bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid Peroxidation and Cherniluminescence during Naproxen Metabolism in Rat Liver Microsomes
Authors: Yokoyama Hiroyuki , Horie Toshiharu , Awazu Shoji 
Published: December 2008

1 Rat liver microsomal suspension containing NADPH and MgCl2 was incubated at 37°C with naproxen, a non-steroidal anti-inflammatory drug. Thiobarbituric acid reactive substances (TBA-RS), high molecular weight protein aggregates and fluorescent substances were formed in the microsomal suspension. 2 Chemiluminescence was produced from the microsomal suspension. This chemiluminescence production was well correlated to the TBA-RS formation, indicating that the chemiluminescence production was closely associated with the lipid peroxidation. 3 The addition of SKF-525A to the microsomal suspension inhibited the production of TBA-RS, chemiluminescence and 6-demethylnaproxen (6-DMN), the oxidative product of naproxen. Further, the antioxidant, α-tocopherol and singlet oxygen quenchers like histidine, dimethylfuran and 1,4-diazabicyclo[2,2,2]octane strikingly inhibited the productions of chemiluminescence and TBA-RS. 4 Neither naproxen nor 6-DMN caused lipid peroxidation in the absence of NADPH. Thus, lipid peroxidation and chemiluminescence during the oxidation of naproxen in liver microsomes was suggested to be provoked by reactive oxygen species and an origin of chemiluminescence was shown to be singlet oxygen.
Altered Urinary Porphyrin Excretion in a Human Po p ulation Chronically Exposed to Arsenic in Mexico
Authors: García-Vargas Gonzalo G. , Del Razo Luz M. , Cebrián Mariano E. , Albores Arnulfo , Ostrosky-Wegman Patricia , Montero Regina , Gonsebatt Maria E. , Lim Chang K. , De Matteis Francesco 
Published: December 2008

1 A detailed study of the urinary excretion pattern of porphyrins in humans chronically exposed to As via drinking water was performed using high performance liquid chromatography (HPLC) 2 Thirty-six individuals (15 men and 21 women) were selected from a town which had 0.400 mg L -1 of As in drinking water. The control group consisted of thirty-one individuals (13 men and 18 women) whose As concentration in drinking water was 0.020 mg L-1. 3 The major abnormalities in the urinary porphyrin excretion pattern observed in arsenic-exposed individuals were: (a) significant reductions in coproporphyrin III excretion resulting in decreases in the COPRO III/COPRO I ratio, and (b) significant increases in uroporphyrin excretion. Both alterations were responsible for the decrease in the COPRO/URO ratio. 4 No porphyrinogenic response was found in individuals with urinary As concentrations below 1,000 μg of As g-1 of creatinine, However, as arsenic concentrations exceeded this value, the excretion of porphyrins (except coproporphyrin III) increased proportionally. 5 The prevalence of clinical signs of arsenicism showed a direct relationship to both As concentration in urine and time-weighted exposure to As. A direct relationship between time-weighted exposure and alterations in urinary porphyrin excretion ratios was also observed. 6 The alterations found are compatible with a lower uroporphyrinogen decarboxylase activity in arsenic-exposed individuals. However, the similarities in the urinary porphyrin excretion pattern between As-exposed individuals and Dubin-Johnson syndrome patients suggest that impairments in the excretion of coproporphyrin isomers may also contribute to the pattern observed.
Effects of Polychlorinated Biphenyls (PCBs) and Dioxins on Growth and Development
Authors: Sauer P.J.J. , Huisman M. , Koopman-Esseboom C. , Morse D.C. , Smits-van Prooije A.E. , van de Berg K.J. , Tuinstra L.G.M.Th. , van der Paauw C.G. , Boersma E.R. , Weisglas-Kuperus N. , Lammers J.H.C.M. , Kulig B.M. , Brouwer A. 
Published: December 2008

Polychlorinated biphenyls (PCBs) and dioxins are potentially toxic compounds which occur widely in the environment. Their effects on the growth and development of infants at the levels currently found in highly industrialised western countries is not well known. This Dutch multicenter study, combining animal and human studies, tries to answer this question. Animal studies showed that PCB 169, given once during pregnancy at a dose of 1.8 g kg-1 bodyweight, has an effect on developmental parameters, dopamine regulation and fertility. Effects on thyroid hormones were also found in animals, probably due to both a competitive binding of PCB metabolites to the thyroxine binding protein and increased glucuronidation, Perhaps to compensate for this, an increased diodase activity in the brain was found. Human studies involved 400 mother-infant pairs, half of them being breast-fed, the other half were fed a formula devoid of PCBs and dioxins. PCB levels were measured in serum and dioxin and PCB levels in breastmilk. Levels were found to be as high as previously found in highly industrialised countries. Growth and development were carefully documented, but no data are as yet available. In pregnant women, a significant negative correlation was found between some dioxin and PCB congeners in milk and plasma thyroid hormones, while newborn infants showed higher thyroid stimulating hormone (TSH) at higher levels of dioxin exposure. In summary, data from this combined multicenter study involving animals and humans increases our insight into the potentially negative effects of PCBs and dioxins on growth and development.
The effect of thyroxine or carbimazole treatment on gentamicin nephrotoxicity in rats
Authors: Ali B.H. , Bashir A.A. , Tanira M.O.M. 
Published: December 2008

1 This study examines the effect of treating rats with gen tamicin (80 mg kg-1 day-1 intramuscularly (i.m.), for 6 days) alone or with either L-thyroxine or the anti-thyroid drug carbimazole. 2 Gentamicin produced significant increases in serum creatinine and urea concentrations, and significantly reduced the activity of Na+,K+ATPase in renal cortex. The concentration of serum triiodothyronine (T3) was unaffect ed by graded doses (20, 40 and 80 mg kg-1) of the antibiot ic. Histopathologically, gentamicin produced necrosis of proximal tubules in the renal cortical tissues of treated rats. 3 Treatment of rats with either L-thyroxine or carbima zole alone did not significantly affect any of the biochemi cal variables investigated. Carbimazole alone produced only mild tubular necrosis. 4 Treatment of rats with either L-thyroxine (100 μg kg-1 day-1, subcutaneously) for 10 days, and gentamicin (80 mg kg-1, i.m. daily during the last 6 days of treatment signifi cantly reduced the gentamicin-induced increases in serum creatinine and urea concentrations, and increased the activity of cortical N+,K+ATPase to control levels. Histopathologically, the severity of gentamicin-induced tubular necrosis was reduced by L-thyroxine treatment. 5 Carbimazole (12 mg ml-1 in drinking water for 21 days) and gentamicin (80 mg kg-1 i.m.) daily during the last 6 days of treatment, stimulated the increase in serum urea concentration produced by gentamicin, but did not signifi cantly affect the gentamicin-induced changes in serum creatinine or cortical N+,K+ATPase.
Study of muscular effects of short-term pyridostigmine treatment in resting and exercising rats
Authors: Hubert Michel , Lison Dominique 
Published: December 2008

1. Pyridostigmine (PYR) pretreatment is used by the mili tary to obtain 20—30% whole blood acetylcholinesterase (AChE) inhibition in order to enhance the effectiveness of the standard therapeutic regimen for poisoning by an organophosphate anticholinesterase agent. The present study was undertaken to investigate in a rat model the potential muscle damage produced by this pretreatment when given alone or combined with physical exercise. 2. Grip strength and biochemical measurements, i.e. serum creatine phosphokinase (CPK) activity and creatine urinary excretion rate, together with histological studies, were performed in resting animals during a period of 14 days of PYR administration in a dose producing 20-30% whole blood acetylcholinesterase inhibition. No evidence was found of a deleterious effect of this treatment on the skeletal muscle. 3. In contrast, following physical exercise, the same treat ment significantly exacerbated the biochemical changes reflecting a loss of integrity in skeletal muscles, namely, increased CPK and urinary creatine excretion rate. The significance of this observation remains to be clarified.
Prevention of drug absorption in simulated theophylline overdose
Authors: Minton Neil A. , Glucksman Edward , Henry John A. 
Published: December 2008

1 The effects of emesis, gastric lavage and oral activated charcoal on theophylline absorption were compared in healthy volunteers. 2 One of four regimes (ipecacuanha-induced emesis, gas tric lavage, oral activated charcoal and no treatment) was randomly chosen one hour after a simulated over dose with sustained-release theophylline on four sepa rate occasions in twelve healthy volunteers. 3 Syrup of ipecacuanha produced emesis in all twelve volunteers but only seven vomited any tablets. Gastric lavage yielded tablets in only one volunteer. 4 The mean systemic availabilities (areas under the con centration-time curves relative to control) of theo phylline for ipecacuanha-induced emesis, gastric lavage and charcoal, were 107.1%, 101.1% and 16.9%, respectively. 5 Oral activated charcoal was thus highly effective, while gastric lavage and emesis were ineffective in pre venting theophylline absorption. Activated charcoal is potentially the most effective first-line treatment for acute overdosage with sustained-release theophylline tablets.
Continuous intravenous infusion in the unrestrained rat — procedures and results
Authors: Cave Desmond A. , Schoenmakers Ankie C.M. , van Wijk Hans J. , Enninga Ilona C. , van der Hoeven Jan C.M. 
Published: December 2008

1 A method of continuous infusion in the unrestrained rat is described, which provides a scientifically accept able and easily maintained rodent model for use in toxicological investigations. 2 Sprague Dawley SPF rats had cannulas implanted into the vena cava via the femoral vein, and were continu ously infused with physiological saline for a total of 28 or 90 days. 3 The results indicate that there was no change in body weight, food consumption, clinical observations or clinical biochemistry of infused rats when compared to non-infused rats. There were small changes in haema tological parameters, however none were toxicological ly significant. Urinary volume was increased and uri nary specific gravity and osmolality were decreased. At macroscopic and microscopic examination there were findings of scar formation associated with the area of surgery and minimal irritation in the area of the vena cava which accommodated the cannula. 4 These results indicate that implantation of a cannula into the vena cava of a rat and subsequent continuous intravenous infusion of physiological saline produces no toxicological adverse effects over a period of 90 days. Consequently, this model can be recommended for the continuous intravenous administration of test substances to rats.
Review : Apoptosis: regulation and relevance to toxicology
Authors: Alison Malcolm R , Sarraf Catherine E 
Published: December 2008

1 Apopotosis is a remarkably stereotyped morphological event across all tissues in response to a vast array of dam aging agents. 2 Our very existence depends upon a willing exchange of old life for new: apoptotic cell death is our guardian and saviour from genetic damage. 3 There is a close link between cell proliferation and apoptosis: When a cell picks up the machinery to prolifer ate it also acquires an abort pathway - 'better dead than wrong'. 4 A wide variety of highly conserved genes have been implicated in triggering apoptosis. 5 The release of DNA loops from the nuclear scaffold is a more crucial intracellular event than DNA 'laddering' in apoptotic cells. 6 The manipulation of apoptotic rates in many of the common diseases in man will be a major therapeutic strategy in the future.
Measurement of the respiratory burst and chemotaxis in polymorphonuclear leukocytes from mercury-exposed workers
Authors: Perlingeiro Rcr , Queiroz Mls 
Published: December 2008

The chemotactic and nitroblue tetrazolium reducing activ ities of neutrophils from 48 mercury-exposed workers were examined and compared with those of non-exposed, age- and sex-matched individuals. At the time of testing, the exposed population had a mean (± s.d.) urinary mer cury concentration of 24.0 ± 20.1 μg g-1 creatinine and in 44 of these workers urinary mercury levels were below the accepted threshold level (TLV) of 50 μg g-1 creatinine. The two neutrophil functions were significantly reduced in the mercury-exposed workers compared with the con trols. In 28 of these workers, chemotaxis was re-evaluated 6 months later. During the intervening 6 months, the level of hygiene was improved throughout the plant and uri nary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, neutrophil migration did not return to within the normal range. These results suggest that 'safe' level mercury exposure may lead to impairment of neutrophil function.
Metal accumulation in human kidney cortex: mutual interrelations and effect of human factors
Authors: López-Artíguez M. , Cameán A. , González G. , Repetto M. 
Published: December 2008

1 Different metals were analysed in 77 post mortem samples of human renal cortex. 2 The concentrations of the metallic ions conformed to known distribution frequencies. In abnormal cases calcu lations were based on non parametric techniques. 3 There was no appreciable difference between the val ues found for each element and those described by other authors in other populations. 4 Statistically established correlations indicated that Zn was the element which was most strongly related to the others. 5 The influence of individual factors on metal concentra tions was considered. Significant differences occurred only in Pb between sexes, and in Cd with age. There was no sign that drug abuse influenced the accumulation of metals in renal cortex.
Changes in connective tissue macromolecular components of Yucatan mini-pig skin following application of sulphur mustard vapour
Authors: Lindsay CD , Rice P. 
Published: December 2008

1 The aim of this study was to determine the nature of the macromolecular alterations in Yucatan mini-pig skin which occur following application of sulphur mustard vapour, with particular reference to laminin and type IV collagen. 2 The immunostaining of transfer blots from skin extracts run on SDS-PAGE gels revealed no evidence of cross-link ing of type IV collagen or laminin. Laminin was, however, found to be partially degraded as determined by the reso lution of 132 and 143 kDa fragments, possibly by the acti vation of proteases, following the application of sulphur mustard to pig skin. Type IV collagen was not subject to this form of degradation in the skin samples exposed to sulphur mustard. 3 Yucatan mini-pig skin was found to develop microblis ters after exposure to sulphur mustard vapour. The immunohistochemical studies of sulphur mustard exposed skin revealed that separation of the epidermis from the dermis was found to occur within the lamina lucida of the subepidermal basement membrane, supporting the con tention that cleavage of laminin networks occurs following mustard challenge. Immunohistochemical staining with anti-type IV collagen antibodies was restricted to the floor of the micro-blister lesions. 4 The results suggest that laminin may be a target for pro tease activation at the dermo-epidermal junction. This may account for the tendency of certain skin models to develop sulphur mustard-induced blistering. The Yucatan mini-pig may be valuable as a model to determine the effi cacy of prophylactic and therapeutic regimes.
Comparative metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices
Authors: Fisher Robyn L , Hasal Steven J , Sipes I Glenn , Gandolfi A Jay , Brendel Klaus 
Published: December 2008

1 Precision-cut liver slices, prepared from Sprague- Dawley and Fischer-344 rats and donated human liver tis sue, were used to identify differences in 1,2-dichloroben zene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB) and 1,4- dichlorobenzene (1,4-DCB) metabolism and how it may relate to toxicity. 2 Rat and human liver slices were incubated with 1 mM of either dichlorobenzene to determine metabolism and toxi city, at 2 and 6 h of organ culture. 3 The human liver slices metabolised the dichloroben zenes to a greater extent than those from either of the rat strains. Liver slices from the Fischer-344 strain had a higher metabolic rate than the slices from the Sprague- Dawley rat strain. 4 The metabolic rate of dichlorobenzene isomers did not consistently correlate with its toxicity. For example, human slices did not exhibit any hepatotoxicity, even though they metabolised these compounds to a greater extent than either rat strain. 5 Cross species covalent binding did not correlate with toxicity endpoints measured in this study. 6 The phase two metabolite profiles for each of the iso mers in human and rat slices were similar in that the glu tathione-cysteine conjugate was the major metabolite. 7 The use of an in vitro system which utilises human liver slices might provide an important bridge between animal derived data and the human situation.
An outbreak of tetrodotoxin poisoning following gastropod mollusc consumption
Authors: Yang Chen-Chang , Han Koh-Chew , Lin Tzeng-Jih , Tsai Wei-Jen , Deng Jou-Fang 
Published: December 2008

Tetrodotoxin, a violent neurotoxin, is present in puffer fish and may occur in a variety of marine animals. Outbreaks of human tetrodotoxin poisoning, following consumption of marine organisms other than puffer fish, has been rare. We here report an outbreak of tetrodotoxin poisoning fol lowing ingestion of gastropod molluscs and its clinical fea tures are discussed.A 71-year-old woman was admitted with hypertension and other neurological symptoms developing after inges tion of some molluscs. A further 16 cases were also found to have typical symptoms of tetrodotoxication after mol lusc consumption.Clinical features in these 17 cases were similar to those conventionally found in tetrodotoxin poisoning, except that there was hypertension in eight cases (47%). All except one case had mild poisoning and recovered well. The molluscs consumed comprised two different species: Nassarius castus and Nassarius conoidalis, both of which were shown to contain various amounts of tetrodotoxin.It is concluded that tetrodotoxin poisoning following mollusc consumption is a possibility. Hypertension, as an unusual feature in tetrodotoxication, is frequent in this outbreak, and should be looked for in future cases. The explanation of hypertension in tetrodotoxication may come either from an exaggerated response to sympathetic stimuli, or due to various responses of the vasomotor centre to a small dose of tetrodotoxin. Further studies are required to answer this question.
Organochlorine compound residues in human milk in the United Kingdom 1989-1991
Authors: Dwarka S. , Harrison DJ , Hoodless RA , Lawn RE , Merson Ghj 
Published: December 2008

1 The concentrations of some organochlorine pesticides and polychlorobiphenyls have been determined in 193 samples of human milk collected between July 1989 and July 1991. 2 Comparison of the results with those from previous studies in 1979-80, and earlier, shows a continuing decline in residue levels except for polychlorobiphenyls. 3 The concentrations of organochlorine pesticides and polychlorobiphenyls in human milk samples from resi dents in the United Kingdom compare favourably with data obtained in other countries.
Time-dependent porphyric response in mice subchronically exposed to arsenic
Authors: García-Vargas G. , Cebrián ME , Albores A. , Lim CK , De Matteis Francesco 
Published: December 2008

1 A time-course study was carried out in mice subchroni cally exposed to As III (as sodium arsenite) or As V (as sodium arsenate), via drinking water, relating the pattern of urinary porphyrin excretion to the renal and hepatic enzyme activities of porphobilinogen deaminase (PBGD), uroporphyrinogen III synthetase (URO III-S), uropor phyrinogen decarboxylase (URO-D) and coproporphyrino gen oxidase (COPRO-O), as well as to the hepatic por phyrin accumulation in the treated animals. 2 A time-dependent, wave-like porphyric response was found in mice exposed to As V, and the increases seen in total urinary porphyrins (at 3 weeks of exposure) corre sponded to an increased activity of PBGD and Uro III-S in liver. 3 Significant decreases in renal URO-D and hepatic and renal COPRO-O activities were found in treated mice; these inhibitions were more pronounced in animals exposed to As III. 4 The combination of these enzymic effects may explain the time-dependent porphyric response of mice subchroni cally exposed to As. Finally, the relative magnitudes of URO-D and COPRO-O inhibitions may determine the pat tern of porphyrin concentration observed in urine and tis sues. 5 The decrease in renal URO-D activity may help to explain the inversion in the coproporphyrin/uroporphyrin ratio previously reported in humans chronically exposed to As; however, there were differences between the uri nary porphyrin profiles found in both species. The possi ble reasons for the similarities and differences are briefly discussed.
HFA-134a (1 ,1, 1, 2-tetrafluoroethane): lack of oncogenicity in rodents after inhalation
Authors: Alexander DJ , Libretto SE , Chevalier H-J. , Imamura T. , Pappritz G. , Wilson J. 
Published: December 2008

1 Groups of 60 male and 60 female B6C3F1 mice or Han- Ibm Wistar rats were exposed to HFA-134a using snout- only inhalation exposure techniques for periods of one hour daily for at least 104 weeks. HFA-134a was deliv ered directly from cylinders at vapour concentrations of 2500, 15 000 and 75 000ppm for mice and from metered-dose inhalers at vapour concentrations of 2500, 10 000 and 50 000ppm for rats. 2 Intended dosages were achieved. 3 Evidence of absorption was found at each dose level and was dose related. 4 Neither species suffered any treatment related effects on survival, clinical signs, body weights, haematology nor on the type, incidence, site or severity of gross lesions. 5 There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats. 6 There were no non-neoplastic findings related to treat ment in mice. 7 HFA-134a was considered not to be oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.
Oxidative biotransformation of oxazepam to reactive and nonreactive products in rat, mouse and human microsomes
Authors: Griffin RJ , Burka LT , Demby KB 
Published: December 2008

1 The oxidative metabolism of oxazepam by human, B6C3F1 mouse and F344 rat microsomes was examined. The major metabolite in all three species was 6-chloro-4- phenyl-2(1H)-quinazolinecarboxylic acid (CPQ-carboxylic acid). In addition, rat microsomes produced 4'-hydroxyox azepam and oxazepam-dihydrodiol in NADPH-containing incubations.2 Covalent protein adducts were increased by the addi tion of NADPH to rat and mouse microsomes but not human microsomes. The magnitude of adduct formation was rats > mice > humans.3 Formation of oxazepam-dihydrodiol was reduced by the addition of cyclohexene oxide and GSH to the incuba tions. Two additional metabolites were produced under these conditions. One of these was tentatively identified as a GSH conjugate. Covalent adduct formation was unaffect ed by GSH or cyclohexene oxide.4 These results suggest that adduct formation occurred via an unknown reactive product rather than via oxazepam-epoxide, and that the relative rates of oxidative metabolism in vitro parallel that in vivo for the three species examined.