Aykut Lale

Trans-anethole concentrations in bogma raki

We read with great interest the article entitled ‘‘Electron Microscopic Examination of Effects of Bogma Raki and Walnut on Cochlea: An Experimental Study’’ by Cevik et al. presenting a 4-week bogma raki, walnut, and bogma raki þ walnut consumption effects on cochlea of Wistar male albino rats by electron microscopy. As the authors mention, the relationship between acute or chronic alcohol consumption and hearing remains unclear. In their study, they utilized bogma raki samples produced by homemade traditional methods, in Turkey. Cevik et al. analyzed samples of bogma raki given to the rats by gas chromatography mass spectrometry and the content of bogma raki was presented as shown in Table 1. Trans-anethole (1-methoxy-4-(1-propenyl) benzene) is the principal aromatic molecule originated from anise in raki and also used for flavor in many alcoholic drinks such as Middle Eastern arak, Colombian aguardiente, French spirits absinthe, anisette and pastis, Greek ouzo, Bulgarian and Macedonian mastika, German Jagermeister, Italian sambuca, Dutch brokmopke, Portuguese, Peruvian, and Spanish anisado, Herbs de Majorca, and Mexican xtabentun. According to the Turkish Food Codex, the minimum limit for trans-anethole in raki is 800 mg/L. Many papers present trans-anethole concentrations found in Turkish raki and bogma raki samples with measurement as ‘‘weight of trans-anethole’’/’’volume of beverage’’. Gueven examines 14 nationally certified brands of raki available in the local markets and stated that trans-anethole levels ranged between 747 mg/L and 1547 mg/L. Trans-anethole levels in bogma raki samples were investigated in a MSc thesis by Bulur, which revealed trans-anethole concentrations ranging between 441.46 mg/L and 2098.10 mg/L in 12 samples. Trans-anethole concentration detected in the study by Cevik et al. is abnormally high, according to our experience. Additionally, in a lately conducted, unpublished, study by our team, trans-anethole level was 1.93% (v/v), in local bogma raki sample. In this context, we did a calculation in order to find out the concentration of trans-anethole in bogma raki sample utilized by Cevik et al. Trans-anethole density is 0.988 g/mL at 25 C. Considering 10.94%v/v volume of trans-antehole in the sample, the concentration of trans-anthole in Cevik et al.’s sample is 108,087 mg/L, which is theoretically impossible compared to the related literature. Although the data regarding to trans-anethole toxicity is insufficient, oral median lethal dose values for trans-anethole were reported to be 1.8–5.0 g/kg in mice; 2.1–3.2 g/kg in rats. Additionally, literature reveals that doses of equal or higher than 120 mg/kg/day cause severe weight loss and dehydration. Considering high trans-anethole concentrations found in calculation above, in the study by Cevik et al., rats given bogma raki regimen should have present

Commentary on: Chen HI, deJong J. Increased lung weights in drug-related fatalities. J Forensic Sci 2017;62(6):1632-4.

Sir, We read the article entitled “Increased Lung Weights in Drugrelated Fatalities” by Heather I-Hsuan Chen and Joyce deJong, with great interest (1). They present increased lung weight as an autopsy finding which potentially indicates the presence of any drug that caused or contributed to death. Out of drug-related fatalities, the authors measured the lung weights and gathered data regarding manner of death, gender, race, age, presence of opioids, presence of pneumonia, and presence of resuscitative efforts, and compared their findings with the data obtained from the studies by Molina and DiMaio (2,3). The study suggested that lung weights in drug-related fatalities are increased, and heavier right lung weights are obtained in cases with pneumonia and resuscitation (1). By this letter, we aim to contribute to discussion of possible mechanism of lung weight increase and to indicate certain major points that might affect results. Apart from other organ and tissues, pulmonary perfusion is produced by entire blood in circulation, which cause acute accumulation of many drugs in the lungs at first period of exposure, administration, and consumption of particularly weak bases and drugs with a pKa value >8 (4). Although total metabolic activity of lung is lower than liver, the metabolic difference is not significant considering cell types of pulmonary tissue. Furthermore, in certain cell types of lungs, enzymatic activity is higher for per cell which might cause impaired cell homeostasis (5). Additionally, depending on administration route, chemicals with physical properties as in hot vapors directly lead cell damage. For example, inhalation of cocaine induces “crack lung” which is presented with microscopic alveolar damage and radiological evidence of alveolitis (6). Alveolar epithelial and endothelial cell damage and migration of inflammatory cells bring out pulmonary edema that is also observed via neurogenic pathways (5). Irritants could evoke Transient Receptor Potential (TRP) channels at nociceptive nerve terminal and trigger neuropeptide-mediated inflammatory response including vasodilatation, plasma protein extravasation, migration, and pulmonary edema (7). Acute lung injury and acute respiratory distress syndrome, possible causes of death, can also result in severe pulmonary edema. On the other hand cardiogenic pulmonary edema could be observed secondary to drug-induced arrhythmia, myocardial ischemia, cardiomyopathy, and cardiac dysfunction (6). Cocaine and amphetamine type drugs induce catecholamine release that cause pulmonary hypertension, endothelial disruption, and cardiac abnormalities, which consequently lead pulmonary edema (8). Pulmonary complications of illicit drugs such as aspiration pneumonia, pulmonary infections, pulmonary granulomatosis, and pulmonary hemorrhage could also cause increase in lung weights (6). Todorovic et al. reported pulmonary histopathological findings of illicit drug users and find out pulmonary edema in 87.3%, acute alveolar hemorrhages in 77.8%, and hemosiderinladen macrophages in 82.54% of cases (9). Ratios of opiate positive to negative case numbers were similar in both studies by Todorovic et al. and Heather I-Hsuan Chen and Joyce deJong. Although the cases with pneumonia were emphasized by Heather I-Hsuan Chen and Joyce deJong, they had not share data about number of cases with pneumonia and histopathological changes in edematous lungs. Unfortunately, lack of this data makes interpretation of actual cause that predominantly increases lung weight impossible. In animal experiments, lung weight was determined as a useful tool for identifying acute lung toxicity, and supportive histopathological alterations are observed in over %80 of animals with increased lung weight (10). As a basic medical knowledge, there are a number of pathophysiological conditions that might cause increased lung weight; however, authors had not specified any interfering possible comorbid pathophysiological condition as exclusion criteria. Chen and deJong included cases underwent cardiopulmonary resuscitation (CPR) while performing statistical analyses in their series (1); however, CPR could directly cause pulmonary changes such as intrapulmonary hemorrhage and might result in increased lung weight. They also used study population of some other studies by Molina and DiMaio (2,3) as control groups. Nevertheless, Molina and DiMaio had not considered CPR as an interfering factor or they might naturally exclude CPR cases while presenting their series. Unfortunately, Chen and deJong had not expressed whether they exclude CPR cases (n:27) while compare their series with Molina and DiMaio. If they did not exclude CPR cases during the comparison, presented results become highly controversial and the actual cause of increased lung weight remains uncertain. Also the authors indicated fourteen cases with other comorbidities which were not also specified in the text. These comorbidities needed to be defined to explain interfering factors. Furthermore, it is not understood whether these cases were excluded during statistical analyses or not. Cutoff level of total lung weight for indication of drug-related fatalities was determined 1000 g in the paper; however, the way of determination of 1000 g is not explained. If this is a statistically obtained cutoff level, the sensitivity, specify of value and ROC curve, which will highly increase the credibility of value, should be presented. In conclusion, lung weight increase could be a valuable finding to support the diagnosis of drug-related fatalities. Further studies are needed to determine other possible causes of increased lung weight and their difference from drug-related fatalities, also the credible cutoff value supporting diagnosis, its sensitivity and specificity.

Evaluation of Methods Used in Diagnosis of Fatal Hypothermia

Post-mortem diagnosis of hypothermia-induced deaths is still a challenging issue, today. Because of lack of findings and markers used for definitive diagnosis, cases of deaths secondary to hypothermia either remain undiagnosed or end up with an exclusion diagnosis. However, thanks to improvements in forensic sciences, literature has reported a great number of considerable methods and markers promising in the diagnosis of fatal hypothermia. In this paper we aimed to attract attention of forensic medicine professionals to the issue by discussing findings and markers suggesting and/or indicating fatal hypothermia, in the light of the literature.