Results of the treatment of Wilson's disease with zinc sulfate and d-penicillamine]

Nine patients with newly diagnosed Wilson's disease were treated with zinc sulphate for 12 months. Polish preparation Zincteral was administered in doses of 200 mg 4 times daily. The neurological status has improved in five cases. No adverse reactions of zinc sulphate were observed. The results were compared with the therapeutic effect, obtained in the group of 10 patients who received d-penicillamine (Cuprenil-Polfa) 1.0-1.5 g daily from the very beginning. In three cases drug was discontinued due to adverse reactions. In remaining seven cases, in five evidence of the clinical improvement of the neurological status was observed, but in one case during 12 months of observation progressing deterioration was noticed. Neurological state of one patient remained unchanged.     

Causes of mortality in the Mute swan Cygnus olor on the River Thames

Over the last 20 years there has been an unprecedented decline of the Mute swan on the River Thames. Between August 1979 and October 1981 a systematic attempt was made to collect as many swan corpses as possible. Of 94 swan corpses examined at post-mortem 57% died from lead poisoning due to ingestion of anglers' weights. Birds dying from lead poisoning had significantly higher liver and kidney lead levels. Kidney proved to be the most useful indicator tissue, the median lead level in birds with lead weights in their gizzard was 908 μg/g DM compared to 8 μg/g DM in birds without weights. More immature birds die from lead poisoning than other factors and significantly more corpses were found between the months of July-October.
Ultra-structure examinations revealed electron dense intra-nuclear inclusions in the cells of proximal convulated tubules of the kidney and X-ray analysis confirmed that these structures consisted of lead.     

Uranyl nitrate induced corpuscular derangement: an early indication of induced acute renal failure.

Erythrocyte structure was studied in rat after uranyl nitrate (UN:5 mg/kg) intoxication. The study of pathogenic progression of UN induced renal failure (ARF) was confined to the early initiation phase (2 hr), late initiation phase (8 hr) and the maintenance phase (24 hr). Erythrocyte structure has been found to be greatly influenced. The UN induced hemolytic syndrome/hypoxia was accompanied by a marked anisocytosis and poikilocytosis during different phases of ARF, which is characteristic of UN poisoning. Subsequent alterations in erythrocyte structure followed by UN administration or during the pathogenic progression of ARF has clinical and diagnostic importance as the alterations were much distinct prior to the clinical manifestation of ARF even at light microscopic level.     

Thallium poisoning. Diagnosis may be elusive but alopecia is the clue.

Thallium is a heavy metal whose salts are used in some rodent poisons and in the manufacture of optical lenses, semiconductors, scintillation counters, low temperature thermometers, and switching devices, green coloured fireworks, and imitation jewelery, and as chemical catalysts. In clinical practice thallium isotopes are used in cardiac scanning, but the use of thallium salts to treat scalp ringworm was abandoned earlier this century because of their toxicity. The sale of thallium in Britain is strictly licensed because of its toxicity and potential for use in murder, which is helped by the fact that thallous salts are colourless, tasteless, and odorless. The more water soluble salts (such as thallium sulphate, acetate, or carbonate) have higher toxicity, and although the toxic dose is variable most deaths occur after the ingestion of 10-15 mg/kg of soluble salt. Most cases of thallium toxicity occur after oral ingestion but severe toxicity has been reported after inhalation of contaminated dust from pyrite burners, in zinc and lead smelting, and in the manufacture of cadmium, after dermal absorption through protective rubber gloves, and after snorting what was thought to be cocaine. The elimination half time of thallium is between 1.7 and 30 days depending on the time since, and chronicity of, ingestion. The elimination time phases are apparent and because of the long terminal elimination half time thallium may act as a cumulative poison. We present two cases of thallium poisoning with intent to kill.     

Lead poisoning in wild populations of Marsh Harriers Circus aeruginosus in the Camargue and Charente-Maritime, France

Lead poisoning of waterfowl, through the ingestion of spent gunshot, has been recognized as a mortality factor for over a century. However, in Europe relatively little attention has been paid to raptors that may ingest shot embedded in the flesh of prey. The present study examines the incidence of lead poisoning in wild Marsh Harriers Circus aeruginosus trapped at two sites in France, the Camargue and Charente-Maritime.
Eight captive Marsh Harriers (controls) had blood lead (PbB) concentrations of 5.3–10.8 μg per dl. Of 94 wild birds trapped during the winters of 1990/1991 and 1991/1992 either in baited clap traps or in mist nets at night roosts, 29 (31%) had elevated (>30 μg/dl) PbB concentrations and 13 (14%) had concentrations indicative of clinical poisoning (> 60 μg/dl). Similar percentages of birds caught using the two trapping methods had elevated (>30 μg/dl) PbB concentrations. However, clap netting appeared to select for more heavily contaminated birds and for juvenile birds, although the two are not necessarily correlated. In the Camargue, significantly more females than males trapped in clap nets had elevated PbB concentrations.
The incidence of shot in regurgitated Marsh Harrier pellets increased significantly between October and December, indicating increased exposure to lead as the hunting season progressed. There appeared to be a parallel increase in PbB concentrations throughout the hunting season, although this could not be clearly demonstrated as sex ratios were different during different sampling periods.
Elevated PbB concentrations of harriers in the Camargue are likely to result primarily from the ingestion of shot in the flesh of crippled or unretrieved waterfowl and in Charente-Maritime, from eating crippled or dead mammals.
Other raptors at risk from lead poisoning and solutions to this problem are discussed.     

Acute human toxicity and mortality after selenium ingestion: A review

BackgroundAlthough selenium is an essential element for humans, acute toxicity has been reported after high oral exposure.MethodsThe published literature on the acute toxicity of oral selenium was gathered and reviewed.ResultsReported symptoms and signs include abdominal symptoms, such as vomiting, diarrhea, pain, and nausea, as well as garlic-like odor on the breath. In cases of severe toxicity, cardiac and pulmonary symptoms may develop and ultimately lead to mortality. Mortality has been described after the ingestion of gun bluing solutions, which often contain selenous acid among other potentially toxic substances. Mortality has also been reported after the ingestion of other forms of selenium. Ingested doses associated with mortality are in the range of 1–100 mg Se/kg body weight. Blood levels associated with mortality are above 300 μg Se/L (normal level: 100 μg/L), whereas urinary levels associated with the same endpoint are above170 μg Se/L (normal level: 20–90 μg/L).ConclusionThe acute toxicity associated with oral selenium ingestion and the blood and urinary levels of selenium in different cases of poisonings were reviewed. Mortality is a risk of acute selenium poisoning. Concentrations of selenium in blood and urine samples in non-fatal cases are close to those observed in fatal cases.     

Metabolism of zinc and copper in the neonate: Zinc thionein in developing rat brain,heart, lung,spleen, and thymus

In a continuing study of the importance of metallothionein (MT) in the growth and development of neonates, zinc and copper metabolism in rat brain, heart, lung, spleen, and thymus has been analyzed in 5, 10, 15, 20 and 25 day old rats. Total, cytosol, and MT zinc and copper concentrations and organ contents were determined. Zinc, but very little, if any copper was associated with MT in these organs. Concentrations ranged from 0.03 to 3.3 μg Zn in MT/g; organ contents ranged from 0.003 to 2.2 μg Zn in MT/organ. Brain exhibited the highest concentrations and contents of zinc in MT, approaching the levels found in kidneys. Rank order of organ contents of zinc in MT was brain > lung > heart, spleen, thymus, during this neonatal growth period. When organ growth was rapid, a large percentage (20–95%) of the cytosolic zinc present in these organs was associated with MT, as has been previously observed with liver, kidneys, and testes. None of these organs undergoes the dramatic changes in zinc and copper metabolism previously observed in neonatal rat liver and gastrointestinal tract, and in maturing testes. They are more comparable to kidneys in their concentrations of zinc in MT. Like testes, little copper is found in these organs.     

Activation of peritoneal macrophages by lysophosphatidylcholine

Lysophosphatidylcholine (lyso-PC), a product of inflammation induced by infectious and other agents, is able to stimulate mouse peritoneal macrophages to ingest target cells coated with IgG but not IgM regardless of the presence of complement. In vitro treatment of mouse resident peritoneal macrophages (adherent cells) alone with lyso-PC stimulated spreading activity but did not enhance ingestion activity of macrophages. However, when mixed cultures of adherent and nonadherent (lymphocytes) cells were treated with lyso-PC, macrophage ingestion activity of IgG-coated target cells (i.e., via Fc-mediated ingestion) was markedly enhanced. Analysis of lyso-PC activation process of macrophages for ingestion activity suggests that nonadherent (lymphocytes) cells are required for the induction of the manifestation of ingestion capacity. This requirement was also met by addition of untreated nonadherent cells to treated adherent cells. Thus, the activation mechanism of macrophages by lyso-PC for ingestion requires contribution of lymphocytes to promote enhanced ingestion activity. Since lyso-PC is a metabolite of a representative membrane phospholipid, we propose that lyso-PC and other lysophospholipids are mediators for activation of macrophages regardless of the type of inflammation-causative agent.     

Adverse health effects in Canada geese (Branta canadensis) associated with waste from zinc and lead mines in the Tri-State Mining District (Kansas, Oklahoma, and Missouri, USA)

Lead and zinc poisoning have been recorded in a variety of bird species, including migrating waterfowl such as Canada Geese (Branta canadensis), at sites contaminated with mine waste from lead and zinc mines in the Tri-State Mining District, Kansas, Oklahoma, and Missouri, USA. The adverse health impacts from mine waste on these birds may, however, be more extensive than is apparent from incidental reports of clinical disease. To characterize health impacts from mine waste on Canada Geese that do not have observable signs of poisoning, four to eight apparently healthy birds per site were collected from four contaminated sites and an uncontaminated reference site, and examined for physical and physiologic evidence of metals poisoning. Tissue concentrations of silver, aluminum, arsenic, barium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, lead, selenium, thallium, vanadium, and zinc were determined by inductively coupled plasma mass spectroscopy. Adverse health effects due to lead were characterized by assessing blood δ-aminolevulinic acid dehydratase (ALAD) enzyme activity. Adverse effects associated with zinc poisoning were determined from histologic examination of pancreas tissues. Elevated tissue lead concentrations and inhibited blood ALAD enzyme activities were consistently found in birds at all contaminated sites. Histopathologic signs of zinc poisoning, including fibrosis and vacuolization, were associated with elevated pancreatic zinc concentrations at one of the study sites. Adverse health effects associated with other analyzed elements, or tissue concentrations indicating potentially toxic exposure levels to these elements, were not observed.     

High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium.

High-dose antioxidant supplementation has recently been recommended for multiple sclerosis (MS) patients. This study tests the clinical safety, the glutathione peroxidase (GSH-px) activity, and the absorption of selenium during such supplementation. Eighteen MS patients were given 6 tablets especially made for this study, equivalent to 6 mg sodium selenite, 2 g vitamin C, and 480 mg vitamin E a day for five wk. GSH-px, which was lower than in non-MS controls before the start of treatment, increased fivefold during 5 wk of treatment. Side effects were scarce. Ten MS patients were subjected to a 24-h selenium absorption study after ingestion of 2 active tablets, equivalent to 2 mg sodium selenite. Selenium, which was low initially, increased 24% during the first 3 h and then stabilized. It is concluded that the tested antioxidant treatment seems to be safe and that MS patients have low GSH-px, which may be increased by the tested antioxidant treatment.     

High dose antioxidant supplementation to MS patients

High-dose antioxidant supplementation has recently been recommended for multiple sclerosis (MS) patients. This study tests the clinical safety, the glutathione peroxidase (GSH-px) activity, and the absorption of selenium during such supplementation. Eighteen MS patients were given 6 tablets especially made for this study, equivalent to 6 mg sodium selenite, 2 g vitamin C, and 480 mg vitamin E a day for five wk. GSH-px, which was lower than in non-MS controls before the start of treatment, increased fivefold during 5 wk of treatment. Side effects were scarce. Ten MS patients were subjected to a 24-h selenium absorption study after ingestion of 2 active tablets, equivalent to 2 mg sodium selenite. Selenium, which was low initially, increased 24% during the first 3 h and then stabilized. It is concluded that the tested antioxidant treatment seems to be safe and that MS patients have low GSH-px, which may be increased by the tested antioxidant treatment.     

Circumstances of Accidental Poisoning in Childhood

Of 377 children with accidental poisoning, the commonest ages were 1, 2, and 3. The most important contributory factor was that the poison was kept in an inappropriate place. Most containers were closed, but the children found them easy to open. In some cases the container itself was unsuitable for the contents.The frequency of poisoning in childhood might be reduced in six main ways: (1) a reduction in the quantity of drugs kept in the home; (2) the provision of drug cupboards; (3) the provision of containers that are difficult for children to open, or individually foil-wrapping tablets; (4) making tablets less attractive to children; (5) clear identification of potential poisons; and (6) increasing parental awareness of the circumstances under which poisoning occurs.A plea is made for further sociomedical research into the prevention of poisoning.     

Comparative study of cases of poisoning by organophosphorous insecticides in various regions of Costa Rica

336 cases of organophosphorous poisoning from case records of hospitals in Costa Rica between 1972 and 1978 were classified in four categories according to signs and symptoms: 8% latent; 25.9% mild; 43.8% moderate and 22.3% severe. Eighteen of the total patients died during hospitalization. Suicidal ingestion was the principal cause of severe and latent poisoning, especially in urban areas, followed by occupational poisoning in agricultural workers in mild and moderate cases. Occupational poisoning was common in men; in women it was attempted suicide and in children accidental poisoning. Under 40 years of age, the main cause was suicidal ingestion among both men and women, and occupational poisoning after 40 years of age. After discharge from the hospital, 19.6% of the total poisoned patients were referred to psychiatric treatment; 22.7% and 18.2% had had mental and alcoholic problems, respectively, prior to poisoning. Attempted suicide was the principal cause of poisoning in 86.4% of these patients, indicating emotional instability. In this study, the incidence in psychiatric consultation after discharge from the hospital is not indicative of a relationship between mental disorders and acute insecticide poisoning. In 42.6% and in 22% of the deceased patients pralidoxime (PAM) and atropine respectively, were not administered as antidotes in the emergency room. Aminophylline and skeletal muscle relaxants among other contraindicated drugs were administered as part of the treatment in these deceased patients. The consequences of this misguided treatment are questioned.     

Mercury poisoning in a wild mink

Mercury poisoning was diagnosed in a clinically-ill wild mink (Mustela vison) on the basis of clinical signs, histopathologic lesions and tissue mercury concentrations. The probable source of mercury was through ingestion of fish from the nearby South Saskatchewan River which is known to be contaminated with mercury. This is believed to be the first documented case of mercury intoxication of a wild animal in North America.     

Experiences of the Czech toxicological information centre with ethylene glycol poisoning

The objective was to evaluate the severity of ethylene glycol (EG) intoxications in a 3-year retrospective study of the calls to the Toxicological Information Centre (TIC). Data about clinical course of patients with EG poisoning reported to the TIC in the years 2000-2002 were analysed. They were completed by the data from discharge records from the hospitals and by toxicological analyses. The chi-square test, Student's t-test, Fisher's test and the calculation of linear correlation coefficient were used for statistical analysis. The significance level was set at 0.05. TIC received total 188 calls concerning EG, from which 33 discharge reports were gained. There were 30 males (age 5-74 years) and 3 females (age 10-54 years). The patients ingested 252 ml on average (30-1000 ml); lethal dose (100 ml) was exceeded in 14 patients. Mean time interval from ingestion to admission was 3 hours (3-24 hours), mean length of hospitalisation 6 days (1-76 days). Fourteen patients developed metabolic acidosis, nine unconsciousness, thirteen signs of nephrotoxicity and nine signs of hepatotoxicity. Three patients died. Antidote ethanol was given in 30 patients. Other treatment included haemodialysis (20 cases) and B vitamins (23 cases). Ingested dose and the time interval between ingestion and admission correlated with severity of kidney damage. These data confirm that EG poisoning could seriously threaten the life. Renal parameters were abnormal in 30 % of patients who were discharged from the hospital. Those patients will be followed to evaluate the reversibility of EG toxic kidney damage.     

Von Hippel-Lindau disease (VHL): a need for a murine model with retinal hemangioblastoma

Von Hippel-Lindau (VHL) disease is a highly penetrant autosomal dominant systemic malignancy that gives rise to cystic and highly vascularized tumors in a constellation of organs. Patients with VHL disease commonly present with hemangioblastomas in the central nervous system and the eye while other manifestations include pheochromocytoma, clear cell renal cell carcinoma, endolymphatic sac tumors of the middle ear, pancreatic cystadenomas, epididymal and broad ligament cystadenomas. Animal models inactivating the VHL gene product in various organ tissues have been constructed over the past 15 years to parse its HIF-associated mechanisms and its link to tumorigenesis. These models, despite advancing our understanding the molecular role of VHL, are by and large unable to recapitulate the more common features of human VHL disease. Up to date, no model exists that develop retinal hemangioblastomas, the most common clinical manifestation. The purpose of this review is: (1) to discuss the need for an ocular VHL model, (2) to review the animal models that recapitulate clinical VHL disease and (3) to propose potential mechanisms of tumorigenesis for the development of ocular VHL.     

Morphofunctional analysis of zinc-accumulating capacity of digestive system organs]

The distribution of zinc and related changes have been studied in zinc--loaded chick pancreas, ileum and liver at the ultrastructural level by sulphide--silver method. White Leghorn chicks fed a high zinc diets (50, 500, 1000, 2000 and 4000 mgZn/kg diet) for 6 weeks, were killed at intervals; portions of their organs were fixed for light and electron microscopy; other samples were analyzed for zinc by AA spectrophotometry. A drastic increase of zinc level in chick pancreas fed 2000 mg Zn/kg diet (as ZnCl2) was associated with acinar cell degeneration. Apoptosis was the predominant form of acinar cell deletion. This study provides support for a previously proposed theory that cell injury stimulates passive zinc accumulation.     

The multidisciplinary approach to safety and toxicity assessment of microalgae-based food supplements following clinical cases of poisoning

Commercially available food supplements based on microalgae such as Spirulina (Cyanobacteria) or Chlorella (Chlorophyta) are becoming increasingly popular. Both are considered as non-toxic per se but the quality and safety of the final product depends on culturing and manufacturing conditions. This study presents two cases of human poisoning following the simultaneous use of Spirulina and Chlorella food products and a multidisciplinary approach to their evaluation: cytotoxic tests using human whole-blood in vitro and a suite of analytical screenings of over 30 elements, arsenic species and cyanotoxins: cylindrospermopsin (CYN), anatoxin-a (ANA) and three microcystin (MC) analogues. To compare metal content the Food Supplement Metal Index and Toxic Elements Contamination Index were also introduced. In all performed analyses two other commercial products were also investigated. Reported clinical symptoms of poisoning included the spreading of atopic dermatitis, nausea, dizziness, headache and fatigue. Extracts of supplements obtained from affected subjects were found to act pro-necrotically in human neutrophils, while tablets contained higher levels of several metals including Cd, Pb and Hg. All analyzed food supplements contained a significant content of Al. Neither CYN, ANA nor MC were present in any examined product. The quality of both Spirulina-based and Chlorella-based food supplements was very doubtful. The contamination problem of some commercially available microalgae-based supplements appears to be pleiotropic. The present study clearly indicates that such products should be subject to strict and routine monitoring before being registered and distributed as some of them may pose a distinct threat to human health.     

Ultrasonic changes in organs in the course of poisoning with mushrooms

A case of the poisoning with mushrooms of severe clinical course is presented. Lesions to parenchymatous organs were diagnosed with ultrasound. The authors stress the value of ultrasound examination in the evaluation of the lesions to internal organs in the course of poisoning and in prognosis.