CLINICAL AND FORENSIC ASPECTS OF PHARMACOBEZOARS

Background: Pharmacobezoars are specific types of bezoars formed when medicines, such as tablets, suspensions, and/or drug delivery systems, aggregate and may cause death by occluding airways with tenacious material or by eluting drugs resulting in toxic or lethal blood concentrations. Objective: This work aims to fully review the state-of-the-art regarding pathophysiology, diagnosis, treatment and other relevant clinical and forensic features of pharmacobezoars. Results: patients of a wide range of ages and in both sexes present with signs and symptoms of intoxications or more commonly gastrointestinal obstructions. The exact mechanisms of pharmacobezoar formation are unknown but is likely multifactorial. The diagnosis and treatment depend on the gastrointestinal segment affected and should be personalized to the medication and the underlying factor. A good and complete history, physical examination, image tests, upper endoscopy and surgery through laparotomy of the lower tract are useful for diagnosis and treatment. Conclusion: Pharmacobezoars are rarely seen in clinical and forensic practice. They are related to controlled or immediate-release formulations, liquid or non-digestible substances, in normal or altered digestive motility/anatomy tract, and in overdoses or therapeutic doses, and should be suspected in the presence of risk factors or patients taking drugs which may form pharmacobezoars.

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

Background: Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver. Methods: Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106 P. chabaudi-parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i. Results: Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd, Rhag, Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1, Ahsp, Acyp1, Gata1, Gfi1b, Tal1, Klf1, Epor, and Cldn13. In vaccination-protected mice, expression of these genes, except Epb4.1, is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i., before declining towards the end of crisis phase on day 11 p.i. Conclusion: The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1-2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi.

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

Background Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi . Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver. Methods Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 10 6 P. chabaudi- parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi -infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i. . Results Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i.. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd , Rhag , Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1 , Ahsp, Acyp1 , Gata1, Gfi1b, Tal1, Klf1, Epor , and Cldn13 . In vaccination-protected mice, expression of these genes, except Epb4.1 , is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i. , before declining towards the end of crisis phase on day 11 p.i. . Conclusion The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1-2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi .

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

Background: Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver. Methods: Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106 P. chabaudi-parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i.. Results: Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i.. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd, Rhag, Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1, Ahsp, Acyp1, Gata1, Gfi1b, Tal1, Klf1, Epor, and Cldn13. In vaccination-protected mice, expression of these genes, except Epb4.1, is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i., before declining towards the end of crisis phase on day 11 p.i.. Conclusion: The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1-2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi.

Effectiveness of the new polyfunctional infusion solution of blood substitutes on the activity of lipid peroxidation and antioxidant protection of heart in acute fatal blood loss

Background: One of the important directions of modern medicine is improving treatment of extreme conditions, the mortality rate of which is still very high, which is often associated with insufficient effectiveness of modern blood substitutes. Purpose of the study was to investigate the efficacy of a new multifunctional blood substitute in acute fatal blood loss on the activity of lipid peroxidation (LPO) and antioxidant system (AOS) of the heart, which showed its high antioxidant efficiency.Methods: Experiment was carried out on 60 rats weighing 180-200 g, clinical death was caused under etaminal anesthesia by acute blood loss from the carotid artery. After bleeding rats were given injection of infusions. Animals were divided into following groups: group I – before blood loss (intact), group II - clinical death, group III (control) – acute fatal blood loss after infusion of saline solution, group IV (comparison) - after acute lethal blood loss with infusion of reo-sorbilact, and group V (main, experimented) - after acute lethal blood loss with the new infusion of multifunctional blood substitute.Results: The level of MDA in clinical death (in group II) had increased by almost 2.0 times, as well as diene ketones, indicators of antioxidant activity decreased. The enzyme activity of GR in heart was 1.2 times lower, GPO - 1.5 times, SOD-2.0 times, catalase-4.4 times. In group III where animals after clinical death were revived with saline solution, AD increased to 45.6±0.4 mm Hg after 1 hour, and CBV increased to 44.8±0.4 ml/kg, the values of these parameters in the intact animals of the first group were 40.2% and 76.6%, respectively. After infusion of saline glomerular filtration rate was 0.61±0.02 ml/min, and diuresis of 0.21±0.02 ml/min compared with the values of these parameters in the intact animals was 46.9% and 65.6%, respectively. Life expectancy of animals after infusion of physiological saline was 12.3±1.2 hours, 30% of the animals survived. After infusion of reosorbilact in group IV, the survival rate was 40%, and after the infusion of a new multifunctional blood substitute in group IV -70%, which is 30% higherConclusions: The infusion of a new multifunctional blood substitute during acute fatal blood loss leads to a more effective delay of LPO processes and restoration of AOS in heart, in comparison with the use of reosorbilact. The use of a new multifunctional blood substitute during acute lethal hemorrhage in rats, compared with infusion of reosorbilact, leads to a more pronounced recovery of hemodynamic parameters, biochemical parameters of blood and ABS.