = 3) treated with Naja n. nigricollis venom alone (2.5 mg/kg) and guinea pigs (n = 21) venom with the extract (400 to 1000 mg/kg) died. The H. aethiopicus completely (100%) blocked the haemorrhagic activity of E. ocellatus in the egg embryo at 3.3 mg/mL of extract. These findings suggest that H. aethiopicus may contain an endogenous inhibitor of venom-induced haemorrhage. PMID:20628507

  3. Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon

    PubMed Central

    Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

    2017-01-01

    This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5′- and 3′-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A2-coralyne-A2 coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs. PMID:28067855

  4. Phytomedical investigation of Najas minor All. in the view of the chemical constituents.

    PubMed

    Topuzovic, Marina D; Radojevic, Ivana D; Dekic, Milan S; Radulovic, Niko S; Vasic, Sava M; Comic, Ljiljana R; Licina, Braho Z

    2015-01-01

    Plants are an abundant natural source of effective antibiotic compounds. Phytomedical investigations of certain plants haven't still been conducted. One of them is Najas minor (N. minor), an aquatic plant with confirmed allelopathy. Research conducted in this study showed the influence of water and ethyl acetate extracts of N. minor on microorganisms, in the view of chemical profiling of volatile constituents and the concentrations of total phenols, flavonoids and tannins. Antimicrobial activity was defined by determining minimum inhibitory and minimum microbicidal concentrations using microdilution method. Influence on bacterial biofilm formation was performed by tissue culture plate method. The total phenolics, flavonoids and condensed tannins were determined by Folin-Ciocalteu, aluminum chloride and butanol-HCl colorimetric methods. Chemical profiling of volatile constituents was investigated by GC and GC-MS. Water extract didn't have antimicrobial activity below 5000 µg/mL. Ethyl acetate extract has shown strong antimicrobial activity on G+ bacteria - Staphylococcus aureus PMFKGB12 and Bacillus subtilis (MIC < 78.13 µg/mL). The best antibiofilm activity was obtained on Escherichia coli ATCC25922 (BIC50 at 719 µg/mL). Water extract had higher yield. Ethyl acetate extract had a significantly greater amount of total phenolics, flavonoids and tannins. As major constituent hexahydrofarnesyl acetone was identified. The ethyl acetate extract effected only G+ bacteria, but the biofilm formation of G-bacteria was suppressed. There was a connection between those in vivo and in vitro effects against pathogenic bacterial biofilm formation. All of this points to a so far unexplored potential of N. minor.

  5. Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

    PubMed

    Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

    2017-01-07

    This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A₂-coralyne-A₂ coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

  6. Phytomedical investigation of Najas minor All. in the view of the chemical constituents

    PubMed Central

    Topuzovic, Marina D.; Radojevic, Ivana D.; Dekic, Milan S.; Radulovic, Niko S.; Vasic, Sava M.; Comic, Ljiljana R.; Licina, Braho Z.

    2015-01-01

    Plants are an abundant natural source of effective antibiotic compounds. Phytomedical investigations of certain plants haven't still been conducted. One of them is Najas minor (N. minor), an aquatic plant with confirmed allelopathy. Research conducted in this study showed the influence of water and ethyl acetate extracts of N. minor on microorganisms, in the view of chemical profiling of volatile constituents and the concentrations of total phenols, flavonoids and tannins. Antimicrobial activity was defined by determining minimum inhibitory and minimum microbicidal concentrations using microdilution method. Influence on bacterial biofilm formation was performed by tissue culture plate method. The total phenolics, flavonoids and condensed tannins were determined by Folin-Ciocalteu, aluminum chloride and butanol-HCl colorimetric methods. Chemical profiling of volatile constituents was investigated by GC and GC-MS. Water extract didn't have antimicrobial activity below 5000 µg/mL. Ethyl acetate extract has shown strong antimicrobial activity on G+ bacteria - Staphylococcus aureus PMFKGB12 and Bacillus subtilis (MIC < 78.13 µg/mL). The best antibiofilm activity was obtained on Escherichia coli ATCC25922 (BIC50 at 719 µg/mL). Water extract had higher yield. Ethyl acetate extract had a significantly greater amount of total phenolics, flavonoids and tannins. As major constituent hexahydrofarnesyl acetone was identified. The ethyl acetate extract effected only G+ bacteria, but the biofilm formation of G-bacteria was suppressed. There was a connection between those in vivo and in vitro effects against pathogenic bacterial biofilm formation. All of this points to a so far unexplored potential of N. minor. PMID:26535038

  7. Through thick and thin: cryptic sympatric speciation in the submersed genus Najas (Hydrocharitaceae).

    PubMed

    Les, Donald H; Peredo, Elena L; King, Ursula M; Benoit, Lori K; Tippery, Nicholas P; Ball, Cassandra J; Shannon, Robynn K

    2015-01-01

    Cryptic sympatric species arise when reproductive isolation is established in sympatry, leading to genetically divergent lineages that are highly similar morphologically or virtually indistinguishable. Although cryptic sympatric species have been reported in various animals, fungi, and protists, there are few compelling examples for plants. This investigation presents a case for cryptic sympatric speciation in Najas flexilis, a widespread aquatic plant, which extends throughout northern North America and Eurasia. The taxon is noted for its variable seed morphology, which earlier research associated with cytotypes; i.e., diploids were characterized by thicker seeds and tetraploids by thinner seeds. However, cytotypes are not patterned geographically with diploid and tetraploid plants often found in close proximity within the same lake. Using digital image and DNA sequence analyses, we found that diploids and tetraploids are well-isolated and remain genetically distinct throughout their sympatric range, where sterile hybrids occur frequently. Incorporation of sequence data from the single-copy nuclear phytoene desaturase locus revealed further that the tetraploids are allopolyploid derivatives of N. flexilis and N. guadalupensis, the latter a closely related species with an overlapping distribution. We conclude that the taxon widely known as N. flexilis actually comprises two cryptic, sibling species, which diverged in sympatry by interspecific hybridization and subsequent chromosomal isolation. By comparing seed morphology of type specimens, we associated the names N. flexilis and N. canadensis to the diploids and tetraploids respectively. Additionally, the narrowly restricted taxon known formerly as N. muenscheri is shown via morphological and genetic evidence to be synonymous with N. canadensis. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Biological activities of Peristrophe bivalvis extracts: promising potential for anti-snake venoms against Naja kaouthia and Trimeresurus albolabris venoms.

    PubMed

    Phaopongthai, Jatuporn; Noiphrom, Jureeporn; Phaopongthai, Supat; Pakmanee, Narumol; Sichaem, Jirapast

    2016-01-01

    This study evaluates the in vitro anti-snake venom potential of Peristrophe bivalvis (PB) extracts against Naja kaouthia (NK) and Trimeresurus albolabris (TA) venoms, including inhibition of cytotoxic effects and enzymatic activities, and the binding-precipitation of extracts and venom proteins analysis. In addition, the antioxidant, cytotoxic and in vivo acute oral toxic activities of PB extracts are also reported. The in vitro cytotoxic and enzymatic analysis reveals that the ethanol extracts of stems and leaves of PB showed good anti-snake venom activity against NK and TA venoms. In addition, the antioxidant result indicated that only the ethanol extract of leaves exhibited weak DPPH radical-scavenging activity. The ethanol whole-plant extract of PB also showed no cytotoxicity against four cell lines. Moreover, the in vivo acute oral toxicity result of the ethanol whole-plant extract showed that all treated rats did not exhibit abnormal toxic signs or deaths.

  9. Detection and neutralization of cobra venom using rabbit antiserum in experimental envenomated mice.

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Saravanan, A; Vimal, S; Madan, N; Majeed, S Abdul; Raj, N Sundar; Hameed, A S Sahul; Babu, V Sarath

    2014-07-01

    A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs, liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h intervals up to 24 h). Whole venom antiserum or individual venom protein antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by Western blotting and ELISA, and antibody titer was also assayed by ELISA. Antiserum raised against cobra venom in rabbit significantly neutralized the toxicity of venom-injected mice at different time intervals after treatment. The assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate, and the venom was detected up to 24 h after venom injection. Venom was detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart, and lungs. Development of a simple, rapid, and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed. © The Author(s) 2014.

  10. Daboia russellii and Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br.

    PubMed

    Chatterjee, Ipshita; Chakravarty, A K; Gomes, A

    2006-06-15

    The present study reports the isolation and purification of lupeol acetate from the methanolic root extract of Indian medicinal plant Hemidesmus indicus (L.) R.Br. (family: Asclepiadaceae) which could neutralize venom induced action of Daboia russellii and Naja kaouthia on experimental animals. Lupeol acetate could significantly neutralize lethality, haemorrhage, defibrinogenation, edema, PLA(2) activity induced by Daboia russellii venom. It also neutralized Naja kaouthia venom induced lethality, cardiotoxicity, neurotoxicity and respiratory changes in experimental animals. Lupeol acetate potentiated the protection by snake venom antiserum action against Daboia russellii venom induced lethality in male albino mice. Venom induced changes in lipid peroxidation and super oxide dismutase activity was antagonized by lupeol acetate. Snake venom neutralization by lupeol acetate and its possible mechanism of action has been discussed.

  11. Effect of geographical variation of Echis ocellatus, Naja nigricollis and Bitis arietans venoms on their neutralization by homologous and heterologous antivenoms.

    PubMed

    Sánchez, Andrés; Coto, Jorge; Segura, Álvaro; Vargas, Mariángela; Solano, Gabriela; Herrera, María; Villalta, Mauren; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

    2015-12-15

    Two antivenoms prepared by using Echis ocellatus, Bitis arietans and Naja nigricollis venoms from different locations in sub-Saharan Africa were compared for their neutralizing ability. Both antivenoms were similarly effective in the neutralization of the venoms of the three species from different locations. However in the case of E. ocellatus venom, antivenom prepared using venom from Nigerian specimens was more effective than antivenom prepared with venom from Cameroon specimens in the neutralization of coagulant activity.

  12. Arsenic accumulation and tolerance in rootless macrophyte Najas indica are mediated through antioxidants, amino acids and phytochelatins.

    PubMed

    Tripathi, Rudra Deo; Singh, Ragini; Tripathi, Preeti; Dwivedi, Sanjay; Chauhan, Reshu; Adhikari, Bijan; Trivedi, Prabodh Kumar

    2014-12-01

    Arsenic (As) accumulation and tolerance response of a submerged rootless macrophyte Najas indica were evaluated during arsenate (As(V); 10-250 μM) and arsenite (As(III); 1-50 μM) exposure. Higher As accumulation at As(III) exposure and more tolerance upon As(V) exposure resulted in more toxicity during As(III) stress than As(V), which was evident through measurement of growth parameters and oxidative stress related parameters viz., lipid peroxidation (MDA content), electrical conductivity (EC) and hydrogen peroxide (H2O2) levels. Antioxidant enzymes and various amino acids were more prominent during moderate exposure of As(V), suggesting their possible role in As tolerance and detoxification. Various non-enzymatic antioxidant metabolites viz., ascorbic acid (ASC), glutathione (GSH), non-protein thiols (NPTs) and phytochelatins (PCs) biosynthesis involving phytochelatin synthase (PCS) activity increased more significantly during As(III) stress. However, PCs content seems inadequate in response to As accumulation leading to lower PC-SH:As molar ratio and higher As phytotoxicity during As(III) stress. N. indica may prove useful plant species for phytoremediation purpose in moderately As contaminated water bodies due to high As accumulation and tolerance potential. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The ghost of a recent invasion in the reduced feeding rates of spitting cobras during the dry season in a rainforest region of tropical Africa?

    NASA Astrophysics Data System (ADS)

    Luiselli, Luca

    2001-12-01

    Two species of cobras ( Naja melanoleuca and Naja nigricollis) are known to occur in south eastern Nigeria, where much of the pristine rainforest surface has been felled in the last thirty years, and where the actual landscape is generally constituted by a mosaic of farmlands, plantations, suburban areas, with a few remnant forest fragments. In this region, Naja nigricollis is currently extending its range, especially by exploiting recently deforested areas. Based on the known general distribution range of this species and on the available literature data, it appears that Naja nigricollis has been colonizing the forested region of south eastern Nigeria, starting from the relatively arid savannas of central Nigeria, where this species aestivates during the driest months. In the forest region, however, snakes do not need to aestivate during the dry season. Nevertheless, whereas Naja melanoleuca has a foraging activity extended all-the-year round, Naja nigricollis reduces feeding rates during the dry months, although it does not suspend above-ground activity in these months. I suggest that rainforest spitting cobras suspend feeding during the dry months because their behaviour is just a 'ghost' of their recent past, when they were 'normal' spitting cobras of dry savana regions, which were thus constrained to aestivate during the dry season as it is the rule in this species in central and northern Nigeria. The 'gost-of-the-past hypothesis' seems to fit well with the 'invading' presence of Naja nigricollis in Nigerian areas where they were reported as rare or, even, absent, up to a few decades ago. Other hypotheses are discussed, and rejected.

  14. The Plastid Genome of Najas flexilis: Adaptation to Submersed Environments Is Accompanied by the Complete Loss of the NDH Complex in an Aquatic Angiosperm

    PubMed Central

    Peredo, Elena L.; King, Ursula M.; Les, Donald H.

    2013-01-01

    The re-colonization of aquatic habitats by angiosperms has presented a difficult challenge to plants whose long evolutionary history primarily reflects adaptations to terrestrial conditions. Many aquatics must complete vital stages of their life cycle on the water surface by means of floating or emergent leaves and flowers. Only a few species, mainly within the order Alismatales, are able to complete all aspects of their life cycle including pollination, entirely underwater. Water-pollinated Alismatales include seagrasses and water nymphs (Najas), the latter being the only freshwater genus in the family Hydrocharitaceae with subsurface water-pollination. We have determined the complete nucleotide sequence of the plastid genome of Najas flexilis. The plastid genome of N. flexilis is a circular AT-rich DNA molecule of 156 kb, which displays a quadripartite structure with two inverted repeats (IR) separating the large single copy (LSC) from the small single copy (SSC) regions. In N. flexilis, as in other Alismatales, the rps19 and trnH genes are localized in the LSC region instead of within the IR regions as in other monocots. However, the N. flexilis plastid genome presents some anomalous modifications. The size of the SSC region is only one third of that reported for closely related species. The number of genes in the plastid is considerably less. Both features are due to loss of the eleven ndh genes in the Najas flexilis plastid. In angiosperms, the absence of ndh genes has been related mainly to the loss of photosynthetic function in parasitic plants. The ndh genes encode the NAD(P)H dehydrogenase complex, believed essential in terrestrial environments, where it increases photosynthetic efficiency in variable light intensities. The modified structure of the N. flexilis plastid genome suggests that adaptation to submersed environments, where light is scarce, has involved the loss of the NDH complex in at least some photosynthetic angiosperms. PMID:23861923

  15. The plastid genome of Najas flexilis: adaptation to submersed environments is accompanied by the complete loss of the NDH complex in an aquatic angiosperm.

    PubMed

    Peredo, Elena L; King, Ursula M; Les, Donald H

    2013-01-01

    The re-colonization of aquatic habitats by angiosperms has presented a difficult challenge to plants whose long evolutionary history primarily reflects adaptations to terrestrial conditions. Many aquatics must complete vital stages of their life cycle on the water surface by means of floating or emergent leaves and flowers. Only a few species, mainly within the order Alismatales, are able to complete all aspects of their life cycle including pollination, entirely underwater. Water-pollinated Alismatales include seagrasses and water nymphs (Najas), the latter being the only freshwater genus in the family Hydrocharitaceae with subsurface water-pollination. We have determined the complete nucleotide sequence of the plastid genome of Najas flexilis. The plastid genome of N. flexilis is a circular AT-rich DNA molecule of 156 kb, which displays a quadripartite structure with two inverted repeats (IR) separating the large single copy (LSC) from the small single copy (SSC) regions. In N. flexilis, as in other Alismatales, the rps19 and trnH genes are localized in the LSC region instead of within the IR regions as in other monocots. However, the N. flexilis plastid genome presents some anomalous modifications. The size of the SSC region is only one third of that reported for closely related species. The number of genes in the plastid is considerably less. Both features are due to loss of the eleven ndh genes in the Najas flexilis plastid. In angiosperms, the absence of ndh genes has been related mainly to the loss of photosynthetic function in parasitic plants. The ndh genes encode the NAD(P)H dehydrogenase complex, believed essential in terrestrial environments, where it increases photosynthetic efficiency in variable light intensities. The modified structure of the N. flexilis plastid genome suggests that adaptation to submersed environments, where light is scarce, has involved the loss of the NDH complex in at least some photosynthetic angiosperms.

  16. Comparative insights using the molecular homology model of BDNF (Brain derived neurotrophic factor) of Varanus komodoensis and the known NGF (Nerve growth factor) structure of Naja atra

    PubMed Central

    Verma, Ankit; Sharma, Dhirendra Kumar; Sarma, Rituparna; Chetia, Hasnahana; Saikia, Juri

    2013-01-01

    BDNF (Brain derived neurotrophic factor) is a secretion protein and a member of the neurotrophin family of growth factors. Structural and functional characterization of BDNF Varanus komodoensis is of interest while its structure remains unknown. Thus, a homology molecular model of BDNF was constructed for gleaning possible structural insights. The model was compared with the structure of the homologous NGF (Nerve growth factor, another member of neuro-trophin family) from Naja atra. Comparative structural analysis of the models showed structural similarities with their predicted cavities for the interpretation of potential functional analogy. PMID:24023416

  17. Comparative insights using the molecular homology model of BDNF (Brain derived neurotrophic factor) of Varanus komodoensis and the known NGF (Nerve growth factor) structure of Naja atra.

    PubMed

    Verma, Ankit; Sharma, Dhirendra Kumar; Sarma, Rituparna; Chetia, Hasnahana; Saikia, Juri

    2013-01-01

    BDNF (Brain derived neurotrophic factor) is a secretion protein and a member of the neurotrophin family of growth factors. Structural and functional characterization of BDNF Varanus komodoensis is of interest while its structure remains unknown. Thus, a homology molecular model of BDNF was constructed for gleaning possible structural insights. The model was compared with the structure of the homologous NGF (Nerve growth factor, another member of neuro-trophin family) from Naja atra. Comparative structural analysis of the models showed structural similarities with their predicted cavities for the interpretation of potential functional analogy.

  18. Tourniquet Application after Cobra Bite: Delay in the Onset of Neurotoxicity and the Dangers of Sudden Release

    DTIC Science & Technology

    1988-01-01

    Poisonous snakebite treatment the monocellate Thai cobra (Naja kaouthia). in the United States. JAMA, 240: 654-656. Am A Trop. Med Hui.. 35: 173-181...198 1. First. aid treatment of poisonous snake- 3. Virava, C., Veeravat, U., Warill, M. J., Theak- bie Are currently recommended procedures sam, R...respiratory paralysis caused by cobra Luzon Island, Philippines, between March 1984 venom is the leading cause of snakebite death in and March 1987

  19. Cobra venom contains a pool of cysteine-rich secretory proteins.

    PubMed

    Osipov, Alexey V; Levashov, Mikhail Yu; Tsetlin, Victor I; Utkin, Yuri N

    2005-03-04

    A large family of cysteine-rich secretory proteins (CRISPs) includes proteins of different origin, the function of the majority of CRISPs being unknown. For CRISPs isolated from snake venom, two types of activities were found: two proteins blocked cyclic nucleotide-gated ion channels, several others blocked potassium-stimulated smooth muscle contraction. Thus, snake CRISPs represent potentially valuable tools for studies of ion channels, which makes promising a search for new CRISPs. Here we report on the isolation of several novel CRISPs from the venoms of Asian cobra Naja kaouthia and African cobra Naja haje using a combination of different types of liquid chromatography. Four CRISP variants were identified in N. kaouthia venom and three proteins, one of them acidic, were found in N. haje venom. Acidic CRISP was found in a reptilian venom for the first time. Our data suggest that each cobra venom contains a pool of different CRISPs.

  20. Reinterpretation of luminiscence properties of neurotoxins from the venom of Middle-Asian corba Naja oxiana eichw.

    PubMed

    Bukolova-Orlova, T G; Permyakov, E A; Burstein, E A; Yukelson, L Y

    1976-08-09

    A new interpretation of previous work (Bukolova-Orlova, T. G., Burstein, E.A. and Yukelson, L. Ya (1974) Biochim. Biophys. Acta 342, 272-280) and some new data on the luminescence of neurotoxins I and II from Naja oxiana venom is given, based on the newer data on their complete amino acid sequences. Very effective excitation energy exchange exists between Trp-27 and Trp-33 in neurotoxin I and between Trp-27 and Trp-28 in neurotoxin II, Which results in the tryptophanyl fluorescence spectra of each of the proteins seeming to be monocomponent ones. The lowered fluorescence quantium yield value, the shortened phosphorescence lifetime (80% of the emission has tau p less than 0.5 s, 20% has tau p = 4.8 s, comparing with usual tau p = 5.5-5.9 s) and decreased phosphorescence to fluorescence ratio (0.042, as compared to the usual 0.4-0.7) for neurotoxin I suggest that the indole chromophore of Trp-27 and/or Trp-33 are in contact with heavy sulfur atoms of disulfide, most probably of Cys(28)-Cys(32). Tryptophanyls in neurotoxin II are exposed to the solvent, however their accessibility in relation to that of the free tryptophan to the negatively charged quencher I- (0.455) is much higher than that for the positively charged Cs+ (0.08), which is probably due to the proximity of cationic Lys-25, Lys-26 and His-31. The difference of accessibility to the negative and positive quenchers is even more pronounced in the case of the neurotoxin I (1.04 and 0 +/- 0.02, respectively), though in its chromophore vicinity along the primary structure there is only one cationic group, Lys-25. This fact together with the analysis of the amino acid sequence, suggest that the space folding of this polypeptide results in the close proximity of Trp-27 and/or Trp-33 with the C-terminal peptide segment 67-73, which contains four cationic groups (His-67, Lys-69, Lys-71 and Arg-72).

  1. Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells.

    PubMed

    Chen, Ying-Jung; Wang, Jeh-Jeng; Chang, Long-Sen

    2011-11-01

    1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells.

  2. Cross neutralisation of Southeast Asian cobra and krait venoms by Indian polyvalent antivenoms.

    PubMed

    Leong, Poh Kuan; Tan, Nget Hong; Fung, Shin Yee; Sim, Si Mui

    2012-12-01

    Cross neutralisation of venoms by antivenom raised against closely-related species has been well documented. The spectrum of paraspecific protection of antivenom raised against Asiatic Naja and Bungarus (krait) venoms, however, has not been fully investigated. In this study, we examined the cross neutralisation of venoms from common Southeast Asian cobras and kraits by two widely used polyvalent antivenoms produced in India: Vins Polyvalent Antivenom (VPAV) and Bharat Polyvalent Antivenom (BPAV), using both in vitro and in vivo mouse protection assays. BPAV was only moderately effective against venoms of N. kaouthia (Thailand) and N. sumatrana, and either very weakly effective or totally ineffective against the other cobra and krait venoms. VPAV, on the other hand, neutralised effectively all the Southeast Asian Naja venoms tested, as well as N. naja, B. candidus and Ophiophagus hannah venoms, but the potency ranges from effective to weakly effective. In an in vivo rodent model, VPAV also neutralised the lethality of venoms from Asiatic Naja and B. candidus. In anesthetised rat studies, both antivenoms effectively protected against the N. kaouthia venom-induced cardio-respiratory depressant and neuromuscular blocking effects. Overall, our results suggest that VPAV could be used as alternative antivenom for the treatment of elapid envenomation in Southeast Asian regions including Malaysia, Thailand and certain regions of Indonesia. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  3. Molecular basis of cardiotoxicity upon cobra envenomation.

    PubMed

    Cher, C D N; Armugam, A; Zhu, Y Z; Jeyaseelan, K

    2005-01-01

    Various clinical manifestations leading to death have been documented in most cases of bites caused by venomous snakes. Cobra envenomation is an extremely variable process and known to cause profound neurological abnormalities. The complexity of cobra venom can induce multiple-organ failure, leading to death in case of severe envenomation. Intramuscular administration of Malayan spitting cobra (Naja sputatrix) crude venom at 1 microg/g dose caused death in mice in approximately 3 h. Analysis of gene expression profiles in the heart, brain, kidney, liver and lung revealed 203 genes whose expression was altered by at least 3-fold in response to venom treatment. Of these, 50% were differentially expressed in the heart and included genes involved in inflammation, apoptosis, ion transport and energy metabolism. Electrocardiogram recordings and serum troponin T measurements indicated declining cardiac function and myocardial damage. This not only sheds light on the cardiotoxicity of cobra venom but also reveals the molecular networks affected during envenomation.

  4. Molecular cloning and characterization of a complement-depleting factor from king cobra, Ophiophagus hannah.

    PubMed

    Zeng, Lin; Sun, Qian-Yun; Jin, Yang; Zhang, Yong; Lee, Wen-Hui; Zhang, Yun

    2012-09-01

    Cobra venom factor (CVF) is an anti-complement factor existing in cobra venom. CVF proteins have been purified from the venoms of Naja haje, Naja siamensis, Naja atra, Naja kaouthia, Naja naja, Naja melanoleuca and Austrelaps superbus, but only three full-length cDNA sequences of CVF are available. In the present work, a cobra venom factor termed OVF was purified from the crude venom of Ophiophagus hannah by successive gel filtration, ion-exchange and heparin affinity chromatography steps. The purified OVF was homogenous on the SDS-PAGE gel with an apparent molecular weight of 140 kDa under non-reducing conditions. Under reducing conditions, OVF was divided into three bands with apparent molecular weight of 72 kDa (α chain), 45 kDa (β chain) and 32 kDa (γ chain), respectively. OVF consumed complement components with anti-complement activity of 154 units per mg. By using Reverse transcription-PCR and 5'-RACE assay, the open reading frame of OVF was obtained. MALDI-TOF and protein sequencing assays confirmed the cloned cDNA coding for OVF protein. The cDNA sequence of OVF is conservative when aligned with that of other CVFs. Phylogenetic analysis revealed OVF is closer to CVF from N. kaouthia than to AVF-1 and AVF-2 from A. superbus. Our results demonstrated that OVF has its unique features as following: 1) The N-terminal amino acid sequence of OVF γ chain is different from that of other known CVFs, suggesting that the OVF γ chain might be further processed; 2) Unlike N. kaouthia CVF and A. superbus AVF-1, which have potential N-linked glycosylation sites located in both α and β chain, OVF only has N-linked glycosylation site in its α chain as revealed by Schiff's reagent staining and protein sequence analysis; 3) In addition to the 27 well conserved cysteine residues in all known CVFs, OVF have an additional cysteine residue in its γ chain. Understanding the importance of above mentioned specific characteristics might provide useful information on structure

  5. Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel.

    PubMed

    Wang, Jing; Shen, Bing; Guo, Min; Lou, Xiaohua; Duan, Yuanyuan; Cheng, Xin Ping; Teng, Maikun; Niu, Liwen; Liu, Qun; Huang, Qingqiu; Hao, Quan

    2005-08-02

    Cysteine-rich secretory proteins (CRISPs) are widespread in snake venoms. Some members of these CRISPs recently have been found to block L-type Ca(2+) channels or cyclic nucleotide-gated ion (CNG) channels. Here, natrin purified from Naja atra venom, a member of the CRISP family, can induce a further contractile response in the endothelium-denuded thoracic aorta of mouse which has been contracted by a high-K(+) solution. Further experiments show it can block the high-conductance calcium-activated potassium (BK(Ca)) channel in a concentration-dependent manner with an IC(50) of 34.4 nM and a Hill coefficient of 1.02, which suggests that only a single natrin molecule is required to bind an ion channel to block BK(Ca) current. The crystal structure of natrin displaying two domains in tandem shows its cysteine-rich domain (CRD) has relatively independent flexibility, especially for the C-terminal long loop (loop I) of CRD to participate in the interface of two domains. On the basis of previous studies of CNG channel and L-Ca(2+) channel blockers, and the sequence and structural comparison of natrin and stecrisp, the deviation of the vital loop I of CRD is suggested to contribute to different effects of some CRISPs in protein-protein interaction.

  6. Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

    PubMed

    Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

    2011-11-01

    CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions.

  7. Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

    PubMed

    Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

    2010-06-15

    CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation.

  8. Structural Insight into Specificity of Interactions between Nonconventional Three-finger Weak Toxin from Naja kaouthia (WTX) and Muscarinic Acetylcholine Receptors*

    PubMed Central

    Lyukmanova, Ekaterina N.; Shenkarev, Zakhar O.; Shulepko, Mikhail A.; Paramonov, Alexander S.; Chugunov, Anton O.; Janickova, Helena; Dolejsi, Eva; Dolezal, Vladimir; Utkin, Yuri N.; Tsetlin, Victor I.; Arseniev, Alexander S.; Efremov, Roman G.; Dolgikh, Dmitry A.; Kirpichnikov, Mikhail P.

    2015-01-01

    Weak toxin from Naja kaouthia (WTX) belongs to the group of nonconventional “three-finger” snake neurotoxins. It irreversibly inhibits nicotinic acetylcholine receptors and allosterically interacts with muscarinic acetylcholine receptors (mAChRs). Using site-directed mutagenesis, NMR spectroscopy, and computer modeling, we investigated the recombinant mutant WTX analogue (rWTX) which, compared with the native toxin, has an additional N-terminal methionine residue. In comparison with the wild-type toxin, rWTX demonstrated an altered pharmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1- and M2-mAChRs, and increased antagonist binding to M3-mAChR. Positively charged arginine residues located in the flexible loop II were found to be crucial for rWTX interactions with all types of mAChR. Computer modeling suggested that the rWTX loop II protrudes to the M1-mAChR allosteric ligand-binding site blocking the entrance to the orthosteric site. In contrast, toxin interacts with M3-mAChR by loop II without penetration into the allosteric site. Data obtained provide new structural insight into the target-specific allosteric regulation of mAChRs by “three-finger” snake neurotoxins. PMID:26242733

  9. Cobra ( Naja spp. ) nicotinic acetylcholine receptor exhibits resistance to Erabu sea snake ( Laticauda semifasciata) short-chain alpha-neurotoxin.

    PubMed

    Takacs, Zoltan; Wilhelmsen, Kirk C; Sorota, Steve

    2004-05-01

    Snake alpha-neutotoxins of Elapidae venoms are grouped into two structural classes, short-chain and long-chain alpha-neutotoxins. While these two classes share many chemical and biological characteristics, there are also distinct dissimilarities between them, including their binding site on the nicotinic acetylcholine receptor (nAChR), specificity among species of Chordata, and the associated pharmacological effects. In the present study we test the hypothesis that structural motifs that evolved to confer natural resistance against conspecific long-chain alpha-neurotoxins in Elapidae snakes also interfere with the biological action of short-chain alpha-neurotoxins. We expressed functional nAChRs that contains segments or single residues of the Elapidae nAChR ligand binding domain and tested the effect of short-chain alpha-neurotoxin erabutoxin-a (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine-induced currents as measured by two-microelectrode voltage clamp. Our results show that the Elapidae nAChR alpha subunit segment T(154)-L(208) ligand binding domain has an inhibitory effect on the pharmacological action of ETX-a. This effect is primarily attributed to the presence of glycosylation at position N(189). If the glycosylation is removed from the T(154)-L(208) segment, the nAChR will be inhibited, however, to a lesser extent than seen in the mouse. This effect correlates with the variations in alpha-neurotoxin sensitivity of different species and, importantly, reflects the evolutionary conservation of the binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of alpha-neurotoxin resistance suggests that alpha-neurotoxin-resistant nAChR evolved first, which permitted the evolution of snake venom alpha-neurotoxins. A model describing alpha-neurotoxin resistance in Elapidae snakes is presented.

  10. How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting.

    PubMed

    Panagides, Nadya; Jackson, Timothy N W; Ikonomopoulou, Maria P; Arbuckle, Kevin; Pretzler, Rudolf; Yang, Daryl C; Ali, Syed A; Koludarov, Ivan; Dobson, James; Sanker, Brittany; Asselin, Angelique; Santana, Renan C; Hendrikx, Iwan; van der Ploeg, Harold; Tai-A-Pin, Jeremie; van den Bergh, Romilly; Kerkkamp, Harald M I; Vonk, Freek J; Naude, Arno; Strydom, Morné A; Jacobsz, Louis; Dunstan, Nathan; Jaeger, Marc; Hodgson, Wayne C; Miles, John; Fry, Bryan G

    2017-03-13

    The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the Hemachatus + Naja and again independently in the king cobras (Ophiophagus). There was a significant increase of cytotoxicity in the Asian Naja linked to the evolution of bold aposematic hood markings, reinforcing the link between hooding and the evolution of defensive cytotoxic venoms. In parallel, lineages with increased cytotoxicity but lacking bold hood patterns evolved aposematic markers in the form of high contrast body banding. The results also indicate that, secondary to the evolution of venom rich in cytotoxins, spitting has evolved three times independently: once within the African Naja, once within the Asian Naja, and once in the Hemachatus genus. The evolution of cytotoxic venom thus appears to facilitate the evolution of defensive spitting behaviour. In contrast, a secondary loss of cytotoxicity and reduction of the hood occurred in the water cobra Naja annulata, which possesses streamlined neurotoxic venom similar to that of other aquatic elapid snakes (e.g., hydrophiine sea

  11. How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting

    PubMed Central

    Panagides, Nadya; Jackson, Timothy N.W.; Ikonomopoulou, Maria P.; Arbuckle, Kevin; Pretzler, Rudolf; Yang, Daryl C.; Ali, Syed A.; Koludarov, Ivan; Dobson, James; Sanker, Brittany; Asselin, Angelique; Santana, Renan C.; Hendrikx, Iwan; van der Ploeg, Harold; Tai-A-Pin, Jeremie; van den Bergh, Romilly; Kerkkamp, Harald M.I.; Vonk, Freek J.; Naude, Arno; Strydom, Morné A.; Jacobsz, Louis; Dunstan, Nathan; Jaeger, Marc; Hodgson, Wayne C.; Miles, John; Fry, Bryan G.

    2017-01-01

    The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the Hemachatus + Naja and again independently in the king cobras (Ophiophagus). There was a significant increase of cytotoxicity in the Asian Naja linked to the evolution of bold aposematic hood markings, reinforcing the link between hooding and the evolution of defensive cytotoxic venoms. In parallel, lineages with increased cytotoxicity but lacking bold hood patterns evolved aposematic markers in the form of high contrast body banding. The results also indicate that, secondary to the evolution of venom rich in cytotoxins, spitting has evolved three times independently: once within the African Naja, once within the Asian Naja, and once in the Hemachatus genus. The evolution of cytotoxic venom thus appears to facilitate the evolution of defensive spitting behaviour. In contrast, a secondary loss of cytotoxicity and reduction of the hood occurred in the water cobra Naja annulata, which possesses streamlined neurotoxic venom similar to that of other aquatic elapid snakes (e.g., hydrophiine sea

  12. Purification and characterization of a novel phospholipase A2 from king cobra (Ophiophagus hannah) venom.

    PubMed

    Chiou, J Y; Chang, L S; Chen, L N; Chang, C C

    1995-08-01

    A novel phospholipase A2, designated as Oh-DE-2, was isolated from the venom of Ophiophagus hannah (king cobra) by successive chromatography on SP-Sephadex C-25, DE-52, and Q-Sepharose columns. Oh-DE-2 with pI 5.1 showed an apparent molecular weight of 14 kD as revealed by SDS-PAGE and gel filtration. The amino acid sequence was homologous with those of PLA2S from Elapidae venoms. Oh-DE-2 was effectively inactivated by p-bromophenacyl bromide, indicating that the conserved His-48 is essential for its enzymatic activity. However, modification of the conserved Trp-19 did not cause a precipitous drop in the enzymatic activity of Oh-DE-2 as observed with PLA2S from Naja naja atra and Bungarus multicinctus venoms. A quenching study showed that the microenvironment of Trp in Oh-DE-2 was inaccessible to acrylamide, iodide, or cesium, a finding which was different from those observed with PLA2S from N. naja atra and B. multicinctus venoms. These results might suggest that, unlike other PLA2 enzymes, Trp-19 in Oh-DE-2 is not directly involved in its enzymatic mechanisms.

  13. Amphiphilic beta-sheet cobra cardiotoxin targets mitochondria and disrupts its network.

    PubMed

    Wang, Chia-Hui; Wu, Wen-guey

    2005-06-06

    Recent advance in understanding the role of toxin proteins in controlling cell death has revealed that pro-apoptotic viral proteins targeting mitochondria contain amphiphilic alpha-helices with pore-forming properties. Herein, we describe that the pore-forming amphiphilic beta-sheet cardiotoxins (or cytotoxins, CTXs) from Taiwan cobra (Naja atra) also target mitochondrial membrane after internalization and act synergistically with CTX-induced cytosolic calcium increase to disrupt mitochondria network. It is suggested that CTX-induced fragmentation of mitochondria play a role in controlling CTX-induced necrosis of myocytes and cause severe tissue necrosis in the victims.

  14. Coarse-grained molecular dynamics simulations of cobra cytotoxin A3 interactions with a lipid bilayer: penetration of loops into membranes.

    PubMed

    Su, Zhi-Yuan; Wang, Yeng-Tseng

    2011-02-10

    Cobra cytotoxins, which are small three-looped proteins composed of approximately 60 amino acid residues, primarily act by destroying the bilayer membranes of cells and artificial vesicles. However, the molecular mechanism governing this process is not yet completely understood. We used coarse-grained molecular dynamics (CGMD) simulations to study the mechanism underlying the penetration of cardiotoxin A3 (CTX A3), the major toxic component of Naja atra (Chinese cobra) venom, into a hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC) lipid bilayer. We performed CGMD simulations for three different conformations of the cobra cytotoxin-the tail, lying, and harrow conformations. The results of our simulations indicate that two of these, the tail and lying conformations, did not penetrate the bilayer system. Further, for the harrow conformation, loops 2 and 3 played important roles in penetration of CTX A3 into the bilayer system.

  15. Hyaluronidase inhibitors (sodium cromoglycate and sodium auro-thiomalate) reduce the local tissue damage and prolong the survival time of mice injected with Naja kaouthia and Calloselasma rhodostoma venoms.

    PubMed

    Yingprasertchai, Senee; Bunyasrisawat, Srisurat; Ratanabanangkoon, Kavi

    2003-11-01

    Experiments have been carried out to find potent inhibitors of hyaluronidases of Naja kaouthia (NK) and Calloselasma rhodostoma (CR) venoms with the aim of reducing local tissue damage and systemic toxicities caused by the venoms. Seven drugs/chemicals known to inhibit hyaluronidases were tested for their activity on venom enzymes. These were: sodium cromoglycate (SC), sodium aurothiomalate (SAT), apigenin, kaemferol, phenylbutazone, oxyphenbutazone and fenoprofen. The results showed that SC or SAT at 10 mM, completely inhibited the enzymes of both venoms. In in vivo experiments, SC or SAT, when incubated with NK venom prior to injection, significantly reduced edema and myonecrosis. In the case of CR venom, hemorrhage, in addition to edema and myonecrosis, was also significantly reduced. In the independent type experiment, SC or SAT were effective if injected within 1 min after the injection of venom. At longer time intervals of 3 and 10 min the inhibitors were effective in reducing some parameters of local tissue necrosis but the extent of inhibition was lower. SC and SAT at 256 and 195 microg/mouse, respectively, significantly prolonged the survival time of mice receiving lethal doses of NK. In the case of CR venoms, the two inhibitors not only prolonged the survival time but also prevented death of mice receiving lethal doses of the venom. The other inhibitors were poorly soluble in water and were studied only on enzyme inhibition and prolongation of survival time; they were mostly ineffective. Thus, SC and SAT when injected immediately at the sites of bites can reduce the systemic and local toxicity of NK and CR venoms. These results suggest that administration of these drugs at the site of venom injection may be useful in reducing venom-induced local tissue damage.

  16. A bradykinin potentiating peptide from Egyptian cobra venom strongly affects rat atrium contractile force and cellular calcium regulation.

    PubMed

    El-Saadani, Muhammad A M; El-Sayed, Muhammad F

    2003-12-01

    Peptide fractions were isolated from venoms of the Egyptian snake Naja haje haje (cobra BPP) and the scorpions Buthus occitanus (BPP(B)) and Leirus quenquestriatus (BPP(L)). The pharmacological effects of these peptides were bioassayed and showed bradykinin potentiating activities. Amino acid analysis revealed that 14 amino acids contribute to the structure of BPP(B) and 16 for BPP(L), while cobra BPP was composed of 15 amino acids. Treatment of rat atrial preparations with 50 microg/ml of cobra BPP caused a significant reduction (P<0.001) in myocardial force. Elevation of extracellular calcium concentration from 1.25 to 5 mM antagonized the effect of cobra BPP in a way that restored the atrial force development. Na(+)-channel blockers did not change the force development at 5 mM Ca(2+). Experiments with (45)Ca revealed that Ca(2+) uptake of cobra BPP treated atria was 0.52+/-0.07 microM/g wet mass and the force at the end of the uptake period was 55.0+/-2.0%. The corresponding values for non-treated preparations were 0.56+/-0.04 microM/g and 92.0%+/-3.0%, respectively. Our results revealed that cobra BPP did not exhibit any effect on Ca(2+) uptake by rat atrial preparations, but strongly affected cellular Ca(2+) regulation.

  17. Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

    PubMed

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-05-13

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

  18. Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

    PubMed Central

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-01-01

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins. PMID:24828754

  19. Cobra cardiotoxin-induced cell death in fetal rat cardiomyocytes and cortical neurons: different pathway but similar cell surface target.

    PubMed

    Wang, Chia-Hui; Monette, Robert; Lee, Shao-Chen; Morley, Paul; Wu, Wen-guey

    2005-09-15

    Cobra cardiotoxins (CTXs) are basic polypeptides with diverse pharmacological functions that are cytotoxic to many different cell types through both necrotic and apoptotic cell death pathways. In this comparative study of the action of CTX A3 from the Taiwan cobra (Naja atra) on fetal rat cardiomyocytes and cortical neurons, it was shown that CTX A3 induced different patterns of elevation of intracellular Ca2+ concentration ([Ca2+]i), CTX internalization, caspase-3 activity and viability. Application of an anti-sulfatide monoclonal antibody, O4 specific for 3-sulfo-galactose lipid, but not in the control experiments using anti-GM3 monoclonal antibody, reduces CTX-induced [Ca2+]i elevation, CTX internalization and toxicity. Therefore, CTX may target similar sulfo-containing cell surface receptors in both fetal rat cardiomyocytes and cortical neurons, but induce cell death through different pathways specific to each cell type.

  20. Cross Neutralization of Afro-Asian Cobra and Asian Krait Venoms by a Thai Polyvalent Snake Antivenom (Neuro Polyvalent Snake Antivenom)

    PubMed Central

    Leong, Poh Kuan; Sim, Si Mui; Fung, Shin Yee; Sumana, Khomvilai; Sitprija, Visith; Tan, Nget Hong

    2012-01-01

    Background Snake envenomation is a serious public health threat in the rural areas of Asian and African countries. To date, the only proven treatment for snake envenomation is antivenom therapy. Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been reported. The present study examined the cross neutralizing potential of a newly developed polyvalent antivenom, termed Neuro Polyvalent Snake Antivenom (NPAV). NPAV was produced by immunization against 4 Thai elapid venoms. Principal Findings In vitro neutralization study using mice showed that NPAV was able to neutralize effectively the lethality of venoms of most common Asiatic cobras (Naja spp.), Ophiophagus hannah and kraits (Bungarus spp.) from Southeast Asia, but only moderately to weakly effective against venoms of Naja from India subcontinent and Africa. Studies with several venoms showed that the in vivo neutralization potency of the NPAV was comparable to the in vitro neutralization potency. NPAV could also fully protect against N. sputatrix venom-induced cardio-respiratory depressant and neuromuscular blocking effects in anesthetized rats, demonstrating that the NPAV could neutralize most of the major lethal toxins in the Naja venom. Conclusions/Significance The newly developed polyvalent antivenom NPAV may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand. Nevertheless, the applicability of NPAV in the treatment of cobra and krait envenomations in Southeast Asian victims needs to be confirmed by clinical trials. The cross-neutralization results may contribute to the design of broad-spectrum polyvalent antivenom. PMID:22679522

  1. In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies

    PubMed Central

    Sakthivel, G.; Dey, Amitabha; Nongalleima, Kh.; Chavali, Murthy; Rimal Isaac, R. S.; Singh, N. Surjit; Deb, Lokesh

    2013-01-01

    The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity. PMID:23533518

  2. Immunoreactivity and two-dimensional gel-electrophoresis characterization of Egyptian cobra venom proteome.

    PubMed

    Almehdar, Hussein Abduelrahman; Adel-Sadek, Mahmoud Abass; Redwan, Elrashdy Moustafa

    2015-01-01

    The first and second (two) dimensional gel electrophoresis has a broad protein resolution power. It was used to separate and identify cobra venom proteome. The importance of characterizing venom proteins contents from the Egyptian elapidae, specifically neurotoxins, is based on the need to produce effective anti-venom. About 30-55distinct protein spots were identified on silver stained two-dimensional gels. Around two-thirds of the venom proteins displayed low a molecular weight and a migration into hydrophobic side. The venoms from Naja haja and Naja nigricollus showed 45-55 spots, while Walternnesia aegyptia had less (31-37) spots. The commercial prepared polyclonal antivenom had a strong signal for anionic and cationic venom protein spots with molecular weight 20-115 kDa. However, it showed weak or non immunoreactivity toward anionic low molecular weight spots (2.5-15 kDa). These results suggest the need to change the immunization schedule to include low molecular weight toxin-proteomes as separate dose or sequester injection.

  3. Spitting cobras: fluid jets in nature as models for technical applications

    NASA Astrophysics Data System (ADS)

    Balmert, Alexander; Hess, David; Brücker, Christoph; Bleckmann, Horst; Westhoff, Guido

    2011-04-01

    Spitting cobras defend themselves by ejecting rapid jets of venom through their fangs towards the face of an offender. To generate these jets, the venom delivery system of spitting cobras has some unique adaptations, such as prominent ridges on the surface of the venom channel. We examined the fluid acceleration mechanisms in three spitting cobra species of the genus Naja. To investigate the liquid-flow through the venom channel we built a three-dimensional 60:1 scale model. First we determined the three-dimensional structure of the channel by using microcomputer tomography. With help of the micro computer tomographical data we then created a negative form out of wax. Finally, silicon was casted around the wax form and the wax removed, resulting in a completely transparent model of the cobrás venom channel. The physical-chemical properties of the cobra venom were measured by micro rheometry and tensiometry. Thereafter, an artificial fluid with similar properties was generated. Particle image velocimetry (PIV) was performed to visualize the flow of the artificial liquid in the three-dimensional model. Our experiments show how the surface structure of the venom channel determines the liquid flow through the channel and ultimately the form of the liquid jet. Understanding the biological mechanisms of venom ejection helps to enhance industrial processes such as water jet cutting and cleaning as well as injection methods in technical and medical sectors, e.g. liquid microjet dissection in microsurgery.

  4. Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah).

    PubMed

    Tan, Choo Hock; Tan, Kae Yi; Fung, Shin Yee; Tan, Nget Hong

    2015-09-10

    The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS. Transcriptomic results reveal high redundancy of toxin transcripts (3357.36 FPKM/transcript) despite small cluster numbers, implying gene duplication and diversification within restricted protein families. Among the 23 toxin families identified, three-finger toxins (3FTxs) and snake-venom metalloproteases (SVMPs) have the most diverse isoforms. These 2 toxin families are also the most abundantly transcribed, followed in descending order by phospholipases A2 (PLA2s), cysteine-rich secretory proteins (CRISPs), Kunitz-type inhibitors (KUNs), and L-amino acid oxidases (LAAOs). Seventeen toxin families exhibited low mRNA expression, including hyaluronidase, DPP-IV and 5'-nucleotidase that were not previously reported in the venom-gland transcriptome of a Balinese O. hannah. On the other hand, the MOh proteome includes 3FTxs, the most abundantly expressed proteins in the venom (43 % toxin sbundance). Within this toxin family, there are 6 long-chain, 5 short-chain and 2 non-conventional 3FTx. Neurotoxins comprise the major 3FTxs in the MOh venom, consistent with rapid neuromuscular paralysis reported in systemic envenoming. The presence of toxic enzymes such as LAAOs, SVMPs and PLA2 would explain tissue inflammation and necrotising destruction in local envenoming. Dissimilarities in the subtypes and sequences between the neurotoxins of MOh and Naja kaouthia (monocled cobra) are in agreement with the poor cross-neutralization activity of N. kaouthia antivenom used against MOh venom. Besides, the presence of cobra venom factor, nerve growth factors

  5. Inhibition by multivalent cations of contraction induced by Chinese cobra venom cardiotoxin in guinea pig papillary muscle.

    PubMed

    Huang, S J; Kwan, C Y

    1996-01-01

    The effects of cardiotoxin (CTX), purified from the venom of Chinese Cobra (Naja naja atra) by a three-step chromatography, on the contractile responses of isolated guinea pig papillary muscle preparation and its antagonism by lanthanum ion (La3+) and divalent cations were examined. CTX induced tonic contraction following a transient augmentation of electrically evoked rhythmic contractions, which is similar to that seen in perfused heart preparation. Multivalent cations, La3+, Ca2+, Mn2+ and Mg2+, concentration-dependently blocked CTX-induced contraction. In Ca(2+)-free medium, CTX did not induce contraction and CTX-induced contraction was not modified in Na(+)-free medium. Nifedipine (1 mumol/L), effectively blocked KCl-induced contracture, but only partially inhibited CTX-induced contraction; thus suggesting that Ca2+ influx induced by CTX utilizes channels other than L-type Ca2+ channels. These cations may compete with CTX for the negatively charged membrane binding site which is responsible for the modulation of Ca2+ movement.

  6. A novel natriuretic peptide from the cobra venom.

    PubMed

    Zhang, Yong; Wu, Jianbo; Yu, Guoyu; Chen, Zhongming; Zhou, Xingding; Zhu, Shaowen; Li, Rui; Zhang, Yun; Lu, Qiumin

    2011-01-01

    Natriuretic peptides (NPs) play crucial roles in human physiology and pathophysiology through natriuresis, dieresis and vasorelaxation. NPs are also one of the important components of snake venoms. However, the low abundance in snake venom hampered the investigation. Here, a novel natriuretic peptide named Na-NP was purified from the cobra Naja atra venom. Na-NP consists of 45 amino acid residues and its molecular weight is 4618.5 Da. A full-length cDNA encoding Na-NP was obtained from the cDNA library constructed from the venom gland. The open reading frame of cloned Na-NP was composed of 498bp and coded for a 165-amino acid residue protein precursor. The nucleotide and deduced protein sequences of Na-NP were remarkably conserved with other elapid NPs while significant different from the viperid NPs. Na-NP showed weak activity to relax the aortic rings precontracted with phenylephrine. Meanwhile, Na-NP showed cGMP-promotion activity against primary cultured rabbit endocardial endothelial cells, but had no effect on human platelet aggregation. In conclusion, this is the first report of a natriuretic peptide from the cobra N. atra venom. Na-NP might be served as a useful tool for the study of human NPs and the development of novel therapeutic drugs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Prolonged cardiac xenograft survival in guinea pig-to-rat model by a highly active cobra venom factor.

    PubMed

    Sun, Qian-Yun; Chen, Gang; Guo, Hui; Chen, Shi; Wang, Wan-Yu; Xiong, Yu-Liang

    2003-09-01

    A highly active cobra venom factor (CVF) was isolated from the venom of Naja kaouthia by sequential column chromatography. It displays strong anticomplementary activity, and has 1515 U of anticomplementary activity per mg protein. A single dose of 0.1 mg/kg CVF given i.v. to rats completely abrogated complement activity for nearly 5 days. Given 0.02 mg/kg of CVF, the complement activity of rats was reduced by more than 96.5% in 6 h. In guinea pig-to-rat heart transplant model, rats treated with a single dose of 0.05 mg/kg CVF had significantly prolonged xenograft survival (56.12+/-6.27 h in CVF-treated rats vs. 0.19+/-0.07 h in control rats, P<0.001).

  8. Redescription of Haemoproteus mesnili (Apicomplexa: Plasmodiidae) and its meronts, with description of a second haemosporidian parasite of African cobras.

    PubMed

    Telford, Sam R

    2007-06-01

    Haemoproteus mesnili (Bouet 1909) Wenyon 1926 is redescribed from the spitting cobra, Naja nigricollis nigricollis, of Tanzania. Mature gametocytes in the acute phase of infection averaged 17.7 X 7.3 jim, with LW 128.1 jim-, and L:W ratio 2.52. Nuclei were visible in both sexes. Both sexes were heavily pigmented, with 31-62 black granules dispersed in macrogametocytes; 20-46 granules were often clumped or concentrated near ends of microgametocytes. The halteridial form was present in 28% of active-phase gametocytes, but in only 8% of those in chronic phase. A few large, possibly first generation, meronts were present in cardiac muscle; uninucleate parasites within parasitophorous vacuoles in splenic cells produced small rounded or ovoid meronts, 12.2 x 9.6 microm, with 12-16 deeply basophilic, square-to-rectangular cytomeres. Meronts with 17-32 cytomeres were 16.9 x 11.9 microm. Meronts, 20 x 16 to 26 x 22 microm, contained 51-57 cytomeres. Mature meronts were ovoid, 13.7 x 11.5 microm, with many rounded merozoites. Haemoproteus balli n. sp, found in an Egyptian cobra, Naja haje haje of Kenya, differs from H. mesnili in average gametocyte dimensions, 10.8 x 7.7 microm; LW, 83.2 microm2; L/W ratio, 1.42; absence of halteridial forms; sparse pigmentation (3-10 granules); and presence of a broad peripheral band, apparently chromatin, along one side of microgametocytes.

  9. Restoration of nerve growth factor in organs of mice injected with cobra venom followed by specific treatment and reversal period.

    PubMed

    Lipps, Binie V

    2002-05-01

    Research from this laboratory reported the decreased levels of endogenously present nerve growth factor (NGF) in organs of mice as a consequence of sub-lethal injection of Naja kaouthia venom. This research reports that the decreased levels of NGF in organs of mice were prevented by (1) specific treatment and (2) restored to normal by a prolonged period. Adult female Balb/c mice were injected intramuscularly (IM) with a sub-lethal dose of cobra venom. The injected mice were divided into five groups. Mice in group I were injected with PBS, group II with anti-cobra venom, and group III with lethal toxin neutralizing factor (LTNF). Mice in group IV were treated IM with synthetic LTNF (LT-10), and mice in group V were treated orally with LT-10. After 24 hr. mice were sacrificed and NGF levels in organ homogenates were assayed and compared with control mice not injected with venom. It was observed that the organs from group I treated with PBS showed a tremendous drop in NGF level in comparison to the organs of the control mice. It was further revealed that the decreased levels of NGF in organs of injected mice were prevented by treatment with anti-cobra venom, LTNF and LT-10 by IM, or oral routes. In the second series of experiments, mice injected with sub-lethal dose of cobra venom were sacrificed after 1, 3, 7, and 10 days, and the organs were assayed for NGF levels. It was observed that the recovery period for normal homeostasis of NGF was between 7 and 10 days in the brain, heart, liver, salivary glands, and ovaries.

  10. A three-compartment open pharmacokinetic model can explain variable toxicities of cobra venoms and their alpha toxins.

    PubMed

    Ismail, M; Aly, M H; Abd-Elsalam, M A; Morad, A M

    1996-09-01

    The pharmacokinetic profiles of labelled Naja melanoleuca, Naja nivea, Naja nigricollis and Naja haje venoms and their alpha neurotoxins were determined following rapid i.v. injection into rabbits. The data obtained fitted a triexponential equation characteristic of a three-compartment open pharmacokinetic model comprising a central compartment 'blood', a rapidly equilibrating 'shallow' tissue compartment and a slowly equilibrating 'deep' tissue compartment. The distribution half-lives for the shallow compartment ranged from 3.2 to 5 min, reflecting the rapid uptake of venoms and toxins compared with 22-47 min for the deep tissue compartment denoting much slower uptake. The overall elimination half-lives, t1/2 beta, ranged from 15 to 29 hr, indicating a slow body elimination. Peak tissue concentration was reached within 15-20 min in the shallow tissue compartment. The corresponding values for the deep tissue compartment were 120 min for N. melanoleuca and N. nigricollis venoms and their toxins and 240 min for N. nivea and N. haje venoms and their toxins. Steady-state distribution between the shallow tissue compartment and the blood gave values of 0.50 and 0.92 (N. melanoleuca), 1.64 and 1.05 (N. nivea), 0.78 and 0.92 (N. nigricollis) and 1.70 and 1.03 (N. haje) for the venoms and their toxins, respectively. The corresponding values for the deep tissue compartment gave ratios of 3.31 and 3.44 (N. melanoleuca), 2.99 and 1.68 (N. nivea), 3.74 and 3.79 (N. nigricollis) and 1.39 and 2.46 (N. haje) for the venoms and their toxins, respectively. Ratios lower than unity indicate lower venom and toxin concentrations in the tissues than in the blood, while larger ratios denote higher tissue concentrations. The values thus reflect a higher affinity of the venoms and their toxins for the central than the shallow tissue compartment and for the deep tissue than the central compartment. The sites of action of the venoms seem to be located in the deep tissue compartment since most

  11. Effects of three cobra venoms on blood coagulation, platelet aggregation, and fibrinolysis

    PubMed Central

    MacKay, N.; Ferguson, J. C.; McNicol, G. P.

    1969-01-01

    The effects of the venoms of Naja melanoleuca, Naja nigricollis, and Ophiophagus hannah on blood coagulation, platelet aggregation, and fibrinolysis were studied in vitro. All three venoms were shown to be anticoagulant. This action appeared to be due to an effect on both the extrinsic and blood thromboplastin mechanisms. Platelet aggregation in Chandler's tubes and adenosine diphosphate reactivity were inhibited by the three venoms, although in the case of Ophiophagus hannah venom they were inhibited only with intermediate concentrations. The three venoms possessed proteolytic properties, but when incorporated into purified caseinolytic systems and euglobulin clot lysis systems inhibition of plasmin activity was observed. PMID:5814735

  12. 3D flow in the venom channel of a spitting cobra: do the ridges in the fangs act as fluid guide vanes?

    PubMed

    Triep, Michael; Hess, David; Chaves, Humberto; Brücker, Christoph; Balmert, Alexander; Westhoff, Guido; Bleckmann, Horst

    2013-01-01

    The spitting cobra Naja pallida can eject its venom towards an offender from a distance of up to two meters. The aim of this study was to understand the mechanisms responsible for the relatively large distance covered by the venom jet although the venom channel is only of micro-scale. Therefore, we analysed factors that influence secondary flow and pressure drop in the venom channel, which include the physical-chemical properties of venom liquid and the morphology of the venom channel. The cobra venom showed shear-reducing properties and the venom channel had paired ridges that span from the last third of the channel to its distal end, terminating laterally and in close proximity to the discharge orifice. To analyze the functional significance of these ridges we generated a numerical and an experimental model of the venom channel. Computational fluid dynamics (CFD) and Particle-Image Velocimetry (PIV) revealed that the paired interior ridges shape the flow structure upstream of the sharp 90° bend at the distal end. The occurrence of secondary flow structures resembling Dean-type vortical structures in the venom channel can be observed, which induce additional pressure loss. Comparing a venom channel featuring ridges with an identical channel featuring no ridges, one can observe a reduction of pressure loss of about 30%. Therefore it is concluded that the function of the ridges is similar to guide vanes used by engineers to reduce pressure loss in curved flow channels.

  13. 3D Flow in the Venom Channel of a Spitting Cobra: Do the Ridges in the Fangs Act as Fluid Guide Vanes?

    PubMed Central

    Triep, Michael; Hess, David; Chaves, Humberto; Brücker, Christoph; Balmert, Alexander; Westhoff, Guido; Bleckmann, Horst

    2013-01-01

    The spitting cobra Naja pallida can eject its venom towards an offender from a distance of up to two meters. The aim of this study was to understand the mechanisms responsible for the relatively large distance covered by the venom jet although the venom channel is only of micro-scale. Therefore, we analysed factors that influence secondary flow and pressure drop in the venom channel, which include the physical-chemical properties of venom liquid and the morphology of the venom channel. The cobra venom showed shear-reducing properties and the venom channel had paired ridges that span from the last third of the channel to its distal end, terminating laterally and in close proximity to the discharge orifice. To analyze the functional significance of these ridges we generated a numerical and an experimental model of the venom channel. Computational fluid dynamics (CFD) and Particle-Image Velocimetry (PIV) revealed that the paired interior ridges shape the flow structure upstream of the sharp 90° bend at the distal end. The occurrence of secondary flow structures resembling Dean-type vortical structures in the venom channel can be observed, which induce additional pressure loss. Comparing a venom channel featuring ridges with an identical channel featuring no ridges, one can observe a reduction of pressure loss of about 30%. Therefore it is concluded that the function of the ridges is similar to guide vanes used by engineers to reduce pressure loss in curved flow channels. PMID:23671569

  14. The role of sulfatide lipid domains in the membrane pore-forming activity of cobra cardiotoxin.

    PubMed

    Wu, Po-Long; Chiu, Chang-Ru; Huang, Wei-Ning; Wu, Wen-Guey

    2012-05-01

    Cobra CTX A3, the major cardiotoxin (CTX) from Naja atra, is a cytotoxic, basic β-sheet polypeptide that is known to induce a transient membrane leakage of cardiomyocytes through a sulfatide-dependent CTX membrane pore formation and internalization mechanism. The molecular specificity of CTX A3-sulfatide interaction at atomic levels has also been shown by both nuclear magnetic resonance (NMR) and X-ray diffraction techniques to reveal a role of CTX-induced sulfatide conformational changes for CTX A3 binding and dimer formation. In this study, we investigate the role of sulfatide lipid domains in CTX pore formation by various biophysical methods, including fluorescence imaging and atomic force microscopy, and suggest an important role of liquid-disordered (ld) and solid-ordered (so) phase boundary in lipid domains to facilitate the process. Fluorescence spectroscopic studies on the kinetics of membrane leakage and CTX oligomerization further reveal that, although most CTXs can oligomerize on membranes, only a small fraction of CTXs oligomerizations form leakage pores. We therefore suggest that CTX binding at the boundary between the so and so/ld phase coexistence sulfatide lipid domains could form effective pores to significantly enhance the CTX-induced membrane leakage of sulfatide-containing phosphatidylcholine vesicles. The model is consistent with our earlier observations that CTX may penetrate and lyse the bilayers into small aggregates at a lipid/protein molar ratio of about 20 in the ripple P(β)' phase of phosphatidylcholine bilayers and suggest a novel mechanism for the synergistic action of cobra secretary phospholipase A2 and CTXs.

  15. Electrophoretic Characterization of Elapid, Viperid and Crotalid Snake Venoms

    DTIC Science & Technology

    1989-08-01

    and patent rights’. UNCLASSIFIED UNCLASSIFIED ABSTRACT This report deals with comparative studies of snake venoms from 21 species representing Elapidae ...Blue Stains Figure 4 shows a pair of typical non-SDS electropherograms of native venom proteins from representative species of Elapidae , Viperidae and...SOURCES OF THE SNAKE VENOMS STUDIED VENOM SPECIES COMMON NAME NO. Elapidae : 14. Naja melanoleuca black cobra 15. 9-ja haje Egyptian cobra 16. Naja naja

  16. Structural difference between group I and group II cobra cardiotoxins: X-ray, NMR, and CD analysis of the effect of cis-proline conformation on three-fingered toxins.

    PubMed

    Chen, Ting-Shou; Chung, Fong-Yu; Tjong, Siu-Cin; Goh, King-Siang; Huang, Wei-Ning; Chien, Kun-Yi; Wu, Po-Long; Lin, Hua-Ching; Chen, Chun-Jung; Wu, Wen-Guey

    2005-05-24

    Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclasses of group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differences in their three-dimensional structures and biological significance remain elusive. We show by circular dichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6 from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn with a cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformation can be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding to the membrane environment, group I CTX undergoes a conformational change to adopt a more extended hydrophobic domain with beta-sheet twisting closer to the one adopted by group II CTX. This result resolves a discrepancy in the CTX structural difference reported previously between solution as well as crystal state and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an important role in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalization are also discussed on the basis of the determined loop I conformation.

  17. Decreased levels of nerve growth factor in organs of mice as a consequence of sub-lethal injection of cobra venom.

    PubMed

    Lipps, B V

    2001-11-01

    Nerve growth factor (NGF) is endogenously present in salivary glands of mice and sex organs of various animals. This research reports the presence of NGF in almost all major organs of mice at varying concentrations. The research further reports that intramuscular injection of a sub-lethal dose of Naja kaouthia venom lowered the levels of NGF in the organs of mice. Adult Balb/C male mice were injected with a half lethal dose of cobra venom. The mice were sacrificed for organs at 2, 8, and 24 hours post injection. Organs were homogenized, centrifuged, and the supernatants were assayed for NGF using anti-NGF by immunological tests enzyme-linked immunosorbent assay (ELISA). The organs of the mice injected with PBS served as controls. Major decrease in the levels of NGF was observed 2 hours after venom injection, and tremendous decrease of NGF was observed in organs of mice 24 hours post injection. The most lowering for NGF was observed in brain, heart, liver, salivary gland, and testis. This is a first-hand investigation showing the pharmacokinetics of NGF in organs of mice as an effect of envenomation.

  18. Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

    PubMed

    Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

    2012-06-01

    Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

  19. Cross-neutralisation of the neurotoxic effects of Egyptian cobra venom with commercial tiger snake antivenom.

    PubMed

    Kornhauser, Rachelle; Isbister, Geoffrey K; O'Leary, Margaret A; Mirtschin, Peter; Dunstan, Nathan; Hodgson, Wayne C

    2013-02-01

    Cross-neutralisation has been demonstrated for haemorrhagic venoms including Echis spp. and Cerastes spp. and for Australia elapid procoagulant toxins. A previous study showed that commercial tiger snake antivenom (TSAV) was able to neutralise the systemic effects of the Egyptian cobra, Naja haje, in vivo but it is unclear if this was true cross-neutralisation. The aim of the current study was to determine whether TSAV can neutralise the in vitro neurotoxic effects of N. haje venom. Both Notechis scutatus (10 μg/ml) and N. haje (10 μg/ml) venoms caused inhibition of indirect (supramaximal V, 0.1 Hz, 0.2 msec.) twitches of the chick biventer cervicis nerve-muscle preparation with t(90) values (i.e. the time to produce 90% inhibition of the original twitch height) of 26 ± 1 min. (n = 4) and 36 ± 4 min.; (n = 4). This effect at 10 μg/ml was significantly attenuated by the prior addition of TSAV (5 U/ml). A comparison of the reverse-phase HPLC profiles of both venoms showed some similarities with peak elution times, and SDS-PAGE analysis elucidated comparable bands across both venoms. Further analysis using Western immunoblotting indicated TSAV was able to detect N. haje venom, and enzyme immunoassay showed that in-house biotinylated polyclonal monovalent N. scutatus antibodies were able to detect N. haje venom. These findings demonstrate cross-neutralisation between different and geographically separated snakes supporting potential immunological similarities in snake toxin groups for a large range of snakes. This provides more evidence that antivenoms could be developed against specific toxin groups to cover a large range of snakes.

  20. COBRA Main Engine Project

    NASA Technical Reports Server (NTRS)

    Snoddy, Jim; Sides, Steve; Lyles, Garry M. (Technical Monitor)

    2002-01-01

    The COBRA (CO-Optimized Booster for Reusable Applications) project include the following: 1. COBRA main engine project team. 2. COBRA and RLX cycles selected. 3. COBRA proto-type engine approach enables mission success. 4. COBRA provides quick, low cost demo of cycle and technologies. 5. COBRA cycle I risk reduction supports. 6. Achieving engine safety. 6. RLX cycle I risk reduction supports. 7. Flight qualification. 9. Life extension engine testing.

  1. Purification and Characterization of Nk-3FTx: A Three Finger Toxin from the Venom of North East Indian Monocled Cobra.

    PubMed

    Das, Diganta; Sharma, Maitreyee; Kumar Das, Hemanga; Pratim Sahu, Partha; Doley, Robin

    2016-02-01

    Snake venom three finger toxins (3FTxs) are a non-enzymatic family of venom proteins abundantly found in elapids. We have purified a 7579.5 ± 0.591 Da 3FTx named as Nk-3FTx from the venom of Naja kaouthia of North East India origin. The primary structure was determined by a combination of N-terminal sequencing and electrospray ionization liquid chromatography-mass spectrometry/mass spectrometry. Biochemical and biological characterization reveal that it is nontoxic to human cell lines and exhibit mild anticoagulant activity when tested on citrated human plasma. Nk-3FTx was found to affect the compound action potential (CAP) and nerve conduction velocity of isolated toad sciatic nerve. This is the first report of a non-conventional 3FTx from Naja kaouthia venom that reduces CAP for its neurotoxic effect. Further studies can be carried out to understand the mechanism of action and to explore its potential therapeutic application.

  2. Antibacterial properties of KwaZulu natal snake venoms.

    PubMed

    Blaylock, R S

    2000-11-01

    The objective was to ascertain whether local snake venoms have antibacterial properties. The venoms of the common night adder (Causus rhombeatus), gaboon adder (Bitis gabonica), puff adder (Bitis arietans), black mamba (Dendroaspis polylepis), eastern green mamba (Dendroaspis augusticeps), forest cobra (Naja melanoleuca), snouted cobra (Naja annulifera) and Mozambique spitting cobra (Naja mossambica) were collected and, by gel diffusion, tested against the bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeriginosa, Bacteriodes fragilis, Bacteroides intermedius, Clostridium sordellii and Clostridium perfringens. All snake venoms showed antibacterial activity, with the adders showing most activity against the aerobes while the cobras showed lesser, but equal activity against the aerobes and anaerobes. Black mamba venom only showed activity against C. perfringens. In conclusion, local snake venoms have antibacterial properties which are dependent on the venom and bacterial type; and in the Naja spp., for anaerobic bacteria, diminish in winter. There is liable to be more than one toxin component responsible.

  3. COBRA contactless detumbling

    NASA Astrophysics Data System (ADS)

    Peters, Thomas V.; Escorial Olmos, Diego

    2016-09-01

    COBRA is the proposed technique to control the motion of a non-cooperative target by means of the interaction between the thruster exhaust gases from the chaser and the target object. In the original ESA SysNova study, the COBRA concept was investigated as an active debris removal system, using contactless technology to deorbit a space debris object and to control its attitude. It was found that the concept is more effective for controlling the attitude of a debris object. An on-orbit experiment was proposed to have a chaser modify the attitude state of a space object in ESA's COBRA IRIDES project, which has now been canceled due to the lack of propellant in the chaser spacecraft. This study presents the results of an internal follow-up study on how to effectively use the COBRA concept for detumbling a large debris object and controlling its attitude motion prior to capture operations in an active debris removal mission.

  4. How COBRA Works Document

    EPA Pesticide Factsheets

    The Co-Benefits Risk Assessment (COBRA) model is a peer reviewed screening tool that inexpensively and quickly estimates the air quality, human health, and associated economic impacts of various state- and county-level emission reduction scenarios.

  5. How COBRA Works

    EPA Pesticide Factsheets

    The Co-Benefits Risk Assessment (COBRA) model is a peer reviewed screening tool that inexpensively and quickly estimates the air quality, human health, and associated economic impacts of various state- and county-level emission reduction scenarios.

  6. Collaborative Beamfocusing Radio (COBRA)

    NASA Astrophysics Data System (ADS)

    Rode, Jeremy P.; Hsu, Mark J.; Smith, David; Husain, Anis

    2013-05-01

    A Ziva team has recently demonstrated a novel technique called Collaborative Beamfocusing Radios (COBRA) which enables an ad-hoc collection of distributed commercial off-the-shelf software defined radios to coherently align and beamform to a remote radio. COBRA promises to operate even in high multipath and non-line-of-sight environments as well as mobile applications without resorting to computationally expensive closed loop techniques that are currently unable to operate with significant movement. COBRA exploits two key technologies to achieve coherent beamforming. The first is Time Reversal (TR) which compensates for multipath and automatically discovers the optimal spatio-temporal matched filter to enable peak signal gains (up to 20 dB) and diffraction-limited focusing at the intended receiver in NLOS and severe multipath environments. The second is time-aligned buffering which enables TR to synchronize distributed transmitters into a collaborative array. This time alignment algorithm avoids causality violations through the use of reciprocal buffering. Preserving spatio-temporal reciprocity through the TR capture and retransmission process achieves coherent alignment across multiple radios at ~GHz carriers using only standard quartz-oscillators. COBRA has been demonstrated in the lab, aligning two off-the-shelf software defined radios over-the-air to an accuracy of better than 2 degrees of carrier alignment at 450 MHz. The COBRA algorithms are lightweight, with computation in 5 ms on a smartphone class microprocessor. COBRA also has low start-up latency, achieving high accuracy from a cold-start in 30 ms. The COBRA technique opens up a large number of new capabilities in communications, and electronic warfare including selective spatial jamming, geolocation and anti-geolocation.

  7. King cobra bite.

    PubMed

    Karnchanachetanee, C

    1994-12-01

    King cobra (Ophiophagus hannah) bite is rare. The milestones of management should have specific antivenom, adequate assisting respirator and appropriate antibiotics against Proteus vulgaris infection. Tourniquet may play some role in delaying venom absorption and allow a greater chance of venom detoxification by the human body.

  8. The modified Cobra Seal

    SciTech Connect

    Ystesund, K.J.; Drayer, D.D.

    1990-01-01

    The Cobra Seal was developed in response to the International Atomic Energy Agency's request for an in situ verifiable seal. The Type E metal cap seal, still widely used by the IAEA, must be removed and returned to Agency headquarters for verification. The Cobra Seal allows an inspector to verify seal identity and integrity on site, without removing the seal. The seal consists of a loop of multi-strand fiber optic cable, which can be routed around or through the object to be sealed, and a seal body that secures the ends of the fiber optic cable. A cutting blade in the seal body randomly cuts a portion of the optical fibers in the cable. After the seal assembly is completed, a reference image is recorded of the unique pattern of light spots produced when the seal face is illuminated. Subsequent photographs of the seal pattern are compared to the original to establish the seal identity and integrity. This paper reviews the improvements and the technology of the cobra seal system. 3 refs., 5 figs.

  9. MOFA Software for the COBRA Toolbox

    SciTech Connect

    Griesemer, Marc; Navid, Ali

    2016-12-08

    MOFA-COBRA is a software code for Matlab that performs Multi-Objective Flux Analysis (MOFA), a solving of linear programming problems. Teh leading software package for conducting different types of analyses using constrain-based models is the COBRA Toolbox for Matlab. MOFA-COBRA is an added tool for COBRA that solves multi-objective problems using a novel algorithm.

  10. Validation of a cell-based assay to differentiate between the cytotoxic effects of elapid snake venoms.

    PubMed

    Kalam, Yasmean; Isbister, Geoffrey K; Mirtschin, Peter; Hodgson, Wayne C; Konstantakopoulos, Nicki

    2011-01-01

    Acanthophis genus (i.e. death adders) and the Naja genus (i.e. cobras) belong to the family elapidae. The current study compared the in vitro cytotoxicity of venoms from four Acanthophis spp. and three Naja spp. on rat aortic smooth muscle cells, A7r5, and rat skeletal muscle cells, L6. The ability of CSL death adder antivenom and SAIMR antivenom, for Acanthophis spp. and Naja spp. venom respectively, to negate the cytotoxicity was also examined. A cell proliferation assay was used to determine cell viability following treatment with venom in the presence or absence of antivenom. Sigmoidal growth curves were obtained, and IC(50) values were determined. Acanthophis spp. and Naja spp. venoms produced concentration-dependent inhibition of cell proliferation in both cell lines. Naja spp. venoms were significantly more cytotoxic than the most potent Acanthophis venom (i.e. A. antarcticus) in both cell lines. Naja spp. venoms also displayed higher sensitivity in L6 cells. SAIMR antivenom significantly inhibited the cytotoxic actions of all Naja spp. venoms in both A7r5 and L6 cells. However, death adder antivenom (CSL Ltd) was unable to negate the cytotoxic effects of Acanthophis spp. venoms. Concentrations of the predominantly cytotoxic Naja spp. venoms used were approximately three times less than the predominantly neurotoxic Acanthophis spp. venoms. SAIMR antivenom was partially effective in neutralising the effects of Naja spp. venoms. Death adder antivenom (CSL Ltd) was not effective in negating the cytotoxic effects of venom from Acanthophis spp. These results indicate that the cell-based assay is suited to the examination of cytotoxic snake venoms and may be used in conjunction with organ bath experiments to pharmacologically characterise snake venoms. Furthermore, the results suggest that the use of a skeletal muscle cell line is likely to be more clinically relevant for the examination of cytotoxic snake venoms. Copyright © 2010 Elsevier Inc. All rights

  11. Chemical modification of methionines in a cobra venom cytotoxin differentiates between lytic and binding domains.

    PubMed

    Stevens-Truss, R; Hinman, C L

    1996-08-01

    Cytotoxin-III from Naja naja atra (CTX) was chemically modified at either or both of its two methionine residues: Over 50% oxidation of methionine-26 occurred with a 1:1 molar ratio of chloramine-T:methionine; at a 5:1 molar ratio, methionine-26 was almost completely oxidized, while methionine-24 was modified only 26%; at a 10:1 molar ratio, both methionines were completely oxidized. Each oxidized derivative demonstrated a lower toxicity toward T-cells than toward heart cells. Conversely, binding to heart cells was affected more than binding to T-cells. Cyanogen bromide cleaved native CTX at both methionines, excising phenyl-alanine-25 and methionine-26 and converting methionine-24 to homoserine lactone. This treatment of CTX eliminated cytotoxicity toward both heart and T-cells, but had only a modest effect upon T-cell binding, as had 50% oxidation of methionine-26, suggesting that CTX lytic and binding regions may be distinct. A selective loss in heart cell binding following oxidation of methionine-24 further suggests that different parts of CTX may interact with the two types of target cells. Perturbation of the relatively flat hydrophobic surface of the CTX' triple-stranded beta-sheet could result from the introduction of negative charge due to methionine-24 oxidation. Alternatively, amino acid side chain participation in a CTX binding domain may be altered by the potential formation of a new hydrogen bond between tyrosine-51 and methionine-24 sulfoxide, as revealed by computer modeling of the completely oxidized CTX derivative.

  12. Cobra Hoods Coming At You

    NASA Image and Video Library

    2004-06-17

    This 3-D image taken by the left and right eyes of the panoramic camera on NASA Mars Exploration Rover Spirit shows the odd rock formation dubbed Cobra Hoods center. 3D glasses are necessary to view this image.

  13. Popsicle-Stick Cobra Wave

    NASA Astrophysics Data System (ADS)

    Boucher, Jean-Philippe; Clanet, Christophe; Quéré, David; Chevy, Frédéric

    2017-08-01

    The cobra wave is a popular physical phenomenon arising from the explosion of a metastable grillage made of popsicle sticks. The sticks are expelled from the mesh by releasing the elastic energy stored during the weaving of the structure. Here we analyze both experimentally and theoretically the propagation of the wave front depending on the properties of the sticks and the pattern of the mesh. We show that its velocity and its shape are directly related to the recoil imparted to the structure by the expelled sticks. Finally, we show that the cobra wave can only exist for a narrow range of parameters constrained by gravity and rupture of the sticks.

  14. Status and perspectives of COBRA

    NASA Astrophysics Data System (ADS)

    Fritts, M.; Zuber, K.

    2013-04-01

    The COBRA experiment is a search for neutrinoless double-beta decay using CdZnTe semiconductor detectors. Currently COBRA is collecting data from 32 coplanar grid (CPG) detectors installed in the Gran Sasso National Laboratory. This serves as a prototype for a proposed design of over 100 kg target mass in order to achieve the sensitivity necessary to probe new parameter space for 0νββ. Pixelated detector allowing tracking and thus particle identification are also explored as a unique option in double beta searches.

  15. 3D Printed Shelby Cobra

    SciTech Connect

    Love, Lonnie

    2015-01-09

    ORNL's newly printed 3D Shelby Cobra was showcased at the 2015 NAIAS in Detroit. This "laboratory on wheels" uses the Shelby Cobra design, celebrating the 50th anniversary of this model and honoring the first vehicle to be voted a national monument. The Shelby was printed at the Department of Energy’s Manufacturing Demonstration Facility at ORNL using the BAAM (Big Area Additive Manufacturing) machine and is intended as a “plug-n-play” laboratory on wheels. The Shelby will allow research and development of integrated components to be tested and enhanced in real time, improving the use of sustainable, digital manufacturing solutions in the automotive industry.

  16. e-MERLIN and the COBRaS legacy Project

    NASA Astrophysics Data System (ADS)

    Peck, Luke

    2011-07-01

    As one of the 12 legacy programmes given ~300 hrs observing time on the newly enhanced e-MERLIN; the Cygnus OB2 Radio Survey (COBRaS) (homepage: http://www.homepages.ucl.ac.uk/~ucapdwi/cobras/) is an intensive deep-field mapping of the Cyg OB2 association in the Cygnus region of our Galaxy. This will provide the most detailed census for the most massive OB association in the northern hemisphere. A range of astrophysical problems and themes will be investigated including: mass loss and evolution of massive stars; the formation, dynamics and content of massive OB associations and the frequency of massive binaries and the incidence of non-thermal radiation. As part of of the initial ground work for this project, extensive meta-data catalogues were amalgamated from various catalogues from the Virtual Observatory database. In this talk I will discuss; investigations into JHK photometric techniques which can help identify possible OB candidates and other spectral classes; theoretical mass loss models as described by Vink et al. 2001 along with stellar parameters from Martins et al. 2005, Searle et al. 2008 and Prinja et al 1990 which pave the way to calculate theoretical mass loss rates for smooth winds of O stars and B supergiants, and the predicted 6cm fluxes resulting from the thermal free-free radiation in their winds. This will be essential for the study of clumped winds which is an early goal for this project. Over the months following from when this abstract was written; the first e-MERLIN pointings are expected. In the event of obtaining data, this will also be included in the presentation as part of the 'early science' from e-MERLIN and COBRaS.

  17. Venomous snakebite in Thailand. I: Medically important snakes.

    PubMed

    Chanhome, L; Cox, M J; Wilde, H; Jintakoon, P; Chaiyabutr, N; Sitprija, V

    1998-05-01

    Thailand has an abundance of venomous snakes. Among the neurotoxic family Elapidae, there are three species of the genus Naja (cobras), three of the genus Bungarus (kraits), and the king cobra of the genus Ophiophagus. Other Elapidae snakes in Thailand include sea snakes and Asian coral snakes of the genus Calliophis. They have potent venoms but rarely bite humans. Tissue and hemotoxic snakes are represented by family Viperidae, subfamilies Viperinae and Crotalinae. They remain an occupational hazard for farmers and rubber tappers, causing serious morbidity but only rare deaths, since competent treatment is now widely available throughout Thailand. Purified equine antivenin is manufactured locally for the monocled and Siamese spitting cobras (Naja kaouthia and N. siamensis), king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus), most green pit vipers (Trimeresurus sp.), Malayan pit viper (Calloselasma rhodostoma), and the Siamese Russell's viper (Daboia russelli siamensis).

  18. 3D Printed Shelby Cobra

    ScienceCinema

    Love, Lonnie

    2016-11-02

    ORNL's newly printed 3D Shelby Cobra was showcased at the 2015 NAIAS in Detroit. This "laboratory on wheels" uses the Shelby Cobra design, celebrating the 50th anniversary of this model and honoring the first vehicle to be voted a national monument. The Shelby was printed at the Department of Energy’s Manufacturing Demonstration Facility at ORNL using the BAAM (Big Area Additive Manufacturing) machine and is intended as a “plug-n-play” laboratory on wheels. The Shelby will allow research and development of integrated components to be tested and enhanced in real time, improving the use of sustainable, digital manufacturing solutions in the automotive industry.

  19. Indian common krait envenomation presenting as coma and hypertension: A case report and literature review

    PubMed Central

    Law, Arjun Datt; Agrawal, Anshu Kumar; Bhalla, Ashish

    2014-01-01

    Neuroparalytic snake bite is a common emergency situation encountered in India. Common krait (Bungarus caeruleus) and cobra (Naja naja) are important snakes causing neuroparalysis in North India. Despite severe neuroparalysis, patients who receive antivenin and ventilator support in time recover completely. Autonomic disturbances resulting in resting tachycardia, labile hypertension and sweating have been described in common krait envenomation. We present a case of common krait (B. caeruleus) envenomation presenting in the locked-in state and severe hypertension that remained in such a state for over 96 h before a gradual and sustained recovery. PMID:24812460

  20. Indian common krait envenomation presenting as coma and hypertension: A case report and literature review.

    PubMed

    Law, Arjun Datt; Agrawal, Anshu Kumar; Bhalla, Ashish

    2014-04-01

    Neuroparalytic snake bite is a common emergency situation encountered in India. Common krait (Bungarus caeruleus) and cobra (Naja naja) are important snakes causing neuroparalysis in North India. Despite severe neuroparalysis, patients who receive antivenin and ventilator support in time recover completely. Autonomic disturbances resulting in resting tachycardia, labile hypertension and sweating have been described in common krait envenomation. We present a case of common krait (B. caeruleus) envenomation presenting in the locked-in state and severe hypertension that remained in such a state for over 96 h before a gradual and sustained recovery.

  1. Field testing of the Cobra Seal System

    SciTech Connect

    Yellin, E.; Vodrazka, P. ); Ystesund, K.; Drayer, D. )

    1990-01-01

    The Cobra Seal System consists of a passive fiber optic seal and verification equipment which have been modified to take advantage of current technology. The seal permits on-site verification without requiring replacement of the seal. The modifications to the original Cobra Seal System extended the maximum fiber optic cable length from 1 meter to 10 meters. This improvement allowed the Cobra Seal to be considered for application on dry irradiated fuel storage canisters at two Canadian facilities. These canisters are located in an exterior environment exposed to extreme weather conditions. This paper describe the application of the Cobra Seal to these canisters, a housing for the protection of the Cobra Seal body from the environment, and some preliminary results of the IAEA field tests. 4 refs.

  2. Cobra communications switch integration program

    NASA Technical Reports Server (NTRS)

    Shively, Robert J.; Haworth, Loran A.; Szoboszlay, Zoltan; Murray, F. Gerald

    1989-01-01

    The paper describes a design modification to reduce the visual and manual workload associated with the radio selection and communications tasks in the U.S. Army AH-1 Cobra helicopter. The modification involves the integration of the radio selection and microphone actuating tasks into a single operation controlled by the transmit-intercom switch. Ground-based and flight tests were conducted to evaluate the modified configuration during twelve flight tasks. The results show that the proposed configuration performs twice as fast as the original configuration.

  3. Isolation and cloning of a metalloproteinase from king cobra snake venom.

    PubMed

    Guo, Xiao-Xi; Zeng, Lin; Lee, Wen-Hui; Zhang, Yun; Jin, Yang

    2007-06-01

    A 50 kDa fibrinogenolytic protease, ohagin, from the venom of Ophiophagus hannah was isolated by a combination of gel filtration, ion-exchange and heparin affinity chromatography. Ohagin specifically degraded the alpha-chain of human fibrinogen and the proteolytic activity was completely abolished by EDTA, but not by PMSF, suggesting it is a metalloproteinase. It dose-dependently inhibited platelet aggregation induced by ADP, TMVA and stejnulxin. The full sequence of ohagin was deduced by cDNA cloning and confirmed by protein sequencing and peptide mass fingerprinting. The full-length cDNA sequence of ohagin encodes an open reading frame of 611 amino acids that includes signal peptide, proprotein and mature protein comprising metalloproteinase, disintegrin-like and cysteine-rich domains, suggesting it belongs to P-III class metalloproteinase. In addition, P-III class metalloproteinases from the venom glands of Naja atra, Bungarus multicinctus and Bungarus fasciatus were also cloned in this study. Sequence analysis and phylogenetic analysis indicated that metalloproteinases from elapid snake venoms form a new subgroup of P-III SVMPs.

  4. Molecular characterization of L-amino acid oxidase from king cobra venom.

    PubMed

    Jin, Yang; Lee, Wen-Hui; Zeng, Lin; Zhang, Yun

    2007-09-15

    An L-amino acid oxidase from Ophiophagus hannah snake venom (Oh-LAAO) was purified by successive gel filtration, ion-exchange and heparin chromatography. Oh-LAAO did not induce platelet aggregation; however, it had potent inhibitory activity on platelet aggregation induced by ADP and U46619, but showed no effect on platelet aggregation induced by thrombin, mucetin, ristocetin and stejnulxin. By RT-PCR and 5'-RACE methods, the complete Oh-LAAO cDNA was cloned from the venom gland total RNA preparations. The cDNA sequence contains an open-reading frame (ORF) of 1476-bp, which encodes a protein of 491 amino acids comprising a signal peptide of 25 amino acids and 466-residue mature protein. The predicted protein sequence of Oh-LAAO was confirmed by N-terminal and trypsin-digested internal peptides sequencing together with peptide mass fingerprinting. cDNAs encoding for ORF of LAAOs from Bungarus fasciatus and B. multicinctus were cloned and reported in this study. In addition, partial cDNA encoding for Naja atra LAAO was also reported. Oh-LAAO shared approximately 50% protein sequence identity with other known snake venom LAAOs. Phylogenetic analysis indicated that Oh-LAAO is evolutionary distant to other snake venom LAAOs.

  5. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins.

    PubMed

    Chen, Ying-Jung; Tsai, Chia-Yu; Hu, Wan-Ping; Chang, Long-Sen

    2016-03-05

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electrophoretic mobility of aptamers against α-Bgt. Analysis of the changes in the fluorescence intensity of carboxyfluorescein-labeled aptamers upon binding toxin molecules revealed that CTX3 and α-Bgt could bind the tested aptamers. Moreover, the aptamers inhibited the membrane-damaging activity and cytotoxicity of CTX3. In addition to CTX3, other N. atra CTX isotoxins also bound to the aptamer against α-Bgt. Taken together, our data indicate that aptamers against α-Bgt show cross-reactivity with CTXs. The findings that aptamers against α-Bgt also suppress the biological activities of CTX3 highlight the potential utility of aptamers in regard to the broad inhibition of snake venom three-fingered proteins.

  6. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins

    PubMed Central

    Chen, Ying-Jung; Tsai, Chia-Yu; Hu, Wan-Ping; Chang, Long-Sen

    2016-01-01

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electrophoretic mobility of aptamers against α-Bgt. Analysis of the changes in the fluorescence intensity of carboxyfluorescein-labeled aptamers upon binding toxin molecules revealed that CTX3 and α-Bgt could bind the tested aptamers. Moreover, the aptamers inhibited the membrane-damaging activity and cytotoxicity of CTX3. In addition to CTX3, other N. atra CTX isotoxins also bound to the aptamer against α-Bgt. Taken together, our data indicate that aptamers against α-Bgt show cross-reactivity with CTXs. The findings that aptamers against α-Bgt also suppress the biological activities of CTX3 highlight the potential utility of aptamers in regard to the broad inhibition of snake venom three-fingered proteins. PMID:26959062

  7. 78 FR 13662 - Cobra Pipeline Ltd.; Notice of Petition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Cobra Pipeline Ltd.; Notice of Petition Take notice that on February 4, 2013, Cobra Pipeline Ltd. (Cobra) filed in Docket No. PR13-32-000 to correct a Tariff Record filed on...

  8. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immediately before that date. (c) If a deductible is computed on a family basis, the remaining deductible for the family on the date that COBRA continuation coverage begins depends on the members of the family electing COBRA continuation coverage. In computing the family deductible that remains on the date COBRA...

  9. Cobra sealing system; From field evaluation to practical safeguards application

    SciTech Connect

    Vodrazka, P.; Cermak, L. )

    1991-01-01

    After a successful conclusion of the Cobra seal IAEA field trials, the Cobra Seal System was installed in two Canadian facilities. The seals permit on-site verification without needing to replace them in extreme weather conditions, thus allowing a substantial time reduction for inspectors as well as minimizing intrusiveness of these activities. The paper describes experiences with practical installations of almost sixty Cobra seals including the selection of environmental conduits and housing. Examples of the results of the first several inspections utilizing a new version of the Cobra seal verifier are also included. Possible future outdoor applications of Cobra seals are described and some suggested improvements are outlined.

  10. Hybrid proteins of Cobra Venom Factor and cobra C3: tools to identify functionally important regions in Cobra Venom Factor.

    PubMed

    Hew, Brian E; Wehrhahn, Daniel; Fritzinger, David C; Vogel, Carl-Wilhelm

    2012-09-15

    Cobra Venom Factor (CVF) is the complement-activating protein in cobra venom. CVF is structurally and functionally highly homologous to complement component C3. CVF, like C3b, the activated form of C3, forms a bimolecular complex with Factor B in serum, called C3/C5 convertase, an enzyme which activates complement components C3 and C5. Despite the high degree of homology, the two C3/C5 convertases exhibit significant functional differences. The most important difference is that the convertase formed with CVF (CVF,Bb) is physico-chemically far more stable than the convertase formed with C3b (C3b,Bb). In addition, the CVF,Bb convertase and CVF are completely resistant to inactivation by the complement regulatory proteins Factor H and Factor I. Furthermore, the CVF,Bb enzyme shows efficient C5-cleaving activity in fluid phase. In contrast, the C3b,Bb enzyme is essentially devoid of fluid-phase C5-cleaving activity. By taking advantage of the high degree of sequence identity at both the amino acid (85%) and DNA levels (93%) between CVF and cobra C3, we created hybrid proteins of CVF and cobra C3 where sections, or only a few amino acids, of the CVF sequence were replaced with the homologous amino acid sequence of cobra C3. In a first set of experiments, we created five hybrid proteins, termed H1 through H5, where the cobra C3 substitutions collectively spanned the entire length of the CVF protein. We also created three additional hybrid proteins where only four or five amino acid residues in CVF were exchanged with the corresponding amino acid residues from cobra C3. Collectively, these hybrid proteins, representing loss-of-function mutants of CVF, allowed the identification of regions and individual amino acid residues important for the CVF-specific functions. The results include the observation that the CVF β-chain is crucially important for forming a stable convertase, whereas the CVF α-chain appears to harbor no CVF-specific functions. Furthermore, the CVF

  11. Similar efficacy and safety of initial COBRA-light and COBRA therapy in rheumatoid arthritis: 4-year results from the COBRA-light trial.

    PubMed

    Konijn, Nicole P C; van Tuyl, Lilian H D; Boers, Maarten; den Uyl, Debby; Ter Wee, Marieke M; van der Wijden, Lindsey K M; Bultink, Irene E M; Kerstens, Pit J S M; Voskuyl, Alexandre E; van Schaardenburg, Dirkjan; Nurmohamed, Michael T; Lems, Willem F

    2017-09-01

    To assess the efficacy and safety of initial COBRA-light vs COBRA therapy in RA patients after a 4-year follow-up period. In the COBRA-light trial, 162 consecutive patients with recent-onset RA were randomized to either COBRA-light (prednisolone and MTX) or COBRA therapy (prednisolone, MTX and SSZ) for 1 year. After 1 year, treatment was continued without protocol, and adjusted by the treating physician according to clinical judgement, preferably with a treat-to-target strategy. Four years after trial initiation, all patients were invited to participate in the COBRA-light extension study, in which patients were interviewed and physically examined, patient reported outcomes were assessed, radiographs were made and clinical records were examined for comorbidities and medication use. In the extension study, 149 out of 162 (92%) original trial patients participated: 72 COBRA-light and 77 COBRA patients. Initial COBRA-light and COBRA therapy showed similar effect on disease activity, physical functioning, radiological outcome and Boolean remission over the 4-year follow-up period. In addition, both treatment groups showed similar survival and major comorbidities, although the power to detect differences was limited. Besides protocolled differences in prednisolone, MTX and SSZ use, the use of other synthetic and biologic DMARDs and intra-articular and intramuscular glucocorticoid injections was similar in both treatment groups over the 4-year period. Early RA patients initially treated with COBRA-light or COBRA therapy had similar efficacy and safety outcomes over a 4-year follow-up period.

  12. Instant Print-Braille Compatibility with COBRA.

    ERIC Educational Resources Information Center

    Durre, Ingeborg K.; Durre, Imke

    1999-01-01

    Describes an eight-dot computer Braille notation, COBRA, with integrated mathematical and scientific notation that achieves immediate print-Braille compatibility through one-to-one representation of letters and other characters. Text can be entered from the Braille or the Qwerty Keyboard and can be viewed simultaneously on the Braille display and…

  13. JNK1/c-Jun and p38 alpha MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2.

    PubMed

    Chen, Ku-Chung; Chiou, Yi-Ling; Chang, Long-Sen

    2009-10-15

    Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A(2) (PLA(2)). PLA(2) treatment induced an increase in intracellular Ca(2+) ([Ca(2+)]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA(2), catalytically inactive PLA(2) treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA(2)-induced increase in Fas and FasL protein expression. Knockdown of p38 alpha MAPK and JNK1 by siRNA proved that p38 alpha MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38 alpha MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA(2) action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA(2) induces Fas and FasL upregulation through p38 alpha MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA(2) catalytic activity is involved in this action. (c) 2009 Wiley-Liss, Inc.

  14. Venom yields from Australian and some other species of snakes.

    PubMed

    Mirtschin, Peter J; Dunstan, Nathan; Hough, Ben; Hamilton, Ewan; Klein, Sharna; Lucas, Jonathan; Millar, David; Madaras, Frank; Nias, Timothy

    2006-08-01

    The wet and dry venom yields for most Australian native dangerous snakes and a number of non-Australian species are presented. Snakes from the Pseudonaja genus yielded higher than previously published amounts and suggest reconsideration be given to increasing the volume of antivenom in each vial. Higher percentage solids were obtained from venoms from the 4 cobra species (Naja) and Pseudechis genus included in this series.

  15. Cobra Fiber-Optic Positioner Upgrade

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.

    2013-01-01

    A prime focus spectrometer (PFS), along with corrective optics, will mount in place of the secondary mirror of the Subaru telescope on Mauna Kea, Hawaii. This will allow simultaneous observations of cosmologic targets. It will enable large-scale galactic archeology and dark energy surveys to help unlock the secrets of the universe. To perform these cosmologic surveys, an array of 2,400 optical fibers needs to be independently positioned within the 498-mm-diameter focal plane of the PFS instrument to collect light from galaxies and stars for spectrographic analyses. To allow for independent re-positioning of the fibers, a very small positioner (7.7 mm in diameter) is required. One hundred percent coverage of the focal plane is also required, so these small actuators need to cover a patrol region of 9.5 mm in diameter. To optimize the amount of light that can be collected, the fibers need to be placed within 5 micrometers of their intended target (either a star or galaxy). The Cobra Fiber Positioner was designed to meet the size and accuracy requirements stated above. Cobra is a two-degrees-of-freedom mechanism that can position an optical fiber in the focal plane of the PFS instrument to a precision of 5 micrometers. It is a theta-phi style positioner containing two rotary piezo tube motors with one offset from the other, which enables the optic fibers to be placed anywhere in a small circular patrol region. The patrol region of the actuator is such that the array of 2,400 positioners allows for full coverage of the instrument focal plane by overlapping the patrol areas. A second-generation Cobra positioner was designed based on lessons learned from the original prototype built in 2009. Improvements were made to the precision of the ceramic motor parts, and hard stops were redesigned to minimize friction and prevent jamming. These changes resulted in reducing the number of move iterations required to position the optical fiber within 5 micrometers of its target. At

  16. The COBRAS/SAMBA space mission

    SciTech Connect

    Mandolesi, N.; Bersanelli, M.; Cesarsky, C.; Danese, L.; Efstathiou, G.; Griffin, M.; Lamarre, J.M.; Norgaard-Nielsen, H.U.; Pace,O.; Puget, J.L.; Raisanen, A.; Smoot, GF.; Tauber, J.; Volonte, S.

    1996-12-04

    COBRAS/SAMBA is an ESA mission designed for extensive, accurate mapping of the anisotropies of the Cosmic Background Radiation, with angular sensitivity from sub-degree scales up to and overlapping with the COBE-DMR resolution. This will allow a full identification of the primordial density perturbations which grew to form the large-scale structures observed in the present universe. The COBRAS/SAMBA maps will provide powerful tests for the inflationary model and decisive answers on the origin of cosmic structure. A combination of bolometric and radiometric instrumentation will ensure the sensitivity and spectral coverage required for accurate foreground discrimination, A far-Earth orbit has been selected to minimize the unwanted emission from the Earth. The project is currently in the Phase A study within the European Space Agency M3 program.

  17. Hyaluronidase and protease activities from Indian snake venoms: neutralization by Mimosa pudica root extract.

    PubMed

    Girish, K S; Mohanakumari, H P; Nagaraju, S; Vishwanath, B S; Kemparaju, K

    2004-06-01

    The aqueous root extract of Mimosa pudica dose dependently inhibited the hyaluronidase and protease activities of Indian snakes (Naja naja, Vipera russelii and Echis carinatus) venom. Copyright 2004 Elsevier B.V.

  18. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... employee and spouse who have no children divorce on May 1, 2001, and the spouse elects COBRA continuation... divorce on June 1, 2001, and one of the children remains with the employee. The spouse elects COBRA... other reference in §§ 54.4980B-1 through 54.4980B-10 to coverage in effect immediately before (or on the...

  19. Evaluation of cytotoxicity of a purified venom protein from Naja kaouthia (NKCT1) using gold nanoparticles for targeted delivery to cancer cell.

    PubMed

    Bhowmik, Tanmoy; Saha, Partha Pratim; Sarkar, Amrita; Gomes, Antony

    2017-01-05

    In our earlier report, gold nanoparticle (GNP) and snake venom protein toxin NKCT1 were conjugated and primary characteristics were done. In this communication, further characteristics of GNP-NKCT1 were done with TGA, BET, Zeta potential, ICP-MS, FTIR, XPS, and in vitro release kinetics for its physicochemical, molecular nature and bonding. TGA and ICP-MS showed that the number of conjugation was 40 ± 5 to 90 ± 8 NKCT1 per gold nanoparticles. FTIR and XPS corresponding to (CO), (NH), (SS) reformulated the conjugation of GNP with NKCT1. The efficacy of GNP-NKCT1 on cancer cells were analyzed by MTT assay which demonstrated superior cytotoxic effects as compared to native NKCT1. IC50 dose of GNP-NKCT1 was less than 4 μg/ml in cancer cell lines, whereas in case of NKCT1 it was average 8 μg/ml. Twice dose of IC50 of GNP-NKCT1 even showed less toxicity compared to unconjugated NKCT1, towards normal epithelial or fibroblast cell and also in peripheral blood mononuclear lymphocytes. Flow cytometry analysis revealed that percentage of apoptotic C6 cells was much higher in GNP-NKCT1 treatment (54.58%) than that of NKCT1 treatment (26.79%). Flow cytometric analysis of cell cycle using GNP-NKCT1 on C6 cancer cells revealed that it arrested the cell cycle at Go/G1 phases. In diethylnitrosamine (DEN) induced in vivo hepatocarcinoma mice, the activities of hepatic enzymes- aspartate transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and activities of antioxidant enzymes- superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) were restored by GNP-NKCT1. This study indicated the capability of gold nanoparticles in enhancing the cancer cell uptake of NKCT1 and also suggested that GNP-NKCT1 might be a good source of anti-carcinoma or anti-sarcoma targeted agent.

  20. Social'naja sreda ucascihsja i ih sansy na uspevaemost' (The Social Background of Students and Their Prospect of Success at School).

    ERIC Educational Resources Information Center

    Ushinsky (K.D) State Scientific Library of the Academy of Pedagogical Sciences, Moscow (USSR).

    This document is an English-language abstract (approximately 1,500 words) of the Soviet response to an IBE questionnaire. It states that various agencies of the Soviet State maintain a continuing concern about school dropouts. A number of measures have been adopted to encourage students to finish school, such as improving educational methods,…

  1. Social'naja sreda ucascihsja i ih sansy na uspevaemost' (The Social Background of Students and Their Prospect of Success at School).

    ERIC Educational Resources Information Center

    Ushinsky (K.D) State Scientific Library of the Academy of Pedagogical Sciences, Moscow (USSR).

    This document is an English-language abstract (approximately 1,500 words) of the Soviet response to an IBE questionnaire. It states that various agencies of the Soviet State maintain a continuing concern about school dropouts. A number of measures have been adopted to encourage students to finish school, such as improving educational methods,…

  2. Seamless Handovers in Cobra Teardrop Satellite Arrays

    NASA Astrophysics Data System (ADS)

    Draim, John E.; Cefola, Paul J.; Ernandes, Kenneth J.

    2007-06-01

    Satellite systems provide the most efficient and possibly the only means of achieving two-way global communications with mobile systems (ships, aircraft, and vehicular traffic). To date, such systems have used only circular orbits, either GEO or LEO. Medium altitude elliptical constellations, on the other hand, can provide an efficient and affordable alternative to these architectures. Users also benefit from their very high average and minimum elevation angles, resulting in minimum signal attenuation. Cobra Teardrop is unique in that it employs time synchronized 8-h left- and right-leaning elliptical orbits giving mid-latitude observers the illusion of viewing a single satellite continuously orbiting almost directly overhead! In reality, observers see six different satellites per day, for 4 h each (while in their active duty cycles). By design, Teardrop satellites are physically in very close proximity at the handover points. This favorable geometry can be utilized to achieve a seamless handover from one satellite to the other (not requiring any electronic buffering). Handover is accomplished at the precise instant that the total path lengths from the transmitting station through both satellites to the receiving station are exactly equal. In these improved Cobra Teardrop arrays, an order of magnitude increase in global communications capacity (equivalent GEO slots) can be realized over earlier Basic Cobra systems. For decades into the future, these new orbital systems could satisfy a widely expanding range of commercial, government, and military high data rate communication requirements. These would include, but not be limited to, satellite cellular, air traffic control, meteorological, and combat net radio systems. With these arrays, a much larger number of system operators could be supported, without mutual electronic interference, than would ever be possible with circular orbits.

  3. Nested X Pinches on the COBRA Generator

    SciTech Connect

    Shelkovenko, T. A.; Pikuz, S. A.; McBride, R. D.; Knapp, P. F.; Wilhelm, H.; Hammer, D. A.; Sinars, D. B.

    2009-01-21

    Recent results of X pinch studies on the COBRA generator at Cornell University (peak current up to 1.2 MA and rise time of 100 ns) are presented. Using an initial configuration of wires before their twisting, similar to nested cylindrical wire arrays enables the assembly of a symmetric configuration at the X pinch crossing region. It also enables an investigation of multilayered X pinches. X pinches with different configurations, including with different materials in the inner and outer wire layers, were tested.

  4. COBRA ARRA subsidies: was the carrot enticing enough?

    PubMed

    Graetz, Ilana; Reed, Mary; Fung, Vicki; Dow, William H; Newhouse, Joseph P; Hsu, John

    2012-10-01

    To help preserve continuity of health insurance coverage during the recent recession, the American Recovery and Reinvestment Act provided a 65 percent Consolidated Omnibus Budget Reconciliation Act (COBRA) premium subsidy for workers laid off in 2008-2010. We examined COBRA enrollment levels with the subsidy and the health, access, and financial consequences of enrollment decisions. Telephone interviews linked with health system databases for 561 respondents who were laid off in 2009 and eligible for the COBRA subsidy (80 percent response rate). Overall, 38 percent reported enrolling in COBRA and 54 percent reported having some gaps in insurance coverage since being laid off. After adjustments, we found that those who had higher cost-sharing, who had higher incomes, were older, or were sicker were more likely to enroll in COBRA. COBRA enrollees less frequently reported access problems or that their health suffered because of poor access, but they reported greater financial stress due to health care spending. Despite the substantial subsidy, a majority of eligible individuals did not enroll in COBRA, and many reported insurance coverage gaps. Nonenrollees reported more access problems and that their health worsened. Without a mandate, subsidies may need to be widely publicized and larger to encourage health insurance enrollment among individuals who suffer a negative income shock. © Health Research and Educational Trust.

  5. Pro-inflammatory activities in elapid snake venoms.

    PubMed Central

    Tambourgi, D. V.; dos Santos, M. C.; Furtado, M. de F.; de Freitas, M. C.; da Silva, W. D.; Kipnis, T. L.

    1994-01-01

    1. Snake venoms from the genera Micrurus (M. ibiboboca and M. spixii) and Naja (N. naja, N. melanoleuca and N. nigricollis) were analysed, using biological and immunochemical methods, to detect pro-inflammatory activities, cobra venom factor (COF), proteolytic enzymes, thrombin-like substances, haemorrhagic and oedema-producing substances. 2. The venoms of the five snake species activate the complement system (C) in normal human serum (NHS) in a dose-related fashion, at concentrations ranging from 5 micrograms to 200 micrograms ml-1 serum. Electrophoretic conversion of C3 was observed with all venoms in NHS containing normal concentrations of Ca2+ and Mg2+, but only by venoms from N. naja and N. melanoleuca when Ca2+ was chelated by adding Mg(2+)-EGTA. 3. Purified human C3 was electrophoretically converted, in the absence of other C components, by the venoms from N. naja, N. nigricollis and M. ibiboboca. However, only the venoms from N. naja and N. melanoleuca contained a 144 kDa protein revealed in Western blot with sera against COF or human C3. 4. All venoms, at minimum concentrations of 30 ng ml-1, were capable of lysing sheep red blood cells, also in a dose-related fashion, when incubated with these cells in presence of egg yolk as a source of lecithin. Although the venoms from M. spixii and N. nigricollis showed detectable thrombin-like activity, these and the other venoms were free of proteolytic activity when fibrin, gelatin and casein, were used as substrates. 5. When tested on mice skin, all five venoms were capable of inducing an increase in vascular permeability and oedema, but were devoid of haemorrhagic producing substances (haemorrhagins).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 Figure 4 PMID:7921595

  6. North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.

    PubMed

    Richardson, William H; Tanen, David A; Tong, Tri C; Betten, David P; Carstairs, Shaun D; Williams, Saralyn R; Cantrell, Frank L; Clark, Richard F

    2006-02-01

    North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non-native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba). A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD50. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log-rank testing to compare survival rates and times. Preliminary studies estimated the venom LD50 to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV-venom groups and normal saline-venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/- 37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study. When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection

  7. INGEN: A COBRA-NC input generator user's manual

    SciTech Connect

    Wheeler, C.L.; Dodge, R.E.

    1986-12-01

    The INGEN (INput GENerator) computer program has been developed as a preprocessor to simplify input generation for the COBRA-NC computer program. INGEN uses several empirical correlations and geometric assumptions to simplify the data input requirements for the COBRA-NC computer code. The simplified input scheme is obtained at the expense of much flexibility provided by COBRA-NC. For more complex problems requiring additional flexibility however, INGEN may be used to provide a skeletal input file to which the more detailed input may be added. This report describes the input requirements for INGEN and describes the algorithms and correlations used to generate the COBRA-NC input. 9 refs., 3 figs., 6 tabs.

  8. The Cobra helmet mounted display system for Gripen

    NASA Astrophysics Data System (ADS)

    Larsson, Jörgen; Blomqvist, Tommy

    2008-04-01

    Selected to meet the stringent requirements of the Gripen swing-role combat aircraft, the Cobra Helmet Mounted Display System, has been integrated as a key component to the Gripen weapon delivery system. Saab Aerosystems has since 2003 together with BAE System been developing the Cobra HMD and in parallel integrating the system in Gripen for South Africa. Work is currently done to prepare other customer for the Cobra HMDS. This paper will highlight some technical challenges and experiences with integrating a HMDS in a small cockpit environment as in Gripen and present an overview of the Cobra HMD design and installation. Furthermore the paper will discuss the importance of having the pilots and users involved during the design phase and throughout the development.

  9. Assessment of the computer code COBRA/CFTL

    SciTech Connect

    Baxi, C. B.; Burhop, C. J.

    1981-07-01

    The COBRA/CFTL code has been developed by Oak Ridge National Laboratory (ORNL) for thermal-hydraulic analysis of simulated gas-cooled fast breeder reactor (GCFR) core assemblies to be tested in the core flow test loop (CFTL). The COBRA/CFTL code was obtained by modifying the General Atomic code COBRA*GCFR. This report discusses these modifications, compares the two code results for three cases which represent conditions from fully rough turbulent flow to laminar flow. Case 1 represented fully rough turbulent flow in the bundle. Cases 2 and 3 represented laminar and transition flow regimes. The required input for the COBRA/CFTL code, a sample problem input/output and the code listing are included in the Appendices.

  10. Status and Perspectives of the COBRA Experiment

    NASA Astrophysics Data System (ADS)

    Wonsak, Björn

    COBRA is a neutrinoless double beta decay (0νββ) experiment using an array of Cadmium-Zinc-Telluride semiconductor detectors, the isotope of interest being 116Cd with a Q-value of 2814 keV. To investigate the experimental challenges of operating CdZnTe detectors in low background mode and to identify potential background components, a demonstrator setup is operated at the Gran Sasso underground laboratory (LNGS) in Italy, while additional studies are proceeding in surface laboratories. The experiment consists of monolithic, calorimetric detectors of coplanar grid design (CPG de- tectors). These detectors have a size of 1×1×1 cm3 and are arranged in four layers of 4×4 detectors. An overview of the current status and of future perspectives is given. Results of pulse shape analyses are presented as well as background estimates using the data collected so far.

  11. COBRA - Neutrinoless Double Beta Decay Experiment

    NASA Astrophysics Data System (ADS)

    Heidrich, Nadine

    2012-08-01

    The COBRA experiment is searching for neutrinoless double beta decay using CdZnTe semiconductor detectors. The main focus is on Cd-116, with a decay energy of 2814keV well above the highest naturally occurring gamma lines. Furthermore, Te-130, with a high natural abundance, and Cd-106, a double β+ emitter, are under investigation. Advantageous is the possibility to operate the detectors at room temperature. Besides coplanar grid detectors, pixelised detectors are considered. The latter ones would allow for particle discrimination, therefore providing efficient background reduction. The current status of the experiment is described, including the upgrade of the R&D set-up in spring 2011 at the LNGS underground laboratory, the different detector concepts and the latest half -life limits. Furthermore, studies on the use of liquid scintillator for background suppression and Monte-Carlo simulations are presented.

  12. Appearance of Acetylcholine Receptors During Differentiation of a Myogenic Cell Line

    PubMed Central

    Patrick, Jim; Heinemann, Stephen F.; Lindstrom, Jon; Schubert, Dave; Steinbach, Joe Henry

    1972-01-01

    Acquisition of acetylcholine receptors during differentiation of a clonal myoblast cell line was monitored with a neurotoxin isolated from venom of the Indian Cobra Naja naja. Toxin bound specifically and reversibly to acetylcholine receptors of the differentiated cells. Specificity of the binding reaction was assayed by measurement of the ability of various cholinergic agonists and antagonists to compete with neurotoxin for its binding site. The rate of toxin binding paralleled the rate of inactivation of functional acetylcholine receptors, as measured by iontophoretic application of acetylcholine. Bound toxin was released from the cells with a half-life of about 7 hr. This release was not associated with a decrease in the total number of toxin-binding sites. A slow hyperpolarizing response to acetylcholine seen in myoblasts was insensitive to toxin; the appearance of toxin-binding sites parallels the appearance of fused fibers during differentiation of the muscle cells in tissue culture. Images PMID:4507600

  13. Species identification from dried snake venom.

    PubMed

    Singh, Chandra S; Gaur, Ajay; Sreenivas, Ara; Singh, Lalji

    2012-05-01

    Illegal trade in snake parts has increased enormously. In spite of strict protection under wildlife act, a large number of snakes are being killed ruthlessly in India for venom and skin. Here, an interesting case involving confiscation of crystallized dried snake venom and subsequent DNA-based species identification is reported. The analysis using the universal primers for cytochrome b region of the mitochondrial DNA revealed that the venom was extracted from an Indian cobra (Naja naja). On the basis of this report, the forwarding authority booked a case in the court of law against the accused for illegal hunting of an endangered venomous snake and smuggling of snake venom. This approach thus has immense potential for rapid identification of snake species facing endangerment because of illegal trade. This is also the first report of DNA isolation from dried snake venom for species identification.

  14. COBRA-Seq: Sensitive and Quantitative Methylome Profiling

    PubMed Central

    Varinli, Hilal; Statham, Aaron L.; Clark, Susan J.; Molloy, Peter L.; Ross, Jason P.

    2015-01-01

    Combined Bisulfite Restriction Analysis (COBRA) quantifies DNA methylation at a specific locus. It does so via digestion of PCR amplicons produced from bisulfite-treated DNA, using a restriction enzyme that contains a cytosine within its recognition sequence, such as TaqI. Here, we introduce COBRA-seq, a genome wide reduced methylome method that requires minimal DNA input (0.1–1.0 μg) and can either use PCR or linear amplification to amplify the sequencing library. Variants of COBRA-seq can be used to explore CpG-depleted as well as CpG-rich regions in vertebrate DNA. The choice of enzyme influences enrichment for specific genomic features, such as CpG-rich promoters and CpG islands, or enrichment for less CpG dense regions such as enhancers. COBRA-seq coupled with linear amplification has the additional advantage of reduced PCR bias by producing full length fragments at high abundance. Unlike other reduced representative methylome methods, COBRA-seq has great flexibility in the choice of enzyme and can be multiplexed and tuned, to reduce sequencing costs and to interrogate different numbers of sites. Moreover, COBRA-seq is applicable to non-model organisms without the reference genome and compatible with the investigation of non-CpG methylation by using restriction enzymes containing CpA, CpT, and CpC in their recognition site. PMID:26512698

  15. COBRA-WC: a version of COBRA for single-phase multiassembly thermal hydraulic transient analysis. [LMFBR

    SciTech Connect

    George, T.L.; Basehore, K.L.; Wheeler, C.L.; Prather, W.A.; Masterson, R.E.

    1980-07-01

    The objective of this report is to provide the user of the COBRA-WC (Whole Core) code a basic understanding of the code operation and capabilities. Included in this manual are the equations solved and the assumptions made in their derivations, a general description of the code capabilities, an explanation of the numerical algorithms used to solve the equations, and input instructions for using the code. Also, the auxiliary programs GEOM and SPECSET are described and input instructions for each are given. Input for COBRA-WC sample problems and the corresponding output are given in the appendices. The COBRA-WC code has been developed from the COBRA-IV-I code to analyze liquid Metal Fast Breeder Reactor (LMFBR) assembly transients. It was specifically developed to analyze a core flow coastdown to natural circulation cooling.

  16. Interfacial Catalysis: The Mechanism of Phospholipase A2

    PubMed Central

    Scott, David L.; White, Steven P.; Otwinowski, Zbyszek; Yuan, Wei; Gelb, Michael H.; Sigler, Paul B.

    2012-01-01

    A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2s. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme’s structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile. PMID:2274785

  17. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Interaction of FMLA and COBRA. 54.4980B-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-10 Interaction of FMLA and COBRA. The... 1993 (FMLA) (29 U.S.C. 2601-2619) affects the COBRA continuation coverage requirements: Q-1: In what...

  18. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Interaction of FMLA and COBRA. 54.4980B-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-10 Interaction of FMLA and COBRA. The... 1993 (FMLA) (29 U.S.C. 2601-2619) affects the COBRA continuation coverage requirements: Q-1: In what...

  19. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Interaction of FMLA and COBRA. 54.4980B-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-10 Interaction of FMLA and COBRA. The... 1993 (FMLA) (29 U.S.C. 2601-2619) affects the COBRA continuation coverage requirements: Q-1: In what...

  20. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Interaction of FMLA and COBRA. 54.4980B-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-10 Interaction of FMLA and COBRA. The... 1993 (FMLA) (29 U.S.C. 2601-2619) affects the COBRA continuation coverage requirements: Q-1: In what...

  1. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Interaction of FMLA and COBRA. 54.4980B-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-10 Interaction of FMLA and COBRA. The... 1993 (FMLA) (29 U.S.C. 2601-2619) affects the COBRA continuation coverage requirements: Q-1: In what...

  2. Verification and validation of COBRA-SFS transient analysis capability

    SciTech Connect

    Rector, D.R.; Michener, T.E.; Cuta, J.M.

    1998-05-01

    This report provides documentation of the verification and validation testing of the transient capability in the COBRA-SFS code, and is organized into three main sections. The primary documentation of the code was published in September 1995, with the release of COBRA-SFS, Cycle 2. The validation and verification supporting the release and licensing of COBRA-SFS was based solely on steady-state applications, even though the appropriate transient terms have been included in the conservation equations from the first cycle. Section 2.0, COBRA-SFS Code Description, presents a capsule description of the code, and a summary of the conservation equations solved to obtain the flow and temperature fields within a cask or assembly model. This section repeats in abbreviated form the code description presented in the primary documentation (Michener et al. 1995), and is meant to serve as a quick reference, rather than independent documentation of all code features and capabilities. Section 3.0, Transient Capability Verification, presents a set of comparisons between code calculations and analytical solutions for selected heat transfer and fluid flow problems. Section 4.0, Transient Capability Validation, presents comparisons between code calculations and experimental data obtained in spent fuel storage cask tests. Based on the comparisons presented in Sections 2.0 and 3.0, conclusions and recommendations for application of COBRA-SFS to transient analysis are presented in Section 5.0.

  3. The functional morphology of hooding in cobras.

    PubMed

    Young, Bruce A; Kardong, Kenneth V

    2010-05-01

    Many snakes, particularly cobras, form as part of a defensive display, a hood, an active lateral expansion of their neck skin and underlying musculature and ribs. We identified muscle groups possibly involved in hooding based on their attachments on the specialized ribs of the neck. We then used a combination of morphology, kinematic analysis, morphometrics, electromyography and muscle stimulation to test hypotheses about the functional basis of hooding. We confirmed that hood protraction and erection is an active process that begins cranially and extends caudally, often in stages, through the combined action of several sets of muscles. One set of axial muscles (levator costae and supracostalis lateralis superior) coursing along a line of action to rib displacement are the prime erectors acting to lift the hood. However, a second set of muscles connecting ribs to skin primarily keep the skin taut, rather than to displace the ribs relative to the vertebrae. A third set of muscles coursing between ribs function primarily to transmit forces between adjacent ribs rather than to move ribs. The maintenance of the erect hood requires continued muscle activity. Hood relaxation is due to both active muscle contraction of a fourth set of axial muscles and to passive recoil events in the costovertebral ligaments. The shape of the fully erect hood is reflective of the morphometrics of the underlying ribs, while the duration and kinematics of hood erection and relaxation are related to the behavioral context of the display.

  4. Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies.

    PubMed

    Pongjanyakul, Thaned; Prakongpan, Sompol; Panomsuk, Suwannee; Puttipipatkhachorn, Satit; Priprem, Aroonsri

    2002-10-01

    Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day(-1)) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P > 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P > 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R(2) > 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies.

  5. Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom.

    PubMed

    Osipov, Alexey V; Terpinskaya, Tatiana I; Kuznetsova, Tatiana E; Ryzhkovskaya, Elena L; Lukashevich, Vladimir S; Rudnichenko, Julia A; Ulashchyk, Vladimir S; Starkov, Vladislav G; Utkin, Yuri N

    2017-09-06

    We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor NGF effect, as well as on NGF-induced changes in EAC histological patterns, the activity of lactate and succinate dehydrogenases in tumor cells and the serum level of some cytokines. NGF, CVF and ketoprofen reduced the tumor volume by approximately 72%, 68% and 30%, respectively. The antitumor effect of NGF was accompanied by an increase in the lymphocytic infiltration of the tumor tissue, the level of interleukin 1β and tumor necrosis factor α in the serum, as well as the activity of lactate and succinate dehydrogenases in tumor cells. Simultaneous administration of NGF with either CVF or ketoprofen abolished the antitumor effect and reduced all other effects of NGF, whereas NGF itself significantly decreased the antitumor action of both CVF and ketoprofen. Thus, the antitumor effect of NGF critically depended on the status of the immune system and was abolished by the disturbance of the complement system; the disturbance of the inflammatory response canceled the antitumor effect as well.

  6. Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rheumatoid arthritis.

    PubMed

    Rasch, Linda A; van Tuyl, Lilian H D; Lems, Willem F; Boers, Maarten

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low. © 2014 S. Karger AG, Basel.

  7. The COBRA/CARMA Correlator Data Processing System

    NASA Astrophysics Data System (ADS)

    Scott, S. L.; Hobbs, R.; Beard, A.; Daniel, P.; Mehringer, D.; Plante, R.; Kraybill, J. C.; Wright, M.; Leitch, E.; Amarnath, N. S.; Pound, M. W.; Rauch, K. P.; Teuben, P. J.

    The Caltech Owens Valley Broadband Reprogrammable Array (COBRA) digital correlator is an FPGA based spectrometer with 16 MHz resolution and 4 GHz total bandwidth that will be commissioned on the Caltech Millimeter-wave Array in November, 2002. The Combined Array for Research in Millimeter-Wave Astronomy (CARMA) will join the Caltech array with the BIMA array on a new high elevation site in 2005. The COBRA hardware and computing architecture described here will be the basis for the two CARMA correlators. The COBRA architecture uses nine computers to provide the hardware interface and initial processing. Data is transported using CORBA to a tenth machine that implements the data processing pipeline as multiple processes passing data through shared memory.

  8. Cobra venom cytotoxins; apoptotic or necrotic agents?

    PubMed

    Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

    2015-12-15

    Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent.

  9. A non-inferiority trial of an attenuated combination strategy (‘COBRA-light’) compared to the original COBRA strategy: clinical results after 26 weeks

    PubMed Central

    den Uyl, Debby; ter Wee, Marieke; Boers, Maarten; Kerstens, Pit; Voskuyl, Alexandre; Nurmohamed, Mike; Raterman, Hennie; van Schaardenburg, Dirkjan; van Dillen, Nancy; Dijkmans, Ben; Lems, Willem

    2014-01-01

    Background Early, intensive treatment of rheumatoid arthritis (RA) with the combination of (initially high dose) prednisolone, methotrexate and sulfasalazine (COBRA therapy) considerably lowers disease activity and suppresses radiological progression, but is infrequently prescribed in daily practice. Attenuating the COBRA regimen might lessen concerns about side effects, but the efficacy of such strategies is unknown. Objective To compare the ‘COBRA-light’ strategy with only two drugs, comprising a lower dose of prednisolone (starting at 30 mg/day, tapered to 7.5 mg/day in 9 weeks) and methotrexate (escalated to 25 mg/week in 9 weeks) to COBRA therapy (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks, methotrexate 7.5 mg/week and sulfasalazine 2 g/day). Method An open, randomised controlled, non-inferiority trial in 164 patients with early active RA, all treated according to a treat to target strategy. Results At baseline patients had moderately active disease: mean (SD) 44-joint disease activity score (DAS44) 4.13 (0.81) for COBRA and 3.95 (0.9) for COBRA-light. After 6 months, DAS44 significantly decreased in both groups (–2.50 (1.21) for COBRA and –2.18 (1.10) for COBRA-light). The adjusted difference in DAS44 improvement between the groups, 0.21 (95% CI –0.11 to 0.53), was smaller than the predefined clinically relevant difference of 0.5. Minimal disease activity (DAS44 <1.6) was reached in almost half of patients in both groups (49% and 41% in COBRA and COBRA-light, respectively). Conclusions At 6 months COBRA-light therapy is most likely non-inferior to COBRA therapy. Clinical Trial Registration Number 55552928. PMID:23606682

  10. Target tracking during venom ‘spitting’ by cobras

    PubMed Central

    Westhoff, Guido; Boetig, Melissa; Bleckmann, Horst; Young, Bruce A.

    2010-01-01

    Spitting cobras, which defend themselves by streaming venom towards the face and/or eyes of a predator, must be highly accurate because the venom they spit is only an effective deterrent if it lands on the predator's cornea. Several factors make this level of accuracy difficult to achieve; the target is moving, is frequently >1 m away from the snake and the venom stream is released in approximately 50 ms. In the present study we show that spitting cobras can accurately track the movements of a potentially threatening vertebrate, and by anticipating its subsequent (short-term) movements direct their venom to maximize the likelihood of striking the target's eye. Unlike other animals that project material, in spitting cobras the discharge orifice (the fang) is relatively fixed so directing the venom stream requires rapid movements of the entire head. The cobra's ability to track and anticipate the target's movement, and to perform rapid cephalic oscillations that coordinate with the target's movements suggest a level of neural processing that has not been attributed to snakes, or other reptiles, previously. PMID:20472765

  11. [Spitting cobras: description of 2 cases in Djibouti].

    PubMed

    Rouvin, B; Kone, M; N'diaye, M; Seck, M; Diatta, B

    2010-02-01

    The purpose of this report is to describe two cases involving ophthalmic exposure to venom from spitting cobras. Based on these cases, readers are reminded that eye injury can be prevented by low-cost treatment consisting of prompt, prolonged saline irrigation. This treatment also reduces pain.

  12. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... coverage: Q-1: What is COBRA continuation coverage? A-1: (a) If a qualifying event occurs, each qualified beneficiary (other than a qualified beneficiary for whom the qualifying event will not result in any immediate... coverage that the qualified beneficiary had on the day before the qualifying event). See Q&A-3 of § 54...

  13. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... who would otherwise lose coverage under the plan as a result of a qualifying event an opportunity to... requirements were added to section 162 by the Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA... added parallel continuation coverage requirements to Part 6 of Subtitle B of title I of the Employee...

  14. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... who would otherwise lose coverage under the plan as a result of a qualifying event an opportunity to... requirements were added to section 162 by the Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA... added parallel continuation coverage requirements to Part 6 of Subtitle B of Title I of the Employee...

  15. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for topics not addressed in §§ 54.4980B-1 through 54.4980B-10? A-2: For purposes of section 4980B, for topics relating to the COBRA continuation coverage requirements of section 4980B that are not...

  16. "Cobra-like" deformation of an Amplatzer septal occluder.

    PubMed

    Mazic, U; Gavora, P; Masura, J

    2001-01-01

    Transcatheter occlusion of secundum atrial septal defects using Amplatzer septal occluders (ASOs) is a safe, simple, and effective alternative to surgical closure. We present the first report of a "cobra-like" shape deformation of the device encountered during inappropriate positioning. The complication is reversible and is easily avoidable.

  17. Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate-dependent transcriptional regulation of endothelial cell adhesion molecules.

    PubMed

    Wang, Yu-Ling; Kuo, Je-Hung; Lee, Shao-Chen; Liu, Jai-Shin; Hsieh, Yin-Cheng; Shih, Yu-Tsung; Chen, Chun-Jung; Chiu, Jeng-Jiann; Wu, Wen-Guey

    2010-11-26

    Cysteine-rich secretory proteins (CRISPs) have been identified as a toxin family in most animal venoms with biological functions mainly associated with the ion channel activity of cysteine-rich domain (CRD). CRISPs also bind to Zn(2+) at their N-terminal pathogenesis-related (PR-1) domain, but their function remains unknown. Interestingly, similar the Zn(2+)-binding site exists in all CRISP family, including those identified in a wide range of organisms. Here, we report that the CRISP from Naja atra (natrin) could induce expression of vascular endothelial cell adhesion molecules, i.e. intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin, to promote monocytic cell adhesion in a heparan sulfate (HS)- and Zn(2+)-dependent manner. Using specific inhibitors and small interfering RNAs, the activation mechanisms are shown to involve both mitogen-activated protein kinases and nuclear factor-κB. Biophysical characterization of natrin by using fluorescence, circular dichroism, and x-ray crystallographic methods further reveals the presence of two Zn(2+)-binding sites for natrin. The strong binding site is located near the putative Ser-His-Glu catalytic triad of the N-terminal domain. The weak binding site remains to be characterized, but it may modulate HS binding by enhancing its interaction with long chain HS. Our results strongly suggest that natrin may serve as an inflammatory modulator that could perturb the wound-healing process of the bitten victim by regulating adhesion molecule expression in endothelial cells. Our finding uncovers a new aspect of the biological role of CRISP family in immune response and is expected to facilitate future development of new therapeutic strategy for the envenomed victims.

  18. AN/FPS-108 COBRA DANE Space Surveillance Mission Evolution

    NASA Astrophysics Data System (ADS)

    Chorman, P.; Boggs, J.

    2013-09-01

    It has been ten years since the COBRA DANE radar was restored to continuous full power operations in a more dedicated role of space debris tracking. Over this time, the satellite catalog population has grown and the overall average RCS value of cataloged objects has decreased dramatically, due to a combination of breakups and collisions together with the increased sensitivity offered by COBRA DANE's support to the network. This shift in catalog composition places new challenges on COBRA DANE and other debris tracking radars (PARCS and Eglin/FPS-85) to consistently track the ever-increasing number of small objects. Space Surveillance Network radars now operate at the limits of their detection performance, tracking several thousand new objects in a size category that only the most powerful and sensitive radars can observe (i.e., < 10 cm diameter). However, for much of the last decade, COBRA DANE's inherent Spacetrack mission software functionality remained better tuned for its original support role against the larger (known) orbital objects than for its more modern role in acquiring and reporting small debris in an appreciable number -- that is, until now. Several newly-identified software changes offer promise of significantly increased data yield that will make COBRA DANE an even more important asset for this evolving mission. In the course of assisting JSpOC, AFSPC, and USSTRATCOM with the ongoing challenges of lost satellite management, it was discovered that the radar's performance is being artificially restricted by mission software, rather than by the system's overall architectural design (power-aperture envelope and radar resources). This paper captures specific opportunities to improve COBRA DANE's Spacetrack mission performance, several of which are currently implemented and slated to become operational with the next two software releases. With one of the more prominent enhancements, COBRA DANE will be capable of autonomously 'fence tasking' all newly

  19. The Arabidopsis COBRA protein facilitates cellulose crystallization at the plasma membrane.

    PubMed

    Sorek, Nadav; Sorek, Hagit; Kijac, Aleksandra; Szemenyei, Heidi J; Bauer, Stefan; Hématy, Kian; Wemmer, David E; Somerville, Chris R

    2014-12-12

    Mutations in the Arabidopsis COBRA gene lead to defects in cellulose synthesis but the function of COBRA is unknown. Here we present evidence that COBRA localizes to discrete particles in the plasma membrane and is sensitive to inhibitors of cellulose synthesis, suggesting that COBRA and the cellulose synthase complex reside in close proximity on the plasma membrane. Live-cell imaging of cellulose synthesis indicated that, once initiated, cellulose synthesis appeared to proceed normally in the cobra mutant. Using isothermal calorimetry, COBRA was found to bind individual β1-4-linked glucan chains with a KD of 3.2 μm. Competition assays suggests that COBRA binds individual β1-4-linked glucan chains with higher affinity than crystalline cellulose. Solid-state nuclear magnetic resonance studies of the cell wall of the cobra mutant also indicated that, in addition to decreases in cellulose amount, the properties of the cellulose fibrils and other cell wall polymers differed from wild type by being less crystalline and having an increased number of reducing ends. We interpret the available evidence as suggesting that COBRA facilitates cellulose crystallization from the emerging β1-4-glucan chains by acting as a "polysaccharide chaperone." © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. The Arabidopsis COBRA Protein Facilitates Cellulose Crystallization at the Plasma Membrane*

    PubMed Central

    Sorek, Nadav; Sorek, Hagit; Kijac, Aleksandra; Szemenyei, Heidi J.; Bauer, Stefan; Hématy, Kian; Wemmer, David E.; Somerville, Chris R.

    2014-01-01

    Mutations in the Arabidopsis COBRA gene lead to defects in cellulose synthesis but the function of COBRA is unknown. Here we present evidence that COBRA localizes to discrete particles in the plasma membrane and is sensitive to inhibitors of cellulose synthesis, suggesting that COBRA and the cellulose synthase complex reside in close proximity on the plasma membrane. Live-cell imaging of cellulose synthesis indicated that, once initiated, cellulose synthesis appeared to proceed normally in the cobra mutant. Using isothermal calorimetry, COBRA was found to bind individual β1–4-linked glucan chains with a KD of 3.2 μm. Competition assays suggests that COBRA binds individual β1–4-linked glucan chains with higher affinity than crystalline cellulose. Solid-state nuclear magnetic resonance studies of the cell wall of the cobra mutant also indicated that, in addition to decreases in cellulose amount, the properties of the cellulose fibrils and other cell wall polymers differed from wild type by being less crystalline and having an increased number of reducing ends. We interpret the available evidence as suggesting that COBRA facilitates cellulose crystallization from the emerging β1–4-glucan chains by acting as a “polysaccharide chaperone.” PMID:25331944

  1. MagLev Cobra: Test Facilities and Operational Experiments

    NASA Astrophysics Data System (ADS)

    Sotelo, G. G.; Dias, D. H. J. N.; de Oliveira, R. A. H.; Ferreira, A. C.; De Andrade, R., Jr.; Stephan, R. M.

    2014-05-01

    The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa2Cu3O7-δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

  2. Developing engineering model Cobra fiber positioners for the Subaru Telescope's prime focus spectrometer

    NASA Astrophysics Data System (ADS)

    Fisher, Charles; Morantz, Chaz; Braun, David; Seiffert, Michael; Aghazarian, Hrand; Partos, Eamon; King, Matthew; Hovland, Larry E.; Schwochert, Mark; Kaluzny, Joel; Capocasale, Christopher; Houck, Andrew; Gross, Johannes; Reiley, Daniel; Mao, Peter; Riddle, Reed; Bui, Khanh; Henderson, David; Haran, Todd; Culhane, Robert; Piazza, Daniele; Walkama, Eric

    2014-07-01

    The Cobra fiber positioner is being developed by the California Institute of Technology (CIT) and the Jet Propulsion Laboratory (JPL) for the Prime Focus Spectrograph (PFS) instrument that will be installed at the Subaru Telescope on Mauna Kea, Hawaii. PFS is a fiber fed multi-object spectrometer that uses an array of Cobra fiber positioners to rapidly reconfigure 2394 optical fibers at the prime focus of the Subaru Telescope that are capable of positioning a fiber to within 5μm of a specified target location. A single Cobra fiber positioner measures 7.7mm in diameter and is 115mm tall. The Cobra fiber positioner uses two piezo-electric rotary motors to move a fiber optic anywhere in a 9.5mm diameter patrol area. In preparation for full-scale production of 2550 Cobra positioners an Engineering Model (EM) version was developed, built and tested to validate the design, reduce manufacturing costs, and improve system reliability. The EM leveraged the previously developed prototype versions of the Cobra fiber positioner. The requirements, design, assembly techniques, development testing, design qualification and performance evaluation of EM Cobra fiber positioners are described here. Also discussed is the use of the EM build and test campaign to validate the plans for full-scale production of 2550 Cobra fiber positioners scheduled to begin in late-2014.

  3. Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?

    PubMed Central

    van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten

    2007-01-01

    Background The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow‐up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. Objective To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. Methods A short structured questionnaire based on social–psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). Results The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high‐dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. Conclusion The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient‐related consequences of the therapy. PMID:17392349

  4. Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?

    PubMed

    van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten

    2007-07-01

    The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow-up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. A short structured questionnaire based on social-psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high-dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient-related consequences of the therapy.

  5. Functional characterization of a tomato COBRA-like gene functioning in fruit development and ripening

    PubMed Central

    2012-01-01

    Background Extensive studies have demonstrated that the COBRA gene is critical for biosynthesis of cell wall constituents comprising structural tissues of roots, stalks, leaves and other vegetative organs, however, its role in fruit development and ripening remains largely unknown. Results We identified a tomato gene (SlCOBRA-like) homologous to Arabidopsis COBRA, and determined its role in fleshy fruit biology. The SlCOBRA-like gene is highly expressed in vegetative organs and in early fruit development, but its expression in fruit declines dramatically during ripening stages, implying a primary role in early fruit development. Fruit-specific suppression of SlCOBRA-like resulted in impaired cell wall integrity and up-regulation of genes encoding proteins involved in cell wall degradation during early fruit development. In contrast, fruit-specific overexpression of SlCOBRA-like resulted in increased wall thickness of fruit epidermal cells, more collenchymatous cells beneath the epidermis, elevated levels of cellulose and reduced pectin solubilization in the pericarp cells of red ripe fruits. Moreover, transgenic tomato fruits overexpressing SlCOBRA-like exhibited desirable early development phenotypes including enhanced firmness and a prolonged shelf life. Conclusions Our results suggest that SlCOBRA-like plays an important role in fruit cell wall architecture and provides a potential genetic tool for extending the shelf life of tomato and potentially additional fruits. PMID:23140186

  6. Antihemorrhagin in the blood serum of king cobra (Ophiophagus hannah): purification and characterization.

    PubMed

    Chanhome, Lawan; Khow, Orawan; Omori-Satoh, Tamotsu; Sitprija, Visith

    2003-06-01

    King cobra (Ophiophagus hannah) serum was found to possess antihemorrhagic activity against king cobra hemorrhagin. The activity was stronger than that in commercial king cobra antivenom. An antihemorrhagin has been purified by ion exchange chromatography, affinity chromatography and gel filtration with a 22-fold purification and an overall yield of 12% of the total antihemorrhagic activity contained in crude serum. The purified antihemorrhagin was homogeneous in disc-PAGE and SDS-PAGE. Its apparent molecular weight determined by SDS-PAGE was 120 kDa. The antihemorrhagin was also active against other hemorrhagic snake venoms obtained in Thailand and Japan such as Calloselasma rhodostoma, Trimeresurus albolabris, Trimeresurus macrops and Trimeresurus flavoviridis (Japanese Habu). It inhibited the proteolytic activity of king cobra venom. It is an acid- and thermolabile protein and does not form precipitin lines against king cobra venom.

  7. COBRA accelerator for Sandia ICF diode research at Cornell University

    NASA Astrophysics Data System (ADS)

    Smith, David L.; Ingwersen, Pete; Bennett, Lawrence F.; Boyes, John D.; Anderson, David E.; Greenly, John B.; Sudan, Ravi N.

    The new COBRA accelerator is being built in stages at the Laboratory of Plasma Studies in Cornell University where its applications will include extraction diode and ion beam research in support of the light ion inertial confinement fusion (ICF) program at Sandia National Laboratories. The 4- to 5-MV, 125- to 250-kA accelerator is based on a four-cavity inductive voltage adder (IVA) design. It is a combination of new ferromagnetically-isolated cavities and self magnetically insulated transmission line (MITL) hardware and components from existing Sandia and Cornell facilities: Marx generator capacitors, hardware, and power supply from the DEMON facility; water pulse forming lines (PFL) and gas switch from the Subsystem Test Facility (STF); a HERMES-3 intermediate store capacitor (ISC); and a modified ion diode from Cornell's LION. The present accelerator consists of a single modified cavity similar to those of the Sandia SABRE accelerator and will be used to establish an operating system for the first stage initial lower voltage testing. Four new cavities will be fabricated and delivered in the first half of FY96 to complete the COBRA accelerator. COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 180(degrees) about their vertical axis. The site preparations, tank construction, and diode design and development are taking place at Cornell with growing enthusiasm as this machine becomes a reality. Preliminary results with the single cavity and short positive inner cylinder MITL configuration will soon be available.

  8. COBRA accelerator for Sandia ICF diode research at Cornell University

    SciTech Connect

    Smith, D.L.; Ingwersen, P.; Bennett, L.F.; Boyes, J.D.; Anderson, D.E.; Greenly, J.B.; Sudan, R.N.

    1995-05-01

    The new COBRA accelerator is being built in stages at the Laboratory of Plasma Studies in Cornell University where its applications will include extraction diode and ion beam research in support of the light ion inertial confinement fusion (ICF) program at Sandia National Laboratories. The 4- to 5-MV, 125- to 250-kA accelerator is based on a four-cavity inductive voltage adder (IVA) design. It is a combination of new ferromagnetically-isolated cavities and self magnetically insulated transmission line (MITL) hardware and components from existing Sandia and Cornell facilities: Marx generator capacitors, hardware, and power supply from the DEMON facility; water pulse forming lines (PFL) and gas switch from the Subsystem Test Facility (STF); a HERMES-III intermediate store capacitor (ISC); and a modified ion diode from Cornell`s LION. The present accelerator consists of a single modified cavity similar to those of the Sandia SABRE accelerator and will be used to establish an operating system for the first stage initial lower voltage testing. Four new cavities will be fabricated and delivered in the first half of FY96 to complete the COBRA accelerator. COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 180{degrees} about their vertical axis. The site preparations, tank construction, and diode design and development are taking place at Cornell with growing enthusiasm as this machine becomes a reality. Preliminary results with the single cavity and short positive inner cylinder MITL configuration will soon be available.

  9. Dermatophilus chelonae in a king cobra (Ophiophagus hannah).

    PubMed

    Wellehan, James F X; Turenne, Christine; Heard, Darryl J; Detrisac, Carol J; O'Kelley, Jeffrey J

    2004-12-01

    A mass was removed from the left flank of a 10-yr-old male king cobra (Ophiophagus hannah), and histologic examination revealed granulomatous dermatitis with intralesional gram-positive cocci and filamentous bacteria. Fourteen months later, a histologically similar subcutaneous mass was removed from a different site. One year later, a large subcutaneous mass at the first surgical site was removed, and histopathologic examination revealed multiloculated granulomas with intralesional gram-positive cocci. An organism was cultured and identified by 16S ribosomal RNA gene sequencing as Dermatophilus chelonae. After a course of antibiotic therapy, no further lesions were seen for 5 mo.

  10. Tritium analyses of COBRA-1A2 beryllium pebbles

    SciTech Connect

    Baldwin, D.L.

    1998-03-01

    Selected tritium measurements have been completed for the COBRA-1A2 experiment C03 and D03 beryllium pebbles. The completed results, shown in Tables 1, 2, and 3, include the tritium assay results for the 1-mm and 3-mm C03 pebbles, and the 1-mm D03 pebbles, stepped anneal test results for both types of 1-mm pebbles, and the residual analyses for the stepped-anneal specimens. All results have been reported with date-of-count and are not corrected for decay. Stepped-anneal tritium release response is provided in addenda.

  11. COBRA System Engineering Processes to Achieve SLI Strategic Goals

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2003-01-01

    The COBRA Prototype Main Engine Development Project was an endeavor conducted as a joint venture between Pratt & Whitney and Aerojet to conduct risk reduction in LOX/LH2 main engine technology for the NASA Space Launch Initiative (SLI). During the seventeen months of the project (April 2001 to September 2002), approximately seventy reviews were conducted, beginning with the Engine Systems Requirements Review (SRR) and ending with the Engine Systems Interim Design Review (IDR). This paper discusses some of the system engineering practices used to support the reviews and the overall engine development effort.

  12. Generation and characterization of transgenic mice expressing cobra venom factor.

    PubMed

    Andrä, Jörg; Halter, Roman; Kock, Michael A; Niemann, Heiner; Vogel, Carl-Wilhelm; Paul, Dieter

    2002-10-01

    Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates the alternative complement pathway, eventually leading to complement consumption. Here, we describe the development of a transgenic mouse model for CVF. We generated a DNA construct containing the full-length cDNA for single-chain pre-pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to achieve liver-specific expression. Linearized DNA was microinjected into murine ovary cells (strain CD(2)F(1) (BALB/cxDBA/2J)) and the newborn mice were analyzed for stable integration of CVF DNA. After establishing the transgene, mice were propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in some animals, in the kidney. CVF protein was detected in small amounts in the serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually absent. The concentration of plasma C3 was significantly reduced. The CVF-transgenic animals show no unusual phenotype. They provide an animal model to study the effect of long-term complement depletion by continued activation, as well as the role of complement in host immune response and pathogenesis of disease.

  13. A fatal cobra-bite in a snake expert.

    PubMed

    Hossain, M Z; Atiqullah, S; Saha, A C; Chowdhury, A J; Jahangir, K M; Faiz, M A

    2010-04-01

    A 35-year-old so called snake-expert from Thakurgaon district was admitted in Medicine department of Rangpur Medical College Hospital (RpMCH), Rangpur, Bangladesh on 2nd November 2007 with history of bites by a cobra snake. He was famous for his outstanding works to establish a snake farm first ever in Bangladesh. He had a collection of more than one hundred snakes of different species. He used to hatch eggs of the snakes, feed the young-snakes, collect venoms and sell those. Everyday many visitors used to visit his farm to watch exciting games with poisonous snakes. Several satellite television (TV) channels and some daily newspapers had covered him on different occasions. He was accidentally bitten by a newly caught hungry cobra snake while recording for a satellite TV channel. Following bites he was brought to the hospital three and a half hours later. By that time, neurotoxicity developed. Repeated doses of Anti Snake Venom (ASV) along with respiratory support and other supportive cares were provided. Despite utmost care feasible at RpMCH, patient expired around 49 hours later.

  14. [CO2 Budget and Atmospheric Rectification (COBRA) Over North America

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The purpose of the CO2 Budget and Rectification Airborne (COBRA) study was to assess terrestrial sources and sinks of carbon dioxide using an air-borne study. The study was designed to address the measurement gap between plot-scale direct flux measurements and background hemispheric-scale constraints and to refine techniques for measuring terrestrial fluxes at regional to continental scales. The initial funded effort (reported on here) was to involve two air-borne campaigns over North America, one in summer and one in winter. Measurements for COBRA (given the acronym C02BAR in the initial proposal) were conducted from the University of North Dakota Citation 11, a twin-engine jet aircraft capable of profiling from the surface to 12 km and cruising for up to 4 hours and 175m/s. Onboard instrumentation measured concentrations of CO2, CO, and H2O, and meteorological parameters at high rates. In addition, two separate flask sampling systems collected discrete samples for laboratory analysis of CO2,CO, CH4, N2O, SF6, H2, 13CO2, C18O16O,O2/N2, and Ar/N2. The project involved a collaboration between a number of institutions, including (but not limited to) Harvard, NOAA-CMDL, the University of North Dakota, and Scripps.

  15. [CO2 Budget and Atmospheric Rectification (COBRA) Over North America

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The purpose of the CO2 Budget and Rectification Airborne (COBRA) study was to assess terrestrial sources and sinks of carbon dioxide using an air-borne study. The study was designed to address the measurement gap between plot-scale direct flux measurements and background hemispheric-scale constraints and to refine techniques for measuring terrestrial fluxes at regional to continental scales. The initial funded effort (reported on here) was to involve two air-borne campaigns over North America, one in summer and one in winter. Measurements for COBRA (given the acronym C02BAR in the initial proposal) were conducted from the University of North Dakota Citation 11, a twin-engine jet aircraft capable of profiling from the surface to 12 km and cruising for up to 4 hours and 175m/s. Onboard instrumentation measured concentrations of CO2, CO, and H2O, and meteorological parameters at high rates. In addition, two separate flask sampling systems collected discrete samples for laboratory analysis of CO2,CO, CH4, N2O, SF6, H2, 13CO2, C18O16O,O2/N2, and Ar/N2. The project involved a collaboration between a number of institutions, including (but not limited to) Harvard, NOAA-CMDL, the University of North Dakota, and Scripps.

  16. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    PubMed

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  17. Study of gas-puff Z-pinches on COBRA

    SciTech Connect

    Qi, N.; Rosenberg, E. W.; Gourdain, P. A.; Grouchy, P. W. L. de; Kusse, B. R.; Hammer, D. A.; Bell, K. S.; Shelkovenko, T. A.; Potter, W. M.; Atoyan, L.; Cahill, A. D.; Evans, M.; Greenly, J. B.; Hoyt, C. L.; Pikuz, S. A.; Schrafel, P. C.; Kroupp, E.; Fisher, A.; Maron, Y.

    2014-11-15

    Gas-puff Z-pinch experiments were conducted on the 1 MA, 200 ns pulse duration Cornell Beam Research Accelerator (COBRA) pulsed power generator in order to achieve an understanding of the dynamics and instability development in the imploding and stagnating plasma. The triple-nozzle gas-puff valve, pre-ionizer, and load hardware are described. Specific diagnostics for the gas-puff experiments, including a Planar Laser Induced Fluorescence system for measuring the radial neutral density profiles along with a Laser Shearing Interferometer and Laser Wavefront Analyzer for electron density measurements, are also described. The results of a series of experiments using two annular argon (Ar) and/or neon (Ne) gas shells (puff-on-puff) with or without an on- (or near-) axis wire are presented. For all of these experiments, plenum pressures were adjusted to hold the radial mass density profile as similar as possible. Initial implosion stability studies were performed using various combinations of the heavier (Ar) and lighter (Ne) gasses. Implosions with Ne in the outer shell and Ar in the inner were more stable than the opposite arrangement. Current waveforms can be adjusted on COBRA and it was found that the particular shape of the 200 ns current pulse affected on the duration and diameter of the stagnated pinched column and the x-ray yield.

  18. Contributing Factors for Complications and Outcomes in Patients With Snakebite: Experience in a Medical Center in Southern Taiwan.

    PubMed

    Hsieh, Yu-Hsuan; Hsueh, Jung-Hua; Liu, Wen-Chung; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Ho, Yen-Yi; Chen, Lee-Wei

    2017-03-01

    Snakebite usually results in various complications, such as significant soft tissue damage, infection, hematological, and neurological deficit. Surgical intervention, usually, is indicated in patients with tissue necrosis, infection, and compartment syndrome. To identify the contributing factors for complications and outcomes in different patients with snakebite so that outcomes can be evaluated and treatment of such patients can be initiated at the earliest. Information was collected regarding age, sex, underlying disease, species of snake, and the course of treatment of the victims of snakebite who visited the emergency department of a medical center in southern Taiwan between 2004 and 2014. The data obtained were analyzed using SPSS 20.0. The bites from Taiwan cobra (Naja naja atra) significantly resulted in more complications than those from other snakes and required surgical intervention. The use of antivenin and antibiotics, immediate presentation to the hospital, and the location of the bite also were significant contributing factors. Taiwan cobra significantly results in higher possibility of prolonged hospitalization, operation, tissue necrosis, infection, and necrotizing fasciitis. Location of the bite, immediate presentation to the hospital, and use of antivenin and antibiotics affect the outcome of snakebite. Knowledge of these factors will help in a better management of patients with snakebite.

  19. Tick infestation on wild snakes in northern part of western Ghats of India.

    PubMed

    Pandit, Pranav; Bandivdekar, Ruta; Geevarghese, G; Pande, Satish; Mandke, Omkar

    2011-05-01

    In total, 167 individuals of 30 species of snakes belonging to 22 genera and five families were examined for tick infestation from November 2008 to March 2010. Only two species of snakes, Ptyas mucosa (L., 1758) (Indian rat snake) and Naja naja (L., 1758) (spectacled cobra), were found infested by ticks. All ticks collected were identified to be Amblyomma gervaisi [previously Aponomma gervaisi (Lucas, 1847) 1. The average prevalence of these ticks on Indian rat snakes (n=48) was 29.16%, with abundance of 7.02 ticks per individual; on spectacled cobras (n=20), average prevalence was 30.00%, with abundance of 6.9 ticks per individual. The nymphs and males were predominant. All the ticks were found on the dorsal aspect of the body of the snake, and no ticks were recorded on the head, tail, or ventral body. The rate of tick infestation was highest in scrubland and was lowest in evergreen forests. Female Indian rat snakes showed higher tick infestation rates than male Indian rat snakes. Using Mann-Whitney U test, we found that longer snakes of both species had significantly higher rate of tick infestation in both the species of snakes.

  20. Synchronization and an application of a novel fractional order King Cobra chaotic system.

    PubMed

    Muthukumar, P; Balasubramaniam, P; Ratnavelu, K

    2014-09-01

    In this paper, we design a new three dimensional King Cobra face shaped fractional order chaotic system. The multi-scale synchronization scheme of two fractional order chaotic systems is described. The necessary conditions for the multi-scale synchronization of two identical fractional order King Cobra chaotic systems are derived through feedback control. A new cryptosystem is proposed for an image encryption and decryption by using synchronized fractional order King Cobra chaotic systems with the supports of multiple cryptographic assumptions. The security of the proposed cryptosystem is analyzed by the well known algebraic attacks. Numerical simulations are given to show the effectiveness of the proposed theoretical results.

  1. Synchronization and an application of a novel fractional order King Cobra chaotic system

    SciTech Connect

    Muthukumar, P. Balasubramaniam, P.; Ratnavelu, K.

    2014-09-01

    In this paper, we design a new three dimensional King Cobra face shaped fractional order chaotic system. The multi-scale synchronization scheme of two fractional order chaotic systems is described. The necessary conditions for the multi-scale synchronization of two identical fractional order King Cobra chaotic systems are derived through feedback control. A new cryptosystem is proposed for an image encryption and decryption by using synchronized fractional order King Cobra chaotic systems with the supports of multiple cryptographic assumptions. The security of the proposed cryptosystem is analyzed by the well known algebraic attacks. Numerical simulations are given to show the effectiveness of the proposed theoretical results.

  2. [Biological and immunological researches on snake venom. V. Application of the immunochemical technics to the titration of specific antibodies to the alpha toxin of Naja nigricollis venom (author's transl)].

    PubMed

    Mangalo, R; Fouque, F; Boquet, P

    1977-01-01

    In order to establish a simple method to titrate antitoxin antibodies in the antivenom sera, we suggest a new immunochemical technic. To a constant dose of a pure toxin extracted from a snake venom, increasing volumes of specific immune serum are added so as an excess of toxin remains free. This residual toxin is titrated by electroimmunodiffusion technic according to Laurell or by radial immunodiffusion method of Mancini. The experimental results in vitro are compared to those obtained in vivo. If a given volume of immune serum neutralize X microgram of toxin by the in vivo technic it will combine in vitro to 2 X or 1.2 X of the same toxin, respectively if we refer to electroimmunodiffusion or to radial immunodiffusion technic results.

  3. Use of Cobra Lily (Darlingtonia californica) & Drosophila for Investigating Predator-Prey Relationships.

    ERIC Educational Resources Information Center

    Pratt, Carl R.

    1994-01-01

    Describes an experiment that uses the cobra lily (Darlingtonia californica) and fruit flies (Drosophila virilis) to investigate predator-prey relationships in a classroom laboratory. Suggestions for classroom extension of this experimental system are provided. (ZWH)

  4. Use of Cobra Lily (Darlingtonia californica) & Drosophila for Investigating Predator-Prey Relationships.

    ERIC Educational Resources Information Center

    Pratt, Carl R.

    1994-01-01

    Describes an experiment that uses the cobra lily (Darlingtonia californica) and fruit flies (Drosophila virilis) to investigate predator-prey relationships in a classroom laboratory. Suggestions for classroom extension of this experimental system are provided. (ZWH)

  5. COBRA-SFS modifications and cask model optimization

    SciTech Connect

    Rector, D.R.; Michener, T.E.

    1989-01-01

    Spent-fuel storage systems are complex systems and developing a computational model for one can be a difficult task. The COBRA-SFS computer code provides many capabilities for modeling the details of these systems, but these capabilities can also allow users to specify a more complex model than necessary. This report provides important guidance to users that dramatically reduces the size of the model while maintaining the accuracy of the calculation. A series of model optimization studies was performed, based on the TN-24P spent-fuel storage cask, to determine the optimal model geometry. Expanded modeling capabilities of the code are also described. These include adding fluid shear stress terms and a detailed plenum model. The mathematical models for each code modification are described, along with the associated verification results. 22 refs., 107 figs., 7 tabs.

  6. The effect of cuff pressure on postoperative sore throat after Cobra perilaryngeal airway.

    PubMed

    Joe, Han Bum; Kim, Dae Hee; Chae, Yun Jeong; Kim, Jong Yeop; Kang, Min; Park, Kwan Sik

    2012-04-01

    The cuff volume of the Cobra perilaryngeal airway (CobraPLA) is larger than that of other alternative airway devices and makes it difficult to predict the effect of cuff pressure on the perilaryngeal mucosa. We tested the hypothesis that adjustment of the cuff pressure of the CobraPLA could reduce the incidence of postoperative sore throat (POST). After induction of general anesthesia and insertion of the CobraPLA by standardized method, the cuff pressure was set to 60 cmH(2)O (group C, n = 87) or adjusted to minimal seal-up pressure +5 cmH(2)O (group A, n = 87). The frequency and severity (0, none; 1, mild; 2, moderate; 3, severe) of throat soreness, pain, discomfort, and adverse effects were evaluated 1 and 24 h after removal of the CobraPLA. Incidence of moderate POST in group C was higher than that in group A (11% vs. 2%, P = 0.021) whereas the overall POST incidence was not different between the two groups (31% vs. 20%, P = 0.092). The inflated air volume of group A was different from that of group C (41 vs. 50 ml, P = 0.009). Adjustment of cuff pressure reduces the incidence of moderate POST after use of the CobraPLA.

  7. Clinical features and treatment experience: a review of 292 Chinese cobra snakebites.

    PubMed

    Wang, Wei; Chen, Quan-Fang; Yin, Rui-Xing; Zhu, Ji-Jin; Li, Qi-Bin; Chang, Hai-Hua; Wu, Yan-Bi; Michelson, Edward

    2014-03-01

    Although Chinese cobra snakebite is the most common type of snake venenation in China, it still lacks a comprehensive and systematic description. Hence, we aimed to study Chinese cobra bite cases with particular attention to demography, epidemiology and clinical profile. In this study, a total of 292 cases of Chinese cobra snakebite, presenting between January 1, 2008 and December 31, 2012, were retrospectively reviewed. To investigate the effect of treatment at different presentation times (time from snakebite to admission), the patients were divided into two groups: group A included 133 cases that presented <12 h after the bite; group B included 159 cases that presented ≥12 h after the bite. To assess the correlation between application of a tourniquet and skin grafting, the cases were re-divided into two groups according to whether or not a tourniquet was used after the snakebite: tourniquet group (n=220) and non-tourniquet group (n=72). The results showed that Chinese cobra snakebites were most commonly seen during the summer, in the upper limbs, and in males, young adults, and snake-hunters. Group A experienced milder intoxication than group B (P<0.001). The rate of skin grafting was significantly higher in the tourniquet group (20.0%, compared with 9.7% in the non-tourniquet group, P<0.05). The results of this study indicate that anti-cobra venom and swift admission (within 12 h of the snakebite) are recommended for Chinese cobra snakebite. Tourniquet use is not recommended.

  8. COBRA ATD minefield detection results for the Joint Countermine ACTD Demonstrations

    NASA Astrophysics Data System (ADS)

    Stetson, Suzanne P.; Witherspoon, Ned H.; Holloway, John H., Jr.; Suiter, Harold R.; Crosby, Frank J.; Hilton, Russell J.; McCarley, Karen A.

    2000-08-01

    The Coastal Battlefield Reconnaissance and Analysis)COBRA) system described here was a Marine Corps Advanced Technology Demonstration (ATD) development consisting of an unmanned aerial vehicle (UAV) airborne multispectral video sensor system and ground station which processes the multispectral video data to automatically detect minefields along the flight path. After successful completion of the ATD, the residual COBRA ATD system participated in the Joint Countermine (JCM) Advanced Concept Technology Demonstration (ACTD) Demo I held at Camp Lejeune, North Carolina in conjunction with JTFX97 and Demo II held in Stephenville, Newfoundland in conjunction with MARCOT98. These exercises demonstrated the COBRA ATD system in an operational environment, detecting minefields that included several different mine types in widely varying backgrounds. The COBRA system performed superbly during these demonstrations, detecting mines under water, in the surf zone, on the beach, and inland, and has transitioned to an acquisition program. This paper describes the COBRA operation and performance results for these demonstrations, which represent the first demonstrated capability for remote tactical minefield detection from a UAV. The successful COBRA technologies and techniques demonstrated for tactical UAV minefield detection in the Joint Countermine Advanced Concept Technology Demonstrations have formed the technical foundation for future developments in Marine Corps, Navy, and Army tactical remote airborne mine detection systems.

  9. First molecular characterization of enteric protozoa and the human pathogenic microsporidian, Enterocytozoon bieneusi, in captive snakes in China.

    PubMed

    Karim, Md Robiul; Yu, Fuchang; Li, Jian; Li, Junqiang; Zhang, Longxian; Wang, Rongjun; Rume, Farzana Islam; Jian, Fuchun; Zhang, Sumei; Ning, Changshen

    2014-08-01

    Enteric protozoa are frequently found in snakes. Nevertheless, few studies regarding genetic characterization of these parasites have been carried out. We describe here the first molecular survey of protozoan pathogens from snakes in China and the first report on Enterocytozoon bieneusi genotyping in snakes in the world. Here, 240 fecal specimens were collected from two species of captive snakes, Naja naja (Indian cobra) and Ptyas mucosus (Oriental rat snake), in Guangxi Province, China, and examined by PCR amplification of the small subunit-ribosomal RNA of enteric protozoa and the internal transcribed spacer of ribosomal RNA of E. bieneusi. Cryptosporidium serpentis was identified in three specimens (2.1%) of Oriental rat snakes. Caryospora was found in 5.4% specimens, including eight from cobras (8.1%) and five from rat snakes (3.6%), and represented six new species-Caryospora sp. SKC-2014a to Caryospora sp. SKC-2014 f. Three new Eimeria species, Eimeria sp. SKE-2014a to Eimeria sp. SKE-2014c, were detected in three specimens (2.1%) from rat snakes. Additionally, Sarcocystis sp. SKS-2014 was detected in one specimen from a cobra. The infection rates of E. bieneusi were 3.0% in cobras and 5.7% in rat snakes. Sequence analysis of 11 PCR products revealed the presence of six E. bieneusi genotypes-two known genotypes (type IV and Henan V) and four new genotypes (CRep-1 to CRep-4). All six E. bieneusi genotypes belonged to the zoonotic group (group 1). This result raised the possibility that E. bieneusi could be present in animals consumed by snakes. This should be taken into consideration to better understand the diversity of the parasite, its transmission through the predator-prey relationship, and public health implications.

  10. Taming the "cobra": an approach to "cobra-like" formation seen in the Occlutech atrial septal defect and patent foramen ovale occluders.

    PubMed

    Aaron, Sagiv; Mainzer, Gur; Lorber, Avraham

    2012-03-01

    Percutaneous closure of secundum atrial septal defect and patent foramen ovale has gained widespread use in recent years. We present a small series of four cases in which a "cobra-like" formation occurred in an Occlutech Figulla device during the deployment of the left disk, and propose a technique that may resolve this problem. Copyright © 2011 Wiley Periodicals, Inc.

  11. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis.

    PubMed

    van Tuyl, Lilian H D; Boers, Maarten; Lems, Willem F; Landewé, Robert B; Han, Huub; van der Linden, S; van de Laar, Mart; Westhovens, Rene; van Denderen, J Christiaan; Westedt, Marie-Louise; Peeters, André J; Jacobs, Piet; Huizinga, Tom W J; van de Brink, Hans; Dijkmans, Ben A C; Voskuyl, Alexandre E

    2010-05-01

    COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests. In all, 152 out of 155 patients yielded at least partial data. After a mean of 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, HR 0.57 (95% CI 0.21 to 1.52). Treatment for hypertension was significantly more prevalent in the COBRA group (p=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolaemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, that is, difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, that is, difference in yearly progression rates similar to that seen in the first 5 years of follow-up. After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

  12. The use of remifentanil to facilitate the insertion of the Cobra perilaryngeal airway.

    PubMed

    Jeon, Woo Jae; Kim, Kyoung Hun; Suh, Jung Kook; Cho, Sang Yun

    2009-05-01

    The use of remifentanil before propofol administration facilitates the insertion of the Laryngeal Mask Airway. We designed the present study to determine whether remifentanil would also create more suitable conditions for providing Cobra Perilaryngeal airway (CobraPLA) insertion when administered with propofol. Both remifentanil and propofol were given as effect-site target-controlled infusions. There were four groups of 25 patients each. The propofol effect-site concentration was set at 6 microg/mL in all groups. Group R1 received a target effect-site remifentanil concentration of 1 ng/mL, Group R2 received remifentanil at 2 ng/mL, Group R3 received remifentanil at 3 ng/mL, and Group R4 received remifentanil at 4 ng/mL before the induction of anesthesia with propofol. The ease of insertion of CobraPLA was graded by the following 3-point scale: Grade 1, excellent, no response to CobraPLA insertion; Grade 2, acceptable, gagging or swallowing with insertion of CobraPLA; Grade 3, poor, unable to open mouth or biting upon insertion of CobraPLA. The most patients ranked as excellent for the first CobraPLA insertion (Grade 1) were found in Group R4, which was significantly higher than Groups R1 and R2 (P < 0.01), whereas no significant difference was found when compared with Group R3. The duration of apnea showed a significant dose-related increase (P < 0.01), especially between Group R2 (median 2.95 min) and R3 (median 7.9 min), but there was no significant difference between Groups R3 and R4. The incidence of hypotension in Group R4 within 1 min after insertion of CobraPLA was significantly more than for Groups R1 and R2 (P < 0.01). No significant differences could be found between the incidence of hypotension between Group R3 and the other groups. The incidence of hypertension at 1 min postinsertion was significantly more common in Groups R1 and R2 than Groups R3 and R4 (P < 0.01). An effect-site concentration of remifentanil of 2 ng/mL provides excellent conditions

  13. The effect of cyclosporine, total lymphoid irradiation, and cobra venom factor on hyperacute rejection.

    PubMed

    Knechtle, S J; Halperin, E C; Murphy, C E; Saad, T; Abernethy, K; Miller, D; Bollinger, R R

    1985-01-01

    Transplantation into sensitized recipients is contraindicated due to the potential for hyperacute rejection. In order to study the mechanism of hyperacute rejection and the role of immunosuppression in the face of presensitization, we evaluated the effect of total lymphoid irradiation, cyclosporine, and cobra venom factor, alone and in combination, on hyperacute rejection of heterotopic rat heart allografts. Lewis rats were sensitized to strongly RT-1-incompatible ACI rats by three successive skin grafts. Heart allografts were then performed, and survived for a mean period of 15.7 +/- 7.4 hours. Neither preoperative treatment of hypersensitized rats with total lymphoid irradiation alone nor with cyclosporine (5 mg/kg/day) resulted in a prolongation of survival (20.4 +/- 16.6 hours and 35.6 +/- 6.2 hours, respectively). However, complement depletion using cobra venom factor significantly prolonged mean graft survival time to 114.4 +/- 31.0 hours (p less than 0.05). Cyclosporine (10 mg/kg/day) also significantly prolonged survival to 149 +/- 29 hours (p less than 0.01), but did not lower the antibody or complement levels. The addition of total lymphoid irradiation or cyclosporine to treatment with cobra venom factor did not result in longer survival than cobra venom factor alone. In conclusion, cobra venom factor and cyclosporine delay but do not prevent hyperacute rejection, while total lymphoid irradiation has no observable effect on hyperacute rejection.

  14. Effect of cyclosporine, total lymphoid irradiation, and cobra venom factor on hyperacute rejection

    SciTech Connect

    Knechtle, S.J.; Halperin, E.C.; Murphy, C.E.; Saad, T.; Abernethy, K.; Miller, D.; Bollinger, R.R.

    1985-09-01

    Transplantation into sensitized recipients is contraindicated due to the potential for hyperacute rejection. In order to study the mechanism of hyperacute rejection and the role of immunosuppression in the face of presensitization, we evaluated the effect of total lymphoid irradiation, cyclosporine, and cobra venom factor, alone and in combination, on hyperacute rejection of heterotopic rat heart allografts. Lewis rats were sensitized to strongly RT-1-incompatible ACI rats by three successive skin grafts. Heart allografts were then performed, and survived for a mean period of 15.7 +/- 7.4 hours. Neither preoperative treatment of hypersensitized rats with total lymphoid irradiation alone nor with cyclosporine (5 mg/kg/day) resulted in a prolongation of survival (20.4 +/- 16.6 hours and 35.6 +/- 6.2 hours, respectively). However, complement depletion using cobra venom factor significantly prolonged mean graft survival time to 114.4 +/- 31.0 hours (p less than 0.05). Cyclosporine (10 mg/kg/day) also significantly prolonged survival to 149 +/- 29 hours (p less than 0.01), but did not lower the antibody or complement levels. The addition of total lymphoid irradiation or cyclosporine to treatment with cobra venom factor did not result in longer survival than cobra venom factor alone. In conclusion, cobra venom factor and cyclosporine delay but do not prevent hyperacute rejection, while total lymphoid irradiation has no observable effect on hyperacute rejection.

  15. Identification of MEDIATOR16 as the Arabidopsis COBRA suppressor MONGOOSE1.

    PubMed

    Sorek, Nadav; Szemenyei, Heidi; Sorek, Hagit; Landers, Abigail; Knight, Heather; Bauer, Stefan; Wemmer, David E; Somerville, Chris R

    2015-12-29

    We performed a screen for genetic suppressors of cobra, an Arabidopsis mutant with defects in cellulose formation and an increased ratio of unesterified/esterified pectin. We identified a suppressor named mongoose1 (mon1) that suppressed the growth defects of cobra, partially restored cellulose levels, and restored the esterification ratio of pectin to wild-type levels. mon1 was mapped to the MEDIATOR16 (MED16) locus, a tail mediator subunit, also known as SENSITIVE TO FREEZING6 (SFR6). When separated from the cobra mutation, mutations in MED16 caused resistance to cellulose biosynthesis inhibitors, consistent with their ability to suppress the cobra cellulose deficiency. Transcriptome analysis revealed that a number of cell wall genes are misregulated in med16 mutants. Two of these genes encode pectin methylesterase inhibitors, which, when ectopically expressed, partially suppressed the cobra phenotype. This suggests that cellulose biosynthesis can be affected by the esterification levels of pectin, possibly through modifying cell wall integrity or the interaction of pectin and cellulose.

  16. Treatment of the first known case of king cobra envenomation in the United Kingdom, complicated by severe anaphylaxis.

    PubMed

    Veto, T; Price, R; Silsby, J F; Carter, J A

    2007-01-01

    We report the first known case of envenomation following snake bite by a king cobra in the UK. The patient required tracheal intubation and ventilation. Treatment with king cobra antivenom resulted in anaphylaxis (bronchospasm and hypotension), requiring adrenaline infusion. The patient's trachea was extubated 11 h after administration of antivenom.

  17. Antihaemolytic and snake venom neutralizing effect of some Indian medicinal plants.

    PubMed

    Kumarapppan, Chidambaram; Jaswanth, Albert; Kumarasunderi, Karpagam

    2011-09-01

    To validate traditional claims of usefulness of the Indian plants in management of poisonous snakebite and evaluate the antivenom properties displayed by the alcoholic extracts of Andrographis paniculata (A. paniculata), Crateva magna (C. magna), Gloriosa superba (G. superba) and Hydrocotyle javanica (H. javanica). These plants were collected, identified and the extracts were prepared by using conventional Soxhlet ethanol extraction technique. The venom neutralization activity was accessed in mice (20-25g) and number of mortalities was observed against clinically important snake (Naja nigricollis) venom. Present study also deals with in vitro membrane stabilizing activity of these plants against hyposaline induced human red blood corpuscles (HRBC). Extracts of H. javanica and G. superba gave 80 % and 90 % protection to mice treated with minimum lethal dose of venom (LD(99)). These two plants showed significant neutralization effect against the venoms of Naja nigricollis venom. H. javanica and G. superba (25-100 mg/mL) produced significant changes of membrane stabilization of human red blood cells (HRBC) exposed to hyposaline-induced haemolysis. We conclude that probably due to presence of various phytochemicals plays an important role in the anti-venom potential of these Indian medicinal plants against Naja nigricollis venom. The above observations confirmed that A. paniculata, C. magna, G. superba and H. javanica plant extracts possess potent snake venom neutralizing capacity and could potentially be used as an adjuvants for antivenin therapy in case of snakebite envenomation, especially against the local effects of cobra venoms. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  18. COBRA/TRAC simulation of the Semiscale S-UT-5 SBLOCA

    SciTech Connect

    Bian, S.H.; Thurgood, M.J.

    1984-11-01

    The purpose of the COBRA/TRAC simulation of Semiscale Test S-UT-5 is to study the capability of COBRA/TRAC to predict the system response in a 2.5% small-break LOCA (SBLOCA) and the effects of upper head injection (UHI) on core behavior. In addition, it serves to verify the capability of the code to simulate the integrated configuration of a PWR. The COBRA/TRAC code uses a set of compressible three-dimensional, two-fluid, three-field equations to represent two-phase flow in the reactor vessel and steam generators. The three fields are the vapor field, the continuous liquid field, and the liquid drop field. A five-equation drift flux model is used to model fluid flow in the primary system piping, pressurizer, pumps, and accumulators. The heat generation rate of the core is specified by input and no reactor kinetics calculations are included in the solution.

  19. Portability of health insurance: COBRA expansions and small group market reform.

    PubMed

    Fronstin, P

    1995-10-01

    Proposals are currently being put forth to change the health care system incrementally. One area of proposed legislation addresses portability, which allows an individual to change insurers without being subjected to a new waiting period for preexisting conditions. These proposals, discussed in this Issue Brief, contain provisions to limit preexisting condition exclusions, guarantee access to health insurance, guarantee renewal of health insurance, allow individuals to contribute to medical savings accounts on a pretax basis, and change the current law under the Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA). The proposals would affect insurers, employers, and insured individuals by potentially increasing the cost of providing and purchasing health insurance. Concern about the portability of health insurance primarily arises in situations where an individual is leaving, or would like to leave, a job. If health insurance is not offered by a prospective employer, if the worker must satisfy a waiting period before becoming eligible for coverage, if the benefits package offered through the prospective employer is less generous, or if the employee (or a dependent) has a medical condition that is considered a preexisting condition and would not be covered by the new plan, the employee may opt to remain with his or her current employer--a situation known as job lock. Expansions of COBRA may not have any effect on portability. Employers can charge up to 102 percent of the premium for COBRA coverage, making it unaffordable for many workers. Because cost is a major factor, if there is no reduction in cost (or health care cost inflation) there could be little or no increase in coverage. According to one survey, in 1994 average COBRA costs were $5,301 per COBRA covered worker, compared with $3,420 for active employees. Any expansion of COBRA would almost certainly increase employer cost for health insurance.(ABSTRACT TRUNCATED AT 400 WORDS)

  20. Improvements and applications of COBRA-TF for stand-alone and coupled LWR safety analyses

    SciTech Connect

    Avramova, M.; Cuervo, D.

    2006-07-01

    The advanced thermal-hydraulic subchannel code COBRA-TF has been recently improved and applied for stand-alone and coupled LWR core calculations at the Pennsylvania State Univ. in cooperation with AREVA NP GmbH (Germany)) and the Technical Univ. of Madrid. To enable COBRA-TF for academic and industrial applications including safety margins evaluations and LWR core design analyses, the code programming, numerics, and basic models were revised and substantially improved. The code has undergone through an extensive validation, verification, and qualification program. (authors)

  1. COBRA-SFS predictions of single assembly spent fuel heat transfer data

    SciTech Connect

    Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.; Rector, D.R.

    1986-04-01

    The study reported here is one of several efforts to evaluate and qualify the COBRA-SFS computer code for use in spent fuel storage system thermal analysis. The ability of COBRA-SFS to predict the thermal response of two single assembly spent fuel heat transfer tests was investigated through comparisons of predictions with experimental test data. From these comparisons, conclusions regarding the computational treatment of the physical phenomena occurring within a storage system can be made. This objective was successfully accomplished as reasonable agreement between predictions and data were obtained for the 21 individual test cases of the two experiments.

  2. COBRA-WC model and predictions for a fast-reactor natural-circulation transient. [LMFBR

    SciTech Connect

    George, T.L.; Basehore, K.L.; Prather, W.A.

    1980-01-01

    The COBRA-WC (Whole Core) code has been used to predict the core-wide coolant and rod temperature distribution in a liquid metal fast reactor during the early part (first 220 seconds) of a natural circulation transient. Approximately one-sixth of the core was modeled including bypass flows and the pressure losses above and below the core region. Detailed temperature and flow distributions were obtained for the two test fuel assemblies. The COBRA-WC model, the approach, and predictions of core-wide transient coolant and rod temperatures during a natural circulation transient are presented in this paper.

  3. Structure-function relationship of king cobra cathelicidin.

    PubMed

    Zhang, Yong; Zhao, Hui; Yu, Guo-Yu; Liu, Xiao-Dong; Shen, Ji-Hong; Lee, Wen-Hui; Zhang, Yun

    2010-08-01

    King cobra cathelicidin (OH-CATH) is composed of 34 amino acid residues having strong antibacterial and very weak hemolytic activities as reported by us recently. OH-CATH can be served as a valuable template to develop novel therapeutic drugs. In this study, OH-CATH and six of its analogs were synthesized to explore their structure-function relationships based on their bactericidal and hemolytic activities. Experimental results of OH-CATH(3-34) and OH-CATH(5-34) indicated that the N-terminal 4 amino acid residues of OH-CATH played an important role on its hemolytic activity but had weak effects on its bactericidal activity. Among OH-CATH and its analogs, OH-CATH(5-34) had the lowest hemolytic activity while maintained strong antimicrobial activity. To evaluate its potential usage, the biological activities of OH-CATH(5-34) were compared with those of pexiganan. The bactericidal activity of OH-CATH(5-34) against 5 different species (11 laboratory strains) was 2-4 times stronger than that of pexiganan (4-16 microg/ml vs 8-32 microg/ml). Hemolytic activity of OH-CATH(5-34) against human erythrocytes was 0.69% while that of pexiganan was 16.5% at the dosage of 200 microg/ml. OH-CATH(5-34) showed very weak cytotoxic activities against primary rabbit ventricular endothelial cells and four human cancer cell lines whereas pexiganan showed strong cytotoxic activity against these five cell lines (IC(50)=20-90 microg/ml). The intravenous LD(50) value of OH-CATH(5-34) on mice was 7-fold higher than that of pexiganan (175 mg/kg vs 25mg/kg). Taken together, our results suggested that OH-CATH(5-34) should be considered as an excellent candidate for developing therapeutic drugs.

  4. Improvements, enhancements, and optimizations of COBRA-TF

    SciTech Connect

    Salko, R. K.; Avramova, M. N.; Hooper, R.; Palmtag, S.; Popov, E.; Turner, J.

    2013-07-01

    The Reactor Dynamics and Fuel Management Group (RDFMG) at The Pennsylvania State University (PSU) has become active in the Consortium for Advanced Simulation of Light Water Reactors (CASL) program by delivering, supporting, and further developing CTF, the PSU version of the Coolant Boiling in Rod Arrays - Two Fluids (COBRA-TF) Thermal/Hydraulic (T/H), sub-channel program. New development work on CTF was primarily geared towards decreasing the execution time of the code so that it may eventually be used for performing pin-by-pin, full-core simulations. Great gains have been made through targeting sections of source code for optimization. For example, wall clock time has been reduced for a one-assembly, three-dimensional model, containing {approx}9,400 mesh cells, from 9.2 min to 1 min. A further improvement has been reduction in code memory usage, which was previously prohibitive for large models. In conjunction with the run time speedups, this has enabled the simulation of a refined quarter-core model ({approx}460,000 mesh cells), which saw a reduction in memory usage from over 130 GB to less than 3 GB. In addition to the optimization work, RDFMG has also created a preprocessor utility for the fast and less error-prone generation of CTF input decks. Furthermore, basic post-processing capabilities have been implemented by creating a CTF subroutine for producing Visualization Tool-Kit (VTK) files that output mesh data and associated simulation results. These VTK files can be opened with visualization software. (authors)

  5. Production of potent polyvalent antivenom against three elapid venoms using a low dose, low volume, multi-site immunization protocol.

    PubMed

    Chotwiwatthanakun, C; Pratanaphon, R; Akesowan, S; Sriprapat, S; Ratanabanangkoon, K

    2001-10-01

    The purpose of this study was to prepare a potent polyvalent antivenom against three elapids namely, the Thai cobra (Naja kaouthia, NK), the King cobra (Ophiophagus hannah, OH) and the banded krait (Bungarus fasciatus, BF). Two groups of horses were immunized. Group 1, comprising five horses, was immunized twice with a mixture of postsynaptic neurotoxins followed by an additional six immunizations with a mixture of crude venoms of the three elapids. Group 2, comprising four horses, was immunized with a mixture of crude venoms throughout the course. For the first immunization, the immunogens were emulsified in Complete Freund's adjuvant and injected using a low dose, low volume multi-site immunization protocol previously developed in this laboratory (Pratanaphon, R., Akesowan, S., Khow, O., Sriprapat, S. and Ratanabanangkoon, K. (1997) Production of highly potent horse antivenom against the Thai cobra (Naja kaouthia). Vaccine 15, 1523-1528). The second immunization was carried out with the immunogens in Incomplete Freund's adjuvant. Blood was drawn to assay the antibody titer by ELISA. Sera at the peak of ELISA titers were pooled and assayed for the median effective dose (ED(50)). The ED(50)'s of antivenom from Group 1 horses against NK, OH and BF venoms were 1.44, 0.22 and 0.23 ml serum/mg venom, respectively, while those from Group 2 horse sera were 0.88, 0.20 and 0.49 ml serum/mg venom, respectively. The potency of sera from Group 2 against BF venom was significantly higher, while the potencies against NK and OH venoms were comparable to those of the corresponding monovalent antivenoms produced under the same protocol. This potent, truly polyvalent antivenom should be useful in saving lives of victims envenomed by these elapids and the immunization protocol should be useful in the production of potent polyvalent antivenoms against other medically important elapids.

  6. Expanding the neutralization scope of the EchiTAb-plus-ICP antivenom to include venoms of elapids from Southern Africa.

    PubMed

    Sánchez, Andrés; Segura, Álvaro; Vargas, Mariángela; Herrera, María; Villalta, Mauren; Estrada, Ricardo; Wu, Francisco; Litschka-Koen, Thea; Perry, Michael Alfred; Alape-Girón, Alberto; León, Guillermo

    2017-01-01

    EchiTAb-plus-ICP is an antivenom prepared from plasma of horses hyperimmunized with the venoms of the carpet viper (Echis ocellatus), the puff adder (Bitis arietans) and the black-necked spitting cobra (Naja nigricollis). Therefore, the use of this antivenom has been limited to Western Africa. In order to expand the neutralization scope of EchiTAb-plus-ICP, we supplemented the immunogenic mixture with the venoms of B. arietans, the black mamba (Dendroaspis polylepis), the Mozambique spitting cobra (Naja mossambica), the snouted cobra (N. annulifera), and the rinkhals (Hemachatus haemachatus) from Swaziland. The ability of the expanded-scope antivenom, hereby named EchiTAb + ICP, to neutralize the venoms of B. arietans, D. polylepis, N. mossambica and H. haemachatus was similar to those of FAV Afrique and the SVA African antivenoms. In comparison to the SAIMR antivenom, the expanded-scope EchiTAb + ICP had lower ability to neutralize the venom of B. arietans, but similar ability to neutralize the venoms of D. polylepis, N. mossambica and H. haemachatus. Owing to its low protein concentration, the expanded-scope EchiTAb + ICP had lower ability to neutralize the venom of N. annulifera than FAV Afrique and the SAIMR antivenoms. However, when formulated at a protein concentration as high as FAV Afrique and SAIMR antivenoms, the expanded-scope EchiTAb + ICP showed similar capacity to neutralize this poorly immunogenic venom. Our results encourage the transition to the new EchiTAb + ICP antivenom, with an expanded neutralization scope that includes venoms of some of the most medically important elapids from Southern Africa. Clinical trials are required to determine the minimum effective-safe dose of the new EchiTAb + ICP for each type of envenomation.

  7. Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development

    PubMed Central

    Nair, Sreejith J.; Zhang, Xiaowen; Chiang, Huai-Chin; Jahid, Md Jamiul; Wang, Yao; Garza, Paula; April, Craig; Salathia, Neeraj; Banerjee, Tapahsama; Alenazi, Fahad S.; Ruan, Jianhua; Fan, Jian-Bing; Parvin, Jeffrey D.; Jin, Victor X.; Hu, Yanfen; Li, Rong

    2016-01-01

    The breast cancer susceptibility gene BRCA1 is well known for its function in double-strand break (DSB) DNA repair. While BRCA1 is also implicated in transcriptional regulation, the physiological significance remains unclear. COBRA1 (also known as NELF-B) is a BRCA1-binding protein that regulates RNA polymerase II (RNAPII) pausing and transcription elongation. Here we interrogate functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduces mammary epithelial compartments and blocks ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. Remarkably, these developmental deficiencies due to Cobra1 knockout are largely rescued by additional loss of full-length Brca1. Furthermore, Brca1/Cobra1 double knockout restores developmental transcription at puberty, alters luminal epithelial homoeostasis, yet remains deficient in homologous recombination-based DSB repair. Thus our genetic suppression analysis uncovers a previously unappreciated, DNA repair-independent function of BRCA1 in antagonizing COBRA1-dependent transcription programme during mammary gland development. PMID:26941120

  8. Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development.

    PubMed

    Nair, Sreejith J; Zhang, Xiaowen; Chiang, Huai-Chin; Jahid, Md Jamiul; Wang, Yao; Garza, Paula; April, Craig; Salathia, Neeraj; Banerjee, Tapahsama; Alenazi, Fahad S; Ruan, Jianhua; Fan, Jian-Bing; Parvin, Jeffrey D; Jin, Victor X; Hu, Yanfen; Li, Rong

    2016-03-04

    The breast cancer susceptibility gene BRCA1 is well known for its function in double-strand break (DSB) DNA repair. While BRCA1 is also implicated in transcriptional regulation, the physiological significance remains unclear. COBRA1 (also known as NELF-B) is a BRCA1-binding protein that regulates RNA polymerase II (RNAPII) pausing and transcription elongation. Here we interrogate functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduces mammary epithelial compartments and blocks ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. Remarkably, these developmental deficiencies due to Cobra1 knockout are largely rescued by additional loss of full-length Brca1. Furthermore, Brca1/Cobra1 double knockout restores developmental transcription at puberty, alters luminal epithelial homoeostasis, yet remains deficient in homologous recombination-based DSB repair. Thus our genetic suppression analysis uncovers a previously unappreciated, DNA repair-independent function of BRCA1 in antagonizing COBRA1-dependent transcription programme during mammary gland development.

  9. Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder.

    PubMed

    Toyoshima, Kuniyoshi; Fujii, Yutaka; Mitsui, Nobuyuki; Kako, Yuki; Asakura, Satoshi; Martinez-Aran, Anabel; Vieta, Eduard; Kusumi, Ichiro

    2017-08-01

    In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearman's correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Complete Assignment of (1)H-NMR Resonances of the King Cobra Neurotoxin CM-11.

    PubMed

    Pang, Yu-Xi; Liu, Wei-Dong; Liu, Ai-Zhuo; Pei, Feng-Kui

    1997-01-01

    The king cobra (Ophiophagus Hannah) neurotoxin CM-Il is long-chain peptide with 72 amino acid residues. Its complete assignment of (1)H-NMR resonances was obtained using various 2D-NMR technologies, including DQF-COSY, clean-TOCSY and NOESY.

  11. Cloning and purification of alpha-neurotoxins from king cobra (Ophiophagus hannah).

    PubMed

    He, Ying-Ying; Lee, Wei-Hui; Zhang, Yun

    2004-09-01

    Thirteen complete and three partial cDNA sequences were cloned from the constructed king cobra (Ophiophagus hannah) venom gland cDNA library. Phylogenetic analysis of nucleotide sequences of king cobra with those from other snake venoms revealed that obtained cDNAs are highly homologous to snake venom alpha-neurotoxins. Alignment of deduced mature peptide sequences of the obtained clones with those of other reported alpha-neurotoxins from the king cobra venom indicates that our obtained 16 clones belong to long-chain neurotoxins (seven), short-chain neurotoxins (seven), weak toxin (one) and variant (one), respectively. Up to now, two out of 16 newly cloned king cobra alpha-neurotoxins have identical amino acid sequences with CM-11 and Oh-6A/6B, which have been characterized from the same venom. Furthermore, five long-chain alpha-neurotoxins and two short-chain alpha-neurotoxins were purified from crude venom and their N-terminal amino acid sequences were determined. The cDNAs encoding the putative precursors of the purified native peptide were also determined based on the N-terminal amino acid sequencing. The purified alpha-neurotoxins showed different lethal activities on mice.

  12. The High-redshift Clusters Occupied by Bent Radio AGN (COBRA) Survey: The Spitzer Catalog

    NASA Astrophysics Data System (ADS)

    Paterno-Mahler, R.; Blanton, E. L.; Brodwin, M.; Ashby, M. L. N.; Golden-Marx, E.; Decker, B.; Wing, J. D.; Anand, G.

    2017-07-01

    We present 190 galaxy cluster candidates (most at high redshift) based on galaxy overdensity measurements in the Spitzer/IRAC imaging of the fields surrounding 646 bent, double-lobed radio sources drawn from the Clusters Occupied by Bent Radio AGN (COBRA) Survey. The COBRA sources were chosen as objects in the Very Large Array FIRST survey that lack optical counterparts in the Sloan Digital Sky Survey to a limit of m r = 22, making them likely to lie at high redshift. This is confirmed by our observations: the redshift distribution of COBRA sources with estimated redshifts peaks near z = 1 and extends out to z≈ 3. Cluster candidates were identified by comparing our target fields to a background field and searching for statistically significant (≥slant 2σ ) excesses in the galaxy number counts surrounding the radio sources; 190 fields satisfy the ≥slant 2σ limit. We find that 530 fields (82.0%) have a net positive excess of galaxies surrounding the radio source. Many of the fields with positive excesses but below the 2σ cutoff are likely to be galaxy groups. Forty-one COBRA sources are quasars with known spectroscopic redshifts, which may be tracers of some of the most distant clusters known.

  13. Thermal ramp tritium release in COBRA-1A2 C03 beryllium pebbles

    SciTech Connect

    Baldwin, D.L.

    1998-03-01

    Tritium release kinetics, using the method of thermal ramp heating at three linear ramp rates, were measured on the COBRA-1A2 C03 1-mm beryllium pebbles. This report includes a brief discussion of the test, and the test data in graph format.

  14. From the Kiss of a Cobra: A Sidelong View of Snakebite, Antivenin, and Serum Sickness.

    ERIC Educational Resources Information Center

    Graham, Douglas H.

    1992-01-01

    Article tells the story of how a New York City customs man was bit by a King Cobra from Thailand and the medical treatment he received. Describes three types of snake venoms: hemotoxins, cytotoxins, and neurotoxins. Explains how horses are used to produce antitoxins and side effects of the antitoxins on humans. (PR)

  15. [Classic laryngeal mask airway vs COBRA-PLA device for airway maintenance during minor urological procedures].

    PubMed

    Wrońska-Sewruk, Agnieszka; Nestorowicz, Andrzej; Kowalczyk, Michał

    2009-01-01

    In recent years, different supraglottic airway devices became popular and new constructions have been proposed. We compared a classic laryngeal mask airway (LMA-classic) with the COBRA-PLA device (a LMA of different design). Fifty adult ASA 1 and 2 adult patients, scheduled for minor urological interventions were randomly allocated to receive the LMA-Classic or the COBRA-PLA. Time to secure airway was shorter for the LMA-Classic (16.8+/- 5 sec vs 33.0 +/- 19.6 sec; p<0.0001). The leak pressure was higher in the COBRA group (29.0+/- 7.5 vs 22.2 +/- 3.5 cm H2O; p=0.001). The cuff pressure, necessary for obtaining adequate seal, was higher for the LMA (83.6 +/- 14.1 vs 60.2 +/- 16.4 cm H2O; p<0.0001). We did not observe statistically significant differences in heart rate, arterial blood pressure, pulse oximetry and frequency of sore throat. The LMA-classic was easier to insert but the COBRA device had more effective seal. These differences were not clinically important; both devices were found equally effective.

  16. Broadened immunity and protective responses with emulsion-adjuvanted H5 COBRA-VLP vaccines.

    PubMed

    Allen, James D; Owino, Simon O; Carter, Donald M; Crevar, Corey J; Reese, Valerie A; Fox, Christopher B; Coler, Rhea N; Reed, Steven G; Baldwin, Susan L; Ross, Ted M

    2017-09-12

    A number of challenges for developing a protective pre-pandemic influenza A vaccine exists including predicting the target influenza strain and designing the vaccine for an immunologically naïve population. Manufacturing and supply of the vaccine would also require implementing ways to increase coverage for the largest number of people through dose-sparing methods, while not compromising the potency of the vaccine. Previously, our group described a novel hemagglutinin (HA) for H5N1 influenza derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This report describes a strategy combining a COBRA-based HA vaccine with an oil-in-water emulsion, resulting in a dose-sparing, immunologically broadened, and protective response against multiple H5N1 isolates. Here, we show that an emulsion-based adjuvant enhances the magnitude and breadth of antibody responses with both a wild-type H5HA (H5N1 WT) and the H5N1 COBRA HA VLP vaccines. The H5N1 COBRA HA VLP, combined with an emulsion adjuvant, elicited HAI specific antibodies against a larger panel of H5N1 viruses that resulted in protection against challenge as efficiently as the homologous, matched vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. From the Kiss of a Cobra: A Sidelong View of Snakebite, Antivenin, and Serum Sickness.

    ERIC Educational Resources Information Center

    Graham, Douglas H.

    1992-01-01

    Article tells the story of how a New York City customs man was bit by a King Cobra from Thailand and the medical treatment he received. Describes three types of snake venoms: hemotoxins, cytotoxins, and neurotoxins. Explains how horses are used to produce antitoxins and side effects of the antitoxins on humans. (PR)

  18. 75 FR 16841 - Proposed Extension of Information Collection Request Submitted for Public Comment; COBRA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... for health care continuation coverage. On December 19, 2009, President Obama signed the Department of... revision of the information collection provisions of its final rule at 29 CFR part 2590, Health Care... access to health care. COBRA provides the Secretary of Labor (the Secretary) with authority under...

  19. Use of Molecular Diagnostic Tools for the Identification of Species Responsible for Snakebite in Nepal: A Pilot Study

    PubMed Central

    Sharma, Sanjib Kumar; Kuch, Ulrich; Höde, Patrick; Bruhse, Laura; Pandey, Deb P.; Ghimire, Anup; Chappuis, François; Alirol, Emilie

    2016-01-01

    Snakebite is an important medical emergency in rural Nepal. Correct identification of the biting species is crucial for clinicians to choose appropriate treatment and anticipate complications. This is particularly important for neurotoxic envenoming which, depending on the snake species involved, may not respond to available antivenoms. Adequate species identification tools are lacking. This study used a combination of morphological and molecular approaches (PCR-aided DNA sequencing from swabs of bite sites) to determine the contribution of venomous and non-venomous species to the snakebite burden in southern Nepal. Out of 749 patients admitted with a history of snakebite to one of three study centres, the biting species could be identified in 194 (25.9%). Out of these, 87 had been bitten by a venomous snake, most commonly the Indian spectacled cobra (Naja naja; n = 42) and the common krait (Bungarus caeruleus; n = 22). When both morphological identification and PCR/sequencing results were available, a 100% agreement was noted. The probability of a positive PCR result was significantly lower among patients who had used inadequate “first aid” measures (e.g. tourniquets or local application of remedies). This study is the first to report the use of forensic genetics methods for snake species identification in a prospective clinical study. If high diagnostic accuracy is confirmed in larger cohorts, this method will be a very useful reference diagnostic tool for epidemiological investigations and clinical studies. PMID:27105074

  20. Snakes of medical importance in India: is the concept of the "Big 4" still relevant and useful?

    PubMed

    Simpson, Ian D; Norris, Robert L

    2007-01-01

    Snakebites continue to be a major medical concern in India. However, there is very little hard evidence of a numerical nature to enable us to understand which species are responsible for mortality and morbidity. For many decades, the concept of the "Big 4" Snakes of Medical Importance has reflected the view that 4 species are responsible for Indian snakebite mortality--the Indian cobra (Naja naja), the common krait (Bungarus caeruleus), the Russell's viper (Daboia russelii) and the saw-scaled viper (Echis carinatus). However, a recent discovery that another species, the hump-nosed pit viper (Hypnale hypnale), is capable of causing lethal envenomation, and that this problem was being concealed by systematic misidentification of this species as the saw-scaled viper, has necessitated a review of the concept of the "Big 4." The concept of the "Big 4" snakes is reviewed to demonstrate its failure to include all currently known snakes of medical significance in India, and its negative effects related to clinical management of snakebite. The emergence of the hump-nosed pit viper (Hypnale hypnale) as a snake of medical significance has rendered the "Big 4" obsolete in terms of completeness. The concept of the "Big 4" is restricting sound epidemiological work and the development of effective snake antivenoms. It should be replaced by the model introduced in the 1980s by the World Health Organization, which has not received adequate circulation and implementation.

  1. Experiments in cardiac xenotransplantation. Response to intrathymic xenogeneic cells and intravenous cobra venom factor.

    PubMed

    Mohiuddin, M; Kline, G; Shen, Z; Ruggiero, V; Rostami, S; DiSesa, V J

    1993-10-01

    Permanent tolerance to an experimental cardiac allograft can be achieved by pretransplantation intrathymic inoculation of donor-specific lymphoid cells. We studied the effects of intrathymic inoculation of xenogeneic cells and intravenous cobra venom factor in a rodent model of cardiac xenotransplantation. Lewis rats underwent intraabdominal heterotopic heart transplantation with Syrian hamster donors. In untreated animals, mean graft survival time was 3 days. Five rats had 1 ml of antilymphocyte serum administered intraperitoneally. One day later, 2.5 x 10(7) hamster spleen cells were inoculated into the thymus under direct vision. Twenty-one days after antilymphocyte serum was given, heterotopic heart transplantation with a hamster donor was carried out. In all cases, rejection was accelerated and occurred between 20 minutes and 1 day after transplantation. Mean graft survival time was 5.2 hours (p < 0.0001 versus control). Six animals treated with antilymphocyte serum and intrathymic xenogeneic cells had 0.5 ml of cobra venom factor, a complement antagonist, administered intravenously 3 hours before transplantation and every other day thereafter. Mean graft survival was 3 days, which was not different from the response of naive animals. Animals treated with antilymphocyte serum only had no prolongation of graft survival (mean survival time 3 days, p = not significant). Animals treated with cobra venom factor alone (n = 5) before transplantation and on alternate days subsequently had mild graft prolongation with a mean survival time of 4 days (p = 0.0133). In contrast to experimental allograft models, intrathymic inoculation of xenogeneic cells produces hyperacute rejection in these naturally concordant species. The administration of cobra venom factor abrogates the hyperacute response, but the combination of cobra venom factor and intrathymic inoculation does not produce long-term graft survival.

  2. Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0

    PubMed Central

    Schellenberger, Jan; Que, Richard; Fleming, Ronan M. T.; Thiele, Ines; Orth, Jeffrey D.; Feist, Adam M.; Zielinski, Daniel C.; Bordbar, Aarash; Lewis, Nathan E.; Rahmanian, Sorena; Kang, Joseph; Hyduke, Daniel R.; Palsson, Bernhard Ø.

    2012-01-01

    Over the past decade, a growing community of researchers has emerged around the use of COnstraint-Based Reconstruction and Analysis (COBRA) methods to simulate, analyze and predict a variety of metabolic phenotypes using genome-scale models. The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented earlier. Here we present a significant update of this in silico ToolBox. Version 2.0 of the COBRA Toolbox expands the scope of computations by including in silico analysis methods developed since its original release. New functions include: (1) network gap filling, (2) 13C analysis, (3) metabolic engineering, (4) omics-guided analysis, and (5) visualization. As with the first version, the COBRA Toolbox reads and writes Systems Biology Markup Language formatted models. In version 2.0, we improved performance, usability, and the level of documentation. A suite of test scripts can now be used to learn the core functionality of the Toolbox and validate results. This Toolbox lowers the barrier of entry to use powerful COBRA methods. PMID:21886097

  3. Efficacy of the New Perilaryngeal Airway (CobraPLA™) Versus the Laryngeal Mask Airway (LMA™) to Improve Oropharyngeal Leak Pressure in Obese and Overweight Patients

    PubMed Central

    Yaghoobi, Siamak; Abootorabi, Seyed Mohamadreza; Kayalha, Hamid; Van Zundert, Tom C

    2015-01-01

    Background: This study aimed to evaluate the applicability of Cobra perilaryngeal airway (Cobra PLA™) for obese patients under general anesthesia and also to compare the results with those of classic laryngeal mask airway (LMA™). Materials and Methods: Seventy-three overweight and obese patients were included in this study. The patients were randomly assigned to LMA™ or Cobra PLA™ groups. Time required for intubation, successful intubation attempt, airway sealing pressure and incidence of complications including blood staining, sore throat and dysphagia were assessed and noted. Results: Thirty-six and 37 patients were randomly allocated to LMA™ and Cobra PLA™ groups, respectively. Most patients were males and had Mallampati Class II airway in both groups. The first attempt and overall insertion success for Cobra PLA™ was significantly higher compared to LMA (P<0.05). Airway insertion was more successful (P = 0.027; 94% vs. 77%) with Cobra PLA™. Insertion times were similar with Cobra PLA™ and LMA™ (Cobra PLA™, 29.94±16.35s; LMA™, 27.00±7.88s). The oropharyngeal leak pressure in the Cobra PLA™ group (24.80±0.90 H2O) was significantly higher than that in LMA™ group (19±1 H2O, p<0.001). Sore throat was more frequent in the LMA™ group although it did not reach statistical significance (Fisher’s exact test, P = 0.33). Blood staining on airway tube was seen in both groups with a higher incidence in the Cobra PLA™ group (Fisher’s Exact test, P = 0.02). Incidence of dysphagia was not different between the two groups. Conclusion: CobraPLA™ was found to be safe with low complications. It provided better airway sealing with high rate of the first insertion success for use in obese and overweight patients. This study recommends the use of CobraPLA™ as a rescue device in emergency situations for obese and overweight patients. PMID:26221151

  4. Successful treatment of neurotoxic king cobra envenomation in Myrtle Beach, South Carolina.

    PubMed

    Gold, B S; Pyle, P

    1998-12-01

    The growing trend toward the collection of exotic snakes by private collectors increases the likelihood that emergency physicians will face the challenge of treating an exotic envenomation. We report a case involving a professional reptile handler who sustained an extremity bite from a king cobra (Ophiophagus hannah ). Rapid, progressive neurotoxicity developed as manifested clinically by bulbar and respiratory paralysis requiring endotracheal intubation and mechanical support. After infusion of Thai Red Cross Society monospecific king cobra antivenin, all neurologic sequelae rapidly resolved within 7 hours after the bite. In treating an exotic envenomation, the emergency physician should contact personnel at the regional poison control center or local zoo. Both are prepared to assist the physician by facilitating the timely acquisition of exotic antivenins and by arranging consultation with experts experienced in the management and treatment of exotic envenomations.

  5. Ophthalmia due to spitting cobra venom in an urban setting--a report of three cases.

    PubMed

    Ang, Leslie Jonathan; Sanjay, Srinivasan; Sangtam, Tiakumzuk

    2014-01-01

    To describe three presentations of spitting cobra venom induced ophthalmia in urban Singapore. Case notes and photographs of three patients with venom ophthalmia who presented to our clinic between 2007 and 2012 were reviewed. Two patients encountered the spitting cobra while working at a job site while the third patient had caught the snake and caged it. The venom entered the eyes in all 3 cases. Immediate irrigation with tap water was carried out before presenting to the Accident and Emergency department. All patients were treated medically with topical antibiotic prophylaxis and copious lubricants. The use of anti-venom was not required in any case. All eyes recovered with no long-term sequelae. If irrigation is initiated early, eyes can recover with no significant complications or sequelae.

  6. COBRA/TRAC simulation of a semiscale small break LOCA. [PWR

    SciTech Connect

    Bian, S.H.; Thurgood, M.J.; Kelley, J.M.

    1983-06-01

    The COBRA/TRAC computer program has been developed to predict the thermal-hydraulic response of nuclear reactor primary coolant systems to small and large break loss-of-coolant accidents and other anticipated transients. The code solves the compressible three-dimensional, two-fluid, three-field equations for two-phase flow in the reactor vessel. The three fields are the vapor field, the continuous liquid field, and the liquid drop field. A five-equation drift flux model is used to model fluid flow in the primary system piping, pressurizer, pumps, and accumulator. In the code modeling of Semiscale Test S-UT-2, the intact and broken loops, and the upper head injection (UHI) systems are represented by one-dimensional components,. The pressure vessel and two steam generators are modeled using the three-dimensional VESSEL component. The results from the COBRA/TRAC calculation give a reasonable match with the measured data.

  7. The COBRA accelerator pulsed-power driver for Cornell/Sandia ICF research

    SciTech Connect

    Smith, D.L.; Ingwersen, P.; Bennett, L.F.; Boyes, J.D.; Anderson, D.E.; Greenly, J.B.; Sudan, R.N.; Hammer, D.A.

    1995-07-01

    This paper introduces and describes the new Cornell Beam Research Accelerator, COBRA, the result of a three and one-half year collaboration. The flexible 4 to 5-MV, 100 to 250-kA, 46-ns pulse width accelerator is based on a four-cavity Inductive Voltage Adder (IVA) design. In addition to being a mix of new and existing components, COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 1800 about their vertical axis. Our tests with negative high voltage on the inner MITL stalk indicate that the vacuum power flow has established reasonable azimuthal symmetry within about 2 ns (or 0.6 m) after the cavity output cap. Preliminary results with the accelerator, single cavity, and MITL are presented alone, with the design details and circuit model predictions.

  8. Complement depletion with humanised cobra venom factor: efficacy in preclinical models of vascular diseases.

    PubMed

    Vogel, Carl-Wilhelm; Fritzinger, David C; Gorsuch, W Brian; Stahl, Gregory L

    2015-03-01

    The complement system is an intrinsic part of the immune system and has important functions in both innate and adaptive immunity. On the other hand, inadvertent or misdirected complement activation is also involved in the pathogenesis of many diseases, contributing solely or significantly to tissue injury and disease development. Multiple approaches to develop pharmacological agents to inhibit complement are currently being pursued. We have developed a conceptually different approach of not inhibiting but depleting complement, based on the complement-depleting activities of cobra venom factor (CVF), a non-toxic cobra venom component with structural and functional homology to complement component C3. We developed a humanised version of CVF by creating human complement component C3 derivatives with complement-depleting activities of CVF (humanised CVF) as a promising therapeutic agent for diseases with complement pathogenesis. Here we review the beneficial therapeutic effect of humanised CVF in several murine models of vascular diseases such as reperfusion injury.

  9. Trigeminal Neuralgia Induced by Cobra Venom Leads to Cognitive Deficits Associated with Downregulation of CREB/BDNF Pathway.

    PubMed

    Zhang, Li; Ding, Xinli; Wu, Zhe; Qian, Xiaoyan; An, Jianxiong; Tian, Ming

    2017-02-01

    Chronic pain often results in cognitive impairment. Our previous study showed that trigeminal neuralgia induced by cobra venom leads to spatial learning and memory deficits, although the underlying mechanism remains unclear. However, recent evidence indicates that the c-AMP-responsive element binding protein (CREB)/brain derived neurotrophic factor (BDNF) pathway plays a critical role in various etiologies of cognitive deficits. Our aim was to explore the CREB/BDNF pathway to determine the molecular mechanisms involved in the pathogenesis of cognitive impairment caused by cobra venom-induced trigeminal neuralgia. A randomized, controlled animal study. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University. Fifty male Sprague-Dawley rats were randomly divided into 3 groups: cobra venom group, sham group, and control group. Cobra venom or saline was injected into the sheath of the infraorbital nerve (ION), respectively. Video recordings and mechanical thresholds were used to analyze changes in behavioral activity 3 days before surgery and 4, 7, 14, 21, 28, and 56 days after surgery. Morris water maze tests were conducted at 4- and 8-week time points after surgery to evaluate spatial learning and memory. We also investigated expression changes of phosphorylated CREB (p-CREB) and BDNF in the hippocampus and prefrontal cortex (PFC) using western blotting and immunohistochemistry. Cobra venom-treated rats exhibited significant changes in face grooming, as well as exploratory and resting behaviors, compared with the control group and sham group (both P < 0.001). Rats in the cobra venom group exhibited slightly impaired acquisition (P < 0.05) without memory deficits (P > 0.05) in the first water maze protocol. In the second water maze test, rats in the cobra venom group exhibited spatial learning and memory deficits, with fewer platform site crossings during the probe trial (P < 0.05). Moreover, results showed decreased p-CREB and BDNF

  10. Effect of cobra venom factor on experimental infection of mice against Clostridium chauvoei.

    PubMed

    Tamura, Y; Kijima, M; Suzuki, S; Takahashi, T; Nakamura, M

    1992-10-01

    The effect of cobra venom factor (CoVF) treatment was examined to clarify the mechanism of resistance of mice to Clostridium chauvoei infection. In CoVF-treated mice inoculated with spores of C. chauvoei, no death occurred and the organisms in the infected muscle progressively decreased, similar to that of non-treated control mice. These results indicated that C3 did not play a significant role in the resistance of mice against C. chauvoei infection.

  11. Functional proteomic approach to discover geographic variations of king cobra venoms from Southeast Asia and China.

    PubMed

    Chang, Hui-Ching; Tsai, Tein-Shun; Tsai, Inn-Ho

    2013-08-26

    This study deciphers the geographic variations of king cobra (Ophiophagus hannah) venom using functional proteomics. Pooled samples of king cobra venom (abbreviated as Ohv) were obtained from Indonesia, Malaysia, Thailand, and two provinces of China, namely Guangxi and Hainan. Using two animal models to test and compare the lethal effects, we found that the Chinese Ohvs were more fatal to mice, while the Southeast Asian Ohvs were more fatal to lizards (Eutropis multifasciata). Various phospholipases A2 (PLA2s), three-finger toxins (3FTxs) and Kunitz-type inhibitors were purified from these Ohvs and compared. Besides the two Chinese Ohv PLA2s with known sequences, eight novel PLA2s were identified from the five Ohv samples and their antiplatelet activities were compared. While two 3FTxs (namely oh-55 and oh-27) were common in all the Ohvs, different sets of 3FTx markers were present in the Chinese and Southeast Asian Ohvs. All the Ohvs contain the Kunitz inhibitor, OH-TCI, while only the Chinese Ohvs contain the inhibitor variant, Oh11-1. Relative to the Chinese Ohvs which contained more phospholipases, the Southeast Asian Ohvs had higher metalloproteinase, acetylcholine esterase, and alkaline phosphatase activities. Remarkable variations in five king cobra geographic samples reveal fast evolution and dynamic translational regulation of the venom which probably adapted to different prey ecology as testified by the lethal tests on mice and lizards. Our results predict possible variations of the king cobra envenoming to human and the importance of using local antivenin for snakebite treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Production of {sup 4}He and tritium from Be in the COBRA-1A2 irradiation

    SciTech Connect

    Greenwood, L.R.

    1998-03-01

    The production of {sup 4}He and tritium has been calculated for beryllium irradiated in the COBRA-1A2 experiment in the Experimental Breeder Reactor II. Reaction rates were based on adjusted neutron spectra determined from reactor dosimetry measurements at three different elevations in the region of the beryllium capsules. Equations are given so that gas production can be calculated for any specific capsule elevation.

  13. Neutron dosimetry and damage calculations for the EBRII COBRA-1A irradiations

    SciTech Connect

    Greenwood, L.R.; Ratner, R.T.

    1997-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint U.S. and Japanese COBRA-1A1 and 1A2 irradiations in the Experimental Breeder Reactor II. The maximum total neutron fluences at midplane were 2.0E+22 and 7.5E+22 n/cm{sup 2}, for the 1A1 and 1A2 irradiations, respectively, resulting in about 8.0 and 30.3 dpa in stainless steel.

  14. An unusual encounter of a "cobra" in the heart: rare appearance of an Amplatzer Septal Occluder.

    PubMed

    Yip, W C; Chan, K Y

    2001-04-01

    This article presents the unusual appearance of a "cobra" due to "acute bending" of the proximal part and partial opening of the distal part of the left atrial disk of an Amplatzer Septal Occluder during the process of transcatheter closure of a secundum atrial septal defect in a 6-year-old boy. The possible reasons and method to overcome this technical problem, which resulted in successful occlusion of the atrial septal defect, are discussed.

  15. Surveillance for Respiratory Infections, Including Severe Acute Respiratory, Syndrome (SARS), in Cobra Gold 2003

    DTIC Science & Technology

    2004-05-10

    to be causal. Respiratory illnesses caused by viruses in the family Coronaviridae have long been recognized.2-13 Two species known to cause human ...tested positive for influenza A, 2 (13%) for coronavirus OC43, 2 (13%) for respiratory syncytial virus , 1 (6%) rhinovirus, 9 and 4 (25%) were...NAVAL HEALTH RESEARCH CENTER SURVEILLANCE FOR RESPIRATORY INFECTIONS , INCLUDING SEVERE ACUTE RESPIRATORY SYNDROME (SARS), IN COBRA

  16. COBRAS/SAMBA: The European space mission to map the CBRanisotropy

    SciTech Connect

    Bersanelli, M.; Mandolesi, N.; Cesarsky, C.; Danese, L.; Efstathiou, G.; Griffin, M.; Lamarre, J.M.; NorgaardNielsen, H.U.; Pace,O.; Puget, J.L.; Raisanen, A.; Smoot, G.F.; Tauber, J.; Volonte, S.

    1996-01-01

    COBRAS/SAMBA is an ESA mission designed for extensive, accurate mapping of the anisotropies of the Cosmic Background Radiation, with angular sensitivity from sub-degree scales up to and overlapping with the COBE-DMR resolution. This will allow a fun identification of the primordial density perturbations which grew to form the large-scale structures observed in the present universe. Here we present the scientific goals and the key characteristics of the model payload and observation strategy.

  17. COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

    SciTech Connect

    Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-05-08

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to the enormous complexity and dynamic nature of their chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions of monomers pertinent to secondary organic aerosol (SOA) formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next one. The simulation generated thousands of molecular structures in the mass range of 120-500 Da, and correctly predicted ~70% of the individual SOA constituents observed by high-resolution mass spectrometry (HR-MS). Selected predicted structures were confirmed with tandem mass spectrometry. Esterification and hemiacetal formation reactions were shown to play the most significant role in oligomer formation, whereas aldol condensation was shown to be insignificant. COBRA is not limited to atmospheric aerosol chemistry, but is broadly applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods.

  18. COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

    PubMed Central

    Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-01-01

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next. The simulation generated thousands of structures in the mass range of 120–500 Da, and correctly predicted ~70% of the individual OA constituents observed by high-resolution mass spectrometry. Select predicted structures were confirmed with tandem mass spectrometry. Esterification was shown to play the most significant role in oligomer formation, with hemiacetal formation less important, and aldol condensation insignificant. COBRA is not limited to atmospheric aerosol chemistry; it should be applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods. PMID:22568707

  19. Development in High-Density Cobra Fiber Positioners for the Subaru Telescope's Prime Focus Spectrometer

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Mic D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger S.

    2012-01-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed "Cobra", will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual "SCARA robot" mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5 micrometers of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  20. The High-Z Clusters Occupied by Bent Radio AGN (COBRA) Survey

    NASA Astrophysics Data System (ADS)

    Golden-Marx, Emmet; Blanton, Elizabeth; Paterno-Mahler, Rachel; Brodwin, Mark; Ashby, Matthew; Wing, Joshua; Anand, Gagandeep; Decker, Bandon

    2017-07-01

    To probe the earliest eras of cluster formation, we need to find clusters with a variety of morphological states and masses across redshift space. Here, we present results from the Clusters Occupied by Bent Radio AGN (COBRA) Survey. The COBRA survey includes 646 bent, double-lobed radio sources selected from the VLA FIRST Survey, infrared observations from Spitzer, and optical observations from the Discovery Channel Telescope. The COBRA survey spans the redshift range 0.5 < z < 3.0 and includes objects with a wide range of masses and dynamical states. The bent radio morphology results from interactions between the AGN host galaxy and the surrounding intracluster medium; the relative motion results in ram pressure acting on the lobes, bending them. Using our IR and optical data, we measure galaxy excesses, locate red sequence galaxies, and determine photometric redshifts. We find that at least 30% of our high-z the bent radio sources are found in clusters or protoclusters. Additionally, we measure galaxy surface densities to trace out the large-scale cluster morphologies.

  1. Development in High-Density Cobra Fiber Positioners for the Subaru Telescope's Prime Focus Spectrometer

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Mic D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger S.

    2012-01-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed "Cobra", will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual "SCARA robot" mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5 micrometers of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  2. Investigation into the efficiency of different bionic algorithm combinations for a COBRA meta-heuristic

    NASA Astrophysics Data System (ADS)

    Akhmedova, Sh; Semenkin, E.

    2017-02-01

    Previously, a meta-heuristic approach, called Co-Operation of Biology-Related Algorithms or COBRA, for solving real-parameter optimization problems was introduced and described. COBRA’s basic idea consists of a cooperative work of five well-known bionic algorithms such as Particle Swarm Optimization, the Wolf Pack Search, the Firefly Algorithm, the Cuckoo Search Algorithm and the Bat Algorithm, which were chosen due to the similarity of their schemes. The performance of this meta-heuristic was evaluated on a set of test functions and its workability was demonstrated. Thus it was established that the idea of the algorithms’ cooperative work is useful. However, it is unclear which bionic algorithms should be included in this cooperation and how many of them. Therefore, the five above-listed algorithms and additionally the Fish School Search algorithm were used for the development of five different modifications of COBRA by varying the number of component-algorithms. These modifications were tested on the same set of functions and the best of them was found. Ways of further improving the COBRA algorithm are then discussed.

  3. COBRA-LIKE2, a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE family, plays a role in cellulose deposition in arabidopsis seed coat mucilage secretory cells.

    PubMed

    Ben-Tov, Daniela; Abraham, Yael; Stav, Shira; Thompson, Kevin; Loraine, Ann; Elbaum, Rivka; de Souza, Amancio; Pauly, Markus; Kieber, Joseph J; Harpaz-Saad, Smadar

    2015-03-01

    Differentiation of the maternally derived seed coat epidermal cells into mucilage secretory cells is a common adaptation in angiosperms. Recent studies identified cellulose as an important component of seed mucilage in various species. Cellulose is deposited as a set of rays that radiate from the seed upon mucilage extrusion, serving to anchor the pectic component of seed mucilage to the seed surface. Using transcriptome data encompassing the course of seed development, we identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as coexpressed with other genes involved in cellulose deposition in mucilage secretory cells. Disruption of the COBL2 gene results in substantial reduction in the rays of cellulose present in seed mucilage, along with an increased solubility of the pectic component of the mucilage. Light birefringence demonstrates a substantial decrease in crystalline cellulose deposition into the cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition into the radial cell walls and the columella appears substantially compromised, as demonstrated by scanning electron microscopy and in situ quantification of light birefringence. Overall, the cobl2 mutants display about 40% reduction in whole-seed crystalline cellulose content compared with the wild type. These data establish that COBL2 plays a role in the deposition of crystalline cellulose into various secondary cell wall structures during seed coat epidermal cell differentiation. © 2015 American Society of Plant Biologists. All Rights Reserved.

  4. Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion.

    PubMed

    Maroko, P R; Carpenter, C B; Chiariello, M; Fishbein, M C; Radvany, P; Knostman, J D; Hale, S L

    1978-03-01

    Components of the complement system are known to play an important role in the cytolytic process and in chemotaxis of leukocytes. Cobra venom factor specifically cleaves C3 activity via activation of the alternative (properdin) complement pathway. It does not act directly on C3. If C3 is involved in tissue necrosis after ischemic injury, cobra venom factor might reduce tissue damage after acute coronary occlusion. Accordingly, in 14 control dogs occlusion of the left anterior descending artery was carried out for 24 h. Epicardial electrograms were recorded 15 min after occlusion, and 24 h later transmural specimens for creatine phosphokinase activity (CPK) and for histological analysis were obtained from the same sites. In another 14 experimental dogs, 20 U/kg cobra venom factor was given intravenously 30 min after occlusion. Serum complement levels fell within 2-4 h to <20% of normal. In the control dogs, the relationship between ST-segment elevation and CPK activity 24 h later was: log CPK = -0.06 ST + 1.48 (n = 111 specimens, 14 dogs, r = 0.77). In the experimental dogs, log CPK = -0.024 ST + 1.46 (n = 111 specimens, 14 dogs, r = 0.60), showing significantly different slopes (P < 0.001), i.e., less CPK depression for any level of ST-segment elevation. Histologically, 69 of 71 sites (97%) with ST-segment elevation exceeding 2 mV in the control dogs showed signs of necrosis 24 h later, whereas in the experimental group only 43 of 79 sites (54%) with abnormal ST-segment elevations showed signs of necrosis (P < 0.0005). At the same time, it was shown that the administration of cobra venom factor did not alter cardiac performance, collateral blood flow to the ischemic myocardium or the clotting system, but infiltration of polymorphonuclear leukocytes into the myocardium was decreased. It is concluded that cobra venom factor, by reducing the amount of C3 and C5 substrate available for chemotactic factor generation, or other as yet undefined mechanisms, protects the

  5. Location of single-stranded and double-stranded regions in rat liver ribosomal 5S RNA and 5.8S RNA.

    PubMed Central

    Toots, I; Metspalu, A; Villems, R; Saarma, M

    1981-01-01

    Rat liver 5S rRNA and 5.8S rRNA were end-labelled with 32P at 5'-end or 3'-end of the polynucleotide chain and partially digested with single-strand specific S1 nuclease and double-strand specific endonuclease from the cobra Naja naja oxiana venom. The parallel use of these two structure-specific enzymes in combination with rapid sequencing technique allowed the exact localization of single-stranded and double-stranded regions in 5S RNA and 5.8 S RNA. The most accessible regions to S1 nuclease in 5S RNA are regions 33-42, 74-78, 102-103 and in 5.8 S RNA 16-20, 26-29, 34-36, 74-80 and a region around 125-130. The cobra venom endonuclease cleaves the following areas in 5S RNA: 7-8, 17-20, 28-30, 49-51, 56-57, 60-64, 69-70, 81-82, 95-97, 106-112. In 5.8S RNA the venom endonuclease cleavage sites are 4-7, 10-13, 21-22, 33-35, 43-45, 51-55, 72-74, 85-87, 98-99, 105-106, 114-115, 132-135. According to these results the tRNA binding sequences proposed by Nishikawa and Takemura [(1974) FEBS Lett. 40, 106-109], in 5S RNA are located in partly single-stranded region, but in 5.8S RNA in double-stranded region. Images PMID:6272219

  6. A new animal model of trigeminal neuralgia produced by administration of cobra venom to the infraorbital nerve in the rat.

    PubMed

    An, Jian-Xiong; He, Ying; Qian, Xiao-Yan; Wu, Jian-Ping; Xie, Yi-Kuan; Guo, Qu-Lian; Williams, John P; Cope, Doris K

    2011-09-01

    Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.

  7. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 2, User's manual

    SciTech Connect

    Rector, D.R.; Cuta, J.M.; Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.

    1986-11-01

    COBRA-SFS (Spent Fuel Storage) is a general thermal-hydraulic analysis computer code used to predict temperatures and velocities in a wide variety of systems. The code was refined and specialized for spent fuel storage system analyses for the US Department of Energy's Commercial Spent Fuel Management Program. The finite-volume equations governing mass, momentum, and energy conservation are written for an incompressible, single-phase fluid. The flow equations model a wide range of conditions including natural circulation. The energy equations include the effects of solid and fluid conduction, natural convection, and thermal radiation. The COBRA-SFS code is structured to perform both steady-state and transient calculations; however, the transient capability has not yet been validated. This volume contains the input instructions for COBRA-SFS and an auxiliary radiation exchange factor code, RADX-1. It is intended to aid the user in becoming familiar with the capabilities and modeling conventions of the code.

  8. NASA TechPort Entry for Coiled Brine Recovery Assembly (CoBRA) CL IR&D Project

    NASA Technical Reports Server (NTRS)

    Pensinger, Stuart

    2014-01-01

    The Coiled Brine Recovery Assembly (CoBRA) project will result in a proof-of-concept demonstration for a lightweight, compact, affordable, regenerable and disposable solution to brine water recovery. The heart of CoBRA is an evaporator that produces water vapor from brine. This evaporator leverages a novel design that enables passive transport of brine from place to place within the system. While it will be necessary to build or modify a system for testing the CoBRA concept, the emphasis of this project will be on developing the evaporator itself. This project will utilize a “test early, test often” approach, building at least one trial evaporator to guide the design of the final product.

  9. Thermal-hydraulic/heat transfer code development for sphere-pac-fueled LMFBRs. [COBRA-3SP code

    SciTech Connect

    Morris, D.G.

    1980-06-01

    Sphere-pac fuel has received much attention recently in light of the development of proliferation-resistant fuel cycles for the Fast Breeder Reactor Program in the United States. However, for sphere-pac fuel to be a viable alternative to conventional pellet fuel, a means to analyze the thermal behavior of sphere-pac-fueled pin bundles is needed. To meet this need, a thermal-hydraulic/heat transfer computer code has been developed for sphere-pac-fueled fast breeder reactors. The code, COBRA-3SP, is a modified version of COBRA-3M incorporating a three-region sphere-pac fuel pin model which permits fuel restructuring. With COBRA-3SP, steady-state and transient analysis of sphere-pac-fueled pin bundles is possible. The validity of the sphere-pac fuel pin model has been verified using experimental results of irradiated sphere-pac fuel.

  10. Cobra-IE Evaluation by Simulation of the NUPEC BWR Full-Size Fine-Mesh Bundle Test (BFBT)

    SciTech Connect

    Burns, C. J. and Aumiler, D. L.

    2006-04-26

    The COBRA-IE computer code is a thermal-hydraulic subchannel analysis program capable of simulating phenomena present in both PWRs and BWRs. As part of ongoing COBRA-IE assessment efforts, the code has been evaluated against experimental data from the NUPEC BWR Full-Size Fine-Mesh Bundle Tests (BFBT). The BFBT experiments utilized an 8 x 8 rod bundle to simulate BWR operating conditions and power profiles, providing an excellent database for investigation of the capabilities of the code. Benchmarks performed included steady-state and transient void distribution, single-phase and two-phase pressure drop, and steady-state and transient critical power measurements. COBRA-IE effectively captured the trends seen in the experimental data with acceptable prediction error. Future sensitivity studies are planned to investigate the effects of enabling and/or modifying optional code models dealing with void drift, turbulent mixing, rewetting, and CHF.

  11. COBRA-SFS thermal-hydraulic analysis code for spent fuel storage and transportation casks: Models and methods

    DOE PAGES

    Michener, Thomas E.; Rector, David R.; Cuta, Judith M.

    2017-09-01

    COBRA-SFS, a thermal-hydraulics code developed for steady-state and transient analysis of multi-assembly spent-fuel storage and transportation systems, has been incorporated into the Used Nuclear Fuel-Storage, Transportation and Disposal Analysis Resource and Data System tool as a module devoted to spent fuel package thermal analysis. This paper summarizes the basic formulation of the equations and models used in the COBRA-SFS code, showing that COBRA-SFS fully captures the important physical behavior governing the thermal performance of spent fuel storage systems, with internal and external natural convection flow patterns, and heat transfer by convection, conduction, and thermal radiation. Of particular significance is themore » capability for detailed thermal radiation modeling within the fuel rod array.« less

  12. COBRA-NC: a thermal hydraulics code for transient analysis of nuclear reactor components. Volume 2. COBRA-NC numerical solution methods

    SciTech Connect

    Thurgood, M.J.; George, T.L.; Wheeler, C.L.

    1986-04-01

    The COBRA-NC computer program has been developed to predict the thermal-hydraulic response of nuclear reactor components to thermal-hydraulic transients. The code solves the multicomponent, compressible three-dimensional, two-fluid, three-field equations for two-phase flow. The three fields are the vapor field, the continuous liquid field, and the liquid drop field. The code has been used to model flow and heat transfer within the reactor core, the reactor vessel, the steam generators, and in the nuclear containment. This volume describes the finite-volume equations and the numerical solution methods used to solve these equations. It is directed toward the user who is interested in gaining a more complete understanding of the numerical methods used to obtain a solution to the hydrodynamic equations.

  13. Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase.

    PubMed

    Li Lee, Mui; Chung, Ivy; Yee Fung, Shin; Kanthimathi, M S; Hong Tan, Nget

    2014-04-01

    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7-amino-actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  14. Purification of native and recombinant cobra venom factor using thiophilic adsorption chromatography.

    PubMed

    Kölln, Johanna; Braren, Ingke; Bredehorst, Reinhard; Spillner, Edzard

    2007-01-01

    The complement activating venom component Cobra Venom Factor (CVF) forms a stable CVF-dependent C3 convertase complex, which initiates continuous activation of the complement system, consumes all downstream complement components and obliterates functional complement. Therefore, native CVF is routinely used as decomplementing agent in vivo and in vitro. However, in most countries, CVF and even unfractionated cobra venom are now becoming unavailable due to the CITES agreement. Although CVF is a complex molecule with three disulfide linked polypeptide chains and pronounced glycosylation, recombinant expression of the active molecule in eukaryotic host cells may provide an alternative source. In this study we describe a strategy for the production and efficient isolation of recombinant CVF from supernatant of mammalian cells. Thiophilic adsorption chromatography (TAC), an efficient procedure for purification of the human homologue C3, was evaluated for its suitability regarding purification of both native as well as recombinant CVF. Native CVF could be purified by TAC in a one-step procedure from cobra venom with yields of 92% compared to 35% by conventional approaches. After establishment of stably transfected mammalian cells recombinant CVF could be obtained and enriched from CHO supernatants by TAC to a purity of 73%, and up to 90% if an additional affinity chromatography step was included. Subsequent characterization revealed comparable hemolytic and bystander lysis activity and of rCVF and nCVF. These data demonstrate that the functional expression in mammalian cells in combination with TAC for purification renders rCVF a highly attractive substitute for its native counterpart.

  15. The Cancer of the Bladder Risk Assessment (COBRA) score: Estimating mortality after radical cystectomy.

    PubMed

    Welty, Christopher J; Sanford, Thomas H; Wright, Jonathan L; Carroll, Peter R; Cooperberg, Matthew R; Meng, Maxwell V; Porten, Sima P

    2017-09-07

    Risk stratification of patients with urothelial carcinoma of the bladder (UCB) after cystectomy has important clinical and research implications. The authors assessed the relative effect of tumor stage and lymph node status on cancer-specific survival (CSS) after cystectomy and developed a simplified risk-assessment tool. In total, 14,828 patients who underwent cystectomy with lymph node dissection for UCB were identified from the Surveillance, Epidemiology, and End Results database (1988-2011). The relative importance of tumor stage and lymph node status with regard to CSS was assessed using stratified Kaplan-Meier and Cox proportional-hazards analyses. The patients were split randomly into development and validation cohorts. Additional validation using overall survival was performed on 19,362 patients from the National Cancer Data Base. The Cancer of Bladder Risk Assessment (COBRA) tool was created using a Cox model incorporating age, tumor stage, and lymph node density. Performance was validated using observed versus expected survival plots and the Harrell concordance index. Patients with muscle invasive (T2), lymph node-positive disease had a survival curve similar to that in patients with extravesical (T3 and T4), lymph node-negative disease (2-year CSS, 67% and 70%, respectively). Each point increase in the COBRA score (range, 0-7) was associated with a 1.61-fold increase (95% confidence interval, 1.56-fold to 1.65-fold increase) in the risk of bladder cancer death in the development cohort. The model accurately stratified patients across risk levels in the development cohort and the 2 validation cohorts (C-index, 0.712, 0.705, and 0.68, respectively). The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. Coiled Brine Recovery Assembly (CoBRA): A New Approach to Recovering Water from Wastewater Brines

    NASA Technical Reports Server (NTRS)

    Pensinger, Stuart J.

    2015-01-01

    Brine water recovery represents a current technology gap in water recycling for human spaceflight. The role of a brine processor is to take the concentrated discharge from a primary wastewater processor, called brine, and recover most of the remaining water from it. The current state-of-the-art primary processor is the ISS Urine Processor Assembly (UPA) that currently achieves 70% water recovery. Recent advancements in chemical pretreatments are expected to increase this to 85% in the near future. This is a welcome improvement, yet is still not high enough for deep space transit. Mission architecture studies indicate that at least 95% is necessary for a Mars mission, as an example. Brine water recovery is the technology that bridges the gap between 85% and 95%, and moves life support systems one step closer to full closure of the water loop. Several brine water recovery systems have been proposed for human spaceflight, most of them focused on solving two major problems: operation in a weightless environment, and management and containment of brine residual. Brine residual is the leftover byproduct of the brine recovery process, and is often a viscous, sticky paste, laden with crystallized solid particles. Due to the chemical pretreatments added to wastewater prior to distillation in a primary processor, these residuals are typically toxic, which further complicates matters. Isolation of crewmembers from these hazardous materials is paramount. The Coiled Brine Recovery Assembly (CoBRA) is a recently developed concept from the Johnson Space Center that offers solutions to these challenges. CoBRA is centered on a softgoods evaporator that enables a passive fill with brine, and regeneration by discharging liquid brine residual to a collection bag. This evaporator is meant to be lightweight, which allows it to be discarded along with the accumulated brine solids contained within it. This paper discusses design and development of a first CoBRA prototype, and reports

  17. Hematology, morphology, cytochemical staining, and ultrastuctural characteristics of blood cells in king cobras (Ophiophagus hannah).

    PubMed

    Salakij, Chaleow; Salakij, Jarernsak; Apibal, Suntaree; Narkkong, Nual-Anong; Chanhome, Lawan; Rochanapat, Nirachara

    2002-01-01

    King cobras (Ophiophagus hannah) have been captive-bred at Queen Saovabha Memorial Institute since 1996 to supply venom for antivenom production. Hematologic tests would be useful for evaluating the health of the snakes, however, basic hematologic data and morphology have not been described for this species. The purpose of this study was to determine basic hematologic values and evaluate light microscopic, cytochemical, and electron microscopic characteristics of king cobra blood cells. Blood samples from 13 wild-caught and 15 captive-bred king cobras were collected into EDTA from the ventral caudal vein. A CBC was done using standard methods. Significant differences between groups were determined using t-tests. Cytochemical stains (periodic acid-Schiff [PAS], Sudan black B [SBB], alpha-naphthyl acetate esterase [ANAE], acid phosphatase [AcP], and beta-glucuronidase [beta-glu]), and scanning and transmission electron microscopy were done using standard techniques. Eighteen snakes (64.3%) were positive for Hepatozoon infection. Hepatozoon organisms were detected nearly twice as frequently in wild-caught (11/13) as in captive-bred (7/15) snakes. Total WBC, azurophil, and lymphocyte counts were higher and fibrinogen concentration was lower in Hepatozoon-positive snakes. Captive-bred snakes had higher RBC values, lower azurophil, heterophil, and punctate reticulocyte percentages, and higher lymphocyte numbers compared with wild-caught snakes. Lymphocytes were the most commonly observed WBCs, and stained positive with PAS, ANAE, AcP, and beta-glu. Azurophil granules stained positive with SBB, PAS, and ANAE. Heterophils were the largest WBCs; their granules stained with SBB, ANAE, and beta-glu. Basophil granules stained with PAS, SBB, ANAE, and beta-glu. Thrombocytes were strongly positive with PAS. Transmission electron microscopic examination revealed organelles within all WBCs except eosinophils and revealed the gamonts of Hepatozoon sp in RBCs and azurophils. These

  18. ATWS Analysis with an Advanced Boiling Curve Approach within COBRA 3-CP

    SciTech Connect

    Gensler, A.; Knoll, A.; Kuehnel, K.

    2007-07-01

    In 2005 the German Reactor Safety Commission issued specific requirements on core coolability demonstration for PWR ATWS (anticipated transients without scram). Thereupon AREVA NP performed detailed analyses for all German PWRs. For a German KONVOI plant the results of an ATWS licensing analysis are presented. The plant dynamic behavior is calculated with NLOOP, while the hot channel analysis is performed with the thermal hydraulic computer code COBRA 3-CP. The application of the fuel rod model included in COBRA 3-CP is essential for this type of analysis. Since DNB (departure from nucleate boiling) occurs, the advanced post DNB model (advanced boiling curve approach) of COBRA 3-CP is used. The results are compared with those gained with the standard BEEST model. The analyzed ATWS case is the emergency power case 'loss of main heat sink with station service power supply unavailable'. Due to the decreasing coolant flow rate during the transient the core attains film boiling conditions. The results of the hot channel analysis strongly depend on the performance of the boiling curve model. The BEEST model is based on pool boiling conditions whereas typical PWR conditions - even in most transients - are characterized by forced flow for which the advanced boiling curve approach is particularly suitable. Compared with the BEEST model the advanced boiling curve approach in COBRA 3-CP yields earlier rewetting, i.e. a shorter period in film boiling. Consequently, the fuel rod cladding temperatures, that increase significantly due to film boiling, drop back earlier and the high temperature oxidation is significantly diminished. The Baker-Just-Correlation was used to calculate the value of equivalent cladding reacted (ECR), i.e. the reduction of cladding thickness due to corrosion throughout the transient. Based on the BEEST model the ECR value amounts to 0.4% whereas the advanced boiling curve only leads to an ECR value of 0.2%. Both values provide large margins to the 17

  19. A bioassay for cobra cardiotoxin activity using semi-isolated cockroach heart.

    PubMed

    Klowden, M J; Vitale, A J; Trumble, M J; Wesson, C R; Trumble, W R

    1992-03-01

    A semi-isolated cockroach heart preparation was used to rapidly determine the activity of cobra cardiotoxin, monitored as a direct response on heart rate. This preparation produced a dose-response curve in the presence of active cardiotoxin and demonstrated that cardiotoxin retained its biological activity after boiling, although cardiotoxin activity was destroyed by heating in the presence of dithiothreitol. Experiments that cross-linked radiolabeled cardiotoxin to solubilized cockroach heart membranes suggested that cardiotoxin bound specifically to a 59,000 mol. wt membrane protein in this tissue.

  20. A parallelization approach to the COBRA-TF thermal-hydraulic subchannel code

    NASA Astrophysics Data System (ADS)

    Ramos, Enrique; Abarca, Agustín; Roman, Jose E.; Miró, Rafael

    2014-06-01

    In order to reduce the response time when simulating large reactors in detail, we have developed a parallel version of the thermal-hydraulic subchannel code COBRA-TF, with standard message passing technology (MPI). The parallelization is oriented to reactor cells, so it is best suited for models consisting of many cells. The generation of the Jacobian is parallelized, in such a way that each processor is in charge of generating the data associated to a subset of cells. Also, the solution of the linear system of equations is done in parallel, using the PETSc toolkit.

  1. Studies of Hot Spots in Imploding Wire Arrays at 1 MA on COBRA

    SciTech Connect

    Pikuz, Sergey A.; Shelkovenko, Tatiana A.; McBride, Ryan D.; Hammer, David A.

    2009-01-21

    We present recent results from hot spot investigations in imploding Al wire array z-pinches on the COBRA generator at Cornell University using x-ray diagnostics. Measurements of the temporal and spatial distribution of hot spots in stagnating plasmas by an x-ray streak-camera are included. Experiments show that hot spots have nanosecond lifetime and appear randomly along the array axis after plasma stagnation in secondary pinches in 8 mm diameter and during plasma stagnation in the arrays with 4 mm diameter.

  2. EM experiments for computational model validation for AH-1S Cobra Helicopter

    SciTech Connect

    Nelson, S.D.

    1997-04-06

    The effort described here describes a set of outdoor experiments performed on the AH-1S Cobra helicopter in order to validate and compare to the computational electromagnetic models of the bulk structure of the airframe in the frequency bands up to 4 GHz. Also included in this were coupling measurements to wires and cables inside of the airframe and various cavity to HPM pulse in this frequency range as part of other activities. Additionally, the low power modeling compression will be completed in this time frame.

  3. Assessment of the Antimicrobial Activity of Few Saudi Arabian Snake Venoms.

    PubMed

    Al-Asmari, Abdulrahman K; Abbasmanthiri, Rajamohamed; Abdo Osman, Nasreddien M; Siddiqui, Yunus; Al-Bannah, Faisal Ahmed; Al-Rawi, Abdulgadir M; Al-Asmari, Sarah A

    2015-01-01

    Venoms of two cobras, four vipers, a standard antibiotic and an antimycotic, were evaluated comparatively, as antimicrobials. Six venom concentrations and three of the standard antibiotic and the antimycotic were run in micro-dilution and diffusion plates against the microorganisms. Echis pyramidum, Echis coloratus and Cerastes cerastes gasperettii highest venom concentrations gave significant growth inhibition zones (GIZ) with respect to a negative control, except Bitis arietans, whose concentrations were significant. The cobra Walterinnesia aegyptia had significant venom concentrations more than Naja haje arabica. The Staphylococcus aureus Methicillin Resistant (MRSA) bacterium was the most susceptible, with a highly (P < 0.001) significant GIZ mean difference followed by the Gram positive Staphylococcus aureus, (P < 0.001), Escherichia coli (P < 0.001), Enterococcus faecalis (P < 0.001) and Pseudomonas aeruginosa which, had the least significance (P < 0.05). The fungus Candida albicans was resistant to both viper and cobra venoms (P > 0.05). The antibiotic Vancomycin was more effective than snake venoms though, they were more efficient in inhibiting growth of the resistant Pseudomonas aeruginosa. This antibiotic was also inactive against the fungus, whilst its specific antifungal Fungizone was highly efficient with no antibacterial activity. These findings showed that snake venoms had antibacterial activity comparable to antibiotics, with a directly proportional relationship of venom concentration and GIZ, though, they were more efficient in combatting resistant types of bacteria. Both venoms and the standard antibiotic, showed no antifungal benefits.

  4. Assessment of the Antimicrobial Activity of Few Saudi Arabian Snake Venoms

    PubMed Central

    Al-Asmari, Abdulrahman K.; Abbasmanthiri, Rajamohamed; Abdo Osman, Nasreddien M.; Siddiqui, Yunus; Al-Bannah, Faisal Ahmed; Al-Rawi, Abdulgadir M.; Al-Asmari, Sarah A.

    2015-01-01

    Background Venoms of two cobras, four vipers, a standard antibiotic and an antimycotic, were evaluated comparatively, as antimicrobials. Methods: Six venom concentrations and three of the standard antibiotic and the antimycotic were run in micro-dilution and diffusion plates against the microorganisms. RESULTS: Echis pyramidum, Echis coloratus and Cerastes cerastes gasperettii highest venom concentrations gave significant growth inhibition zones (GIZ) with respect to a negative control, except Bitis arietans, whose concentrations were significant. The cobra Walterinnesia aegyptia had significant venom concentrations more than Naja haje arabica. The Staphylococcus aureus Methicillin Resistant (MRSA) bacterium was the most susceptible, with a highly (P < 0.001) significant GIZ mean difference followed by the Gram positive Staphylococcus aureus, (P < 0.001), Escherichia coli (P < 0.001), Enterococcus faecalis (P < 0.001) and Pseudomonas aeruginosa which, had the least significance (P < 0.05). The fungus Candida albicans was resistant to both viper and cobra venoms (P > 0.05). The antibiotic Vancomycin was more effective than snake venoms though, they were more efficient in inhibiting growth of the resistant Pseudomonas aeruginosa. This antibiotic was also inactive against the fungus, whilst its specific antifungal Fungizone was highly efficient with no antibacterial activity. Conclusions: These findings showed that snake venoms had antibacterial activity comparable to antibiotics, with a directly proportional relationship of venom concentration and GIZ, though, they were more efficient in combatting resistant types of bacteria. Both venoms and the standard antibiotic, showed no antifungal benefits. PMID:26668657

  5. A Summary of Aquatic Vegetation Monitoring at Selected Locations in Pools 4, 8, 13, and 26 and La Grange Pool of the Upper Mississippi River System. 1993 Annual Status Report,

    DTIC Science & Technology

    1998-07-01

    Najas guadalupensis (Spreng.) Magnus Nymphaeaceae American lotus Nelumbo lutea (Willd.) Pers. Nymphaeaceae White waterlily Nymphaea odorata Ait... Nymphaeaceae Yellow pondlily Nuphar lutea (L.) Sm Onagraceae Floating primrosewillow Jussiaea repens L. Pontederiaceae Water stargrass, Heteranthera dubia

  6. Molecular identification of three Indian snake species using simple PCR-RFLP method.

    PubMed

    Dubey, Bhawna; Meganathan, P R; Haque, Ikramul

    2010-07-01

    Three endangered Indian snake species, Python molurus, Naja naja, and Xenochrophis piscator are known to be significantly involved in illegal trade. Effective authentication of species is required to curb this illegal trade. In the absence of morphological features, molecular identification techniques hold promise to address the issue of species identification. We present an effective PCR-restriction fragment length polymorphism method for easy identification of the three endangered snake species, Python molurus, Naja naja, and Xenochrophis piscator. A 431-bp amplicon from cytochrome b gene was amplified using novel snake-specific primers following restriction digestion with enzymes Mbo II and Fok I. The species-specific reference fragment patterns were obtained for the target species, which enabled successful identification of even highly degraded shed skin sample confirming the utility of the technique in case of poor-quality DNA. The assay could be effectively used for forensic authentication of three Indian snake species and would help strengthen conservation efforts.

  7. Ohanin, a novel protein from king cobra venom: its cDNA and genomic organization.

    PubMed

    Pung, Yuh Fen; Kumar, Sanjeed Vijaya; Rajagopalan, Nandhakishore; Fry, Bryan G; Kumar, Prakash P; Kini, R Manjunatha

    2006-04-26

    Ohanin, from king cobra venom, is a novel protein which induces hypolocomotion and hyperalgesia in mice [Pung, Y.F., Wong, P.T.H., Kumar, P.P., Hodgson W.C., Kini, R.M., 2005. Ohanin, a novel protein from king cobra venom induces hypolocomotion and hyperalgesia in mice. J. Biol. Chem. 280, 13137-13147.]. It is weakly similar to PRY-SPRY domains (B30.2-like domain). Here we report the complete cDNA and genomic organization of ohanin. Interestingly, cDNA sequence does not show significant sequence similarity to any known sequences, including those of B30.2-like domain-containing proteins. Its full-length cDNA sequence of 1558 bp encodes for prepro-ohanin with a propeptide segment at the C-terminal. Ohanin is the first member of a new subfamily of proteins containing B30.2-like domain with short N-terminal segment. We named this subfamily as vespryns. There are two mRNA subtypes differing in their 5'-untranslated regions. Southern hybridization study shows that ohanin is encoded by a single gene. Its genomic sequence is 7086 bp with five exons and four introns, and the two types of mRNAs are generated by alternative splicing of exon 2. Our results indicate that ohanin and vespryns may have evolved from the same ancestral gene as B30.2 domain.

  8. COBRA-SFS: A thermal-hydraulic analysis code for spent fuel storage and transportation casks

    SciTech Connect

    Michener, T.E.; Rector, D.R.; Cuta, J.M.; Dodge, R.E.; Enderlin, C.W.

    1995-09-01

    COBRA-SFS is a general thermal-hydraulic analysis computer code for prediction of material temperatures and fluid conditions in a wide variety of systems. The code has been validated for analysis of spent fuel storage systems, as part of the Commercial Spent Fuel Management Program of the US Department of Energy. The code solves finite volume equations representing the conservation equations for mass, moment, and energy for an incompressible single-phase heat transfer fluid. The fluid solution is coupled to a finite volume solution of the conduction equation in the solid structure of the system. This document presents a complete description of Cycle 2 of COBRA-SFS, and consists of three main parts. Part 1 describes the conservation equations, constitutive models, and solution methods used in the code. Part 2 presents the User Manual, with guidance on code applications, and complete input instructions. This part also includes a detailed description of the auxiliary code RADGEN, used to generate grey body view factors required as input for radiative heat transfer modeling in the code. Part 3 describes the code structure, platform dependent coding, and program hierarchy. Installation instructions are also given for the various platform versions of the code that are available.

  9. Developments in high-density Cobra fiber positioners for the Subaru Telescope's Prime Focus Spectrometer

    NASA Astrophysics Data System (ADS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Michael D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger M.

    2012-09-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed “Cobra”, will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual “SCARA robot” mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5μm of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  10. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

    PubMed Central

    Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Heimberg, Alysha M.; Jansen, Hans J.; McCleary, Ryan J. R.; Kerkkamp, Harald M. E.; Vos, Rutger A.; Guerreiro, Isabel; Calvete, Juan J.; Wüster, Wolfgang; Woods, Anthony E.; Logan, Jessica M.; Harrison, Robert A.; Castoe, Todd A.; de Koning, A. P. Jason; Pollock, David D.; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B.; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S.; Ribeiro, José M. C.; Arntzen, Jan W.; van den Thillart, Guido E. E. J. M.; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P.; Spaink, Herman P.; Duboule, Denis; McGlinn, Edwina; Kini, R. Manjunatha; Richardson, Michael K.

    2013-01-01

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection. PMID:24297900

  11. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

    PubMed

    Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha M; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wüster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, José M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, R Manjunatha; Richardson, Michael K

    2013-12-17

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.

  12. Merit Pay in Arkansas: An Evaluation of the Cobra Pride Incentive Program in the Fountain Lake School District

    ERIC Educational Resources Information Center

    Jensen, Nathan C.

    2012-01-01

    Starting in the 2010-11, administrators at the Fountain Lake School District implemented the Cobra Pride Incentive Program (CPIP), a merit pay program designed to financially reward all school employees with year-end bonuses primarily for significant improvements in student achievement. At the conclusion of the 2010-11 school year, over $800,000…

  13. Merit Pay in Arkansas: An Evaluation of the Cobra Pride Incentive Program in the Fountain Lake School District

    ERIC Educational Resources Information Center

    Jensen, Nathan C.

    2012-01-01

    Starting in the 2010-11, administrators at the Fountain Lake School District implemented the Cobra Pride Incentive Program (CPIP), a merit pay program designed to financially reward all school employees with year-end bonuses primarily for significant improvements in student achievement. At the conclusion of the 2010-11 school year, over $800,000…

  14. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention.

    PubMed

    Landewé, Robert B M; Boers, Maarten; Verhoeven, Arco C; Westhovens, Rene; van de Laar, Mart A F J; Markusse, Harry M; van Denderen, J Christiaan; Westedt, Marie Louise; Peeters, Andre J; Dijkmans, Ben A C; Jacobs, Piet; Boonen, Annelies; van der Heijde, Désirée M F M; van der Linden, Sjef

    2002-02-01

    The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor

  15. Complete amino acid sequence of an acidic, cardiotoxic phospholipase A2 from the venom of Ophiophagus hannah (King Cobra): a novel cobra venom enzyme with "pancreatic loop".

    PubMed

    Huang, M Z; Gopalakrishnakone, P; Chung, M C; Kini, R M

    1997-02-15

    A phospholipase A2 (OHV A-PLA2) from the venom of Ophiophagus hannah (King cobra) is an acidic protein exhibiting cardiotoxicity, myotoxicity, and antiplatelet activity. The complete amino acid sequence of OHV A-PLA2 has been determined using a combination of Edman degradation and mass spectrometric techniques. OHV A-PLA2 is composed of a single chain of 124 amino acid residues with 14 cysteines and a calculated molecular weight of 13719 Da. It contains the loop of residues (62-66) found in pancreatic PLA2s and hence belongs to class IB enzymes. This pancreatic loop is between two proline residues (Pro 59 and Pro 68) and contains several hydrophilic amino acids (Ser and Asp). This region has high degree of conformational flexibility and is on the surface of the molecule, and hence it may be a potential protein-protein interaction site. A relatively low sequence homology is found between OHV A-PLA2 and other known cardiotoxic PLA2s, and hence a contiguous segment could not be identified as a site responsible for the cardiotoxic activity.

  16. Maintaining health insurance during a recession: likely COBRA eligibility: an updated analysis using the Commonwealth Fund 2007 Biennial Health Insurance Survey.

    PubMed

    Doty, Michelle; Rustgi, Sheila D; Schoen, Cathy; Collins, Sara R

    2009-01-01

    As the U.S. economic downturn continues and job losses mount, more working Americans are likely to lose access to affordable health benefits subsidized by their employers. Analysis of the 2007 Commonwealth Fund Biennial Health Insurance Survey finds that two of three working adults would be eligible to extend job-based coverage, under the 1985 Consolidated Omnibus Budget Reconciliation Act (COBRA) if they became unemployed. Under COBRA, however, unemployed workers would have to pay four to six times their current contribution at a time of sharply reduced income. In fact, the latest national figures indicate that, because of high premiums, only 9 percent of unemployed workers have COBRA coverage. Substantial financial assistance of 75 percent to 85 percent of premiums could help laid-off workers maintain coverage. In addition, expansion of Medicaid and the State Children's Health Insurance Program would benefit low-income, laid-off workers and their families who are ineligible for COBRA.

  17. Determination of the Secondary Structure of the king Cobra Neurotoxin CM-11.

    PubMed

    Pang, Yu-Xi; Liu, Wei-Dong; Liu, Ai-Zhuo; Pei, Feng-Kui

    1997-01-01

    The king cobra neurotoxin CM-11 is a small protein with 72 amino acid residues. After its complete assignments of (1)H-NMR resonance's were obtained using various 2D-NMR technologies, including DQF-COSY, clean-TOCSY and NOESY, the secondary structure was analysed by studying the various NOEs extracted from the NOESY spectra and the distribution of chemical shifts. The secondary structure was finally determined by MCD as follows: a triple-strand antiparallel beta sheet with I20-W26, R37-A43 and V53-S59 as its beta strands, a short alpha helix formed by W30-G35 and four turns formed by P7-K1O, C14-G17, K50-V53 and D61-N64.

  18. Purification and characterization of acetylcholinesterase from desert cobra (Walterinnesia aegyptia) venom.

    PubMed

    Duhaiman, A S; Alhomida, A S; Rabbani, N; Kamal, M A; al-Jafari, A A

    1996-01-01

    Acetylcholinesterase (AChE) has been identified and purified from the venom of desert cobra (W aegyptia) to apparent homogeneity using a TSK G 3000 SW gel filtration column and a Mono Q anion-exchange column. AChE was purified to homogeneity as established by sodium dodecylsulfate/polyacrylamide gel electrophoresis. The specific activity of AChE was 357 IU/mg with acetylthiocholine iodide as substrate. The denatured W aegyptia venom AChE displayed a molecular mass of 67000 +/- 3000 Da suggesting it was a single polypeptide. Isoelectric focusing of AChE revealed that the enzyme exists in different isoforms, with isoelectric points ranging between pH 7.4-7.9. The kinetic parameters (Km and Vmax) and IC50 of AChE inhibition by procaine, tetracaine and physostigmine were investigated in the present study.

  19. Preliminary crystallographic study of an acidic phospholipase A2 from Ophiophagus hannah (king cobra).

    PubMed

    Xu, Sujuan; Gu, Lichuan; Wang, Qiuyan; Shu, Yuyan; Lin, Zhengjiong

    2002-10-01

    An acidic phospholipase A(2) (OH APLA(2)-II) with an isoelectric point (pI) of 4.0 was recently isolated from Ophiophagus hannah (king cobra) from Guangxi province, China. Comparison of this enzyme to a previously reported homologous phospholipase A(2) from the same venom shows that it lacks toxicity and exhibits a greater phospholipase activity. OH APLA(2)-II has been crystallized by the hanging-drop vapour-diffusion method using 1,6-hexanediol and magnesium chloride as precipitants. The crystal belongs to space group P6(3), with unit-cell parameters a = b = 98.06, c = 132.39 A. The diffraction data were collected under cryoconditions (100 K) and reduced to 2.1 A resolution. A molecular-replacement solution has been determined and shows that there are six molecules in one asymmetric unit.

  20. Hannahpep: A novel fibrinolytic peptide from the Indian King Cobra (Ophiophagus hannah) venom.

    PubMed

    Gomes, A; De, P

    1999-12-20

    A novel fibrinolytic peptide (Hannahpep) was isolated and purified from the venom of the Indian King Cobra (Ophiophagus hannah) by thin-layer chromatography followed by reverse-phase high-performance liquid chromatography. The MW of the peptide was found to be 610 Da and the amino acid sequence of Hannahpep was determined to be Arg, His, Ala, Arg, His, Asp. Hannahpep produced defibrinogenating activity in male albino mice. It exhibited significant fibrinolytic and fibrinogenolytic activity in vitro. Hannahpep showed plasma-anticlotting activity. However, it lacked hemolytic, hemorrhagic, or phospholipase activity. This peptide may have possible therapeutic application in the management of thrombosis or occlusion of a blood vessel. Copyright 1999 Academic Press.

  1. Calibration of CryojetHT and Cobra Plus Cryosystems used in X-ray diffraction studies

    NASA Astrophysics Data System (ADS)

    Dudka, A. P.; Verin, I. A.; Smirnova, E. S.

    2016-07-01

    CryoJetHT (Oxford Instruments) and Cobra Plus (Oxford Cryosystems) cryosystems, which are used for sample cooling in X-ray diffraction experiments, have been calibrated. It is shown that the real temperature in the vicinity of the sample differs significantly (the deviation is as high as 8-10 K at low temperatures) from the temperature recorded by authorized sensors of these systems. The calibration results are confirmed by measurements of the unit-cell parameters of GdFe3(BO3)4 single crystal in the temperature range of its phase transition. It is shown that, to determine the real temperature of a sample, one must perform an independent calibration of cryosystems rather than rely on their ratings.

  2. A lethal neurotoxic protein from Indian king cobra (Ophiophagus hannah) venom.

    PubMed

    De, Pallabi; Dasgupta, S C; Gomes, A

    2002-12-01

    A lethal neurotoxin protein (Toxin CM36) was isolated and purified from the Indian King Cobra (Ophiophagus hannah) venom by CM-Sephadex ion exchange chromatography and HPLC. The purified toxin had a SDS-molecular weight of 15 +/- 0.5 kD. The UV absorption spectra of Toxin CM36 showed a peak at 280 nm and an Emax at 343.8 nm, when excited at 280 nm fluorescence. Toxin CM36 had an LD50 of 3.5 microg/20 g (i.v.) in male albino mice. It exhibited neurotoxicity and produced irreversible blockade of isolated chick biventer cervicis and rat phrenic nerve diaphragm. The neurotoxicity was found to be Ca2+ dependent. Toxin CM36 had no significant effect on isolated guineapig heart and auricle. It also had no effect on blood pressure of cat and rat but produced respiratory apnoea in rat and guineapig. Toxin CM36 lacked phospholipase activity.

  3. Role of heparan sulfates and glycosphingolipids in the pore formation of basic polypeptides of cobra cardiotoxin.

    PubMed

    Wu, Wen-Guey; Tjong, Siu-Cin; Wu, Po-Long; Kuo, Je-Hung; Wu, Karen

    2010-01-01

    Cobra venom contains cardiotoxins (CTXs) that induce tissue necrosis and systolic heart arrest in bitten victims. CTX-induced membrane pore formation is one of the major mechanisms responsible for the venom's designated cytotoxicity. This chapter examines how glycoconjugates such as heparan sulfates (HS) and glycosphingolipids, located respectively in the extracellular matrix and lipid bilayers of the cell membranes, facilitate CTX pore formation. Evidences for HS-facilitated cell surface retention and glycosphingolipid-facilitated membrane bilayer insertion of CTX are reviewed. We suggest that similar physical steps could play a role in the mediation of other pore forming toxins (PFT). The membrane pores formed by PFT are expected to have limited lifetime on biological cell surface as a result of membrane dynamics during endocytosis and/or rearrangement of lipid rafts.

  4. Radiative properties of argon gas puff z-pinch implosions on COBRA

    NASA Astrophysics Data System (ADS)

    Ouart, N. D.; de Grouchy, P. W. L.; Qi, N.; Giuliani, J. L.; Dasgupta, A.; Shelkovenko, T. A.; Pikuz, S. A.; Hammer, D. A.; Kusse, B. R.; Apruzese, J. P.; Clark, R. W.

    2016-10-01

    Spatially resolved and time-integrated x-ray spectroscopy, combined with modeling of the spectra with detailed radiation kinetics and transport, is a powerful method to study the conditions in a hot moving plasma. K-shell argon spectra were measured from gas puff implosions with different center jet masses on the 1 MA COBRA generator at Cornell University. The outer to inner plenum pressures (1 and 3 psia, respectively) were the same for all shots producing an outer to inner mass ratio of 1:1. This paper uses non-local thermodynamic equilibrium kinetic modeling to infer the ion density, electron temperature, K-shell radiating mass, and K-shell powers from stagnating argon gas puff z-pinch implosion. We find that the implosions with a center jet produced bright spot regions of plasma with higher temperature and density than those without a jet.

  5. von Bertalanffy 1.0: a COBRA toolbox extension to thermodynamically constrain metabolic models.

    PubMed

    Fleming, Ronan M T; Thiele, Ines

    2011-01-01

    In flux balance analysis of genome scale stoichiometric models of metabolism, the principal constraints are uptake or secretion rates, the steady state mass conservation assumption and reaction directionality. Here, we introduce an algorithmic pipeline for quantitative assignment of reaction directionality in multi-compartmental genome scale models based on an application of the second law of thermodynamics to each reaction. Given experimental or computationally estimated standard metabolite species Gibbs energy and metabolite concentrations, the algorithms bounds reaction Gibbs energy, which is transformed to in vivo pH, temperature, ionic strength and electrical potential. This cross-platform MATLAB extension to the COnstraint-Based Reconstruction and Analysis (COBRA) toolbox is computationally efficient, extensively documented and open source. http://opencobra.sourceforge.net.

  6. Testing and COBRA-SFS analysis of the VSC-17 ventilated concrete, spent fuel storage cask

    SciTech Connect

    McKinnon, M.A.; Dodge, R.E.; Schmitt, R.C.

    1992-04-01

    A performance test of a Pacific Sierra Nuclear VSC-17 ventilated concrete storage cask loaded with 17 canisters of consolidated PWR spent fuel generating approximately 15 kW was conducted. The performance test included measuring the cask surface, concrete, air channel surface, and fuel temperatures, as well as cask surface gamma and neutron dose rates. Testing was performed using vacuum, nitrogen, and helium backfill environments. Pretest predictions of cask thermal performance were made using the COBRA-SFS computer code. Analysis results were within 15{degrees}C of measured peak fuel temperature. Peak fuel temperature for normal operation was 321{degrees}C. In general, the surface dose rates were less than 30 mrem/h on the side of the cask and 40 mrem/h on the top of the cask.

  7. von Bertalanffy 1.0: a COBRA toolbox extension to thermodynamically constrain metabolic models

    PubMed Central

    Fleming, Ronan M. T.; Thiele, Ines

    2011-01-01

    Motivation: In flux balance analysis of genome scale stoichiometric models of metabolism, the principal constraints are uptake or secretion rates, the steady state mass conservation assumption and reaction directionality. Here, we introduce an algorithmic pipeline for quantitative assignment of reaction directionality in multi-compartmental genome scale models based on an application of the second law of thermodynamics to each reaction. Given experimental or computationally estimated standard metabolite species Gibbs energy and metabolite concentrations, the algorithms bounds reaction Gibbs energy, which is transformed to in vivo pH, temperature, ionic strength and electrical potential. Results: This cross-platform MATLAB extension to the COnstraint-Based Reconstruction and Analysis (COBRA) toolbox is computationally efficient, extensively documented and open source. Availability: http://opencobra.sourceforge.net Contact: ronan.mt.fleming@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21115436

  8. Endotracheal intubation with intubating laryngeal mask airway (ILMA), C-Trach, and Cobra PLA in simulated cervical spine injury patients: a comparative study.

    PubMed

    Mathew, Deepak G; Ramachandran, Rashmi; Rewari, Vimi; Trikha, Anjan; Chandralekha

    2014-10-01

    The aim of our study was to evaluate the success rate of fiberoptic-guided endotracheal intubation through an Intubating Laryngeal Mask Airway (ILMA), a Cobra Perilaryngeal Airway (Cobra PLA), and a C-Trach Laryngeal Mask Airway (C-Trach) in patients whose necks are stabilized in a hard cervical collar. One hundred and eighty ASA I-II patients were randomized to undergo endotracheal intubation after general anesthesia via an ILMA (group ILMA), a C-Trach (group C-Trach) or a Cobra PLA (group CPLA) with the application of an appropriately-sized hard cervical collar. A fiberoptic bronchoscope was used for intubation via the ILMA and Cobra PLA. Rate of successful insertion of an endotracheal tube through the three devices was the primary aim. Other parameters compared were time taken for device insertion, endotracheal intubation, hemodynamic changes, incidence of hypoxia, and mucosal injury during the procedure. The incidence of postoperative sore throat was also compared between the three groups. The success rates of intubation in the ILMA, C-Trach, and CPLA groups were 100, 100, and 98% respectively. The first-attempt success rate was significantly better with the C-Trach compared to Cobra PLA (100 vs. 85%, p < 0.05). The time taken for device insertion was significantly more with the Cobra PLA as compared to that taken with an ILMA or a C-Trach (35.7 vs. 30.3 and 27.5 s, respectively). Intubation through a C-Trach took the least amount of time (84.4 s) as compared to an ILMA (117.9 s) or a Cobra PLA (139.2 s). The incidence of hypoxia and airway morbidity was similar between the groups. The success rates of fiberoptic-guided endotracheal intubation through an ILMA and a Cobra PLA are similar to the success rate of intubation using a C-Trach in patients whose cervical spines are immobilized with a hard cervical collar.

  9. King cobra (Ophiophagus hannah) bites in Myanmar: venom antigen levels and development of venom antibodies.

    PubMed

    Tun-Pe; Aye-Aye-Myint; Warrell, D A; Tin-Myint

    1995-03-01

    Venom, venom IgG and IgM antibody and total serum IgG levels following king cobra bites in two reptile handlers were measured by enzyme immunoassay. The patient in case 1 received antivenom while the patient in case 2 did not. Case 1 made a complete recovery following the bite and produced a high titre short-lived antibody. Venom antigen was not detected in the sample taken 11 hr after antivenom. Case 2 had experienced two recent minor king cobra bites and had received traditional immunization 4 weeks before the accident reported here. He had developed only local swelling and suffered no neurological symptoms. Venom antigen measured at 1.45 hr after the bite was 132 ng/ml; this rapidly fell to 45 ng/ml over the next 30 min, and was no longer detectable 14 hr after the bite. The pattern of venom IgG and IgM antibody responses in both cases was comparable, except that in case 2 the venom IgG peak was maintained for 13 days, compared with 1 day in case 1; in case 2 it subsequently fell to low levels 8 weeks after the bite. Venom IgM appeared 1 day after the bite, peaked at day 7-9, rapidly tailed off on day 12-16 and was then undetectable from day 20 onwards in both. Total IgG level remained within normal limits in both. It is possible that previous bites and recent immunization contributed to the boosting of the venom IgG response in case 2.

  10. BiKEGG: a COBRA toolbox extension for bridging the BiGG and KEGG databases.

    PubMed

    Jamialahmadi, Oveis; Motamedian, Ehsan; Hashemi-Najafabadi, Sameereh

    2016-10-18

    Development of an interface tool between the Biochemical, Genetic and Genomic (BiGG) and KEGG databases is necessary for simultaneous access to the features of both databases. For this purpose, we present the BiKEGG toolbox, an open source COBRA toolbox extension providing a set of functions to infer the reaction correspondences between the KEGG reaction identifiers and those in the BiGG knowledgebase using a combination of manual verification and computational methods. Inferred reaction correspondences using this approach are supported by evidence from the literature, which provides a higher number of reconciled reactions between these two databases compared to the MetaNetX and MetRxn databases. This set of equivalent reactions is then used to automatically superimpose the predicted fluxes using COBRA methods on classical KEGG pathway maps or to create a customized metabolic map based on the KEGG global metabolic pathway, and to find the corresponding reactions in BiGG based on the genome annotation of an organism in the KEGG database. Customized metabolic maps can be created for a set of pathways of interest, for the whole KEGG global map or exclusively for all pathways for which there exists at least one flux carrying reaction. This flexibility in visualization enables BiKEGG to indicate reaction directionality as well as to visualize the reaction fluxes for different static or dynamic conditions in an animated manner. BiKEGG allows the user to export (1) the output visualized metabolic maps to various standard image formats or save them as a video or animated GIF file, and (2) the equivalent reactions for an organism as an Excel spreadsheet.

  11. [Effects of intratumoral injection of microspheres containing cobra venom cytotoxin on transplanted human hepatoma in nude mice].

    PubMed

    Wang, Yan; Lin, Li-wu; Chen, Zhi-kui; Xue, En-sheng; Lin, Xiao-dong; Yu, Li-Yun; Lin, Zhen-hu

    2009-09-01

    To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)microm. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong

  12. Sphaerechinorhynchus ophiograndis n. sp. (Acanthocephala:Plagiorhynchidae:Sphaerechinorhynchinae), described from the intestine of a king cobra, Ophiophagus hannah.

    PubMed

    Bolette, D P

    1997-04-01

    Six acanthocephalan specimens of an undescribed species of Sphaerechinorhynchus Johnston and Deland, 1929, were found attached to the mucosal surface of the proximal small intestine of a legally imported king cobra, Ophiophagus hannali (Cantor, 1836). These specimens are described as Sphaerechinorhynchus ophiograndis n. sp., the third species of the genus from snakes native to the Indo-Australian region, and the second species described from adults in the king cobra. Sphaerechinorhynchus ophiograndis n. sp. differs from Sphaerechinorhynchus serpenticola Schmidt and Kuntz, 1966 and Sphaerechinorhynchus rotun docapitus (Johnston, 1912) Johnston and Deland. 1929, by differences in proboscis and hook morphology, lemniscus length and appearance, testes presentation, number of cement glands, and, additionally from S. ronundocapitus, by overall trunk size and location of attachment within the host species.

  13. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 1, Mathematical models and solution method

    SciTech Connect

    Rector, D.R.; Wheeler, C.L.; Lombardo, N.J.

    1986-11-01

    COBRA-SFS (Spent Fuel Storage) is a general thermal-hydraulic analysis computer code used to predict temperatures and velocities in a wide variety of systems. The code was refined and specialized for spent fuel storage system analyses for the US Department of Energy's Commercial Spent Fuel Management Program. The finite-volume equations governing mass, momentum, and energy conservation are written for an incompressible, single-phase fluid. The flow equations model a wide range of conditions including natural circulation. The energy equations include the effects of solid and fluid conduction, natural convection, and thermal radiation. The COBRA-SFS code is structured to perform both steady-state and transient calculations: however, the transient capability has not yet been validated. This volume describes the finite-volume equations and the method used to solve these equations. It is directed toward the user who is interested in gaining a more complete understanding of these methods.

  14. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 3, Validation assessments

    SciTech Connect

    Lombardo, N.J.; Cuta, J.M.; Michener, T.E.; Rector, D.R.; Wheeler, C.L.

    1986-12-01

    This report presents the results of the COBRA-SFS (Spent Fuel Storage) computer code validation effort. COBRA-SFS, while refined and specialized for spent fuel storage system analyses, is a lumped-volume thermal-hydraulic analysis computer code that predicts temperature and velocity distributions in a wide variety of systems. Through comparisons of code predictions with spent fuel storage system test data, the code's mathematical, physical, and mechanistic models are assessed, and empirical relations defined. The six test cases used to validate the code and code models include single-assembly and multiassembly storage systems under a variety of fill media and system orientations and include unconsolidated and consolidated spent fuel. In its entirety, the test matrix investigates the contributions of convection, conduction, and radiation heat transfer in spent fuel storage systems. To demonstrate the code's performance for a wide variety of storage systems and conditions, comparisons of code predictions with data are made for 14 runs from the experimental data base. The cases selected exercise the important code models and code logic pathways and are representative of the types of simulations required for spent fuel storage system design and licensing safety analyses. For each test, a test description, a summary of the COBRA-SFS computational model, assumptions, and correlations employed are presented. For the cases selected, axial and radial temperature profile comparisons of code predictions with test data are provided, and conclusions drawn concerning the code models and the ability to predict the data and data trends. Comparisons of code predictions with test data demonstrate the ability of COBRA-SFS to successfully predict temperature distributions in unconsolidated or consolidated single and multiassembly spent fuel storage systems.

  15. Purification, sequencing and structural characterization of the phospholipase A1 from the venom of the social wasp Polybia paulista (Hymenoptera, Vespidae).

    PubMed

    Santos, Lucilene D; Santos, Keity S; de Souza, Bibiana M; Arcuri, Helen A; Cunha-Neto, Edécio; Castro, Fabio Morato; Kalil, Jorge Elias; Palma, Mario S

    2007-12-01

    The biochemical and functional characterization of wasp venom toxins is an important prerequisite for the development of new tools both for the therapy of the toxic reactions due to envenomation caused by multiple stinging accidents and also for the diagnosis and therapy of allergic reactions caused by this type of venom. PLA(1) was purified from the venom of the neotropical social wasp Polybia paulista by using molecular exclusion and cation exchange chromatographies; its amino acid sequence was determined by using automated Edman degradation and compared to the sequences of other vespid venom PLA(1)'s. The enzyme exists as a 33,961.40 Da protein, which was identified as a lipase of the GX class, liprotein lipase superfamily, pancreatic lipases (ab20.3) homologous family and RP2 sub-group of phospholipase. P. paulista PLA(1) is 53-82% identical to the phospholipases from wasp species from Northern Hemisphere. The use restrained-based modeling permitted to describe the 3-D structure of the enzyme, revealing that its molecule presents 23% alpha-helix, 28% beta-sheet and 49% coil. The protein structure has the alpha/beta fold common to many lipases; the core consists of a tightly packed beta-sheet constituted of six-stranded parallel and one anti-parallel beta-strand, surrounded by four alpha-helices. P. paulista PLA(1) exhibits direct hemolytic action against washed red blood cells with activity similar to the Cobra cardiotoxin from Naja naja atra. In addition to this, PLA(1) was immunoreactive to specific IgE from the sera of P. paulista-sensitive patients.

  16. Rare cardiac sequelae of a hump-nosed viper bite.

    PubMed

    Thillainathan, Sharmila; Priyangika, Dilani; Marasinghe, Indika; Kanapathippillai, Karunayokiny; Premawansa, Gayani

    2015-09-14

    The hump-nosed pit viper (Hypnale hypnale) is the commonest cause for venomous snakebites in Sri Lanka. Previously, it was thought to cause only local envenomation. However recently, several systemic effects and even mortality has been reported. Along with other snakes, such as the Indian cobra (Naja naja), the common krait (Bungarus caeruleus), the Russell's viper (Daboia russelii) and the saw-scaled viper (Echis carinatus), the hump-nosed viper is now also considered capable of causing lethal envenomation. Unlike other snake species, the systemic manifestations occurring through the bite of a hump-nosed viper, such as acute renal failure, thrombotic microangiopathy etc are rare and unpredictable. A 49-year-old Sri Lankan Tamil male presented with a hump-nosed viper bite, which had resulted in a cardiac arrest within half an hour of envenomation. On arrival to the Emergency Treatment Unit, he was unconscious and without spontaneous breathing. Electrocardiography monitoring revealed ST elevation in leads II, III and aVF with reciprocal changes in leads I and aVL-indicating inferior wall infarction-as well as atrial fibrillation. Glasgow Coma Scale was 7/15, which indicated severe brain injury and electroencephalogram on day 10 revealed a low amplitude pattern compatible with diffuse brain damage. This case describes an authenticated case of myocardial infarction in a 49-year-old male following envenomation by a hump-nosed viper in Sri Lanka. This systemic effect of this viper's bite has not previously been described in the literature. This case report is intended to increase the vigilance for myocardial infarction following hump-nosed viper envenomation.

  17. Development of dot-ELISA for the detection of venoms of major Indian venomous snakes.

    PubMed

    Shaikh, Innus K; Dixit, Prashant P; Pawade, Balasaheb S; Waykar, Indrasen G

    2017-10-09

    India remained an epicenter for the snakebite-related mortality and morbidities due to widespread agricultural activities across the country and a considerable number of snakebites offended by Indian cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). Presently, there is no selective test available for the detection of snake envenomation in India before the administration of snake antivenin. Therefore, the present study aimed to develop rapid, sensitive assay for the management of snakebite, which can detect venom, responsible snake species and serve as a tool for the reasonable administration of snake antivenin, which have scarcity across the world. The selective envenomation detection assay needs venom specific antibodies (VSAbs) for that monovalent antisera was prepared by hyperimmunization of rabbits with specific venom. However, obtained antibodies exhibit maximum activity towards homologous venom as well as quantifiable degree of cross-reactivity with heterologous venoms. Use of these antibodies for development of selective envenomation detection assay may create ambiguity in results, therefore needs to isolate VSAbs from monovalent antisera. The cross-reacting antibodies were specifically removed by immunoaffinity chromatography to obtain VSAbs. For the development of venom detection ELISA test (VDET), two different species of antibodies were used that offers enhanced sensitivity along with selective identification of the venoms of the responsible snakes. In conclusion, the developed VDET is rapid, specific, yet sensitive to detect venoms of offending snake species, and its venom concentration down to 1.0 ng/ml. However, the device observed with lowest venom concentration detection ability in the range <1.0 ng/ml from experimentally envenomated samples. The implementation of VDET will help in avoiding unnecessary usage and adverse reactions of snake antivenin. The test has all the

  18. Comparison of three classes of snake neurotoxins by homology modeling and computer simulation graphics.

    PubMed

    Juan, H F; Hung, C C; Wang, K T; Chiou, S H

    1999-04-13

    We present a systematic structure comparison of three major classes of postsynaptic snake toxins, which include short and long chain alpha-type neurotoxins plus one angusticeps-type toxin of black mamba snake family. Two novel alpha-type neurotoxins isolated from Taiwan cobra (Naja naja atra) possessing distinct primary sequences and different postsynaptic neurotoxicities were taken as exemplars for short and long chain neurotoxins and compared with the major lethal short-chain neurotoxin in the same venom, i.e., cobrotoxin, based on the derived three-dimensional structure of this toxin in solution by NMR spectroscopy. A structure comparison among these two alpha-neurotoxins and angusticeps-type toxin (denoted as FS2) was carried out by the secondary-structure prediction together with computer homology-modeling based on multiple sequence alignment of their primary sequences and established NMR structures of cobrotoxin and FS2. It is of interest to find that upon pairwise superpositions of these modeled three-dimensional polypeptide chains, distinct differences in the overall peptide flexibility and interior microenvironment between these toxins can be detected along the three constituting polypeptide loops, which may reflect some intrinsic differences in the surface hydrophobicity of several hydrophobic peptide segments present on the surface loops of these toxin molecules as revealed by hydropathy profiles. Construction of a phylogenetic tree for these structurally related and functionally distinct toxins corroborates that all long and short toxins present in diverse snake families are evolutionarily related to each other, supposedly derived from an ancestral polypeptide by gene duplication and subsequent mutational substitutions leading to divergence of multiple three-loop toxin peptides.

  19. Cross-reactivity and neutralization of Indian King cobra (Ophiophagus hannah) venom by polyvalent and monovalent antivenoms.

    PubMed

    Gowtham, Yashonandana J; Mahadeswaraswamy, Y H; Girish, K S; K, Kemparaju

    2014-07-01

    The venom of the largest venomous snake, the king cobra (Ophiophagus hannah), is still out of league for the production of therapeutic polyvalent antivenom nor it is characterized immunologically in the Indian subcontinent. In the present study, the king cobra venom is comparatively studied for the cross-reactivity/reactivity and toxicity neutralization by the locally available equine therapeutic polyvalent BSV and VB antivenoms, and monovalent antivenom (OH-IgG) prepared in rabbit. None of the two therapeutic antivenoms procured from two different firms showed any signs of cross-reactivity in terms of antigen-antibody precipitin lines in immunodouble diffusion assay; however, a weak and an insignificant cross-reactivity pattern was observed in ELISA and Western blot studies. Further, both BSV and VB antivenoms failed to neutralize proteolytic, hyaluronidase and phospholipase activities as well as toxic properties such as edema, myotoxicity and lethality of the venom. As expected, OH-IgG showed strong reactivity in immunodouble diffusion, ELISA and in Western blot analysis and also neutralized both enzyme activities as well as the toxic properties of the venom. Thus, the study provides insight into the likely measures that are to be taken in cases of accidental king cobra bites for which the Indian subcontinent is still not prepared for. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Rat Model of Trigeminal Neuralgia Using Cobra Venom Mimics the Electron Microscopy, Behavioral, and Anticonvulsant Drug Responses Seen in Patients.

    PubMed

    Zhao, Qian-Qian; Qian, Xiao-Yan; An, Jian-Xiong; Liu, Cai-Cai; Fang, Qi-Wu; Wang, Yong; Jiang, Yi-De; Cope, Doris K; Williams, John P

    2015-11-01

    A new animal model of trigeminal neuralgia produced by injecting cobra venom into the infraorbital nerve (ION) trunk in rats had been developed. We tested and extended the model by observing the ultrastructural alterations of neurons and ameliorative effect of pregabalin in cobra venom-induced pain behaviors of rats. The goal of this study was to prove the feasibility of the cobra venom-induced model of trigeminal neuralgia and to demonstrate the demyelination change of ION and medulla oblongata is the major pathological change of trigeminal neuralgia. An experimental study. Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. Experiments were carried out on male Sprague-Dawley rats. Video recordings were taken after the cobra venom injection and pregabalin administration. Ultrastructural alterations of ION and medulla oblongata were observed at the electron microscopic level. We also observed alteration in pain behaviors by analysis of video recordings. Compared to the preoperative and sham-operated group rats, experimental group rats exhibited significant changes in exploratory, resting, face-grooming, and head-shake behaviors on 3, 7, 14 days after operation (P < 0.01). The demyelination changes of ION and medulla oblongata were evident after administration of cobra venom to the ION. Compared to the pre-treated (no pregabalin administration) and control group rats, pregabalin group rats showed profound changes in exploratory, resting, face-grooming, and head-shake behaviors throughout the 14 day study period after treatment with drugs (P < 0.01). Ultrastructural alterations of ION and medulla oblongata were not examined after the treatment with pregabalin. Video recordings of free behaviors and pregabalin application prove the feasibility of the rat model of trigeminal neuralgia. The results of electron micrographs are consistent with a previous study in humans showing that the

  1. Snake bite in Nigeria.

    PubMed

    Habib, A G; Gebi, U I; Onyemelukwe, G C

    2001-09-01

    Four families of venomous snakes are found in Nigeria--Viperidae, Elapidae, Colubridae and Actraspididae but three species carpet viper (Echis ocellatus), black-necked spitting cobra (Naja nigricollis) and puff adder (Bitis arietans), belonging to the first two families, are the most important snakes associated with envenoming in Nigeria. The incidence of bites has been reported as 497 per 100,000 population per year with a 12 percent natural mortality, with Echis ocellatus accounting for at least 66 percent in certain foci. Bites occur more often while victims were farming, herding or walking although the spitting cobra may bite victims who roll upon it in their sleep. Carpet viper venom contains a prothrombin activating procoagulant, haemorrhagin and cytolytic fractions which cause haemorrhage, incoagulable blood, shock and local reactions/ necrosis. The spitting cobra bite manifests with local tissue reaction and occassionally with bleeding from the site of bite, but no classic neurotoxic feature has been observed except following Egyptian cobra (N. haje) bites. Cardiotoxicity and renal failure may occassionally occur following bites by the carpet viper and the puff adder. In the laboratory, haematological and other features are noted and immunodiagnosis has a role in species identification. Immobilisation of the bitten limb is probably the single most important first aid measure. Antivenom should be used cautiously when indicated. As only 8.5 percent of snake bite victims attend hospitals in Nigeria, health education should be the main preventive measure, mean-while, the study of immunisation of occupationally predisposed individuals in endemic areas should be intensified. A new Fab fragment antivenom specific to Nigerian Echis ocellatus was investigated clinically, just as the local herbs-Aristolochia spp, Guiera spp and Schummaniophyton spp are investigated experimentally.

  2. Surgery in management of snake envenomation in children.

    PubMed

    Laohawiriyakamol, Suppawat; Sangkhathat, Surasak; Chiengkriwate, Piyawan; Patrapinyokul, Sakda

    2011-11-01

    Snakebite is common in children especially in the developing countries. This study was undertaken to determine the role of surgery in the treatment of venomous snake bite in pediatric patients. The clinical data of 58 pediatric patients aged 0-16 years who had been treated for venomous snakebite from January 1999 to December 2008 were analyzed. Of the 58 patients, 43 (74.6%) were male. Peak age incidence was around 2-3 years (28.8%). The majority of envenomations occurred in the summer and rainy seasons, especially in the latter, during flooding. The bites occurred during 6 pm to 12 pm in 27 patients (49.0%). The main bite site was the lower extremities in 49 patients (83.9%). The main species of the snake were Malayan pit viper (Calloselasma rhodostoma) in 28 patients (47.5%) and cobra (Ophiophagus hunnah or Naja spp.) in 21 patients (35.6%). Soft tissue necrosis occurred more in cobra bites (47.6%) than viper bites (3.6%). The most common organism identified in necrotic tissue was Morganella morgagnii. Four patients with cobra bite had respiratory failure that required ventilatory support. Compartment syndrome was suspected in 2 patients. Surgical intervention was necessary in 13 patients. Most procedures involved serial wound debridement, followed by skin grafting. One case needed a toe amputation because of necrosis. The average length of hospital stay in patients who needed surgical management was 18.8 days (range: 12.1-25.5 days). There were no mortalities. Surgery plays an important role in the management of snakebite patients, especially for those with cobra bite with tissue necrosis.

  3. Comparison of the air-Q intubating laryngeal airway and the cobra perilaryngeal airway as conduits for fiber optic-guided intubation in pediatric patients

    PubMed Central

    Girgis, Karim K.; Youssef, Maha M. I.; ElZayyat, Nashwa S.

    2014-01-01

    Background: One of the methods proposed in cases of difficult airway management in children is using a supraglottic airway device as a conduit for tracheal intubation. The aim of this study was to compare the efficacy of the Air-Q Intubating Laryngeal Airway (Air-Q) and the Cobra Perilaryngeal Airway (CobraPLA) to function as a conduit for fiber optic-guided tracheal intubation in pediatric patients. Materials and Methods: A total of 60 children with ages ranging from 1 to 6 years, undergoing elective surgery, were randomized to have their airway managed with either an Air-Q or CobraPLA. Outcomes recorded were the success rate, time and number of attempts required for fiber optic-guided intubation and the time required for device removal after intubation. We also recorded airway leak pressure (ALP), fiber optic grade of glottic view and occurrence of complications. Results: Both devices were successfully inserted in all patients. The intubation success rate was comparable with the Air-Q and the CobraPLA (96.7% vs. 90%), as was the first attempt success rate (90% vs. 80%). The intubation time was significantly longer with the CobraPLA (29.5 ± 10.9 s vs. 23.2 ± 9.8 s; P < 0.05), but the device removal time was comparable in the two groups. The CobraPLA showed a significantly higher ALP (20.8 ± 5.2 cmH2O vs. 16.3 ± 4.5 cmH2O; P < 0.001), but the fiber optic grade of glottic view was comparable with the two devices. The CobraPLA was associated with a significantly higher incidence of blood staining of the device on removal and post-operative sore throat. Conclusion: Both the Air-Q and CobraPLA can be used effectively as a conduit for fiber optic-guided tracheal intubation in children. However, the Air-Q proved to be superior due to a shorter intubation time and less airway morbidity compared with the CobraPLA. PMID:25422603

  4. Protease inhibitor homologues from mamba venoms: facilitation of acetylcholine release and interactions with prejunctional blocking toxins.

    PubMed

    Harvey, A L; Karlsson, E

    1982-09-01

    1 Five polypeptides, which were isolated from elapid snake venoms and which are structurally related to protease inhibitors, were tested for action on isolated biventer cervicis nerve-muscle preparations of the chick. 2 Dendrotoxin from the Eastern green mamba (Dendroaspis angusticeps) and toxins K and I from the black mamba (Dendroaspis polylepis polylepis) increased to indirect stimulation without affecting responses to exogenous acetylcholine, carbachol of KCl. 3 The two other protease inhibitor homologues, HHV-II from Ringhals cobra (Hemachatus haemachatus) and NNV-II from Cape cobra (Naja nivea) did not increase responses to nerve stimulation. Trypsin inhibitor from bovine pancreas also had no facilitatory effects on neuromuscular transmission. 4 The facilitatory toxins from mamba venoms interacted with the prejunctional blocking toxins, beta-bungarotoxin, crotoxin and notexin, but not with taipoxin. The blocking effects of beta-bungarotoxin were reduced by pretreatment with the mamba toxins, whereas the blocking actions of crotoxin and notexin were enhanced. 5 The results indicate that protease inhibitor homologues from mamba venoms form a new class of neurotoxin, which acts to increase the release of acetylcholine in response to motor nerve stimulation. 6 From the interaction studies it is concluded that the facilitatory toxins bind to motor nerve terminals at sites related to those occupied by the prejunctional blocking toxins. However, differences in interactions with individual toxins suggest that there must be several related binding sites on the nerve terminals.

  5. New and already known acanthocephalans from amphibians and reptiles in Vietnam, with keys to species of Pseudoacanthocephalus Petrochenko, 1956 (Echinorhynchidae) and Sphaerechinorhynchus Johnston and Deland, 1929 (Plagiorhynchidae).

    PubMed

    Amin, Omar M; Ha, Ngyuen Van; Heckmann, Richard A

    2008-02-01

    Adults of 2 new species in 2 orders of acanthocephalans obtained from the intestines of terrestrial amphibians and reptiles collected between 1998 and 2004 in Vietnam are described here. Pseudoacanthocephalus nguyenthileae n. sp. (Palaeacnthocephala: Echinorhynchidae) was collected from 5 species of terrestrial amphibians: (1) the common Sunda toad Bufo melanostictus Schneider (Bufonidae); (2) Paa verucospinosa (Bourret); (3) Gunther's Amoy frog Rana guentheri Boulenger; (4) Taipei frog R. taipehensis Denburgh (Ranidae), and (5) the Burmese whipping frog Polypedates mutus (Smith) (Racophoridae); as well as from the Chinese cobra Naja atra Cantor (Reptilia: Elapidae) and house gecko Hemidactylus frenatus Dumeril and Bibron (Reptilia: Gekkonidae). Sphaerechinorhynchus maximesospinus n. sp. (Plagiorhynchidae: Sphaerechinorhynchinae) was isolated from a king cobra Ophiophagus hannah (cantor) (Reptilia: Elapidae). Cystacanths of Porrorchis houdemeri (Joyeux and Baer, 1935) Schmidt and Kuntz, 1967 (Plagiorhynchidae: Porrorchinae) obtained from the mesenteries of banded krait Bungarus fasciatus (Schneider) (Reptilia: Elapidae), a paratenic host, are reported for the first time. Keys to the species of Pseudoacanthocephalus and Sphaerechinorhynchus are included. Characteristic features distinguishing the new species from related taxa include: P. nguyenthileae has 15-19 (usually 16-18) proboscis hook rows, each with 5-6 hooks that progressively increase in length and size posteriorly. The largest, intermediate, and smallest proboscis hooks of S. maximesospinus are the middle, anterior, and posterior hooks, respectively; the proboscis and neck are enclosed in a membrane. Morphometric characteristics of P. nguyenthileae show host-related variability.

  6. Interaction of toxic venoms with the complement system

    PubMed Central

    Birdsey, Vanessa; Lindorfer, Jean; Gewurz, H.

    1971-01-01

    Thirty-nine venoms from various vertebrate and invertebrate species were tested for their ability to consume haemolytic complement (C) activity upon incubation in fresh guinea-pig serum. Nineteen had `anti-complementary' activity, and these were provisionally sorted into the following groups: Pattern I—exemplified by the Naja haje (Egyptian cobra) and six other Elapidae species (all cobras), which induced selective consumption of C3—C9, and led to formation of a stable C3—C9-consuming intermediate; Pattern II—exemplified by the Agkistrodon rhodostoma (Malayan pit viper), Bitis arietans (puff adder), Bothrops jararaca (South American pit viper), Bothrops atrox (Fer de Lance) and three other species, which induced marked consumption of C4 and C2, as well as C3—C9, but did not form a stable C3—C9-consuming intermediate; and individual animals, e.g. the Lachesis muta (bushmaster), which induced other patterns (III—VI) of complement component consumption. Active fractions of representative venoms were partially purified by ion exchange and gel filtration chromatography and their interactions with the complement system characterized further. It is anticipated that these enzymes, with a capacity to activate the complement system in unique ways, will prove to be of further experimental usefulness. PMID:4398349

  7. Bell P–63A King Cobra at the Aircraft Engine Research Laboratory

    NASA Image and Video Library

    1944-01-21

    The Army Air Forces lent the National Advisory Committee for Aeronautics (NACA) Aircraft Engine Research Laboratory a Bell P–63A King Cobra in October 1943 to complement the lab's extensive efforts to improve the Allison V–1710 engine. The V–1710-powered P–63A was a single-seat fighter that could reach speeds of 410 miles per hour and an altitude of 43,000 feet. The fighter, first produced in 1942, was an improvement on Bell’s P–39, but persistent performance problems at high altitudes prevented its acceptance by the Air Corps. Instead many of the P–63s were transferred to the Soviet Union. Almost every test facility at the NACA’s engine lab was used to study the Allison V–1710 engine and its supercharger during World War II. Researchers were able to improve the efficiency, capacity and pressure ratio of the supercharger. They found that improved cooling significantly reduced engine knock in the fuel. Once the researchers were satisfied with their improvements, the new supercharger and cooling components were installed on the P–63A. The Flight Research Division first established the aircraft’s normal flight performance parameters such as speed at various altitudes, rate of climb, and peak altitude. Ensuing flights established the performance parameters of the new configuration in order to determine the improved performance. The program increased V–1710’s horsepower from 1650 to 2250.

  8. Functional analysis of Cobra Venom Factor/human C3 chimeras transiently expressed in mammalian cells.

    PubMed

    Kölln, Johanna; Matzas, Mark; Jänner, Nathalie; Mix, Thorsten; Klensang, Katrin; Bredehorst, Reinhard; Spillner, Edzard

    2004-05-01

    The complement activating venom component Cobra Venom Factor (CVF), a functional and structural homologue of the human complement component C3, forms a stable CVF-dependent C3 convertase complex, which, in contrast to C3-dependent convertase effects continuous activation of the complement and, thereby, decomplementation. In order to elucidate the mechanism underlying the enhanced activity of CVF compared to human C3, we generated two CVF/C3 chimeras and established different affinity-based assay systems for functional analysis of these constructs. To allow for convenient expression and subsequent functional characterisation, the CVF/C3 chimeras as well as CVF and C3 were transiently expressed in mammalian cells. Problems due to the low concentration of the recombinant proteins in the supernatants of transient expressions were circumvented by fusion to peptide tags enabling their efficient immobilisation onto suitable surfaces and subsequent characterisation. In an alternative approach monoclonal antibody fragments generated from a semisynthetic phage display scFv library were employed for concentrating the recombinant proteins by immunoprecipitation. Utilising both approaches all transiently expressed proteins could be characterised for their complement consumption activity. The data obtained with the CVF/C3 chimeras demonstrate that the increased stability of the CVFBb complex is independent of the domains in CVF corresponding to binding sites of factor B and H and the cleavage sites of factor I in the human C3 molecule.

  9. Structure of a king cobra phospholipase A2 determined from a hemihedrally twinned crystal.

    PubMed

    Xu, Sujuan; Gu, Lichuan; Wang, Qiuyan; Shu, Yuyan; Song, Shiying; Lin, Zhengjiong

    2003-09-01

    An acidic PLA(2) (OH APLA(2)-II) from the venom of Ophiophagus hannah (king cobra) shows greater phospholipase A(2) activity and weaker cardiotoxic and myotoxic activity than a homologous acidic PLA(2) from the same venom. The crystal of the enzyme belongs to space group P6(3). The crystals are invariably hemihedrally twinned, exhibiting perfect 622 Laue symmetry. The structure was determined by molecular replacement and refined using a hemihedral twinning program at 2.1 A resolution. The final model has reasonable stereochemistry and a crystallographic R factor of 19.5% (R(free) = 21.5%). The structure reveals the molecular arrangement and the mode of twinning. There are six independent molecules in the asymmetric unit. Owing to the presence of a non-crystallographic twofold parallel to the hemihedral twinning twofold, the molecular packing in the twinned crystal is extremely similar to that in an untwinned crystal for four of the molecules. This unique molecular arrangement may be related to the difficulty in recognizing the twinning. The structure was compared with the previously determined structure of a homologous acidic PLA(2) from the same source. The comparison shows structural changes that might be implicated in the increased catalytic activity and weakened toxicity.

  10. Disulfide isomers of alpha-neurotoxins from King cobra (Ophiophagus hannah) venom.

    PubMed

    Lin, S R; Chang, L S; Chang, C C

    1999-01-08

    Two novel alpha-neurotoxins, Oh-6A and Oh-6B, isolated from the king cobra (Ophiophagus hannah) venom, consist of 70 amino acid residues with 10 cysteine residues and share the same amino acid sequences as determined by Edman degradation on the peptide fragments generated from the proteolytic hydrolysates. Their sequences share 46-53% homology with Oh-4, Oh-5, Toxin a, and Toxin b from the same venom. The finding that Oh-6A and Oh-6B had different retention times in the reversed-phase column suggested that the two toxin molecules should not have the same conformation. Selective reduction on the disulfide bond, Cys26--Cys30, at the tip of their loop II structures resulted in the production of the partially reduced derivatives eluted at the same position. Under redox conditions, the partially reduced Oh-6A and 6B exclusively converted into native Oh-6A as evidenced by HPLC analyses. This suggests that Oh-6A and Oh-6B are disulfide isomers which probably arise from cis-trans isomerization of the Cys26--Cys30 disulfide bond. Alternatively, the two toxins exhibited binding activity toward nAChR and lethal toxicity equally. It reflects that the diversity around the extra loop at the loop II structure does not exert a significant effect on the manifestation of the neurotoxicity of Oh-6A and Oh-6B. Copyright 1999 Academic Press.

  11. Chemical modification of tryptophan residues in alpha-neurotoxins from Ophiophagus hannah (king cobra) venom.

    PubMed

    Chang, C C; Lin, P M; Chang, L S; Kuo, K W

    1995-02-01

    Two alpha-neurotoxins, Oh-4 and Oh-7, from the king cobra (Ophiophagus hannah) venom were subjected to Trp modification with 2-nitrophenylsulfenyl chloride (NPS-Cl). One major NPS derivative was isolated from the modified mixtures of Oh-4 and two from Oh-7 by HPLC. Amino acid analysis and sequence determination revealed that Trp-27 in Oh-4, and Trp-30 and Trp-26 and 30 in the two Oh-7 derivatives, were modified, respectively. Sulfenylation of Trp-27 in Oh-4 caused about 70% drop in lethal toxicity and nicotinic acetylcholine receptor-binding activity. Modification of Trp-30 in Oh-7 resulted in the decrease of lethal toxicity by 36% and binding activity by 61%. The activities were further lost when the conserved Trp-26 in Oh-7 was modified. Sulfenylation of the Trp residues did not significantly affect the secondary structure of the toxins as revealed by the CD spectra. These results indicate that the Trp residues in these two long alpha-neurotoxins may be involved in the receptor binding.

  12. [Sequencing and analysis of the complete mitochondrial genome of the King Cobra, Ophiophagus hannah (Serpents: Elapidae)].

    PubMed

    Chen, Nian; Lai, Xiao-Ping

    2010-07-01

    We obtained the complete mitochondrial genome of King Cobra(GenBank accession number: EU_921899) by Ex Taq-PCR, TA-cloning and primer-walking methods. This genome is very similar to other vertebrate, which is 17 267 bp in length and encodes 38 genes (including 13 protein-coding, 2 ribosomal RNA and 23 transfer RNA genes) and two long non-coding regions. The duplication of tRNA-Ile gene forms a new mitochondrial gene rearrangement model. Eight tRNA genes and one protein genes were transcribed from L strand, and the other genes were transcribed genes from H strand. Genes on the H strand show a fairly similar content of Adenosine and Thymine respectively, whereas those on the L strand have higher proportion of A than T. Combined rDNA sequence data (12S+16S rRNA) were used to reconstruct the phylogeny of 21 snake species for which complete mitochondrial genome sequences were available in the public databases. This large data set and an appropriate range of outgroup taxa demonstrated that Elapidae is more closely related to colubridae than viperidae, which supports the traditional viewpoints.

  13. A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah).

    PubMed

    Pu, X C; Wong, P T; Gopalakrishnakone, P

    1995-11-01

    The pharmacological effects of a purified neurotoxin from king cobra (Ophiophagus hannah) venom were studied. Using the hot-plate test, it is shown that this neurotoxin increased latency time dose-dependently when administered i.p. Similar analgesic action was observed when it was administered p.o. or i.c.v. The rota-rod performance, which is a good index for neurological deficits including sedation, muscle relaxant and impairment of motor activity and coordination, was not significantly affected in the dose range of 16-32 ng/g that caused analgesia. The toxin did not increase the convulsion threshold in the dose range of 8-64 ng/g in the maximal electroshock seizure tests. These results demonstrated that this neurotoxin produced analgesia in the dose range of 16-32 ng/g (i.p.) without causing any neurological or muscular deficits. It is further shown that such analgesic action was blocked by naloxone and L-NG-nitro-arginine methyl ester, suggesting the possible involvement of the opioid and nitric oxide systems, respectively. In view of the source of this neurotoxin (O. hannah) and its potent analgesic action, it is proposed that this toxin be named hannalgesin.

  14. Chemical modification of cationic residues in toxin a from king cobra (Ophiophagus hannah) venom.

    PubMed

    Lin, S R; Chi, S H; Chang, L S; Kuo, K W; Chang, C C

    1996-01-01

    The cationic groups of arginine and lysine residues in alpha-neurotoxin, Toxin a, isolated from king cobra (Ophiophagus hannah) venom were subjected to modification with trinitrobenzene sulfonate (TNBS) and p-hydroxyphenylglyoxal (HPG), respectively. The trinitrophenylated (TNP) derivatives of Toxin a at Lys-10, 56, or 71 showed approximately 25% residual lethality, and modifications on Lys-10 and 56 or Lys-10 and 50 resulted in a decrease of lethality by 84% and 86%, respectively. Modifications on Arg-34, 37, and 70 and Arg-34, 37, and 72 in Toxin a caused a decrease in lethality by 92% and 93%, respectively, and it almost completely lost its lethality and binding activity to nicotinic acetylcholine receptor (nAChR) when all four arginine residues were modified. These results indicate that in addition to the cationic residues on loop II (Arg-34, 37), loop III (Lys-50, 56), and the C-terminal tail (Arg-70, 72; Lys-71), Lys-10 on loop I is also related to the neurotoxicity of Toxin a.

  15. Ohanin, a novel protein from king cobra venom, induces hypolocomotion and hyperalgesia in mice.

    PubMed

    Pung, Yuh Fen; Wong, Peter T H; Kumar, Prakash P; Hodgson, Wayne C; Kini, R Manjunatha

    2005-04-01

    We have identified, purified, and determined the complete amino acid sequence of a novel protein, ohanin from Ophiophagus hannah (king cobra) venom. It is a small protein containing 107 amino acid residues with a molecular mass of 11951.47 +/- 0.67 Da as assessed by electrospray ionization-mass spectrometry. It does not show similarity to any known families of snake venom proteins and hence is the first member of a new family of snake venom proteins. It shows similarity to PRY and SPRY domain proteins. It is nontoxic up to 10 mg/kg when injected intraperitoneally in mice. Ohanin produced statistically significant and dose-dependent hypolocomotion in mice. In a pain threshold assay, it showed dose-dependent hyperalgesic effect. The ability of the protein to elicit a response at greatly reduced doses when injected intracerebroventricularly as compared with intraperitoneal administration in both the locomotion and hot plate experiments strongly suggests that ohanin acts on the central nervous system. Since the natural abundance of the protein in the venom is low (approximately 1 mg/g), a synthetic gene was constructed and expressed. The recombinant protein, which was obtained in the insoluble fraction in Escherichia coli, was purified under denaturing condition and was refolded. Recombinant ohanin is structurally and functionally similar to native protein as determined by circular dichroism and hot plate assay, suggesting that it will be useful in future structure-function relationship studies.

  16. The COBRA experiment – Status and prospects on the search of neutrinoless double beta-decay

    SciTech Connect

    Zatschler, S.

    2015-10-28

    The Cadmium-Zinc-Telluride 0-ν Double Beta Research Apparatus (COBRA) [1] is a next-generation experiment searching for the existence of neutrinoless double beta-decay (0νββ-decay). The observation of 0νββ-decay would be an unambiguous sign for physics beyond the Standard Model such as lepton number violating processes and would prove the Majorana character of neutrinos. Furthermore, the study of 0νββ-decay could probe the absolute neutrino mass and allows for the identification of the neutrino mass hierarchy realized in nature assuming light Majorana neutrino exchange. Currently a demonstrator setup at the underground facility LNGS (Italy) built of 4×4×4 coplanar grid (CPG) detectors collects high quality low background physics data with FADC pulse shape sampling. The detectors are made of natural abundant CdZnTe (CZT), which is a commercially available room temperature semiconductor. It contains several double beta isotopes, the most promising of which is {sup 116}Cd with a Q-value of 2813.5 keV – which is well above the highest naturally occurring prominent γ-lines.

  17. Pulse-shape discrimination techniques for the COBRA double beta-decay experiment at LNGS

    NASA Astrophysics Data System (ADS)

    Zatschler, S.; COBRA collaboration

    2017-09-01

    In modern elementary particle physics several questions arise from the fact that neutrino oscillation experiments have found neutrinos to be massive. Among them is the so far unknown nature of neutrinos: either they act as so-called Majorana particles, where one cannot distinguish between particle and antiparticle, or they are Dirac particles like all the other fermions in the Standard Model. The study of neutrinoless double beta-decay (0νββ-decay), where the lepton number conservation is violated by two units, could answer the question regarding the underlying nature of neutrinos and might also shed light on the mechanism responsible for the mass generation. So far there is no experimental evidence for the existence of 0νββ-decay, hence, existing experiments have to be improved and novel techniques should be explored. One of the next-generation experiments dedicated to the search for this ultra-rare decay is the COBRA experiment. This article gives an overview of techniques to identify and reject background based on pulse-shape discrimination.

  18. X-ray radiation from puff-on-wire implosion on the COBRA generator

    NASA Astrophysics Data System (ADS)

    Ouart, N.; Engelbrecht, J.; de Grouchy, P.; Qi, N.; Shelkovenko, T.; Pikuz, S.; Kusse, B.; Hammer, D.; Giuliani, J.; Dasgupta, A.; Velikovich, A.; Apruzese, J.; Clark, R.

    2016-10-01

    Substantial progress has been made in developing plasma radiation sources from Z-pinch implosions. University pulsed power machines provide a cost effective platform to study alternative mechanisms of producing x-rays that may provide guidance in search of further improvements on the larger machines. Radiation from puff-on-wire implosions were previously studied. We report recent observations and modeling of puff-on-wire implosions using the 1 MA COBRA generator in the long pulse mode. The gas puff used Ne, Ar, or Kr and the wire material was either Cu or manganin 290 (84% Cu, 12% Mn, 4% Ni). The diagnostics include time-integrated pinhole cameras and an axially resolved spectrometer, multiple filtered PCDs and Si-diodes, and time-gated XUV cameras. X-ray radiation from the gas puff and the K-alpha line from wire material was detected. A 1-D multi-zone non-LTE kinetics code with radiation transport will be used to model the radiation to infer the plasma conditions. Work supported by DOE/NNSA.

  19. Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.

    PubMed

    Ye, Yong; Li, Yue; Fang, Fei

    2014-05-05

    Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role.

  20. The COBRA experiment - Status and prospects on the search of neutrinoless double beta-decay

    NASA Astrophysics Data System (ADS)

    Zatschler, S.

    2015-10-01

    The Cadmium-Zinc-Telluride 0-ν Double Beta Research Apparatus (COBRA) [1] is a next-generation experiment searching for the existence of neutrinoless double beta-decay (0νββ-decay). The observation of 0νββ-decay would be an unambiguous sign for physics beyond the Standard Model such as lepton number violating processes and would prove the Majorana character of neutrinos. Furthermore, the study of 0νββ-decay could probe the absolute neutrino mass and allows for the identification of the neutrino mass hierarchy realized in nature assuming light Majorana neutrino exchange. Currently a demonstrator setup at the underground facility LNGS (Italy) built of 4×4×4 coplanar grid (CPG) detectors collects high quality low background physics data with FADC pulse shape sampling. The detectors are made of natural abundant CdZnTe (CZT), which is a commercially available room temperature semiconductor. It contains several double beta isotopes, the most promising of which is 116Cd with a Q-value of 2813.5 keV - which is well above the highest naturally occurring prominent γ-lines.

  1. Early time studies of cylindrical liner implosions at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Atoyan, L.; Byvank, T.; Cahill, A. D.; Hoyt, C. L.; de Grouchy, P. W. L.; Potter, W. M.; Kusse, B. R.; Hammer, D. A.

    2014-12-01

    Tests of the magnetized liner inertial fusion (MagLIF) concept will make use of the 27 MA Z machine at Sandia National Laboratories, Albuquerque, to implode a cylindrical metal liner to compress and heat preheated, magnetized plasma contained within it. While most pulsed power machines produce much lower currents than the Z-machine, there are issues that can still be addressed on smaller scale facilities. Recent work on the Cornell Beam Research Accelerator (COBRA) has made use of 10 mm long and 4 mm diameter metal liners having different wall thicknesses to study the initiation of plasma on the liner's surface as well as axial magnetic field compression [P.-A. Gourdain et al., Nucl. Fusion 53, 083006 (2013)]. This report presents experimental results with non-imploding liners, investigating the impact the liner's surface structure has on initiation and ablation. Extreme ultraviolet (XUV) imaging and optical 12 frame camera imaging were used to observe and assess emission non-uniformities as they developed. Axial and side-on interferometry was used to determine the distribution of plasma near the liner surface, including the impact of non-uniformities during the plasma initiation and ablation phases of the experiments.

  2. [The effect of Chinese cobra venom factor on guinea pig to rat cardiac xenotransplantation].

    PubMed

    Peng, M H; Meng, K W; Yang, D H

    2001-07-01

    In the guinea pig-to-rat cardiac xenotransplantation model, the effect of complement depletion by using Chinese Cobra Venom Factor(CVF) on hyperacute rejection was evaluated. Cardiac xenograft from guinea pig was transplanted into the abdomen of rat after the recipient being given i.p. a dose of CVF 0.20 microgram/g. the recipients were divided into group A (control group), group B (only given CVF), group C (CVF + Cytoxan + Splenectomy), group D (Cytoxan + Splenectomy) Cytoxan was injected into the abdominal cavity with a dose of 60 mg/Kg. The survival time of xenograft was measured and histologic observation was carried out after the cardiac arrest. The survival time of xenograft ranged from 15 to 3,120 minutes. There were significant difference among group A compared with group B and C (P < 0.01), and no difference between group A and group D, as well as group B and C (P > 0.05). There were significant difference between group B and D, as well as group C and D(P < 0.01). The histologic observation proved that the hyperacute rejection in group A and D was milder than group B and C. The study reveals that CVF can prolong the xenograft time by depleting complement activities and restricting hyperacute rejection in this model. Further basic and clinical study of effect of CVF in xenograft transplantation is worthwhile.

  3. Ice clouds optical properties in the Far Infrared from the ECOWAR-COBRA Experiment

    NASA Astrophysics Data System (ADS)

    Rizzi, Rolando; Tosi, Ennio

    ECOWAR-COBRA (Earth COoling by WAter vapouR emission -Campagna di Osservazioni della Banda Rotazionale del vapor d'Acqua) field campaign took place in Italy from 3 to 17 March 2007 with the main goal of studying the scarcely sensed atmospheric emission occurring beyond 17 microns. Instrumentation involved in the campaign included two different Fourier Transforms Spectrometers (FTS) : REFIR-PAD (at Testa Grigia Station, 3500 m a.s.l.) and FTIR-ABB (at Cervinia Station, 1990 m a.s.l.). In this work cloudy sky data have been ana-lyzed. A cloud properties retrieval methodology (RT-RET), based on high spectral resolution measurements in the atmospheric window (800-1000 cm-1), is applied to both FTS sensors. Cloud properties determined from the infrared retrievals are compared with those obtained from Raman lidar taken by the BASIL Lidar system that was operating at Cervinia station. Cloud microphysical and optical properties retrieved by RT-RET are used to perform forward simulations over the entire FTSs measurements spectral interval. Results are compared to FTS data to test the ability of single scattering ice crystals models to reproduce cloudy sky radiances in the Far Infra-Red (FIR) part of the spectrum. New methods to retrieve cloud optical and microphysical properties exploiting high spectral resolution FIR measurements are also investigated.

  4. Impact of Membrane Partitioning on the Spatial Structure of an S-type Cobra Cytotoxin.

    PubMed

    Dubovskii, Peter V; Dubinnyi, Maxim A; Volynsky, Pavel E; Pustovalova, Yulia E; Konshina, Anastasia G; Utkin, Yuri N; Arseniev, Alexander S; Efremov, Roman G

    2017-10-09

    Cobra cytotoxins (CTs) belong to the three-fingered protein family. They are classified into S- and P-types, the latter exhibiting higher membrane-perturbing capacity. In this work we investigated the interaction of CTs with phospholipid bilayers, using coarse-grained (CG) and full-atom (FA) molecular dynamics (MD). The object of this work is a CT of an S-type, cytotoxin I (CT1) from N.oxiana venom. Its spatial structure in aqueous solution and in the micelles of dodecylphosphocholine (DPC) were determined by (1)H-NMR spectroscopy. Then, via CG- and FA MD-computations, we evaluated partitioning of CT1 molecule into palmitoyloleoylphosphatidylcholine (POPC) membrane, using the toxin spatial models, obtained either in aqueous solution, or detergent micelle. The latter model exhibits minimal structural changes upon partitioning into the membrane, while the former deviates from the starting conformation, loosing the tightly-bound water molecule in the loop-2. These data show that the structural changes elicited by CT1 molecule upon incorporation into DPC micelle take place likely in the lipid membrane, although the mode of the interaction of this toxin with DPC micelle (with the tips of the all three loops) is different from its mode in POPC membrane (primarily with the tip of the loop-1 and both the tips of the loop-1 and loop-2).

  5. Nerve growth factor from cobra venom inhibits the growth of Ehrlich tumor in mice.

    PubMed

    Osipov, Alexey V; Terpinskaya, Tatiana I; Kryukova, Elena V; Ulaschik, Vladimir S; Paulovets, Lubov V; Petrova, Elena A; Blagun, Ekaterina V; Starkov, Vladislav G; Utkin, Yuri N

    2014-02-26

    The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved.

  6. Nerve Growth Factor from Cobra Venom Inhibits the Growth of Ehrlich Tumor in Mice

    PubMed Central

    Osipov, Alexey V.; Terpinskaya, Tatiana I.; Kryukova, Elena V.; Ulaschik, Vladimir S.; Paulovets, Lubov V.; Petrova, Elena A.; Blagun, Ekaterina V.; Starkov, Vladislav G.; Utkin, Yuri N.

    2014-01-01

    The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved. PMID:24577582

  7. High-Z Pusher Experiments on the Cobra Triple Nozzle Gas-Puff Z-Pinch

    NASA Astrophysics Data System (ADS)

    de Grouchy, Philip; Qi, Niansheng; Kusse, Bruce; Seyler, Charles; Atoyan, Levon; Byvank, Tom; Cahill, Adam; Greenly, John; Hoyt, Cad; Pikuz, Sergei; Shelkovenko, Tania; Hammer, David

    2014-10-01

    For inertial confinement fusion application and as efficient hard x-ray sources, the imploding sheath of a gas-puff z-pinch or thin liner must be accelerated to the highest possible velocity before hydrodynamic instabilities significantly disrupt the implosion symmetry. Much recent work has focused on increasing implosion stability using radially structured mass-density profiles produced by multi-nozzle gas-puff valves. The introduction of a high-Z element such as xenon into the outer gas shells in such experiments can modify radiation output during the implosion phase as well as at stagnation. In these experiments xenon is introduced into the triple-nozzle gas valve fielded on the (1 MA, 200 ns) COBRA z-pinch machine at Cornell University. The xenon is introduced only in the outer shell, only in the inner shell or in both, to investigate the radiative effects on implosion hydrodynamics and x-ray yield. Results are compared to those obtained during pure argon implosions with the same mass-density profile. Sheath thicknesses and stability are recorded using laser interferometry (532 nm) and multi-frame imaging systems. The distribution of flow velocities and of high-Z material across the pinch is investigated using a (5 GW, 527 nm) Thomson scattering probe. Work supported by DOE Grant No. DE-NA0001836.

  8. Improvement of COBRA-TF for modeling of PWR cold- and hot-legs during reactor transients

    NASA Astrophysics Data System (ADS)

    Salko, Robert K.

    COBRA-TF is a two-phase, three-field (liquid, vapor, droplets) thermal-hydraulic modeling tool that has been developed by the Pacific Northwest Laboratory under sponsorship of the NRC. The code was developed for Light Water Reactor analysis starting in the 1980s; however, its development has continued to this current time. COBRA-TF still finds wide-spread use throughout the nuclear engineering field, including nuclear-power vendors, academia, and research institutions. It has been proposed that extension of the COBRA-TF code-modeling region from vessel-only components to Pressurized Water Reactor (PWR) coolant-line regions can lead to improved Loss-of-Coolant Accident (LOCA) analysis. Improved modeling is anticipated due to COBRA-TF's capability to independently model the entrained-droplet flow-field behavior, which has been observed to impact delivery to the core region[1]. Because COBRA-TF was originally developed for vertically-dominated, in-vessel, sub-channel flow, extension of the COBRA-TF modeling region to the horizontal-pipe geometries of the coolant-lines required several code modifications, including: • Inclusion of the stratified flow regime into the COBRA-TF flow regime map, along with associated interfacial drag, wall drag and interfacial heat transfer correlations, • Inclusion of a horizontal-stratification force between adjacent mesh cells having unequal levels of stratified flow, and • Generation of a new code-input interface for the modeling of coolant-lines. The sheer number of COBRA-TF modifications that were required to complete this work turned this project into a code-development project as much as it was a study of thermal-hydraulics in reactor coolant-lines. The means for achieving these tasks shifted along the way, ultimately leading the development of a separate, nearly completely independent one-dimensional, two-phase-flow modeling code geared toward reactor coolant-line analysis. This developed code has been named CLAP, for

  9. CobraPLUS and Cookgas air-Q versus Fastrach for blind endotracheal intubation: a randomised controlled trial.

    PubMed

    Erlacher, Wolfgang; Tiefenbrunner, Heide; Kästenbauer, Thomas; Schwarz, Sylvia; Fitzgerald, Robert D

    2011-03-01

    CobraPLUS and Cookgas air-Q are supraglottic airways expected to allow safe ventilation as well as reliable blind intubation. In a prospective, controlled trial, we hypothesised that quality of ventilation and success rate of blind endotracheal intubation of these new devices would be superior to the Fastrach intubating laryngeal mask airway (ILMA). When blind intubation failed the quality of fibrescope-guided intubation was investigated. To allow identification of those patients in whom blind intubation would be difficult, we investigated the predictive value of currently used predictors for ease of endotracheal intubation. One hundred and eighty adult patients with documented BMI, Mallampati score, Cormack-Lehane classification, interincisor gap and thyromental distance were randomised into three groups according to the device used. Ventilation conditions were rated as excellent, good or difficult. When blind intubation failed, fibrescope-guided intubation conditions were rated as well. Statistical analysis was performed by a χ-test. The quality of ventilation was excellent for all devices. Three patients in the CobraPLUS group and two patients in the ILMA and the Cookgas groups needed a slight reposition. Blind intubation through the CPLA was successful in 47%, through the Cookgas in 57%, whereas the Fastrach group had a success rate of 95%. Fibreoptic intubation was possible in all but one patient. None of the registered scores and measures allowed prediction of difficult blind intubation. All devices appeared to be safe airways. The Fastrach ILMA proved to be a reliable facilitator for blind intubation. CobraPLUS and Cookgas air-Q allowed an easy fibrescopic intubation. Failed blind intubations could not be predicted by the used parameters.

  10. A case report of the new Polyzene™-F COBRA PzF™ Nanocoated Coronary Stent System (NCS): Addressing an unmet clinical need.

    PubMed

    Styllou, Panorea; Silber, Sigmund

    2016-01-01

    Because of anticipated antiplatelet medication risks, patients who are not DES candidates or who are at particularly high risk for bleeding events have been targeted initially for treatment with the COBRA PzF Coronary Stent System. We report the case of a successful experience with a new, Polyzene™-F COBRA PzF™ Coronary Stent System, designed to impart thrombo-resistance and reduce inflammation, to achieve shorter dual antiplatelet therapy duration while reducing restenosis incidence in a high risk patient with atrial fibrillation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Crystallization and preliminary X-ray analysis of cardiotoxic phospholipase A2 from Ophiophagus hannah (king cobra).

    PubMed

    Wang, Z; Zhuang, M; Shu, Y; Zhang, H; Song, S; Lin, Z

    2001-05-01

    An acidic phospholipase A2 exhibiting cardiotoxicity, myotoxicity and anti-platelet activity was isolated from Ophiophagus hannah (king cobra) from Guangxi, China. It contains an unusual 'pancreatic loop'. The enzyme was purified to homogeneity and crystallized using polyethylene glycol and ethylene glycol as precipitants. The crystal belongs to space group C2, with unit-cell parameters a = 117.92, b = 62.94, c = 57.16 A, beta = 100.93 degrees. Diffraction data were collected to 2.6 A.

  12. [Localization of binding sites in rat muscles and brain for cobra neurotoxin and serum immunoglobulins from patients with myasthenia].

    PubMed

    Smirnov, V A; Vladeeva, N V; Lobzin, V S; Paniukov, A N

    1986-09-01

    Using the immunohistochemical technique, it was revealed that serum immunoglobulins of patients with myasthenia gravis (Ig) were irreversibly attached to the myoneuronal connections of the rat intercostal muscles like the marker of the nicotin cholinireceptors--the cobra venom neurotoxin (CT). In addition, Ig differs from CT in the binding to nervous cells of the claustrum and diencephalon reticular formation and with certain cells of the nucleus caudatus and hemispheric cerebral cortex. It is suggested that the autoimmune processes in patients with myasthenia gravis do not only involve myoneuronal connection but also participate in central mechanisms of the disease genesis.

  13. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry

    SciTech Connect

    Fooshee, David R.; Aiona, Paige K.; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey; Baldi, Pierre

    2015-10-22

    Squalene is a major component of skin and plant surface lipids, and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1,300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0-1450 Da, which correspond to about 27,000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. Simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces, and contribute to their redox capacity.

  14. Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

    PubMed

    Bhattacharya, Sourav; Chakraborty, Mousumi; Mukhopadhyay, Piyasi; Kundu, P P; Mishra, Roshnara

    2014-08-01

    Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to

  15. Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model

    PubMed Central

    OBERHOLZER, J; YU, D; TRIPONEZ, F; CRETIN, N; ANDEREGGEN, E; MENTHA, G; WHITE, D; BUEHLER, L; MOREL, P; LOU, J

    1999-01-01

    Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno-islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)-decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4- and CD8-positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement-mediated cytotoxicity on rat islet cells was evaluated by a 3-(4,5-dimethythiazolyl)-2.5-diphenyl-2H-tetrazolium-bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement-mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4- and CD8-positive leucocyte infiltration, led to significant inhibition of complement-mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21·3 versus 8·5 days; P <0·01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration. PMID:10447729

  16. COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.

    PubMed

    Nevalainen, N; Riklund, K; Andersson, M; Axelsson, J; Ögren, M; Lövdén, M; Lindenberger, U; Bäckman, L; Nyberg, L

    2015-07-01

    Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging.

  17. Occurrence of a unique protein toxin from the Indian King Cobra (Ophiophagus hannah) venom.

    PubMed

    Gomes, A; De, P; Dasgupta, S C

    2001-01-01

    A unique (lethal-cardiotoxic-hemorrhagic) protein toxin (Toxin CM55) was isolated and purified from Indian King Cobra (Ophiophagus hannah) venom by CM-sephadex ion exchange chromatography and reverse phase HPLC. The purified toxin had an SDS-molecular weight of 22 +/- 0.5 kD. UV absorption spectra of Toxin CM55 showed a peak at 280 nm, whereas when excited at 280 nm fluorescence, Toxin CM55 showed an E(max) at 333.4 nm. Toxin CM55 had an LD(50) of 28.28 microg/20 g (i. v.) in albino mice. The cardiotoxic action of the toxin was established on isolated guinea pig/rabbit heart and guinea pig auricle. In rats, Toxin CM55 caused ECG abnormalities including widened QRS complex and monomorphic ventricular tachycardia suggesting that the possible site of action of Toxin CM55 was the ventricle. Toxin CM55 produced significant vasoconstriction on peripheral blood vessels. It produced significant contraction of isolated guinea pig ileum, rat fundus and rat uterus, which was completely antagonised by methysergide. The toxin was found to release a significant amount of serotonin from rabbit platelets. Toxin CM55 produced cutaneous hemorrhage in albino mice, which was also produced in reserpine and p-chloro phenylalanine pretreated animals. Rabbit antiserum was raised against Toxin CM55, which gave prominent bands in immunogel diffusion and immunoelectrophoresis. The antiserum provided 2 LD(50) protection against Toxin CM55-induced lethality in mice and also neutralised 3 MHD hemorrhagic dose of the toxin.

  18. Brittle Culm1, a COBRA-like protein, functions in cellulose assembly through binding cellulose microfibrils.

    PubMed

    Liu, Lifeng; Shang-Guan, Keke; Zhang, Baocai; Liu, Xiangling; Yan, Meixian; Zhang, Lanjun; Shi, Yanyun; Zhang, Mu; Qian, Qian; Li, Jiayang; Zhou, Yihua

    2013-01-01

    Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity.

  19. Topical monotherapy with clobetasol propionate spray 0.05% in the COBRA trial.

    PubMed

    Menter, Alan

    2007-11-01

    The Clobex Spray Community-Based Research Assessment (COBRA) trial, a large, 4-week, open-label, observational trial, evaluated the use of twice-daily clobetasol propionate spray 0.05% in subjects with moderate to severe plaque psoriasis affecting 3% to 20% body surface area (BSA). The study was designed to augment existing phase 3 clinical trial data. In this trial, 1254 subjects in the effectiveness-evaluable (EE) population were treated with clobetasol propionate spray 0.05% as monotherapy. Clinical effectiveness was evaluated at weeks 2 and 4 using a 6-point target plaque severity (TPS) scale and 7-point investigators' global assessment of improvement (GAI) scale. Psoriasis TPS at week 0 (baseline) was rated as moderate to severe in more than 90% of subjects. After 2 weeks of clobetasol propionate spray 0.05% monotherapy, statistically significant improvement in TPS was seen at weeks 2 and 4 (P < .001). In addition, statistically significant improvement was seen at week 4 versus week 2 (P < .001) using the GAI scale. Clobetasol propionate spray 0.05% monotherapy was well-tolerated as assessed by erythema, peeling/scaling, dryness, stinging/burning, telangiectasia, skin atrophy, pruritus, and folliculitis. Skin and subcutaneous tissue disorders as well as general disorders and application-site conditions defined as possibly or probably related to therapy occurred in 1.0% and less than 1.0% of subjects, respectively. In addition, more than 90% of subjects were reported by investigators as being very satisfied or somewhat satisfied with their treatment at week 4. Based on these data, clobetasol propionate spray 0.05% is an effective and convenient topical monotherapy for moderate to severe plaque psoriasis.

  20. Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy.

    PubMed

    Kobayashi, T; Taniguchi, S; Neethling, F A; Rose, A G; Hancock, W W; Ye, Y; Niekrasz, M; Kosanke, S; Wright, L J; White, D J; Cooper, D K

    1997-11-15

    This study sought to (i) investigate the efficacy of cobra venom factor (CVF) in preventing hyperacute rejection (HAR) after pig-to-baboon heart transplantation, (ii) examine the effect of additional splenectomy (Spx) and pharmacologic immunosuppression (IS), and (iii) study delayed graft rejection when HAR is avoided by complement depletion. Eleven recipient baboons received heterotopic pig heart transplants. Three received either no therapy or IS (cyclosporine + methylprednisolone +/- cyclophosphamide +/- methotrexate) at clinically well-tolerated doses, with graft survival for only 40, 32, and 15 min, respectively. Two received CVF+/-Spx, which extended survival to 5 and 6 days, respectively. Six underwent Spx + CVF therapy + IS; graft survival was 3 hr (technical complication), 6 days (death from sepsis), 10, 12, and 22 days (vascular rejection), and <25 days (euthanized for viral pneumonia with a functioning graft that showed histopathologic features of vascular rejection). Dense deposition of IgM and, to a lesser extent, IgG and IgA were seen on the endothelial cells within 1 hr of transplantation, but only trace levels of complement deposition were present in CVF-treated recipients. Within approximately 5-12 days, cardiac xenografts showed progressive infiltration by mononuclear cells, consisting primarily of activated macrophages producing tumor necrosis factor-alpha and small numbers of natural killer cells; T and B cells were absent. We conclude that (i) CVF prevents HAR, (ii) the addition of Spx + IS delays rejection, but (iii) the early deposition of antibody leads to progressive graft injury, resulting in (iv) delayed vascular rejection. Our findings indicate that the features of delayed xenograft rejection described in small animal models also occur in the pig-to-baboon model, and that rejection may occur in a complement-independent manner from the effects of antibody and/or host macrophages.

  1. Prolonged cardiac allograft survival in mouse model after complement depletion with Yunnan cobra venom factor.

    PubMed

    Wu, W; Wang, H-D; Zhu, X-X; Lan, G; Yang, K

    2009-12-01

    Activation of the complement system is the leading mechanism that causes antibody-mediated acute rejection and hyperacute rejection after xenotransplantation. The major cause of acute rejection in allogeneic transplantation is the T cell-mediated specific immune response. We studied the effects of complement on acute rejection after cardiac allotransplantation using complement depletion with cobra venom factor (CVF) in the mouse. The Balb/c-C57 mouse model of heterotopic cardiac allograft was used. The mice were divided into 2 groups, a control group and a CVF-treated group. After intravenous injection of CVF, the experimental group was observed for allograft survival time. Twelve mice from the control and experimental groups were sacrificed on days 3, 5, and 7 after the operation. The pathologic grade of acute rejection, deposition of C3 in tissue, extent of infiltration by CD4+ and CD8+ T cells, and expression of MHC-II, B7-1, and B7-2 were compared between the 2 groups. In the CVF-treated group, mean (SD) survival of the cardiac allograft was 26.2 (1.7) days, and in the control group was 8.4 (0.4) days (P < .01). Pathologic examination and immunohistochemistry demonstrated that the grade of acute rejection, deposition of C3 in tissue, extent of infiltration of CD4+ and CD8+ T cells, and expression of MHC-II, B7-1, and B7-2 were significantly decreased in the CVF-treated group. Depletion of complement in the serum with CVF inhibits acute cardiac allograft rejection in the mouse.

  2. A randomized comparison of balloon angioplasty versus rotational atherectomy in complex coronary lesions (COBRA study).

    PubMed

    Dill, T; Dietz, U; Hamm, C W; Küchler, R; Rupprecht, H J; Haude, M; Cyran, J; Ozbek, C; Kuck, K H; Berger, J; Erbel, R

    2000-11-01

    Rotablation is a widely used technique for the treatment of complex coronary artery lesions but is so far only poorly supported by controlled studies. The Comparison of Balloon-Angioplasty versus Rotational Atherectomy study (COBRA) is a multicentre, prospective, randomized trial to compare short- and long-term effects of percutaneous transluminal coronary angioplasty (PTCA) and rotablation in patients with angiographically pre-defined complex coronary artery lesions. At seven clinical sites 502 patients with pre-defined complex coronary artery lesions were assigned to either PTCA (n=250) or rotablation (n=252). Primary end-points were procedural success, 6-month restenosis rates in the treated segments, and major cardiac events during follow-up. Procedural success was achieved in 78% (PTCA), and 85% (rotablation) (P=0.038) of cases. Crossover from PTCA to rotablation was 4% and 10% vice versa (P=0.019). There was no difference between PTCA and rotablation with respect to procedure-related complications such as Q wave infarctions (2.4% each), emergency bypass surgery (1.2% versus 2.4%), and death (1.6% versus 0.4%). However, more stents were required after PTCA (14.9% versus 6.4%, P<0.002), predominantly for bailout or unsatisfactory results. Including bail-out stents as an end-point, the procedural success rates were 73% for angioplasty and 84% for rotablation (P=0.006). At 6 months, symptomatic outcome, target vessel reinterventions and restenosis rates (PTCA 51% versus rotablation 49%, P=0.33) were not different. Complex coronary artery lesions can be treated with a high level of success and low complication rates either by PTCA with adjunctive stenting or rotablation. The long-term clinical and angiographic outcome is comparable.

  3. Developing a guideline to standardize the citation of bioresources in journal articles (CoBRA).

    PubMed

    Bravo, Elena; Calzolari, Alessia; De Castro, Paola; Mabile, Laurence; Napolitani, Federica; Rossi, Anna Maria; Cambon-Thomsen, Anne

    2015-02-17

    Many biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles. As standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors' networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops. The European Association of Science Editors has adopted BRIF's suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual "reference [BIORESOURCE]" according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their "guidelines under development" section. Evaluating bioresources' use and impact requires that publications accurately cite such resources. Adopting the standard citation scheme described here will improve the quality of bioresource

  4. Brittle Culm1, a COBRA-Like Protein, Functions in Cellulose Assembly through Binding Cellulose Microfibrils

    PubMed Central

    Zhang, Baocai; Liu, Xiangling; Yan, Meixian; Zhang, Lanjun; Shi, Yanyun; Zhang, Mu; Qian, Qian; Li, Jiayang; Zhou, Yihua

    2013-01-01

    Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity. PMID:23990797

  5. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry.

    PubMed

    Fooshee, David R; Aiona, Paige K; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey A; Baldi, Pierre F

    2015-11-17

    Squalene is a major component of skin and plant surface lipids and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0 and 1450 Da, which correspond to about 27 000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. The simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces and contribute to their redox capacity.

  6. Viper and Cobra Venom Neutralization by Alginate Coated Multicomponent Polyvalent Antivenom Administered by the Oral Route

    PubMed Central

    Bhattacharya, Sourav; Chakraborty, Mousumi; Mukhopadhyay, Piyasi; Kundu, P. P.; Mishra, Roshnara

    2014-01-01

    Background Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. Methodology/Principal Findings To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. Conclusions/Significance Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra

  7. COBRA-LIKE2, a Member of the Glycosylphosphatidylinositol-Anchored COBRA-LIKE Family, Plays a Role in Cellulose Deposition in Arabidopsis Seed Coat Mucilage Secretory Cells1,2[OPEN

    PubMed Central

    Ben-Tov, Daniela; Abraham, Yael; Stav, Shira; Thompson, Kevin; Loraine, Ann; Elbaum, Rivka; de Souza, Amancio; Pauly, Markus; Kieber, Joseph J.; Harpaz-Saad, Smadar

    2015-01-01

    Differentiation of the maternally derived seed coat epidermal cells into mucilage secretory cells is a common adaptation in angiosperms. Recent studies identified cellulose as an important component of seed mucilage in various species. Cellulose is deposited as a set of rays that radiate from the seed upon mucilage extrusion, serving to anchor the pectic component of seed mucilage to the seed surface. Using transcriptome data encompassing the course of seed development, we identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as coexpressed with other genes involved in cellulose deposition in mucilage secretory cells. Disruption of the COBL2 gene results in substantial reduction in the rays of cellulose present in seed mucilage, along with an increased solubility of the pectic component of the mucilage. Light birefringence demonstrates a substantial decrease in crystalline cellulose deposition into the cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition into the radial cell walls and the columella appears substantially compromised, as demonstrated by scanning electron microscopy and in situ quantification of light birefringence. Overall, the cobl2 mutants display about 40% reduction in whole-seed crystalline cellulose content compared with the wild type. These data establish that COBL2 plays a role in the deposition of crystalline cellulose into various secondary cell wall structures during seed coat epidermal cell differentiation. PMID:25583925

  8. Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

    PubMed

    Petras, Daniel; Heiss, Paul; Süssmuth, Roderich D; Calvete, Juan J

    2015-06-05

    We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.

  9. Characterization and cytotoxicity of L-amino acid oxidase from the venom of king cobra (Ophiophagus hannah).

    PubMed

    Ahn, M Y; Lee, B M; Kim, Y S

    1997-06-01

    The aim of this project was to determine the cytotoxic components from the venom of king cobra, Ophiophagus hannah. Venom was purified by a combination of gel-filtration, ion-exchange and reversed-phase chromatographic steps. The biochemical properties of the cytotoxic component were consistent with those of L-amino acid oxidase. The molecular weight of the enzyme was estimated to be 150,000 by gel filtration and 70,000 under the denaturing conditions of SDS-PAGE, indicating a dimer. It has an isoelectric point of 4.5 and is a glycoprotein. The N-terminal sequence of L-amino acid oxidase from the king cobra venom was determined to be SVINLEESFQEPEYE. The cytotoxicity of L-amino acid oxidase was observed in stomach cancer, murine melanoma, fibrosarcoma, colorectal cancer and Chinese hamster ovary cell lines. Cytotoxicity resulted in the loss of ability in attachment and inhibition of cell proliferation. The cytotoxic protein decreased the level of cell proliferation by 74% according to [3H]thymidine uptake assay. The mechanism of enzyme action may be related to the inhibition of thymidine incorporation and an interaction with DNA.

  10. Occurrence of non-protein low molecular weight cardiotoxin in Indian King Cobra (Ophiophagus hannah) Cantor 1836, venom.

    PubMed

    Saha, Archita; Gomes, Aparna; Giri, B; Chakravarty, A K; Biswas, A K; Dasgupta, S C; Gomes, A

    2006-04-01

    Pathophysiology due to snakebite is a combined effect of various actions of the complex venom constituents. Importance of protein toxins in snake envenomation is well known. The present investigation reports the existence of nonprotein/nonpetide low molecular weight toxin in Indian King Cobra venom, which plays an important role in envenomation consequences in experimental animal models. A group of non-peptidic toxins (OH-NPT1) was isolated from Indian King Cobra Ophiophagus hannah by thin layer chromatography and silica gel column chromatography. UV, IR, NMR and (ESI) TOF-MS studies characterized the OH-NPT1 as a mixture of aliphatic acids having molecular weights 256, 326 and 340Da. The minimum lethal dose of OH-NPT1 was found to be 2.5 microg/20g (iv) and 4microg/20g (ip) in male albino mice. The cardiotoxic property of OH-NPT1 was established through studies on isolated guinea pig heart and auricle preparations, ECG studies in albino rat and estimation of LDH1/LDH and CPK-MB/CPK ratio in Swiss albino mice. Commercial antiserum failed to neutralize the lethality and cardiotoxicity of the toxin. However, calcium and magnesium effectively neutralized the lethal action.

  11. COBRA-SFS thermal analysis of a sealed storage cask for the Monitored Retrievable Storage of spent fuel

    SciTech Connect

    Rector, D.R.; Wheeler, C.L.

    1986-01-01

    The COBRA-SFS (Spent Fuel Storage) computer code was used to predict temperature distributions in a concrete Sealed Storage Cask (SSC). This cask was designed for the Department of Energy in the Monitored Retrievable Storage (MRS) program for storage of spent fuel from commercial power operations. Analytical results were obtained for nominal operation of the SSC with spent fuel from 36 PWR fuel assemblies consolidated in 12 cylindrical canisters. Each canister generates 1650 W of thermal power. A parametric study was performed to assess the effects on cask thermal performance of thermal conductivity of the concrete, the fin material, and the amount of radial reinforcing steel bars (rebar). Seven different cases were modeled. The results of the COBRA-SFS analysis of the current cask design predict that the peak fuel cladding temperature in the SSC will not exceed the 37/sup 0/C design limit for the maximum spent fuel load of 19.8 kW and a maximum expected ambient temperature of 37.8/sup 0/C (100/sup 0/F). The results of the parametric analyses illustrate the importance of material selection and design optimization with regard to the SSC thermal performance.

  12. Efficacy evaluations of Mimosa pudica tannin isolate (MPT) for its anti-ophidian properties.

    PubMed

    Ambikabothy, Jamunaa; Ibrahim, Halijah; Ambu, Stephen; Chakravarthi, Srikumar; Awang, Khalijah; Vejayan, Jaya

    2011-09-01

    Evaluations of the anti-snake venom efficacy of Mimosa pudica tannin isolate (MPT) obtained from root of the plant. MPT was investigated in vitro and in vivo for its efficacy against the venom of Naja kaouthia snake. In vitro: (1) mice injected i.p. with MPT pre-incubated with Naja kaouthia venom at concentrations as low as 0.625 mg/ml showed 100% survival after a 24-h observation period. (2) In the proteomics study, mice injected with MPT pre-incubated with the Naja kaouthia venom showed down-regulation of five serum proteins. (3) In the protein-dye-binding study, the percentage of Bradford dye-protein binding showed a reduction relative to the decrease in MPT concentration used to incubate with the venom. In vivo: the results from the animal studies showed that MPT had no in vivo protection against the Naja kaouthia venom (0.875 mg/kg) in four different rescue modes and in an oral pre-treatment experiment. The study indicated the promising ability of MPT to neutralize the Naja kaouthia venom in in vitro experiments but fell short in its in vivo potential. As such, the use of Mimosa pudica (Mimosaceae) as therapeutics for snake bites is questionable as all the possible in vivo rescue studies and pre-treatment of the active constituents showed no protection against the affected mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Assessment of macro and microelement accumulation capability of two aquatic plants.

    PubMed

    Baldantoni, Daniela; Alfani, Anna; Di Tommasi, Paul; Bartoli, Giovanni; De Santo, Amalia Virzo

    2004-07-01

    The concentrations of four macroelements (C, N, P, S) and eight trace metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn) were measured in the leaves and roots of the emergent plant, Phragmites communis Trin., and in the shoots and roots of the submersed Najas marina L., taken from Lake Averno (Naples, Italy). Phragmites communis leaves showed higher concentrations of carbon, nitrogen and phosphorus than roots, while the roots exhibited significantly higher concentrations of sulphur and trace metals. Najas marina roots also showed higher concentrations of sulphur and trace metals than shoots, but these differences were less marked than in Phragmites communis except for sulphur. Sulphur was the only macronutrient to show the highest concentrations in the roots. Phragmites communis roots had higher values of Cr, Cu, Fe, Mn and Ni than Najas marina roots. By contrast, Cd, Cr, Fe, Ni, Pb and Zn concentrations were higher in Najas marina shoots than in Phragmites communis leaves. Phragmites communis, available through the year, showing high capability to accumulate trace metals in the roots, appears a good monitor of lake contamination, better than Najas marina.

  14. Cocktail of H5N1 COBRA HA vaccines elicit protective antibodies against H5N1 viruses from multiple clades.

    PubMed

    Crevar, Corey J; Carter, Donald M; Lee, Kevin Y J; Ross, Ted M

    2015-01-01

    Pandemic outbreaks of influenza are caused by the emergence of a pathogenic and transmissible virus to which the human population is immunologically naïve. Recent outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype are of particular concern because of the high mortality rate (60% case fatality rate) and novel subtype. In this study, we have engineered an influenza virus-like particle (VLP) that contains a synthetic, consensus-based HA molecule using a new methodology, computationally optimized broadly reactive antigen (COBRA). Three COBRA H5N1 HA proteins have been engineered based upon (1) human clade 2 H5N1 sequences, (2) human and avian clade 2 sequences, and (3) all H5N1 influenza sequences recorded between 2005-2008. Each hemagglutinin protein retained the ability to bind the appropriate receptors, as well as the ability to mediate particle fusion, following purification from a mammalian expression system. COBRA VLP vaccines were administered to mice and the humoral immune responses were compared to those induced by VLPs containing an HA derived from a primary viral isolate. Using a single vaccination (0.6 ug HA dose with an adjuvant) all animals vaccinated with COBRA clade 2 HA H5N1 VLPs had protective levels of HAI antibodies to a representative isolate from each subclade of clade 2, but lower titers against other clades. The addition of avian sequences from other clades expanded breadth of HAI antibodies to the divergent clades, but still not all of the 25 H5N1 viruses in the panel were recognized by antibodies elicited any one H5N1 COBRA VLP vaccine. Vaccination of mice with a cocktail of all 3 COBRA HA VLP vaccines, in a prime-boost regimen, elicited an average HAI titer greater than 1:40 against all 25 viruses. Collectively, our findings indicate that the elicited antibody response following VLP vaccination with all 3 COBRA HA vaccine simultaneously elicited a broadly-reactive set of antibodies that recognized H5N1 viruses from 11

  15. Cobra venom cardiotoxin induces perturbations of cytosolic calcium homeostasis and hypercontracture in adult rat ventricular myocytes.

    PubMed

    Wang, H X; Lau, S Y; Huang, S J; Kwan, C Y; Wong, T M

    1997-10-01

    The effects of Cobra venom cardiotoxin (CTX) on the cellular morphology, twitch amplitude and intracellular calcium ([Ca2+]i) of the ventricular myocytes were studied. [Ca2+]i and twitch amplitude were determined with a fluorometric ratio method using Fura-2/AM and Calcium Green-1 as calcium indicators, and a videomicroscopic technique, respectively. Addition of 0.001-1 microM CTX led to a time-dependent loss of rod shaped cells, beginning at 1 min, and remaining stable by 20 min. CTX 1 microM initially caused a transient augmentation in amplitude of the electrically induced-[Ca2+]i transient and twitch amplitude in the single cardiac myocyte. This was followed by a prolongation in duration of [Ca2+]i. Eventually, cells became inexcitable and abruptly underwent contracture, and [Ca2+]i remained elevated. In the absence of electrical stimulation, 1 microM CTX induced a Ca2+ spike followed by a sustained elevation of [Ca2+]i, an effect different from that of 40 mm KCl or 10 mm caffeine, which caused a transient elevation in [Ca2+]i. Digital imaging microscopy of Calcium Green-1 fluorescence revealed that the increase in [Ca2+]i was accompanied by changes in cell shape without leakage of fluorescence dye in the early stage after administration of the toxin. In the absence of [Ca2+]o, the initial [Ca2+]i spike was reduced, but the second phase of elevation of [Ca2+]i still occurred. In addition, experiments using Mn2+ quench technique suggested that Ca2+-influx was induced by CTX, and that both ryanodine and thapsigargin, known to deplete Ca2+ from its intracellular pool, abolished the second phase of the elevation of [Ca2+]i. The effects of cardiotoxin were abolished by 10 mM Ni2+ and 10 mM -Ca2+-o, but not by 5 microM verapamil. In conclusion, the observations indicate that CTX causes an initial increase followed by a second sustained elevation in [Ca2+]i, which is accompanied by changes in cell shape-from rod to round-and hypercontracture. The initial [Ca2+]i spikes

  16. Development of uncertainty methodology for COBRA-TF void distribution and critical power predictions

    NASA Astrophysics Data System (ADS)

    Aydogan, Fatih

    specimens among the sample with a bias lower than the experimental uncertainty. Besides, the rankings of dominant phenomena are observed with the second comparison method (sensitivity analysis). Simple Random Sampling, Order Statistics, Richardson Extrapolation are some of the methods that are in the developed methodology. This uncertainty methodology was implemented for the COBRA-TF predictions. The uncertainty and sensitivity results are presented in the dissertation.

  17. The New Perilaryngeal Airway (CobraPLA™)1 Is as Efficient as the Laryngeal Mask Airway (LMA™)2, But Provides Better Airway Sealing Pressures

    PubMed Central

    Akça, Ozan; Wadhwa, Anupama; Sengupta, Papiya; Durrani, Jaleel; Hanni, Keith; Wenke, Mary; Yücel, Yüksel; Lenhardt, Rainer; Doufas, Anthony G.; Sessler, Daniel I.

    2006-01-01

    The Laryngeal Mask Airway (LMA) is a frequently-used efficient airway device, yet it sometimes seals poorly, thus reducing the efficacy of positive-pressure ventilation. The Perilaryngeal Airway (CobraPLA) is a novel airway device with a larger pharyngeal cuff (when inflated). We tested the hypothesis that the CobraPLA was superior to LMA with regard to insertion time and airway sealing pressure and comparable to LMA in airway adequacy and recovery characteristics. After midazolam and fentanyl, 81 ASA I-II outpatients having elective surgery were randomized to receive an LMA or CobraPLA. Anesthesia was induced with propofol (2.5 mg/kg, IV), and the airway inserted. We measured 1) insertion time; 2) adequacy of the airway (no leak at 15-cm-H2O peak pressure or tidal volume of 5 ml/kg); 3) airway sealing pressure; 4) number of repositioning attempts; and 5) sealing quality (no leak at tidal volume of 8 ml/kg). At the end of surgery, gastric insufflation, postoperative sore throat, dysphonia, and dysphagia were evaluated. Data were compared with unpaired t-tests, chi-square tests, or Fisher’s Exact tests; P<0.05 was significant. Patient characteristics, insertion times, airway adequacy, number of repositioning attempts, and recovery were similar in each group. Airway sealing pressure was significantly greater with CobraPLA (23±6 cm H2O) than LMA (18±5 cm H2O, P<0.001). The CobraPLA has insertion characteristics similar to LMA, but better airway sealing capabilities. PMID:15281543

  18. A New Animal Model of Brachial Plexus Neuralgia Produced by Injection of Cobra Venom into the Lower Trunk in the Rat.

    PubMed

    Liu, CaiCai; Qian, XiaoYan; JianXiong, A N; Wang, Yong; Fang, QiWu; Jiang, YiDe; Cope, Doris K; Williams, John P

    2015-09-01

    To establish a new animal model for the study of neuropathic pain developed by administration of cobra venom to the brachial plexus (BP) lower trunk. Fifty-eight adult male Sprague-Dawley rats were randomly divided into 5 groups. Under pentobarbital sodium anesthesia, cobra venom was injected into the lower trunk or sham operation was performed in the animals. On postoperative day 1 and day 12, pregabalin was administered intragastricly at 30 mg/kg in two groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were used to analyze the spontaneous behaviors. Meanwhile, our model was confirmed by observing ultrastructural alterations of the BP and cervical cord (C8-T1) via electron microscope examination. In comparison to the blank and sham-operated group, cobra venom-treated rats showed a profound decrease in the MWT, exploratory and increase in grooming behaviors (P<0.05). The changes were long-lasting (up to 60 days), in both ipsilateral and contralateral paws. Furthermore, it was observed under microscopic examination that the myelin sheath was demyelinated in the BP and cervical cord (C8-T1) after injection of cobra venom to the lower trunk. Pregabalin group rats showed changes in MWT and spontaneous behaviors after pregabalin treatment at postoperative day 1 (P>0.05), compared with the control and sham-operated groups. In pregabalin test POD12 group, the decreased MWT and the increased grooming behavior were improved at 20 days after operation. However, pregabalin had no effect on exploratory activity. Results indicate that pregabalin effectively attenuates mechanical hyperalgesia in acute period. The cobra venom model can be used as a model to induce neuropathic pain and to enable study of the mechanism and treatment. Wiley Periodicals, Inc.

  19. Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom

    PubMed Central

    2013-01-01

    Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom’s primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras. PMID:24074353

  20. Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom.

    PubMed

    Nekaris, K Anne-Isola; Moore, Richard S; Rode, E Johanna; Fry, Bryan G

    2013-09-27

    Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom's primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras.

  1. Antimicrobial activity of plants used as medicinals on an indigenous reserve in Rio das Cobras, Paraná, Brazil.

    PubMed

    Moura-Costa, Gislaine F; Nocchi, Samara R; Ceole, Ligia F; de Mello, João Carlos P; Nakamura, Celso Vataru; Dias Filho, Benedito Prado; Temponi, Livia G; Ueda-Nakamura, Tania

    2012-09-28

    A considerable percentage of global biodiversity is located in Brazil, a country that also has rich cultural and ethnic diversity. In the community of Rio das Cobras, Paraná, plants are still widely used in the health care not only by indigenous people but also by the non-indigenous population that inhabits the region. The investigation of the efficacy and safety of these plants in the treatment of infectious diseases provides insights for future studies of these species allowing the appropriated use by the indigenous people, since few or none study has been conducted so far. Evaluate the antimicrobial activity and cytotoxicity of some plants used as medicinal on an indigenous reserve in Rio das Cobras, Paraná, Brazil. The aqueous extracts were obtained by decoction and the 50% and 70% hydroalcoholic extracts by turbo extraction. The extracts were tested against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Candida parapsilosis, Candida tropicalis, Leishmania amazonensis, Poliovirus and HSV-1. Cytotoxicity assay using VERO cells were also performed. None of the extracts had a selectivity index (SI)>1 for any of the tested bacteria. Only Campomanesia eugenioides and Schinus terebinthifolius had an SI>1.0 for all of the tested Candida species. The best anti-Leishmania activity was obtained with Zanthoxylum rhoifolium and Schinus terebinthifolius. Extracts of Cordia americana were the most effective against herpes simplex virus type 1. Zanthoxylum rhoifolium was the most effective against Poliovirus, and Ocimum gratissimum was effective against both Poliovirus and Herpes Simplex virus. Among the plants investigated in the present study, Zanthoxylum rhoifolium had the fewest cytotoxic effect. The plants investigated in the present study exhibited potential for future pharmacological uses, but additional studies, especially with regard to in vivo toxicity, must be conducted. The results of this

  2. Continental-Scale Trace Gas Measurements During COBRA and the Case for Airborne Flask Measurements in the NACP

    NASA Astrophysics Data System (ADS)

    Miller, J. B.; Stephens, B. B.; Bakwin, P.; Tans, P. P.; Gerbig, C.; Lin, J.; Wofsy, S.; Andrews, A.; Daube, B.

    2002-12-01

    Intensive airborne sampling of trace gases is envisioned as a major component of the planned North American Carbon Program (NACP). During August 2000 we sampled air between the surface and 10,000 m in the eastern two thirds of the conterminous United States as part of the CO2 Budget and Rectification-Airborne (COBRA) study. Our experience from COBRA can help inform our airborne sampling strategy for the NACP. In COBRA, CO2 and CO were measured in situ by continuous instrumentation, and CO2, CO, CH4, N2O, H2, SF6 and δ13CO2 were measured in the laboratory. Although the data density of the continuous measurements is much higher than that of the flask-based ones, flasks samples are an important complement to the in situ. Laboratory measurements of CO2 and CO provide quality control, while high precision measurements of CH4, δ13CO2 and other species cannot be made in situ. Significant vertical gradients were observed for all species as a result of emissions from biogenic, fossil-fuel related and biomass burning sources. Simultaneously measuring multiple species can help isolate the biogenic component from this mix. For example, if we know emission ratios, measurements of CO and SF6 can be used to identify the fossil fuel and biomass burning contributions to observed CO2. Measurements indicate substantial surface sources of both CH4 and N2O, and a surface sink for H2, in different parts of the United States. As is the case for CO2, the magnitudes and signs of the fluxes are geographically variable. When combined, the vertical gradients CO2 and δ13C can be related to the extent of isotopic discrimination that takes place during plant photosynthesis. This, in turn, is related to plant type and metabolism. Within the data assimilation context of the NACP, measurements of these biologically mediated trace gases will add information on the functioning of the biosphere and thus help to constrain estimates of CO2 fluxes. How much information is lost by taking flask samples

  3. Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial.

    PubMed

    ter Wee, Marieke M; den Uyl, Debby; Boers, Maarten; Kerstens, Pit; Nurmohamed, Mike; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E; Lems, Willem F

    2015-06-01

    Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA). To assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept. An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39. Both groups showed major improvements in DAS44 after 52 weeks: mean (SD) -2.41 (1.2) in the COBRA and -2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it. Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation. ISRCTN55552928. Published by the BMJ

  4. Analysis of locus-specific changes in methylation patterns using a COBRA (combined bisulfite restriction analysis) assay.

    PubMed

    Boyko, Alex; Kovalchuk, Igor

    2010-01-01

    DNA methylation is a major mechanism for the reversible control of gene expression, chromatin structure, and genome stability. Methylation analysis at a given locus allows one to evaluate levels of chromatin packaging, gene expression, and even homologous recombination. We have shown that the combined bisulfite restriction analysis (COBRA) assay makes it possible to analyze methylation levels at a defined locus. The major steps are: bisulfite conversion of nonmethylate cytosines to uracils, locus-specific PCR amplification of converted DNA, restriction digestion, and analysis of restriction patterns on the gel. Due to the availability of various restriction enzymes that have cytosines in the restriction recognition sequence, the assay allows analysis of various cytosines, including those potentially targeted for symmetrical and nonsymmetrical methylation.

  5. Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles.

    PubMed

    Napolitani, Federica; Calzolari, Alessia; Cambon-Thomsen, Anne; Mabile, Laurence; Rossi, Anna Maria; De Castro, Paola; Bravo, Elena

    2016-08-01

    Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The "BRIF (Bioresource Research Impact Factor) and journal editors" subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing.

  6. Experimental Analysis of Steady-State Maneuvering Effects on Transmission Vibration Patterns Recorded in an AH-1 Cobra Helicopter

    NASA Technical Reports Server (NTRS)

    Huff, Edward M.; Dzwonczyk, Mark; Norvig, Peter (Technical Monitor)

    2000-01-01

    Flight experiment was designed primarily to determine the extent to which steady-state maneuvers influence characteristic vibration patterns measured at the input pinion and output annulus gear locations of the main transmission. If results were to indicate that maneuvers systematically influence vibration patterns, more extensive studies would be planned to explore the response surface. It was also designed to collect baseline data for comparison with experimental data to be recorded at a later date from test stands at Glenn Research Center. Finally, because this was the first vibration flight study on the Cobra aircraft, considerable energy was invested in developing an in-flight recording apparatus, as well as exploring acceleration mounting methods, and generally learning about the overall vibratory characteristics of the aircraft itself.

  7. Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles

    PubMed Central

    Calzolari, Alessia; Cambon-Thomsen, Anne; Mabile, Laurence; Rossi, Anna Maria; De Castro, Paola; Bravo, Elena

    2016-01-01

    Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The “BRIF (Bioresource Research Impact Factor) and journal editors” subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing. PMID:27314833

  8. Development of burnup dependent fuel rod model in COBRA-TF

    NASA Astrophysics Data System (ADS)

    Yilmaz, Mine Ozdemir

    The purpose of this research was to develop a burnup dependent fuel thermal conductivity model within Pennsylvania State University, Reactor Dynamics and Fuel Management Group (RDFMG) version of the subchannel thermal-hydraulics code COBRA-TF (CTF). The model takes into account first, the degradation of fuel thermal conductivity with high burnup; and second, the fuel thermal conductivity dependence on the Gadolinium content for both UO2 and MOX fuel rods. The modified Nuclear Fuel Industries (NFI) model for UO2 fuel rods and Duriez/Modified NFI Model for MOX fuel rods were incorporated into CTF and fuel centerline predictions were compared against Halden experimental test data and FRAPCON-3.4 predictions to validate the burnup dependent fuel thermal conductivity model in CTF. Experimental test cases from Halden reactor fuel rods for UO2 fuel rods at Beginning of Life (BOL), through lifetime without Gd2O3 and through lifetime with Gd 2O3 and a MOX fuel rod were simulated with CTF. Since test fuel rod and FRAPCON-3.4 results were based on single rod measurements, CTF was run for a single fuel rod surrounded with a single channel configuration. Input decks for CTF were developed for one fuel rod located at the center of a subchannel (rod-centered subchannel approach). Fuel centerline temperatures predicted by CTF were compared against the measurements from Halden experimental test data and the predictions from FRAPCON-3.4. After implementing the new fuel thermal conductivity model in CTF and validating the model with experimental data, CTF model was applied to steady state and transient calculations. 4x4 PWR fuel bundle configuration from Purdue MOX benchmark was used to apply the new model for steady state and transient calculations. First, one of each high burnup UO2 and MOX fuel rods from 4x4 matrix were selected to carry out single fuel rod calculations and fuel centerline temperatures predicted by CTF/TORT-TD were compared against CTF /TORT-TD /FRAPTRAN

  9. Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics.

    PubMed

    Melani, Rafael D; Skinner, Owen S; Fornelli, Luca; Domont, Gilberto B; Compton, Philip D; Kelleher, Neil L

    2016-07-01

    Characterizing whole proteins by top-down proteomics avoids a step of inference encountered in the dominant bottom-up methodology when peptides are assembled computationally into proteins for identification. The direct interrogation of whole proteins and protein complexes from the venom of Ophiophagus hannah (king cobra) provides a sharply clarified view of toxin sequence variation, transit peptide cleavage sites and post-translational modifications (PTMs) likely critical for venom lethality. A tube-gel format for electrophoresis (called GELFrEE) and solution isoelectric focusing were used for protein fractionation prior to LC-MS/MS analysis resulting in 131 protein identifications (18 more than bottom-up) and a total of 184 proteoforms characterized from 14 protein toxin families. Operating both GELFrEE and mass spectrometry to preserve non-covalent interactions generated detailed information about two of the largest venom glycoprotein complexes: the homodimeric l-amino acid oxidase (∼130 kDa) and the multichain toxin cobra venom factor (∼147 kDa). The l-amino acid oxidase complex exhibited two clusters of multiproteoform complexes corresponding to the presence of 5 or 6 N-glycans moieties, each consistent with a distribution of N-acetyl hexosamines. Employing top-down proteomics in both native and denaturing modes provides unprecedented characterization of venom proteoforms and their complexes. A precise molecular inventory of venom proteins will propel the study of snake toxin variation and the targeted development of new antivenoms or other biotherapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. 9-Month Clinical and Angiographic Outcomes of the COBRA Polyzene-F NanoCoated Coronary Stent System.

    PubMed

    Cutlip, Donald E; Garratt, Kirk N; Novack, Victor; Barakat, Mark; Meraj, Perwaiz; Maillard, Luc; Erglis, Andrejs; Jauhar, Rajiv; Popma, Jeffrey J; Stoler, Robert; Silber, Sigmund

    2017-01-23

    The aim of this study was to assess the safety and effectiveness of the COBRA Polyzene-F NanoCoated Coronary Stent System (CeloNova Biosciences, San Antonio, Texas) for the treatment of de novo coronary artery lesions. Polyzene-F-coated coronary stents have shown reduced thrombogenicity and inflammation in preclinical studies. Patients with de novo coronary artery lesions meeting eligibility criteria were enrolled in a nonrandomized, prospective clinical trial. The primary endpoint was target vessel failure (TVF) (defined as a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization) at 9 months. A pre-specified subset was planned for routine repeat angiographic follow-up at 9 months. The powered secondary endpoint was mean late lumen loss (LL). The comparator was a performance goal derived from meta-analysis of historical bare-metal stent trials of 19.62% for TVF and 1.1 mm for LL. Other secondary endpoints were clinically driven target lesion revascularization and definite or probable stent thrombosis. Of 296 enrolled patients, 287 (97%) completed primary endpoint analysis; 130 were planned for angiographic follow-up and 115 (88%) completed. At 9 months, TVF had occurred in 33 patients (11.5%; upper 95% confidence boundary: 15.07%), including 1 (0.3%) cardiac death, 20 (7.0%) myocardial infarctions (17 periprocedural), and 17 (5.9%) target vessel revascularizations. LL was 0.84 ± 0.48 mm (upper 95% confidence boundary: 0.92). Target lesion revascularization occurred in 13 patients (4.6%). There were no stent thrombosis events. The COBRA Polyzene-F stent met performance goals for TVF and LL at 9 months. There was an excellent safety profile, with infrequent late myocardial infarction and no stent thrombosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Activities of cobra venom cytotoxins toward heart and leukemic T-cells depend on localized amino acid differences.

    PubMed

    Stevens-Truss, R; Hinman, C L

    1997-05-01

    Several studies have suggested that along the concave surface of cobra venom cytotoxins, a hydrophobic region flanked by positively charged amino acid side-chains, as well as by tyrosine and/or serine/threonine, allows these toxins to depolarize muscle or cause cytolysis. Comparison of biological activities among structurally homologous toxins, however, has revealed significant functional diversity. The objective of the present study was to examine several toxins purified from different cobra venoms with regard to their ability to bind to and kill human T-lymphocytes and rat heart cell myoblasts. The activities observed were then correlated with differences in amino acid residues which occur in restricted regions of the toxins. The absence of an aromatic residue at position 11 (Loop 1) resulted in a lower cytolytic response at every concentration tested. A simple inversion of two residues in the amino acid sequence of toxin Loop 3 selectively impaired heart cell binding and cytolysis, but had no effect on T-cells. Loss of a positively charged residue in the tip of Loop 2 minimally affected binding but significantly reduced cytolysis. Replacement of valine at positions 27 and 32, along with the introduction of a negative charge at the tip of Loop 2, interfered with binding to either cell type and caused a reduction in cytolysis. The results of this study suggest that no one loop or region is solely responsible for the toxin's biological activity. However, because the binding and cytolytic sites within these toxins are distinct, it may become possible to develop toxin derivatives in which only selected activities are enhanced.

  12. [The effect of Asian cobra venom on the content of rat heart and liver mitochondrial phospholipids and the protective effect of benzonal].

    PubMed

    Shirinova, I A; Nurdinov, Sh Sh; Klemesheva, L S; Almatov, K T

    2005-01-01

    Administration of a cobra venom to rats resulted in decrease of heart and liver mitochondrial cardiolipins (1.88 and 1.82 times), phosphatidylethanolamines (1.56 and 1.42 times) and phosphatidic acid (1.14 and 1.29 times), whereas the content of phosphadtidylcholins increased by 1.42 and 1.51-fold, respectively. The content of phosphadtidylinositol increased by 3.09 times in liver mitochondria and decreased by 1.28 times in heart mitochondria. Administration of benzonal not only normalized liver mitochondrial phosphadtidylserine content impaired after the venom administration but even exceeded it. Benzonal also minimized changes in mitochondrial phospholipid induced by the cobra venom, and also reduced liver and heart phosphatidic acid content by 1.36 and 1.7 times.

  13. Antibacterial action of a heat-stable form of L-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom.

    PubMed

    Lee, Mui Li; Tan, Nget Hong; Fung, Shin Yee; Sekaran, Shamala Devi

    2011-03-01

    The major l-amino acid oxidase (LAAO, EC 1.4.3.2) of king cobra (Ophiophagus hannah) venom is known to be an unusual form of snake venom LAAO as it possesses unique structural features and unusual thermal stability. The antibacterial effects of king cobra venom LAAO were tested against several strains of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. For comparison, the antibacterial effects of several antibiotics (cefotaxime, kanamycin, tetracycline, vancomycin and penicillin) were also examined using the same conditions. King cobra venom LAAO was very effective in inhibiting the two Gram-positive bacteria (S. aureus and S. epidermidis) tested, with minimum inhibitory concentration (MIC) of 0.78μg/mL (0.006μM) and 1.56μg/mL (0.012μM) against S. aureus and S. epidermidis, respectively. The MICs are comparable to the MICs of the antibiotics tested, on a weight basis. However, the LAAO was only moderately effective against three Gram-negative bacteria tested (P. aeruginosa, K. pneumoniae and E. coli), with MIC ranges from 25 to 50μg/mL (0.2-0.4μM). Catalase at the concentration of 1mg/mL abolished the antibacterial effect of LAAO, indicating that the antibacterial effect of the enzyme involves generation of hydrogen peroxide. Binding studies indicated that king cobra venom LAAO binds strongly to the Gram-positive S. aureus and S. epidermidis, but less strongly to the Gram-negative E. coli and P. aeruginosa, indicating that specific binding to bacteria is important for the potent antibacterial activity of the enzyme. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. The maize (Zea mays L.) roothairless3 gene encodes a putative GPI-anchored, monocot-specific, COBRA-like protein that significantly affects grain yield

    PubMed Central

    Hochholdinger, Frank; Wen, Tsui-Jung; Zimmermann, Roman; Chimot-Marolle, Patricia; da Costa e Silva, Oswaldo; Bruce, Wesley; Lamkey, Kendall R; Wienand, Udo; Schnable, Patrick S

    2008-01-01

    Summary The rth3 (roothairless 3) mutant is specifically affected in root hair elongation. We report here the cloning of the rth3 gene via a PCR-based strategy (amplification of insertion mutagenized sites) and demonstrate that it encodes a COBRA-like protein that displays all the structural features of a glycosylphosphatidylinositol anchor. Genes of the COBRA family are involved in various types of cell expansion and cell wall biosynthesis. The rth3 gene belongs to a monocot-specific clade of the COBRA gene family comprising two maize and two rice genes. While the rice (Oryza sativa) gene OsBC1L1 appears to be orthologous to rth3 based on sequence similarity (86% identity at the protein level) and maize/rice synteny, the maize (Zea mays L.) rth3-like gene does not appear to be a functional homolog of rth3 based on their distinct expression profiles. Massively parallel signature sequencing analysis detected rth3 expression in all analyzed tissues, but at relatively low levels, with the most abundant expression in primary roots where the root hair phenotype is manifested. In situ hybridization experiments confine rth3 expression to root hair-forming epidermal cells and lateral root primordia. Remarkably, in replicated field trials involving near-isogenic lines, the rth3 mutant conferred significant losses in grain yield. PMID:18298667

  15. ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy).

    PubMed

    Tagliaferri, Luca; Kovács, György; Autorino, Rosa; Budrukkar, Ashwini; Guinot, Jose Luis; Hildebrand, Guido; Johansson, Bengt; Monge, Rafael Martìnez; Meyer, Jens E; Niehoff, Peter; Rovirosa, Angeles; Takàcsi-Nagy, Zoltàn; Dinapoli, Nicola; Lanzotti, Vito; Damiani, Andrea; Soror, Tamer; Valentini, Vincenzo

    2016-08-01

    Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection. GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group. Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of "brokers", data can be extracted directly from the single center's storage systems through a connection with "structured query language database" (SQL-DB), Microsoft Access(®), FileMaker Pro(®), or Microsoft Excel(®). The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of "on-purpose data projection". The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called "distributed learning" approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared. Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the center's own data storing technologies, procedures, and habits. Furthermore, the method

  16. ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy)

    PubMed Central

    Tagliaferri, Luca; Kovács, György; Budrukkar, Ashwini; Guinot, Jose Luis; Hildebrand, Guido; Johansson, Bengt; Monge, Rafael Martìnez; Meyer, Jens E.; Niehoff, Peter; Rovirosa, Angeles; Takàcsi-Nagy, Zoltàn; Dinapoli, Nicola; Lanzotti, Vito; Damiani, Andrea; Soror, Tamer; Valentini, Vincenzo

    2016-01-01

    Purpose Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection. Material and methods GEC-ESTRO (Groupe Européen de Curiethérapie – European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group. Results Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of “brokers”, data can be extracted directly from the single center's storage systems through a connection with “structured query language database” (SQL-DB), Microsoft Access®, FileMaker Pro®, or Microsoft Excel®. The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of “on-purpose data projection”. The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called “distributed learning” approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared. Conclusions Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the center's own data storing

  17. Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom.

    PubMed

    Liu, Hui; Qian, Xiao-Yan; An, Jian-Xiong; Liu, Cai-Cai; Jiang, Yi-De; Cope, Doris K; Williams, John P

    2016-03-01

    Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. Controlled animal study. Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not

  18. Identification and characterization of novel reptile cathelicidins from elapid snakes.

    PubMed

    Zhao, Hui; Gan, Tong-Xiang; Liu, Xiao-Dong; Jin, Yang; Lee, Wen-Hui; Shen, Ji-Hong; Zhang, Yun

    2008-10-01

    Three cDNA sequences coding for elapid cathelicidins were cloned from constructed venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus hannah. The open reading frames of the cloned elapid cathelicidins were all composed of 576bp and coded for 191 amino acid residue protein precursors. Each of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a conserved cathelin domain of 135 amino acid residues and a mature antimicrobial peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in mammals, the nucleotide and deduced protein sequences of the three cloned elapid cathelicidins were remarkably conserved. All the elapid mature cathelicidins were predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature cathelicidin from king cobra, was chemically synthesized and it showed strong antibacterial activity against various bacteria with minimal inhibitory concentration of 1-20microg/ml in the presence of 1% NaCl. Meanwhile, the synthetic peptide showed no haemolytic activity toward human red blood cells even at a high dose of 200microg/ml. Phylogenetic analysis of cathelicidins from vertebrate suggested that elapid and viperid cathelicidins were grouped together in the tree. Snake cathelicidins were evolutionary closely related to the neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake cathelicidins also showed a close relationship with avian fowlicidins (1-3) and chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as models for the development of novel therapeutic drugs.

  19. Comparative analysis of the venom proteome of four important Malaysian snake species

    PubMed Central

    2014-01-01

    Background Naja kaouthia, Ophiophagus hannah, Bungarus fasciatus and Calloselasma rhodostoma are four venomous snakes indigenous to Malaysia. In the present study, their proteomic profile by two-dimensional gel electrophoresis (2-DE) have been separated and compared. Results The 2-DE of venoms of the four species snake demonstrated complexity and obvious interspecies differences in proteome profiles. A total of 63 proteins were identified in the four species: C. rhodostoma – 26, N. kaouthia – 16, O. hannah – 15 and B. fasciatus – 6. Conclusions Despite the identifications of major proteins in the four snake species, a large number of protein spots from the 2-DE were unidentified even though the spots displayed high-quality MALDI-TOF-MS spectra. Those identified included phospholipase A2 proteins in all four venoms, long neurotoxins in both cobra species and the C. rhodostoma venom found with the most varied types of peptidases, i.e. metalloproteinase kistomin, halystase and L-amino acid oxidase. PMID:24593956

  20. Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2.

    PubMed

    Vulfius, Catherine A; Kasheverov, Igor E; Starkov, Vladislav G; Osipov, Alexey V; Andreeva, Tatyana V; Filkin, Sergey Yu; Gorbacheva, Elena V; Astashev, Maxim E; Tsetlin, Victor I; Utkin, Yuri N

    2014-01-01

    Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea stagnalis neurons to acetylcholine or cytisine and to inhibit α-bungarotoxin binding to nicotinic acetylcholine receptors and acetylcholine-binding proteins. Here we present the evidence that phospholipases A2 from venoms of vipers Vipera ursinii and V. nikolskii, cobra Naja kaouthia, and krait Bungarus fasciatus from different snake families suppress the acetylcholine- or cytisine-elicited currents in L. stagnalis neurons and compete with α-bungarotoxin for binding to muscle- and neuronal α7-types of nicotinic acetylcholine receptor, as well as to acetylcholine-binding proteins. As the phospholipase A2 content in venoms is quite high, under some conditions the activity found may contribute to the deleterious venom effects. The results obtained suggest that the ability to interact with nicotinic acetylcholine receptors may be a general property of snake venom phospholipases A2, which add a new target to the numerous activities of these enzymes.

  1. Trypanosoma cf. varani in an imported ball python (Python reginus) from Ghana.

    PubMed

    Sato, Hiroshi; Takano, Ai; Kawabata, Hiroki; Une, Yumi; Watanabe, Haruo; Mukhtar, Maowia M

    2009-08-01

    Peripheral blood from a ball python (Python reginus) imported from Ghana was cultured in Barbour-Stoenner-Kelly (BSK) medium for Borrelia spp. isolation, resulting in the prominent appearance of free, and clusters of, trypanosomes in a variety of morphological forms. The molecular phylogenetic characterization of these cultured trypanosomes, using the small subunit rDNA, indicated that this python was infected with a species closely related to Trypanosoma varani Wenyon, 1908, originally described in the Nile monitor lizard (Varanus niloticus) from Sudan. Furthermore, nucleotide sequences of glycosomal glyceraldehyde-3-phosphate dehydrogenase gene of both isolates showed few differences. Giemsa-stained blood smears, prepared from the infected python 8 mo after the initial observation of trypanosomes in hemoculture, contained trypomastigotes with a broad body and a short, free flagellum; these most closely resembled the original description of T. varani, or T. voltariae Macfie, 1919 recorded in a black-necked spitting cobra (Naja nigricollis) from Ghana. It is highly possible that lizards and snakes could naturally share an identical trypanosome species. Alternatively, lizards and snakes in the same region might have closely related, but distinct, Trypanosoma species as a result of sympatric speciation. From multiple viewpoints, including molecular phylogenetic analyses, reappraisal of trypanosome species from a wide range of reptiles in Africa is needed to clarify the relationship of recorded species, or to unmask unrecorded species.

  2. Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex

    PubMed Central

    Barnwal, Bhaskar; Jobichen, Chacko; Girish, Vallerinteavide Mavelli; Foo, Chun Shin; Sivaraman, J.; Kini, R. Manjunatha

    2016-01-01

    Anticoagulant therapy is used for the prevention and treatment of thromboembolic disorders. Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of Hemachatus haemachatus (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from Naja atra. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC50 of 123.8 ± 9.54 nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki’ of 84.25 ± 3.53 nM and 152.5 ± 11.32 nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95 Å resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin. PMID:27173146

  3. Inhibition of Nicotinic Acetylcholine Receptors, a Novel Facet in the Pleiotropic Activities of Snake Venom Phospholipases A2

    PubMed Central

    Vulfius, Catherine A.; Kasheverov, Igor E.; Starkov, Vladislav G.; Osipov, Alexey V.; Andreeva, Tatyana V.; Filkin, Sergey Yu.; Gorbacheva, Elena V.; Astashev, Maxim E.; Tsetlin, Victor I.; Utkin, Yuri N.

    2014-01-01

    Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea stagnalis neurons to acetylcholine or cytisine and to inhibit α-bungarotoxin binding to nicotinic acetylcholine receptors and acetylcholine-binding proteins. Here we present the evidence that phospholipases A2 from venoms of vipers Vipera ursinii and V. nikolskii, cobra Naja kaouthia, and krait Bungarus fasciatus from different snake families suppress the acetylcholine- or cytisine-elicited currents in L. stagnalis neurons and compete with α-bungarotoxin for binding to muscle- and neuronal α7-types of nicotinic acetylcholine receptor, as well as to acetylcholine-binding proteins. As the phospholipase A2 content in venoms is quite high, under some conditions the activity found may contribute to the deleterious venom effects. The results obtained suggest that the ability to interact with nicotinic acetylcholine receptors may be a general property of snake venom phospholipases A2, which add a new target to the numerous activities of these enzymes. PMID:25522251

  4. Epidemiology of snakebite in Eshowe, KwaZulu-Natal, South Africa.

    PubMed

    Blaylock, Roger

    2004-02-01

    Three hundred and thirty-three patients admitted to Eshowe Hospital with snakebite were analysed. Forty-one were non-envenomed, 282 exhibited painful progressive swelling (PPS), seven showed progressive weakness (PW), and there were three cases of minor envenomations that were unclassifiable. Offending dead venomous snakes included Naja mossambica (Mozambique spitting cobra), Bitis arietans (puff adder), Atractaspis bibronii (stiletto snake), Causus rhombeatus (common night adder) and Dendroaspis polylepis (black mamba). Most bites occurred on the leg in the wet summer months during the first three decades of the patients' lives. The majority of patients used a first-aid measure. The snake was most commonly sighted if the patient was bitten on an upper limb or above the ankle. Severe envenomation was associated with quicker arrival at hospital, and multiple bites occurred more frequently in sleeping patients. Non-envenomation following snakebites was more common in winter, in adult females, and if the patient was bitten proximally on a limb or on a hand. Patients with PPS developed bite site complications (42), compartment syndromes (4), femoral vessel entrapment (1), deep vein thrombosis (1), and respiratory complications (4). Severe swelling was associated with spring and early summer, proximal limb bites and children who were most at risk of necrosis. Fingers and hands were most prone to necrosis and permanent disability. Four patients with PW developed respiratory failure. Antivenom was administered to 12 patients, five of whom developed an acute adverse reaction. There was one death.

  5. Effects of plant lectin from cobra lily, Arisaema curvatum Kunth on development of melon fruit fly, Bactrocera cucurbitae (Coq.).

    PubMed

    Singh, Kuljinder; Kaur, Manpreet; Rup, Pushpinder J; Singh, Jatinder

    2008-11-01

    The lectin from tubers of cobra lily, Arisaema curvatum Kunth was purified by affinity chromatography using asialofetuin-linked amino activated porous silica beads. The concentration dependent effect of lectin was studied on second instar larvae (64-72 hr) of Bactrocera cucurbitae (Coq.). The treatment not only resulted in a significant reduction in the percentage pupation and emergence of the adults from treated larvae but it also prolonged the remaining larval development period. A very low LC50 value, 39 mgl(-1) of lectin was obtained on the basis of adult emergence using probit analysis. The activity of three hydrolase enzymes (esterases, acid and alkaline phosphatases), one oxidoreductase (catalase) and one group transfer enzyme (GSTs: Glutathione S-transferases) was assayed in second instar larvae under the influence of the LC50 of lectin at increasing exposure intervals (0, 24, 48 and 72 hr). The Arisaema curvatum lectin significantly decreased the activity of all the enzymes except for esterases, where the activity increased as compared to control at all exposure intervals. The decrease in pupation and emergence as well as significant suppression in the activities of two hydrolases, one oxidoreductase and one GST enzyme in treated larvae of B. cucurbitae indicated that this lectin has anti-metabolic effect on the melon fruit fly larvae.

  6. Joseph Clover and the cobra: a tale of snake envenomation and attempted resuscitation with bellows in London, 1852.

    PubMed

    Ball, C

    2010-07-01

    The Industrial Revolution saw the creation of many new jobs, but probably none more curious than that of zookeeper. The London Zoological Gardens, established for members in 1828, was opened to the general public in 1847. In 1852 the "Head Keeper in the Serpent Room", Edward Horatio Girling, spent a night farewelling a friend departing for Australia. He arrived at work in an inebriated state and was bitten on the face by a cobra that he was handling in a less than sensible manner. He was taken by cab to University College Hospital where he was resuscitated by a number of doctors, including Joseph Clover then the resident medical officer to the hospital and later to become the leading anaesthetist in London. Clover recorded this event in his diary along with the resuscitation method used. The patient eventually died but his treatment created a flurry of correspondence in the medical and lay press. Interestingly, the attempted resuscitation was with bellows, which had been abandoned by the Royal Humane Society twenty years earlier Clover records other cases of resuscitation with bellows at University College Hospital during his time as a resident medical officer there (1848 to 1853). There is a casebook belonging to Joseph Clover in the Geoffrey Kaye Museum, in Melbourne. This story is one of the many interesting stories uncovered during a study of this book and Clover's other personal papers.

  7. Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).

    PubMed

    Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J; Kini, R Manjunatha

    2010-03-12

    Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.

  8. Chemical modification of cationic groups of a novel alpha-neurotoxin (Oh-4) from king cobra (Ophiophagus hannah) venom.

    PubMed

    Lin, S R; Chi, S H; Chang, L S; Kuo, K W; Chang, C C

    1995-08-01

    The cationic groups of arginine and lysine residues in Oh-4, a novel alpha-neurotoxin from king cobra (Ophiophagus hannah) venom were subjected to modification with p-hydroxyphenylglyoxal (HPG) and trinitrobenzene sulfonate (TNBS), respectively. Monoderivatization of Arg-35, resulted in a drastic loss in neurotoxicity to 25% of the native toxin. The activity was decreased to a greater extent with the derivative extensively modified on Arg-35, -9, and -37. The Arg-35-modified derivative retained about a half of the antigenicity of the native toxin, and extensive modification on Arg-9 and Arg-37 caused a further decrease in the antigenicity of the toxin molecule. Selective trinitrophenylation (TNP-) of Lys-51 caused losses of neurotoxicity and antigenicity by 77 and 83%, respectively. These results indicate that Arg-35 and Lys-51 in Oh-4 have important roles in the neurotoxicity. In contrast to the Arg residues at 9, 35, and 37, Lys-51 plays a more critical role in the antigenicity.

  9. Solution structure of toxin b, a long neurotoxin from the venom of the king cobra (Ophiophagus hannah).

    PubMed

    Peng, S S; Kumar, T K; Jayaraman, G; Chang, C C; Yu, C

    1997-03-21

    The solution structure of toxin b, a long neurotoxin (73 amino acids and 5 disulfides) from the venom of Ophiophagus hannah (king cobra), has been determined using 1H NMR and dynamical simulated annealing techniques. The structures were calculated using 485 distance constraints and 52 dihedral angle restraints. The 21 structures that were obtained satisfy the experimental restraints and possess good nonbonded contacts. Analysis of the converged structures revealed that the protein consists of a core region from which three finger-like loops extend outwards. The regular secondary structure in toxin b includes a double and a triple stranded antiparallel beta sheet. Comparison with the solution structures of other long neurotoxins reveals that although the structure of toxin b is similar to those of previously reported long neurotoxins, clear local structural differences are observed in regions proposed to be involved in binding to the acetylcholine receptor. A positively charged cluster is found in the C-terminal tail, in Loop III, and in the tip of Loop II. This cationic cluster could be crucial for the binding of the long neurotoxins to the acetylcholine receptor.

  10. CNS and anticonvulsant activity of a non-protein toxin (KC-MMTx) isolated from King Cobra (Ophiophagus hannah) venom.

    PubMed

    Saha, A; Gomes, A; Chakravarty, A K; Biswas, A K; Giri, B; Dasgupta, S C; Gomes, A

    2006-03-01

    In the present study, King Cobra (Ophiophagus hannah) venom was subjected to TLC followed by column chromatography/HPLC to isolate and purify a non-protein toxin designated as KC-MMTx. (1)H NMR, IR and EIMS studies showed KC-MMTx likely to be a 282 D unsaturated aliphatic acid having molecular formula C18H34O2. The minimum lethal dose of KC-MMTx was 200 microg/kg (i.v.) and 350 microg/kg (i.p.) in Swiss albino male mice. It significantly increased pentobarbitone induced sleeping time and significantly decreased the body temperature of male albino mice. It provided protection against amphetamine aggregate toxicity in mice but failed to protect amphetamine stereotypy in male albino rats. KC-MMTx provided significant protection against drug (strychnine, pentylenetetrazole, yohimbine) induced convulsions in male albino mice. It increased serum Na+ and decreased serum Ca2+ significantly in male mice. MAO activity and brain neurotransmitter levels in male mice were altered significantly. Further detailed study is warranted on the CNS, anticonvulsant potential of KC-MMTx, which may lead to the development of newer therapeutic tools in the near future.

  11. Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom.

    PubMed

    He, Ying-Ying; Liu, Shu-Bai; Lee, Wen-Hui; Qian, Jin-Qiao; Zhang, Yun

    2008-10-01

    Snake venom Kunitz/BPTI members are good tools for understanding of structure-functional relationship between serine proteases and their inhibitors. A novel dual Kunitz/BPTI serine proteinase inhibitor named OH-TCI (trypsin- and chymotrypsin-dual inhibitor from Ophiophagus hannah) was isolated from king cobra venom by three chromatographic steps of gel filtration, trypsin affinity and reverse phase HPLC. OH-TCI is composed of 58 amino acid residues with a molecular mass of 6339Da. Successful expression of OH-TCI was performed as the maltose-binding fusion protein in E. coli DH5alpha. Much different from Oh11-1, the purified native and recombinant OH-TCI both had strong inhibitory activities against trypsin and chymotrypsin although the sequence identity (74.1%) between them is very high. The inhibitor constants (K(i)) of recombinant OH-TCI were 3.91 x 10(-7) and 8.46 x10(-8)M for trypsin and chymotrypsin, respectively. To our knowledge, it was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom that had equivalent trypsin and chymotrypsin inhibitory activities.

  12. Comprehensive Analysis of the COBRA-Like (COBL) Gene Family in Gossypium Identifies Two COBLs Potentially Associated with Fiber Quality

    PubMed Central

    Niu, Erli; Shang, Xiaoguang; Cheng, Chaoze; Bao, Jianghao; Zeng, Yanda; Cai, Caiping; Du, Xiongming; Guo, Wangzhen

    2015-01-01

    COBRA-Like (COBL) genes, which encode a plant-specific glycosylphosphatidylinositol (GPI) anchored protein, have been proven to be key regulators in the orientation of cell expansion and cellulose crystallinity status. Genome-wide analysis has been performed in A. thaliana, O. sativa, Z. mays and S. lycopersicum, but little in Gossypium. Here we identified 19, 18 and 33 candidate COBL genes from three sequenced cotton species, diploid cotton G. raimondii, G. arboreum and tetraploid cotton G. hirsutum acc. TM-1, respectively. These COBL members were anchored onto 10 chromosomes in G. raimondii and could be divided into two subgroups. Expression patterns of COBL genes showed highly developmental and spatial regulation in G. hirsutum acc. TM-1. Of them, GhCOBL9 and GhCOBL13 were preferentially expressed at the secondary cell wall stage of fiber development and had significantly co-upregulated expression with cellulose synthase genes GhCESA4, GhCESA7 and GhCESA8. Besides, GhCOBL9 Dt and GhCOBL13 Dt were co-localized with previously reported cotton fiber quality quantitative trait loci (QTLs) and the favorable allele types of GhCOBL9 Dt had significantly positive correlations with fiber quality traits, indicating that these two genes might play an important role in fiber development. PMID:26710066

  13. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex.

    PubMed

    Janssen, Bert J C; Gomes, Lucio; Koning, Roman I; Svergun, Dmitri I; Koster, Abraham J; Fritzinger, David C; Vogel, Carl-Wilhelm; Gros, Piet

    2009-08-19

    Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a 'loading' and 'activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics.

  14. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity.

    PubMed

    Rajagopalan, Nandhakishore; Pung, Yuh Fen; Zhu, Yi Zhun; Wong, Peter Tsun Hon; Kumar, Prakash P; Kini, R Manjunatha

    2007-11-01

    Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker.

  15. Comprehensive Analysis of the COBRA-Like (COBL) Gene Family in Gossypium Identifies Two COBLs Potentially Associated with Fiber Quality.

    PubMed

    Niu, Erli; Shang, Xiaoguang; Cheng, Chaoze; Bao, Jianghao; Zeng, Yanda; Cai, Caiping; Du, Xiongming; Guo, Wangzhen

    2015-01-01

    COBRA-Like (COBL) genes, which encode a plant-specific glycosylphosphatidylinositol (GPI) anchored protein, have been proven to be key regulators in the orientation of cell expansion and cellulose crystallinity status. Genome-wide analysis has been performed in A. thaliana, O. sativa, Z. mays and S. lycopersicum, but little in Gossypium. Here we identified 19, 18 and 33 candidate COBL genes from three sequenced cotton species, diploid cotton G. raimondii, G. arboreum and tetraploid cotton G. hirsutum acc. TM-1, respectively. These COBL members were anchored onto 10 chromosomes in G. raimondii and could be divided into two subgroups. Expression patterns of COBL genes showed highly developmental and spatial regulation in G. hirsutum acc. TM-1. Of them, GhCOBL9 and GhCOBL13 were preferentially expressed at the secondary cell wall stage of fiber development and had significantly co-upregulated expression with cellulose synthase genes GhCESA4, GhCESA7 and GhCESA8. Besides, GhCOBL9 Dt and GhCOBL13 Dt were co-localized with previously reported cotton fiber quality quantitative trait loci (QTLs) and the favorable allele types of GhCOBL9 Dt had significantly positive correlations with fiber quality traits, indicating that these two genes might play an important role in fiber development.

  16. Effect of complement depletion by cobra venom factor on fowlpox virus infection in chickens and chicken embryos.

    PubMed Central

    Ohta, H; Yoshikawa, Y; Kai, C; Yamanouchi, K; Taniguchi, H; Komine, K; Ishijima, Y; Okada, H

    1986-01-01

    The course of infection with an attenuated strain of fowlpox virus (FPV), which is known to induce antibody-independent activation of complement via the alternative pathway, was investigated in 1- to 3-day-old chickens and 14-day-old chicken embryos by treatment with cobra venom factor (CVF). CVF was found to inhibit complement activity transiently via the alternative pathway but not via the classical pathway. In chickens treated with CVF, virus growth in the skin was enhanced, and pock lesions tended to disseminate, leading to fatal infection in some birds. Histologically, an acute inflammation at an early stage of infection (within 3 days) was inhibited, and virus content in the pock lesion was increased. In chicken embryos with immature immune capacities, CVF treatment caused changes in pock morphology from clear pocks to diffuse ones, an increase in virus content in the pock, and inhibition of cell infiltration. Thus, FPV infection was aggravated in both CVF-treated chickens and chicken embryos. These results are discussed in relation to roles of complement in the elimination of virus at an early stage of FPV infection. Images PMID:3003397

  17. Implementation of the LAX-Wendroff Method in Cobra-TF for Solving Two-Phase Flow Transport Equations

    SciTech Connect

    Salko, Robert K; Wang, Dean; Ren, Kangyu

    2016-01-01

    COBRA-TF (Coolant Boiling in Rod Arrays Two Fluid), or CTF, is a subchannel code used to conduct the reactor core thermal hydraulic (T/H) solution in both standalone and coupled multi-physics applications. CTF applies the first-order upwind spatial discretization scheme for solving two-phase flow conservation equations. In this work, the second-order Lax-Wendroff (L-W) scheme has been implemented in CTF to solve the two-phase flow transport equations to improve numerical accuracy in both temporal and spatial discretization. To avoid the oscillation issue, a non-linear flux limiter VA (Van Albada) is employed for the convective terms in the transport equations. Assessments have been carried out to evaluate the performance and stability of the implemented second-order L-W scheme. It has been found that the L-W scheme performs better than the upwind scheme for the single-phase and two-phase flow problems in terms of numerical accuracy and computational efficiency.

  18. Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and cobra venom cytotoxin.

    PubMed

    Zhang, Xiu-Juan; Ke, Li-Ming; Yang, Jing; Lin, Li-Wu; Xue, En-Sheng; Wang, Yan; Yu, Li-Yun; Chen, Zhi-Kui

    2012-07-01

    Cobra venom cytotoxin (CVC) loaded in poly (lactide-co-glycolide) (PLGA) microspheres was mixed with ricin and encapsulated in a thermosensitive PLGA-PEG-PLGA hydrogel for this study. This sequential sustained-release preparation (SSRP) containing ricin and CVC could avoid burst release effect of CVC from microspheres. In addition, in SSRP, the two biotoxins have different drug release rates and antitumor mechanisms, which can be complementary to each other. Ricin has a faster release rate than CVC. It can combine with the tumor cell membrane and enter the cell, inhibiting protein synthesis within 2 weeks. Whereas CVC releases slowly in 5 weeks directly dissolving the tumor cell membrane and killing the cells which are less-sensitive to ricin. The in vivo experiments showed that intratumoral injection of SSRP could inhibit hepatocellular carcinoma growth significantly, and the tumor growth inhibition rate reached 73.5%. It appears that a new medicine preparation for cancer local treatment should be further studied for clinical applications.

  19. Initial magnetic field compression studies using gas-puff Z-pinches and thin liners on COBRA

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.; Concepcion, R. J.; Evans, M. T.; Greenly, J. B.; Hammer, D. A.; Hoyt, C. L.; Kroupp, E.; Kusse, B. R.; Maron, Y.; Novick, A. S.; Pikuz, S. A.; Qi, N.; Rondeau, G.; Rosenberg, E.; Schrafel, P. C.; Seyler, C. E.; Shelkovenko, T. C.

    2013-08-01

    This magnetic compression of cylindrical liners filled with DT gas has promise as an efficient way to achieve fusion burn using pulsed-power machines. However, to avoid rapid cooling of the fuel by transfer of heat to the liner an axial magnetic field is required. This field has to be compressed during the implosion since the thermal insulation is more demanding as the compressed DT plasma becomes hotter and its volume smaller. This compression of the magnetic field is driven both by the imploding liner and plasma. To highlight how this magnetic field compression by the plasma and liner evolves we have separately studied Z-pinch implosions generated by gas puff and liner loads. The masses of the gas puff and liner loads were adjusted to match COBRA's current rise times. Our results have shown that Ne gas-puff implosions are well described by a snowplow model where electrical currents are predominately localized to the outer surface of the imploding plasma and the magnetic field is external to the imploding plasma. Liner implosions are dominated by the plasma ablation process on the inside surface of the liner and the electrical currents and magnetic fields are advected into the inner plasma volume; the sharp radial gradient associated with the snowplow process is not present.

  20. Cost and outcome of behavioural activation versus cognitive behavioural therapy for depression (COBRA): a qualitative process evaluation

    PubMed Central

    Finning, Katie; Moore, Lucy; Ekers, David; McMillan, Dean; Farrand, Paul A; O’Mahen, Heather A; Watkins, Edward R; Wright, Kim A; Fletcher, Emily; Rhodes, Shelley; Woodhouse, Rebecca; Wray, Faye

    2017-01-01

    Objective To explore participant views on acceptability, mechanisms of change and impact of behavioural activation (BA) delivered by junior mental health workers (MHWs) versus cognitive behavioural therapy (CBT) delivered by professional psychotherapists. Design Semistructured qualitative interviews analysed using a framework approach. Participants 36 participants with major depressive disorder purposively sampled from a randomised controlled trial of BA versus CBT (the COBRA trial). Setting Primary care psychological therapies services in Devon, Durham and Leeds, UK. Results Elements of therapy considered to be beneficial included its length and regularity, the opportunity to learn and not dwelling on the past. Homework was an important, although challenging aspect of treatment. Therapists were perceived as experts who played an important role in treatment. For some participants the most important element of therapy was having someone to talk to, but for others the specific factors associated with BA and CBT were crucial, with behavioural change considered important for participants in both treatments, and cognitive change unsurprisingly discussed more by those receiving CBT. Both therapies were considered to have a positive impact on symptoms of depression and other areas of life including feelings about themselves, self-care, work and relationships. Barriers to therapy included work, family life and emotional challenges. A subset (n=2) of BA participants commented that therapy felt too simple, and MHWs could be perceived as inexperienced. Many participants saw therapy as a learning experience, providing them with tools to take away, with work on relapse prevention essential. Conclusions Despite barriers for some participants, BA and CBT were perceived to have many benefits, to have brought about cognitive and behavioural change and to produce improvements in many domains of participants’ lives. To optimise the delivery of BA, inexperienced junior MHWs should

  1. Molecular mechanism of cell death induced by king cobra (Ophiophagus hannah) venom l-amino acid oxidase.

    PubMed

    Fung, Shin Yee; Lee, Mui Li; Tan, Nget Hong

    2015-03-01

    Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Amino acid sequence and chemical modification of a novel alpha-neurotoxin (Oh-5) from king cobra (Ophiophagus hannah) venom.

    PubMed

    Lin, S R; Leu, L F; Chang, L S; Chang, C C

    1997-04-01

    A novel alpha-neurotoxin, Oh-5, was isolated from king cobra (Ophiophagus hannah) venom and purified by successive SP-Sephadex C-25 column chromatography and reversed-phase HPLC. The complete sequence of Oh-5 was determined by Edman degradation of peptide fragments generated by endopeptidases, i.e., trypsin, Saccharomyces aureus V8 protease and lysyl endopeptidase. This novel toxin comprises 72 amino acid residues with 10 cysteines. The sequence shows 89% sequence homology with Oh-4, and 60% with Toxins a and b from the same venom. The tyrosine, tryptophan, lysine and arginine residues in Oh-5 were modified with tetranitromethane (TNM), 2-nitrophenylsulfenyl (NPS) chloride, trinitrobenzene sulfonate (TNBS), and p-hydroxyphenylglyoxal (HPG), respectively. Modification of Tyr-4 or Trp-27 did not affect the lethal toxicity at all, while the Tyr-4 and 23 nitrated derivative retained about 50% of the lethality of native toxin. Selective trinitrophenylation of Lys-51 or 69 resulted in a decrease in lethality by 29%, and 50% lethality was retained after modification of Lys-2, 51, and 69. A drastic decrease in lethality to 26% was observed when both Arg-35 and 37 were modified. The neurotoxicity was further decreased when Arg-9 was additionally modified. These results suggest that the aromatic residues, Tyr-4 and Trp-27, are not crucial for the neurotoxicity, whereas the cationic residues are involved in multipoint contact between the toxin molecule and the nicotinic acetylcholine receptor (nAChR). The residues Tyr-23 and Arg-35 and 37 in the central loop of Oh-5 seem to contribute greatly to the neurotoxicity.

  3. Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy.

    PubMed

    Li, R; Chen, G; Guo, H; Wang, D W; Xie, L; Wang, S S; Wang, W Y; Xiong, Y L; Chen, S

    2006-12-01

    Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) could almost completely abrogate complement activity and successfully prevent hyperacute rejection in some xenotransplant models without any obvious toxicity. In this study we investigated whether depletion of complement by Y-CVF prevented acute humoral allograft rejection in presensitized rats thereby prolonging graft survival. Presensitization was achieved in Lewis rats by sequential grafting of three full-thickness skin pieces from Brown Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in vitro complement-dependent microcytotoxicity assay. After presensitization, each Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y-CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart beat, allograft rejection was confirmed by pathologic as well as IgG and C3 immunohistochemical examinations. The mean graft survival time was significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and immunohistochemical examination, acute humoral rejection was mainly exhibited in the control group, whereas acute cellular rejection was mainly displayed in the Y-CVF therapy group. Our study demonstrated that complement depletion by Y-CVF significantly inhibited acute humoral allograft rejection in presensitized rats. As a therapeutic immunointervention tool for complement, Y-CVF has shown potential efficacy across ABO incompatible and positive cross-match barriers.

  4. Cost and outcome of behavioural activation versus cognitive behavioural therapy for depression (COBRA): a qualitative process evaluation.

    PubMed

    Finning, Katie; Richards, David A; Moore, Lucy; Ekers, David; McMillan, Dean; Farrand, Paul A; O'Mahen, Heather A; Watkins, Edward R; Wright, Kim A; Fletcher, Emily; Rhodes, Shelley; Woodhouse, Rebecca; Wray, Faye

    2017-04-13

    To explore participant views on acceptability, mechanisms of change and impact of behavioural activation (BA) delivered by junior mental health workers (MHWs) versus cognitive behavioural therapy (CBT) delivered by professional psychotherapists. Semistructured qualitative interviews analysed using a framework approach. 36 participants with major depressive disorder purposively sampled from a randomised controlled trial of BA versus CBT (the COBRA trial). Primary care psychological therapies services in Devon, Durham and Leeds, UK. Elements of therapy considered to be beneficial included its length and regularity, the opportunity to learn and not dwelling on the past. Homework was an important, although challenging aspect of treatment. Therapists were perceived as experts who played an important role in treatment. For some participants the most important element of therapy was having someone to talk to, but for others the specific factors associated with BA and CBT were crucial, with behavioural change considered important for participants in both treatments, and cognitive change unsurprisingly discussed more by those receiving CBT. Both therapies were considered to have a positive impact on symptoms of depression and other areas of life including feelings about themselves, self-care, work and relationships. Barriers to therapy included work, family life and emotional challenges. A subset (n=2) of BA participants commented that therapy felt too simple, and MHWs could be perceived as inexperienced. Many participants saw therapy as a learning experience, providing them with tools to take away, with work on relapse prevention essential. Despite barriers for some participants, BA and CBT were perceived to have many benefits, to have brought about cognitive and behavioural change and to produce improvements in many domains of participants' lives. To optimise the delivery of BA, inexperienced junior MHWs should be supported through good quality training and ongoing

  5. Cost and outcome of behavioural activation versus cognitive behaviour therapy for depression (COBRA): study protocol for a randomised controlled trial.

    PubMed

    Rhodes, Shelley; Richards, David A; Ekers, David; McMillan, Dean; Byford, Sarah; Farrand, Paul A; Gilbody, Simon; Hollon, Steven D; Kuyken, Willem; Martell, Christopher; O'Mahen, Heather A; O'Neill, Emer; Reed, Nigel; Taylor, Rod S; Watkins, Ed R; Wright, Kim A

    2014-01-21

    Cognitive behaviour therapy (CBT) is an effective treatment for depression. However, CBT is a complex therapy that requires highly trained and qualified practitioners, and its scalability is therefore limited by the costs of training and employing sufficient therapists to meet demand. Behavioural activation (BA) is a psychological treatment for depression that may be an effective alternative to CBT and, because it is simpler, might also be delivered by less highly trained and specialised mental health workers. COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial, including clinical, economic, and process evaluations comparing CBT delivered by highly trained professional therapists to BA delivered by junior professional or para-professional mental health workers to establish whether the clinical effectiveness of BA is non-inferior to CBT and if BA is cost effective compared to CBT. Four hundred and forty patients with major depressive disorder will be recruited through screening in primary care. We will analyse for non-inferiority in per-protocol and intention-to-treat populations. Our primary outcome will be severity of depression symptoms (Patient Health Questionnaire-9) at 12 months follow-up. Secondary outcomes will be clinically significant change and severity of depression at 18 months, and anxiety (General Anxiety Disorder-7 questionnaire) and health-related quality of life (Short-Form Health Survey-36) at 12 and 18 months. Our economic evaluation will take the United Kingdom National Health Service/Personal Social Services perspective to include costs of the interventions, health and social care services used, plus productivity losses. Cost-effectiveness will explored in terms of quality-adjusted life years using the EuroQol-5D measure of health-related quality of life. The clinical and economic outcomes of this trial will provide the evidence to help policy makers, clinicians and guideline developers decide on the merits of

  6. A study of snake bite among children presenting to a paediatric ward in the main Teaching Hospital of North Central Province of Sri Lanka

    PubMed Central

    2014-01-01

    Background Snake bite is a common problem in the North Central province of Sri Lanka. Common krait (Bungarus careuleus), Ceylon krait (Bungarus ceylonicus), Cobra (Naja naja), Russell’s viper (Daboia russelii), Saw-scaled viper (Echis carinatus) and Hump-nosed pit viper (Hypnale hypnale) are the six species of venomous land snakes in Sri Lanka. A significant number of adults and children are bitten by snakes every year. However, the majority of research studies done in Sri Lanka and other countries show adults bitten by snakes and studies describing children bitten by snakes are very sparse. Methods A descriptive cross sectional study was performed in the Teaching Hospital Anuradhapura in the North Central Province of Sri Lanka from May 2010 to 2011 May to describe the characteristics associated with cases of snake bite. Results There were 24 males and 20 females. The highest numbers of bites (48%) were in the range of ages 6-12 years. The majority of the bites occurred between 6 pm to 6 am (59%).The foot was the most common bitten site (48%). Out of all the venomous bites, the Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number (44%) and Russell’s viper (Daboia ruselii) accounted for the second highest number (27%). A significant number of venomous bites occurred indoors while sleeping (22%). Antivenom serum was given to (39%) of venomous bites. Deaths occurred in (11%) of the venomous bites. Conclusions Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number of venomous bites. Majority of the bites occurred between 6 pm and 6 am. Foot was the most common bitten site. A significant number of venomous bites occurred indoor while sleeping. Antivenom serum was given to a significant number of venomous bites. Educating the public on making their houses snake proof and using a torch when going out during night time will help in the prevention of getting bitten by snakes. PMID:25073710

  7. Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes.