bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary effect on mixed function P450 1A2 activity assayed by estimation of caffeine metabolism in man
Authors: Kall MA , Clausen J.
Published: December 2008

Two studies were performed in order to evaluate cytochrome P450 1A2 mediated caffeine metabolism dur ing different nutritional conditions.

1 In the first study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed diet to a stan dard diet in 6 days. The 6 day's standard diet was based on bread, potatoes, rice and boiled meat. Thus, broccoli, cabbage and other cruciferous vegetables, spinach, leeks, onion, parsley, grapefruit, toasted bread, fried and charcoal grilled food, smoked fish and meat, ham and sausages were avoided.

2 In the second study, 33 healthy non-smoking subjects, 24 men and nine women mean age 25 years, volun teered. The study was designed to compare a customary home dietary period with the 6 day period of low dietary P450 induction and with a 5 day supplementary dietary period, i.e. ingestion of known dietary inducers. None of the women were using oral contraceptives or were pregnant during the experimental period.

In the period of diet supplementation, the volunteers received charcoal grilled hamburger as a supplement to the standard low induction diet for lunch for 5 days. The hamburgers were made with 150 g beef (18-20% fat) and were grilled on charcoal for 10 min on each side until they were 'well done'.

In the present study P450 1A2 activity was estimated from the caffeine metabolic ratio, the so-called CYP 1A2 index:(AFMU + 1-MX + 1-MU/ 17 -DMU) of the caffeine metabolites formed after oral ingestion of 200 mg caffeine. Urine was collected 4-8 h after caffeine ingestion in study 1 and 5 h after caffeine ingestion in study 2.

In study 1 the CYP 1A2 index decreased from 4.28 ± 0.98 in the customary home dietary period to 3.87 ± 0.69 in the standard dietary period corresponding to 10.6% ( P < 0.06) decrease in the CYP 1A2 index.

In study 2 the CYP 1A2 index decreased from 4.47 ± 1.76 in the customary home dietary period to 3.90 ± 1.12 in the standard dietary period corresponding to a 14.6% decrease ( P < 0.2) in P450 1A2 activity. The female sub jects had a mean index value of 3.89 ± 1.14 which was 16.8% ( P = 0.09) lower than the mean male index value of 4.68 ± 1.76 during the home dietary period.

After the 5 day period with charcoal grilled hamburgers as a dietary supplement, the CYP 1A2 index increased to almost the same level as in the customary home dietary period. The index increased to 4.45 ± 1.57 in the whole group of volunteers, corresponding to a 14.1% ( P < 0.05) increase. The mean increase in the CYP 1A2 index cov ered a large inter-individual variation in response to ingestion of charcoal grilled meat ranging from a 29% decrease to a 147% increase.
Mortality due to poisoning in a developing agricultural country: trends over 20 years
Authors: Senanayake N. , Peiris H.
Published: December 2008

The cause of death as recorded in 37 125 death certificates (DCs) issued in the Kandy District over 20 years at 5-year intervals beginning in 1967 were analysed to determine the trends in mortality caused by poisoning in the commu nity. Poisoning accounted for 718 (19.3 per 1000) deaths, the highest number being in the third decade of life (41.9%). Male:female ratio was 3:1. The agent responsible for 77% of the deaths was pesticides. Acids and chemicals accounted for 6.9% of the deaths. Other poisons each con tributing to less than 1% of the deaths were: plant poi sons, food items, drugs, kerosine oil and alcohol. Nearly half the deaths had occurred outside the town area, at home or in small hospitals in the periphery. Mortality due to poisoning showed an increasing trend during the 20 years, from 11.8 to 43/1000 deaths, and this increase was most marked in the periphery, from 8/1000 to 70/1000. This increase paralleled the increase in suicide figures in the country. Our findings call for a shift in emphasis in public education towards first-aid management of intoxi cation. Health services of developing countries should pro vide appropriate resuscitative equipment, and ensure a regular supply of antidotes and other medication to all rural hospitals. Management of pesticide poisoning should be emphasised in the curricula for medical graduates, nurses, and paramedics.
An in vitro and an in vivo unscheduled DNA synthesis assay with a zinc oxide/ hexachloroethane (Zn/HCE) smoke
Authors: Andersonl D. , Blowers SD , Marrs TC , Rice P.
Published: December 2008

1 Since Zn/HCE smoke has been shown previously to be weakly positive in the Ames test, and negative in the bone marrow micronucleus assay, other assays including a second in vivo assay examining unscheduled DNA synthesis (UDS) in rat hepatocytes has been carried out, as recommended by the UK Department of Health guide lines.

2 Zn/HCE smoke was assessed for its ability to induce DNA repair in an UDS assay both in vitro in cultured rat hepatocytes and in rat hepatocytes after in vivo treatment by inhalation.

3 For the in vitro investigation, two studies were carried out assessing media exposed to Zn/HCE smoke using at least seven concentrations up to a toxic level. At the highest concentration of Zn/HCE smoke, where some viable cells were seen, an increase in UDS was observed in both experiments. However this was not statistcally significant, was only seen at a level where toxicity was observed and was therefore considered not to be biologically significant.

4 In the in vivo investigation, one study was carried out in three separate parts, assessing two doses of Zn/HCE smoke characterised by their zinc content as approxi mately 20 and 56 μg l -1 air. A dose-related increase in UDS was observed which was not statistically sig nificant. The positive control behaved as anticipated, showing a highly statistically significant response. 5 It was concluded that Zn/HCE smoke did not induce unscheduled DNA repair in the in vitro or in vivo UDS assays under the conditions used in the studies. The overall lack of genotoxic effect of this smoke in this and previous studies in this laboratory would not suggest a major health hazard.
Reduced survival after isoprenaline/ dopamine in d,l-propranolol intoxicated rats
Authors: Toet AE , te Biesebeek JD , Vleeming W. , Wemer J. , Meulenbelt J. , de Wildt DJ
Published: December 2008

1 Respiratory and cardiovascular failure are principle toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats.

2 The effect of β-adrenoceptor agonists on respiratory and cardiovascular failure in β-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg -1 h-1) intoxication in spontaneously breathing rats.

3 Neither the aselective, hydrophilic β-agonist isoprena line (10, 25, 50 μg kg-1 min-1), nor the β 1-selective, lipophilic β-agonist flerobuterol (1,3,10 μ g kg-1 min-1) and the β2-selective, lipophilic β-agonist clenbuterol (10, 25, 50 μg kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats.

4 Isoprenaline (10 μg kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l -propranolol intoxicated rats either.

5 Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decrease in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6 Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.
Poly (D,L-Lactide) glycolide polymer microsphere entrapped tetanus toxoid: safety evaluation in Wistar rats
Authors: Chaudhury M. Roy , Sharma K. , Giri DK
Published: December 2008

A vaccine preparation consisting of tetanus toxoid (TT) encapsulated in biodegradable poly (D,L-Lactide) glyco lide polymer has been developed. The toxicity of the preparation was evaluated in adult male and female Wistar rats injected IM with 20, 100 and 200 Lf tetanus toxoid, in polymer in 0.5 ml vehicle. No adverse effect of the vaccine could be seen, except for a granulomatous reaction at the site of injection. The vaccine was considered safe based on the findings in rats of both sexes.
Organochlorine compounds in human brain
Authors: Corrigan FM , French M. , Murray L.
Published: December 2008

Having observed polychlorinated biphenyls (PCBs) in brain tissue obtained post mortem from two men we have carried out a study of organochlorine compounds in frontal cortex from patients with Parkinson's disease (PD) and from controls. No PCBs were found in any of those samples. There was no difference in the concentra tion of the DDT metabolite pp'-DDE in the PD brain samples. Dieldrin (HEOD) was significantly decreased in PD brain when analysed by lipid weight. While these findings would not support the hypothesis that PCBs may contribute to the development of Parkinson's disease in humans it remains possible that they may cause damage to the basal ganglia before being displaced from brain tissue.
Embryotoxicity and teratogenicity studies of poly (DL-Lactide-co-Glycolide) microspheres incorporated tetanus toxoid in Wistar rats
Authors: Chandrasekaran R. , Giri DK , Chaudhury M Roy
Published: December 2008

Tetanus Toxoid loaded biodegradable microspheres (MTT) (poly (DL-Lactide-co-Glycolide) were administered intramuscularly to pregnant Wistar rats from Days 6 to 15 of gestation, at 1, 5 and 10-times the human equivalent dose of TT. Developmental defects in relation to soft tissues and skeleton, weight and sex of live pups and early fetal deaths from treated and control rats were analysed. The findings in treatment groups were comparable to those in the controls. These observations show that MTT was safe for pregnant rats and developing pups.
Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death
Authors: Hughes J Neil , Lindsay Christopher D , Griffiths Gareth D
Published: December 2008

Cultures of bovine pulmonary endothelial (BPE) cells were exposed to LC70 doses of ricin or abrin (15.5 and 4.5 pM respectively) over a period of up to 40 h. The viability of the cultures (as determined by the neutral red (NR) dye retention assay) declined after 6 h exposure to the toxins. From 15 h onwards, cellular material in toxin exposed cultures became detached from the substra tum of the culture vessels. Hoffman modulation contrast photomicrography showed that this process was due to ricin and abrin exposed cells collapsing into membrane bound vesicles which retained the NR dye, became detached and floated into the medium. These apoptotic-like structural changes were further investi gated by transmission electron microscopy (TEM) and by agarose gel electrophoresis of DNA from control and exposed cultures. Many of the characteristic changes associated with apoptotic cell death were seen using TEM, including heterochromatin condensation at the nuclear periphery, crenulation of the nuclear mem brane and progressive degeneration of residual nuclear and cytoplasmic structures. The plasma membrane of many cells remained intact, and contained nuclear and cytoplasmic debris. Agarose gel electrophoresis of DNA extracted from toxin-treated cells revealed oligonucleosome sized DNA fragments, characteristic of apoptosis, from adherent cells at 7 h and both adherent and floating populations when harvested from 15 h; DNA from unexposed control cells did not show this fragmentation. The identification of apopto sis as being a significant additional mechanism of toxicity following exposure to ricin and abrin holotox ins raises the possibility of developing new therapeutic strategies against poisoning by these phytotoxins.
Severe metabolic acidosis in the alcoholic: differential diagnosis and management
Authors: Höjer Jonas
Published: December 2008

1 A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome.

2 The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a β- hydroxybutyrate dominated ketoacidosis.

3 Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis.

4 The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided.

5 The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment.

6 The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps.

7 It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recom mended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication.
Influences of gold on zinc, copper and metallothionein kinetics in liver and kidney of the rat
Authors: Hinck-Kneip Christiane , Alsen-Hinrichs Carsten
Published: December 2008

1 Single, very low dose of gold (500 μg/kg body weight) was given intramuscularly to male Sprague-Dawley rats (mean body weight: 200 g) as aurothiokeratinate (Auro-Detoxin dissolved in 0.9% NaCl.

2 Blood, liver and kidney were samples at autopsy 0.5,1, 2, 3, 6 and 12 h after the gold injection (six animals per time). 12 rats were treated with 0.9% saline only as controls. The zinc (Zn), copper (Cu), gold and metallothionein (MT) concentrations were determined in homogenates and cytosols of liver and kidney using atomic absorption spectrometry and gel chromatogra phy, respectively.

3 The main changes in metal and MT concentrations occurred in the kidney, where an increase of gold was found 0.5 h after the injection, followed by an increase in Cu and MT concentrations after 6 h. Zn homeostasis did not change.

4 The results suggest that gold by itself induces an increase of MT-like peptides in the kidney cytosol, which was accompanied by an increase in the concentration of Cu mainly bound to these MT-like peptides.
A different transformation
Authors: Hinton Richard
Published: December 2008

The pattern of mRNA expression for liver-specific proteins and liver-enriched transcription factors were studied in two models of facultative gut epithelial progenitor cells activation: D-galactosa mine (GalN)-induced liver injury and dietary copper depletion leading to pancreatic acinar atrophy. After 5 weeks of copper deficiency (CuD, pancreatic acini of Fischer 344 rats underwent atrophy, associated with intense proliferation of small ductlike cells with oval-shaped nuclei. These cells resemble morphologically epithelial progenitor cells of the liver that proliferate after GalN administration. Activated pancreatic epithelial cells express mRNAs for five liver specific genes normally expressed in fetal liver, including α 1 antitrypsin, glucose-6-phosphatase, and others, but not genes that are turned on after birth such as serine dehydratase, tyrosine aminotransferase, and multidrug resistance gene-1b. They express mRNAs for liver-enriched transcription factors including HNF-1α, HNF-3β and γ, HNF-4, and members of the CCAAT-enhancer binding protein (C/EBP) family. The only mRNA for a liver-enriched transcription factor not detected in the pancreas of CuD animals was HNF-3α. Expression of HNF-3α, β and γ, and C/EBP-β mRNA was highly activated in proliferating liver epithelial cells on days 2 and 3 after GalN injury. Increased expression of C/EBP-δ was observed first in the liver on day 1 after GalN administration and in the pancreas at 4 weeks after initiating CuD. We suggest that C/EBP-δ could not be involved in the initial activation of epithelial progenitor cells and that HNF-3α, β and γ, and C/EBP-β might participate in their maturation. We conclude further that pancreatic epithelial progeni tor cells undertake differentiation through the hepatocyte lineage but cannot complete the differ entiation program within the pancreatic milieu.
Something completely different?
Authors: Hardwick James P , Liping Chen
Published: December 2008

Three cDNAs clones, designated 4f-8, 4f-34 and 4f- 41, coding for three new forms of cytochrome P450 belonging to the CYP4F subfamily were isolated from an untreated rat brain cDNA library. CDNA 4f- 8, 4f-34 and 4f-41 coded for proteins of 522, 526 and 537 amino acids, respectively, and their amino acid sequence similarity to CYP4F ranged from 71 to 80%. These new P450s were thus named CYP4F4, 4F5 and 4F6, respectively. Northern blot analysis revealed that the expression levels of these forms of P450 in the brain were somewhat low and that similar forms of subfamily 4F P450 were expressed in liver and kidney at a relatively high level compared with brain. No CYP4A expression was detected by Northern blot analysis in untreated rat brain mRNA. All three clones were in vitro- translatable using a reticulocyte lysate system. These results show that multiple forms of subfamily 4F P450 exist in the brain and that the subfamily 4F P450 may be one of the major forms of P450 in the brain.
No changes in behaviour, nigro-striatal system neurochemistry or neuronal cell death following toxic multiple oral paraquat administration to rats
Authors: Widdowson PS , Farnworth MJ , Upton R. , Simpson MG
Published: December 2008

We have examined whether the widely used herbicide, paraquat (1,1'-dimethyl-4,4'dipyridylium) may accumu late in rat brain following multiple oral dosing (5 mg paraquat ion/kg/day) for 14 days and whether this dosing regime may produce signs of neurotoxicity. This dosing regime may determine whether low dose exposure to mammals may be neurotoxic.

Using [14C]paraquat to measure tissue and plasma paraquat concentrations, we observed significantly higher plasma and tissue paraquat concentrations in brain, liver, lungs and kidneys of rats which received multiple doses for 14 days, as compared to paraquat concentrations in tissues of rats which received only a single paraquat dose. Brain paraquat concentrations measured 24 h after dosing were tenfold higher in rats receiving 14 daily oral doses of paraquat, as compared to concentrations follow ing a single oral dose.

A neuropathological study of the rat brain yielded no evidence that multiple paraquat dosing resulted in neuronal cell damage. Particular attention was paid to the nigrostriatal system. The paraquat treated rats gained approximately 10% less body weight over the 15 day experimental period as compared with controls demon strating that the dose of paraquat was toxic to the animals. Measurements of locomotor activity using open field tests or activity monitors did not reveal any statistically significant differences between control animals and those receiving paraquat. Fore- and hind-limb grip strength were not significantly different between the paraquat treated and control rats at any time point during the dosing regime, nor was there any evidence for locomotor co ordination deficits in any of the animals receiving paraquat. Densities of dopamine D1 and D2, NMDA, muscarinic and benzodiazepine receptors in the cerebral cortex and striatum were not significantly different between controls and rats which had received multiple paraquat doses.

Concentrations of catecholamine neurotransmitters in the striatum, hypothalamus and frontal cerebral cortex were also measured to examine whether there was evidence for catecholamine depletion in these brain regions. We did not observe any significant reductions in dopamine, noradrenaline or DOPAC concentrations in any brain region of paraquat treated rats as compared with controls. On the contrary, dopamine concentrations in the striatim were significantly elevated in paraquat treated animals following a 15 day paraquat dosing regime. We attribute these changes in catecholamine concentrations to the general toxicity of paraquat which produces a stress response.

In conclusion, we could not find any evidence that multiple paraquat dosing can lead to changes in locomotor activity or grip strength. In addition, the absence of neuropathology or changes in neurochemistry in the nigrostriatal tract demonstrates that paraquat does not behave like MPP+(N-methyl-4-phenylpyridinium), the neurotoxic metabolite of MPTP
Spermatotoxic effects of carbaryl in rats
Authors: Pant N. , Shankar R. , Srivastava SP
Published: December 2008

The spermatotoxic effect of carbaryl in adult and young male rats has been examined. Carbaryl 50 and 100 mg/kg b.wt. Male fed 5 d/week for 60 days, caused dose and age- dependent decline in epididymal sperm count and sperm motility, an increase in sperm with abnormal morphology. The dose of 25 mg/kg/d was a 'No observed effect level' for the indices studied. Young animals in comparison to adults exhibited pronounced spermatotoxic effects.
Research into individual predisposition to develop acute rhabdomyolysis attributed to fenoverine
Authors: Jouglard Jacqueline , Kozak-Ribbens Geneviève , de Haro Luc , Cozzone Patrick J
Published: December 2008

A xenobiotic, well tolerated by the majority of treated patients, can cause serious complications in patients with individual susceptibility. Based on the hypothesis that such a phenomenon may occur in rare cases of rhabdo myolysis attributed to fenoverine (DCI), we designed a protocol to look for a genetic predisposition. Six patients were included who had previously had an episode of rhabdomyolysis after taking fenoverine. A seventh patient was added, who had only experienced myalgia without cytolysis. All patients were investigated by the following tests: 31-phosphorus nuclear magnetic resonance spectro scopy, histopathological examination of the muscle, muscle contraction tests and biochemical analysis of the muscle.

All patients examined proved to have muscle abnorm alities. The pathology found varied greatly from patient to patient: mitochondrial myopathy, lipid storage myopathy, sensitivity to malignant hyperthermia or disorders of oxidative metabolism.

The probability of finding by chance such rare muscle disorders associated with the equally rare rhabdomyo lysis attributed to fenoverine is practially zero. We conclude that there is a cause and effect link between underlying abnormalities and the muscular cytolysis attributed to fenoverine.
Clinical and biochemical changes in greenhouse sprayers chronically exposed to pesticides
Authors: Parrón T. , Hernández AF , Pla A. , Villanueva E.
Published: December 2008

1 This study was conducted with the aim of evaluating the impact on health produced by the use of different types of pesticides in greenhouses. It is based on the need to practice and develop biological monitoring techniques to assess exposure and predict health risk in workers occupationally exposed to pesticides.

2 Two groups of greenhouse workers with either high or low exposure to a combination of pesticides was taken in Almeria, a Spanish province where cultures under plastic are very extended.

3 One hundred and five sprayers were interviewed to collect information about symptoms and signs related to past exposures. Each pesticide sprayer was exam ined by a physician, and a blood sample was drawn for plasma and red blood cell cholinesterases, complete blood count, and liver and renal function tests.

4 Exposure of workers to a combination of pesticides resulted in 37% of the workers showing toxic signs and symptoms. The main toxic effects observed were a high incidence of spontaneous abortion, depression, and certain neurologic disorders like headache, tremor and paraesthesia.

5 The major analytical change was a decrease of the mean corpuscular haemoglobin concentration in 38% of the cases. However, no significant decrease in both serum and erythrocyte cholinesterase activities was observed.

6 The sprayers were not usually aware of the potential hazards of pesticides and did not try their best to maintain personal hygiene.
Pharmacokinetics of verapamil in overdose
Authors: Kivistö Kari T , Neuvonen Pertti J , Tarssanen Leo
Published: December 2008

The information on the pharmacokinetics of verapamil in overdose is scanty. We report two adults who ingested 3.2 g and 4 g ofverapamil, respectively. Both patients had hypotension and a severe bradycardia. The highest plasma verapamil concentration in these patients was about 2200 ng/ml and 2700 ng/ml, respectively. The decline in plasma verapamil and norverapamil concen trations followed first-order kinetics, and the half-life of verapamil was 7.8 h and 15.1 h, respectively. The free fraction of verapamil (non-protein bound) was higher at total concentrations exceeding 2000 ng/ml (12 -15%) than at lower concentrations (2-6%). There seems to be no marked saturation ofthe metabolism of verapamil in acute poisoning. The apparent concentration-dependent changes in the free fraction may be due to therapeutic measures.
Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat
Authors: Crevel RWR , Buckley P. , Robinson JA , Sanders IJ
Published: December 2008

1 Groups of male rats were given different doses of cyclosporin A, ranging from the maximum tolerated dose (20 mg/kg/day) downwards, 7 days a week for 28 days using a protocol derived from OECD test guide line 407.

2 At the end of the test, one set of animals underwent a detailed necropsy and histopathological examination of lymphoid tissues. Immune function was assessed using the lymphoproliferative response and natural killer cell activity of their spleen cells. Another set of animals was immunised with sheep erythrocytes on day 25 and used to evaluate the ability to produce specific anti-sheep red blood cell antibody.

3 Cyclosporin A produced detectable effects on the immune system at all doses and at doses lower than other toxic effects. Both histopathological techniques and one of the immune function tests were able to identify changes at the lowest dose, 1.25 mg/kg/day.

4 The results of this investigation suggest that conven tional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to im mune function tests.
α-glutathione s-transferase (α-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat
Authors: Clarke H. , Egan DA , Heffernan M. , Doyle S. , Byrne C. , Kilty C. , Ryan MP
Published: December 2008

1 The use of the cytoplasmic enzyme, alpha glutathione s-transferase (α-GST) as an early index of carbon tetrachloride (CCl4) toxicity in the rat was investigated and compared with a standard enzyme marker, aspartate aminotransferase (AST). The hepatotoxic effects of CCl 4 in the rat were determined in a time and dose-response study.

2 Following CCl 4 exposure, α-GST release was shown to be an earlier and more sensitive biomarker of hepatotoxicity than AST.

3 Significant increases in α-GST were detected 2 h after CCl4 exposure. Using the enzyme marker AST, this early hepatotoxic injury went undetected. At 6 and 16 h, α-GST was also a more sensitive indicator of hepatotoxicity than AST.

4 α-GST release was significantly increased at a dose of 5 μl/kg, the lowest concentration of CCl4 administered and clearly responded in a dose-dependent manner with increasing doses of CCl4. In contrast, release of AST did not reach statistical significance until a dose of 25 μl/kg.

5 Thus, these findings indicate that α-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.
Leaded gasoline abuse: the role of tetraethyl lead
Authors: Tenenbein Milton
Published: December 2008

Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations,hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.
In utero and lactational exposure of carbofuran to rats: Effect on testes and sperm
Authors: Pant N. , Shankar R. , Srivastava SP
Published: December 2008

1 Male offspring of adult females treated with 0.2 or 0.4 mg/kg during either the whole of pregnancy or the whole of the lactation period did not induce general ised toxic effects.

2 A significant alteration in enzymatic activities i.e. SDH (decreased), LDH and Y-GT (increased) were observed in testes only at 0.4 mg/kg.

3 A decrease in sperm motility, sperm count along with increase in percent abnormal sperm was observed at 0.4 mg/kg dose level.

4 Histopathological examination revealed loss of sper mato-genesis, degenerative changes in Sertoli cells which are well supported with biochemical studies indicating that carbofuran interferes with the matura tion process of testis.

5 No such effects were observed at 0.2 mg/kg.

6 The testicular and spermatotoxic effects observed in rats given in utero or lactational exposure may be due to transfer of carbofuran or its metabolites through placenta or mothers milk.
Small-intestinal absorption of cadmium and the significance of mucosal metallothionein
Authors: Elsenhans B. , Strugala GJ , Schäfer SG
Published: December 2008

1 Although food intake is among the most important routes of Cd exposure, not many details are known about the intestinal absorption mechanisms of Cd. In this respect Cd is representative of most other nonessential, merely toxic metals.

2 Based on a concept of two distinguishable steps, intestinal absorption of Cd is characterized by high accumulation within the intestinal mucosa and a low rate of diffusive transfer into the organism.

3 After uptake into the mammalian organism, Cd is sequestered into hepatic metallothionein (MT). It is assumed that hepatic Cd-MT then gradually redis tributes Cd to the kidney, which is the main target organ for chronic Cd toxicity.

4 When feeding low levels of dietary CdCl2, however, Cd accumulates preferentially in the kidney and to a lesser degree in the liver, a distribution pattern also found after intravenous and peroral administration of the Cd-MT complex itself. As dietary Cd induces intestinal MT, intestinal Cd-MT complexes could be at least partly responsible for the renal accumulation of dietary Cd.

5 For this mechanism, however, serosal release of mucosal Cd-MT is required. In fact, in vitro findings in rats reveal a concentration-dependent release of intestinal MT to the serosal side of the small intestine. These results indicate that endogenous intestinal MT may deliver Cd-MT to other inner organs, thus contributing to the preferential renal accumulation of ingested Cd.
Digoxin toxicit in chronic renal failure: treatment by multiple dose activated charcoal intestinal dialysis
Authors: Critchley Julian AJH , Critchley Lester AH
Published: December 2008

1 Digoxin toxicity can result from overdose or iatrogenic causes, especially if renal function is impaired.

2 We present a case of digoxin toxicity presenting with severe bradycardia and hypotension in a 66 year old man with chronic renal failure. Regular haemodia lysis had, as predicted, failed to reduce his plasma digoxin concentration. Digoxin specific antibody fragments (Fab) were not readily available and their use was probably inappropriate as they are normally renally eliminated.

3 The patient was successfully treated by two prolonged courses of intestinal dialysis with repeated doses of activated charcoal over 48 and 72 h and totaling 400 g and 600 g, respectively. However, the patient found the activated charcoal extremely unpalatable.

4 Multiple dose activated charcoal intestinal dialysis (MDACID) has been recently advocated for use in a wide range of poisonings. The technique takes advantage of the large surface area of the small intestine to eliminate drugs and metabolites, over several days if necessary. The pharmacokinetics of digoxin toxicity in chronic renal failure make intest inal dialysis an appropriate method of treatment but the realisation of the true potential of this technique awaits a more palatable absorbent or formulation.
One Comprehensive System? A Historical Perspective on Federal Disability Policy
Authors: Scotch Richard K. , Berkowitz Edward D.
Published: December 2008

We examine the historical development of federal disability policy; we assess the scope of the social security disability system, as well as inconsistencies between that attempt at a comprehensive system and programs such as vocational rehabilitation, veterans' programs, and special entitlements for blind people; and we conclude with a list of the questions that our analysis raises for the conduct of disability studies.
Secondary Disability Prevention: Involving Consumers in the Development of a Public Health Surveillance Instrument
Authors: Seekins Tom , Smith Naomi , McCleary Tim , Clay Julie , Walsh Jim
Published: December 2008

Recent legislation has directed the Centers for Disease Control of the Public Health Service to develop a program of disability prevention. Importantly, this new program focuses attention on preventing secondary disabilities—conditions that occur after an individual has acquired a primary (or first) disability. An important influence on the agenda of secondary disability prevention involves identifying the conditions that define the problem for intervention. In public health, this is often accomplished through surveillance systems. In this paper we describe the development of a consumer-directed secondary disability surveillance tool that is consistent with consumer control tenets of independent living philosophy.
Parents with Mental Retardation
Authors: Tymchuk Alexander J.
Published: December 2008

The topic of parenting by people with mental retardation has a long and controversial history during which it was assumed that, as a result of that mental retardation, they were unable to provide adequate parenting. More recently, individual researchers and practitioners have attempted to demonstrate that, while some parents with mental retardation do not provide adequate child care, many currently do so and are able to improve their parenting skills. Unfortunately, there have been limited responses to systematically address this area. In this report the author presents what we do and do not know about parents with mental retardation and, based upon his experience in the mental retardation field for the past two decades, makes recommendations for a national strategy.
Mainstreaming the Deaf Student
Authors: Foster Susan , Emerton Greg
Published: December 2008

In most areas of special education, Public Law 94-142 has been hailed as a breakthrough. By stipulating that children with disabilities be educated within the least restrictive environment, the law promotes schooling of these children with their nondisabled peers. However, interpretation of the impact of this law has taken a different turn in the case of people who are deaf. Instead of welcoming the idea of mainstreaming and corresponding closing of separate schools for deaf students, many people have raised strong concerns and objections regarding mainstreaming for deaf children. Is mainstreaming good or bad for deaf students? In this paper, issues on both sides are presented in the form of a debate, in which introduction of one point leads to rebuttal, and the entire piece becomes an exercise in point and counterpoint.
Disability Policy Issues in Developing Countries
Authors: Barnartt Sharon N.
Published: December 2008

Few developing countries have articulated disability policies, although disability prevalence in developing countries may be higher than in developed countries. This paper presents a definition of disability policy which includes both manifest and latent aspects of policies in the areas of education, rehabilitation, economics, and civil rights. Educational issues relate to the economics of mainstreaming and whether it is an improvement over no education at all. The rehabilitation issue focuses on whether services can or should be centralized/specialized or decentralized/non-specialized. In economics the issues are sources of money and control over expenditures. Civil rights has not yet received the attention in developing countries that it has begun to receive in developed countries.
Moral Entrepreneurship and the Promise of the ADA
Authors: Altman Barbara M. , Bamartt Sharon N.
Published: December 2008

A sociological analysis of the passage of the Americans with Disabilities Act uses theories of deviance and social movements to examine the process which led to enactment of the law. Changes in the makeup of the "moral entrepreneurs" pushing for the Act and in the "framing" of the discourse surrounding the issues are two important elements contributing to the enactment. The role of "moral entrepreneurs" in the implementation and enforcement of the Act, since its passage, is also explored. Their continued active involvement in the process may be necessary if the full potential of the law is to be realized.
Challenges and Dilemmas in Implementing Disability Rights Policies
Authors: Percy Stephen L.
Published: December 2008

The passage of the Americans with Disabilities Act (ADA) in 1990 created a powerful civil rights mandate which built and expanded upon the mandates created in earlier disability rights policies. While it is too soon to evaluate the impact of the ADA—compliance deadlines only recently having passed—it is not too early to consider strategies for effective implementation and to identify potential areas of difficulty in program execution. This paper reviews evidence on the implementation of earlier disability rights policies and speculates on potential obstacles and challenges that administrators will face in effectively implementing the ADA.
The Use of Personal Assistance Services by Persons With Spinal Cord Injury
Authors: Nosek Margaret A. , Fuhrer Marcus J. , Rintala Diana H. , Hart Karen A.
Published: December 2008

Previous discussions of personal assistance have focused on census data and descriptions of service programs. The current study examines patterns of usage of personal assistance among a community-based sample of 284 persons with spinal cord injury and how these patterns relate to other aspects of their lives. Expected significant relationships were found among variables of who provides assistance, whether they are paid, and with whom participants live, and between the amount of assistance received and severity of disability. Unexpectedly high rates of use of unpaid nonrelatives and paid relatives were found, as was the use of a combination of relatives and nonrelatives as assistants. Use of nonrelatives increased with education level. The effect of usage pattern on productivity could not be examined due to a staggeringly high unemployment rate (89%). Implications of these results for development of a national policy on providing personal assistance services, the expansion of formal service delivery systems, and the further investigation of the use of personal assistance are discussed.
Who Should Fight?
Authors: Mlawer Mark A.
Published: December 2008

In the attempt to help parents become better educational advocates for their children with disabilities, an "advocacy expectation" has been created. This expectation runs counter to the philosophy of normalization. The advocacy expectation and its effects are critically discussed. To counter the expectation and its effects, changes in professional roles, funding priorities, and program development are recommended.
Overcoming Treatment Barriers to Providing Services for Adults With Dual Diagnosis
Authors: Drainoni Mari-Lynn , Bachman Sara S.
Published: December 2008

A large and growing proportion of individuals with permanent and total disability are adults dually diagnosed with mental illness and substance-abuse disorders. These dually diagnosed individuals are frequently hospitalized, often unable to work, and thus are dependent on public systems for care. As the prevalence of clients with dual diagnosis continues to increase, states must examine how to best manage services for these individuals. This paper discusses some issues involved in serving this population, barriers to treatment, and program approaches for overcoming the barriers to providing effective services to individuals who are dually diagnosed.
Asian Pacific Americans
Authors: Yang Haiou , Leung Paul , Wang Jerry , Shim Neil
Published: December 2008

The Rehabilitation Act Amendments of 1992 mandate that state and federal public vocational rehabilitation extend efforts to further include “traditionally underserved” populations. Section 2 1 of the Rehabilitation Act Amendments specifies the Asian Pacific American population as an “underserved group, and other data indicate that they are the fastest growing minority population in the United States. Yet, current data related to rehabilitation and disability at the national level are unavailable for Asian Pacific Americans. This article uses data taken from the Hawaii vocational rehabilitation program to illustrate the need for Asian Pacific American data to be reported, not only in aggregate form, but also for each ethnic group within the aggregate. It proposes a policy change for the way data are gathered and collected for the Asian Pacific American population.
Assessing Employment Discrimination Charges Filed by Individuals With Psychiatric Disabilities Under the Americans With Disabilities Act
Authors: MOSS KATHRYN , JOHNSEN MATTHEW , ULLMAN MICHAEL
Published: December 2008

This article presents findings from analyses of nationwide data on employment discrimination charges filed under the Americans With Disabilities Act (ADA). In conducting the analyses, emphasis was placed on understanding the extent to which the ADA charge process differentially affects individuals with psychiatric disabilities. We found that 16.3% of individuals whose charges were closed as of June 30, 1995, received benefits from filing charges; individuals with psychiatric disabilities were only somewhat less likely to experience benefits from filing charges than were individuals with nonpsychiatric disabilities; individuals with schizophrenia had a strikingly lower benefit rate than all other individuals with other types of psychiatric disorders; and there was considerable variation among individuals with different kinds of nonpsychiatric disabilities in benefit rates.
Reading Problems in Children
Authors: Paul Samuel E.
Published: December 2008

An evaluation of the relationship of reading to cerebral dominance and maturation.
The Child with Learning Disabilities in a Spelling Class
Authors: Crawford Lee
Published: December 2008

Specific suggestions for helping learning-disabled children to learn to spell, taking into consideration the individual's particular area of difficulty.
Teaching Spelling to Children with Specific Language Disability
Authors: Aho Martha S.
Published: December 2008

A specific technique, the Slingerland Adaptation of the Orton-Gillingham Multisensory Approach is described for teaching children who have specific language disability to spell.
Approaching Vision Training
Authors: Forrest Elliott B.
Published: December 2008

A guide to the behavioral concepts of vision.
Getting the Parents Involved
Authors: McPhail Gail
Published: December 2008

An educationally handicapped student was working in an informal testing session with a teacher before being admitted to a special class. As the teacher was concluding the testing session, the child's mother walked through the door and asked: "Well, how dumb is he?"
Let Your Fingers Do the Walking
Authors: Pecchenino Eve Hill , John Jeanne St.
Published: December 2008

Acupressure in the classroom is a new thrust that promises to promote learning and a feeling of wellbeing.
Ten Reasons Why Peer Tutoring Won't Work
Authors: Harris Joey , Aldridge Jerry
Published: December 2008

If peer tutoring isn't working, it may indicate a breakdown of the component parts. Careful planning and implementation will solve the problem.
Home Visiting the LD Child
Authors: Boe Marilyn J.
Published: December 2008

The benefits of a single home visit can follow the child throughout the entire school year in terms of student-teacher understanding and rapport.
Individualized Instruction
Authors: Kates Carol M.
Published: December 2008

Preplanning, timing/scheduling, evaluation, and organizing work materials are important elements for facilitating individualized instruction.
Teaching Figurative Language
Authors: Fisher Elissa L. , White June Miller , Fisher James H.
Published: December 2008

Figurative language, so commonly used in everyday language, can present communication difficulties but specific techniques will solve this problem.
Generalization
Authors: Mastropieri Margo A. , Scruggs Thomas E.
Published: December 2008

Specific instructional strategies will allay transitional problems when the student moves from a special education to a mainstream setting.
Helping LD Students make Transitions
Authors: Slade David
Published: December 2008

Teachers of the learning disabled must consider many different factors to minimize transition difficulties.
Learning Disabled? Maybe, Maybe Not!
Authors: May Jo Whitten
Published: December 2008

We may need more than one label to identify children who demonstrate learning differences.
Mainstreaming the Special Educator
Authors: Reynolds Catharine J. , Volkmar Janet Notheis
Published: December 2008

The Mainstreamed Special Educator Model provides a smooth transition from the resource room to the regular classroom for the mildly handicapped.
Developmental Aspects of Learning to Spell
Authors: Gentry J. Richard
Published: December 2008

For learning disabled and normally developing children alike, more is being learned about how to teach spelling.
Orthographic Problem-Solving
Authors: Hall Robert J.
Published: December 2008

Spelling-error analysis can produce intervention techniques that may promote greater generalization of spelling skills for problem spellers.
Who'll Help my Disabled Child when I'm Gone?
Authors: Apolloni Tony
Published: December 2008

Careful estate planning is critical for the future of a disabled youngster.
LD'S—What Happens when they are no longer Children?
Authors: Kroll Laura G.
Published: December 2008

An examination of existing research on the LD adult in terms of educational, vocational, social and other implications
Improving Memory for Facts
Authors: Scruggs Thomas E. , Mastropieri Margo A.
Published: December 2008

The “keyword” technique is particularly useful in helping to improve learning and memory skills of special education students.
A Place for Everyone
Authors: Macklem Gayle L.
Published: December 2008

A structured learning program for high school students unable to function adequately in mainstream settings
Helping the LD Child with Homework
Authors: Landers Mary F.
Published: December 2008

Valuable tips on how to help an LD child with out-of school assignments
UGAP
Authors: Gleason Joni J.
Published: December 2008

A technique to aid failing students who do not meet the criteria for special services
Hand-Eye Coordinations
Authors: Getman G.N.
Published: December 2008

It is imperative that we find better ways to lead every youngster to his ultimate potential in the uniquely human ability of written expression.
Individualized Reading
Authors: Hoover John J.
Published: December 2008

A method that will enable teachers to be more accountable in determining if the basic steps in reading have been mastered and retained
Help for the LD College Student
Authors: Decker Thomas W. , Polloway Edward A. , Decker Barbara Brundige
Published: December 2008

College programs must become responsive to the needs of LD students. Here are specific recommendations for intervention oriented to common problems.