Chronic pancreatitis in farmed pigs fed excessive zinc oxide.

Most of the pigs on a farm in Aichi Prefecture, Japan had chronic diarrhea and severe wasting. The pigs had consumed 8,000 ppm zinc oxide (ZnO) as a feed additive. The pancreas of each of 4 autopsied pigs was less than half the normal size. Acinar cells were considerably decreased. Epithelial duct-like cells were increased and tested positive for cytokeratin AE1/AE3, Ki67, PGP9.5, and Sox9. Pancreatic islet cells were decreased and shrunken. The α and δ cells were relatively decreased, and their distribution was abnormal. Islet cells were positive for PGP9.5. The livers and kidneys had high accumulations of zinc (Zn; 788 µg/g and 613 µg/g, respectively). Copper was deficient in the liver, likely as a result of Zn poisoning. Our immunohistologic examination suggested that the high dose of ZnO could influence the function of islet cells in addition to that of acinar cells. Given that colistin sulfate has been banned as a feed additive in order to reduce antimicrobial use in Japan, the use of ZnO in the livestock industry is expected to increase. Zn supplementation of pig feed must be monitored to prevent Zn poisoning and contamination of soil and water.

Treatment of zinc toxicosis in a dog with chelation using d-penicillamine.

OBJECTIVE: To describe chelation therapy with d-penicillamine for treatment of zinc toxicosis in a dog. CASE SUMMARY: A 1.5-year-old intact female Maltese dog weighing 2.7 kg was presented with acute, progressive anorexia, lethargy, pigmenturia, and melena. The owner reported that the dog had ingested a hook from a dog leash made of a zinc-based alloy 9 days prior. A blood transfusion was administered and an abdominal radiograph revealed a metal-dense foreign body in the stomach. Laboratory findings revealed a serum zinc concentration of 1845.12 µg/dL (reference interval, 70-200 µg/dL) and a decreased hematocrit that remained low despite removal of the zinc foreign body. On day 3, another blood transfusion was performed and d-penicillamine therapy was instituted. After the administration of d-penicillamine, the clinical signs and hemogram progressively improved and the dog was discharged 2 days later. On day 9 after initial presentation, the hematocrit and platelet values were within normal limits and the serum zinc concentration was 280.16 µg/dL. NEW OR UNIQUE INFORMATION PROVIDED: This case demonstrates the use of d-penicillamine in the treatment of zinc toxicosis. Serum zinc concentration appeared to decline more rapidly after administration of d-penicillamine than before chelation therapy. This is the first report to evaluate serial serum zinc concentrations before and during chelation therapy with d-penicillamine.

Zinc deficiency and toxicity in pediatric practice.

PURPOSE OF REVIEW: Zinc is a commonly overlooked deficiency in developed countries, occurring in infants, children, and adolescents during critical growth periods. The purpose of this review is to present the evidence of zinc deficiencies and toxicities as well as treatment in pediatrics. RECENT FINDINGS: During the last decade, the significance of zinc deficiency in childhood growth, morbidity, and mortality has been recognized by a number of large-scale supplementation trials in underdeveloped countries. Recognition of the recent nationwide shortage of injectable zinc available for total parenteral nutrition supplementation over the last 2 years focused attention on the possibility of zinc deficiency in the United States. SUMMARY: Although primarily thought of as a problem reserved for underdeveloped countries, zinc deficiency has increasing pediatric prevalence in the USA. Zinc is an essential trace element in the body that is responsible for numerous structural, catalytic, and biochemical functions. Deficiencies can occur because of poor dietary intake, long-term parenteral nutrition without supplementation, and enteral causes such as malabsorption. Zinc deficiency is closely associated with stunting, respiratory infections, diarrhea, and dermatitis. Deficiency is hard to define solely by the serum levels. Clinicians should utilize a combination of serum zinc levels, presenting signs and symptoms, and nutritional intake via oral, enteral, and parenteral routes to accurately assess the deficiency risk and diagnosis.

Zinc-Excess Intake Causes the Deterioration of Renal Function Accompanied by an Elevation in Systemic Blood Pressure Primarily Through Superoxide Radical-Induced Oxidative Stress.

Using rats fed 22 g/d of a control diet containing 0.005% zinc (Zn) or 2 Zn-excess diets containing 0.05% or 0.2% Zn for 4 weeks, we examined the mechanisms involved in the deterioration of renal function induced by Zn-excess intake. An increase in Zn intake elevated mean blood pressure (BP) and reduced renal blood flow (RBF) and inulin clearance in a dose-dependent manner. This decline in inulin clearance may be derived from a fall in RBF. Administration of the nitric oxide (NO) synthase inhibitor, Nω-nitro-l-arginine methyl ester, markedly increased mean BP and significantly decreased RBF in the 3 groups of rats. Administration of the exogenous superoxide radical (OO-) scavenger, tempol, significantly decreased mean BP and substantially increased RBF in all groups of rats. These observations suggest that both an elevation in systemic BP and a reduction in RBF seen in the 2 Zn-excess diet groups result from a decrease in the action of the vasodilator, NO, through the formation of peroxynitrite based on the nonenzymatic reaction of NO and increased OO- Indeed, the activity of the endogenous OO- scavenger, copper/Zn-superoxide dismutase, was significantly reduced in the vessel wall of rats fed 2 Zn-excess diets versus a control diet. 8-Hydroxy-2'-deoxyguanosine formation caused by OO- generation was notably elevated in the kidneys of rats fed 2 Zn-excess diets relatively to rats fed a control diet. Thus, Zn-excess intake leads to the aggravation of renal function concomitantly with an increase in systemic BP predominantly through the oxidative stress caused by OO^.

Zinc poisoning from excessive denture fixative use masquerading as myelopolyneuropathy and hypocupraemia.

A 50-year-old man presented with a four-year history of unsteadiness, with recent falls and tingling in his fingers. Neurological examination found an ataxic gait, with a positive Romberg's sign. There was distal wasting and weakness in all four limbs and impaired co-ordination, with pseudoathetosis in the arms. Initial investigations showed a normochromic, normocytic anaemia, leucopenia, neutropenia and a low vitamin B(12) (172 ng/L). Treatment with intramuscular cobalamin injections showed no clinical improvement. Further investigations showed an undetectable caeruloplasmin (<0.085 g/L), a very low serum copper (1.1 µmol/L) and a markedly raised serum zinc concentration (36.2 µmol/L). On detailed questioning it became apparent that he had ill-fitting dentures requiring excessive use of denture fixative with high zinc content. The patient was switched to a non-zinc containing denture fixative and commenced copper supplementation. Although within three months the bone marrow suppression had resolved, there was no clinical improvement in neurological presentation. Questioning a patient about their denture fixative usage and checking if zinc is an ingredient may be considered during an investigation for myelopolyneuropathy when vitamin B(12) deficiency is not a cause.

Zinc transmetallation and gadolinium retention after MR imaging: case report.

A patient with chronic zinc poisoning from denture cream retained gadolinium after a magnetic resonance imaging procedure, likely due to transmetallation. During chelation therapy, high levels of gadolinium in excreted urine (up to 89 µg/d, 29 days after gadolinium administration) were present, indicating that gadolinium had been retained. Almost 2½ years after gadolinium exposure, a 24-hour urine collection indicated that the gadolinium level remained in the elevated range (0.6 µg/d). This single case report suggests that patients with elevated zinc exposure may be at increased risk of gadolinium retention.

Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease.

BACKGROUND: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically. OBJECTIVE: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion. METHODS: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals. RESULTS: Zinc concentrations ranging from about 17,000 to 34,000 mug/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified. CONCLUSION: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.

Hyperzincaemia in a pet African giant rat (Cricetomys gambianus Waterhouse, 1840).

Presented is an African giant rat (Cricetomys gambianus) following zinc ingestion. The sick rat was lethargic, withdrawn, had soft, mucus-impregnated faeces and diahorrea, foot twitching and icterus. Comparative age, sex and body weight (b.wt.)-matched analyses were made with a healthy giant rat. Twelve-hourly Urine volume (UV), Haematocrit (Hct), urinary glucose, plasma zinc and Alkaline Phosphatase (ALP) were performed over an 8-week period. Full blood counts were performed and differential WBC counts and microscopic observations were made on blood smears obtained from both healthy and sick rats. Consecutive blood samples were drawn at the end of each week (Weeks <2-6 treatment; Weeks 7-8 post-treatment). Treatment involved oral vitamin B12 supplement at 4 microg/day and 2 ml diethylenetriaminepentaacetic acid (DTPA) intramuscular injections at 1 ml/450g b.wt./5 wks (Week 2 - 6). Day 1 showed neutropaenia, Heinz bodies on RBCs (reticulocytes and immature forms). Zinc (Day 1 - end Week 7), glucose (Day 1 - end Week 4), ALP (Day 1 -Week 4) and UV were elevated (Day 1 - end Week 6). Indications of moderate zinc toxicosis following ingestion and stress-associated glucosuria were concluded.

Zinc and infection: a review.

Dietary zinc deficiency is widespread in developing countries and is often aggravated by intercurrent acute and chronic infections. Recent studies have demonstrated that zinc supplementation can significantly reduce the morbidity and mortality of apparently well-nourished children and shorten the time to recovery from acute infectious diseases. This review summarises current knowledge of the role of zinc in childhood diarrhoea, acute respiratory infections and malaria, and its potential role in diseases associated with impaired cellular immunity, namely tuberculosis, lepromatous leprosy and leishmaniasis, and explores avenues for future research.

Diagnosis and treatment of zinc poisoning in a dog.

Acute zinc poisoning has been observed in dogs following the ingestion of metallic zinc objects. A 1 1/2-y-old female miniature bull terrier exhibiting anorexia, vomiting, depression, fever (39.9 C), icterus and intravascular hemolysis was diagnosed with acute zinc poisoning. Anemia, Heinz body production, azotemia and bilirubinemia were also evident. Abnormal pancreatic, hepatic and renal functions were also apparent. A radio opaque object was observed in the stomach. Based upon an elevated plasma zinc level of 28.6 ppm, a tentative diagnosis of zinc poisoning was made. Following surgical removal of the metallic zinc object, a blood transfusion and fluid therapy were given to restore the normal blood volume. Heparin, Cephazolin and Raniditine were also given, although chelation therapy was not provided. Zinc levels in the plasma declined in a steady fashion (half-life = 7.6 d). Complications, such as disseminated intravascular coagulation, chronic pancreatitis, renal or hepatic failure, were not observed. By 20 d post surgery, only mild elevation of liver enzymes was evident. Measurements of the half-life of zinc may provide a useful indication of prognosis and the success of treatment.

Transmission electron microscopy study of the effects of zinc overdose on mouse liver tissue.

Thirty adult male mice were divided into three groups. The animals in group I were used as controls and drank only water during the entire period of experimentation. Group II animals drank water containing 1.5 g/100 mL zinc as ZnSO4, and group III animals received 2.5 g/100 mL zinc. After 3 wk supplementation with high doses of zinc, the animals were killed and the livers were removed and examined by electron microscopic techniques. After the supplementation period, the animals in groups II and II showed various degrees of degenerative changes in the hepatocytes, such as increased size and the presence of spaces and an abundance of lipid globules in the cytoplasm. The mitochondria showed a crystalline appearance, a diluted matrix, and dense aggregations. Some smooth endoplasmic reticulum tubules showed dilation and were filled with a dense substance. None of these changes were present in the group I control animals.

The concentration levels of Cd, Pb, Hg, Cu, Zn and Se in blood of the population in the Czech Republic.

Knowledge of normal levels of concentrations of trace elements (Cd, Pb, Hg, Cu, Zn, and Se) in the population serves, among others, in design of regulations concerning health protection, determination of exposure limits and prevention of diseases caused by deficiency of trace elements. Concentrations of the named elements in whole blood of the Czech population were determined by means of atomic absorption spectrometry. The blood was collected during 1996-1998 from 1,216 blood donors (896 males and 320 females, average age 33 years) and 758 children (397 boys and 361 girls, average age 9.9 years). Mineralisation in a microwave digestion system was used in sample preparation. The accuracy of results was checked by means of the Control material Seronorm Whole Blood 404107 and Seronorm Serum 704121, Nycomed. Values of concentrations of the trace elements in blood found for adult (medians) were 0.7 microgram Cd.l-1, 800 micrograms Cu.l-1, 0.78 microgram Hg.l-1, 41 micrograms Pb.l-1, 76 micrograms Se.l-1, and 5,800 micrograms Zn.l-1, respectively. Statistically significant differences between men and women have been found in the concentrations of Cu, Hg, Pb, and Zn. In the juvenile population following medians of concentrations have been found: 0.15 microgram Cd.l-1, 1,047 micrograms Cu.l-1, 0.46 microgram Hg.l-1, 34 micrograms Pb.l-1, 69 micrograms Se.l-1, and 8,180 micrograms Zn.l-1. Statistically significant differences between boys and girls were found only in Pb and Zn concentrations. Concentrations of the studied elements correspond to the published values concerning population not exposed professionally.

Retrospective study of toxic metal analyses requested at a veterinary diagnostic toxicology laboratory in Ontario (1990-1995).

During the 5-year period from January 1, 1990, to December 31, 1995, 887 diagnoses of metal toxicosis in domestic animals and wild birds were documented at the Veterinary Laboratory Services Branch of the Ontario Ministry of Agriculture, Food and Rural Affairs. Most of these cases involved cattle, sheep, and birds. Lead toxicosis was diagnosed in 399 cases, copper toxicosis in 387, zinc toxicosis in 49, mercury toxicosis in 44, iron toxicosis in 4, and selenium in 4 cases. Trends in species affected and sources of metals are discussed.

Accidental ingestion of a zinc and copper sulfate preparation.

CASE REPORT: An 86-year-old woman accidentally ingested a preparation containing zinc and copper sulfate. At ninety minutes after ingestion, the peak plasma concentration was 1979 micrograms/dL for zinc and 209 micrograms/dL for copper, suggesting preferential absorption of zinc. The major complications were gastric and bronchial inflammation due to the corrosive properties of these compounds. Systemic manifestations also developed with cardiovascular failure and renal insufficiency, but the patient made a complete recovery. In addition to symptomatic treatment, chelation therapy with dimercaprol and D-penicillamine was given for 48 h. CONCLUSION: The available clinical and toxicokinetic data do not support the benefits of chelation in addition to supportive therapy.

Pure white cell aplasia and health food products.

The safety of 'health' foods and complementary medicine products is increasingly questioned. We report a case of pure white cell aplasia developing in a patient who took a variety of such products leading to an excessive intake of zinc. Recovery was complete following the withdrawal of her 'medications'. The aetiology of the pure white cell aplasia is discussed with respect to the ingredients of the products ingested.

[Zinc phytotoxicity and induction of stress proteins in bean (Phaseolus vulgaris L.)]. / Phytotoxicité du zinc et induction de protéine(s) de stress chez le haricot (Phaseolus vulgaris L.).

Bean seedlings (Phaseolus vulgaris L., cv. fin de Bagnol) were grown for ten days in nutrient solutions at 0, 50, 100, 500 and 1000 microM ZnS0(4). The results obtained show that Zn treatment is followed by a pathological behaviour, the precocity and intensity of which are dependent on the applied dose. In addition to the depressive effects on the biomass yield and the tissue water content, a decrease in the proteins contents was also observed. Zinc toxicity seems to induce synthesis of low molecular weight proteins in Zn-treated bean stems, but not in the roots and leaves. These peptides, in stems, may protect, hypothetically, the susceptibles metabolic sites in foliar parenchyma against the zinc deleterious effects.

Copper deficiency and microcytic anemia resulting from prolonged ingestion of over-the-counter zinc.

Isolated copper deficiency occurred in a 57-yr-old man who had ingested massive quantities of zinc for more than 18 months. The patient presented with microcytic anemia and had normal gastrointestinal function with no evidence of occult blood loss. Dietary zinc in large doses leads to copper deficiency by antagonizing copper absorption. With discontinuance of zinc, the anemia and hypocupremia promptly corrected. The relationship between zinc, copper deficiency, and iron metabolism is reviewed.

Intoxicación por raticida y status epilepticus / Intoxication with raticide and status epilepticus

La intoxicación por raticidas (Fosfuro de Zinc) es potencialmente letal y cuando existen manifestaciones clínicas del sistema nervioso central, la mortalidad alcanza hasta el 70%de los casos. Se presenta el caso de un preescolar con intoxicación por fosfuro de zinc. La ingestión de este tóxico causó estado epiléptico, cuya evolución fué satisfactoria, con recuperación neurológica completa.