[Criteria for the safety of transfusion of colloidal solutions in patients with acute lung lesions].

The prospective study explored the hemodynamic effects of colloidal solution replacement therapy and the criteria for its safety in patients with acute lung parenchymatous lesions (ALPL) attended by hypoalbuminemia and coagulopathy. There were 68 observations of the effects of colloidal solutions: 20% albumin solution (n=25), freshly frozen plasma (FFP) (n=20), 6% hydroxyethylated starch (HES) 130/0.4 9:1 (n=23). The colloidal solutions were infused at a constant rate; the infusion was stopped until pulmonary wedge pressure (PWP) was 25% greater than its baseline value. Before and after infusion, the parameters of central hemodynamics and oxygen transport, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and colloid-osmotic pressure (COP) were measured. The infusion volumes were 3.8 +/- 0.4, 13.7 +/- 1.4, and 13.4 +/- 1.3 ml/kg for 20% albumin solution, 6% HES 130/0.4, and FFP, respectively. The PWP-COP gradient increased in all groups. After FFP infusion, there was an increase in ELWI and lung shunt. After 20% albumin solution, there was a delayed increase in ELWI. There was no rise in ELWI after 6% HES administration. In the 20% albumin solution group, the increased ELWI was recorded in patients who had positive baseline PWP-COP gradients (p < 0.05). A combination of higher PVPI and a positive PWP-COP value causes a greater increase in ELWI after 20% albumin solution infusion than in the normal PVPI group. In patients with ALPL, FFP infusion may lead to an increase in the accumulation of extravascular lung water. A negative preinfusion PWP-COP gradient is a safety criterion for the infusion of 20% albumin solution in patients with ALPL. The increased PVPI in combination with a positive PWP-COP gradient is an aggravating factor.

[Effect of Triton X-100 on accumulation and therapeutic effect of doxorubicin in mice with leukemia P-388 with induced resistance to cytostatic agents]. / Vliianie tritona X-100 na nakoplenie i lechebnoe deistvie doksorubitsina u myshei s leikozom P-388 s indutsirovannoi rezistentnost'iu k tsitostatiku.

Using P 388 and P 388/Dx tumour-bearing mice BDF1 it has been studied effect Tritton X-100 on accumulation and therapeutic action of doxorubicin (Dx). It has been shown that LD50 of Tritton X-100 is 153.6 mg/kg and MTD is 80 mg/kg body weight of animals. It has been shown that Tritton X-100 in dose 40 mg/kg body weight increases initial level of Dx in P 388/Dx cells to 215% and doesn't change accumulation of Dx in P 388 cells. It has been shown that Tritton X-100 doesn't influence the therapeutic effect of Dx in P 388 and P 388/Dx tumour-bearing mice.

[Changes in glutathione-S-transferase activity during induction of resistance of leukemia P 388 and Ehrlich ascitic tumor cells to doxorubicin]. / Izmenenie aktivnosti glutation-S-transferaz pri induktsii rezistentnosti kletok leikoza P 388 i astsitnoi opukholi Erlikha k doksorubitsinu.

We have studied by uridine short term test the level of resistance of murine leukemia cell lines P 388/Dx and ELD/Dx carcinoma cells with induced resistance to doxorubicin, P 388/Fp + Dx cells with induced resistance to combination of finoptOFF++ and doxorubicin in vivo. It was shown that the level of resistance was 6 fold for P 388/Dx cells, 4.5 fold for ELD/Dx cells and 2 fold for P 388/Fp + Dx cells. It was shown that the P 388/Dx cells and P 388/Fr + Dx cells had a 3.5 and 4.4 fold increase level of glutathione-S-transferase activity than P 388 cells. No increase in the activity of glutathione-S-transferase was detected in ELD/Dx cells. We conclude that increase of cellular glutathione-S-transferase activity is not associated with the development of resistance to doxorubicin.

[The effect of finoptin on the metabolism and pharmacological action of cyclophosphane in vivo and in vitro]. / Vliianie finoptina na metabolizm i farmakologicheskoe deistvie tsiklofosfana in vivo i in vitro.

Phynoptin (Ph) and cyclophosphamide (CP) gave rise to a type I spectral changes with liver microsomal fraction. KS were 15 microM and 2150 microM, respectively. Ph increases the concentration of NBP product(s) of CP and acrolein in the blood plasma of animals. Ph increases a toxicity of CP. LD50 was 388.0 +/- 13.9 mg/kg for CP and LD50 was 342.8 +/- 16.9 mg/kg for CP in combination with Ph. Ph changes a therapeutic action of CP in mice with hemocytoblastosis La. Pharmacokinetic interactions have been demonstrated between calcium antagonists Ph and CP.

[The expression of P-glycoprotein in leukemia P388 cells with induced doxorubicin resistance]. / Ekspressiia P-glikoproteina v kletkakh leikoza P 388 s indutsirovannoi ustoichivost'iu k doksorubitsinu.

beta-D-galactose-containing glycoproteins were prepared from cells P-388 leukemia and from P-388 leukemia cells with induced resistance to doxorubicin. It was shown by HPLC method that plasma membranes from resistant cells contain 4-4.5% P-glycoproteins and plasma membranes from sensitive cells contain P-glycoproteins about 10 times lower.

[Comparative accumulation of the Hoechst 33258 fluorescent probe in leukemia P388 cells sensitive and resistant to doxorubicin]. / Issledovanie sravnitel'nogo nakopleniia fliuorestsentnogo zonda Khekhst 33258 v kletkakh leikoza P 388, chuvstvitel'nykh i ustoichivykh k doksorubitsinu.

The authors studied accumulation of the fluorescent probe Hoechst 33258 in leukemia P 388 sensitive (P 388/0) and resistant to doxorubicin (P 388/DOX) cells. It was shown that intensity of fluorescence of the dye increased after binding with nuclear DNA during 25 min for both lines of the cells. Intensity of fluorescence was 40% greater in sensitive than resistant cells. If Triton X-100 was added no difference between two lines of the cell was observed. When doxorubicin was added to the cells with dye, the intensity of fluorescence decreased. It was suggested to use Hoechst 33258 for assessment extent doxorubicin accumulation in nuclei of the cells.

[Modification of doxorubicin action with artificial hyperglycemia]. / Modifikatsiia deistviia doksorubitsina iskusstvennoi giperglikemiei.

Approximately a 1.6-fold increase in the antitumor action of doxorubicin used in combination with artificial hyperglycemia was shown on mice C57B1/6 with hemocytoblastosis La. Artificial hyperglycemia was found to change the doxorubicin pharmacokinetics in the experimental animals evident from increased in antibiotic half-life to 42.3 min against 26.5 min in the controls, the apparent initial concentration of doxorubicin being increased 1.6 times. Accumulation of doxorubicin in the bone marrow cells of the mice did not change with artificial hyperglycemia. It was suggested that the increase in the therapeutic effect of doxorubicin used in combination with artificial hyperglycemia was associated with changes in drug pharmacokinetics.

[The effect of finoptin on doxorubicin accumulation in leukemia P-388 cells with induced resistance to the combination of finoptin and doxorubicin]. / Vliianie finoptina na nakoplenie doksorubitsina v kletkakh leikoza P-388 s indutsirovannoi ustoichivost'iu k kombinatsii finoptina s doksorubitsinom.

Using hybrid mice BDF1 doxorubicin (Dx) accumulation has been determined in leukemia P388 cells (P388/0), P388 cells with induced resistance to Dx (P388/Dx) and P388 cells with induced resistance to the finoptin (Fp) + Dx combination (P388/Fp + Dx). It has been shown that Fp doesn't affect Dx accumulation in or elimination from leukemia cells P388/0 or P388/Fp + Dx. The resistance of P388/Fp + Dx cells to the Fp + Dx combination develops during 6 passages. It can be concluded that Fp application doesn't abolish the problem of tumor cells' resistance to cytostatics.

Verapamil effect on the accumulation of doxorubicin in the leukemia P388 cells with induced antibiotic resistance.

Using mice BDF1 it has been shown that the period of retention of Doxorubicin (Dx) is shorter in the leukemia P388 cells with induced antibiotic resistance (P388/Dx) as compared to P388 cells sensitive to Dx. Administration of Verapamil (Vp) to animals leads to an increase of Dx concentration in the leukemia P388/Dx cells during a 240 min observation period. Vp promotes the therapeutic effect of Dx on P388/Dx bearing mice. It can be suggested that the mechanism of Vp action consists in the damaged Dx elimination from cells with induced resistance, since Vp doesn't change the period of circulation of the antibiotic in the blood plasma of mice.

[The effect of finoptin on the accumulation of doxorubicin in leukemia P388 cells with induced resistance to the antibiotic]. / Vliianie finoptina na nakoplenie doksorubitsina v kletkakh leikoza P388 s indutsirovannoi ustoichivost'iu k antibiotiku.

Using male mice BDF1, it has been shown that the retention period of doxorubicin (DOX) is shorter in the leukemia P 388 cells with induced antibiotic resistance (P 388/DOX) as compared to the P 388 cells, sensitive to DOX. Administration of finoptin (FP) to animals leads to the increase of DOX concentration in the leukemia P 388/DOX cells during 240 min observation. FP promotes the therapeutic effect of DOX on mice bearing leukemia P 388/DOX. It can be suggested that the mechanism of FP action is the damaged DOX elimination from cells with induced resistance, since FP doesn't change the period of antibiotic circulation in the murine blood plasma.

[Changes in amino acid metabolism at the onset of colchicine resistance in Dzungarian hamster fibroblast cell culture]. / Izmenenie obmena aminokislot pri vozniknovenii ustoichivosti k kolkhitsinu v kul'ture kletok fibroblastov dzhungarskogo khomiachka.

We have studied amino acid up-take from incubation media by colchicine-resistant and colchicine-sensitive Djungarian hamster fibroblast cells. It has been shown that arginine and asparagine amino acid contents in the medium are different for colchicine-sensitive and colchicine-resistant cells. Amino acids concentration is not reduced in the medium after incubation of resistant cells, while it is decreased after incubation of sensitive cells. We can suggest that penetration of low-weight sources of nitrogen into sensitive cells is hampered. It can also be suggested that protein macromolecules are the main source of nitrogen for these cells. The protein up-take levels from the incubation medium, as assessed by the ammonia and amino acid contents of cell counts don't exceed 5% of their initial concentrations in the medium.