bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ochratoxin A in human blood in relation to nephropathy in Tunisia
Authors: Maaroufi K. , Achour A. , Hammami M. , El May M. , Betbeder AM , Ellouz F. , Creppy EE , Bacha H. 
Published: December 2008

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of conta mination is between 0.7 to 7.8 ng ml-1for the general popu lation and 12 to 55 ng ml-1for people suffering from chron ic renal failure. It appears that 21 to 64% of people suffer ing from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropa thy resembling Balkan endemic nephropathy. The classifi cation of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is signifi cantly different from the other groups, and from the con trol (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia.The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe.Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.
Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice
Authors: Kim DH , Kim EJ , Han SS , Roh JK , Jeong TC , Park JH 
Published: December 2008

1 The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo.2 Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O- deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethy lase(ERDM) activities, respectively. It was found that hist amine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities.3 Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibito ry effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY- 80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism.4 It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory.5 The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes.
Dietary effect on mixed function P450 1A2 activity assayed by estimation of caffeine metabolism in man
Authors: Kall MA , Clausen J. 
Published: December 2008

Two studies were performed in order to evaluate cytochrome P450 1A2 mediated caffeine metabolism dur ing different nutritional conditions.1 In the first study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed diet to a stan dard diet in 6 days. The 6 day's standard diet was based on bread, potatoes, rice and boiled meat. Thus, broccoli, cabbage and other cruciferous vegetables, spinach, leeks, onion, parsley, grapefruit, toasted bread, fried and charcoal grilled food, smoked fish and meat, ham and sausages were avoided.2 In the second study, 33 healthy non-smoking subjects, 24 men and nine women mean age 25 years, volun teered. The study was designed to compare a customary home dietary period with the 6 day period of low dietary P450 induction and with a 5 day supplementary dietary period, i.e. ingestion of known dietary inducers. None of the women were using oral contraceptives or were pregnant during the experimental period.In the period of diet supplementation, the volunteers received charcoal grilled hamburger as a supplement to the standard low induction diet for lunch for 5 days. The hamburgers were made with 150 g beef (18-20% fat) and were grilled on charcoal for 10 min on each side until they were 'well done'.In the present study P450 1A2 activity was estimated from the caffeine metabolic ratio, the so-called CYP 1A2 index:(AFMU + 1-MX + 1-MU/ 17 -DMU) of the caffeine metabolites formed after oral ingestion of 200 mg caffeine. Urine was collected 4-8 h after caffeine ingestion in study 1 and 5 h after caffeine ingestion in study 2.In study 1 the CYP 1A2 index decreased from 4.28 ± 0.98 in the customary home dietary period to 3.87 ± 0.69 in the standard dietary period corresponding to 10.6% ( P < 0.06) decrease in the CYP 1A2 index.In study 2 the CYP 1A2 index decreased from 4.47 ± 1.76 in the customary home dietary period to 3.90 ± 1.12 in the standard dietary period corresponding to a 14.6% decrease ( P < 0.2) in P450 1A2 activity. The female sub jects had a mean index value of 3.89 ± 1.14 which was 16.8% ( P = 0.09) lower than the mean male index value of 4.68 ± 1.76 during the home dietary period.After the 5 day period with charcoal grilled hamburgers as a dietary supplement, the CYP 1A2 index increased to almost the same level as in the customary home dietary period. The index increased to 4.45 ± 1.57 in the whole group of volunteers, corresponding to a 14.1% ( P < 0.05) increase. The mean increase in the CYP 1A2 index cov ered a large inter-individual variation in response to ingestion of charcoal grilled meat ranging from a 29% decrease to a 147% increase.
An in vitro and an in vivo unscheduled DNA synthesis assay with a zinc oxide/ hexachloroethane (Zn/HCE) smoke
Authors: Andersonl D. , Blowers SD , Marrs TC , Rice P. 
Published: December 2008

1 Since Zn/HCE smoke has been shown previously to be weakly positive in the Ames test, and negative in the bone marrow micronucleus assay, other assays including a second in vivo assay examining unscheduled DNA synthesis (UDS) in rat hepatocytes has been carried out, as recommended by the UK Department of Health guide lines. 2 Zn/HCE smoke was assessed for its ability to induce DNA repair in an UDS assay both in vitro in cultured rat hepatocytes and in rat hepatocytes after in vivo treatment by inhalation. 3 For the in vitro investigation, two studies were carried out assessing media exposed to Zn/HCE smoke using at least seven concentrations up to a toxic level. At the highest concentration of Zn/HCE smoke, where some viable cells were seen, an increase in UDS was observed in both experiments. However this was not statistcally significant, was only seen at a level where toxicity was observed and was therefore considered not to be biologically significant. 4 In the in vivo investigation, one study was carried out in three separate parts, assessing two doses of Zn/HCE smoke characterised by their zinc content as approxi mately 20 and 56 μg l -1 air. A dose-related increase in UDS was observed which was not statistically sig nificant. The positive control behaved as anticipated, showing a highly statistically significant response. 5 It was concluded that Zn/HCE smoke did not induce unscheduled DNA repair in the in vitro or in vivo UDS assays under the conditions used in the studies. The overall lack of genotoxic effect of this smoke in this and previous studies in this laboratory would not suggest a major health hazard.
Reduced survival after isoprenaline/ dopamine in d,l-propranolol intoxicated rats
Authors: Toet AE , te Biesebeek JD , Vleeming W. , Wemer J. , Meulenbelt J. , de Wildt DJ 
Published: December 2008

1 Respiratory and cardiovascular failure are principle toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats. 2 The effect of β-adrenoceptor agonists on respiratory and cardiovascular failure in β-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg -1 h-1) intoxication in spontaneously breathing rats. 3 Neither the aselective, hydrophilic β-agonist isoprena line (10, 25, 50 μg kg-1 min-1), nor the β 1-selective, lipophilic β-agonist flerobuterol (1,3,10 μ g kg-1 min-1) and the β2-selective, lipophilic β-agonist clenbuterol (10, 25, 50 μg kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats. 4 Isoprenaline (10 μg kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l -propranolol intoxicated rats either. 5 Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decrease in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6 Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.
Severe metabolic acidosis in the alcoholic: differential diagnosis and management
Authors: Höjer Jonas 
Published: December 2008

1 A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome. 2 The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a β- hydroxybutyrate dominated ketoacidosis. 3 Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis. 4 The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided. 5 The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment. 6 The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps. 7 It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recom mended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication.
Influences of gold on zinc, copper and metallothionein kinetics in liver and kidney of the rat
Authors: Hinck-Kneip Christiane , Alsen-Hinrichs Carsten 
Published: December 2008

1 Single, very low dose of gold (500 μg/kg body weight) was given intramuscularly to male Sprague-Dawley rats (mean body weight: 200 g) as aurothiokeratinate (Auro-Detoxin dissolved in 0.9% NaCl. 2 Blood, liver and kidney were samples at autopsy 0.5,1, 2, 3, 6 and 12 h after the gold injection (six animals per time). 12 rats were treated with 0.9% saline only as controls. The zinc (Zn), copper (Cu), gold and metallothionein (MT) concentrations were determined in homogenates and cytosols of liver and kidney using atomic absorption spectrometry and gel chromatogra phy, respectively. 3 The main changes in metal and MT concentrations occurred in the kidney, where an increase of gold was found 0.5 h after the injection, followed by an increase in Cu and MT concentrations after 6 h. Zn homeostasis did not change. 4 The results suggest that gold by itself induces an increase of MT-like peptides in the kidney cytosol, which was accompanied by an increase in the concentration of Cu mainly bound to these MT-like peptides.
No changes in behaviour, nigro-striatal system neurochemistry or neuronal cell death following toxic multiple oral paraquat administration to rats
Authors: Widdowson PS , Farnworth MJ , Upton R. , Simpson MG 
Published: December 2008

We have examined whether the widely used herbicide, paraquat (1,1'-dimethyl-4,4'dipyridylium) may accumu late in rat brain following multiple oral dosing (5 mg paraquat ion/kg/day) for 14 days and whether this dosing regime may produce signs of neurotoxicity. This dosing regime may determine whether low dose exposure to mammals may be neurotoxic. Using [14C]paraquat to measure tissue and plasma paraquat concentrations, we observed significantly higher plasma and tissue paraquat concentrations in brain, liver, lungs and kidneys of rats which received multiple doses for 14 days, as compared to paraquat concentrations in tissues of rats which received only a single paraquat dose. Brain paraquat concentrations measured 24 h after dosing were tenfold higher in rats receiving 14 daily oral doses of paraquat, as compared to concentrations follow ing a single oral dose. A neuropathological study of the rat brain yielded no evidence that multiple paraquat dosing resulted in neuronal cell damage. Particular attention was paid to the nigrostriatal system. The paraquat treated rats gained approximately 10% less body weight over the 15 day experimental period as compared with controls demon strating that the dose of paraquat was toxic to the animals. Measurements of locomotor activity using open field tests or activity monitors did not reveal any statistically significant differences between control animals and those receiving paraquat. Fore- and hind-limb grip strength were not significantly different between the paraquat treated and control rats at any time point during the dosing regime, nor was there any evidence for locomotor co ordination deficits in any of the animals receiving paraquat. Densities of dopamine D1 and D2, NMDA, muscarinic and benzodiazepine receptors in the cerebral cortex and striatum were not significantly different between controls and rats which had received multiple paraquat doses. Concentrations of catecholamine neurotransmitters in the striatum, hypothalamus and frontal cerebral cortex were also measured to examine whether there was evidence for catecholamine depletion in these brain regions. We did not observe any significant reductions in dopamine, noradrenaline or DOPAC concentrations in any brain region of paraquat treated rats as compared with controls. On the contrary, dopamine concentrations in the striatim were significantly elevated in paraquat treated animals following a 15 day paraquat dosing regime. We attribute these changes in catecholamine concentrations to the general toxicity of paraquat which produces a stress response. In conclusion, we could not find any evidence that multiple paraquat dosing can lead to changes in locomotor activity or grip strength. In addition, the absence of neuropathology or changes in neurochemistry in the nigrostriatal tract demonstrates that paraquat does not behave like MPP+(N-methyl-4-phenylpyridinium), the neurotoxic metabolite of MPTP
Research into individual predisposition to develop acute rhabdomyolysis attributed to fenoverine
Authors: Jouglard Jacqueline , Kozak-Ribbens Geneviève , de Haro Luc , Cozzone Patrick J 
Published: December 2008

A xenobiotic, well tolerated by the majority of treated patients, can cause serious complications in patients with individual susceptibility. Based on the hypothesis that such a phenomenon may occur in rare cases of rhabdo myolysis attributed to fenoverine (DCI), we designed a protocol to look for a genetic predisposition. Six patients were included who had previously had an episode of rhabdomyolysis after taking fenoverine. A seventh patient was added, who had only experienced myalgia without cytolysis. All patients were investigated by the following tests: 31-phosphorus nuclear magnetic resonance spectro scopy, histopathological examination of the muscle, muscle contraction tests and biochemical analysis of the muscle. All patients examined proved to have muscle abnorm alities. The pathology found varied greatly from patient to patient: mitochondrial myopathy, lipid storage myopathy, sensitivity to malignant hyperthermia or disorders of oxidative metabolism. The probability of finding by chance such rare muscle disorders associated with the equally rare rhabdomyo lysis attributed to fenoverine is practially zero. We conclude that there is a cause and effect link between underlying abnormalities and the muscular cytolysis attributed to fenoverine.
Clinical and biochemical changes in greenhouse sprayers chronically exposed to pesticides
Authors: Parrón T. , Hernández AF , Pla A. , Villanueva E. 
Published: December 2008

1 This study was conducted with the aim of evaluating the impact on health produced by the use of different types of pesticides in greenhouses. It is based on the need to practice and develop biological monitoring techniques to assess exposure and predict health risk in workers occupationally exposed to pesticides. 2 Two groups of greenhouse workers with either high or low exposure to a combination of pesticides was taken in Almeria, a Spanish province where cultures under plastic are very extended. 3 One hundred and five sprayers were interviewed to collect information about symptoms and signs related to past exposures. Each pesticide sprayer was exam ined by a physician, and a blood sample was drawn for plasma and red blood cell cholinesterases, complete blood count, and liver and renal function tests. 4 Exposure of workers to a combination of pesticides resulted in 37% of the workers showing toxic signs and symptoms. The main toxic effects observed were a high incidence of spontaneous abortion, depression, and certain neurologic disorders like headache, tremor and paraesthesia. 5 The major analytical change was a decrease of the mean corpuscular haemoglobin concentration in 38% of the cases. However, no significant decrease in both serum and erythrocyte cholinesterase activities was observed. 6 The sprayers were not usually aware of the potential hazards of pesticides and did not try their best to maintain personal hygiene.
Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat
Authors: Crevel RWR , Buckley P. , Robinson JA , Sanders IJ 
Published: December 2008

1 Groups of male rats were given different doses of cyclosporin A, ranging from the maximum tolerated dose (20 mg/kg/day) downwards, 7 days a week for 28 days using a protocol derived from OECD test guide line 407. 2 At the end of the test, one set of animals underwent a detailed necropsy and histopathological examination of lymphoid tissues. Immune function was assessed using the lymphoproliferative response and natural killer cell activity of their spleen cells. Another set of animals was immunised with sheep erythrocytes on day 25 and used to evaluate the ability to produce specific anti-sheep red blood cell antibody. 3 Cyclosporin A produced detectable effects on the immune system at all doses and at doses lower than other toxic effects. Both histopathological techniques and one of the immune function tests were able to identify changes at the lowest dose, 1.25 mg/kg/day. 4 The results of this investigation suggest that conven tional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to im mune function tests.
α-glutathione s-transferase (α-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat
Authors: Clarke H. , Egan DA , Heffernan M. , Doyle S. , Byrne C. , Kilty C. , Ryan MP 
Published: December 2008

1 The use of the cytoplasmic enzyme, alpha glutathione s-transferase (α-GST) as an early index of carbon tetrachloride (CCl4) toxicity in the rat was investigated and compared with a standard enzyme marker, aspartate aminotransferase (AST). The hepatotoxic effects of CCl 4 in the rat were determined in a time and dose-response study. 2 Following CCl 4 exposure, α-GST release was shown to be an earlier and more sensitive biomarker of hepatotoxicity than AST. 3 Significant increases in α-GST were detected 2 h after CCl4 exposure. Using the enzyme marker AST, this early hepatotoxic injury went undetected. At 6 and 16 h, α-GST was also a more sensitive indicator of hepatotoxicity than AST. 4 α-GST release was significantly increased at a dose of 5 μl/kg, the lowest concentration of CCl4 administered and clearly responded in a dose-dependent manner with increasing doses of CCl4. In contrast, release of AST did not reach statistical significance until a dose of 25 μl/kg. 5 Thus, these findings indicate that α-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.
In utero and lactational exposure of carbofuran to rats: Effect on testes and sperm
Authors: Pant N. , Shankar R. , Srivastava SP 
Published: December 2008

1 Male offspring of adult females treated with 0.2 or 0.4 mg/kg during either the whole of pregnancy or the whole of the lactation period did not induce general ised toxic effects. 2 A significant alteration in enzymatic activities i.e. SDH (decreased), LDH and Y-GT (increased) were observed in testes only at 0.4 mg/kg. 3 A decrease in sperm motility, sperm count along with increase in percent abnormal sperm was observed at 0.4 mg/kg dose level. 4 Histopathological examination revealed loss of sper mato-genesis, degenerative changes in Sertoli cells which are well supported with biochemical studies indicating that carbofuran interferes with the matura tion process of testis. 5 No such effects were observed at 0.2 mg/kg. 6 The testicular and spermatotoxic effects observed in rats given in utero or lactational exposure may be due to transfer of carbofuran or its metabolites through placenta or mothers milk.
Small-intestinal absorption of cadmium and the significance of mucosal metallothionein
Authors: Elsenhans B. , Strugala GJ , Schäfer SG 
Published: December 2008

1 Although food intake is among the most important routes of Cd exposure, not many details are known about the intestinal absorption mechanisms of Cd. In this respect Cd is representative of most other nonessential, merely toxic metals. 2 Based on a concept of two distinguishable steps, intestinal absorption of Cd is characterized by high accumulation within the intestinal mucosa and a low rate of diffusive transfer into the organism. 3 After uptake into the mammalian organism, Cd is sequestered into hepatic metallothionein (MT). It is assumed that hepatic Cd-MT then gradually redis tributes Cd to the kidney, which is the main target organ for chronic Cd toxicity. 4 When feeding low levels of dietary CdCl2, however, Cd accumulates preferentially in the kidney and to a lesser degree in the liver, a distribution pattern also found after intravenous and peroral administration of the Cd-MT complex itself. As dietary Cd induces intestinal MT, intestinal Cd-MT complexes could be at least partly responsible for the renal accumulation of dietary Cd. 5 For this mechanism, however, serosal release of mucosal Cd-MT is required. In fact, in vitro findings in rats reveal a concentration-dependent release of intestinal MT to the serosal side of the small intestine. These results indicate that endogenous intestinal MT may deliver Cd-MT to other inner organs, thus contributing to the preferential renal accumulation of ingested Cd.