Impurity profiling/comparative analyses of samples of 1-phenyl-2-propanone.

1-Phenyl-2-propanone (P-2-P), also known as benzyl methyl ketone (BMK), is the main precursor used in amphetamine synthesis. In recent years, the number of seizures of P-2-P from both licit and illicit drug manufacture has increased. The present article comprises a discussion of some of the largest seizures of P-2-P diverted from regular production to the illicit market. It also presents the methods used in clandestine laboratories to synthesize P-2-P and a forensic approach to identify and differentiate between these methods. To that end, and to facilitate the monitoring of the P-2-P market, a method of P-2-P impurity profiling was designed for comparative purposes and for the identification of the synthesis route. P-2-P samples were analysed by means of gas chromatography/mass spectrometry (GC/MS). Out of 36 identified impurities, 14 were selected as markers for sample comparison. On the basis of the GC peak areas of those 14 markers, a cluster analysis was carried out, resulting in three clusters, each corresponding to a given P-2-P synthesis route. The results of P-2-P impurity profiling are stored in both a forensic database and a police database. The forensic database comprises chemical data, such as those on P-2-P purity, additives and specific impurities, as well as information on seized P-2-P samples having a similar impurity profile. Data stored in the police database, which is linked with the forensic database by case identification number, cover the circumstances of seizures and personal details of offenders. The databases enable the full use of forensic data in intelligence work and police investigative activities.

Particular fractions of microproteinuria in patients with stabile angina pectoris and without a clinical nephropathy.

The determination of microalbuminuria is a valuable method in the diagnosis of renal and vascular diabetes or hypertension complications. Recently, microalbuminuria appeared to be the predictor of coronary heart diseases (CHD). The presented study comprised 26 patients with stable angina pectoris (AP) and 27 healthy volunteers. We simultaneously evaluated microproteinuria during the first morning and afternoon miction and the 24-h blood pressure. Amongst patients with AP all urine protein concentrations were increased (results in g/mol creatinine): alpha-1-microglobulin (1.04 + 0.13 vs. 0.47 + 0.05, p < 0.001) albumin (0.95 + 0.15 vs. 0.61 + 0.05, p < 0.05) and IgG (1.00 + 0.17 vs. 0.55 + 0.05, p < 0.01) were higher, in comparison to control group values. Indices for diurnal blood pressure rhythm were significantly lower in the AP group for both systolic (1.07 + 0.01 vs. 1.14 + 0.01 p < 0.001) and diastolic (1.09 + 0.02; vs. 1.21 + 0.03 p < 0.01) pressures. A physiological increase of albumin from the afternoon sample was only observed in the control group. Thus, our AP patients demonstrated signs of subclinical nephropathy in both the proximal tubuli and glomeruli.

[The effect of human recombinant erythropoietin on distribution of membrane phospholipids in blood platelets of patients with uremia treated with repeated hemodialysis]. / Wplyw ludzkiej rekombinowanej erytropoetyny na rozmieszczenie fosfolipidów blonowych krwinek plytkowych u chorych z mocznica leczonych powtarzanymi hemodializami.

An important role in the formation of hemostasis defects in uremic patients is attributed to platelet dysfunction. An essential role in platelet structure and function is played by membrane phospholipids (PL). They are asymmetrically distributed within the platelet membrane: outer surface is composed mainly of sphingomyelin (Sph) and phosphatidylcholine (PC). During platelet activation a translocation of phosphatidylserine (PS) and phosphatidylethanolamine (PE) from inner to outer membrane surface is observed. Phosphatidylinositol (PI) is not translocated. Lipid abnormalities are common in uremic patients. According to some authors erythropoietin (EPO) has been reported to alter lipid metabolism. In our recent works a positive influence of EPO on platelet PL composition in uremic patients has been indicated. The aim of this study was the assessment of the EPO influence (applied 4000 U per week) on platelet membrane PL distribution in chronically hemodialyzed patients. The PL distribution was determined using nonpenetrating tracer (TNBS) by Vale method, and using high purified phospholipases hydrolysis according to Chap method. Our results indicate that during EPO therapy the PS, PE, Sph and PC exposition at the outer surface of platelet membrane (in patients hemodialyzed without EPO widely disturbed compared with healthy controls) approaches to normal values. These results confirm our recent observations that EPO profoundly interferes with lipid metabolism. The smaller PS exposition at the outer platelet surface during EPO treatment suggests less platelet activation, and might partially explains the positive EPO influence on platelet hemostasis.

[The influence of recombinant human erythropoietin on platelet phospholipid fatty acid composition in patients on long term hemodialysis]. / Wplyw rekombinowanej ludzkiej erytropoetyny na sklad kwasów tluszczowych fosfolipidów krwinek plytkowych u chorych przewlekie hemodializowanych.

The disturbances of blood platelet activity play an important role in the formation of haemostasis disorders in patients with end-stage renal failure (ESRF). Phospholipids and their fatty acids play an essential role in the structure and function of the platelet. In patients with ESRF, changed lipid metabolism and also changed platelet phospholipid composition are observed. Data is available on the positive influence of recombinant human erythropoietin (rHuEPO) on some lipid metabolism disorders in patients with ESRF. The aim of this study was to demonstrate the influence of rHuEPO on the fatty acid composition of platelet phospholipids in patients with ESRF treated with repeated haemodialysis. The study material included 25 patients divided into two groups: group I--14 patients treated with repeated haemodialysis, group II--11 patients also treated with haemodialysis in whom rHuEPO was administered subcutaneously in doses 2000 U twice weekly. In group I great differences in fatty acid composition were noted in comparison to the control group. In general, decreased content of unsaturated fatty acids was found in all phospholipid classes, except for phosphatidylcholine. In group II the changes in fatty acid composition were considerably less pronounced than in group I, in the case of many acids reaching the values observed in the control group. The obtained results suggest that rHuEPO improves changed platelet lipid metabolism in patients with ESRF treated with repeated haemodialysis.

Day/night ratio of microproteinuria and blood pressure rhythm in type II diabetes.

The paper discusses the results of the studies conducted with a group of patients with type II diabetes without clinical nephropathy. The aim of the study was to attempt to determine the markers for early stages of diabetic nephropathy in NIDDM patients. The following examinations were carried out: the level of selected microproteinuric components, 24 h monitoring of arterial blood pressure, and electrocardiogram (ECG). Among the patients examined, the level of alfa-1-microglobulin, albumin and immunoglobulin G (IgG) in diabetic patients was higher than in the control group, and the increased activity of beta NAG was observed. The 24 h profile of blood pressure and the ratio afternoon/night of albumin excretion flattened in the majority of diabetic patients. The results of the study suggest that the proximal tubules and the membranes of renal glomeruli are damaged as early as during the period of subclinical diabetic nephropathy.

[Microproteinuria and circadian rhythm of blood pressure in patients with arterial hypertension]. / Mikroproteinuria i rytm dobowy cisnienia u pacjentów z nadcisnieniem tetniczym.

Microproteinuria is a recognized sign of early nephropathy in the course of arterial hypertension. There is few data concerning the excretion of proteins other than albumin in this group of patients. The aim of the study was to examine circadian rhythm of alfa-l-microglobulin (AlMG), albumin (ALB), immunoglobulin G (IgG) excretion and N-acetyl-beta-glukosaminidase (beta NAG)-activity, then to compare the results with the results of 24 hour ambulatory monitoring of arterial blood pressure in patients with arterial hypertension. The study comprised 28 patients. The control group included 27 healthy volunteers. Albumin concentration was determined by Beckman ICS2 nephelometer, using Beckman and Dako reagents. Blood pressure and ECG were monitored by analysis with ABP-system (AMP-USA). In patients with arterial hypertension significantly higher levels of ALB, AlMG, IgG and increased beta NAG activity were observed in morning urine samples. Despite hypotensive treatment blood pressure values were slightly, though significantly higher than in the control group. Among patients in the study circadian BP rhythm was disturbed. The results obtained suggest that in this group of patients subclinical nephropathy develops involving renal glomeruli and proximal tubules--probably resulting from vascular and humoral disorders, with accompanied hypertension.

[The effect of human recombinant erythropoietin on levels of plasma phospholipids in patients chronically treated with hemodialysis]. / Wplyw ludzkiej rekombinowanej erytropoetyny na stezenie fosfolipidów osocza u chorych przewlekle hemodializowanych.

In uremic patients a disturbed lipid metabolism is observed. In our former works a positive effect of erythropoietin (EPO) on blood platelet phospholipids composition in uremic patients was indicated. In this study we examined the EPO influence on blood plasma phospholipids in chronically hemodialyzed patients. Phospholipids were measured by thin layer chromatography method before and 3 months after the beginning of EPO treatment. EPO was administered subcutaneously, 2000 U twice a week. Decreased phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine levels were shown in patients before EPO treatment, compares with the control group. During EPO therapy the phospholipid levels approached to normal values. Conclusion is that EPO administration has a positive influence on blood plasma phospholipids in hemodialyzed patients. The detailed importance of this event has been not known yet, but our observations suggest that EPO profoundly interferes with lipid metabolism.

Human erythropoietin improves the blood platelet phospholipid composition in chronically hemodialyzed patients.

Phospholipids play an essential role in platelet structure and function. In uremic patients an abnormal platelet phospholipid pattern is observed. We examined the influence of recombinant human erythropoietin (rhuEPO) on platelet phospholipid composition in hemodialyzed patients. Before rhuEPO therapy, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine were significantly reduced as compared with a healthy control group. After rhuEPO treatment, the phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine concentrations showed a significant increase. We conclude that rhuEPO partially normalizes the platelet phospholipid composition in uremia.

[Change of platelet function after the beginning of repeated hemodialysis treatment in patients with uremia]. / Zmiana czynnosci krwinek plytkowych po rozpoczeciu leczenia powtarzanymi hemodializami u chorych z mocznica.

The disturbances of platelet function in end-stage renal failure varies in dialysed and non-dialysed patients. We examined some platelet function in 11 uremic patients treated conservatively (TC) and, again in the same patients, 3-month after the beginning of repeated hemodialysis treatment (HD). The blood samples were taken before hemodialysis. In TC patients normal platelet count, prolonged bleeding time, normal platelet aggregation, unchanged PF4 activity and decreased PF3 availability were shown, compared with control group. In HD patients also normal platelet count and prolonged bleeding time were noted, but increased platelet aggregation, increased PF4 activity and PF3 availability were observed, compared with control group and with TC patients. We conclude that in TC patients rather decreased platelet function was observed; after the beginning of hemodialysis treatment some platelet function became significantly enhanced, which suggests platelet activation. Moreover, in HD patients the disturbances of platelet function before dialysis were shown, then it is possible that platelet activation persists in interdialytic period.