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PubMed1992

The influence of ascorbic acid on lipid peroxidation in guinea pigs intoxicated with cadmium.

Cadmium (as CdCl2) administered at a dose of 1 mg Cd/animal/day in drinking water to guinea pigs with a low intake of ascorbic acid (2 mg/animal/day) increased lipid peroxidation (LPO) in the kidney, liver and serum after 5 wk of treatment. A high intake of ascorbic acid (100 mg/animal/day) decreased LPO (determined from malondialdehyde levels) in the kidney, liver and serum of Cd-treated guinea pigs. Administration of Cd to guinea pigs with a low intake of ascorbic acid significantly increased LPO in the kidney at 5 wk, in comparison with controls given low levels of ascorbic acid but no Cd. However, at 12 wk, LPO in the kidney of Cd-treated guinea pigs was significantly lower than in the controls. These results indicate that the level of lipid peroxides in the kidney of guinea pigs with a low intake of ascorbic acid depends on the amount of accumulated cadmium.

Administration, Oral↗
PubMed1992

A transient rise in plasma beta-endorphin after a traditional 47 degrees C hot-spring bath in Kusatsu-spa, Japan.

To clarify the mechanism of the intoxicating feeling attained after a traditional 47 degrees C hot-spring bath called 'jikan-yu' in Kusatsu-spa, Japan, we examined the change in plasma levels of beta-endorphin and methionine enkephalin in 7 healthy subjects. The mean sublingual temperature rose from 36.8 degrees C to 38.6 degrees C and the plasma beta-endorphin level from 16.2 pg/ml to 49.5 pg/ml 2 minutes after completing a 3-minute bath in 47 degrees C hot-spring water. However, the plasma methionine enkephalin level was not changed. This feeling of intoxication may be explained by the transient rise in plasma beta-endorphin level.

Adult↗
PubMed1999

Lead intoxication impairs the generation of a delayed type hypersensitivity response.

The effect of oral administration of lead, as Pb-acetate, via the drinking water on the murine delayed type hypersensitivity (DTH) response was investigated. The DTH response of BALB/c mice sensitized intravenously with sheep red blood cells (SRBC) was found to be suppressed markedly in lead-intoxicated mice. Suppression of the DTH correlated with increasing blood Pb concentration. Suppression of the DTH response by Pb intoxication depended on the route of administration of the sensitizing antigen, as Pb intoxication did not impair the DTH reaction when mice were sensitized to SRBC via intraperitoneal injection. Since DTH reactions are regulated in large part by Th1 cells, these data establish an in vivo model system based on a rational route of Pb exposure in which to study further the modulation of Th1-mediated immune effector function by Pb.

Administration, Oral↗
PubMed1983

Urinary coproporphyrin in lead intoxication: a study in the rabbit.

Lead acetate was administered to adult New Zealand White rabbits in their drinking water. Their mean blood lead level rose to 4.5 mumol/l within a week and then remained relatively constant. The rabbits developed a marked coproporphyrinuria. Plasma levels of coproporphyrin increased but not in proportion to the urine excretion. Thus the renal clearance of coproporphyrin rose from a mean of 1.8 ml/min to 32.2 ml/min whilst creatinine clearance remained constant. The concentration of coproporphyrin in renal venous blood from control rabbits was found to be slightly lower than that in arterial blood. In the lead intoxicated rabbits the concentration of coproporphyrin in renal venous blood was approximately three times higher than the arterial concentration. Significantly higher levels of lead, porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin were found in renal tissue than in brain, heart or liver. Renal tissue homogenates from control rabbits were able to synthesize porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin when incubated with 5-aminolaevulinic acid. Renal tissue from lead intoxicated rabbits was also able to synthesize these haem precursors although at a reduced rate. Three enzymes from the haem biosynthetic pathway were assayed in renal mitochondria. Compared with those from controls, mitochondria from lead intoxicated rabbits showed no significant difference in ferrochelatase activities, but the activities of coproporphyrinogen oxidase were decreased, and those of 5-aminolaevulinate synthase were increased. It was concluded that a large portion of the excess coproporphyrin excreted by the lead intoxicated rabbits was of renal origin.

Animals↗
PubMed1993

Permeability and surface area of the blood-nerve barrier in galactose intoxication.

The blood-nerve movement of a small molecular weight non-electrolyte was studied in control and galactose-fed rats by measuring the permeability-surface area (PSA) product of the blood-nerve interface to [14C]mannitol in sciatic nerve using an in vivo injection method. PSA products were measured after 9 to 11 months of feeding control rats a diet containing 0% galactose and galactose-intoxicated rats a diet containing 40% galactose. Nerves of the galactose-fed group were hydrated as reflected by a significant increase in nerve water content and wet weight to dry weight ratio (both P < 0.05). Compared to controls, PSA products were increased by 51% (P < 0.01) in galactose-fed animals when referenced to nerve dry weight (13.59 +/- 2.90 x 10(-5) ml/s/g dry wt. versus 8.99 +/- 1.59 x 10(-5) ml/s/g dry wt.; mean +/- S.D.; galactose vs. control, respectively) or by 30% (P < 0.001) when referenced to nerve length (2.43 +/- 0.43 x 10(-5) ml/s/mm vs. 1.87 +/- 0.48 x 10(-5) ml/s/mm) but not when referenced to nerve wet weight. It is suggested that in galactose intoxication, where endoneurial volume changes reflect increases in nerve water content, PSA products are best normalized to dry weight or length, which are not affected by volume changes. Normalized to dry weight, the blood-nerve barrier surface area (i.e. vessels and perineurium) was determined by morphometric methods to be increased by 34% in the galactose-intoxicated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

A successful method for development of voluntary alcohol intoxication in mice.

Eight strains of male mice, C57BL, C3H SWM, SW, KK, KSB, KR and DBA, were fed on a standard pelletized diet and offered a choice of water or 10% sake solution (sake containing 10% alcohol). Both young (3 months of age) and old (8 months of age) groups were studied simultaneously. The degree of intoxication was measured by recording the drinking behavior on a pulse recorder, by calculating gaschromatographically the blood alcohol concentration, by taking depth electroencephalogram readings and so on. Intoxication, shown by lack of coordination such as grossly impaired gait, was observed only in the older mice of strain with a moderate natural alcohol preference such as C3H, SWM, SW, KK and KSB. In general, the intoxicated mice were over 9 months of age, tended to consume fluids regardless of the time of day or night and suffered a loss of body weight. The blood alcohol levels of them were over 4.6%. The threshold elevation of the ascending reticular activating system on electroencephalogram in a intoxicated mouse reached about 167%. The present study provides a successful method for the development of voluntary alcohol intoxication in mice.

Age Factors↗
PubMed1985

Age-related differences in blood ethanol parameters and subjective feelings of intoxication in healthy men.

Healthy men within 4 age groups, 20-29, 30-39, 40-49 and 50-59 years (N = 12 per group), drank 0.68 g/kg ethanol as neat whisky after fasting overnight. The drink was finished within 20 min and the concentrations of ethanol in capillary blood were determined at 30-60 min intervals for 7 hr. At the time of blood sampling, the men were asked to estimate their feelings of intoxication according to an arbitrary scale on which the score 10 indicated 'tipsy' or a 'little high'. The time course of blood ethanol concentration was similar in all 4 groups with the curve for 50-59-year-old men on the highest level and 20-29-year-old men lowest. Subjective intoxication scores were significantly less in the youngest age group and the maximum score for each subject was correlated with age (r = 0.45, P less than 0.01). Total body water (TBW) was not correlated with age directly (r = 0.17, P greater than 0.05) but when it was expressed as percent of body weight a strong negative correlation was found (r = -0.77, P less than 0.001). The mean total body water estimated from ethanol dilution was 46.7 +/- 4.1 l. (+/- SD, N = 48) and this corresponds to 58% of mean body weight of the men. The distribution volume of ethanol/kg body weight (Vd) decreased with ageing (r = -0.59, P less than 0.001) being 0.72, 0.71, 0.68 and 0.66 l/kg on average in the 20-29, 30-39, 40-49 and 50-59-year-old age groups respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Changes in physicochemical properties of mitochondrial membranes during the formation process of megamitochondria induced by hydrazine.

Changes in some biochemical and physico-chemical properties of rat liver mitochondrial membranes during the formation process of megamitochondria induced by hydrazine were analyzed. Hepatic mitochondria obtained from rats placed on a 1% hydrazine diet for 3 days became slightly enlarged and sometimes elongated, while they became gigantic after 7 days of hydrazine intoxication. Changes were observed in mitochondria from rats treated with hydrazine for 3 days. Total amounts of phospholipids extracted from mitochondria and submitochondrial fractions were increased. Among phospholipid species, relative amounts of acidic phospholipids were increased. Contents of Ca2+ in mitochondria were increased. Differential scanning calorimetric analysis of mitochondria, especially that of the outer membrane fraction, showed that the thermotropic lipid phase transition temperatures were elevated accompanying the broadening of thermograms and the increase in transition enthalpy. Contents of water in mitochondria were increased significantly with the ratio of freezable water to unfreezable water unchanged. Among the changes observed was that the total amount of phospholipids (except for that of the outer membrane fraction) and the contents of water and Ca2+ nearly returned to normal in megamitochondria after 7 days of hydrazine intoxication. Relative amounts of phospholipids and thermotropic lipid phase transition temperatures of megamitochondria did not return to normal levels and yet changes were smaller than those obtained from 3 days of hydrazine intoxication. The fluidity of mitochondrial membranes was not affected by hydrazine treatment. These data would suggest that hydrazine-induced megamitochondrial formation is not due simply to the swelling of mitochondria, but might be due to the fusion of adjacent mitochondria by Ca2+-acidic phospholipid interactions, and once megamitochondria are formed the mitochondrial membranes are stabilized.

Animals↗
PubMed2004

Prosecution after an outbreak of subacute aluminum intoxication in a hemodialysis center.

Criminal prosecution of physicians for the death of patients has been extraordinarily rare, but there seems to be a rising trend. This case report describes the medical and judicial implications of criminal prosecution of two doctors at a hemodialysis clinic in the Netherlands Antilles that had to stand trial over the death of 10 dialysis patients. The patients died of subacute aluminum intoxication when aluminum leached from the cement lining of a newly installed water distribution pipe into the water supply of the dialysis center that did not make use of a water treatment system (WTS). Data of the case history of the dialysis patients, the criminal prosecution, preliminary judicial inquiry, the defense arguments and verdicts are reviewed. The prosecutor first decided to dismiss the case, but after an appeal by the families, the Court of Appeal decided to pursue prosecution for gross negligence. It held that the dialysis center should have used a WTS and also held that the dialysis staff reacted insufficiently on extra alarms on the dialysis machines in the two days after the new water distribution pipe was put in use. From June 6, 1998 until January 1999 a preliminary judicial inquiry was performed in The Netherlands and on Curaçao. After a cross-examination of 13 court-appointed experts by the prosecutor and the investigative judge, the prosecutor charged the two physicians of gross negligence manslaughter for not testing the composition of the water after the construction at the water distribution network. A prison sentence with probation of 6 months was demanded. The District Court disagreed on all issues with the prosecutor, but nevertheless held the medical director of Diatel guilty for performing hemodialysis without a WTS. In May 2000, the Court of Appeal held that it was not allowed to rule on the omission to install a WTS because this issue was not included in the charge and overturned the conviction. Medical personnel in charge of potentially dangerous procedures should be prepared for unexpected changes in the quality of their treatment. Because court-appointed experts might have an extraordinary role in the decision making process, guidelines should be prepared to ensure the trustworthiness of their testimony.

Aluminum↗
PubMed1994

Histopathological evidence of vitamin C protection against Cd-nephrotoxicity in guinea pigs.

The critical organ of chronic cadmium (Cd) exposure are kidneys. Long-term exposure leads to Cd accumulation in kidneys and causes renal tubular dysfunctions. Cd-induced renal changes are irreversible, so the primary prevention by different nutrients can play an important role. In this study, male guinea pigs which, like humans, do not synthetize ascorbic acid (AA) received low (2 mg/animal/day) or high (100 mg/animal/day) dosage of AA and cadmium (1 mg Cd/animal/day) in drinking water for 12 weeks. Characteristic finding in renal morphology of Cd-intoxicated guinea pigs was dilatation of interstitial veins with apparent paravenous lymphatic infiltrates. Histomorphological changes were more evident in Cd-intoxicated guinea pigs with low AA intake. High AA intake apparently reduced in Cd-intoxicated guinea pigs the extent of renal damage. Cadmium significantly increased serum creatinine and urea levels in the group of guinea pigs with low AA intake but not in guinea pigs receiving high concentration of AA. The results showed that AA can be effective in the protection of Cd-induced nephrotoxicity.

Animals↗
PubMed2000

Percutaneous toxicity of uranyl nitrate: its effect in terms of exposure area and time.

Different groups have undertaken research work focusing their attention on the biological effects of uranium and have described kidney and bone to be the main target organs in uranium poisoning. In this study we used the skin as the route of entry of uranium. We carried out two sets of experiments in adult rats: in one of them topical applications with uranyl nitrate (UN) over different areas were performed; in the other topical applications with UN on a given area over different times were carried out. In the latter experiment the exposure to UN was stopped by removing it from skin with soap and water. Kidney and bone samples were removed for histological studies. This work is based on the determination of the survival rate of the exposed animals and on the effects elicited in kidney and bone. There is a relation between the area of the surface exposed to uranium and the time of exposure and the subsequent percutaneous toxicity. There were no surviving animals following topical application of UN to an 8 cm2 area nor when the time of exposure was 24 h. The survival rate of the animals increased when either the topical area or the time of exposure to UN was reduced. Although the inhibition of bone formation in metaphysical bone has been previously described by our group as a result of UN poisoning, this is the first time that such an effect is found after percutaneous exposure for such short periods of time. The general toxic effects of UN, evidenced as kidney histological alterations, increased in severity as either one of the two variables studied increased. This is a condition that could be considered as hazardous for those workers engaged in uranium processing and purification. It is noteworthy that a simple method such as washing with soap and water is an effective method to reduce the lethality of UN percutaneous intoxication.

Administration, Topical↗
PubMed2000

An unusual case of organophosphate intoxication of a worker in a plastic bottle recycling plant: an important reminder.

A young man was sent to our emergency unit because he had suffered from vomiting and cold sweating for 2 days. At the time he was admitted, he had no acute abdominal pains or gastrointestinal symptoms, and a physical examination revealed nothing but a faster heart rate and moist, flushing skin. The patient had worked for 6 years at a plastic bottle-recycling factory, but none of his co-workers had the same symptoms. Nevertheless, because the plant also recycled pesticide bottles, we suspected organophosphate pesticide intoxication. The patient's plasma acetylcholinesterase level was checked, revealing 1498.6 microU/L (normal range: 2,000-5, 000) on the first day and 1,379 microU/L on the second day. Upon questioning, the patient recalled that one of his shoe soles had been damaged and that his foot had been wet from walking all day in rain collected on the factory floor on the day that his symptoms first occurred. We conducted a study in the change of preshift and postshift acetylcholinesterase levels among six of his co-workers on a rainy day. We used the Wilcoxon signed rank test to compare the preshift and postshift plasma acetylcholinesterase levels; no significant difference was revealed (p = 0.600), leaving contamination via the damaged shoe sole suspect. We reviewed the literature on organophosphate intoxication; pesticide bottle-recycling factories were reported to be at a low risk of organophosphate toxicity in the working environment. However, because the potential risk of intoxication is still present, protective equipment such as clothing, gloves, and water-proof shoes should be worn, and employees should be educated on the potential risks.

Acetylcholinesterase↗
PubMed1976

[The effect of tri-iodinated contrast media on acetylcholinesterase of human erythrocytes (author's transl)].

The side effects of water soluble iodinated contrast media often mimic the clinical picture of acetylcholine intoxication. This prompted us to determine the amount of inhibition of human acetylcholinesterase by the following contrast media in vivo and in vitro: methyl glucamineiodipamide (Biligrafin forte), methylglucamine iothalamate (Conray 60), sodium-iothalamate (Conray 80). In vivo no correlation could be found between clinically manifest adverse reaction and enzyme inhibition after contrast media application. The in vitro values for 50% inhibition of erythrocyte acetylcholinesterase are: methylglucamine-iodipamide: 0.036 M, methylglucamine-iothalamate: 0.158 M, sodium-iothalamate: 0.3 M. Since in vitro, the maximal inhibitory effect of a given dose of contrast media can only be registered after a time interval when most of the contrast media in vivo has already been excreted by the kidneys or extracted by the liver, it seems very improbable that the enzyme inhibition seen in vitro should have any consequence whatsoever under clinical conditions. The in vitro inhibition of acetylcholinesterase is quickly reversible, with nearly all the activity regained 15 min after the removal of the contrast media.

Acetylcholinesterase↗
PubMed1994

2,5-Hexanedione alters elemental composition and water content of rat peripheral nerve myelinated axons.

Effects of 2,5-hexanedione on elemental concentrations and water content of peripheral nerve myelinated axons were determined using electron probe x-ray microanalysis. Axons (small, medium, and large) were analyzed in unfixed cryosections from rat tibial and proximal sciatic nerve samples. Animals were intoxicated with 2,5-hexanedione by two dosing paradigms: intraperitoneal or oral. Regardless of the route of exposure, internodal axoplasm of small and medium axons from both nerve regions exhibited selective, progressive reductions in dry weight K concentrations and water content. When calculated on a wet weight basis, K levels were comparable to or slightly above control values in tibial nerve, whereas in sciatic nerve, small transient decreases in wet weight K were evident. These changes in K and water correlated with the development of axonal atrophy. The wet and dry weight internodal elemental changes reported here do not suggest a metabolic or axolemmal defect, but rather imply a homeostatic response possibly related to the process of axonal atrophy. Giant axonal swellings were primarily associated with oral 2,5-hexanedione intoxication, and corresponding analyses revealed few changes in element or water content compared with control. The absence of significant alterations in these swellings is consistent with mechanical expansion of the axon probably as a function of accumulating neurofilaments.

Animals↗
PubMed1993

Lead exposure and latent learning ability of adult female rats.

The present report investigates the effects of lead exposure during the pre- and postnatal period on the latent learning ability in a maze. Rats were submitted to lead acetate intoxication by giving their dams 0.5, 1.0, or 4.0 mM lead acetate or deionized water. Rats were weaned at 21 days, and the treatment was continued by giving the same solution of lead acetate in the drinking water until behavioral testing. Under a nonappetitive condition, rats were exposed either to an open field or to a maze apparatus. They were thereafter deprived of food and tested in the maze apparatus. Lead treatment induced an increase in locomotor activity in the open field during training sessions, and animals failed to habituate to the environment. Nevertheless, both lead-treated and control rats that had been previously exposed to the maze performed better than those exposed to the open field. These results suggest that rats intoxicated with lead are able to learn about the environment when no immediate reinforcement is involved.

Animals↗