Evaluation of capillary miR-122 as a prognostic biomarker of paracetamol-induced liver toxicity.

INTRODUCTION: Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. METHODS: In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12 h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100 IU/L collected at 10 or 20 h after the start of treatment. Pearson's correlation analyses were performed. RESULTS: In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10 h and at 20 h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). CONCLUSION: This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.

Foodborne Botulism: Clinical Diagnosis and Medical Treatment.

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain-Barré syndrome-Miller-Fisher variant, Eaton-Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure.

Latrodectism in Italy: First report of successful treatment of L. tredecimguttatus envenomation using L. mactans antivenom from North America.

INTRODUCTION: Latrodectism is a rare, but potentially severe, clinical syndrome caused by spider of the genus Latrodectus. L. tredecimguttatus is widespread in Italy and its bite cause the injection of α-latrotoxin that cause depletion of acetylcholine at motor nerve endings and release of catecholamines at adrenergic nerve endings. We describe the first clinical case of L. tredecimguttatus poisoning successfully treated with L. mactans antivenom from North America. CASE REPORT: A healthy 60-year-old patient was admitted to the emergency department after unknown insect sting or arachnid/snake bite. In the early morning, the patient was working in the countryside when he felt a sting-like pain in the medial area of the right lower leg, associated with an intense burning sensation. An hour later he developed agitation, hoarseness, sweating, abdominal distress and intense pain in his right leg. In the emergency room vital signs showed a hypertensive crisis, tachycardia and peripheral oxygen desaturation. ECG was normal and ABE showed mixed acid-base disorder. Blood tests showed leukocytosis with neutrophilia, high levels of myoglobin, with normal coagulation and normal plasmatic cholinesterase. Neck, thorax and abdomen CT scan, with and without contrast medium, was negative. Four hours after admission hypertension worsened with board like rigid abdomen and onset of fasciculations, tremors, miosis and intense regional sweating. The definitive diagnosis of poisoning by L tredecimguttatus was based on the clinical picture. Within short time the antidote was provided by the Poison Centre and administered. A marked improvement of the symptomatology was noted after 30 minutes, and 1 hour later all symptoms were under control. The patient was discharged after 2 days. CONCLUSIONS: The clinical presentation of a patient suffering from latrodectism places the clinician in front of a challenging differential diagnosis. Following the suspicion, the first-line doctor is invited to discuss the case with a toxicologist, in order to confirm or exclude the diagnosis and implement all therapeutic measures. In our clinical case, the absence of organic lesions, laboratory tests not suggestive for other causes, and the presence of typical clinical feature suggested the diagnosis of L tredecimguttatus poisoning. This hypothesis was then supported by the close temporal relation between antivenom administration and symptoms improvement. With this case, we report the first use of L mactans antivenom from North America to treat L.tredecimguttatus poisoning and we confirm its effectiveness in counteracting latrodectism caused by this spider.

Serum uric acid levels and different phases of illness in bipolar I patients treated with lithium.

Recent findings support the role of purinergic system dysfunction in the pathophysiology of bipolar disorder (BD). The present study aimed to evaluate the pattern of serum uric acid levels in a sample of 98 BD I patients followed-up prospectively in a naturalistic study and treated with lithium monotherapy or in association with other mood stabilizers (valproate or carbamazepine), in relation to different phases of illness and to pharmacological treatment. The results showed that uric acid levels were significantly higher in patients suffering from a manic/mixed episode, than in those euthymic or during a depressive phase. Further, these levels were related to the Clinical Global Impression-Bipolar Version (CGI-BP) scale score for the severity of manic symptoms. A positive correlation was found also with male sex and with serum lithium levels. These findings suggest that a dysregulation of the purinergic system may occur during manic/mixed episodes, and they support a possible role of serum uric acid levels as a state-dependent marker of BD manic phases.