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LD50
Terms modified by LD50 Selected AbstractsAssessing the Potential Impact of Cane Toads on Australian SnakesCONSERVATION BIOLOGY, Issue 6 2003BEN L. PHILLIPS Anecdotal reports suggest that the invasion of toads into an area is followed by dramatic declines in the abundance of terrestrial native frog-eating predators, but quantitative studies have been restricted to nonpredator taxa or aquatic predators and have generally reported minimal impacts. Will toads substantially affect Australian snakes? Based on geographic distributions and dietary composition, we identified 49 snake taxa as potentially at risk from toads. The impact of these feral prey also depends on the snakes' ability to survive after ingesting toad toxins. Based on decrements in locomotor (swimming) performance after ingesting toxin, we estimate the LD50 of toad toxins for 10 of the at-risk snake species. Most species exhibited a similar low ability to tolerate toad toxins. Based on head widths relative to sizes of toads, we calculate that 7 of the 10 taxa could easily ingest a fatal dose of toxin in a single meal. The exceptions were two colubrid taxa (keelbacks [ Tropidonophis mairii] and slatey-grey snakes [ Stegonotus cucullatus]) with much higher resistance to toad toxins (up to 85-fold) and one elapid (swamp snakes [ Hemiaspis signata]) with low resistance but a small relative head size and thus low maximum prey size. Overall, our analysis suggests that cane toads threaten populations of approximately 30% of terrestrial Australian snake species. Resumen: Los sapos (Bufo marinus) son anuros grandes muy tóxicos que fueron introducidos a Australia en 1937. Reportes anecdóticos sugieren que la invasión de sapos a un área es seguida de declinaciones dramáticas en la abundancia de depredadores terrestres nativos que se alimentan de ranas, pero los estudios cuantitativos se han restringido a taxones no depredadores o a depredadores acuáticos y generalmente han indicado impactos mínimos. ¿Los sapos afectarán sustancialmente a las serpientes australianas? Basado en la distribución geográfica y la composición de la dieta, identificamos 49 taxones de serpientes como potencialmente en riesgo por los sapos. El impacto de estas presas también depende de la habilidad de las serpientes para sobrevivir después de ingerir toxinas, estimamos la LD50 de toxinas de sapo para 10 de las especies de serpientes "en riesgo." La mayoría de las especies presentaron la misma poca habilidad para tolerar toxinas de sapo. Tomando en cuenta la anchura del cráneo en relación al tamaño de los sapos, calculamos que 7 de las 10 especies podrían fácilmente ingerir una dosis letal en una sola comida. Las excepciones fueron dos taxones de colúbridos (Tropidonophis mairii y Stegonotus cucullatus) con mucha más resistencia (hasta 85 veces más) a toxinas de sapos y un elápido (Hemiaspis signata) con resistencia baja pero de tamaño cefálico relativamente pequeño (y por lo tanto, tamaño máximo de presa pequeño). En general, nuestro análisis sugiere que los sapos amenazan a 30% de las poblaciones de especies de serpientes terrestres de Australia aproximadamente. [source] Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulationDIABETES OBESITY & METABOLISM, Issue 11 2008R. R Ortiz-Andrade Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source] Effects of hunger level and nutrient balance on survival and acetylcholinesterase activity of dimethoate exposed wolf spidersENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2002Lars-Flemming Pedersen Abstract The influence of two nutritional factors (food quantity and quality) on the responses of a wolf spider, Pardosa prativaga (L.K.), to a high dose of the insecticide dimethoate, was investigated in a fully factorial experimental design. Spider groups with different (good and bad) nutrient balance were created by feeding them fruit flies of either high or low nutrient content for 28 days. Both groups were then split into satiated and 14 days starved subgroups. Each of these was further divided into insecticide treated and control halves. Survivorship and acetylcholinesterase (AChE) activity measured on the survivors were used as response variables. Survivorship after topical dimethoate exposure (LD50; 48 h) was influenced by spider body weight, nutrient balance, and starvation. Furthermore, AChE activity was significantly inhibited by dimethoate exposure. A significant interaction between nutrient balance, starvation, and dimethoate exposure revealed synergistic effects of starvation and nutrient imbalance on AChE inhibition by dimethoate in surviving spiders. These results show that the tolerance of non-target arthropods to dimethoate may vary depending on the nutritional history of the animal. [source] Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in miceENVIRONMENTAL TOXICOLOGY, Issue 5 2007R. Jayaraj Abstract Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that represents acute and chronic hazards to animal and human health. Identification of suitable chemprotectants against microcystin is essential considering human health hazards. In the present study, we have evaluated the protective efficacy of three flavanoids namely quercetin (200 mg/kg), silybin (400 mg/kg), and morin (400 mg/kg)] pretreatment against microcystin toxicity (0.75 LD50, 57.5 ,g/kg) in mice. Various biochemical variables were measured to study the recovery profile of protected animals at 1- and 3-days post-toxin treatment. The serum alanine amino transferase (ALT) shows 17-fold increase in MC-LR treated animals compared with control group at 1 day. The silybin and quercetin group showed a decrease in level of ALT compared with MC-LR group but still higher than control group. No significant protection was observed with aspartate aminotransaminase (AST) and lactate dehydrogenase (LDH) levels in flavanoid-treated groups at 1-day post-treatment. But at 3 days, the serum levels of AST and ALT were normalized to control values, but the serum LDH levels were still significantly higher than the control group. No significant changes were observed in glutathione peroxidase and reduced glutathione levels at both 1- and 3-day postexposure. The catalase activity shows a significant decrease in quercetin-treated animals at 3-day postexposure. The protein phosphatase was significantly inhibited in MC-LR group compared to control. The silybin pretreated group showed recovery after 1 day. At 3 days, the PPAse activity was reversed to control values in all the flavanoid-treated groups. Immunoblotting analysis showed microcystin-PPAse adduct in liver tissues of toxin-treated as well as flavanoid-treated mice even after 3 days. The results of this study show that flavanoids, quercetin, silybin, and morin could reverse the hepatotoxic effects of MC-LR in vivo. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 472,479, 2007. [source] Toxicity of oral exposure to 2,4,6-trinitrotoluene in the western fence lizard (Sceloporus occidentalis),ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2008Craig A. McFarland Abstract Contamination of the soil with the explosive 2,4,6-trinitrotoluene (TNT) has been found at military sites, many of which are habitats used by reptiles. To provide data useful in assessing ecological risk for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted with the western fence lizard (Sceloporus occidentalis). Oral median lethal dose (LD50) values for TNT in corn oil were 1,038 and 1,579 mg/kg of body weight for male and female lizards, respectively. Overt signs of toxicity included chromaturia, abdominal enlargement, and tremors. A 14-d subacute study followed in which male lizards were orally dosed with TNT (corn oil) at 0, 33, 66, 132, 263, 525, and 1,050 mg/kg of body weight each day. Clinical signs of toxicity, while similar to the LD50 study, were more subtle and noted in lizards receiving TNT amounts of at least 66 mg/kg/d. Chromaturia was an early consistent sign, often preceding the onset of adverse effects. Male lizards in the 60-d subchronic study were dosed at 0, 3, 15, 25, 35, and 45 mg/kg/d with nearly complete survival (>90%) for lizards in all treatments. Changes in food consumption and body weight were observed at 35 and 45 mg/kg/d. Alterations in hematological end points; blood chemistries (albumin, total protein, alkaline phosphatase, calcium); kidney, spleen, and liver weights; and adverse histopathology were observed in lizards exposed at 25 to 45 mg/kg/d. Testosterone concentration, sperm count, and motility were variable between treatments. Although not significant, incidences of hypospermia and testicular atrophy were observed in some individuals. Together, these data suggest a lowest-observed-adverse effect level of 25 mg/kg/d and a no-observed-adverse effect level of 15 mg/kg/d in S. occidentalis. [source] Dose-related effects following oral exposure of 2,4-dinitrotoluene on the western fence lizard, Sceloporus occidentalisENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Jamie G. Suski Abstract 2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. [source] Effects of an organophosphorous insecticide on survival, fecundity, and development of Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2006Lingling Deng Abstract The effects of an organophosphorous insecticide, methamidophos, on fecundity and development of the spider Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae) were assessed under laboratory conditions. Susceptibility of adults of both sexes to the insecticide and its influence on fecundity of females and development of offspring were investigated. At 48 h after topical application in adults, the median lethal dose (LD50) and 10% lethal dose (LD10) were 0.35 and 0.12 ,g/spider, respectively, for males and 0.52 and 0.16 ,g/spider, respectively, for females. Methamidophos had detrimental effects on fecundity of females; number of eggs per clutch, total egg mass, and clutch size decreased significantly. The hatching rate of eggs from LD10-treated females was slightly higher than the rate in the controls, but the hatching rate of eggs from LD50-treated females was lower than the rate in the controls. However, no significant differences were observed in hatching time and development time across treatments. Development time of spiderlings from LD50-treated females was significantly longer than the time in the controls, and body sizes of the first spiderlings from insecticide-treated females were larger than those in the controls. However, matured offspring were smaller than those in the controls. It was concluded that methamidophos has long-term effects on H. graminicola, and that this may affect the development of spider populations in the field. [source] Discrepancy between acute and chronic toxicity induced by imidacloprid and its metabolites in Apis melliferaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2001Séverine Suchail Abstract Imidaclopridi a systemic nitroguanidine insecticide that belongs to theneonicotinoid family. As an agonist of the acetylcholine receptor, it attacks the insect nervous system and is extremely effective against various sucking and mining pests. Oral acute and chronic toxicity of imidacloprid and its main metabolites (5-hydroxyimidacloprid, 4,5-dihydroxyimidacloprid, desnitroimidacloprid, 6-chloronicotinic acid, olefin, and urea derivative) were investigated in Apis mellifera. Acute intoxication by imidacloprid or its metabolites resulted in the rapid appearance of neurotoxicity symptoms, such as hyperresponsiveness, hyperactivity, and trembling and led to hyporesponsiveness and hypoactivity. For acute toxicity tests, bees were treated with doses of toxic compounds ranging from 1 to 1,000 ng/bee (10,10,000 ,g/kg). Acute toxicity (LD50) values of imidacloprid were about 60 ng/bee (600 ,g/kg) at 48 h and about 40 ng/bee (400 ,g/kg) at 72 and 96 h. Out of the six imidacloprid metabolites tested, only two (5-hydroxyimidacloprid and olefin) exhibited a toxicity close to that of imidacloprid. Olefin LD50 values were lower than those of imidacloprid. The 5-hydroxyimidacloprid showed a lower toxicity than imidacloprid with a LD50 four to six times higher than that of imidacloprid. Urea also appeared as a compound of nonnegligible toxicity by eliciting close to 40% mortality at 1,000 ng/bee (10,000 ,g/kg). However, no significant toxicity was observed with 4,5-dihydroxyimidacloprid, 6-chloronicotinic acid, and desnitroimidacloprid in the range of doses tested. To test chronic toxicity, worker bees were fed sucrose solutions containing 0.1, 1, and 10 ,g/L of imidacloprid and its metabolites for 10 d. Fifty percent mortality was reached at approximately 8 d. Hence, considering that sucrose syrup was consumed at the mean rate of 12 ,l/d and per bee, after an 8-d period the cumulated doses were approximately 0.01, 0.1, and 1 ng/bee (0.1, 1, and 10 ,g/kg). Thus, all tested compounds were toxic at doses 30 to 3,000 (olefin), 60 to 6,000 (imidacloprid), 200 to 20,000 (5-OH-imidacloprid), and >1,000 to 100,000 (remaining metabolites) times lower than those required to produce the same effect in acute intoxication studies. For all products tested, bee mortality was induced only 72 h after the onset of intoxication. [source] Toxic responses of medaka, D-rR strain, to polychlorinatednaphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessmentENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Sergio A. Villalobos Abstract Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlo-rinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3,30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ± 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments. [source] Hyperefficient PrPSc amplification of mouse-adapted BSE and scrapie strain by protein misfolding cyclic amplification techniqueFEBS JOURNAL, Issue 10 2009Aiko Fujihara Abnormal forms of prion protein (PrPSc) accumulate via structural conversion of normal PrP (PrPC) in the progression of transmissible spongiform encephalopathy. Under cell-free conditions, the process can be efficiently replicated using in vitro PrPSc amplification methods, including protein misfolding cyclic amplification. These methods enable ultrasensitive detection of PrPSc; however, there remain difficulties in utilizing them in practice. For example, to date, several rounds of protein misfolding cyclic amplification have been necessary to reach maximal sensitivity, which not only take several weeks, but also result in an increased risk of contamination. In this study, we sought to further promote the rate of PrPSc amplification in the protein misfolding cyclic amplification technique using mouse transmissible spongiform encephalopathy models infected with either mouse-adapted bovine spongiform encephalopathy or mouse-adapted scrapie, Chandler strain. Here, we demonstrate that appropriate regulation of sonication dramatically accelerates PrPSc amplification in both strains. In fact, we reached maximum sensitivity, allowing the ultrasensitive detection of < 1 LD50 of PrPSc in the diluted brain homogenates, after only one or two reaction rounds, and in addition, we detected PrPSc in the plasma of mouse-adapted bovine spongiform encephalopathy-infected mice. We believe that these results will advance the establishment of a fast, ultrasensitive diagnostic test for transmissible spongiform encephalopathies. [source] Domain V of m-calpain shows the potential to form an oblique-orientated ,-helix, which may modulate the enzyme's activity via interactions with anionic lipidFEBS JOURNAL, Issue 22 2002Klaus Brandenburg The activity of m-calpain, a heterodimeric, Ca2+ -dependent cysteine protease appears to be modulated by membrane interactions involving oblique-orientated ,-helix formation by a segment, GTAMRILGGVI, in the protein's smaller subunit. Here, graphical and hydrophobic moment-based analyses predicted that this segment may form an ,-helix with strong structural resemblance to the influenza virus peptide, HA2, a known oblique-orientated ,-helix former. Fourier transform infrared spectroscopy showed that a peptide homologue of the GTAMRILGGVI segment, VP1, adopted low levels of ,-helical structure (, 20%) in the presence of zwitterionic lipid and induced a minor decrease (3 °C) in the gel to liquid-crystalline phase transition temperature, TC, of the hydrocarbon chains of zwitterionic membranes, suggesting interaction with the lipid headgroup region. In contrast, VP1 adopted high levels of ,-helical structure (65%) in the presence of anionic lipid, induced a large increase (10 °C) in the TC of anionic membranes, and showed high levels of anionic lipid monolayer penetration (,SP = 5.5 mN·m,1), suggesting deep levels of membrane penetration. VP1 showed strong haemolytic ability (LD50 = 1.45 mm), but in the presence of ionic agents, this ability, and that of VP1 to penetrate anionic lipid monolayers, was greatly reduced. In combination, our results suggest that m-calpain domain V may penetrate membranes via the adoption of an oblique-orientated ,-helix and electrostatic interactions. We speculate that these interactions may involve snorkelling by an arginine residue located in the polar face of this ,-helix. [source] Effects of ultraviolet radiation on the eggs of landlocked Galaxias maculatus (Galaxiidae, Pisces) in northwestern PatagoniaFRESHWATER BIOLOGY, Issue 3 2000M. Battini Summary 1Ultraviolet radiation (UVR) damages early life stages of several fish species. Galaxias maculatus is a small catadromous fish, with landlocked forms occurring in many lakes within the Nahuel Huapi National Park (Patagonia, Argentina). In this work, the vulnerability of G. maculatus eggs exposed to both natural and artificial UVR was investigated in relation to water transparency. 2Field experiments were performed in two lakes differing in UVR attenuation. Galaxias maculatus eggs were exposed to in situ levels of UVR in quartz tubes incubated at various depths. For laboratory experiments, the eggs were exposed to five levels of artificial UVB radiation. 3Exposure to natural UVR causes various degrees of egg mortality depending on water transparency and incubation depth. In the less transparent lake (Kd320 = 3.08 m -1), almost complete mortality was observed near the surface. At a depth of 43 cm the observed mortality was only 22%, but was still significantly different from the dark control. In the most transparent lake (Kd320 = 0.438 m -1), almost total mortality was observed in tubes incubated at 2.56 m or shallower. A gradual decline in mortality was recorded from that depth to 3.78 m where the values approached those in the dark control treatments. 4A monotonic relationship between mortality and UV exposure could be observed both in field and laboratory experiments. Using the results from field incubations, a LD50 of 2.5 J cm -2 nm -1 was estimated. In a few mountain lakes, this value would be exceeded even if the eggs were laid at the maximum depth of the lake. Thus UVR seems a sufficient cause to explain the absence of G. maculatus populations in some mountain lakes. For most lakes, however, UVR is probably one of several important environmental factors, which together determine the habitat suitability. [source] A QSAR analysis of toxicity of Aconitum alkaloidsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Angélica M. Bello-Ramírez Abstract Biological activity of Aconitum alkaloids may be related to their toxicity rather than to a specific pharmacological action. A Quantitative structure-activity relationships (QSAR) analysis was performed on the following two groups of alkaloids: compounds with an aroyl/aroyloxy group at R14 position (yunaconitine, bulleyaconitine, aconitine, beiwutine, nagarine, 3-acetyl aconitine, and penduline), and compounds with the aroyloxy group at R4 position (N -deacetyllappaconitine, lappaconitine, ranaconitine, N -deacetylfinaconitine, N -deacetylranaconitine). The LD50 (,mol/kg) of the 12 alkaloids were obtained from the literature. LD50 was significantly lower in group 1 than in group 2. The steric and core,core repulsion energies were significantly higher in group 1. The total energy and heat of formation and electronic energies were significantly lower in group 1. The reactivity index of N, C1,, C4, and C6, were similar between groups. The reactivity index of C2, was significantly higher and the reactivity index of C3, and C5, were significantly lower in group 1. Log P and pKa were similar between groups. Molecular weight was significantly higher in group 1. A significant linear relationship was observed between log LD50 and either analgesic log ED50 or local anesthetic log ED50. The LD50/analgesic ED50 obtained from average values was 5.9 for group 1 and 5.0 for group 2. However, the LD50/local anesthetic ED50 was 40.4 and 318, respectively. The study supports that the analgesic effects of these alkaloids are secondary to their toxic effects whereas alkaloids from group 2 are susceptible to be further studied as local anesthetic agents. [source] Preparation, antimicrobial activity, and toxicity of 2-amino-4-arylthiazole derivativesHETEROATOM CHEMISTRY, Issue 4 2006Pedro Morales-Bonilla Seven 2-amino-4-aryl-1,3-thiazoles (1a,g) and their corresponding 2-aminoacetyl (2a,g) and 2-aminoacetyl-5-bromo (3a,g) derivatives were synthesized and tested in vitro against 11 reference strains, three Gram-positive and four Gram-negative bacteria, two yeasts, and two moulds. Toxicity of the compounds was also evaluated using the brine shrimp test. Compounds 1a, 1b, 1e,g, and 3b showed moderate antimicrobial activity at different concentrations. The results indicated that acetylation of the amino group and bromination at position 5 of the thiazole moiety cause lost of activity. Compounds 1a, 1e, and 1f showed toxicity to brine shrimp nauplii below 10 ppm. Most other compounds showed moderate toxicity, LD50 above 100 ppm. Structures of all compounds were confirmed by NMR and MS data. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:254,260, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20182 [source] An evaluation of garlic lectin as an alternative carrier domain for insecticidal fusion proteinsINSECT SCIENCE, Issue 6 2008Elaine Fitches Abstract The mannose-binding lectin GNA (snowdrop lectin) is used as a "carrier" domain in insecticidal fusion proteins which cross the insect gut after oral ingestion. A similar lectin from garlic bulb, ASAII, has been evaluated as an alternative "carrier". Recombinant ASAII delivered orally to larvae of cabbage moth (Mamestra brassica; Lepidoptera) was subsequently detected in haemolymph, demonstrating transport. Fusion proteins comprising an insect neurotoxin, ButaIT (Buthus tamulus insecticidal toxin; red scorpion toxin) linked to the C-terminal region of ASAII or GNA were produced as recombinant proteins (GNA/ButaIT and ASA/ButaIT) by expression in Pichia pastoris. In both cases the C-terminal sequence of the lectin was truncated to avoid post-translational proteolysis. The GNA-containing fusion protein was toxic by injection to cabbage moth larvae (LD50, 250 ,g/g), and when fed had a negative effect on survival and growth. It also decreased the survival of cereal aphids (Sitobion avenae; Homoptera) from neonate to adult by >70% when fed. In contrast, the ASA-ButaIT fusion protein was non-toxic to aphids, and had no effect on lepidopteran larvae, either when injected or when fed. However, intact ASA-ButaIT fusion protein was present in the haemolymph of cabbage moth larvae following ingestion, showing that transport of the fusion had occurred. The stabilities of GNA/ButaIT and ASA/ButaIT to proteolysis in vivo after injection or ingestion differed, and this may be a factor in determining insecticidal activities. [source] Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus)INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2008Mark S. Lever Summary Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD50 for B. anthracis Ames strain in the marmoset was 1.47 × 103 colony-forming units, compared with a published LD50 of 5.5 × 104 spores in the rhesus macaque and 4.13 × 103 spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection. [source] Evidence of pesticide resistance in medium-sized mammalian pests: a case study with 1080 poison and Australian rabbitsJOURNAL OF APPLIED ECOLOGY, Issue 4 2002Laurie E. Twigg Summary 1Toxicant-resistance is a potential, or very real, problem with many pest-control programmes world-wide. However, apart from rodents, pesticide-resistance has not been well documented in vertebrates. We assessed the potential impact of developing resistance to 1080 in rabbit populations with differing levels of historical exposure to 1080-baiting programmes in south-western Australia. 2The sensitivity to 1080 of three out of the four populations of rabbits Oryctolagus cuniculus examined had decreased significantly since Australian rabbits were last tested over 25 years ago. The lethal dose50 (LD50) values for these populations, as determined from formal toxicity trials, ranged from 0·744 to 1·019 mg pure 1080 kg,1, and were significantly greater (P < 0·05) than the previously reported values for Australian rabbits (LD50 range 0·34,0·46 mg pure 1080 kg,1). The LD50 value for the fourth population (0·584 mg pure 1080 kg,1), which has had the least exposure to 1080, did not differ from that reported previously (P > 0·05). 3The lethal dose99 (LD99) values for the four rabbit populations tested ranged from 1·181 to 1·666 mg pure 1080 kg,1, and suggested that, theoretically, all rabbits should be killed during routine baiting campaigns provided that there is no loss of active ingredient from the bait. In reality, the efficacy of 1080 poison bait laid in trails for controlling free-ranging rabbits was reduced in those populations where rabbits had decreased sensitivity to 1080. Mean reductions in rabbit numbers 7,9 days after trail baiting of resistant and sensitive populations ranged from 51·2% to 65·2%, and from 76·4% to 76·5%, respectively. 4These findings suggest that genetic resistance to 1080 is developing in at least some populations of Australian rabbits. This has world-wide implications for agricultural protection and wildlife conservation programmes that rely on a 1080-baiting strategy for reducing the impact of vertebrate pests. [source] Effects of azadirachtin and of simpler epoxy-alcohols on survival and behaviour of Galleria mellonella (Lepidoptera)JOURNAL OF APPLIED ENTOMOLOGY, Issue 7 2007C. Charbonneau Abstract:, Investigations into the toxicity of three simpler molecules based on the epoxy-alcohol fragment of azadirachtin have revealed insecticidal activity on the greater wax moth Galleria mellonella L. larvae. The simpler epoxy-alcohols doses giving 50% mortalities (LD50) for G. mellonella larvae were in the increasing order from glycidol (0.022 mg/g), 4,5-epoxy-2-pentanol (0.068 mg/g) and finally, glycerol diglycidyl ether (0.147 mg/g). The three epoxy-alcohols exhibited higher insecticidal activity when compared with the commercial neem product for which the dose giving 50% mortalities was 10.6 mg/g and to azadirachtin that killed the larvae only by injection (dose of 0.20 mg/g of larvae body weight). Our results confirm the importance of the epoxy-alcohol junction between the two parts of the azadirachtin molecule for the biological activity. Other effects of the epoxy-alcohols tested were blackening of larvae and morphological deformities of some adults hatching. In future, the molecules should be complexified (degree of ramification, length of chain and presence of bulky ramified substituent) to obtain an insecticide as toxic for insects only and environmentally safe as azadirachtin but more stable, and their physiological activities on insect's tissues and cells should be studied. [source] Effect of the antimicrobial peptide indolicidin on the green peach aphid Myzus persicae (Sulzer)JOURNAL OF APPLIED ENTOMOLOGY, Issue 2 2007R. R. Le-Feuvre Abstract:, The green-peach aphid, Myzus persicae (Sulzer) (Hem., Aphididae), is a major agricultural pest of a wide range of host plants, causing damage by feeding and indirectly by transmitting viruses. In this study we tested the effect of the antimicrobial peptide indolicidin on M. persicae survival and on its essential bacterial endosymbionts. Artificial diet bioassays showed a significant dose-dependent lethal response of indolicidin on M. persicae survival (LD50 of 209 ± 60 ,g/ml). Histological analysis of indolicidin-treated aphids revealed a lower number of distorted mycetocytes, whereas control aphids showed abundant number of rounded and filled mycetocytes. These results suggest that aphid survival could be affected via reduction of its endosymbionts. Thus, aphid control based on antimicrobial substances against endosymbionts could be a promising strategy that needs to be further explored. [source] Bioefficacy and mode of action of rocaglamide from Aglaia elaeagnoidea (syn. A. roxburghiana) against gram pod borer, Helicoverpa armigera (Hübner)JOURNAL OF APPLIED ENTOMOLOGY, Issue 3 2004O. Koul Abstract:, Rocaglamide, a highly substituted benzofuran, was isolated and identified as the main biologically active component in Aglaia elaeagnoidea (syn. A. roxburghiana) for gram pod borer Helicoverpa armigera (Hübner). Addition of rocaglamide to an artificial diet retarded the growth of neonate larvae in a dose-dependent manner with EC50 values of 0.76 p.p.m. These values compared favourably with azadirachtin (EC50 = 0.23 p.p.m.). However, azadirachtin was apparently more potent than rocaglamide in inducing growth inhibition via oral administration to these first stadium larvae. The candidate compound was found to have LD50 and LD95 values of 0.40 and 1.02 ,g per larva, respectively, in topical application against third instar larvae 96 h post-treatment. However, these values for azadirachtin were 8.16 and 25.8 ,g per larva for the same period. This shows that azadirachtin was less effective against third instar H. armigera larvae in inducing acute toxicity via topical treatment in comparison with rocaglamide. However, severe morphological larval deformities were observed in such azadirachtin-treated larvae during the process of ecdysis. The cytotoxic nature of rocaglamide was established by evaluating dietary utilization and the results did not implicate any antifeedant effect but the toxicity-mediated effect due to reduced efficiency of conversion of ingested food. It was obvious that feeding deterrence is not the primary mode of action but a centrally mediated effect, which could be due to the induced cytotoxicity at non-specific cellular levels. [source] Compatibility of a natural enemy, Coleomegilla maculata lengi (Col., Coccinellidae) and four insecticides used against the Colorado potato beetle (Col., Chrysomelidae)JOURNAL OF APPLIED ENTOMOLOGY, Issue 3 2004É. Lucas Abstract:, ,The toxicity of four insecticides used to control the Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), imidacloprid (Admire®), cryolite (Kryocide®), cyromazine (Trigard®), and Bacillus thuringiensis var. tenebrionis (Novodor®), to one of its natural enemies, the 12-spotted lady beetle, Coleomegilla maculata lengi Timberlake (Coleoptera: Coccinellidae) was determined in the laboratory. Toxicity assays against C. maculata adults and larvae consisted of (1) topical applications and (2) exposures to treated foliage and prey, using concentrations up to 10 times the manufacturer's recommendations. Over a 6-day period, cyromazine (insect growth regulator) and B. t. var. tenebrionis (microbial insecticide) had no lethal effects on first and third instars C. maculata. For both larval and adult stages, cryolite (inorganic insecticide) caused very low predator mortality when topically applied and moderate mortality when ingested through contaminated eggs of Colorado potato beetles. Imidacloprid (systemic organic insecticide) was highly toxic to adult and larval C. maculata. Its estimated LD50 at 6 days following treatment, corresponded to 0.02,0.09 times the recommended field concentration, depending on the developmental stage and mode of contamination. These results indicate that integrated pest management programmes for Colorado potato beetles using imidacloprid or, to a lesser degree, cryolite, would be detrimental to C. maculata. Cyromazine and B. t. var. tenebrionis seem to present a better compatibility with the protection of C. maculata populations. [source] Enhancement of the efficacy of erythromycin in multiple antibiotic-resistant gram-negative bacterial pathogensJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2008S. Saha Abstract Aims:, To improve the efficacy of erythromycin, a hydrophobic antibiotic, against multiple antibiotic-resistant gram-negative bacterial pathogens by enhancing their outer membrane permeability. Methods and Results:, Fifty-one nonrepeat gram-negative bacterial pathogens of various genera, resistant to multiple antibiotics, including erythromycin, were selected by disc agar diffusion tests. The amphiphilic cationic steroid antibiotic, Ceragenin CSA-13, a potent permeabilizer of bacterial outer membranes, reduced the minimum inhibitory concentration of erythromycin in 92% of the bacterial pathogens selected for the test, when supplemented with erythromycin. A synergistic effect of Ceragenin CSA-13 and erythromycin in combination was also observed. Spectrofluorimetric study confirmed that Ceragenin CSA-13 acts by depolarizing the bacterial outer membrane. The toxicity of Ceragenin CSA-13 was evaluated to be insignificant by measuring ,median lethal dose' (LD50) on mouse model. Conclusions:, Ceragenin CSA-13 may be useful as an agent to make erythromycin effective against infections caused by multiple antibiotic resistant gram-negative bacteria. Significance and Impact of the Study:, The outcome of the study suggests erythromycin,Ceragenin combination as a new approach to overcome the problem associated with the rapid emergence of multi-drug-resistant pathogens. The insignificant toxicity of Ceragenin CSA-13, as found, supports the possibility of the application of this compound for human therapeutics. [source] Antibacterial activity of plant extracts from northwestern ArgentinaJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007J.R. Soberón Abstract Aims:, To determine the antibacterial and cytotoxic activities of aqueous and ethanolic extracts of northwestern Argentinian plants used in folk medicine. To compare the mentioned activities with those of five commercial antibiotics. To identify the compounds responsible for the antibacterial activity. Methods and Results:, Plant extracts were prepared according to traditional uses in northwestern Argentina. Antibacterial activity was assayed by agar dilution in Petri dishes and broth dilution in 96-well plates. Lethal dose 50 (LD50) was determined by the Artemia salina assay. Phytochemical analysis was performed by sample adsorption on silica gel, thin-layer chromatography (TLC), bioautography and UV-visible spectra. The results showed that Tripodanthus acutifolius aqueous extracts have lower minimal inhibitory concentrations (MIC) (502 and 506 ,g of extracted material (EM) per ml for infusion and decoction, respectively) than cefotaxim MIC (640 ,g ml,1) against Acinetobacterfreundii (303). These data were lower than their LD50. Tripodanthus acutifolius tincture showed lower MIC (110 ,g of EM per ml) and minimal bactericidal concentration (MBC) (220 ,g of EM per ml) than cefotaxim (MIC and MBC of 320 ,g ml,1) for Pseudomonasaeruginosa. This extract also showed a MIC/MBC of 110/220 ,g of EM per ml, lower than oxacillin (MIC/MBC of 160/220 ,g ml,1) for Staphylococcus aureus (ATCC 25923). The cytotoxicity of all extracts were compared with that of commercial antibiotics. Rutin (3,3,,4,,5,7-pentahydroxyflavone 3- , -rhamnosilglucoside), iso -quercitrin (3,3,,4,,5,7-pentahydroxyflavone 3- , -glucoside) and a terpene would be partially responsible for the antibacterial activity of T. acutifolius infusion. Conclusions:,Tripodanthus acutifolius extracts had the ability to inhibit bacterial growth. The antibacterial activity differs with the applied extractive method, and it could be partially attributed to glycoflavonoids. This paper contributes to the knowledge of antibacterial capacity of plants from northwestern Argentina. Significance and Impact of the Study:, These antibacterial activities support further studies to discover new chemical structures that can contribute to alleviate or cure some illnesses. [source] Survival of spores of Rhizopus stolonifer, Aspergillus niger, Botrytis cinerea and Alternaria alternata after exposure to ethanol solutions at various temperaturesJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2004F. Mlikota Gabler Abstract Aims:, To quantify and model the toxicity of brief exposures of spores of Rhizopus stolonifer, Aspergillus niger, Botrytis cinerea and Alternaria alternata to heated, aqueous ethanol solutions. These fungi are common postharvest decay pathogens of fresh grapes and other produce. Sanitation of produce reduces postharvest losses caused by these and other pathogens. Methods and Results:, Spores of the fungi were exposed to solutions containing up to 30% (v/v) ethanol at 25,50°C for 30 s, then their survival was determined by germination on semisolid media. Logistical, second-order surface-response models were prepared for each fungus. Subinhibitory ethanol concentrations at ambient temperatures became inhibitory when heated at temperatures much lower than those that cause thermal destruction of the spores by water alone. At 40°C, the estimated ethanol concentrations that inhibited the germination of 50% (LD50) of the spores of B. cinerea, A. alternata, A. niger and R. stolonifer were 9·7, 13·5, 19·6 and 20·6%, respectively. Conclusions:, Ethanol and heat combinations were synergistic. Control of spores of these fungi could be accomplished with much lower temperatures and ethanol concentrations when combined compared with either used alone. Botrytis cinerea and A. alternata were less resistant to the combination than A. niger or R. stolonifer. [source] Minireview: does in-vitro testing of oximes help predict their in-vivo action after paraoxon exposure?JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009D. E. Lorke Abstract K-oximes have recently been developed in the search for efficacious broad-band reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OPC). Before clinical use, their toxicity and efficacy need to be assessed, and there is clear demand for simple in vitro tests that can predict in vivo performance. This article summarizes our in vitro data obtained for conventional and experimental oximes in human and rat blood exposed to the OPC paraoxon and correlates them with our in vivo results. The intrinsic AChE inhibitory activity of oximes, as reflected by their in vitro IC50, is strongly correlated with their LD50 (rat): oximes with a high IC50 (K-27, K-48, pralidoxime and obidoxime) also show a high LD50 and are thus relatively non-toxic, whereas oximes K-105, K-108 and K-113 have a low IC50, a low LD50 and are far more toxic. The IC50 is also correlated with the in vivo capacity to protect from paraoxon-induced mortality: oximes with a higher IC50 reduce the relative risk of death more. In contrast, the protective ability as assessed in vitro by the slope of the IC50 shift (tan,), is not correlated with in vivo protection from paraoxon-induced mortality: the best in vivo protectors (K-27 and K-48) show a much lower tan, value (around 2) than K-110 and K-113 (tan, around 10), which hardly reduce the relative risk of death after paraoxon exposure. The partition coefficient logP of the individual oximes is inversely correlated with their IC50 and with their LD50 and is therefore an indicator of toxicity: strongly hydrophilic oximes tend to be less toxic than less hydrophilic ones. These data highlight the good predictive value of in vitro IC50 testing for in vivo toxicity and the limited practical significance of in vitro assessment of protective potency. Copyright © 2009 John Wiley & Sons, Ltd. [source] Vinylic telluride derivatives as promising pharmacological compounds with low toxicityJOURNAL OF APPLIED TOXICOLOGY, Issue 7 2008V. C. Borges Abstract The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting , -ALA-D activity (, -aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 µmol kg,1, respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic , -ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated , -ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Activation of mitogen activated protein kinase (MAPK) pathways after soman poisoning in rat cerebellar granule neuronsJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008J. Pejchal Abstract The expression of activated p38 mitogen-activated protein kinase (MAPK) and activated MAPK transcription factors c-jun, c-myc and elk-1 were examined in rat cerebellum after soman poisoning to determine the pathogenetic mechanism of the non-specific long-term effects of nerve agents. Male Wistar rats were poisoned by intramuscular administration of soman at a dose 60 µg kg,1 (70% LD50) and samples were taken 1, 7 and 14 days after poisoning, immunohistochemically stained and p-p38MAPK, p-c-jun, p-c-myc and p-elk-1 expressions were measured using image analysis. Control groups were administered with saline instead of soman. The expression of activated p38MAPK and c-myc increased 14 days after soman poisoning while c-jun and elk-1 expressions remained unchanged 1, 7 and 14 days after soman poisoning. Delayed activation of p38 MAPK and its targets might be involved in the pathogenetic mechanism of the long-term neurophysiological toxic effects of nerve agents. Copyright © 2007 John Wiley & Sons, Ltd. [source] Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamideJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2007Sergey V. Kuznetsov Abstract A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD50 and subcutaneously to infant rats at LD100 or 1/10 LD50. Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks. Copyright © 2007 John Wiley & Sons, Ltd. [source] Phenotypic, serological and genetic characterization of Pseudomonas anguilliseptica strains isolated from cod, Gadus morhua L., in northern EuropeJOURNAL OF FISH DISEASES, Issue 11 2007S Balboa Abstract The biochemical, serological and genetic characteristics of six strains of Pseudomonas anguilliseptica isolated from cod, Gadus morhua, in Scotland were compared to well characterized isolates of this same bacterial species but of different origin. Biochemical and physiological analyses showed that this group of isolates was highly homogeneous, their characteristics matching previous descriptions of the pathogen. Similar results were obtained for the six cod isolates in the serological assays, all of them belonging to the serotype O1. Marked homogeneity was observed also in the genetic study, analysed by means of RAPD, ERIC-PCR and REP-PCR procedures, showing that they were similar to isolates from gilthead seabream, Sparus aurata, black spot seabream, Pagellus bogaraveo, and turbot, Psetta maxima. Virulence assays demonstrated that the cod isolates were highly pathogenic for turbot and sole, Solea senegalensis, with LD50 between 7.6 × 104 and 5 × 107 bacterial cells per fish. [source] Atypical Aeromonas salmonicida infection in naturally and experimentally infected cod, Gadus morhua L.JOURNAL OF FISH DISEASES, Issue 10 2002B Magnadóttir Abstract Cod, Gadus morhua L., of wild origin, were reared at different temperatures for 12 months. During this period, moribund and newly dead fish were examined and samples collected for bacteriology and histopathology. Atypical Aeromonas salmonicida was isolated from 10 individuals reared at or above 7 °C. The isolates were homogeneous with respect to biochemical and antibiogram characters and similar to the ssp. achromogenes National Collection of Industrial and Marine Bacteria, UK, type strain 1110 and reference strains that have been isolated from salmonids and haddock in Iceland. Histopathological analysis of the naturally infected cod showed typical ulceration associated with atypical A. salmonicida infection and also widespread granulomatous formations. One-year-old cod of farmed origin, kept at 9 °C, received intraperitoneal or intramuscular injection with different doses of atypical A. salmonicida, isolated from the above wild cod. Mortalities were monitored for 28 days and the LD50 calculated. The route of bacterial injection influenced the mortality rate and LD50 value and affected, to some extent, the pathological changes observed and humoral immune parameters. Pathological changes, including haemorrhage, early stages of granuloma formation and necrotic changes, were seen in several organs. Infection appeared to induce non-specific antibody activity against trinitrophenyl (TNP)-haptenated protein and may have activated the complement system. Specific antibody response against atypical A. salmonicida was not detected. [source] | |||||||||||||||||||||||||||||||