Citrinin mycotoxicosis in the rabbit.

In three trials, single or multiple doses of citrinin dissolved in 0.5 N-NaOH and adjusted to neutral pH with HCl were given to rabbits by either the oral or intraperitoneal route. The 72-hr LD50 was 50 mg/kg body weight by intraperitoneal administration and 134 mg/kg by the oral route. The primary clinical sign in rabbits receiving a single oral dose of 125-150 mg citrinin/kg was fluid diarrhoea commencing 8 hr after dosing. Pathological alterations were generally confined to the kidney and consisted of degeneration and necrosis of proximal convoluted tubules and straight segments. In rabbits given a single oral dose of citrinin (130 mg/kg) the earliest histopathological change, seen 8 hr after dosing, was cytoplasmic vacuolation of tubular epithelial cells. Rabbits given a single oral dose of 120 mg citrinin/kg had regeneration of renal tubular epithelium accompanied by slight tubular cell necrosis when examined 7 days after dosing. Rabbits given multiple sublethal doses of citrinin (33.5 or 77 mg/kg daily for 7 days) had renal alterations of mild tubular degeneration and necrosis, and tubular regeneration.

Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin.

INTRODUCTION: Nebivolol, a beta blocker with 3-10 times more beta1 cardioselectivity than metoprolol, has caused hypotension and bradycardia in overdose. We report a nebivolol-induced cardiac arrest in the setting of a polydrug ingestion, successfully resuscitated with intravenous fat emulsion (IFE) and high-dose insulin (HDI). CASE REPORT: A 48-year-old man was brought to the emergency department after ingesting nebivolol and ethanol, along with possibly diazepam and cocaine. He had a heart rate of 71/min and a blood pressure of 98/61 mmHg. The initial ECG showed sinus rhythm with a QTc of 483 ms and a QRS of 112 ms. Over the subsequent 4 h, he became bradycardic and hypotensive and developed bradyasystolic cardiac arrest. Standard resuscitation including epinephrine had no effect. Spontaneous circulation returned 30 s after a 100 mL bolus of 20% IFE, and the patient then became briefly hypertensive and tachycardic with heart rate and blood pressure measured as high as 123/min and 251/162 mmHg, respectively. His care included IFE infusion along with HDI bolus and infusion with doses as high as 21.8 units/kg/h. With subsequent hypotension, vasopressors were withheld in favor of HDI and supportive care. He was discharged with baseline neurologic function. DISCUSSION: We hypothesize that after the administration of IFE the epinephrine was able to exert its effect on receptors previously occupied with the nebivolol. This would be congruent with the lipid sink theory of IFE mechanism. CONCLUSION: We report an overdose involving nebivolol in a polydrug ingestion resulting in cardiac arrest, successfully treated with IFE and a very HDI infusion.

Clinical features, laboratory findings and imaging appearances of venous diethylene glycol poisoning in patients with liver disease.

BACKGROUND: There was a hospital outbreak of venous diethylene glycol poisoning in Guangzhou, China. It is the only massive episode of venous diethylene glycol poisoning in history. Here we report its clinical features, laboratory findings, and imaging appearances. METHODS: The clinical features of 15 venous diethylene glycol poisoning patients with liver disease were analyzed and summarized. Their laboratory findings and imaging appearances were comparatively analyzed before and after poisoning. RESULTS: All poisoned patients presented with oliguric acute renal failure with anuria after a mean of 6 days. Carbon dioxide combination power of 13 patients dropped after a mean of 9 days with valley value on the 10th day, when metabolic acidosis developed. Gastroenteric symptoms or aggravation of gastroenteric symptoms were displayed in 11 patients after a mean of 9 days. Neurological system impairment was observed in 10 patients after a mean of 14 days. Seven patients had low fever after a mean of 6 days. Causes of death of 14 patients included multiple organ dysfunction syndrome, severe lung infection and massive haemorrhage of digestive tract. Blood creatinine and urea nitrogen were abnormal after a mean of 5 days with peak value on the 11th and 14th days, respectively. Serum calcium had no obvious change, and phosphorus was distinctively increased. Liver functions did not change significantly. Poisoned patients had higher white blood cell counts, but lower red blood cell counts and hemoglobin value. Of the 7 patients who exhibited mild, moderate or severe patchy consolidation shadowing in the lung, 2 manifested mild or severe gaseous distention and dilation of gastroenteric tract. CONCLUSIONS: Main features of venous diethylene glycol poisoning in patients with liver disease include oliguric acute renal failure, metabolic acidosis, gastroenteric symptoms or aggravation of gastroenteric symptoms, neurological system impairment and low fever, with a mortality rate of 93.33% in poisoned patients. There is also higher white blood cell counts and anemia, patchy consolidation shadowing in the lung, gaseous distention and dilation of gastroenteric tract, which occurs later than mild patchy consolidation shadowing and earlier than moderate patchy consolidation shadowing in the lung.

Acute immunoallergic hemolysis with acute renal failure induced by catechin.

A young woman, 25 years old, being treated for her veinous system with EucatexR (a drug including catechins) presented an acute intravascular hemolysis with an acute renal failure. The finding of anti-Eucatex and anti-catechins antibodies in the serum and on the red cells of the patient proved the immuno-allergic nature of this hemolysis. A renal biopsy showed lesions of acute tubular nephritis but no immune depots. The patient recovered after a treatment by hemodialysis.

Citrinin mycotoxicosis in the rabbit: ultrastructural alterations.

Citrinin was given to rabbits as a single oral dose of 120 or 67 mg/kg. Rabbits were killed at 4, 6, 8, 10, and 12 hours post dosing, and the kidneys were fixed by intravascular perfusion. Ultrastructural alterations were evident by 4 hours after treatment. In the proximal tubule, alterations were brush border disruption, cytoplasmic rarefaction, and swelling of interdigitating processes. At higher doses, mitochondria were condensed and distorted. Medullary and straight cortical distal tubules had marked distention of the intercellular spaces and disorganization of interdigitating processes. Changes in cortical and outer medullary collecting ducts were similar but less severe. Renal alterations were suggestive of damage to membrane structure and/or transport functions and interference with cellular bioenergetics. Leukocytic infiltration was associated with damaged tubules indicating a contribution of inflammation to the development of the lesions.

[Acute beta 1-selective beta-receptor blocker nebivolol poisoning in attempted suicide]. / Akute Intoxikation mit dem beta 1-selektiven beta-Rezeptorenblocker Nebivolol in suizidaler Absicht.

HISTORY AND ADMISSION FINDINGS: A 17-year-old girl had swallowed 80-100 tablets of Nebivolol, 5 mg each, with suicidal intent. She was referred to hospital 8 hours later by an emergency duty physician. On admission she was sweaty and pale, but there were no other obvious abnormalities. Neurological examination revealed decreased responsiveness and slowed movements. She was known to have type 1 diabetes mellitus. INVESTIGATIONS: Blood pressure was 105/55 mmHg, the ECG showed sinus bradycardia of 55 beats/min. Biochemical tests revealed hypoglycaemia (2.1 mmol/l), hypokalaemia (3.4 mmol/l) and respiratory failure (pO2 6.16 kPa, O2 saturation 82%, pCO2 6.55 kPA). Heart and lung were unremarkable on physical examination as were chest radiogram and echocardiogram. Plasma level of nebivolol was 480 ng/ml on admission (therapeutic range 88-195 ng/ml). TREATMENT AND COURSE: After gastric lavage and administration of charcoal and sodium sulphate a temporary pacemaker was connected and glucagon infused intravenously as an antidote. The cardiovascular state stabilized with falling plasma level of nebivolol. Glucose was administered initially, but transient intravenous insulin infusion became necessary to counteract hyperglycaemia. The patient was transferred from the intensive care unit in a stable cardiovascular state after 2 days. CONCLUSION: This case demonstrates that swallowing 400-500 mg nebivolol, resulting in a plasma level of 480 ng/ml, need not be fatal. But the outcome in this patient should not be taken as necessarily applying to similar cases. It depends on the individual patient's metabolic state whether higher plasma levels might be reached with the same amount of ingested nebivolol.

Study on the pathogenic factors of Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic osteoarthritic disease, endemic in parts of China. Its etiology is unknown. Selenium deficiency, high concentration of organic matter (mainly fulvic acid) in drinking water, and severe contamination of grain by fungi have been proposed environmental causes. Free radicals, possible mediators between the environmental factors and origin of KBD, have been studied in this work. Drinking water from KBD-affected areas contains a higher level of semiquinone radicals than that from disease-free areas. In animal experiments, fulvic acid (FA) accumulated in the skeletal system as semiquinone radicals. Contamination of grain by Fusarium oxysporum or Alternaria alternata significantly increased the content of semiquinone radicals. Furthermore, corn grown in endemic areas had a higher content of radicals than that from disease-free areas. The g factor values for these radicals from contaminated corn were about 2.0040, in the range of semiquinone radical. In monolayer culture of human embryonic chondrocytes, FA and aqueous extracts of grain contaminated by Fusarium injured the chondrocytes and enhanced lipid peroxidation. Selenite and superoxide dismutase (SOD) protected the cells from injury by these toxins and reduced lipid peroxide. Lower glutathione peroxidase activities and higher levels of lipid peroxidation were also found in the children living in KBD-affected regions. Thus, FA and the mycotoxin, which are seen as exogenous free-radical carriers, are important environmental factors in the pathogenesis of Kashin-Beck disease; and selenium, vitamin C, and vitamin E, which inhibit free-radical formation, are considered to be protective.