bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetry and pathology of 237Np in female rats
Authors: Sontag W. , Wirth R. , Luz A. , Schäffer E. , Volf V.
Published: December 2008

Female Sprague-Dawley rats, 10-12-week old and weigh ing about 240 g, were injected intravenously with 237Np nitrate. In the toxicological study 77 rats served as controls and 28 rats per group received single doses of 5.2 and 26 kBq, respectively, per kg body weight. In addition, 12 rats of each injection level, sacrificed at defined points in time, were used for dosimetric studies. During the whole life-span the body weight and 237Np whole body-content of each animal were recorded. After death a detailed pathological examination was made of each animal in the cronical study. One day after injection 48% of the injected activity was in the skeleton, 9.3% in the liver, 3% in the kidneys and 4.4% in the rest of the organs. Whereas in all organs the activity decreased very fast, the half-life in the skeleton was about 1400 days. The bodyweights were comparable in the three groups, but the life span decreased from 800 days (control group) to 644 days after injection (26 kBq kg -1 body weight group). The main lesions in the female rats were mammary tumors (73%) and pituitary gland tumors (52%). With increasing activity the incidence of pituary gland tumors decreased and that of osteosarco mas increased from 1.3% (control group) to 32% (26 kBq kg-1 body weight group), whereas the remaining lesions showed no influence on the activity.
Membrane attack induced by HlyA, a pore-forming toxin of Vibrio cholerae
Authors: Huntley James S , Sathyamoorthy Venugopal , Hall Robert H , Hall Andrew C
Published: December 2008

Determining the activity of purified toxins has generally provided the basis for establishing their role in the host- pathogen relationship. The bacterial genus Vibrio pro duces a number of exotoxins in addition to cholera toxin, including haemolysin A (HIyA; Vibrio cholerae) and thermostable direct haemolysin (TDH; Vibrio parahae molyticus) , both of which possess membrane-targeting cytolytic activity. The action of HlyA has been analyzed using protocols previously applied to TDH: lysis and flux experiments on human erythrocytes showed that HlyA similarly causes lysis after cell swelling (by colloid osmosis) due to an elevation of cation permeability. However, kinetic measurements of flux, haemolysis and cation selectivity showed that HlyA and TDH form pores with distinct and characteristic features.
Protection of A549 cells against the toxic effects of sulphur mustard by hexamethylenetetramine
Authors: Lindsay Christopher D , Hambrook Joy L
Published: December 2008

The A549 cell line was used as a model of the deep lung to study the toxicity and mechanism of action of sulphur mustard (HD), using the neutral red (NR) dye retention and gentian violet (GV) assays as indices of cell viability. It was found that exposure to concentrations in excess of 40 μM HD resulted in a rapid onset of toxicity. Exposure to 1000 μM HD reduced viability in A549 cell cultures to 61% after 2 h (control cultures=100%), whereas exposure to 40 μM HD did not result in deleterious effects until 26 h at which point viability fell to only 84% (NR assay). Agarose gel electrophoresis of cell cultures exposed to 40 and 1000 μM HD and harvested at 4.5, 19 and 43 h after exposure to HD, indicated that cell death was due to necrosis, despite the observation that at the higher concentration of HD cells displayed many of the features common to cells undergoing apoptotic death.

The ability of hexamethylenetetramine (HMT) to protect A549 cells against the effects of an LC50 challenge dose of HD was assessed using the GV and NR assays. It was found that HMT (15 mM) could protect cells against the effects of HD though HMT had to be present at the time of HD challenge. Cultures treated with HD only were 49% viable at 48 h after HD challenge, compared to 101% for protected cultures (NR assay) and 58% and 91% for unprotected and protected cultures respectively using the GV assay. Morphological observations of GV and NR stained cultures confirmed these findings. HMT concen trations of 2.5 to 25 mM were used. Maximal protection against the toxic effects of HD (LC50) was found at 10 to 25 mM HMT. Over this concentration range, HMT did not exert any toxic effects on A549 cells.

Pretreatment of A549 cultures with HMT followed by its removal prior to HD challenge had no protective effect. Similarly, treating cultures with HD followed by addition of HMT did not increase the viability of the cultures, even if the HMT was added immediately after HD exposure. HMT was found to protect against the toxic effects ofHD, though it must be present at the time ofHD challenge. A549 cells were found to be a valuable experimental model for studying the toxicology of HD and other lung damaging agents, and for screening other compounds for potential therapeutic efficacy as a prelude to studies with non- transformed cell culture systems and in vivo models.
Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis
Authors: Rio B. , Parent-Massin D. , Lautraite S. , Hoellinger H.
Published: December 2008

The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis.

The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Ery throid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the develop ment of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentia tion showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10-4 M) that have no adverse effect on cellular proliferation.
Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers
Authors: Crosbie Sarah J , Blain PG , Williams Faith M
Published: December 2008

1 The in vitro metabolism ofn-hexane was studied in rat liver, lung, brain and skeletal muscle microsomes and in microsomes prepared from cell lines expressing human cytochrome P-450 2E1 or 2B6. The hydro xylated metabolites ofn-hexane were quantified by gas chromatography-mass spectometry.

2 Rat liver and extensor digitorum longus (EDL, fast- twitch skeletal muscle) microsomes and the CYP 2B6 microsomes produced the pre-neurotoxic metabolite of n-hexane, 2-hexanol as a major metabolite in contrast to the other rat tissues examined.

3 Inhibition of 2- and 3-hexanol production from n- hexane by rat lung microsomes using metyrapone, an inhibitor of cytochrome P-450 2B1 activity, resulted in almost complete inhibition of lung microsomal activ ity.

4 Production of all three hexanols was significantly increased with phenobarbital-induced rat liver micro somes, with a 10-fold increase in 2- and 3-hexanol production. A slight increase in 2-hexanol production with phenobarbital-induced rat EDL and brain micro somes was observed. No increase in n-hexane meta bolism was noted following induction with β- naphthoflavone or with ethanol.
An investigation into the role of rat skeletal muscle as a site for xenobiotic metabolism using microsomes and isolated cells
Authors: Crosbie Sarah J , Blain PG , Williams Faith M
Published: December 2008

1 The role of skeletal muscle microsomes as a site of extrahepatic xenobiotic metabolism using n-hexane as a model substrate was investigated. The observed cytochrome P450-dependent metabolism was com pared with that found with liver, and brain micro somal fractions.

2 Rat skeletal muscle microsomes metabolised n-hexane to 1-, 2- and 3-hexanol at rates 40 - 300 times lower than observed with rat liver microsomes.

3 Fast-twitch extensor digitorum longus muscle (EDL) microsomes had twice as much n-hexane hydroxylase activity as the slow-twitch soleus and furthermore the EDL microsomes produced 2-hexanol, a bioactivation product of n-hexane, as a major metabolite.

4 Metabolism of hexane to 1-, 2- and 3- hexanol and 2- hexanone was demonstrated in cultured rat myoblasts.

5 Ethoxyresorufin and pentoxyresorufin O-dealkylation were not detected in either muscle microsomes or myoblasts although immunocytochemical localisation studies were suggestive of the presence of cytochrome P-450.

6 In conclusion, rat skeletal muscle has a low level of xenobiotic metabolism activity. The relevance to neuromuscular toxicity of n-hexane is discussed.
Phenytoin-mediated oxidative stress in serum of female epileptics: A possible pathogenesis in the fetal hydantoin syndrome
Authors: Liu Chin-San , Wu Hong-Ming , Kao Shu-Huei , Wei Yau-Huei
Published: December 2008

1 The concentration of serum malondialdehyde (MDA) was measured as the index of lipid peroxidation in female epileptics with phenytoin (PHT) monotherapy. Sera from 20 female epileptics with PHT monotherapy, 12 female epileptics without anticonvulsant therapy and 20 female healthy controls were sampled. The levels of serum copper (S-Cu), serum zinc (S-Zn), copper/zinc superoxide dismutase (CuZn-SOD), and reduced glutathione (GSH) were analyzed as inter active factors of the oxidative stress.

2 For the female epileptics with PHT monotherapy, serum MDA concentration (2.6 ± 0.7 μM vs control 1.8 ± 0.6 μM, P < 0.05), CuZn-SOD activity (178.2 ± 63.5 U/dL vs control 97.1 ± 36.4 U/dL, P < 0.01), and S-Cu content (126.2 ± 36.1 μg/dL vs control 98.4 ± 16.7 μg/dL, P < 0.05) were significantly in creased, but GSH level (27.5±6.8 μM vs control 32.2 ± 5.7 μM, P < 0.05) was significantly decreased. The level of serum MDA was associated with the elevation of CuZn-SOD activity ( r=0.54, P < 0.05) and S-Cu content ( r=0.44, P < 0.05) in all the samples collected from epileptics and controls. However, there were no significant differences in all the above parameters between the female epileptics without anticonvulsant therapy and healthy controls.

3 These results indicated that oxidative stress was enhanced in the female epileptics with PHT-mono therapy. Apart from the reactive PHT intermediate, the abnormal metabolism of S-Cu, CuZn-SOD, and GSH was highly involved in the PHT-mediated toxicity. Supplement of GSH, modification of CuZn-SOD enzyme activity and reduction of the absorption of copper may prevent the incidence of fetal hydantoin syndrome during pregnancy.
Granulocyte-colony stimulating factor in the treatment of colchicine poisoning
Authors: Critchley Julian AJH , Critchley Lester AH , Yeung Elce Au , Young Robert P , Young Robert J , Chan Thomas YK , Goh Victor KM
Published: December 2008

1 Colchicine is a highly active alkaloid used in the treatment of gouty arthritis and pseudogout. In over dose colchicine inhibits cell division effecting organs with a high rate of cell turn-over, such as the gastrointestinal tract and bone marrow. Early fatality results from cardiovascular collapse and respiratory failure, however pancytopenia and overwhelming septicaemia can occur later.

2 We describe a case of suicidal ingestion of 25 - 30 mg of colchicine in a previously healthy 43-year-old woman. Initial symptoms were mainly gastrointestinal. By day 5 she had developed severe pancytopenia and early sepsis, which were successfully treated using granu locyte colony stimulating factor (G-CSF) 600 μg s.c.

3 In vitro G-CSF is produced by the haematopoietic system. However, G-CSF can now be produced by recombinant DNA cloning technology and thus is available clinically.

4 There is no recognised antidote for colchicine poison ing and treatment is symptomatic. Fab fragments may have a promising future in eliminating colchicine from the body, but are currently not clinically available. In those patients that survive the initial phase of poisoning, G-CSF offers an effective method of treating the pancytopenia and preventing overwhelming septi caemia. Daily monitoring of the patient's haematolo gical status is strongly recommended.
Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-Dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat
Authors: Stott Ian , Murthy Anupama , Robinson Alex , Thomas Norman W , Fry Jeffrey R
Published: December 2008

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepato toxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.
Study of oxidative-stress in rifampicin-induced hepatic injury in growin rats with and without protein-energy malnutrition
Authors: Chhinder Pal Sodhi  , Rana Satyavati , Mehta Saroj , Vaiphei Kim , Ramesh Chand Goel  , Satish Kumar Mehta
Published: December 2008

1 Rifampicin (RMP) induced hepatic injury was investi gated in growing rats. The interaction of moderate and severe protein-energy malnutrition (PEM) was also investigated.

2 Status of oxidative/antioxidative profile was studied by the mechanistic approach, to enumerate the nature of injury.

3 Successful hepatic injury in rats was produced by giving intraperitoneal injection of RMP (50 mg/kg/ day).

4 Hepatic lipid peroxidation was significantly increased in all the RMP treated rats.

5 Superoxide dismutase, catalase and glutathione per oxidase activities in the hepatic tissue decreased with RMP treatment.

6 Hepatic thiols represented as total and protein-bound thiols, showed significant elevation, whereas the non protein thiols remain unchanged with RMP treatment.

7 Glutathione-S-transferases also showed significant elevation against 1,2-dichloro-4 nitrobenzene (DCNB) and ethacrynic acid (EA) as substrates.

8 The oxidative/antioxidative profile was observed to be more severely affected with coexistence of malnutri tion.

9 Histopathological correlation showed an additional fatty infiltration of hepatocytes with coexistence of malnutrition.

10 Thus, in conclusion, it can be speculated that an altered oxidative/antioxidative profile is the closely associated with production of RMP induced hepatic injury.
Changes in the arterial blood pressure, heart rate and normal ECG parameters of rat after envenomation with Egyptian cobra (Naja haje) venom
Authors: Omran Mohamed Alaa A , Abdel-Nabi Ismail M
Published: December 2008

1 The effect of Egyptian cobra (Naja haje) venom on the normal electrical activity of the cardiac muscles (ECG) and arterial blood pressure of envenomated rats were investigated in this study.

2 Rats were divided into three groups. The first group was injected im with saline and considered as control group. Rats of the second and third groups were injected IM with 0.02 μg and 0.04 μg cobra venom/ gim b.wt, respectively.

3 Mean blood pressure (MBP), heart rate (HR) and four different ECG parameters (PR and QT intervals, R and T wave amplitudes) were measured over 1 h following envenomation.

4 The low dose (0.02 μg/g) of N. haje venom caused hypotension accompanied by an increase in the HR, whereas hypertension and bradycardia developed after injection of the high dose (0.04 μg/g) of venom.

5 There was a decrease in the P-R interval after administration of the low dose and prolongation of it after the high dose. The Q-T interval and R-wave amplitude were significantly increased after injection of both doses. T-wave amplitude was significantly elevated only after injection of the high dose.

6 The present results indicate that the Egyptian cobra (N. haje) venom significantly alters the arterial blood pressure and ECG parameters of envenomated rats. This suggests that impairment of the electrical activity of cardiac muscle may be one of the reasons why victims of cobra bite die.
Pharmacological protection of NSAID- induced intestinal permeability in the rat: effect of tempo and metronidazole as potential free radical scavengers
Authors: Davies Neal M , Jamali Fakhreddin
Published: December 2008

Recently, NSAID-induced changes in both the structure and function of the distal intestine have been found to occur more frequently and with greater toxicological significance than previously thought. We have previously validated a suitable animal model to evaluate intestinal permeability changes using orally administered 51Cr- EDTA that correlates with intestinal ulceration. In this study we investigated the suitability of metronidazole and the nitroxide stable free radical scavenger (tempo) as protective agents against NSAID-induced intestinal per meability. Male Sprague-Dawley rats were dosed with two doses of metronidazole (50 mg/kg, 12 and 1 h pre-NSAID) or a single 100 mg/kg dose of tempo 1 h prior to NSAIDs. The urinary excretion of the orally administered marker 51Cr-EDTA was measured. Both tempo and metronidazole dramatically reduced indomethacin (20 mg/kg) and flur biprofen (10 mg/kg)-induced intestinal permeability. All the animals exposed to indomethacin alone died within 48-96 h and presented with histological evidence of drug- induced enteropathy, ulceration and frank peritonitis. Protection by tempo and metronidazole suggests that free radicals and/or bacteria may be important mediators in the pathogenesis of intestinal mucosal damage induced by NSAIDs. Nitric oxide donor compounds used concomi tantly with NSAIDs may protect gastrointestinal tract.
Media composition modulates excitatory amino acid - induced death of rat cerebellar granule cells
Authors: Wood Anita M , Tiwari Priyanka , Bristow David R
Published: December 2008

This study examined the effects of maintaining cells in different media and the role of serum in glutamate and NMDA - induced neurotoxicity in rat cerebellar granule cells. Glutamate stimulated a concentration - dependent cell death with similar potency in cerebellar granule cells grown in BME and Neurobasal media without serum. However, the maximal cell death to glutamate and N- methyl-D-aspartate (NMDA) varied in the different media compositions. In the presence of serum, glutamate and NMDA - induced excitotoxicity was abolished, suggesting a factor(s) in serum which influences glutamate - receptor mediated death. The protective effect of serum could be overcome by chronic stimulation with high doses of glutamate. The glutamate - stimulated increase in intra cellular calcium load was attenuated in the presence of serum, resulting from an elevated basal calcium level, suggesting an association between raised basal calcium and neuroprotection.
Are we ready to replace dimercaprol (BAL) as an arsenic antidote?
Authors: Mückter Harald , Lieb Bernhard , Reich Franz-Xaver , Hunder Göran , Walther Udo , Fichtl Burckhard
Published: December 2008

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulpho nate sodium (DMPS) and meso-2,3-dimercaptosucci nic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour.

2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication - espe cially with lipophilic organoarsenicals - may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular avail ability.

3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (=Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine.

4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL when ever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of- no-return is a limiting factor, BAL may still have a place as an arsenic antidote.
Cholinesterase status, pharmacokinetics and laboratory findings during obidoxime therapy in organophosphate poisoned patients
Authors: Thiermann H. , Mast U. , Klimmek R. , Eyer P. , Hibler A. , Pfab R. , Felgenhauer N. , Zilker T.
Published: December 2008

1 The effectiveness of oxime therapy in organophos phate poisoning is still a matter of debate. It appears, however, that the often cited ineffectiveness of oximes may be due to inappropriate dosing. By virtue of in vitro findings and theoretical considerations we concluded in the preceding paper that oximes should preferably be administered by continuous infusion following an initial bolus dose for as long as reactiva tion of inhibited acetylcholinesterase (AChE) can be expected. This conclusion has called for a clinical trial to evaluate such oxime therapy on the basis of objective parameters.

2 Before transfer to the intensive care unit (ICU), 5 patients received primary care by an emergency physician. In the ICU, atropine sulphate was adminis tered IV upon demand according to the endpoints: no bronchorrhoea, dry mucous membranes, no axillary sweating, heart rate of about 100/min. Obidoxime (Toxogonin®) was given as an IV bolus (250 mg) followed by continuous infusion of 750 mg/24 h.

3 Intoxication and therapy were monitored by determin ing erythrocyte AChE (eryAChE) activity, reactivat ability of the patient's eryAChE ex vivo, plasma cholinesterase activity, the presence of AChE inhibit ing compounds, as well as the concentrations of obidoxime and atropine in plasma.

4 Obidoxime was effective in life-threatening parathion poisoning, in particular when the dose absorbed was comparably low. In mega-dose poisoning, net reacti vation was not achieved until several days after ingestion, when the concentration of active poison in plasma had declined. Reactivatability in vivo lasted for a longer period than expected from in vitro experiments.

5 Obidoxime was quite ineffective in oxydemeton- methyl poisoning, when the time elapsed between ingestion and oxime therapy was longer than 1 day. When obidoxime was administered shortly after ingestion (1 h) reactivation was nearly complete.

6 Obidoxime levels of 10-20 μM were achieved by our regimen, and atropine could rapidly be reduced to approx. 20 nM, as attained by continuous infusion of 1 mg atropine sulphate/h. Maintenance of the desired plasma levels was not critical even when renal function deteriorated.

7 Signs of transiently impaired liver function were observed in patients who showed transient multi- organ failure. In the present stage of knowledge, we feel it advisable to keep the plasma concentration of obidoxime at 10 - 20 μM, although the full reactivating potential of obidoxime will not then be exploited. Still, the reactivation rate, with an apparent half-time of some 3 min, is twice that estimated for a tenfold higher pralidoxime concentration.
Paracetamol poisoning in the North East of England: presentation, early management and outcome
Authors: Thomas Shl , Horner JE , Chew K. , Connolly J. , Dorani B. , Bevan L. , Bhattacharyya S. , Bramble MG , Han KH , Rodgers A. , Sen B. , Tesfayohannes B. , Wynne H. , Bateman DN
Published: December 2008

1 Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning.

2 To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994.

3 There were 400 presentations (attendance rate 1.14/103 population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R=0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination.

4 In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h.

5 One patient died, from arrhythmias caused by co- ingested dothiepin.

6 Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentra tions, but those who do often present late and antidotal treatment may be delayed inappropriately.
Laryngeal survey in glyphosate intoxication: a pathophysiological investigation
Authors: Hung Dong-Zong , Deng Jou-Fang , Wu Tain-Chen
Published: December 2008

Respiratory aspiration is a serious potential complication of glyphosate-surfactant herbicide intoxication. From October 1, 1992 to June 30, 1996, we performed laryngeal evaluations in 53 cases to investigate the possible pathophysiological mechanism of glyphosate intoxica tion. There were 36 cases with significant laryngeal injury. The blood WBC count were significantly higher and the hospital stays were significantly longer in patients with laryngeal injury, when compared with patients with no laryngeal injury (Student t-test, P < 0.005). Laryngeal injury was strongly correlated with aspiration pneumoni tis (X2 =4.449, P<0.05). We concluded that laryngeal injury may be the major cause of aspiration that leads to some degree of morbidity and mortality, following concentrated glyphosate-surfactant herbicide intoxica tion. Laryngeal survey may be indicated in cases of glyphosate-surfactant intoxication, to evaluate the sever ity of mucosal injury, and to apply adequate supportive management as early as possible to prevent from aspiration complications and even mortality.
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 and distribution of lindane through skin was examined using human volunteers. Two different preparations were employed, one with acetone as the vehicle and the other, a commercial product, consisting primarily of white spirit as the solvent base.

2 The mean peak plasma concentrations of lindane following exposure to the acetone and white-spirit based applications were 0.91 and 0.47 ng/ml, respec tively. The similarity between these levels did not reflect the 40-fold higher dose of lindane in the acetone vehicle. White spirit enhanced the penetration of lindane with respect to the acetone vehicle, high lighting the influence of vehicle upon percutaneous absorption. Low levels of trichlorophenol glucuronide metabolites, but no lindane, were detected in the urine.

3 The exposure site was washed at 6 h to mimic a decontamination procedure at the end of a working day. The proportion of the applied dose unabsorbed by 6 h was 80% and 10% for the acetone and the white spirit-based formulation, respectively. Small areas of the exposed site were tape stripped at 6 and 24 h to assess any lindane that may be associated with the stratum corneum. High levels were observed in the stratum corneum at 6 h exposure (up to 30% of the applied dose for the white spirit based formulation). However, this level had decreased by 24 h (by at least 90% of the amount found at 6 h). A gauze or gauze/shirt combination covering the application site between 6 and 24 h did account for some of this loss of lindane from the stratum corneum attributed to friction and removal of exfoliated cells. The unaccounted propor tion was presumed to have been absorbed through the skin into the systemic circulation. This demonstrates the absorption of chemicals can occur from a depot in the stratum corneum even following a wash proce dure.
Acetonitrile as a possible marker of current cigarette smoking
Authors: Houeto P. , Hoffman JR , Got P. , Dang Vu B. , Band FJ
Published: December 2008

Volatile nitriles are present in cigarette smoke. We tested the hypothesis that the presence of any of four nitriles in the blood can serve as a marker of recent cigarette smoking. We determined the sensitivity and specificity of these nitriles as indicators of daily cigarette smoking in 24 smokers (Group A) and 18 non-smokers (Group B), as well as the correlation between intensity of daily smoking and the blood concentration of acetonitrile. A new head space GLC assay method was used. Of the four nitriles, only acetonitrile was present in the blood of any study subject. Acetonitrile was moderately sensitive (67%) and entirely specific (100%) for self-reported daily smoking. There was fair correlation between blood acetonitrile concentration and the average daily number of cigarettes smoked (r2=0.39; P=0.001), and the mean blood acetonitrile concentration was significantly higher (P=0.03) among subjects with higher ( > 10 cigarettes per day) current cigarette exposure (148.3 ± 18.0 ?g/l) than among smokers with low or minimal (1-10 cigarettes per day) exposure (43.3 ± 6.0 ?g/l). Thus, acetonitrile in blood appears to be highly specific and a moderately sensitive marker of cigarette smoking with a dose-effect relationship. As such, acetonitrile shows promise as a marker of current cigarette exposure.
In vitro toxicity of trichothecenes on human erythroblastic progenitors
Authors: Rio B. , Lautraite S. , Parent-Massin D.
Published: December 2008

Trichothecenes are mycotoxins produced by various species of fungi which can occur on various agricultural products. Among these compounds, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) are the most naturally encountered and potent trichothe cenes. Consumption of trichothecene contaminated foods by farm animals and humans leads to mycotoxicoses. Trichothecenes are known to induce haematologic dis orders such as neutropenia, thrombopenia, and aplastic anemia in human and animals.

The aim of our investigations is to explore the effects of trichothecenes on the haematopoietic progenitors. The four trichothecenes previously demonstrated to be strongly cytotoxic for human CFU-GM have been tested on human BFU-E. For this purpose, a culture model of human erythroblastic progenitors (BFU-E) optimized for toxicological studies was used to determine the effects of T-2, HT-2, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) on red blood cell precursor proliferation and differentiation. Results showed that human BFU-E are as sensitive to trichothecenes as human CFU-GM, except for DON, in the range of concentrations tested. Differentiation of erythroblastic progenitors could be perturbed by these mycotoxins. Human erythroblastic progenitors are also a target of trichothecenes.
Mitigation of nitrofurantoin-induced toxicity in the perfused rat lung
Authors: Bernard Craig E , Magid Amani A , Benedict Yen TS , Hoener Betty-ann
Published: December 2008

1 Nitrofurantoin is an antimicrobial agent which pro duces pulmonary toxicity via the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress.

2 In the isolated perfused rat lung, nitrofurantoin induced a decrease in tissue levels of glutathione but not protein thiols by the end of the 180 min experi ment. There was no decline in tissue levels of angiotensin converting enzyme (a marker of cell disruption). However, edema was extensive as mon itored in real time by weight gain (2.71 ± 0.56 g vs 0.63 ± 0.53 g in control, P<0.05, n=4) and lung mechanical functioning. The edema was matched by an increase in lavage proteins (85 ± 15 mg vs 16 ± 9 mg in controls, P<0.05, n=4). Electron microscopic examination of tissue indicated that the endothelial cells were detached from the basement membrane which would account for the edema.

3 Co-infusion of penicillamine, N-acetylcysteine or N- (2-mercaptopropionyl)-glycine which can protect tissue from oxidative stress failed to mitigate NFT induced edema. Allopurinol, an inhibitor of xanthine oxidase and a metal chelator, significantly decreased weight gain but did not prevent the loss of glutathione. These results suggested that allopurinol was not blocking metabolic activation of NFT by xanthine oxidase but scavenging metal cations which can initiate and/or propagate the oxidative stress cascade.

4 We concluded that, in the isolated perfused rat lung, the classic pathway of oxidative stress induced by NFT is interrupted at the stage of GSH loss. These experiments demonstrated that organ function was compromised more than the individual cells. They also suggested that allopurinol may prove beneficial in modulating NFT pulmonary toxicity.
Supported Community Life
Authors: Ferguson Philip M. , Hibbard Michael , Leinen James , Schaff Sandra
Published: December 2008

The paper describes an emerging model for dramatically restructuring disability policy in America. This model for policy reform attempts to escape the excessive individualism and loss of community that many social critics find at the heart of our current "system" of disability services. First, we review the failures of the existing mélange of disability programs. The sociological construct of mediating structures is used to understand how these programmatic failures have tended to perpetuate the social isolation of people with disabilities and their families. Then we identify some common features of progressive reform efforts now occurring within the field of developmental disabilities. We argue that, taken together, these features outline a new model for disability policy that can renew a sense of community and mutual support. Examples of programs consistent with the Supported Community Life Model are presented from the specific area of family policy. The paper concludes with some cautionary comments about potential misapplications of the Supported Community Life Model.
Rating Consistency on Successive Statewide Assessments of Disability Concerns
Authors: Mathews R. Mark , Petty C. Ray , Fawcett Stephen B.
Published: December 2008

The Disabled Citizens' Concerns Report Method is a survey research strategy designed to assess community strengths and problems from the perspective of people with disabilities. The present study examines the consistency of ratings obtained using the instrument in two successive statewide applications. Results suggest that survey responses, which were collected from the same 405 people at eighteen-month intervals, produced highly consistent scores. Thus, information obtained may be viewed as a reliable measure of these consumers' concerns and an efficient way of generating consumer involvement in policy development and planning for rehabilitation services.
Supported Employment Implementation
Authors: Rhodes Larry , Mank David , Sandow Dennis , Buckley Jay , Albin Joyce
Published: December 2008

The national proliferation of supported employment services for people with severe disabilities has governmental funders and regulators scrambling for standards upon which to judge the adequacy of these new services. The task is complicated by the variability in both employer needs and service requirements for supported employees as well as the community resources available to meet these needs. Conventional monitoring provides some safeguards against major abuses to persons receiving services, but does little to satisfy consumer, advocate, or policymaker interest in promoting quality assurance in service provision.

Issues are raised within this paper regarding the appropriateness and effectiveness of methods traditionally used by states to monitor or promote quality assurance. Guidelines are suggested for developing state quality assurance systems that will promote continuous improvement. It is maintained that states should promote the development of systems that move beyond conventional monitoring approaches, and that tie program assistance to areas where needed improvements are identified that directly benefit individuals with severe disabilities.
Issues and Problems in the Treatment of Traumatic Brain Injury
Authors: Noble John H. , Conley Ronald W. , Laski Frank , Noble Mary Anne
Published: December 2008

Adequacy, equity, efficiency, legal rights, and dynamism in programs for people with traumatic brain injury are examined. Adequacy of services is compromised by costly care, restricted payments by third party carriers, restrictions on the use of available funds, and limited data for judging the types and amounts of services to provide. Compromised adequacy lowers efficiency, raises social costs, and causes horizontal and vertical inequity. Finding less costly and more effective treatment is impeded by a lack of information about the benefits and costs of services, the conservatism of service providers, and financial disincentives to change that are inherent to the existing disability service system. Rigorous research and development are needed to provide a factual basis for federal and state policy making. Greatly improved data are essential to the task of revising the current system of disability programs in the 1990s.
Access to Early Intervention Services in New York State
Authors: Bird William A. , Castellani Paul J. , Nemeth Chris
Published: December 2008

The results of a study of the availability of and access to early intervention services in twelve counties in upstate New York are presented here. Factor analyses of the availability of these services identified three groups: entry, direction, and specialized therapeutic services. While early intervention services were found to be broadly available, specialized services were substantially less available than those that were largely concerned with screening, advocating, funding, transporting, and similar activities instrumental to linking the child and family to direct therapeutic interventions. Analyses of the sources of referral and waiting times for a sample of children showed that pediatricians were the largest source of referrals to services, and referrals from this group had the shortest waiting times. Specific direction and coordination services that had been established in the locales had the lowest percentage of referrals and the longest waiting times. The implications of the study for public policymaking are shown to be important in two respects. The first concerns the relative efforts to provide early intervention services which focus more on instrumental activities than therapeutic interventions. The second is whether mechanisms designed to enhance the linkage of children to services actually achieve the desired results. The results of this study raise questions in both regards.
Out of Mind, Out of Sight?
Authors: Wolf Jessica
Published: December 2008

National disability advocacy groups have increasingly sought legal guarantees to define and protect the rights of people with disabilities, including mental illness. The battle to secure the rights of people with mental illness to live in communities has taken place as policy emphasis has shifted from community residential facilities toward personal choice of where, how, and with whom to live.

This article describes efforts in Connecticut to assure access to housing and public accommodations by people with mental illness. It describes and analyzes the evolution of policy, legislative efforts, and service development. The Connecticut experience is viewed in relationship to national efforts to promote consumer choice and assure equal protection for people with disabilities.
Investing in People: Launching Supported Employment on a Crowded Public Agenda (Part 1)
Authors: Elder Jean K.
Published: December 2008

When historians look back on American politics of the 1980s, they will be tempted to see the "Reagan Era" as a distinctive movement in American government. I am hopeful that there will be a general mention of the significant policy issues addressed in the disability area, and specifically, that attention will be given to launching supported employment on a crowded public agenda.

The "how" of getting supported employment on the Reagan policy agenda, highlighting the budget context, demographics, and program data supporting such a change and policy advocacy within the administration, is detailed elsewhere in this volume by Tom Bellamy and Dick Melia. Here, I will address the broader political context.
Supported Employment in New York State: A Comparison of Benefits and Costs
Authors: Noble John H. , Conley Ronald W. , Banerjee Sarbani , Goodman Stanley
Published: December 2008

The rapid growth of supported employment programs in the last five years has been accompanied by the strong belief that through such programs many people with severe disabilities would be more satisfied with their lives and receive higher earnings than in sheltered workshops, work activity centers, and adult day care. This paper presents data collected in New York State that test these propositions and compare the benefits with the costs of operating the supported employment program.
Programs and Services Received by Persons With Mental Retardation in Three Models of Small Community Residences
Authors: Lakin K. Charlie , Amado Angela N. , Bruininks Robert H. , Hayden Mary F. , Li Xiaoming
Published: December 2008

Programs and services received by a national sample of 336 persons with mental retardation in 181 foster homes, non-Intermediate Care Facility for the Mentally Retarded (ICF-MR) group homes, and ICF-MR-certified group homes of 6 or fewer residents are described. In the previous 12 months 85% of residents had been visited at least twice by a case manager, 99% had seen a physician, and 95% had visited a dentist. In all, 95% of 750 residents of the 181 sampled facilities had day time vocational or developmental programs away from the residence, but supported or competitive jobs were held by only 5% of the adults below age 65. Specialized services (e.g., those services provided by medical specialists, therapists, counselors, and psychologists) utilization was considerably higher for residents of ICF-MR-certified group homes as were the per resident costs of care. Multiple regression analysis found living in an ICF-MR to be a better predictor of hours of specialized services received than the physical, sensory, intellectual, or functional characteristics of residents.
National and Community Service
Authors: White Glen W.
Published: December 2008

The recently implemented National and Community Service Act of 1990 calls for Americans of all race, age, ability, and economic status to return to service in their community. To help facilitate this call to service, the National Commission on Community Service has allocated approximately 70 million dollars in grants. The Act focuses on the involvement of youth, including those who are economically disadvantaged and with disabilities. This paper discusses the challenges and opportunities faced by community service program planners and disability organizations, in their efforts to integrate volunteers with disabilities in service to the community. The paper concludes with a discussion of informal and formal approaches to involving participants of varying abilities.
Disability Statistics, What We Count and What It Tells Us
Authors: Zola Irving K.
Published: December 2008

This paper begins with four reinterpretations about the prevalence, trends, temporality, and spread of disability. Together they lead to a different view of disability as quite pervasive in terms of sheer numbers, length of disability experience, and domains of life, as well as organ systems affected. The denial of this reality is related to our attempt to make disability "fixed" and "dichotomous," whereas it is better conceived of as "fluid" and "continuous." The costs of maintaining the former position are traced in notions of disability's "real" numbers and measurement, as well as in research, policy, and advocacy arenas. A redirection is suggested in terms of a more multidimensional approach and a purging of the inherent negative elements in current conceptions and measurement of disability.
The Economic Consequences of Disability
Authors: Burkhauser Richard V. , Daly Mary C.
Published: December 2008

Using two longitudinal data sets, the Panel Study of Income Dynamics and the German Socio-Economic Panel, we compare the relative success of United States and German disability policy in ameliorating the consequences of work-related health impairments. Comparing cross sections, we find Germans with disabilities on average earn only slightly less and enjoy the same household income as those without disabilities, while Americans with disabilities earn substantially less and face an income gap of more than 25% compared to those without disabilities. However, when we use our multiperiod data to follow the transition into disability of previously nondisabled individuals, the associated change in income is smaller than that suggested by our cross-sectional estimates. Our results suggest that even if the Americans With Disabilities Act is successful in increasing the earnings of people with disabilities, it may not close the income gap for those whose disabilities compound more fundamental labor-market disadvantages such as poor education or lack of job skills.
Privatizing Vocational Rehabilitation
Authors: Weaver Carolyn L.
Published: December 2008

This paper will explore several options for increasing individual choice and expanding competition in the supply of rehabilitation services. Chief among these is a proposal for rehabilitation vouchers. Also considered are proposals for tax credits and federal loans for rehabilitation expenses and direct contracting for privately supplied rehabilitation services. The likely impact of these options on the well-being of people with disabilities as well as on program accountability, performance, and cost-effectiveness will be assessed.
Self-Employment as a Vocational Rehabilitation Closure
Authors: Arnold Nancy L. , Seekins Tom
Published: December 2008

The operation and funding of federal and state offices of vocational rehabilitation (VR) are governed by the Rehabilitation Act of 1973. Under the Rehabilitation Act, an individual can work toward the goal of attaining one of a range of employment options, including self-employment. While federal law appears not to favor one type of employment situation over another, self employment as a VR closure is not used as often as might be expected. Although self-employment is not an often used VR option, it may be an important one for people living in rural locations where employers and jobs are scarce, wages are low, and the jobs that are available often require physical effort. This article describes an analysis of state policies governing the use of self-employment as a VR option. Results show a wide range of policies and suggest a framework for a comprehensive policy and procedures for governing the use of self-employment as a VR closure.