Joanna Nowicka

Prevalence of hydrogen cyanide and carboxyhaemoglobin in victims of smoke inhalation during enclosed-space fires: a combined toxicological risk

Background. Hydrogen cyanide (HCN) is one of the most toxic components of fire smoke, but insufficient attention is paid to its potential role as a cause of injury or death in victims (alive or dead) of enclosed-space fires. Objective. To analyse the prevalence of toxic HCN exposure in fire victims and factors that may influence its toxicity, particularly the co-presence of carbon monoxide (CO) and ethanol. Materials and methods. Blood samples from fire victims and persons rescued from fires were analysed. Results. A positive result for HCN (mean concentration 16.83 mg/l) was detected in blood samples from 169 of 285 fire-related deaths (59%). Ethanol was present in 91 (65%) of 139 samples with coincident presence of HCN and carboxyhaemoglobin (COHb). HCN (mean 4.0 mg/l) was also detected in 20 of 40 (50%) fire survivors. Discussion. The high prevalence of coincident CO and HCN in enclosed-space, fire-related deaths should alert clinicians to suspect toxic HCN exposure in all persons rescued from fire with signs and symptoms of respiratory distress. Conclusions. Medical procedures in persons rescued from enclosed-space fires, especially in the pre-hospital setting, should be augmented to cover the possibility of toxic HCN exposure, particularly in individuals who do not respond to standard supportive therapy. Likewise, post-mortem investigations should routinely include assays for HCN when determining probable cause of death.

Comments on 'Measuring insulin in human vitreous humour using LC-MS/MS' by Thevis et al.

We have read the article by Prof. Mario Thevis and his team titled ‘Measuring insulin in human vitreous humour using LC-MS/MS’ with great interest. Congratulations to the authors on the first successful mass-spectrometry-based analysis of post-mortem material related to an insulin poisoning case. It is another step forward in the post-mortem diagnostics of insulin overdose. The vitreous humour (also called a ‘vitreous body’) is a very valuable material for chemical-toxicological analyses and easy to obtain during autopsy. Its main advantage is anatomical isolation, useful especially in the case of advanced autolytic and putrefactive changes. Insulin is a very important peptide hormone in forensic toxicology for two reasons: (1) its casual or intentional overdose may be lethal and (2) it is also one of the most frequently used anabolic doping agents in sport. The case presented of a 55-year-old non-diabetic victim who died from an insulin overdose is quite interesting, especially because of the availability of ante-mortem blood samples. We have to remember that such a situation is very rare in routine forensic practice, however, where we may analyze only post-mortem biological material and non-biological specimens, like syringes, ampoules, vials, or remnants of the infusion solution and tubings, as in the commented article. The interpretation of insulin levels in the post-mortem biological material is very difficult. The number of published papers dealing with this problem is relatively low. The time of survival after insulin injection depends on many different factors: type of insulin (differentiated onset of action and insulin half-life), method of administration (injection or insulin infusion pump), localization of injection sites on the body (different rate of absorption), etc. The time of survival certainly influences the insulin levels detected in the post-mortem material. Unfortunately, in forensic practice, we do not usually know that time, because the cadavers are frequently found a long time after death, for example when the victim is living alone. The processes of anteand post-mortem elimination, distribution, and insulin transport across the blood-ocular barrier need to be studied more. Further to the Thevis et al.’ article, we want to shortly present our own, so far unpublished experiences in insulin determination in autopsy blood and vitreous humour. So far we have only presented this work during the 9th National Congress of the Polish Society of Toxicology in Szczyrk in 2008. In contrast to the authors of the commented article we used immunoradiometric assay (IRMA KIT IMMUNOTECH), routinely used for in vitro determination of insulin in human serum and plasma. This method is very sensitive, specific and – what is important – relatively cheap,

Biogenic amines in striatum of rats that had been treated with ethanol, and their brains later stored in different temperatures.

The purpose of this study was to investigate how ethanol pretreatment and storage temperatures of brain striatum affect levels of biogenic amines in this tissue. Adult Wistar male rats were injected with 25% ethanol (5.0 g/kg i.p.) while the control rats were administered i.p. with the same volume of saline. Two hours later the rats were decapitated, their brains removed, and the striatum separated. Each striatum was divided into three parts: one part was immediately frozen on dry ice and kept at -70 degrees C; a second fragment was kept in a household refrigerator (+4 degrees C); and the third fragment was kept at +22 degrees C. Twenty-four hours later, levels of DA, DOPAC, HVA, 3-MT, 5-HT, and 5-HIAA in the striatum were assayed by HPLC/ED. Immediately after decapitation; ethanol levels were assayed in the serum of ethanol-pretreated and saline-pretreated rats using gas chromatography. Our results indicate that levels of striatal DA, DOPAC, and HVA in saline-pretreated rats decreased significantly when the storage temperature of the striatum was raised from -70 degrees C, through +4 degrees C, to +22 degrees C, while levels of striatal 5-HT and 5-HIAA remained constant within the temperature range tested and levels of 3-MT fluctuated. In ethanol-pretreated rats, striatal levels of DOPAC, HVA, and 5-HIAA were increased in all three storage temperatures, while levels of DA, 5-HT, and 3-MT were decreased in those temperatures. Those decreases were most profound in striatal samples kept at +22 degrees C. We conclude that concern about possible interactions between drugs and biogenic amines should be exercised.

The influence of L-carnitine on methanol biotransformation in rats

There persists a need for potent and safe inhibitors of alcohol dehydrogenase (ADH), to effectively treat methanol poisoning by slowing its rate of biotransformation to there toxic products, formaldehyde and formic acid. Only a few former papers have reported on the significant effectiveness of L-carnitine in treating ethanol poisoning as well as alcohol abuse. As are no reports on the effectiveness of L-carnitine in treating methanol poisoning till now, the current studies were conducted to investigate the influence of L-carnitine on both oxydative metabolism and elimination of methanol in rats. Male Sprague-Dawley rats, aged 3 months with the body weight of 200-230 g were divided into 6 groups at random, with two of the groups considered to be control. Rats were given drinking water (control) or methanol in two different doses of 3220 mg/kg b.m. or 6440 mg/kg b.m. intragastrically and 0.9% NaCl (control) or 6.2 mmol/kg b.m. of L-carnitine intraperitionelly. Within 96 hours after the administration of methanol and 0.9% NaCl or L-carnitine, the urine was collected and then the animals were decapitated. To determine methanol there were taken blood samples for clot, and to determine carnitine and its derivatives blood was taken into heparinized test tubes. During the autopsy liver was also secured. In all the experimental time points stated the methanol concentrations in blood, urine and liver homogenate were determined by a head-space gas chromatography.

The ketogenic diet affects the social behavior of young male rats

The positive effects of the ketogenic diet (KD) on social behavior have been recently reported in patients and rodent models of autism spectrum disorder (ASD). Given the beneficial effects of the KD on epilepsy, mitochondrial function, carbohydrate metabolism, and inflammation, treatment based on the KD has the potential to reduce some of the ASD-associated symptoms, including abnormal social interactions. It is not known whether the KD influences sociability by reducing the pathological processes underlying ASD or through some independent mechanism. The aim of the present study was to evaluate the influence of the KD on the social behavior of rats. Four-week-old Long-Evans males were treated with the KD for 4 subsequent weeks. Afterwards, behavioral tests were performed in order to evaluate sociability, locomotor activity, working memory, and anxiety-related behaviors. Additionally we performed the social interaction test in animals that were receiving β-hydroxybutyrate or acetone. We have observed that rats fed with the KD showed increased social exploration in three different experimental settings. We did not observe any changes in the level of social interactions in animals treated with exogenous ketone bodies. The results did not show any difference in mobility or anxiety-related behaviors or working memory between the animals fed with the KD or standard rodent chow. In conclusion, we showed that the KD affects the social behavior of wild-type young adult male rats, which was not associated with other behavioral changes.

Patient’s death as a result of mistakenly injection of pancuronium

Pancuronium is a typical non-depolarizing, curare-mimetic, very potent muscle relaxant. Besides application in anesthesiology and intensive care, it is used in execution as a part of lethal injection. In medico-legal practice, there are cases of using this substance in order to commit suicide or to deprive other people of their lives. Accidental pancuronium intoxications are very rare. The authors present such case ended in sudden death of hospitalized woman after mistakenly injection of the drug. 57-year-old female alcoholic was admitted to the Acute Poisoning Centre after ethylene glycol ingestion. During the fifth day of treatment the nurse by mistake, instead of furosemide, intravenously administered her pancuronium. Sudden respiratory and circulatory arrest occurred, so she was intubated and resuscitation with artificial ventilation were undertaken, however within 1 hour and 45 minutes the patient died. Due to the vague background of a sudden deterioration in the patients condition, the case was brought for prosecution. The autopsy and histopathological studies did not reveal the cause of death, but undertaken chemico-toxicological examinations identified the presence of pancuronium in blood, liver and kidney (190 ng/ml, 70 ng/g and 125 ng/g, respectively). Chemico-toxicological analysis proved that the cause of death of the 57-year-old hospitalized woman was pancuronium intoxication due to evident medical error during drug administration. In our case the concentration of pancuronium in blood was in therapeutic range (200-600 ng/ml). However, even a therapeutic pancuronium dose administered to patient the breath of whom is not supported and monitored can be a threat to his life.