bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant poisonings in children
Authors: Lamminpää Anne , Kinos Marja 
Published: December 2008

1 Plant poisonings comprise 5% of all hospitalizations due to poisonings in children and plant inquiries to Poison Information Centre consist about 28% of calls concerning children. 2 A search of 71 cases of hospitalization due to plants in a 5 year period obtained from two children's hospitals in Helsinki were reviewed and 105 plant inquiries concern ing poisonings among children to the Poison Information Centre in a 6 month period were studied. 3 The most frequent plant poisonings involved lily-of the-valley, dumb cane and cotoneaster plant. Only 11% of the cases treated in hospital were evaluated to be unequivocal poisonings. 4 Mezereon, snowberry, cotoneaster plant, honeysuckle, and woody nightshade caused the most serious symptoms. Symptoms in mezereon poisoning were increased saliva excretion, haematuria and diarrhoea in a 1.2-year-old girl. Snowberries caused a semicomatose state and difficulty in urination, cotoneaster caused severe stomach ache, honeysuckle abudant gastrointestinal symptoms and muscle cramps, and nightshade led to prolonged high fever and sweating. 5 It appears that almost all plant poisonings could be treated with medical charcoal. Gastric evacuation is seldom required.
Elevated amylase is related to the development of respiratory failure in organophosphate poisoning
Authors: Matsumiya N. , Tanaka M. , Iwai M. , Kondo T. , Takahashi S. , Sato S. 
Published: December 2008

1 A retrospective study of organophosphate(OP) poison ing in the intensive care unit was performed to analyze the incidence of respiratory failure. 2 The patients were treated initially with gastrointest inal decontamination including gastric lavage and the administration of activated charcoal with cathartic. Further management included intravenous pralidoxim and atropine and ventilatory support. 3 Of the 32 OP poisoning patients, 16 patients developed respiratory failure and received ventilatory support. 4 An increase in plasma amylase above the normal range on the day of admission was related to the development of respiratory failure. 5 In OP poisoning, the elevation of amylase level was predictive of the subsequent respiratory failure.
Potentiation of occupational carbon tetrachloride toxicity by ethanol abuse
Authors: Manno M. , Rezzadore M. , Grossi M. , Sbrana C. 
Published: December 2008

1 Two separate cases of acute occupational poisoning following exposure to vapours of a fire extinguishing liquid are described. Analytical, clinical, pathological and toxicological data leave little doubt that toxicity was due, in both cases, to inhalation of carbon tetrachloride present at high concentrations (>15% and 78% by weight, respectively) in the fire extinguishing liquid. 2 Both subjects were admitted to hospital, 4 and 8 days after exposure, respectively, and developed severe hepato-nephrotoxicity with hepatomegaly, increased va lues of serum transaminases, blood urea nitrogen (BUN), creatinine, γ-glutamyl-transpeptidase (γ-GT), bilirubin and uric acid and, finally, anuria. They recovered in about three to four weeks, after several haemodialytic sessions. 3 Interestingly, in both cases the other workers exposed under the same conditions and for the same period of time as the two patients showed no signs or symptoms of toxicity. The reason for the observed different suscept ibility to CCl4 is attributable to an abnormally high ethanol abuse by the two workers, as reported in the clinical records and confirmed by their relatives and collegues (120 and 250 g per day, respectively). Daily ethanol intake by the coworkers was less than 50 g for all subjects. 4 Although the potentiating effect of ethanol on the toxicity of CCl4 is well known in experimental animals, as a result of cytochrome P-450 induction, direct evidence in humans reported in the literature so far was limited by the lack of information, in all published reports, on the presence or absence of effects in non-alcoholic exposed 'controls', when these were present.
Morphological alterations in the hippocampus following hypobaric hypoxia
Authors: Shukitt-Hale B. , Kadar T. , Marlowe BE , Stillman MJ , Galli RL , Levy A. , Devine JA , Lieberman HR 
Published: December 2008

1 The morphological consequences of hypobaric hypox ia, exposure to reduced pressure atmospheres, were examined in the hippocampus of male Fischer 344 rats. Severe chronic hypoxia can produce permanent neuronal damage with hippocampal structures being especially vulnerable. 2 Hippocampal morphology was studied using histolo gical observations after a 4 day exposure to sea level, 5500 m, or 6400 m. Two groups tested at 6400 m were sacrificed at different intervals following exposure, 72 and 144 h, to examine the effect of post-exposure time on neuronal damage. 3 Histological damage was observed in rats' brains following exposure to altitude, with cell degeneration and death increasing as altitude increased. In addition, it was found that the longer the time following exposure before sacrifice, the more noticeable the damage, suggest ing delayed neurotoxicity. Increases in the number of damaged cells following altitude were significant for the CA3 region of one 6400 m group; however, other differ ences did not reach statistical significance. Rats exposed to altitude for 4 days ate less and lost significantly more weight than did animals at sea level. 4 It appears that 4 days of exposure to altitudes less than or equal to 6400 m does produce changes in the CA3 subfield, but the damage is different than that seen with other models of non-transient ischemia.
Nitric oxide contributes to desipramine- induced hypotension in rats
Authors: Pentel PR , Wananukul W. , Scarlett W. , Keylerl DE 
Published: December 2008

1 Anesthetized rats received the TCA desipramine (DMI) 60 mg kg-1i.p. Administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester-(L-NAME) 15 min after DMI reversed hypotension within 5 min (P < 0.05). In contrast to its beneficial effect on blood pressure, L-NAME worsened DMI-induced prolongation of the electrocardiographic QRS interval. Dexamethasone, an inhibitor of NOS induction, did not prevent DMI-induced hypotension.2 To study the effect of L-NAME on survival, DMI was administered to anesthetized rats as a continuous i.v. infusion until death. Despite initially improving blood pressure, L-NAME decreased the mean survival time by 33% (P < 0.01) compared to control treatment. Adminis tration of the nitric oxide (NO) donor nitroglycerine to rats during DMI infusion likewise decreased the mean survival time.3 L-NAME partially reversed the hypotensive effect of nitroprusside in both anesthetized and awake rats.4 These data suggest that NO production attributable to constitutive NOS ( cNOS) activity aggravates the hypoten sion associated with DMI toxicity in the anesthetized rat, and contributes to the pathophysiology of this overdose. The shortened survival time produced by both increasing and decreasing NO production suggests that cNOS activity during DMI overdose is regulated and adaptive. Ongoing cNOS activity also contributed to nitroprusside-induced hypotension, and may represent a feature common to other drug-induced hypotensive states.
Perspective on the carcinogenic potential of phenytoin based on rodent tumor bioassays and human epidemiological data
Authors: Dethloff Lloyd A , Graziano Michael J , Goldenthal Edwin , Gough Alexander , de la Iglesia Felix A 
Published: December 2008

1 Phenytoin is a hydantoin-type anticonvulsive agent used extensively for nearly sixty years in the prophylactic treatment of grand mal and psychomotor seizures.2 Based upon somewhat contentious evidence of pheny toin-induced lymphoma in mice and upon epidemiologic evidence of an association between anticonvulsive ther apy and lymphoma in epilepsy patients, the International Agency for Research on Cancer (IARC) has collectively regarded these data as limited evidence of carcinogeni city.3 Two year carcinogenicity studies of standard bioassay design conducted in mice and rats yielded statistically significant increased incidence of hepatocellular adeno mas in mice at phenytoin plasma concentrations approx imating the therapeutic anticonvulsive range. Tumor incidence in rats was not affected. Previous carcinogeni city studies have found similar increases in hepatic tumor incidence in mice.4 Phenytoin is a known enzyme inducer and shows tumor promoting activity in chemically initiated mouse liver. Evidence for genotoxicity is weak or equivocal, consequently phenytoin-induced liver tumors appear to occur through nongenotoxic mechanisms.5 Finally, despite six decades of extensive therapeutic use and thorough epidemiologic evaluation, there is no evidence for an association between liver cancer and phenytoin therapy in epilepsy patients. Thus, hepatocel lular neoplasia in phenytoin-treated rodents appears to be of little significance to man.
Experimental study of the detrimental effect of dopamine/glucagon combination in d,l- propranolol intoxication
Authors: Toet AE , Wemer J. , Vleeming W. , te Biesebeek JD , Meulenbelt J. , de Wildt DJ 
Published: December 2008

1 Respiratory and cardiovascular failure are the princi ple toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats.2 The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovas cular function and survival time in β-blocker overdose was investigated in a model of acute d, l-propranolol (resp. 30 and 15 mg kg-1h-1in rat and rabbit) intoxication in spontaneously breathing rats and artifically ventilated rats and rabbits.3 Glucagon (initial dose of 100 μg kg-1(bolus), followed by 1 μg kg-1min-1), dopamine (25 μg kg-1min-1) or the combination of glucagon/dopamine did not im prove survival time (ST) in d, l-propranolol intoxicated spontaneously breathing rats and artificially venti lated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVPmax) and the differentiated left ventricular pressure (LVdp/ dtmax) temporarily improved.4 Survival time was considerably reduced in d,l- propranolol intoxicated spontaneously breathing and artifically ventilated rats treated with a combination of glucagon /dopamine, which induced a decrease in PaO2and pH and an increase in PaCO2partly due to ventilation/perfusion mismatch.5 The combination of glucagon/dopamine should be used carefully in the treatment of β-blocker overdose in man.
CYP enzymes catalyze the formation of a terminal olefin from 2-ethylhexanoic acid in rat and human liver
Authors: Pennanen S. , Kojo A. , Pasanen M. , Liesivuori J. , Juvonen RO , Komulainen H. 
Published: December 2008

1 The metabolism of 2-ethylhexanoic acid (2-EHA) was studied in rat, mouse and human liver microsomes in vitro. The metabolites of 2-EHA were identified as methylated derivatives by gas chromatography-mass spectrometry.2 2-Ethyl-1,6-hexanedioic acid was the main metabolite produced in rat, mouse and human liver microsomes. Unsaturated 2-ethyl-5-hexenoic acid, a terminal ole fin, was produced only in human liver microsomes and phenobarbital-induced rat liver microsomes. The cytochrome P450 (CYP) inhibitors metyrapone, SKF 525A, triacetyloleandomycin (TAO), quinidine and the cytochrome P450 reductase antibody abolished its formation both in rat and human microsomes.3 The metabolites were analyzed also in vivo in urine of 2-EHA-exposed rats and in urine of sawmill workers exposed occupationally to 2-EHA. Both rat and human urine contained 2-ethyl-1,6-hexanedioic acid as the main metabolite and also 2-ethyl-5-hexenoic acid. Metyrapone, SKF 525A and TAO all decreased drastically the formation of 2-ethyl-5-hexenoic acid in the rat.4 The data indicate that (1) several CYP families (CYP2A, CYP2B, CYP2D and CYP3A) could be responsible for the hepatic metabolism of 2-EHA, (2) the same metabolites were formed in rats and man and (3) an unsaturated terminal olefin, 2-ethyl-5-hexenoic acid is formed in the liver.
Formation of DNA-adducts by selected sex steroids in rat liver
Authors: Feser W. , Blode RS Kerdar H , Reimann R. 
Published: December 2008

1 We are reporting investigations into the potential of the steroid hormones chlormadinone acetate (CMA), cyproterone acetate (CPA), ethinylestradiol (EE2) gestodene (GEST), megestrol acetate (MGA), norethis terone acetate (NET-Ac), estradiol (E2), and progester one (P) to form DNA-adducts in rat liver in vivo.2 Compound-related DNA-adduct spots were detected in male and female rat liver following CMA, CPA, and MGA using the32P-postlabeling-technique. Substance- specific DNA-adducts were also observed in male rats after administration of E2. The other compounds showed no DNA-adduct formation. After treatment with CMA, CPA or MGA, the relative adduct labeling (RAL) differed sex- and substance-specifically.
Changes in sexual behavior of adult male and female rats neonatally treated with vitamin D3
Authors: Mirzahosseini S. , Karabélyos Cs , Dobozy O. , Csaba G. 
Published: December 2008

1 Neonatal treatment of rats with vitamin D3 resulted in a change of sexual behavior in adulthood. 2 2.5 mg vitamin D 3 completely inhibited the ejaculation of males without any apparent influence on sexual desire. 250 mg vitamin D3 influenced both the desire and ejaculation. 3 Sexual activity of females was depressed by both doses. 4 The experiments demonstrate that vitamin D3, a steroid in structure, given in the critical period of hormonal imprinting may influence steroid hormone-receptor commanded events for life, in a way similar to the effects exhibited by synthetic steroid hormone analo gues and benzpyrene in earlier studies.
Hepatotoxicity of N,N-dimethylformamide (DMF) in acute poisoning with the veterinary euthanasia drug T-61
Authors: Buylaert W. , Calle P. , De Paepe P. , Verstraete A. , Samyn N. , Vogelaers D. , Vandenbulcke M. , Belpaire F. 
Published: December 2008

1 We report on a patient who was resuscitated after a suicide attempt with the veterinary euthanasia pro duct T-61 and treated with N-acetylcysteine (NAC) to prevent hepatotoxicity from N,N-dimethylformamide (DMF), the solvent of T-61. 2 Serum concentrations of DMF were high as compared with values published on occupational exposure. 3 The patient showed only a transient increase in liver enzymes with eventually a full recovery. 4 The hepatoprotective effect of NAC was studied in a rat model using the rise in serum sorbitol dehydrogenase (SDH) as a marker for DMF-induced hepatotoxicity. 5 Four series of randomized, controlled and double- blind experiments were carried out and consistently showed a lower increase in SDH in NAC-treated animals in each series. The difference was statistically significant only when the data of the 4 series were pooled. This is probably due to the large interindivi dual variations in the effect of DMF. 6 We hypothesize that in the rat NAC may have a protective effect. Whether NAC is also protective in patients, in which it is administered after exposure to DMF, cannot be concluded from the present experi ments.
Reference values for young normal Sprague-Dawley rats: weight gain, hematology and clinical chemistry
Authors: Lillie Len E , Temple Norman J , Florence L. Zack 
Published: December 2008

1 Arterial blood from 63 male (315 - 500 g) and 60 female (210 - 290 g) healthy Sprague-Dawley rats was ana lyzed for 16 hematological and 22 clinical chemistry parameters. 2 Nine of these parameters were associated with growth and developmental changes in males between 38 - 78 days and females 49 - 89 days of age. 3 Weight gain in both sexes followed patterns consistent with other studies using this strain, but interexperi mental variation was as much as ± 22%. 4 Rectal temperatures of females averaged 37.28°C, being statistically greater (P < 0.05) than the average male at 36.99°C. 5 The data provide reference values for use in toxicolo gical and other investigations.
Experimental studies on multiorgan toxicity of cyclosporine-A in rats using a radiopharmaceutical and comparison with histopathological findings
Authors: Shihab-Eldeen A. , Owunwanne A. , Junaid TA , Yacoub T. 
Published: December 2008

Iodine-125 HIPDM was evaluated as a screening agent for studying multiorgan toxicity due to Cyclosporine-A (CsA) and the results were compared to histopathological findings of the tissues. The rats were injected subcuta neously with 50 mg/kg (body weight) of CsA or with equal volume of the vehicle, Cremophor-EL, for 7 consecutive days. A dose of 10 μCi of I-125 HIPDM was injected intravenously at the end of the treatment period. The results indicated that there was a significant increase in the uptake of 1-125 HIPDM in the kidney, liver, heart and blood compared to control rats (P < 0.05). However, there was a significant decrease in the uptake of 1-125 HIPDM in the spleen compared to control animals (P < 0.001). The lung and brain of CsA treated rats showed no change in the uptake of I-125 HIPDM when compared to control rats. The change in the uptake of I-125 HIPDM in these organs was assumed to indicate tissue response to the toxic effects of CsA. The radiopharmaceutical results were compar able with the histopathological findings in which the organs showed varying degrees of tissue degeneration. It is concluded that the lipophilic radiopharmaceutical, 1-125 HIPDM, can be used as an effective screening agent to study multiorgan toxicity due to CsA.
Markedly altered colchicine kinetics in a fatal intoxication: Examination of contributing factors
Authors: Borron Stephen W , Scherrmann JM , Baud Frédéric J 
Published: December 2008

1 Colchicine poisoning, which is relatively rare, is associated with significant morbidity and mortality. Whilst a new treatment modality, in the form of colchicine-specific Fab fragments is on the horizon, currently available therapy is largely supportive. 2 The elimination of colchicine occurs primarily by hepatic metabolism, following a first-order process, with significant enterohepatic circulation. Renal extraction is responsible for approximately 20% of colchicine elimination. 3 We report a case of colchicine intoxication, compli cated by the presence of co-ingestants, in which serum colchicine concentrations remained quasi-constant over the 3 days of the patient's survival, consistent with marked alterations both in metabolism and excretion. The initial presentation was relatively benign but the subsequent course was one of severe colchicine poisoning, resulting in death. 4 Severe colchicine toxicity appears to have resulted in a vicious cycle of progressive organ dysfunction and impaired elimination. 5 Josamycin, one of the co-ingestants and an inhibitor of P-glycoprotein, the membrane pump responsible for multidrug resistance, may have played a significant role in impeding the cellular and biliary elimination of colchicine. Co-ingested opioid and anticholinergic compounds may have altered colchicine absorption and gastrointestinal transit. 6 This case serves as a reminder of the need for attention to co-ingested drugs, to early aggressive therapy, and if available, to consideration of immunotherapy.
Characterisation and uptake of paraquat by rat renal proximal tubular cells in primary culture
Authors: Chan Bsh , Lazzaro VA , Seale JP , Duggin GG 
Published: December 2008

1 Uptake of the herbicide paraquat (PQ), by rat proximal tubular cells (PTC) in primary culture grown on a collagen coated support was investigated.2 The uptake of PQ by PTC was predominantly from the basolateral side. The basolateral uptake of PQ was saturable with time and increasing concentrations, energy dependent and could be inhibited by certain organic cations. Using Michaelis Menten kinetics, the apparent Km was 778 ± 241 μM and Vmaxwas 0.97 ± 0.24 pmol/μg protein/15 min for the basolateral uptake of PQ. Cimetidine (5.7 ± 0.4 pg/μg protein/ 30 min, P < 0.001) was the most potent inhibitor of PQ uptake, followed by quinine (6.5 ± 0.4 pg/μg pro tein/30 min, P < 0.01) and then tetraethylammonium (8.2 ± 0.5 pg/μg protein/30 min, P < 0.05) when com pared with control (11 ± 1 pg/μg protein/30 min). N- methylnicotinamide, p-aminohippurate and putres cine did not inhibit the basolateral uptake of PQ. The sodium hydrogen exchange inhibitors, amiloride and its analogue, 5-(N,N hexamethylene) amiloride (HMA) inhibited both the apical and basolateral uptake of PQ.3 The apical uptake of PQ was not saturable with increasing concentrations and was not inhibited by 2,4-dinitrophenol, but it was reduced by cimetidine ( P < 0.01), quinine ( P < 0.05) and a sodium potassium ATPase inhibitor, ouabain ( P<0.01).4 It is concluded that PQ was taken up from the basolateral side of primary cultured rat PTC by an energy dependent transport system.
In vitro drug adsorption to charcoal, silicas, acrylate copolymer and silicone oil with charcoal and with acrylate copolymer
Authors: Cassidy SL , Hale A. , Buss DC , Routledge PA 
Published: December 2008

1 The relative binding constants of four drugs to charcoal, silicone oil silicas and acrylate copolymers was studied using an in-vitro binding technique. 2 The maximum adsorption capacity (K2) was chosen as a measure of the degree of binding and calculated by fitting to the Langmuir equation. 3 Charcoal alone was shown to be the most effective of the adsorbents chosen. The possible use of silicone oils as an adsorbent delivery vehicle in treatment of overdose is discussed.
Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells
Authors: Nicod Laurence , Viollon Catherine , Regnier Any , Jacqueson Alain , Richert Lysiane 
Published: December 2008

Acetaminophen (APAP) induced a concentration-depen dent (0-30 mM) cytotoxic effect in human HepG2 hepatoma cells which was significantly increased when intracellular reduced glutathione (GSH) content was decreased. The cytotoxic effect of APAP (0-30 mM) was significantly lower in day 3-treated compared to day 1- treated HepG2 cells. A 3-day preincubation of HepG2 cells with 5 ?M 3-methylcholanthrene (3MC), 50 ?M rifampicin (RFP) or 1 mM isoniazid (INH) significantly increased 15- 30 mM APAP cytotoxicity, of about 15-20% for INH and RFP and 35-50% for 3MC. The cytotoxicity of 10 mM APAP was also increased (about 20%) by a 3-day preincubation with INH but was not affected by 3MC and RFP.INH induced a concentration-dependent (0 - 40 mM) cytotoxic effect in day-1 treated HepG2 cells and not significantly affected by decreases in intracellular GSHconcentrations. INH was not cytotoxic in day 3-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 50 ?M RFP or 1 mM INH significantly increased 10- 40 mM INH cytotoxicity, respectively of about 10% and 10 - 25%. A 3-day preincubation with 3MC did not modify the cytotoxic effect of INH at these concentrations.This is to our knowledge the first report of increases by INH and RFP of APAP and INH cytotoxicity in vitro in hepatocellular cells of human origin. It is in accordance with clinical observations of severe hepatotoxicity asso ciated with APAP or INH usage in patients receiving multiple drug therapy (INH, RFP) for tuberculosis or in alcoholics.