Programmed Cell Death and Functional Activity of Platelets in Case of Oncohematologic Diseases.

Programmed cell death of non-nucleated blood cells - platelets - could be associated with pathophysiology of oncologic and oncohematologic diseases. It contributes to both bleedings (caused by the thrombocytopenia, which is induced by elimination of the platelets) and thrombosis (caused by the processes of blood coagulation on the surface of phosphatidylserine exposing platelets). Here we characterized functional responses of platelets from the patients with various oncological disorders undergoing chemotherapy and compared them to the platelets from the healthy donors and platelets pre-incubated with apoptosis inducer ABT-737. Some patients exhibited diminished capability of platelets to aggregate. Immunophenotyping of these platelets revealed their pre-activation in comparison to the platelets from the healthy donors. Calcium signaling analysis revealed that in the patient-derived platelets, as well as in the apoptotic platelets, intracellular calcium levels were increased in resting cells. However, moderate level of this increase together with weak expression of phosphatidylserine allows us to assume that apoptotic processes in the circulating platelets from the patients are limited.

Protective effect of antiinflammatory corticosteroid triamcinolone in cisplatin nephrotoxicity.

The corticosteroid, triamcinolone, was examined as a potential antagonist for the nephrotoxicity of cisplatin in female Wistar rats. The changes in renal function and renal morphology were assessed on the 3rd day after administration of cisplatin (7.5 mg/kg BW) and in animals given triamcinolone retard (4 mg/kg BW) 6 h before administration of cisplatin. Pretreatment with triamcinolone resulted in much less severe changes in renal function after cisplatin administration (serum urea: triamcinolone plus cisplatin 14.29 +/- 1.90 mg/l, cisplatin alone 21.60 +/- 2.34 mg/l, p < 0.05, control 2.78 +/- 0.19 mg/l, serum creatinine: triamcinolone plus cisplatin 0.21 +/- 0.02 mg/l, cisplatin alone 0.30 +/- 0.02 mg/l, p < 0.05, control 0.06 +/- 0.01 mg/l). In contrast to cisplatin-treated animals in triamcinolone-pretreated rats alterations of water content were found neither in renal cortex (triamcinolone plus cisplatin 3.39 +/- 0.16 g/g dry weight, cisplatin alone 4.07 +/- 0.07 g/g dry weight, control 3.07 +/- 0.07 g/g dry weight) nor in outer medulla (triamcinolone plus cisplatin 4.20 +/- 0.22 g/g dry weight, cisplatin alone 4.98 +/- 0.21 g/g dry weight, control 3.84 +/- 0.11 g/g dry weight) compared to control. The structure of the kidney following cisplatin administration demonstrated extensive lesions of S3 segments of the proximal tubule. The changes in proximal convoluted tubules were widespread and ranged from the decrease of the amount of microvilli to loss of brush border or even to cell death. In triamcinolone-pretreated rats the structure of the cortex appeared to be virtually normal and tissue of medulla was only slightly damaged.

The effect of hydroxyl-containing dithiocarbamates on cisplatin-induced long-term renal dysfunction in Wistar rats.

The possibility of a slow, longer term deterioration in renal function following the administration of cisplatin has been little studied in animal models. To obtain data on this we have examined renal function and histopathology at 30 days post i.p. cisplatin (5 mg/kg) treatment in female Wistar rats with and without the administration of hydroxyl-containing dithiocarbamates as a protective measure. In contrast to the studies terminated at shorter times, the degree of protection furnished by the use of dithiocarbamates at longer times post-treatment is less impressive. Results suggest that a continuing deterioration in renal function occurs at times greater than 1 week post-treatment when such dithiocarbamates are administered at 1 and 3 h post cisplatin. This was evidenced in both several measures of renal function and in the histopathology of the S3 segment of the proximal tubule.

Development of the metanephros in the chick: maturation of glomerular size and nephron length.

In the avian kidney three nephron types may be identified: mammalian-type nephrons with long (MTN-I) and short (MTN-II) loops of Henlé, and reptilian-type nephrons (RTN). By the method of microdissection the maturation of the nephrons of domestic fowl kidney has been studied. From the 14th day of incubation it is possible to isolate the MTN-I which appear first; all three nephron types may be isolated after 18 days of incubation. The thin limb of Henlé's loop in MTN-I appears after hatching, and the length of this segment in 1-day-old chicks is 0.1-0.13 mm. In 60-day-old chicks its length has approximately doubled. The transition of the thin segment to the thick segment is situated in the descending part of Henlé's loop. In the course of development, the relative length of all nephron segments in MTN-I increases uniformly, while in MTN-II and in RTN the relative length of the proximal and distal convoluted tubules increases. At all stages of development, MTN-I are the longest among the three groups of nephrons and have the largest glomeruli. The comparison between developing avian and mammalian kidneys shows great similarities in the process of maturation in analogous nephron types in these two classes of vertebrates.

The prevention of cisplatin-induced renal dysfunction by hydroxyl-containing dithiocarbamates.

Two hydroxyl containing dithiocarbamates, sodium N-methyl-D-glucamine dithiocarbamate (NaG) and sodium dihydroxyethyl dithiocarbamate (NaY) have been examined as agents for the control of the renal dysfunction in rats given cisplatin. Of these, NaG was found to be the more effective in controlling such renal dysfunction when administered at 1 and 3 h after 5 mg cisplatin kg-1, i.p. Renal function was examined 5 days after the administration of cisplatin by measurement of serum and urinary levels of creatinine and urea, creatinine clearance, serum and urinary levels of Na+, K+, Mg2+, Ca2+, as well as the concentrations of these ions in the renal medulla and cortex. Treatment of rats given cisplatin with NaG at 1 and 3 h post cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin. The sole difference was found to be a slight increase in renal cortical Na+ concentration.

Secretion of endogenous lithium in teleost kidneys as a probable reflection of Na+ and water secretion in their renal proximal tubules.

Unlike mammals with renal reabsorption of lithium (Li+), in freshwater and, particularly, marine teleosts net secretion of this trace element by kidneys was discovered. The ratio of Li+ natural concentration (measured by mass spectrometric isotope dilution technique) in urine to that in blood plasma--(U/P)Li--lies in the range 2-6 in the freshwater species and between 5 and 14 in marine species, i.e. as a rule it is essentially higher than the inulin concentration index (U/P)In. It is supposed that the in vivo observed lithium net secretion in whole kidney reflects and quantitatively estimates Na+ and water secretion in renal proximal tubules of teleosts.