bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined multichannel intraluminal impedance–pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication
Authors: Mainie I , Tutuian R , Agrawal A , Adams D , Castell D O
Published: October 2006

Background

Combined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events. It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring.

Method

A prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal reflux disease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients who had undergone fundoplication at this institution. Follow-up after fundoplication was by periodic telephone interview and review of clinical records.

Results

Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7–78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow-up of 14 (range 7–25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow-up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months.

Conclusion

Patients with a positive symptom index resistant to PPIs with non-acid or acid reflux demonstrated by MII-pH monitoring can be treated successfully by laparoscopic Nissen fundoplication.
Surgical strategies for gastric cancer with synchronous peritoneal carcinomatosis
Authors: Gretschel S , Siegel R , Estévez-Schwarz L , Hünerbein M , Schneider U , Schlag P M
Published: October 2006

Background

Gastric cancer frequently spreads to the peritoneal cavity. Whether laparoscopy is useful in planning therapy remains controversial. The aim of this study was to investigate the value of laparoscopy and to develop a therapeutic algorithm.

Methods

Six hundred and sixty consecutive patients with gastric cancer were included in this prospective observational study. The sensitivity of abdominal ultrasonography, computed tomography (CT) and laparoscopy for detecting peritoneal carcinomatosis was compared. The lesions were biopsied and classified as P1, P2 or P3 according to the recommendations of the Japanese Research Society for Gastric Cancer. Prognosis was determined according to the stage of peritoneal carcinomatosis and therapeutic procedure adopted.

Results

One hundred and ten (16·7 per cent) of 660 patients presented with synchronous peritoneal carcinomatosis. The sensitivity for detecting peritoneal carcinomatosis was 85 per cent for laparoscopy compared with 19 per cent for ultrasonography and 28 per cent for CT. Patients with P3 disease did not benefit from additional surgery compared with chemotherapy alone. Those with P1 carcinomatosis had improved survival rates after complete resection followed by chemotherapy.

Conclusion

Laparoscopy improves the detection and classification of peritoneal carcinomatosis, and offers patients with gastric cancer a more individualized and effective therapy.
Synthesis, Crystal Structures and Photoluminescent Properties of Three Novel Cadmium(II) Compounds Constructed from 5‐Sulfoisophthalic Acid (H3SIP)
Authors: Liu Qing‐Yan , Wang Yu‐Ling , Xu Li
Published: October 2006

Hydrothermal reactions of Cd(NO3)2 and NaH2SIP (5‐sulfoisophthalic acid monosodium salt) at pH = 2 and 7 produce [Cd2(μ2‐OH2)2(HSIP)2(H2O)6] (1) and [Cd5(μ2‐OH)2(μ3‐OH)2(SIP)2(H2O)5]n (2), respectively. A similar hydrothermal reaction in the presence of dpp [1,3‐bis(4‐pyridyl)propane] yields {[Cd3(SIP)2(dpp)6]·4(H2O)}n (3). Single‐crystal X‐ray diffraction reveals that compound 1 has a discrete dinuclear structure with the [Cd2(μ2‐OH2)2] unit. Polymer 2 features an inorganic layer, which has centrosymmetric 12‐ and 24‐membered rings composed of chair‐shaped [Cd4(μ3‐OH)2] units and Cd(μ2‐OH)2(CO2) units, and is interconnected by SIP into a 3D framework. Complex 3 contains a 1D ladder‐like [Cd4(SIP)4]n unit with four cadmium atoms co‐planar, which is interconnected by dpp into a 2D nanosized layered structure. In the solid state, compounds 1 and 3 exhibit blue‐violet photoluminescence with maxima at 436 and 409 nm upon excitation at 342 and 350 nm, respectively. However, compound 2 shows photoluminescence with the maximum at 306 nm upon excitation at 270 nm.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
DNA Biosensor Concepts Based on a Change in the DNA Persistence Length upon Hybridization
Authors: Mearns Freya J. , Wong Elicia L. S. , Short Ken , Hibbert D. Brynn , Gooding J. Justin
Published: October 2006

Hybridization‐induced physical changes of DNA are exploited in the development of DNA switchable surfaces for electrochemical biosensing purposes. Two types of biosensing concepts are explored, both based on the same basic switchable surface. The interface is designed so that the end‐tethered DNA is able to switch from a flexible state to a rigid one upon hybridization. The first biosensing concept described is a label‐free system that uses air oxidation of the interface, followed by the change in accessibility of the surface upon hybridization to detect complementary target DNA. The second is a ferrocene‐labeled system exploiting the change in DNA flexibility alone. Atomic force microscopy studies of the DNA switching surface are described.
Testing of Bacteria Gluconobacter oxydans and Electron Transport Mediators Composition for Application in Biofuel Cell
Authors: Reshetilov Anatoly , Alferov Sergey , Tomashevskaya Ludmila , Ponamoreva Ol'ga
Published: October 2006

The dependence of EMF, current and voltage at a fixed load, and the fuel cell inner resistance on anolyte composition has been studied using microbial fuel cell (MFC) model. Strain Gluconobacter oxydans subsp. industrius VKM B‐1280 was a biocatalyst; glucose was used as a fuel. The following anolyte compositions were considered: (1) water‐soluble mediator 2,6‐dichlorophenol indophenol (DCPIP) in combination with suspension and immobilized bacteria and (2) hydrophobic mediators ferrocene and 1,1′‐dimethylferrocene in combination with immobilized bacteria. It was shown that DCPIP in combination with immobilized bacteria versus the cell suspension increases the generated EMF for 36%, current for 25%, power for 56%, and inner resistance for 14%. Ferrocene seems to be more preferable as compared with 1,1′‐dimethylferrocene. Ferrocene gives higher values of the generated EMF (for 8%) and current (for 47%), as well as decreases the inner resistance of MFC for 38%. The proposed system can be used for rapid qualitative and quantitative assessment of the “fuel‐cell‐mediator‐electrode” interaction under charge transfer and is used in the search of effective anolyte compositions.
DNA microelectrophoresis using double focus fluorescence correlation spectroscopy
Authors: Bayer Johannes , Rädler Joachim O.
Published: October 2006

Double focus fluorescence correlation spectroscopy (dfFCS) was used to determine electrophoretic mobilities of short double‐stranded DNA (dsDNA)‐fragments (75 base pairs (bp) ‐1019 bp) in microfluidic channels. The electrokinetic flow profile across a microchannel was measured with 1 µm spatial resolution and separated in electroosmotic and electrophoretic contributions. Experiments show that the free solution mobility is independent of DNA length. The diffusion constant is additionally determined by FCS and follows a length dependent rod‐diffusion model. We interpret the electrophoretic mobilities using a modified Nernst Einstein relation, which additionally takes Manning condensation and counterion induced hydrodynamic retardation forces into account. In 3% w/v polyethylene oxide (PEO)‐network (Mr 3 ·105 Dalton) the electrophoretic velocities become size‐dependent with a power‐law exponent be‐tween 0.28 and 0.31. Mixtures of dsDNA‐fragments exhibit distinguishable peaks in the dfFCS cross‐correlation function. The potential of dfFCS for realtime micro‐analysis in terms of speed and spatial resolution is discussed.
Marginal role of impaired aldehyde metabolism in m‐xylene vapour‐induced biochemical effects in the rat
Authors: Elovaara E. , Pfäffli P. , Savolainen H. , Vainio H.
Published: October 2006

Rats were exposed to 300 ppm m‐xylene vapour for 1 or 2 weeks, 6 h daily, 5 days a week. One group was simultaneously given disulfiram in the drinking water (53 μmol kg−1, daily). The disulfiram treatment inhibited propionaldehyde dehydrogenase; such inhibition did not occur when m‐methylbenzaldehyde (i.e., the aldehyde of m‐xylene metabolism) was used as the substrate. Gastric gavage with higher drug doses (0.5 g kg−1, administered one or three times) confirmed this finding. Intermittent inhalation exposure to m‐xylene for 2 weeks lowered the non‐protein sulphhydryl group content in liver and increased the activities of microsomal NADPH‐cytochrome c reductase, 7‐ethoxycoumarin O‐deethylase and UDP‐glucuronosyltransferase in liver. Concomitantly, the oxidation of m‐xylene in vitro was also enhanced. Combined exposure to the solvent and the drug somewhat inhibited the increases in the hepatic drug metabolism and in the rate of microsomal xylene oxidation in vitro which m‐xylene had induced, whereas the renal drug metabolism remained almost unaffected. Despite the changes in the monooxygenase, the solvent burden in the perirenal fat remained comparable. The significance of impaired aldehyde metabolism in m‐xylene toxicity could not be confirmed in male Wistar rats at the above exposure levels.
Toxic substances in the food of animals: Some recent findings of australian poisonous plant investigations
Authors: Seawright A. A. , Hrdlicka J. , Lee J. A. , Ogunsan E. A.
Published: October 2006

Some of the more interesting and significant recent Australian studies of plant toxins are those dealing with furanosesquiterpenoid essential oils, irritant diterpene esters, thiaminase I, trihydroxyindolizidine, carboxyatractyloside and oxalates. Furanosesquiterpenes, found mainly in Myoporum spp., require activation by microsomal mixed‐function oxygenases in order to produce injury in the tissues in which they accumulate. One such compound isolated from M. deserti, deisopropylngaione, causes necrotizing lesions in the liver, kidney and lung. The native pteridophyte Marsilea drummondii contains thiaminase I at such a high level of activity that it can cause clinical thiamine deficiency in adult sheep which graze it at times of the year when it is growing profusely. Potent diterpene esters (which have been found to be potent cocarcinogens in mice) are to be found in thymelaeaceous plants such as Pimelea spp. One such compound, simplexin, also causes marked contraction of vascular smooth muscle, giving rise to the cardiopulmonary and hepatic circulatory disorder in cattle, known as St. George Disease. Carboxyatractyloside has recently been found to be the toxin in Xanthium spp. The compound is a hypoglycaemic agent, an inhibitor of mitochondrial oxidative phosphorylation and causes acute liver necrosis. Swainsona spp. contain the a‐mannosidase inhibitor trihydroxyindolizidine. Consumption of the plants by animals results in the typical lysosomal storage disease a‐mannosidosis. Oxalate or acid oxalate ions in plants normally cause toxicity per se in grazing animals, but when present in low levels in various native and introduced grasses eaten by horses, they can produce negative calcium balance and secondary nutritional hyperparathyroidism within several months.
Heavy metals in Tasmanian shellfish. 2 — The influence of heavy metal ratios on the accumulation and detoxification mechanisms in rats fed contaminated oysters
Authors: Thrower Stephen J. , Olley June
Published: October 2006

The contamination of estuaries in Tasmania by ore processing plants and wolfram mines, and subsequent closure of oyster harvesting leases provided oysters, contaminated with different ratios of heavy metals, for the study of metal interactions. The high atomic ratios of zinc to cadmium (˜ 1200–1400:1) found at certain times in oysters in the Derwent estuary appeared to suppress food intake, growth and feed conversion in rats fed diets containing cadmium in excess of 15 μg g−1 (dry weight). Little cadmium was deposited in the usual target organs, the liver and kidney. Models for prediction of cadmium deposition in these organs based on the zinc and cadmium contents of the diet are discussed. From these models it can be seen that little cadmium would be deposited in target organs from ingestion of shellfish containing levels of metals permitted by health regulations, but the ratios of metals found in shellfish in the Derwent estuary may lead to the instability of metallothioneins in animals consuming the shellfish.
Effect of chlorine and monochloramine in drinking water on the developing rat fetus
Authors: Abdel‐Rahman Mohamed S. , Berardi Mark R. , Bull Richard J.
Published: October 2006

Chlorine dioxide (ClO2) or monochloramine (NH2Cl) may be considered as an alternative to chlorine (HOCl) as a disinfectant in public water supplies, since chlorination produces trihalomethanes. This study was conducted to determine the effect of chlorine and monochloramine on rat fetuses. Female rats were administered 0, 1, 10 or 100 mg l−1 NH2Cl or HOCl daily in the drinking water for 2 1/2 months prior to and throughout gestation. Rats were sacrificed on Day 20 of gestation and fetuses were preserved for soft‐tissue and skeletal examination. No significant increase in fetal resorptions was found in any treated group. A slight increase in skeletal variants (such as incompletely ossified or missing sternebrae, or rudimentary ribs) was seen in 10 and 100 mg l−1 HOCl groups. Soft‐tissue defects, mainly improper orientation of the heart or adrenal agenesis, were observed in the 100 mg l−1 HOCl group. The percentage of total defects (skeletal and soft‐tissue) was increased significantly over control in the 100 mg l−1 HOCl group; however, monochloramine did not produce any significant changes in rat fetuses at any dose level.
Comparative toxicokinetics of 2,3‐14C‐ and 1‐14C‐acrylonitrile in the rat
Authors: Ahmed Ahmed E. , Farooqui Mohammed Y. H. , Upreti Raj K. , El‐Shabrawy Osama
Published: October 2006

The tissue distribution, elimination and covalent binding of 2,3‐14C‐ and 1‐14C‐acrylonitrile (VCN) were studied in male Sprague—Dawley rats given an oral dose of 46.5 mg kg−1. Exhalation of unchanged VCN, 14CO2 and H14CN was monitored at selected intervals. Only 5% of the total dose administered was recovered as unchanged VCN. Rats given 2,3‐14C‐VCN exhaled only 2% of 14C activity as 14CO2 and none was recovered as H14CN, whereas rats given 1‐14C‐VCN exhaled about 12% of 14C activity as 14CO2 and 0.5% as H14CN. In the initial 24 h, 40% of radioactivity from 1‐14C‐VCN appeared in urine, while 60% was recovered in the urine of rats given 2,3‐14C‐VCN. The red blood cells retained significant amounts of radioactivity from both the compounds for more than 10 days after administration, whereas the 14C activity in plasma declined sharply. The highest level of radioactivity from both compounds was recovered in the gastrointestinal tract. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the unbound percent radioactivity decreased, while irreversible percent covalent binding to macromolecules in relation to total increased concomitantly. Subcellular fractionation of the tissues showed that most of the covalently bound radioactivity was distributed in non‐cytosolic fractions. As compared to 1‐14C‐VCN administered animals, the percentage of covalent binding of 2,3‐14C‐VCN was significantly higher even 72 h after dosing. The relationship between covalent binding and acrylonitrile toxicity is discussed.
Genetic Toxicology Association – Fall Meeting 1984
Authors: Szabo Paul , Henderson Ann S. , D'Eustachio Peter
Published: October 2006

The Fall Meeting of GTA was held on 15 November 1984 at Eatontown, New Jersey. The topic for this meeting, ‘Molecular Approaches to Cancer', was addressed by three invited speakers: Paul Szabo, Ann Henderson and Peter D’ Eustachio. A panel discussion, moderated by Ronald Pero, followed these talks. The following are abstracts of the talks given by the main speakers.
Effects of phthalic acid esters on drug metabolizing enzymes of rat liver
Authors: Gollamudi R. , Lawrence W. H. , Rao R. H. , Autian J.
Published: October 2006

Di(2‐ethylhexyl)phthalate (DEHP) inhibited UDP‐glucuronyltransferase activity of rat liver in vitro and in vivo. Diethyl phthalate and dimethoxyethyl phthalate also inhibited this enzyme in vitro. On the other hand, DEHP did not inhibit the activity of the cytosolic enzyme N‐acetyltransferase; it also did not alter the levels of rat liver microsomal cytochrome P‐450 in vitro. It is suggested that DEHP may alter the composition of microsomal phospholipids.
The effect of exposure duration on the blood level of glucose pyruvate and lactate in acute carbon monoxide intoxication in man
Authors: Sokal J. A.
Published: October 2006

Blood glucose, pyruvate and lactate were examined during hospitalization of 13 cases of acute carbon monoxide poisoning developing from short (≦ 1.5 h) or long (10–14 h) exposure. CO intoxication resulted in increased blood levels of all carbohydrate metabolites studied. Increased levels of pyruvate and lactate were much more pronounced and lasted for a longer time following long, compared with short, CO exposure despite similar blood COHb level (about 40% at the beginning of hospitalization).

The results showed difference in biochemical effect of short and long single exposure to CO that could not be detected by the measurement of COHb.
Toxicity of aromatic disulphides. III. In vivo haemolytic activity of aromatic disulphides
Authors: Munday R. , Manns E.
Published: October 2006

Diphenyl disulphide, 4,4′‐diaminodiphenyl disulphide, 2,2′‐diaminodiphenyl disulphide, 4,4′‐dimethyl‐diphenyl disulphide and 4,4′‐dintrodiphenyl disulphide, when administered orally to rats, induced haematological and pathological changes indicative of erythrocyte destruction in vivo. No evidence of haemolysis was detected, however, in animals receiving diphenyl disulphide‐2,2′‐dicarboxylic acid or dibenzyl disulphide. The order of activity of the various aromatic disulphides in provoking in vivo haemolysis was similar to that previously recorded for ‘active oxygen’ generation and erythrocyte damage in vitro.

The results of this investigation suggest that in vivo haemolysis may be anticipated from any disulphide or thiol which undergoes appreciable autoxidation at neutral pH. While aromatic or αβ‐unsaturated thiols and disulphides would be expected to be the most active haemolytic agents, other thiols or disulphides may precipitate the destruction of erythrocytes whose defences against oxidative attack are deficient.
Chronic effects on the respiratory tract of hamsters, mice and rats after long‐term inhalation of high concentrations of filtered and unfiltered diesel engine emissions
Authors: Heinrich U. , Muhle H. , Takenaka S. , Ernst H. , Fuhst R. , Mohr U. , Pott F. , Stöber W.
Published: October 2006

A long‐term exposure study with hamsters, mice and rats inhaling filtered and unfiltered diesel engine exhaust was carried out to investigate effects of chronic toxicity and, predominantly, carcinogenicity in the respiratory tract. The level of diesel exhaust in the exposur chambers corresponded to a concentration close to 4 mg m−3 in the unfiltered diesel exhaust. Satellite groups of animals were additionally treated with BaP, DBahA or nitrosamines in order to check for syncarcinogenic effects.

In hamsters and rats, alveolar lung clearance and mechanical lung function tests as well as biochemical and cytological measurements in lung lavage fluids showed significant changes only after exposure to unfiltered diesel exhaust and, predominantly, in rats.

No lung tumors were found in hamsters. Spontaneous tumor rates occurred in mice and both types of diesel exhaust increased the incidence of adenocarcinomas in the lungs. In rats, only the unfiltered diesel exhaust caused a lung tumor incidence. It amounted to 16% with no tumors in the controls.

The heavy load of particulate matter in the lungs of rats was caused by an exposure‐related impairment of the alveolar lung clearance and may have been instrumental in the induction of squamous cell tumors. However, an effect of particle‐associated PAH cannot be excluded. Syncarcinogenic effects of diesel exhaust after initial carcinogen treatment were found only in the respiratory tract of rats.
Changes in cerebral glycogenolysis and related enzymes in diazinon treated hyperglycaemic animals
Authors: Matin M. A. , Husain Kazim
Published: October 2006

Effect of diazinon (10,20 and 40 mg/kg, i.p.) on the level of blood glucose in rats was investigated. Hyperglycaemia peaked 2 h after i.p. treatment with 40 mg/kg diazinon. The cerebral acetylcholinesterase activity was significantly reduced. The blood level of pyruvic acid was unchanged while that of lactic acid was significantly increased. Convulsions and biochemical changes caused by diazinon (40 mg/kg) were prevented by diazepam injected immediately after diazinon. In diazinon‐treated hyperglycaemic animals, the glycogen content of the brain was depleted, the activities of glycogen phosphorylase, phosphogiucomutase and hexokinase were significantly increased and the activity of glucose‐6‐phosphatase remained unchanged. Lactate dehydrogenase activity was also increased by treatment with diazinon. The induced changes may compensate for the energy requirement of stimulatory effects caused by diazinon.
The relationships of urinary metallothionein with other indicators of renal dysfunction in people living in a cadmium‐polluted area in Japan
Authors: Tohyama Chiharu , Mitane Yuko , Kobayashi Etsuko , Sugihira Naoko , Nakano Atsuhiro , Saito Hiroshi
Published: October 2006

An epidemiologic investigation was carried out to study the significance of urinary excretion of metallothionein (MT) in people aged 50 years and over living in a cadmium (Cd)‐polluted area in Japan. The urinary level of MT was compared with various parameters (age, urinary α1‐microglobulin (α1‐MG), β2‐microglobulin (β2‐MG), total protein, Cd, copper (Cu), and zinc (Zn), and relative clearances to creatinine of α1‐MG, β2‐MG, phosphate and uric acid). It was found that the urinary excretion of MT is closely associated with Cd and the indices of renal dysfunction listed above. This observation was more remarkable in women than men. When subjects with signs of renal dysfunction were compared as a group to those with normal renal functions, the excreted amount of MT in the former is significantly greater. The results support the notion that the urinary excretion of MT reflects not only Cd exposure levels but also renal dysfunction caused by long‐term Cd exposure.
Hemoglobin adducts in animals exposed to gasoline and diesel exhausts 1. Alkenes
Authors: Törnqvist M. , Kautiainen A. , Gatz R. N. , Ehrenberg L.
Published: October 2006

Blood samples from rats and hamsters exposed to automotive engine exhausts in the Committee of Common Market Automobile Constructors long‐term inhalation study at Battelle‐Geneva were analysed for the levels of 2‐hydroxyethylvaline (HOEtVal) and 2‐hydroxypropylvaline (HOPrVal) in hemoglobin (Hb). These adducts to the N‐terminus of the Hb chains were determined by gas chromatography‐mass spectrometry of derivatives obtained by a modified Edman degradation that specifically cleaves off alkylated N‐terminal amino acids (valine in Hb).

The adduct levels found correspond to the metabolic conversion of about 5–10% of inhaled ethene and propene to ethylene oxide and propylene oxide, respectively, in agreement with results from earlier studies on mice inhaling radio‐labelled alkenes. It is concluded that the alkenes, via epoxides, are the main sources of the observed HOEtVal and HOPrVal. From calculated doses and estimates of genotoxic potency the contribution from ethene in urban air to human cancer risk is discussed.
Toxicity of gallium oxide particles following a 4‐week inhalation exposure
Authors: Wolff R. K. , Henderson R. F. , Eidson A. F. , Pickrell J. A. , Rothenberg S. J. , Hahn F. F.
Published: October 2006

To evaluate the inhalation toxicity of Ga2O3, F344 rats were exposed nose‐only to 0.2 μm Ga2O3 particles 2 h/day, 5 days/week for 4 weeks. The exposure concentration was 23 ± 5 mg/m3 (mean ± SD) resulting in lung burdens of 0.8 ± 0.1 mg Ga2O3/lung (mean ± SE) at the end of 4 weeks of exposure. Analysis of bronchoalveolar lavage fluid of exposed rats showed marked responses. One day after termination of exposure, lactate dehydrogenase was increased 6‐fold, and the lysosomal enzyme, beta‐glucuronidase, was increased 38‐fold in rats exposed to Ga2O3 compared to sham exposed controls. Alkaline phosphatase, glutathione reductase, glutathione peroxidase, white blood cells, acid proteinase, and protein were increased 3‐ to 4‐fold. Responses remained elevated 6 and 12 months after exposure. Lung clearance of radiolabeled tracer particles was evaluated 4 days and 6 months after the end of 4 weeks of Ga2O3 exposures. Long‐term clearance half‐times were significantly longer| (3–4 fold, P <0.01) in rats exposed to Ga2O3 than in the sham‐exposed control rats at both 4 days and 6 months, indicating persistent impairment of particle clearance. Histopathological lesions consisted primarily of alveolar proteinosis 1 day after 4 weeks exposure, progressing in severity to large focal lesions of alveolar histiocytosis and septal fibrosis 6 and 12 months after exposure. Inhaled Ga2O3 produced cytotoxic, inflammatory, and fibrogenic responses of comparable or greater magnitude than those seen after similar exposures of rats to inhaled quartz particles in other studies. These data show that inhaled Ga2O3 particles produce considerable toxicity and exposures in the work place should be limited.
Reaction of macrophages activated by agents in vivo to quartz dust in vitro
Authors: Kaw Jawahir Lal , Waseem Mohd
Published: October 2006

A comparative study was made of the cytotoxic action of quartz dust in vitro on macrophages activated in vivo by intraperitoneal inoculation of physiological saline, thioglycolate and starch. The liberation of lactate dehydrogenase (LDH) into the supernatant culture medium, adherence to a plastic surface, extent of acid dye exclusion and ultrastructural alteration in the surface morphology of macrophages were taken as parameters of the cytotoxic action of the dusts. Thioglycolate and starch stimulated cells when exposed in vitro to quartz dust released more LDH into the supernatant culture medium and resulted in a greater decrease in macrophage adherence than similarly exposed cells derived from saline stimulated animals. No difference was observed between cells obtained from differently stimulated animals in increased acid dye uptake, loss of surface filopodia and rounding of cells which phagocytosed quartz particles. The results show that quartz is cytotoxic for macrophages, irrespective of their degree of activation and the extent of damage induced is related to the chemical agent used for activation of macrophages in vivo.
Developmental and sex differences in cadmium distribution and metallothionein induction and localization
Authors: Blazka Mark. E. , Nolan Canice V. , Shaikh Zahir A.
Published: October 2006

Age‐ and sex‐related differences in hepatic and renal distribution of cadmium (Cd) and the effect of Cd injection (10 μmol/kg) on tissue zinc (Zn), copper (Cu) and metallothionein (MT) levels were investigated in 2‐ to 84‐day old rats. Renal Cd accumulation increased with age of the animal. Sex differences in renal Cd accumulation were noted in young animals where the 2‐ and 8‐day old males had significantly greater concentration than the females. There were no clear effects of Cd on renal Zn. Renal Cu levels, however, were elevated in the adults. The adult females contained about twice as much MT as the adult males. Cd treatment had no effect on renal MT levels of 8‐ to 84‐day old animals but depressed the levels in 2‐day old. Age‐related increase in hepatic Cd accumulation was also found; the pattern was more clear cut in females than in males. In addition, in the females the hepatic Cd concentration was significantly higher than in the males. Cd‐injection significantly increased hepatic Zn and MT concentrations only in weaned animals. While there were no sex differences in MT levels in the young animals, the weaned females had significantly more MT than the corresponding males. Immunohistochemical staining for MT showed positive staining in both cytoplasm and nuclei of the parenchymal cells. The number of MT‐positive nuclei was dependent on the relative MT concentration of the liver. In spite of the intense nuclear staining in 2‐day old controls and 84‐day old Cd‐injected rats, less than 1% of the hepatic MT was present in the nuclear fraction. The above data on the tissue distribution of Cd point to the possible effects of sex hormones on Cd metabolism. The results of the intracellular distribution of MT suggest that nuclear MT represents only a minute fraction of the total cellular MT, even in the neonatal rat.
Instability and apparent lack of metabolism of phomopsin a during incubation with ovine rumen fluid
Authors: Vogel Paul
Published: October 2006

To investigate the stability and possible metabolism of phomopsin A in rumen fluid, phomopsin A was incubated in ovine rumen fluid ‐ buffer mixtures for 24 h. High performance liquid chromatographic analysis of extracted incubation mixtures demonstrated that although phomopsin A was degraded, metabolism by rumen microorganisms appears not to be important during 24 h incubation.
Mitochondrial and microsomal lipid peroxidation in rat liver after acute acetaldehyde and ethanol intoxication
Authors: Uysal Müjdat , Özdemirler Gül , Kutalp Güldal , Öz Hikmet
Published: October 2006

The effects of acetaldehyde and ethanol treatments on hepatic lipid peroxidation are compared in rats after the administration of toxically corresponding doses. Wistar rats were given a single dose of acetaldehyde (0.5 g/kg) or ethanol (5 g/kg) intraperitoneally. The animals were killed 1/2, 1, 2, 4, 6, 9, 12 and 24 h after treatments. The results indicate that acetaldehyde, like ethanol, stimulates hepatic lipid peroxidation and also selectively affects the hepatic mitochondria.
The effects of thiamin on the tissue distribution of lead
Authors: Kim Jin Suk , Blakley Barry R. , Rousseaux Colin G.
Published: October 2006

The effects of thiamin on the tissue distribution of lead were evaluated in Sprague–Dawley rats exposed to 1000 ppm lead acetate in drinking water and treated daily with thiamin (25 or 50 mg kg−1 body weight, i.p.), calcium ethylenediamine tetraacetic acid (50 mg kg−1 body weight, i.p.) or their combination for 8 weeks. The subtoxic dose of lead did not alter weight gains, feed and water consumption during the treatment period. Thiamin decreased the blood (P > 0.0001), liver (P < 0.0001) and kidney (P < 0.0001) concentrations of lead. Thiamin (50 mg kg−1 body weight) reduced the lead concentrations in tissues more effectively than thiamin (25 mg kg−1 body weight). The combined treatment was more effective than the respective individual treatments.
Isoniazid potentiation of a guinea pig model of halothane‐associated hepatotoxicity
Authors: Lind Richard C. , Gandolfi A. Jay , de la M. Hall Pauline
Published: October 2006

Isoniazid (INH) is a selective inducer of cytochrome P‐450 isozymes that are involved in the biotransformation of organohalogen anesthetics. It has been used to produce a rat model of halothane‐associated hepatotoxicity that was linked to enhanced oxidative biotransformation of the anesthetic. Guinea pigs were pretreated with INH in order to potentiate halothane‐induced hepatic necrosis and to study the oxidative pathway as a hepatotoxic mechanism in this species. The animals received either 12.5, 25.0 or 50.0 mg kg−1 INH i.p. for 7 days. Following halothane exposure, there were dose‐dependent increases in plasma levels of the oxidative halothane metabolite, trifluoracetic acid. These increases were associated with increases in 48 h plasma alanine aminotransferase (ALT) levels. When combined with halothane exposure, the two higher doses of INH killed the animals before planned termination. These deaths were not attributable to hepatic failure. Dividing the 25 mg kg−1 INH dose into twice daily injections of 12.5 mg kg−1 reduced deaths. INH pretreatment control animals exhibited occasional non‐dose‐dependent increases in ALT as well as the occurrence of fatty vacuolization of hepatocytes at the highest dose. Even though INH pretreatment enhanced oxidative halothae biotransformation and subsequent hepatotoxicity, sensitivity of guinea pigs to the deleterious actions of INH would contraindicate its use as a cytochrome P‐450 induction agent.
Characterization of lymphocyte subpopulations in the blood of the cynomolgus monkey using flow cytometry
Authors: Sagara Nami , Furuhama Kazuhisa , Onodera Takeshi
Published: October 2006

This study was performed to assess the usefulness of flow cytometry in comparison with acid alpha‐naphthyl acetate esterase (ANAE) staining for the enumeration of lymphocyte subpopulations in cynomolgus monkeys. For flow cytometry, use was made of mouse antihuman leukocyte monoclonal antibody (T11), recognized to undergo cross‐reaction with monkey T lymphocytes or antimonkey IgG serum labelled with fluoroscein isothiocyanate. The percentages of lymphocyte subpopulations in mononuclear cells of thirty healthy female cynomolgus monkeys were 72.1 ± 2.4% for T cells and 24.6 ± 2.4% for B cells as assayed by flow cytometry evaluation, and 63.8 ± 2.5% for T cells and 15.8 ± 2.2% for B cells as determined by ANAE staining. Although the percentage of T cells shown by ANAE staining was significantly lower than that seen with flow cytometry, the coefficient of correlation indicated a close correlation in both T and B cell subsets between these two methods. In monkeys receiving 20 mg kg−1 cyclophosphamide daily for 14 days, counts of all leukocytes and T and B cells were decreased, whereas animals treated with 1.0 mg kg−1 muroctasin daily for 14 days showed higher monocyte and neutrophil counts without changes in T or B cells. These results suggest that flow cytometry evaluation has several advantages over ANAE staining with respect to rapidity and precision in toxicological studies using large numbers of monkeys.
Influence of metyrapone and phenobarbital on sodium dichromate nephrotoxicity in developing rats
Authors: Appenroth D. , Gambaryan S. , Friese K.‐H. , Bräunlich H.
Published: October 2006

After the administration of equal doses of sodium dichromate, chromium concentrations in the kidney were lower in young than in adult rats. To test the age‐dependent sensitivity to the nephrotoxicity of dichromate, young and adult rats were given doses to achieve identical chromium conceätrations in the kidney. At equal renal concentrations, young rats had less functional and morphological damage than adult rats. As phenobarbital treatment in young rats enhanced the symptoms of nephrotoxicity and metyrapone treatment in adult rats decreased the symptoms of nephrotoxicity, age‐dependent differences in chromate nephrotoxicity may be linked to an increase in the enzymatic reduction of Cr(VI) with age.
A genotoxicological study of the new local anesthetic carbamate derivatives Carbisocaine, heptacaine and pentacaine
Authors: Siekel Peter
Published: October 2006

The potential mutagenic activity of three carbamate derivatives with local anesthetic activity was investigated. Genotoxic activity was observed after application of Carbisocaine on Euglena gracilis, whereas no activity was detected by Carbisocaine, Heptacaine and Pentacaine on Salmonella typhimurium, Escherichia coli and Drosophila melanogaster.
Effects of aflatoxin on lymphoid cells of weanling rat
Authors: Raisuddin  , Singh K. P. , Zaidi S. I. A. , Saxena A. K. , Ray P. K.
Published: October 2006

Aflatoxin (AF), the hepatocarcinogenic food contaminant produced by the Aspergillus flavus group of fungi, is known to interact with various vital processes, including the immune function. Effects of long‐term treatment of three dose levels of aflatoxin B1 (AFB1) on lymphoid cells of weanling rats were studied. AFB1 treatment caused a reduction in body weight gain, significantly (P<0.01) at the 700 μg level. There was also a significant decrease in the weight of spleen and thymus in AFB1‐treated animals in comparison to control. Similarly, AFB1 depleted cell populations of thymus and bone marrow and WBC and RBC counts. There was a marked reduction in the population and phagocytic capacity of macrophages due to AFB1 administration‐at dose levels of 350 and 700 μg kg−1 body weight. Macromolecular synthesis of DNA, RNA and protein in macrophages was affected, as there was significant inhibition in the incorporation of [3H]‐thymidine, [3H]‐uridine and [3H]‐leucine. The hampered functioning of macrophages may be due to the cytotoxic action of AFB1.
Influence of chronic lead exposure on hormone levels in developing rats
Authors: Vyskočil Adolf , Fiala Zdeněk , Ettlerová Eva , Tenjnorová Iva
Published: October 2006

The effect of five months' exposure to 0.5% lead acetate in drinking water on hormone levels of developing rats was studied. The hypothalamic and striatic concentrations of noradrenaline (NA) were decreased in both sexes. In female but not in male rats, blood and adrenal catecholamines and serum corticosterone concentrations were aiso increased. No changes were observed in serum thyroxine and 3,5,3′‐triiodothyronine levels. Our results indicate that female developing rats are more susceptible to lead than male rats. In female rats, both the hypothalamo‐pituitary‐adrenal and sympatho‐adrenal systems seem to be affected by this lead exposure; in male rats, only the latter system is affected.
Prevention of hydrolysable tannin toxicity in goats fed clidemia hirta by calcium hydroxide supplementation
Authors: Murdiati Tri Budhi , McSweeney Christopher S. , Campbell Roderick S. F. , Stoltz Douglas S.
Published: October 2006

Although plants containing hydrolysable tannins can be hepatotoxic, such poisoning has not been reported in Indonesia despite the presence of these plants. In order to determine the hepatotoxic potential of Indonesian plants, goats were intoxicated experimentally with the Indonesian plant Climedia hirta (harendong), which cuntained 19% hydrolysable tannin. The prophylactic effect of Ca(OH)2 supplementation on the disease was also examined. Two groups of goats were fed for 28 days with grain‐based pellets containing 50% harendong leaf or 50% harendong leaf + 8% Ca(OH)2. Two control groups were fed similar pellets containing 50% of the non‐toxic elephant grass (Pennisetum purpureum) with and without 8% Ca(OH)2. Serum enzymes indicative of liver damage were monitored during the experiment and histopathological examination of selected tissues was done at the conclusion of the experiment. In goats given unsupplemented harendong pellets there was a significant increase in aspartate aminotransferase and glutamate dehydrogenase from 50.2 and 20.6 U I−1 to 219.6 and 63.3 U I−1, respectively. These changes were associated with moderate to severe nuclear pleomorphism, vacuolation and megalocytosis of hepatocytes and deposits of brown pigment in the Kupffer cells. There was also nephrosis of the renal convoluted tubules and collecting ducts, abomasitis and enteritis. Biochemical and histological changes were reduced significanty in the harendong + Ca(OH)2 group and virtually absent from control groups. It is concluded that hydrolysable tannins in harendong leaf are hepato‐ and nephrotoxic and associated with gastroenteritis, but that poisoning may be ameliorated by Ca(OH)2 supplementation.
Evaluation of the onset and duration of response to cold air inhalation challenge in Cynomolgus monkeys (Macaca fascicularis)
Authors: Biagini R. E. , Clark J. C. , Moorman W. J. , Knecht E. A.
Published: October 2006

Cold air inhalation challenge (CAIC) for the evaluation of bronchial reactivity has been proposed as a physical agent alternative to chemical agent challenges (methacholine or histamine), especially suitable for the occupational environment. The present investigation describes and evaluates a method for performing cold air inhalation challenge in Cynomologus monkeys (Macaca fascicularis), a species shown to be useful in animal modeling studies of occupational asthma. Six adult male anesthetized monkeys were ventilated by changes in external pressure while breathing cold air (−25°C to −30°C). Pulmonary function testing was performed at 10, 25, 40 and 55 min post‐challenge. Significant increases (P<0.05) in average pulmonary flow resistance (RL) and decreases in dynamic compliance (CL dyn) were observed, with maximum impairment occurring at 25 min post‐challenge, with a trend towards a return to baseline values at 55 min post‐challenge. Peak expiratory flow rate (PEFR), forced expiratory volume in 0.5 s/forced vital capacity (FEV0.5/FVC) and forced expiratory flow at 50% forced vital capacity (FEF50) showed the same general pattern of reduction as seen with RL; however, these results were not statistically significant, most probably owing to individual monkey variability and the small number of monkeys (N = 6) used. A repeat challenge at 25 min after a primary challenge yielded increased RL in one monkey, suggesting that no absolute refractory period is present from CAIC. Results of these studies demonstrate that CAIC causes bronchoconstriction in monkeys and may be useful in further animal modeling studies designed to determine the asthmogenic/airway irritant potential of occupational toxicants.
Biochemical assessment of cardiac function and damage in animal species A Review of the Current Approach of the Academic, Governmental and Industrial Institutions Represented by the Animal Clinical Chemistry Association
Authors: Evans G. O.
Published: October 2006

Species differences in metabolism, tissue localization, specificity and sensitivity for cardiac damage influence the choice of biochemical investigation used in the assessment of cardiotoxicity. The tests currently used in toxicological studies are broadly categorized herein as enzymes and other proteins, lipids and electrolytes; some limitations of these tests are also discussed.
Evaluation of the embryolethality of butyl benzyl phthalate by conventional and pair‐feeding studies in rats
Authors: Ema Makoto , Itami Takafumi , Kawasaki Hironoshin
Published: October 2006

The embryolethality of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at dosages of 0 (control) and 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intake of BBP was 974 mg kg−1 for the 2.0% BBP group. In this group, all dams exhibited complete resorption of all the implanted embryos, and their food consumption, body weight gain and adjusted weight gain (body weight gain excluding the gravid uterus) during pregnancy were markedly lowered. To determine whether the embryolethality was the result of reduced food consumption during pregnancy, a pair‐feeding study was performed in which the pregnant rats received the same amount of diet consumed by the 2.0% BBP‐treated pregnant rats. The pair‐fed and 2.0% BBP‐treated pregnant rats showed significant and comparable reductions in the adjusted weight gain. In the pair‐fed group, the incidences of postimplantation and total losses were higher than those in the control group, and the number of live fetuses per litter was lower than the control value. However, the complete resorption of all the implanted embryos was not found in any of the pair‐fed pregnant rats. It could be concluded that the embryolethality observed in the 2.0% BBP‐treated pregnant rats is attributable to the effects of dietary BBP but not to the maternal malnutrition from reduced food consumption during pregnancy.
In situ assessment of the rat heart during chronic carbon monoxide exposure using nuclear magnetic resonance imaging
Authors: Bambach Gregory A. , Penney David G. , Negendank William G.
Published: October 2006

Ventricular hypertrophy induced in male Sprague‐Dawley rats by inhalation of 500 ppm carbon monoxide (40% carboxyhemoglobin level) for 0–62 days was assessed by contiguous 2‐mm thick axial cardiac crosssections, using 32 accumulated averages of ungated fast‐scan gradient‐recalled nuclear magnetic resonance (NMR) images. Following final imaging, the rats were sacrificed and the hematocrit and heart mass were determined. The mean outside diameter of the left ventricle plus interventricular septum (LV + S) showed a strong correlation (r = 0.73, P<0.01) with the duration of CO exposure, while the correlation coefficients for the LV + S Iumen diameter and wall thickness were marginally significant. The mean pleural space diameter also increased significantly (r = 0.64, P<0.05) with the duration of CO exposure. The ratio of LV + S wall thickness and the Iumen radius was 0.53 in the rats exposed to CO for 0–8 days; this value did not change with longer CO exposure. The LV + S outside and Iumen diameter showed significant correlations to the hematocrit (r = 0.72, p<0.05 and r = 0.66, P<0.05, respectively), and the LV + S outside diameter correlated with the increase in the LV + S mass (r = 0.72, P<0.05). The results achieved with NMR imaging are consistent with past morphometric studies of CO‐induced ventricular hypertrophy, where heart dimensions were determined in relaxed frozen tissue, and corroborate the eccentric nature of CO‐induced ventricular hypertrophy.
Cyanide‐induced alteration of the adenylate energy pool in a rat neurosecretory cell line
Authors: Maduh Edward U. , Borowitz Joseph L. , Isom Gary E.
Published: October 2006

Cultures of a rat PC12 pheochromocytoma neurosecretory cell line were used to determine the responsiveness of oxidative energy status of isolated neuronal cells to cyanide exposure. Intracellular levels of ATP and its immediate metabolites, ADP and AMP, were measured in monolayer cultures of PC12 cells incubated for 0–30 min with KCN (10 mM). Over the period 2.5–30 min, cyanide treatment decreased ATP levels by 32–51% but ADP and AMP levels were not altered significantly. Additionally, ATP/ADP and ATP/AMP ratios were significantly reduced in KCN‐intoxicated cells. These alterations in energy status may explain the prompt ablation of ion homeostasis reported previously in this model upon exposure to KCN. The energy‐depleting actions of cyanide were not modified by pretreatment of cells with diltiazem, a calcium channel antagonist demonstrated to possess cytoprotective activity against histotoxic hypoxia induced by cyanide. Since PC12 cells rapidly respond to cyanide, with predictable depletions of the cell adenylate energy pool, this cell line can serve as a suitable in vitro model for studies of neurotoxicity involving ischemic/hypoxic conditions.