HPLC in biopharmaceutical investigations of drugs representing pyrimidine derivatives (A review)

Pyrimidine derivatives are widely used for the treatment of viral diseases and cancer. The analysis of pyrimidine derivatives is typically performed using various chromatographic techniques, in particular, reversed-phase high performance liquid chromatography (HPLC). The separation is typically carried out with (7–30)-cm-long C₈ and C₁₈ silica gel columns, mainly at room temperature, and a 1–1.5 ml-min eluent flow rate. The column is eluted in an isocratic or gradient system, and a variety of mobile phases have been proposed. The detection is based on optical absorption or fluorescence measurements, or makes use of mass spectrometry. Various methods of extraction of pyrimidine derivatives from biological samples are discussed, and the corresponding detection limits are presented. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 5, pp. 26–34, May, 2007.     

Synthesis and antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil hydrobromide and its liposomal medicinal form

The antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil (BCMU) and its liposomal medicinal form was studied in comparison to 5-fluorouracil (5-FU), a well-known antitumor drug widely used in oncological practice. The half-lethal dose of BCMU is 14.8 ± 4.2 mg/kg, while the optimum effective dose of the drug is 6 mg/kg. In this dose, BCMU combines low toxicity with significant antitumor activity, which is manifested by increased tumor growth inhibition (TGI) at a 19% increase in the lifetime (LT) of experimental animals. The antitumor activity of the liposomal form of BCMU is quantitatively and qualitatively superior to that of the nonmodified compound and 5-FU, which is manifested by the most pronounced TGI value and by a significant LT increase. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 6, pp. 6–7, June, 2006.     

In vivo effects of hypothermia on the microcirculation during extracorporeal circulation.

OBJECTIVE: Induced hypothermia has been shown to be protective during cardiac surgery, but also in traumatic, ischemic, burn, and neurological injury. In previous in vivo animal experiments, we documented increased leukocyte/endothelial (L/E) cell interaction following normothermic extracorporeal blood circulation (ECC). This study was carried out to investigate whether reduced core temperature during ECC affects the damage to the microcirculation as evidenced by leukocyte adherence and edema formation. METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in Syrian golden hamsters. ECC was introduced via a micro-rollerpump (1 ml/min) and a 60 cm silicon tube (1mm inner diameter) shunted between the carotid artery and the jugular vein after application of 300IE Heparin/kg per body weight. Experiments were performed in chronically instrumented, awake animals (age 10-14 weeks, weight 65-75 g). Animals of the experimental group were cooled to 18 degrees C body temperature while ECC, followed by a rewarming period (n=7), controls experienced ECC under normothermia (37 degrees C, n=7). RESULTS: 30 min ECC at 18 degrees C resulted in a decrease of rolling and adherent leucocytes (stickers) in postcapillary venules after 1, 4 and 8h compared with the control group (119+/-46 vs. 274+/-113 n/mm2, P<0.05, mean+/-SD; n=7 in each group). Functional capillary density was significantly reduced during hypothermia (80+/-16 vs. 148+/-16 cm/cm2, P<0.05), but restored after rewarming. In contrast, edema formation was markedly increased during hypothermia. CONCLUSIONS: Hypothermia during ECC significantly reduced L/E cell interaction in the early post-ECC period. Hypothermia markedly reduced microvascular perfusion, but was completely restored upon rewarming. Despite a reduced number of adherent leukocytes, no protection of endothelial barrier function was seen as a consequence of induced hypothermia.     

Isolation and characterization of endometrial leukocyte populations by flow cytometry

Potentialities of the flow cytornetry method in studies of the qualitative and quantitative composition of endometrial immunocompetent cells are demonstrated. The studied leukocyte populations are found to occur in negligible quantities in the endometrium. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 68–71, January, 1994.     

Value of dosimetric control of ultraviolet irradiation of autologous blood in surgical practice

Photometric measurements have shown that during UV irradiation of autoblood in the apparatus "Izolda" the dose of the falling UV irradiation does not remain constant. It becomes less with the term of work of the quartz-mercury lamp and at the expense of the film formed on the walls of the quartz flask of blood cells and plasma components. Therefore for the comparative assessment of the biological and clinical effects in photomodification of autoblood and its transfusion it is necessary to measure the dose of the falling UVI.     

Intracortical Synchronization of Epileptic Discharges at Different Stages of Ultrastructural Rearrangements in a Completely Neuronally Isolated Area of Rat Neocortex

Cross-correlation functions were used to study the time delay (a measure of synchronization) in the appearance of epileptic discharges in distant areas of the cortex in the intact cortex and in neuronally isolated cortical strips in Wistar rats. Experiments were performed at different stages of axon sprouting 30 and 90 days after isolation of cortical areas and in intact cortex. Significant increases in the number of synapses in layer V of isolated cortical strips at 30 days correlated with significant decreases in the time delay, while decreases in the number of synapses at 90 days correlated with a significant increase in the time delay. This is evidence that newly formed synapses increase the extent of synchronization and thus affect epileptogenesis. The data obtained here suggest that large pyramidal cells in layer V of the rat neocortex form a neural network in pathological conditions, this supporting intracortical synchronization of epileptic discharges.