E Bloch-Bogusławska

A Fatal Case of Pentedrone and α-Pyrrolidinovalerophenone Poisoning

We report a fatal case of combined α-pyrrolidinovalerophenone (α-PVP) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) poisoning. A 28-year-old man was taken to hospital in asystole. Despite resuscitation efforts over 30 min, he died. The forensic autopsy showed pulmonary edema and moderately advanced atherosclerotic lesions of the arteries. Microscopic observation revealed chronic changes in the heart. Confirmation of the presence of pentedrone, α-PVP, and its metabolite 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP) in tissues and fluids were achieved using gas chromatography-mass spectrometry analysis after liquid-liquid extraction. A quantitative validated liquid chromatography-mass spectrometry method was used to determine the concentrations of the above designer drugs in postmortem samples. Pentedrone, α-PVP, and OH-α-PVP concentrations were 8,794, 901 and 185 ng/mL in whole blood, respectively; 100,044, 2,610 and 2,264 ng/g in the liver, respectively; 22,102, 462 and 294 ng/g in the kidney, respectively; 13,248, 120 and 91 ng/g in the brain, respectively and 500,534, 4,190 and 47 ng/g in the stomach contents, respectively. This is the first known reported death attributed to the combined use of α-PVP and pentedrone. Additionally, this article is the first to report the distribution of pentedrone in postmortem human samples.

The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue.

Abstract Functional evidence suggests that the stimulation of peripheral and central opioid receptors (ORs) is able to modulate heart function. Moreover, selective stimulation of either cardiac or central ORs evokes preconditioning and, therefore, protects the heart against ischemic injury. However, anatomic evidence for OR subtypes in the human heart is scarce. Human heart tissue obtained during autopsy after sudden death was examined immunohistochemically for mu- (MOR), kappa- (KOR), and delta- (DOR) OR subtypes. MOR and DOR immunoreactivity was found mainly in myocardial cells, as well as on sparse individual nerve fibers. KOR immunoreactivity was identified predominantly in myocardial cells and on intrinsic cardiac adrenergic (ICA) cell-like structures. Double immunofluorescence confocal microscopy revealed that DOR colocalized with the neuronal marker PGP9.5, as well as with the sensory neuron marker calcitonin gene-related peptide (CGRP). CGRP-immunoreactive (IR) fibers were detected either in nerve bundles or as sparse individual fibers containing varicose-like structures. Our findings offer the first hint of an anatomic basis for the existence of OR subtypes in the human heart by demonstrating their presence in CGRP-IR sensory nerve fibers, small cells with an eccentric nucleus resembling ICA cells, and myocardial cells. Taken together, this suggests the role of opioids in both the neural transmission and regulation of myocardial cell function.

Enkephalin, its precursor, processing enzymes, and receptor as part of a local opioid network throughout the respiratory system of lung cancer patients

Evidence is accumulating regarding the local opioid regulation of physiologic respiratory functions. However, anatomical evidence for a local opioid network of the respiratory system is scarce. In this study, tissue samples from 12 lung cancer patients undergoing lobectomy or pneumonectomy were examined immunohistochemically for the expression of the opioid network components met-enkephalin, the respective precursor proenkephalin, the key processing enzymes prohormone convertases 1 and 2, carboxypeptidase E, and the delta opioid receptor in different areas of human lung. Colocalization of proenkephalin with met-enkephalin, prohormone convertase 1, prohormone convertase 2, and carboxypeptidase E was demonstrated by double-immunofluorescence confocal microscopy in alveolar macrophages, submucosal glands, cancerous cells, and pulmonary neuroendocrine cells of bronchial epithelium. Corresponding delta opioid receptor was identified on cells of all these functionally relevant anatomical structures and on substance P-immunoreactive sensory nerve fibers arborizing within bronchial epithelium. Our findings provide evidence of a local opioid network, that is, the exact anatomical localization of proenkephalin, its functionally active peptide met-enkephalin, and the key processing enzymes as well as corresponding delta opioid receptor, linked to functionally important structures of the respiratory system. These findings encourage future studies to examine the functional role of local opioid peptides within the respiratory system.

Local pulmonary opioid network in patients with lung cancer: a putative modulator of respiratory function

Recently, there has been growing interest in the opioid regulation of physiological respiratory function. However, evidence for a local opioid network that includes endogenous opioid peptides and their receptors is scarce. Tissue samples from patients with lung cancer were examined by immunohistochemistry to identify the components of the opioid network: beta-endorphin (END); its precursor, proopiomelanocortin (POMC); the key processing enzymes prohormone convertase 1 and 2; carboxypeptidase E; and ENDs corresponding opioid receptor, the mu-opioid receptor (MOR). Additionally, we tested pulmonary function parameters in a patient with advanced lung cancer after inhalation of nebulized morphine. Confocal immunofluorescence microscopy revealed that the opioid precursor POMC colocalizes with its active peptide END, key processing enzymes and MOR in alveolar macrophages, submucosal glands, cancerous cells, and pulmonary neuroendocrine cells within the bronchial epithelium. In addition, MOR was identified on sensory nerve endings within the bronchial epithelium. Furthermore, nebulized morphine improved pulmonary function parameters in advanced lung cancer. These findings provide evidence of a local opioid network in functionally important anatomical structures of the respiratory system; this network consists of all the machinery required for POMC processing into active peptides, such as END, and contains the receptors for END. Our findings indicate a need for further clinical trials to elucidate the modulatory function of peripheral endogenous opioids in the human lung.

Extracellular purine metabolism in blood vessels (Part II): Activity of ecto-enzymes in blood vessels of patients with abdominal aortic aneurysm.

Both platelet aggregation and high blood pressure are associated with development of atherosclerosis. Among other factors that modulate platelet aggregation and blood pressure, extracellular purines (e-purines) influence these processes via purinoceptors P1 and P2 for which they are natural ligands. We hypothesized that ecto-enzymes such as nucleoside triphosphate diphosphohydrolases (NTPDases), adenylate kinase, 5′-nucleotidase, and adenosine deaminase that regulate the level of e-purines may be involved in the development of atherosclerosis. The enzymatic assays were performed either on the fragments of human abdominal aortas obtained after death or on abdominal aneurysm samples collected during surgery. The substrates and products such as adenine nucleosides and nucleotides were analyzed using reverse phase high-performance liquid chromatography (HPLC) method. Here, we estimated and demonstrated the activities of these ecto-enzymes in the patients with atherosclerosis or atherosclerosis-like diseases such as abdominal aneurysm, myocardial infarction, or Leriche syndrome (LS) with worse thrombosis of extremities. In particular, we noticed reduction in activity of NTPDase1app, NTPDase2app, ecto-adenylate kinase app, and ecto-adenosine deaminaseapp; however, ecto-5 ′-nucleotidaseapp that hydrolyzed e-adenosine monophosphate (e-AMP) into e-adenosine did not show any significant changes. This led us to suggest that alteration of the activity of examined ecto-enzymes is responsible for the development of atherosclerosis or atherosclerosis-like diseases.

Ostre zatrucia u dzieci i młodzieży

Wstep Ostre zatrucia stanowią powazny problem medyczny i spoleczny, a ich czestośc nie wykazuje tendencji spadkowej. Zmieniający sie obraz kliniczny ostrych zatruc oraz postep w zakresie intensywnej terapii toksykologicznej zobowiązują do systematycznego aktualizowania wiedzy w tym zakresie. Cel pracy Celem pracy byla analiza czestości i przebiegu klinicznego ostrych zatruc u pacjentow w wieku rozwojowym. Pacjenci i metody Material stanowila dokumentacja medyczna pacjentow hospitalizowanych w Klinice Pediatrii, Alergologii i Gastroenterologii Collegium Medicum im. L. Rydygiera w Bydgoszczy oraz w Wojewodzkim Szpitalu Dzieciecym im. J. Brudzinskiego w Bydgoszczy w okresie od 01.01.2004 roku do 31.07.2007 roku. W pracy oceniano czestośc zatruc w stosunku do liczby dzieci hospitalizowanych, wiek pacjentow i rodzaj substancji toksycznej, a takze przebieg kliniczny i czas hospitalizacji. Wyniki W latach objetych analizą 441 dzieci hospitalizowano z powodu ostrych zatruc. Bylo to 230 dziewczynek i 211 chlopcow w wieku od 9 miesiecy do ukonczenia 18 roku zycia. Najczestszą przyczyną zatruc byly leki, a zatrucia dotyczyly najcześciej pacjentow w wieku od 13 do 18 lat. Miejsce zamieszkania mialo istotny wplyw na wystepowanie określonych rodzajow zatruc. Przebieg kliniczny zatruc i czas hospitalizacji zalezaly od rodzaju zatrucia oraz podjetych czynności terapeutycznych. Wnioski Najczestszą przyczyną ostrych zatruc byly leki. Czestośc zatruc zalezala od wieku i miejsca zamieszkania pacjenta. U mlodziezy i dzieci przedszkolnych dominowaly zatrucia lekami, natomiast u niemowląt i dzieci w wieku szkolnym przewazaly zatrucia innymi ksenobiotykami. Ostre zatrucia cześciej dotyczyly dzieci ze środowiska miejskiego. Rodzaj intoksykacji oraz wdrozonego postepowania terapeutycznego mial wplyw na przebieg kliniczny zatrucia i czas hospitalizacji.

APPLICATION OF RIGID ENDOSCOPES FOR FORENSIC EXAMINATION OF STAB WOUNDS

Most methods of clinical diagnostics, such as different radiological, ultrasonographic or finally endoscopie examinations have very limited use in forensic medicine. It is the result of the fact, that a pathologist can evaluate almost everything directly, with no application of any device. There are only a few published papers concerning the forensic autopsies assisted with such methods [1–7].