bluuebunny/crossref_metadata_2025 huggingface dataset:
Interspecies differences in enzymes reacting with organophosphates and their inhibition by paraoxon in vitro
Authors: Kaliste-Korhonen E. , Tuovinen K. , Hänninen O.
Published: December 2008

1 Inhibition of cholinesterases (ChE) and carboxyles terases (CaE) by paraoxon (Px) was studied in vitro in the serum, liver, lung and muscle of mouse, guinea pig, rabbit and man (serum only). Moreover, the role ofPx hydrolyzing enzyme (Pxase) in the detoxification of Px was studied by inhibiting its activity with EDTA.

2 The ChE and CaE activities as well as their sensitivity to Px varied in different tissues and species. The ChEs were more sensitive than CaEs to Px except in the liver. The CaE activity in human and rabbit sera was low and resistant to Px, indicating that it may have a minor importance for the binding of Px.

3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and rabbit sera during 24 h. In mouse, also the CaE activity was recovered. The presence of EDTA in the incubation medium prevented this reactivation indicating that Pxase takes part in the reactivation process.

4 In rabbit, the serum Pxase activity was very high suggesting a good Px detoxifying capacity of the rabbit serum.

5 The results show that amounts and sensitivities of esterases to OPs in rodents may markedly differ from that in man. Possible species-related differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing activity should be taken into the con sideration, when animal data are extrapolated to man.
Effects of pyridostingmine on acetylcholinesterase in different muscles of the mouse
Authors: Lintern Maxine C , Smith Margaret E , Ferry C Brian
Published: December 2008

1 Pyridostigmine bromide was administered subcuta neously in mice, in a dose of 0.4 or 2.0 ?moles/kg, and the activity of the predominant (G1, G4, and A12) molecular forms of acetylcholinesterase were exam ined in diaphragm, extensor digitorum longus (EDL), and soleus muscles at 3 h, 6 h, 24 h and 5 days.

2 In diaphragm, no effect was apparent after the low dose, but after the high dose there was a reduction in activity of the functional A12 form at 24 h, followed by an increase which had overshot the control level at 5 days.

3 In the fast EDL, after the low dose, all three molecular forms were decreased at 3 h, but had returned to normal by 6 h. This effect was not apparent after the high dose.

4 In the slow soleus the low dose caused a significant increase in total enzyme activity at 5 days, but the high dose caused significant increases in all molecular forms at 3 hours.

5 Thus pyridostigmine had delayed effects on the levels of acetylcholinesterase. The three muscles displayed different sensitivities to the drug, but the changes were consistent with initial inhibition of the activity leading to down-regulation of the enzyme followed by up- regulation, which could overshoot the normal levels.
The effects of multiple low doses of organophosphates on target enzymes in brain and diaphragm in the mouse
Authors: Williams Faith M , Charlton C. , de Blaquière Gail E , Mutch Elaine , Kelly SS , Blain PG
Published: December 2008

1 Multiple low doses of the direct acting organopho sphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and ecothiopate than for mipafox.

2 Ecothiopate did not inhibit brain acetylcholinesterase but there was a small increase in activity.

3 Mipafox also had a cumulative inhibitory effect on brain neuropathy target esterase.

4 These results have particular implication for the use of multiple low doses of organophosphates occupation- ally by man.
Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation
Authors: Dalsenter PR , Faqi AS , Webb J. , Merker H-J. , Chahoud I.
Published: December 2008

1 Reproductive toxicity and toxicokinetics of lindane during lactation were studied. For the reproductive toxicity study the dams were treated with a single dose of 6 mg/kg on day 9 or 14 of lactation, or with 1 mg/kg on days 9 to 14 of lactation. The male offspring were investigated at puberty and adulthood. For the toxicokinetic study, two groups of dams were treated with 6 mg/kg on day 9 or 14 of lactation. The concentration of lindane was measured in maternal plasma and milk, as well as in male offspring organs.

2 At adulthood, testicular weight and the number of sperm and spermatids were significantly reduced in all treated groups.

3 The testosterone level of the groups treated with 6 mg/ kg was significantly reduced to approximately 50% at puberty as well as in adulthood. In the group treated with 1 mg/kg, the testosterone level was in both age periods reduced, however, only at puberty was the reduction statistically significant.

4 The concentration oflindane in the testis was similar to that found in brain and was half the concentration found in the liver.

5 Histologically some areas of the testis exhibited distinct alterations ranging from small changes to a pronounced effect.

6 Exposure to lindane during lactation induces repro ductive hazards to male offspring rats which are detectable at adulthood.
Covert poisoning with difenacoum: clinical and toxicological observations
Authors: McCarthy PT , Cox AD , Harrington DJ , Evely RS , Hampton E. , Al-Sabah AI , Massey E. , Jackson H. , Ferguson T.
Published: December 2008

1 The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 year old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described.

2 Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarbox yprothrombin (DCP) unexpectedly increased.

3 Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1).

4 Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion ofthe vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.
Positron emission tomography studies of healthy volunteers-no effects on the dopamine terminals and synthesis after short term exposure to toluene
Authors: Edling C. , Hellman B. , Arvidson B. , Johansson G. , Andersson J. , Hartvig P. , Valind S. , Långström B.
Published: December 2008

Despite extensive research, the mechanisms for the effects of organic solvents on the central nervous system are still unknown. One mechanism proposed is that solvents interfere with the synthesis of neurotransmitters. In the present study 11 male healthy volunteers were exposed during 15 min to 100 p.p.m. toluene at light physical exercise, and the dopamine decarboxylase activity and number of terminals in putamen were measured before and after exposure by positron emission tomography. Two different tracers were used, [β-11C]L-DOPA for decarbox ylase activity during the in vivo synthesis of dopamine, and [11C] nomifensine to estimate the number of terminals. Although there was a slight increase in the rate of dopamine synthesis in the putamen after the exposure, this difference was not statistically significant (P=0.4). No effect was observed with regard to the uptake of nomifensine. There was no significant relationship between the dose of toluene and rate of dopamine synthesis, and no significant correlation between the time from end of exposure to start of the PET-camera and DOPA. Our findings indicate that short term exposure to 100 p.p.m. of toluene does not affect the rate of dopamine synthesis or the number of presynaptic terminals.
Effect of perinatal vitamin A or retinoic acid treatment (hormonal imprinting) on the sexual behavior of adult rats
Authors: Csaba György , Gaál Annamária
Published: December 2008

Single neonatal treatment with vitamin A (retinol) dramatically reduced the sexual activity of adult male rats. In females there was a significant decrease in the Meyerson index and a non significant decrease in the lordosis quotient. The effect of three perinatal treatments (at the first, third and fifth day) with all-trans retinoic acid was much weaker, causing only a significant increase in the time of the first ejaculation in males and non- significant decrease in the lordosis quotient of females.

The experiments call attention to the false imprinting provoking effect of materials acting on members of the steroid receptor superfamily with possible human health aspect.
Induction of cytochrome P450 3A by retinoids in rat hepatocyte culture
Authors: Jurima-Romet M. , Neigh S. , Casley WL
Published: December 2008

1 Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all- trans-retinoic acid, 9- cis-retinoic acid, 13- cis-retinoic acid or fenreti nide.

2 Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold in hepatocytes treated with the retinoids compared to control cultures.

3 CYP1A1 and CYP1A2 RNA levels were only slightly affected or unaffected by the retinoids.

4 The induction of CYP3A by these therapeutically- useful retinoids suggests that they may share a common mechanism for accelerated drug catabolism and acquired clinical resistance.
The efficacy of calcium gluconate in ocular hydrofluoric acid burns
Authors: Beiran Itzchak , Miller Benjamin , Bentur Yedidia
Published: December 2008

1 Although calcium gluconate (CG) is recommended in the treatment of hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and controlled human or animal studies are limited. The study's objective is to compare the efficacy of 1% CG and normal saline irrigation for the treatment of HF eye injury in animals.

2 0.05 ml 2% HF was instilled to anesthetized rabbit's eyes. One minute later, four treatment groups were studies: (1) irrigation with normal saline followed by topical antibiotics, corticosteroids and cycloplegics for 48 h ( n=10); (2) irrigation with 1% CG followed by the same topical treatment ( n=9); (3) as group 1 and 1% CG drops over 48 h ( n=10); (4) as group 3, and injection of 1% CG subconjunctivally after irrigation ( n=9).

3 Corneal erosion area, corneal haziness, conjunctival status, vascularization (pannus) and acidity were assessed before injury, immediately after intitial treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein staining.

4 Conjunctival pH dropped from 6.0 - 6.5 to 2.5 - 3 after injury and increased to 6 - 6.5 after irrigation. Corneal erosion: smaller in groups 2, 3, significantly so at 2 days, but not different at 14 days. Corneal haziness: more severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2 - 4 eyes in each group.

5 It seems that for HF injury 1% CG did not have any significant advantage over saline irrigation and topical treatment only. It might have some initial and temporary effect on healing process especially that involving erosion. Given subconjunctivally, 1% CG may be toxic and worsens clinical outcome.
Reproductive toxicity testing of pharmaceutical compounds to support the inclusion of women in clinical trials
Authors: Parkinson Chris , Thomas Kate E , Lumley Cyndy E
Published: December 2008

1 The potential for toxicity to reproduction and the developing fetus is an important concern requiring attention during the development of new medicines. However, there are differences in the opinions of the regulatory authorities in Europe, Japan and the USA regarding the nature and amount of data from reproductive toxicity tests that should be available at the various stages of clinical development.

2 Forty-one companies or their subsidiaries from Eur ope, Japan and the USA provided data for a ques tionnaire-based study, carried out in 1994, to ascertain the practices of pharmaceutical companies and their views on an ideal approach to the timing of reproduc tion and development toxicity studies in relation to clinical investigation.

3 Differences were identified in the stage of drug development at which animal studies were completed, the sequence of completion of specific studies, and the extent of reproduction testing completed to support the inclusion of women in clinical trials.

4 A harmonised, but flexible, guideline, encompassing the timing of reproductive toxicity studies in relation to clinical trials, would permit better integration between clinical and non-clinical studies in an international drug development programme.
Pro- and anti-oxidant parameters in rat liver after short term exposure to hexachlorobenzene
Authors: Almeida MG , Fanini F. , Davino SC , Aznar AE , Koch OR , Barros SB de M
Published: December 2008

The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated. After 30 days of treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome P450 system, increase in microsomal super oxide anion generation accompanied by increased levels of liver lipid peroxidation, as measured by the production of thiobarbituric acid reactants and by spontaneous visible chemiluminescence. Concomitantly, liver antiox idant defenses are slightly modified, with decreased activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase contributing to an oxidative stress condition of the liver. These liver biochemical alterations are closely related to increased levels of urinary coproporphyrin, plasma AST and ALT activities and to the onset of liver morphological lesions
Ocular injury with xylene - a report of two cases
Authors: Ansari Ejaz A
Published: December 2008

1 Xylene is a hydrocarbon solvent found in various industrial preparations such as paint and is widely used in pathology laboratories.

2 When inadvertently instilled into the eye significant ocular injury can occur with the potential for blindness.

3 Such injuries to the ocular surface resemble those due to alkali.

4 Ocular surface injury due to xylene has not been reported previously in the literature. We strongly recommend that these injuries be treated as emergen cies in a similar way to alkali burns in the Eye department since the chemical mixture of which xylene forms a part may be alkaline. Such an approach is vital in order to save sight.
Acute hydrogen selenide gas poisoning admissions in one of the hospitals in Delhi, India: case report
Authors: Banerjee BD , Dwivedi S. , Singh S.
Published: December 2008

Acute gas poisoning is one of the most important medicosocial problems in the developing countries. An outbreak of acute inhalation exposure to hydrogen selenide occurred in Delhi, India. This report includes our findings on epidemiological, clinical and biochemical investigations in 31 cases hospitalized immediately after the gas poisoning.
Intravenous organophosphate injection: an unusual way of intoxication
Authors: Güven Muhammed , Ünlühizarci Kürşad , Göktaş Zeliha , Kurtoğlu Selim
Published: December 2008

Organophosphate insecticides strongly inhibit both true cholinesterase and pseudocholinesterase activities. In this report, we have reported a patient who injected himself a strong organophosphate compound, methamidophos, and showed the typical clinical picture of organophosphate intoxication. As far as we know, this is the first case of intoxication by intravenous (i.v.) injection. With the appropriate therapy, his symptoms disappeared in a few days.
Lead exposure in papier mâché workers
Authors: Wahid A. , Koul PA , Shah SU , Khan AR , Bhat MS , Malik MA
Published: December 2008

Lead exposure was assessed in a random cohort of 70 male papier mâché workers and compared with 35 age and sex matched controls. Blood lead levels in workers were significantly higher than in controls (Mean 68.07 ± 44.64 ug/dl vs 25.52 ± 16.56 ug/dl respectively; P < 0.001). Urinary lead was also higher in workers (128.53 ± 52.61 ug/l) compared to controls (91.18 ± 27.06, P < 0.001), but excretion of urinary coproporphyrin in the two groups was not significantly different (102.78 ± 153.42 vs 70.03 ± 27.06 ug/l, P > 0.05). Blood levels bore a significant correlation with age but did not bear any correlation with the duration of exposure. Various modes of exposure to lead included hand mixing of paints, skin application of the paint to match shades and making point of the brush using lips and the tongue.
Trichloroethylene radicals generated by ionizing radiation. An EPR/spin trapping study
Authors: Carmichael Alasdair J , Steel-Goodwin Linda
Published: December 2008

Trichloroethylene (TCE) was exposed in the presence of the spin trap N- tert-butyl-α-phenyl nitrone (PBN, 0.1 M) to ionizing radiation from two different sources in an attempt to determine the origin of the spin-trapped radicals generating the EPR spectra in precision cut liver slices. TCE samples were irradiated with 18 MeV electrons to a total dose of 1000 Gy in a linear accelerator (LINAC) or exposed to 60Co γ-rays to total doses of 100 Gy and 1000 Gy. The results show that three PBN adducts were generated during the LINAC radiations. Two of these spin adducts correspond to the addition of carbon-centered radicals to PBN, and the third adduct is consistent with a decomposition product of PBN. The predominant carbon- entered radical yields a PBN adduct that is more stable, persists for over 24 h and has identical hyperfine coupling constants (a N=1.61 mT, aHβ=0.325 mT) to the PBN adduct obtained when precision-cut liver slices were exposed to TCE. Gamma radiation (100 Gy) of TCE yields PBN adducts with lower primary nitrogen hyperfine coupling constants (aN=1.45 mT and aN=1.54 mT). The results (y- radiation) suggest that the carbon-centered radical is formed on a single TCE carbon that is different than the predominant radical formed during LINAC radiations. This difference is confirmed by experiments using 13C- TCE. The results further suggest that, during γ-radiation of TCE, the radicals are formed by dechlorination at the TCE carbon containing two chlorine atoms. The results obtained during LINAC radiations suggest that the predominant radical is formed by dechlorination at the TCE carbon containing a single chlorine and a single proton. In addition, it is possible that this radical is the initial TCE radical formed during exposure of liver slices to TCE.
Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning
Authors: Worek F. , Bäcker M. , Thiermann H. , Szinicz L. , Mast U. , Klimmek R. , Eyer P.
Published: December 2008

1 In vitro studies with human erythrocyte acetylcholin esterase (AChE) and the mouse diaphragm model were performed to unravel the various microscopic reaction parameters that contribute to the dynamic equilibrium of AChE inhibition, ageing and reactivation. These data may help to define more precisely the indications and limitations of oxime therapy in organophosphate (OP) poisoning.

2 Diethylphosphoryl-AChE resulting from intoxications with parathion, chlorpyrifos, chlorfenvinphos, diazi non and other OPs is characterized by slow sponta neous reactivation and low propensity for ageing. This kind of phosphorylated enzyme is particularly sus ceptible to reactivation by oximes.

3 None of the oximes tested (pralidoxime, obidoxime, HI 6 and HLö 7) can be regarded as a universally suitable reactivator. Obidoxime turned out to be the most potent and most efficacious oxime in reactivating AChE inhibited by various classes of OP insecticides and tabun. Obidoxime, however, was inferior to HI 6 against soman, sarin, cyclosarin and VX. Pralidoxime was generally less potent.

4 The kinetic data of reactivation established for diethylphosphoryl-AChE of human red cells indicate that the usually recommended dosage to attain a plasma concentration of 4 μg/ml does not permit exploitation of the full therapeutic potential of the oximes, in particular of pralidoxime. However, in suicidal mega-dose poisoning, oximes, even at optimal plasma concentrations, may be unable to cope with the fast re-inhibition of reactivated AChE in the first days following intoxication.

5 It is suggested that oximes be administered by continuous infusion following an initial bolus dose as long as reactivation can be expected and until permanent clinical improvement is achieved.
MCS (Multiple Chemical Sensitivity): Cooperation between toxicology and psychology may facilitate solutions of the problems: commentary
Authors: Bock Karl Walter , Birbaumer Niels
Published: December 2008

This commentary is the result of a discussion between the authors. After outlining the problem of MCS (A), to which the toxicologist was increasingly and painfully exposed, he was surprised to realise that the problem was well recognised in psychology. (B) In the second round of the discussion therapeutic implications are discussed.
Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water
Authors: Vojdani Aristo , Mordechai Eli , Brautbar Nachman
Published: December 2008

1 In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce pro grammed cell death.

2 Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene- 5 contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene.

3 Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry.

4 When apoptotic lymphocytes from exposed indivi duals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 ± 1.8 and 12.1 ± 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals ( P<0.0001, Mann-Whitney U-Test). MTBE and ben- a zene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumu lated at the S-G2/M boundaries.

One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kB). NF-kB was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kB activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kB activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.
Transplacental passage of aluminium from pregnant mice to fetus organs after maternal transcutaneous exposure
Authors: Anane Rachid , Bonini Michèlle , Creppy Edmond Ekué
Published: December 2008

Aluminium is present in tap water, antiperspirants and cosmetics up to 20%. Teratogenicity of aluminium was clearly identified after per os or intravenous administra tion. Malformations and other alterations by aluminium intoxication were evaluated in fetus. In the present study, we investigated the possible transplacental passage of aluminium and its accumulation in the tissue after cutaneous uptake. Female Swiss mice received alumi nium chloride by cutaneous way (0.4 μg/day) during 20 days of gestation. The samples were assayed for alumi nium quantification by graphite furnace atomic absorp tion with Zeeman correction. This treatment led to an increase of aluminium in maternal and fetus samples (serum, amniotic fluid and organs) as compared to controls.
Ganciclovir induces reproductive hazards in male rats after short-term exposure
Authors: Faqi AS , Klug A. , Merker H-J. , Chahoud I.
Published: December 2008

1 The effect of short-term treatment of ganciclovir on male reproduction in adult rats was studied. The animals were treated subcutaneously with either a single dose of 60 mg/kg daily for 5 days (Gan5day) or with 100 mg/kg administered three times at 4 h- intervals (Gan1day). The effects were investigated every 2 weeks up to 8 weeks, followed by investigations 16 and 24 weeks after treatment to detect the potential of recovery.

2 Time to mating was significantly increased in Gan1day group. The pregnancy index and outcome were only decreased 8 weeks (Gan5day and Gan1day) or 16 weeks (Gan1day) after treatment.

3 The lowest values of sperm variables studied were registered 8 weeks after treatment: The number of spermatid was reduced up to 4% (Gan5day) or 2% (Gan1day) of control; the sperm number was 5% and 8% of control in Gan5day and Gan1day, respectively. Over 80% of sperm were abnormal in Gan5day group, and only few normal sperm was detected in Gan1day group.

4 Morphological investigation of testes revealed a clear- cut time-dependency effect. Four weeks after treat ment distinct alterations were located exclusively in the peripheral part of the tubuli which included fat inclusions, cell and pyknotic nuclear debris and swellings of Sertoli cells. The effect was reversible 24 weeks after treatment.

5 Ganciclovir induces testicular damage and affects sperm variables after short-term exposure. The in tensity and degree of the hazards varied in between the time of investigation after treatment.
Transgenerational effect of a single neonatal benzpyrene treatment (imprinting) on the sexual behavior of adult female rats
Authors: Csaba G. , Karabélyos Cs
Published: December 2008

Male and female rats were neonatally treated with a single dose of benzpyrene. The adult animals were mated inter se, forming control-control, benzpyrene (female)-control, benzpyrene (male)-control, and benzpyrene-benzpyrene treated couples. In the F 1 and F2 generations (without any further treatment) the females's sexual behavior was tested to Meyerson index and lordosis quotient after ovariectomy and hormone treatment, using experienced males. In the F1 generation both indices were significantly reduced in the maternally treated, paternally untreated groups, however this reduction was not present in the group where the treatment was maternal and paternal alike. In the F2 generation, beside the more expressed reduction in the grandmaternally treated group, a moderate reduction in the sexual activity of progenies having treated grandfather or two treated grandparents were observed. The experiment call attention to the transgenerational sexual behavioral effect of a dangerous environment pollutant, benzpyrene.
The myelotoxicity of chloramphenicol: in vitro and in vivo studies: I. In vitro effects on cells in culture
Authors: Holt DE , Ryder TA , Fairbairn A. , Hurley R. , Harvey D.
Published: December 2008

1 Chloramphenicol is used extensively in non-industria lized countries for the treatment of life-threatening infections because it is cheap and effective, despite its known hemotoxicity and linkage to fatal aplastic anaemia. It is important to define the mechanism of toxicity so that means can be devised to ameliorate the toxic effects in order to produce safer usage.

2 Chloramphenicol, at concentrations from 5 mM to 2 mM initiated apoptosis in dividing cells from a monkey kidney-derived cell line and in haematopoie tic progenitor cells from human neonatal cord blood.

3 Growth of progenitor cells was suppressed at concen trations of chloramphenicol which would be consid ered less than therapeutic during patient treatment.

4 These effects could be ameliorated in progenitor cells by co-culture with the antioxidant mercaptoethyla mine and in monkey kidney cells by co-culture with vitamin C.

5 This is the first report of apoptosis in chloramphenicol toxicity and suggests a possible link between a metabolic event i.e. the production of free radicals; a morphological effect, apoptosis; and a clinical effect, bone marrow suppression and aplastic anaemia.
Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non smokers by No2
Authors: Dandrea Tiziana , Ba Tu  , Blomberg Anders , Sandström Thomas , Sköld Magnus , Eklund Anders , Cotgreave Ian
Published: December 2008

Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture super natants were collected 4 h after the exposure and assayed for secreted TNF-α, IL-1β, IL-8 and MIP-1α. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-α and IL-1β, but not IL-8 (MIP-1α not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-,1.5- and 3-fold the amounts of IL-1β, IL-8, TNF-α and MIP-1α, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration- dependent inhibition of the secretion of all cytokines except IL-1β from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-α from non-smoker's cells was inhibited by the gas in a concentration- dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-α. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1β mRNA. However, exposure to the gas inhibited LPS- induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcrip tional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.
The role of mouse intestinal microflora in the metabolism of trichloroethylene, an in vivo study
Authors: Moghaddam AP , Abbas R. , Fisher JW , Lipscomb JC
Published: December 2008

1 Both trichloroethylene and its metabolite, dichloroa cetic acid, produce liver tumors peroxisome prolifera tion and other adverse cellular alterations in rodents.

2 The hepatic mechanism by which dichloroacetic acid is formed is not conclusively demonstrated, but pharmacokinetic models have successfully associated its formation with trichloroacetic acid as immediate precursor.

3 Previous investigations have shown that dichloroace tic acid is formed from trichloroacetic acid by gut microflora isolated in vitro.

4 To determine the impact of gut microflora on dichlor oacetic acid formation from a trichloroethylene dose in vivo, we developed a procedure which reduced gut microflora some 3 orders of magnitude below pub lished levels.

5 The administration of trichloroethylene to control mice and to mice whose gut was practically sterile resulted in equivalent concentrations of dichloroace tic acid and other metabolites in blood and liver, but significantly different content of these metabolites in cecum contents.

6 These data indicate that gut microflora contribute minimally, if at all, to the formation of circulating dichloroacetic acid under these conditions.
The percutaneous absorption and skin distribution of lindane in man
Authors: Dick Ian P , Blain Peter G , Williams Faith M
Published: December 2008

1 The absorption of lindane through human skin was assessed in vitro using static diffusion cells with 50% aqueous ethanol as the receptor fluid. Four formula tions of lindane were applied, three of which were commercial preparations. The dermal distribution of lindane within the skin was also examined, focusing particularly on any association of lindane to the stratum corneum. The results were then compared with a parellel in vivo study.

2 Two of the formulations contained white spirit as the predominant solvent, and lindane absorption was greatest from these preparations in terms of the percentage of the applied dose (15-25% by 24 h). Absorption was less from an aqueous spray dilution (3% by 24 h), with absorption from acetone being the least ( < 1% by 24 h). Similar amounts of lindane penetrated by 24 h for the acetone and white spirit- based applications (approx. 8 ?g). This supported the in vivo observation that similar plasma lindane levels were recorded following exposure to the acetone solution and the white spirit-based formulation A, although the lindane concentration in acetone was 40- fold higher.

3 For the acetone and water-based preparations, a soap/ water swab of the skin surface at 6 h contained the majority of the applied dose (around 75%). Substantial amounts of lindane were recovered in tape-strippings taken at 6 h (representative of stratum corneum content) which were significantly greater than lindane in the remainder of the skin, for the acetone solution and formulation A. This provided a strong indication that lindane had accumulated in the stratum corneum, a property that has been linked with other lipophilic chemicals.
Inhibitory effects of antibiotics on platelet aggregation in vitro
Authors: Kariyazono Hiroko , Nakamura Kazuo , Shinkawa Terutoshi , Moriyama Yukinori , Toyohira Hitoshi , Taira Akira , Yamada Katsushi
Published: December 2008

1 We evaluated in vitro inhibitory effects of six types of antibiotic, aztreonam (AZT), cefamandole (CMD), cefmetazole (CMZ), cefotiam (CTM), flomoxef (FMOX) and latamoxef (LMOX), on platelet aggregation, using healthy volunteers' blood. Four types-FMOX, LMOX, CTM and CMD-inhibited, in concentration of 2500 ?g/ml, the secondary aggregation induced by 3.0 ?M adenosine diphosphate (ADP), and also inhibited the aggregation induced by 0.5 ?g/ml collagen. AZT in the same concentration, did not inhibit the aggregation induced by collagen, and it inhibited only ADP induced aggregation. CMZ, in the same concentration, inhibited neither of the two aggregations.

2 The inhibitory effects of the antibiotics on collagen- induced aggregation were dependent on the concen tration of respective antibiotics. When classified by the strength of inhibitory action, LMOX and FMOX were strong, followed by CTM and CMD. The action of AZT and CMZ was weak. In particular, LMOX showed a 32% inhibitory effect at concentration of 50 ?g/ml, a level near the blood concentration obtained with clinical usual dose.

3 No relationship was observed between inhibitory effects of antibiotics on ADP- or collagen-induced aggregation and the presence or absence of carboxyl group and/or N-methyltetrazolethiol group in the chemical structure.
Compartmental transfer of mercury released from amalgam
Authors: Halbach S. , Kremers L. , Willruth H. , Mehl A. , Welzl G. , Wack FX , Hickel R. , Greim H.
Published: December 2008

The number of amalgam-covered surfaces and the occlusal area of the fillings, the concentrations of total mercury in plasma, erythrocytes and urine, the urinary excretion rate, and the absorbed daily doses estimated by two separate methods from intra-oral Hg emission were determined in 29 volunteers with a low amalgam load. The transfer ofHg from the fillings via the oral cavity and blood to urinary excretion was evaluated by multiple correla tions between these variables. In addition, the combina tion of variables most representative of the entire compartmental transfer of amalgam Hg was determined. Urinary excretion (1), Hg concentration in plasma (2) and absorbed dose (3) were most closely correlated to each other, followed by correlations with the variables of the fillings (4). Correlation coefficients were 0.75 for variables 1 vs 2 and 2 vs 3, and 0.49 for variables 3 vs 4. It was concluded that variables 1-3 best reflected the transfer of mercury from amalgam fillings throughout the organism and that they were relatively insensitive to dietary mercury. The determination of total mercury in plasma and of its urinary excretion rate appears, under practical aspects, most suitable for the investigation of Hg uptake from amalgam.
Amitraz poisoning in children: Clinical and laboratory findings of eight cases
Authors: Aydin Kürsad , Kurtoglu Selim , Poyrazoglu M. Hakan , Üzüm Kazim , Üstünbas H. Basri , Hallaç I. Kurtulus
Published: December 2008

Amitraz poisoning is a rare disorder characterised by central nervous system and respiratory depression, bradycardia, hypotension, hypothermia, hyperglycemia, vomiting, convulsion and glycosuria. In this study, eight pediatric patients with amitraz poisoning were presented. This study revealed that clinical manifestations of poisoning by oral and dermal route emerged within 30- 120 min and that central nervous system depression which is the most important sign resolved with 8-18 h and others 36-48 h. All cases were discharged as recovered after 48 h. To our knowledge only six cases have been reported in the literature. Because of the limited information in the literature, the cases were reported.
Should Rehabilitation Be Mandatory in Workers' Compensation Programs?
Authors: Berkowitz Monroe
Published: December 2008

When workers' compensation and public vocational rehabilitation programs began in the first decades of this century they were closely allied but now have drifted apart. In an effort to bring the benefits of rehabilitation to work-injured persons, some state workers' compensation programs, beginning with California in 1975, mandated the referral of workers to rehabilitation, but not necessarily to the public program. It has proven most difficult to mandate those services. Decisions about when to intervene, how to intervene, and what services ought to be provided—decisions once left to the parties—must be specified in detail if the services are compulsory. In recent years there has been a retreat from the mandatory provisions. Some states have repealed the provisions outright; others have provided different financing devices. The controversy about mandatory rehabilitation illustrates how little we know about the basic mechanics and economics of the process, or at least how little we know which is convincing to state legislatures. Some modest proposals are made for increasing our knowledge in these areas.
Into the Private Sector
Authors: Bowe Frank G.
Published: December 2008

Until late 1988, American social policy proscribed discrimination against people with disabilities only in the public (government or government-assisted) sector of the economy. Title V of the 1973 Rehabilitation Act (PL 93-112), for example, regulated employment practices in federal agencies, federal contractors, and entities receiving federal financial assistance. The Americans with Disabilities Act (S.933 and H.R.2273, pending), however, reaches deep into the private sector and builds upon the precedent set by the 1988 Fair Housing Amendments Act (PL 100-430). In this article, the major provisions of the ADA are outlined and rationales are offered for the choices made in shaping the legislation; the focus is upon the Senate because the House had not completed action at press time. The bill represents a growing consensus by Republicans as well as Democrats that private-sector regulation is essential if people with disabilities are to gain access to telecommunications, places of public accommodation, transportation, and employment. It responds to data showing that few Americans with disabilities attend sporting events, see movies or plays in public theatres, or eat in restaurants (Harris, 1986) and that employment of persons with disabilities has actually fallen (Bennefield & McNeil, 1989) since the Rehabilitation Act of 1973 was passed, in large part because most new jobs created by the American economy since that time have been in small, private companies, very few of which are covered by that act's Title V requirements.
Migration and the Demand for Developmental Disabilities Services
Authors: Weller Robert H. , Terrie E. Walter , Serow William J.
Published: December 2008

Synthetic estimation techniques are used to project the number of developmentally disabled persons in Florida in the year 2000. This yields an idea of the future number of these persons if migration continues at its current pace. Next, the population is projected on the assumption that no net migration occurs in the future and the same prevalence rates are applied to that projection. The difference in the number of persons with developmental disabilities yielded by the two sets of synthetic projections illustrates the effects of migration upon demand. Demand for developmental disabilities services is projected to increase by 36% over 1985 levels by the year 2000. Only 11% of the projected increase is due to reproductive change among persons already resident in Florida in 1985. The remainder is due to net migration into Florida. Because the movement of persons who are developmentally disabled seems to be part of a general stream of migration to Florida rather than a separate one, the demands placed upon the state's infrastructure to prevent deterioration of per capita service levels is affected by decisions made elsewhere and the state must largely react to changes in service demand created by population change rather than playing an active role in shaping it.
Setting an Employment Agenda: A Demonstration with the Epilepsy Foundation of America
Authors: Roessler Richard T. , Schriner Kay Fletcher , Troxell Jim
Published: December 2008

The Epilepsy Foundation of America (EFA) participated in the National Agenda for Employment of People with Disabilities project, co-sponsored by the President's Committee on Employment of People with Disabilities and the Arkansas Research and Training Center in Vocational Rehabilitation. The organizational agenda creation process involves three phases: (a) collection of consumer data regarding employment concerns, (b) discussion of the implications of the data by providers and people with epilepsy, and (c) development of an organizational agenda based on phases one and two. Results of the three-step process are discussed in this article.
Medical Specialty Board Examinations and Physicians with Disabilities: An Investigation into Current Practices
Authors: Gerber Paul J. , Popp Patricia
Published: December 2008

Special testing accommodations is an issue that affects both medical specialty boards and physicians with disabilities in the administration of medical specialty examinations. To assess practices of medical specialty boards when physicians with disabilities request nonstandardized testing, all of the medical specialty boards were surveyed. It was found that there is great variance in policies, procedures, and practices regarding such testing. Flexible systems, both formal and informal, are currently in place that provide ample opportunities for reasonable accommodations when physicians take specialty board examinations.
A Historical Overview of Research in Supported Employment: Implications for the Next Decade
Authors: DeStefano Lizanne
Published: December 2008

A goal of this paper is to overview the nature of research methodology used in studies of supported employment and to discuss implications for the next decade of supported employment research. Because of the similarities between the two initiatives, a methodological framework or cycle developed to analyze research on transition was used as the organizer for this overview of supported employment.
Personal Assistance Services
Authors: Nosek Margaret A.
Published: December 2008

Affordable, attainable, high-quality personal assistance services could enable millions of people with severe physical disabilities to lead productive and independent lives. Indeed, the degree to which these services are available and adequate in large part determines the potential of such persons to be employed and to be active participants in community life, regardless of the individual's inherent capability to achieve these goals. This article defines and estimates the need for such services and reviews literature that addresses issues of funding and service delivery mechanisms. The article analyses implications of a public policy focus on redirecting existing funding channels, the possibility of incorporating consumer control and other independent living concepts and techniques into existing service structures, the impact of reliance on family, and methods for making services available to a larger segment of the population in need.
Evidence on the Occupational Segregation of Women With Disabilities
Authors: Baldwin Marjorie
Published: December 2008

Differences in the occupational segregation of disabled and nondisabled women were investigated. A logit model of occupational choice was estimated with data from the 1984 panel of the Survey of Income and Program Participation (SIPP). The dependent variable in the model equaled 1 if the woman was employed in a predominantly male occupation. Independent variables in the model controlled for workers' labor force attachment, health status, and for the demand for labor in predominantly male occupations. The results indicated no significant differences in the occupational segregation of the two groups of women. Disabled women encounter just as much segregation in the labor market as do nondisabled women.
Emotional and Behavioral Disorders
Authors: Swartz Stanley L. , Mosley William J. , Koenig-Jerz Georgianna
Published: December 2008

An analysis of state definitions ( N = 51, including the District of Columbia) of the emotionally disturbed/behaviorally disordered category of handicapped children, entrance and exit criteria, and procedures for referral, evaluation, and program placement is reported. Lack of definitional consensus and eligibility agreement were found. A detailed analysis of each state and an overall analysis are reported. Lack of agreement among states and with the federal definition are reviewed and discussed.
Financing Personal Assistance Services
Authors: Litvak Simi
Published: December 2008

Existing publicly funded personal assistance service (PAS) programs are inadequate. How to pay for adequate programs is now the critical question. This article outlines some of the options for increasing the availability of PAS in the U.S. The options discussed fall into three broad categories: (a) reallocation of funds currently used for institutional placement, (b) expansion of existing programs with or without additional expenditures, and (c) consolidation of existing programs along with additional expenditures. Financing recommendations include suggestions for action at both the federal and state levels.