bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for behavioral teratogenicity in humans
Authors: Nelson B. K. 
Published: October 2006

AbstractCentral to both the scientific development of behavioral teratology and the attention paid to this field as an important area of study is establishing that prenatal exposure of pregnant females to exogenous agents leads to neurobehavioral disorders in their offspring. This tenet may not be questioned by the majority of toxicologists, but others may not be convinced. This paper serves as a brief review of the accumulated evidence that prenatal exposure to a number of drugs and environmental/industrial agents produces behavioral disorders in human infants.
Effects of short‐term oral dosing of polychlorotrifluoroethylene (polyCTFE) on the rhesus monkey
Authors: Jones Christopher E. , Ballinger Michael B. , Mattie David R. , Delraso Nicholas J. , Seckel Constance , Vinegar Allen 
Published: October 2006

AbstractPolychlorotrifluoroethylene (polyCTFE—primarily oligomers with 3–4 monomer units), a non‐flammable hydraulic fluid for aircraft, was given daily for 15 days by oral gavage to four Rhesus monkeys at a concentration of 0.725 g kg−1. The administered dose was at a level that had caused toxicity in rats. Steady‐state blood and liver concentrations reached were the same in both species. In monkeys, polyCTFE did not cause the electrolyte, serum protein, liver enzyme and anemic disturbances previously seen in rats. Liver sections taken at 15 days, analyzed for palmitoyl Co‐A beta‐oxidation rates or by electron microscopy, showed no significant indication of peroxisomal proliferation. An increased blood urea nitrogen (BUN) at 15 days was the only clinical pathological abnormality seen in both monkeys and rats. Previously unobserved effects were increased triglycerides and glycogen depletion.
Neurotoxic esterase activity in brain, spinal cord and platelets of certain birds and mammals
Authors: Husain K. , Mirza M. A. , Matin M. A. 
Published: October 2006

AbstractThe level of neurotoxic esterase in brain, spinal cord and platelets of certain birds and mammals has been determined. The enzyme activity for the birds was maximal in hens and for the mammals was maximal in rats. The activity decreased progressively in the cerebral cortex, corpus striatum, spinal cord and blood platelets of the birds as well as the mammals. The difference in the susceptibility of birds and mammals to organophosphate‐induced delayed neurotoxicity may be related to differences in the relative concentrations of the enzyme in the different species.
Evaluation of potential chemoprotectants against microcystin‐LR hepatotoxicity in mice
Authors: Hermansky S. J. , Stohs S. J. , Eldeen Z. M. , Roche V. F. , Mereish K. A. 
Published: October 2006

AbstractMicrocystin‐LR (MCLR) is a potent cyclic heptapeptide hepatotoxin produced by the blue‐green algae, Microcystis aeruginosa. Toxic blooms of this cyanobacteria have been reported throughout the temperate world. In spite of the potential economic loss and health hazard posed by this toxin, few studies on the development of an antidote have been conducted. Thus, a number of biologically active compounds were tested in mice for effectiveness in preventing the toxicity of a lethal dose of MCLR (100 μg kg−1). Efficacy was evaluated based upon the percentage of surviving mice, time to death and serum lactate dehydrogenase activity 45 min after treatment with the toxin. The biologically active compounds were separated into groups based upon proposed mechanisms of action. Enzyme induction by phenobarbital but not by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) resulted in partial protection against toxicity. Calcium channel blockers, free‐radical scavengers and water‐soluble antioxidants produced little protection against toxicity. The membrane‐active antioxidants vitamin E and silymarin, as well as glutathione and the monoethyl ester of glutathione, produced significant protection from lethality. Rifampin and cyclosporin‐A, both immunosuppressive and membrane‐active agents, which also block the bile acid uptake system of hepatocytes, produced complete protection from the toxicity of MCLR. Thus, lipophilic antioxidants provide partial protection against MCLR toxicity while cyclosporin‐A and rifampin are highly effective and potentially useful antidotes. The toxicity of MCLR may depend upon stimulation of the immune system and may be mediated by membrane alterations.
Interactions between verapamil and metoprolol in the developing chick embryo heart
Authors: Nishikawa Toshio , Kasajima Takeshi , Kanai Takao 
Published: October 2006

AbstractA calcium blocking agent, verapamil, and a β1‐adrenoreceptor blocking agent, metoprolol, were administered alone or in combination to 4‐day‐old chick embryos (Hamburger‐Hamilton developmental stage 24). Embryos co‐administered with verapamil (0.05 nmol) and metoprolol (0.1 or 1.0 nmol), neither of which alone caused significant teratogenicity, showed cardiovascular malformations, including ventricular septal defects associated with or without dextroposition of the aorta (overriding aorta). The alteration of calcium movement into the myocyte and/or the haemodynamic change following impaired calcium transport are suggested to be possible causative factors.
Cardiotonic drugs inhibit purified mammalian acetylcholinesterase
Authors: Hanke D. W. , Nelson M. E. , Baskin S. I. 
Published: October 2006

AbstractOxime‐ and non‐oxime‐related drugs, as well as cardiotonic drugs (CDs), have been used to treat the effects of organophosphorus (OP) poisoning. We conducted our experiments to determine what effects CDs may have on acetylcholinesterase (AChE), and how CDs interact with other treatment drugs as well as with OP‐inhibited AChE. True AChE (EC 3.1.1.7) was purified from fetal bovine serum, and enzyme activity was measured according to Ellman et al. The CDs coumingine, cassaine, proscillaridin and convallatoxin were incubated with AChE at 550 μM at pH 7.6 and 25°C. The CD ouabain was incubated with AChE at 500 μM. The CDs inhibited AChE by 97%, 89%, 10%, 7% and 6%, respectively. The mean AChE activities for these experiments, except for ouabain, were significantly different (P = 0.05) from their controls, as determined by the two‐tailed Student's t‐test. In a separate experiment, the oxime TMB‐4·2Br (100 μM), which did not inhibit AChE, increased the inhibitory effect of proscillaridin from 4% to 11% (a 3.7‐fold increase). When AChE was inhibited 39% with 37 nM VX, the addition of proscillaridin increased the inhibition to 51% (a 1.3‐fold increase). When TMB‐4 was added to the proscillaridin‐ and VX‐inhibited AChE mixture, the inhibition decreased from 50% to 32% (a 0.37‐fold decrease), whereas TMB‐4 alone added to VX‐inhibited AChE decreased the inhibition from 39% to 24% (a 0.38‐fold decrease). The results show that TMB‐4 increases the inhibition of AChE by proscillaridin. However, TMB‐4 decreases the inhibition of AChE by VX and proscillaridin combined. The inhibition of AChE by the CDs alone may help in part to account for the cardiac parasympathetic response of CDs.
Urinary cyclophosphamide excretion in rats after intratracheal, dermal, oral and intravenous administration of cyclophosphamide
Authors: Sessink P. J. M. , van den Broek P. H. H. , Bos R. P. 
Published: October 2006

AbstractThe urinary excretion of unmetabolized cyclophosphamide was studied in rats after intratracheal, dermal, oral and intravenous administration. Rats were given two doses of 1 mg kg−1 cyclophosphamide 48 h apart and urine was collected for 96 h after the first treatment.With the help of a phosphor‐specific filter in a flame photometer attached to a gas chromatograph, low levels of cyclophosphamide were determined after derivatization with trifluoroacetic anhydride.Cumulative excretion as a percentage of dose ranged from 4.0 to 6.9 after the first dose and 2.7 to 5.5 after the second dose. The highest rate of excretion after the second administration was observed in rats treated intratracheally, while cumulative excretion was higher (6.9%) after the first than after the second (2.7%) intravenous treatment. The most prolonged excretion was observed after dermal application.
Anamnestic responses to contact allergens: Application in the murine local lymph node assay
Authors: Kimber I. , Weisenberger C. 
Published: October 2006

AbstractThe murine local lymph node assay, an alternative predictive test for the identification of contact sensitizing chemicals, is based upon the fact that skin allergens induce proliferation in lymph nodes draining the site of application. In the present study we have examined whether pre‐exposure to the test chemical at a distant site enhances subsequent draining lymph node cell proliferation and, thereby, the sensitivity of the assay. Experiments were performed using both in vitro and in situ measurement of induced lymph node cell proliferation. It was found that, with the exception of potent skin sensitizers such as picryl chloride and oxazolone, which impair subsequent proliferative activity as a consequence of induced immunoregulatory processes, pre‐treatment with the test allergen resulted in enhanced proliferation. Evidence is presented that the local lymph node assay response to a variety of skin allergens (including eugenol, isoeugenol, dihydrocoumarin, 4‐vinylpyridine, cinnamic aldehyde and 2,4,5‐trichlorophenol) was augmented when mice received a single exposure to the same chemical 5 days earlier.It is concluded that the use of a modified protocol, incorporating pre‐exposure to the test material, can enhance local lymph node assay responses to all but the most potent skin allergens, and may be of particular value when increased sensitivity is required.
Methylthiazolidine‐4‐carboxylate for treatment of acute T‐2 toxin exposure
Authors: Frick Robert F. , Jorge Juan 
Published: October 2006

AbstractThe effect of T‐2 toxin on hepatic glutathione content and the protective effect of 2‐methyl‐thiazolidine‐4‐carboxylate (MTCA), an L‐cysteine prodrug, were studied in mice. Acute exposure to T‐2 toxin (4 mg kg−1, s.c.) resulted in a progressive decrease in glutathione content, reaching a minimum 6–8 h after toxin administration. Because T‐2 toxin caused decreased food consumption, a condition known to deplete hepatic glutathione, glutathione was measured in both fed and fasted control and toxin‐treated mice. Glutathione content (μmol g−1 tissue) was 9.01 ± 0.66 (control) and 4.26 ± 0.41 (toxin) for fed mice, 4.45 ± 0.39 (control) and 2.45 ± 0.26 (toxin) for 16‐h fasted mice, and 7.18 ± 0.26 (control) and 3.76 ± 0.65 (toxin) for mice fed before, but fasted after exposure to toxin. In all cases, toxin treatment resulted in significant decreases in glutathione content compared to controls. Treatment of T‐2‐intoxicated mice with MTCA (750 mg kg−1, i.p.) not only maintained glutathione content at control levels or higher but significantly improved survival as well. Therefore, the toxicity and lethality of T‐2 toxin may be associated with decreased hepatic glutathione content, since MTCA maintained glutathione content and improved survival.
Nephrotoxicity of paracetamol in the rat—mechanistic and therapeutic aspects
Authors: Möller‐Hartmann W. , Siegers C.‐P. 
Published: October 2006

AbstractBesides hepatotoxicity, paracetamol may exert nephrotoxic effects in experimental animals and patients. The present study in rats shows that antidotes known to protect against hepatotoxicity, such as methionine or N‐acetylcysteine, are not effective in preventing paracetamol‐induced kidney damage. Only diethyldithiocarbamate, an inhibitor of microsomal monooxygenases, provided complete protection against both hepato‐ and nephrotoxicity. While a marked depletion of glutathione was observed in the liver, no such effect was seen in the kidney. These data suggest that the mechanism of paracetamol nephrotoxicity seems to be quite different from that responsible for the hepatotoxicity. The hypothesis that a C–S‐Iyase‐mediated final metabolism of paracetamol–S conjugates in the kidney might be responsible for nephrotoxicity needs support by further experimental investigations.
Inhalation toxicity of methyl isocyanate: Biochemical and cytological profile of bronchoalveolar lavage fluid in rats
Authors: Gupta G. S. D. , Kaw J. L. , Naqvi Syed H. N. , Dixit Renu , Ray P. K. 
Published: October 2006

AbstractAcute pulmonary injury in rats following a single inhalation exposure to methyl isocyanate (3.2 mg I−1) was reflected by alterations in the biochemical and cytological constituents of bronchoalveolar lavage fluid (BALF) over a period of 30 days. Total protein, sialic acid and lactic acid contents of BALF were increased followed by a gradual decline to normalcy between day 3 and day 30 post‐exposure. The activity of lactic dehydrogenase also increased progressively with time. The cellularity of BALF was increased significantly and primarily comprised of polymorphonuclear neutrophils at 8 days. The adherence of macrophages was unchanged but their viability was lowered at 30 days post‐exposure. The results indicate the significance of bronchoalveolar lavage analysis in monitoring pulmonary toxicity by methyl isocyanate, which is characterized by the hypoxic condition and reduced cellular defence. Some toxic manifestations are potentially reversible with time after cessation of exposure.
Assessment of cadmium‐induced osteopenia by measurement of serum bone gla protein, parathyroid hormone, and 1α,25‐dihydroxyvitamin D
Authors: Kido Teruhiko , Honda Ryumon , Tsuritani Ikiko , Ishizaki Masao , Yamada Yuichi , Nogawa Koji , Nakagawa Hideaki , Dohi Yoshiko 
Published: October 2006

AbstractTo assess the osteopenia induced by environmental cadmium (Cd) exposure by measurement of serum bone Gla protein (BGP), parathyroid hormone ((PTH) and 1α,25‐dihydroxyvitamin D (1α, 25(OH)2D), 29 men and 41 women who lived in a Cd‐polluted area and showed renal tubular dysfunction were selected. To evaluate the degree of osteopenia, microdensitometry (MD) was used. Compared with the non‐exposed subjects, the levels of serum creatinine and BGP, urinary Cd and β2‐microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd‐exposed group. In simple correlation matrix, BGP showed significant correlations with serum alkaline phosphatase (S‐Al‐p) and MD indicators in the Cd‐exposed men, and also correlations with S‐Al‐p and 1α‐25(OH)2D in the Cd‐exposed women.Applying multivariate analysis to the Cd‐exposed subjects, BGP, %TRP and base excess were found to show significant associations with the MD indicators in the men. In the women, PTH, age, blood Cd and BGP were associated significantly with the MD indicators.Only serum BGP showed a significant correlation in both sexes of the Cd‐exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia.These results suggest that serum BGP has a close independent association with the osteopenia induced by Cd exposure and that BGP, which has a different biological function from that of PTH or 1α,25(OH)2D, may be a useful indicator to detect bone damage in Cd‐exposed subjects.
Trichloroethylene interactions with muscle cells
Authors: Kössler F. 
Published: October 2006

AbstractThe toxic effect of trichloroethylene (TCE) was investigated on isolated muscles prepared from frog and rats. Twitch and tetanic contractions as well as caffeine‐induced contractures, were recorded. Trichloroethylene at a concentration of 0.25–4.0 mM depressed the force development of both twitch and tetanic tension in a dose‐dependent manner. This effect was not influenced by the type of muscle. As TCE shortened the time to peak of twitch contractions, it may alter the Ca2+ binding kinetics.Subthreshold caffeine concentrations applied after pre‐exposure to TCE (1 or 2mM) induced contractures. The same TCE exposure enhanced regular caffeine contractures through increasing the speed of tension development and the absolute force. Exposure to 5 or 10 mM TCE did not affect the first caffeine‐induced contracture but enhanced the potency of the second caffeine dose given 15 min after the first. The results suggest that the interaction of TCE with membrane sites is responsible for Ca2+ release for contractile processes.
Effectiveness of some chelating agents on distribution and excretion of vanadium in rats after prolonged oral administration
Authors: Gómez M. , Domingo J. L. , Llobet J. M. , Corbella J. 
Published: October 2006

AbstractVanadium has been shown to have a number of insulin‐like effects and has been demonstrated to be beneficial in the treatment of streptozotocin‐diabetic rats when included in the drinking water. However, some signs of toxicity and vanadium accumulation in all analysed tissues were reported in vanadium‐treated animals. In the present study, the effect of repeated intraperitoneal administration of sodium 4,5‐dihydroxybenzene‐1,3‐disulfonate (Tiron), ascorbic acid and deferoxamine mesylate (DFOA) or 2‐mercaptosuccinic acid on the distribution and excretion of vanadium was determined in male Sprague‐Dawley rats. Rats received sodium metavanadate (NaVO3) or vanadyl sulphate pentahydrate (VOSO4·5H2O) in the drinking water at concentrations of 0.15 mg ml−1 (NaVO3) and 0.31 mg ml−1 (VOSO4·5H2O) for 6 weeks. After the end of this exposure period, chelating agents were administered for 2 weeks (3 days per week) at doses approximately equal to one‐tenth of their respective LD50. Urine was collected on days 1, 7 and 14 of treatment. Twenty‐four hours after the final chelator injection, rats were killed and vanadium concentrations were determined in various tissues. Tiron and DFOA were effective compounds in mobilizing vanadium after NaVO3 administration, whereas Tiron was the most effective chelator after vanadyl sulphate administration. Ascorbic acid neither increased urinary elimination nor decreased tissue vanadium concentrations.
Kelthane residues in tissues of the tropical penaeid prawn, Metapenaeus monoceros (fabricius), under sublethal chronic exposure—a monitoring study
Authors: Surendranath P. , Rao K. V. Ramana 
Published: October 2006

AbstractMonitoring the biodegradation and bioaccumulation of kelthane residues were undertaken during reclamation through oxygen consumption (respiration) and target enzyme activity assays. Even after 30 days of reclamation, non‐recovery in respiration and target enzyme assays revealed the accumulation of kelthane as a residue in tissues. Thin‐layer chromatography demonstrated the presence of kelthane residues as spots in tissue extracts of midgut gland and muscle after a 30‐day recovery period. This confirms that kelthane is a persistent insecticide of low biodegradability and capable of accumulating in tissues as residues even at sublethal concentration under chronic exposure.
Comparative studies of the covalent binding of [14C]‐2‐chloro‐4‐acetotoluidide by liver and kidney slices of the starling
Authors: Giri Shri N. , Siegel David M. 
Published: October 2006

AbstractIn tissue slices of female starlings, binding of [14C]‐2‐chloro‐4‐acetotoluidide (CAT) radioactivity to liver proteins was almost five times greater than binding to kidney proteins after 2 h of incubation. Binding to protein of liver slices increased in a log linear fashion with increasing CAT concentrations. Binding to protein of kidney slices also increased with increasing concentrations but not in a log linear fashion. Mixed‐function oxidase inhibitors, SKF 525‐A and α‐naphthoflavone, decreased binding to liver slices but did not affect binding to kidney slices. Anaerobic incubation conditions inhibited binding to both tissues. P‐Hydroxymercuribenzoate and sodium cyanide did not affect the binding of radioactivity associated with [14C]‐CAT to proteins of either liver or kidney slices. Diethyl maleate increased binding of the radioactivity to proteins of the kidney slices but not to liver slices. Cysteine also increased binding in kidney slices. Binding in liver slices did not increase significantly with cysteine. The cysteine‐induced increase in protein binding in kidney slices did not appear to depend on the formation of sulfate from the metabolism of cysteine. There was no sex‐dependent difference in starlings as to the binding of radioactivity in either liver or kidney slices. Male chicken kidney slices bound a much higher amount of radioactivity associated with [14C]‐CAT than male starling kidney slices, while the liver slices bound comparable amounts. Male hamster liver slices bound much more radioactivity than did male starling liver slices. However, hamster kidney slices bound much less than did starling kidney slices. Male mouse liver and kidney slices bound much less radioactivity than the comparable tissue slices of male starlings. It was concluded that in vivo metabolism of CAT in starlings plays an important role in covalent binding of [14C]‐CAT radioactivity to kidney proteins and this may be responsible for nephrotoxicity.
The production of hepatic cirrhosis in rats
Authors: Tomaszewski Konrad E. , Harries Gina C. , Jeffrey Phillip 
Published: October 2006

AbstractThis study investigated the conditions necessary to produce a predictable yield of cirrhosis in rats. A previously published method, using carbon tetrachloride, was used as a basis for the study. Histopathology was used in a semi‐quantitative manner to examine which observations could be used for the prediction of progression and final yield of cirrhosis. A comparison of different vehicles for oral carbon tetrachloride administration showed no effect of vehicle on the final yield of cirrhosis. Also, there were no observations during the study that could be used for prediction. Variability in the severity of hepatic impairment is an inherent feature of this model, and supporting histopathology is essential. We recommend a simple protocol for the initiation of cirrhosis in rats using carbon tetrachloride.
Poisoning by Gyromitra esculenta–a review
Authors: Michelot Didier , Toth Bela 
Published: October 2006

AbstractGyromitra esculenta (Pers.: Fr.) Fr. and a few other mushrooms have caused severe poisonings and even deaths in humans. Clinical data are characterized primarily by vomiting and diarrhea, followed by jaundice, convulsions and coma. Gastrointestinal disorders distinguish this poisoning. Frequent consumption can cause hepatitis and neurological diseases.The species of concern are mainly G. esculenta and G. gigas (Kromb.) Cooke (non Phill.). Nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other Ascomycetes species also may prove toxic.Gyromitrin (acetaldehyde methylformylhydrazone, G) and its homologues are toxic compounds that convert in vivo into N‐methyl‐N‐formylhydrazine (MFH), and then into N‐methylhydrazine (MH). The toxicity of these chemicals, which are chiefly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments using animals, cell cultures and biochemical systems. When we consider the chemical nature and the reactivity of these natural compounds, we suggest that chemical and biochemical mechanisms may explain their intrinsic biological activity.