Search

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.

Platelets are anucleate blood cells with reported roles in hemostasis and immune responses, which possess a functional receptor for bacterial lipopolysaccharides (LPSs), the well-known inducers of inflammation. However, LPSs effects on platelets are contradictory. Here we aim to investigate mechanisms of platelet functioning in the presence of LPS and to find the cause of the discrepancy in the previously published data. Cell activity was analyzed by flow cytometry, western blotting, and aggregometry. Thrombus growth was assessed by fluorescent microscopy. LPS' activity was checked by their capability to induce PMN activation. However, LPSs did not substantially affect either thrombus growth in flow chambers, irreversible platelet aggregation, or platelet responses to strong activation. Platelet aggregation in response to 1 μM of ADP was significantly inhibited by LPSs. Flow cytometry analysis revealed that platelet activation responses to weak stimulation were also diminished by LPSs, while VASP phosphorylation was weakly increased. Additionally, LPSs were capable of inhibition of ADP-induced P2-receptor desensitization. Incubation of platelets with a pan-PDE inhibitor IBMX significantly enhanced the LPSs-induced platelet inhibition, implying cAMP/cGMP dependent mechanism. The discrepancy in the previously published data could be explained by LPS-induced weak inhibition of platelet activation and the prevention of platelet desensitization.

The structure of nephrons in 83 species of fishes, amphibians, and reptiles was investigated by microdissection. Glomerular diameter, nephron length, length of nephron segments, and the ratios between glomerular size and nephron length are presented. In diifferent groups of fishes (Elasmobranchii, Acipenseridae, Teleostei), the adaptation to freshwater or seawater environment may lead to diverse changes of nephron structure. The kidneys of euryhaline teleosts capable of living in fresh water may be aglomerular, as are those of some marine fishes. In contrast, the diameter of glomeruli in some marine fishes is larger than in true freshwater fishes. In amphibians, the adaptation to freshwater environment, as in teleost fishes, has led to different changes of nephron structure. The size of glomeruli in freshwater reptiles is larger in comparison to terrestrial animals, and the distal tubule in desert and freshwater reptiles is longer than in nondesert species. This probably reflects the adaptive changes of the reptilian nephron to freshwater and desert environments. The results of this study show that the nephron structure of lower vertebrates is predominantly determined by the different environments they occupy rather than by progressive changes within the vertebrate sequence. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley-Liss, Inc.)

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 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.

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.

Introduction: The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting., Methods: Platelet aggregation was induced by ADP in diluted PRP in the presence of 2 mM calcium at 23 °C. The study included healthy adults (n = 30), healthy children (n = 20), and pediatric patients with suspected or diagnosed platelet function abnormalities (n = 25)., Results: The assay parameters were stable for at least 3 h after isolation of PRP and were sensitive to plasma dilution in the range of 2-8%. The initial aggregation velocity was significantly reduced in pediatric patients compared with healthy children (p < 0.05). ADP-induced light transmission amplitude was moderately correlated with LaSca amplitude of aggregation in healthy children (p = 0.52, p < 0.05) but not in pediatric patients., Conclusions: We standardized the protocol for platelet aggregation assessment by LaSca and characterized the influence of preanalytical and analytical variables on it., (© 2024. Japanese Society of Hematology.)

The renal glomerulus is a unique structure that distinguishes the nephrons of vertebrates from the nephridia of invertebrate animals, providing a direct link between the circulatory and excretory systems and the most effective control of the composition of the internal environment due to significant intensification of filtration. Here, we address the modern ideas on the structure of the glomerular filtration barrier (GFB) in representatives of all major vertebrate taxa (cyclostomes, fish, amphibians, reptiles and birds, mammals) with a focus on the significance of the charge of GFB components for its selectivity. We also describe the approaches to probing the contribution of anionic glomerular components to preventing the loss of plasma proteins, and consider the main functional models of the glomerular filter available in the literature. We demonstrate that the negative charge is a distinctive feature of the glomerular filter in all vertebrates. A multiple increase in the glomerular filtration rate (from lower vertebrates to birds and mammals) was accompanied by a number of structural alterations that ensured the passage of a significant volume of water and low molecular weight solutes through the GFB, e.g., an increase in the number and ordering of glomerular capillary endothelial fenestrae, thinning of the glomerular basement membrane, and total exclusion of cellular elements from its composition. A comparative physiological analysis of the data on the GFB in diverse vertebrate taxa provides a strong validation of the electrokinetic glomerular filtration model, as it explains most convincingly the importance of the evolutionarily conserved structure of podocytes and the role of overall fixed negative charges in the filter wall for preventing the loss of macromolecules (primarily proteins) from blood at different ultrafiltration intensities. [ABSTRACT FROM AUTHOR]

Activation of the cAMP pathway by β-adrenergic stimulation and cGMP pathway by activation of guanylate cyclase substantially affects red blood cell (RBC) membrane properties in mammals. However, whether similar mechanisms are involved in RBC regulation of lower vertebrates, especially teleosts, is not elucidated yet. In this study, we evaluated the effects of adenylate cyclase activation by epinephrine and forskolin, guanylate cyclase activation by sodium nitroprusside, and the role of Na + /H + -exchanger in the changes of osmotic fragility and regulatory volume decrease (RVD) response in crucian carp RBCs. Western blot analysis of protein kinase A and protein kinase G substrate phosphorylation revealed that changes in osmotic fragility were regulated via the protein kinase A, but not protein kinase G signaling pathway. At the same time, the RVD response in crucian carp RBCs was not affected either by activation of adenylate or guanylate cyclase. Adenylate cyclase/protein kinase A activation significantly decreased RBC osmotic fragility, i.e., increased cell rigidity. Inhibition of Na + /H + -exchanger by amiloride had no effect on the epinephrine-mediated decrease of RBC osmotic fragility. NO donor SNP did not activate guanylate cyclase, however affected RBCs osmotic fragility by protein kinase G-independent mechanisms. Taken together, our data demonstrated that the cAMP/PKA signaling pathway and NO are involved in the regulation of crucian carp RBC osmotic fragility, but not in RVD response. The authors confirm that the study has no clinical trial., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Exploring biomarkers for easy and reliable diagnosis of periprosthetic joint infection (PJI) has attracted an increasing attention. Coagulation parameters have been found to be associated with infections, but their role in diagnosing PJI is not well understood. The aim of this study was to explore the diagnostic value of coagulation parameters in PJI.Methods: We retrospectively recruited patients who underwent revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) from January 2014 to December 2020. Patients were grouped into PJIs or non-PJIs, and PJIs were further divided into culture positive and culture negative groups. The diagnostic value of coagulation parameters including fibrin degradation product (FDP), D-dimer, platelet count (PC), and platelet count to mean platelet volume ratio (PVR) was evaluated by using receiver operating characteristic curve, in comparison with traditional biomarkers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).Results: A total of 186 patients including 136 THA and 50 TKA were studied. There were 105 PJI and 81 non-PJI patients. The coagulation parameters showed an inferior performance to CRP and ESR, with the area under the curve (AUC) of FDP, D-dimer, PC, PVR, CRP, and ESR being 0.805, 0.571, 0.703, 0.704, 0.882, and 0.824, respectively. The diagnostic performance of those coagulation parameters was similar in THA and TKA PJIs and was not superior to ESR or CRP in either culture-positive or culture-negative PJIs.Conclusion: Coagulation parameters FDP, D-dimer, PC, and PVR are of limited value for the diagnosis of periprosthetic joint infection in both THA and TKA patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to obtain the information about kidney evolution in Huso huso. According to the results on the 1st (day of post hatching (dph)), the pronephros with collecting canal and hemato-poietic tissue was distinguished. On the 3rd (dph), the primordial mesonephric tubules, rounded cell clusters, and a primary coelom cavity were observed. On the 6th (dph), the pronephros was gradually degenerated and changed to mesonephros. On the 15th (dph), the collecting canal was resembled as a small canal, and three parts, head, body, and caudal, could be distinguished in the kidney. The tubules were differentiated to proximal, distal, and collecting tubules. On the 21st (dph), the structure was similar to the 15th (dph), but with decrease of hemato-poietic tissue and developed of renal corpuscles. SPSS ANOVA version 19 was used for statistical analysis. According to stereological results in H. huso from the 1st (dph) to 21st (dph), the total volume of kidney was significantly increased ( P < 0.05). [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used antitumor agent; however, tumor resistance and severe side effects limit its use. It is well accepted that cisplatin toxicity can be modulated in vitro in cell cultures by copper salts. In the present work, mice with different blood serum copper status were treated with a single intraperitoneal cisplatin injection at a dose of 5 mg/kg, monitored for 3 days in metabolic cages and analyzed for renal function. Both copper-deficient and copper-overloaded mice displayed more severe early proteinuria and retarded platinum excretion than control mice. The effects of copper status on cisplatin-induced nephrotoxicity are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate whether upregulated p21, a cell cycle-inhibitory protein, contributes to cisplatin (CDDP)-induced acute renal failure (ARF) and to acquired resistance to rechallenge injury with CDDP in rats. ARF was induced in rats by injection of CDDP (5 mg/kg) and rechallenge injury to CDDP by the same dose of CDDP 14 days after the first CDDP injection. Rats were treated with p21 antisense oligodeoxynucleotide (ODN) or its vehicle, p21 sense ODN, every 36 h from days 0 to 5 for single CDDP and from days 13 to 19 for rechallenge injury and killed at day 3, 5, 16, or 19. The uptake of FTTC-labeled p21 antisense ODNs by cortical proximal tubule (PT) cells was much greater than by PT cells in the outer stripe of outer medulla (OSOM). Administration of antisense induced partial downregulation of p21 mRNA and protein levels in whole kidneys with single CDDP treatment and its rechallenge injury. Antisense significantly aggravated PT necrosis and decreased the number of p21-positive PT cells in the cortex but not in the OSOM in both CDDP-induced ARF and its rechallenge injury. However, antisense did not alter serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Our findings suggested that p21 plays, at least in part, a cytoprotective role in cortical PTs exposed to CDDP, although this does not contribute to renal dysfunction when judged by Scr and BUN levels. Because antisense may not adequately be taken up and/or function in PTs in the OSOM, the role of p21 in PTs in the OSOM in CDDP-induced ARF remains to be clarified. [ABSTRACT FROM AUTHOR]

Previous studies have concluded that a juxtaglomerular apparatus evolved in phylogenetic groups 'higher' than elasmobranch fishes. The present study shows for the first time a distinct juxtaglomerular apparatus in four marine elasmobranchs, the spiny dogfish ( Squalus acanthias), the smooth dogfish ( Mustelus canis), the little skate ( Raja erinacea), and the cownose ray ( Rhinoptera bonasus). Serial semithin sections of these fishes' kidneys reveal the four morphological components of a juxtaglomerular apparatus at the vascular pole of the renal corpuscle: (1) an afferent arteriole surrounded by smooth muscle cells which have granules containing a material exhibiting a periodic substructure comparable to that of renin granules in higher vertebrates; (2) an efferent arteriole usually devoid of smooth muscle cells but having pericyte-like cells; (3) a macula densa portion of the distal tubule juxtaposed between the afferent and efferent arterioles; and (4) elongated, fusiform cells (Goormaghtigh cells), which are in continuity with similar cells of the abundant intra-glomerular mesangium, and fill the space bordered by the distal tubule and by the afferent and efferent vessels. The distal tubule, from the site where it lies close to the afferent arteriole, moves directly toward the urinary pole, frequently indenting the renal corpuscle. Within this indentation, the tubule may be flanked by the efferent vessel, by the extraglomerular mesangium, or by Bowman's capsule only. Facing these structures the tubular epithelial cells possess basally dilated intercellular spaces. Endothelial cells of the efferent vessel(s) are fenestrated, possessing pores which are closed by a diaphragm. Conclusion: marine elasmobranch fish possess the morphological components of a juxtaglomerular apparatus which suggests that these fishes, like most other vertebrates, possess a renin-angiotensin system and a glomerulartubular feedback mechanism. [ABSTRACT FROM AUTHOR]

Presents a study on the effects of sudden changes in salinity on the metabolic activity in terms of oxygen consumption of the spotted sea bass at the Korea Ocean Research and Development Institute. Methodology of the study; Results and discussion; Conclusion.

Cisplatin is an active cytostatic that became successful in the treatment of several types of solid tumours after its nephrotoxic potential was controlled by hydration and diuresis. Thiol compounds were tested to reduce further cisplatin-induced nephrotoxicity. Thiosulphate is rapidly excreted by the kidneys and protects against cisplatin-induced nephrotoxicity by inactivating reactive platinum species in the kidney. Due to inactivation of cisplatin in the circulation, thiosulphate also interferes with its antitumour activity. Therefore, it is mainly used in two-route schedules, whereby cisplatin is delivered locally to the tumour (i.p. or i.a.) while systemic (i.v.) thiosulphate protects the kidneys. Diethyldithiocarbamate was shown to protect against cisplatin-induced nephrotoxicity in several animal models by reversing cellular damage. However, in the clinic it has been less successful, partly due to its central nervous system toxicity. The endogenous thiol compounds glutathione and metallothionein have been shown to reduce cisplatin-induced toxicity both in animal models and in clinical trials. However, the results are rather preliminary and a reduction in therapeutic efficacy may be expected, for both glutathione and metallothionein have been reported to be involved in platinum resistance. The thioether methionine has been shown to reduce cisplatin-induced nephrotoxicity in animal models but it has not yet been tested in the clinic. Cisplatin-induced acute emesis can be sufficiently controlled with a new class of 5-hydroxytryptamine-3 (5HT3)-receptor blockers, but delayed emesis remains a problem. High-dose cisplatin regimens with protection of the kidneys induces ototoxicity, peripheral neuropathy and myelotoxicity, which become dose-limiting. Neurotoxicity was partly reversed by the neurogenerative agent ORG2766, but this agent does not reduce other cisplatin-induced toxicities. Therefore, an agent capable of protecting multiple non-tumour tissues is needed. Carboplatin is a second-generation analogue of cisplatin with less nephro-, neuro- and ototoxicity. Carboplatin is at least as active as cisplatin at its maximum tolerated dose, which is defined by its myelotoxicity. Protection from carboplatin-induced myelotoxicity may be controlled by autologous bone marrow transplantation and/or hematopoietic growth factor infusions. High-dose carboplatin schedules may cause nephrotoxicity, neurotoxicity and ototoxicity. Again, the protection of multiple non-tumour tissues is needed. WR2721 appears to be such a modulating agent capable of protecting multiple non-tumour tissues. It was shown to be preferentially metabolized and taken up as the thiol metabolite WR1065 by non-tumour tissues as compared with (hypoxic) solid tumours. It was shown to protect mice from cisplatin-induced nephrotoxicity and from cisplatin- and carboplatin-induced myelotoxicity without interfering with the antitumour activity.(ABSTRACT TRUNCATED AT 400 WORDS) [ABSTRACT FROM AUTHOR]

An examination of the comparative nephrotoxicity in the rat of cisplatin, its hydrolysis product (mostly cis-[Pt(NH3)2Cl(H2O)]+ under the conditions applied), and cis-[Pt(NH3)2(guanosine)2]2+ revealed that these compounds differed significantly in the extent of renal damage they produced following their i.v. injection in Sprague-Dawley rats. The hydrolysis product was found to be the most toxic of the three complexes studied and produced nephrotoxicity at doses lower than those at which cisplatin was nephrotoxic. Under the conditions used, the i.v. administration of cis-[Pt(NH3)2(guanosine)2]2+ resulted in no observable signs of nephrotoxicity at levels at which an equimolar dose of cisplatin produces clear evidence of renal function impairment and morphological alterations. The nephrotoxicity of these complexes appears to be generally related to the ease with which they undergo nucleophilic substitution reactions. The lack of substantial nephrotoxicity found for cis-[Pt(NH3)2(guanosine)2]2+ suggests that the products resulting from the action of the DNA repair processes on platinated DNA do not contribute significantly to the nephrotoxicity of cisplatin. Renal platinum levels found following the administration of these compounds correlated with the degree of nephrotoxicity produced by each compound, but no general correlation of nephrotoxicity and renal platinum levels was found. The nephrotoxicity of cis-[Pt(NH3)2Cl(H2O)+ on a molar basis was estimated to be approximately 3 times as great as that of cisplatin itself. [ABSTRACT FROM AUTHOR]

The effects of a seawater challenge on coho salmon Oncorhynchus kisutch, previously exposed to didecyldimethyl ammonium chloride (DDAC) were examined. In one experiment, salmon were exposed to three sublethal concentrations of DDAC over three durations followed by aa 24-h seawater challenge in a computer-con trolled, intermittent-flow respirometer to measure effects on several biochemical variables. After a 144-h dose, plasma cortisol, glucose, and gill Na +/K +- ATPase activity were significantly increased at a nominal DDAC concentration of 0.2 mg/L. In the second experiment, animals were exposed to five different concentrations for 24 h followed by a 24-h seawater challenge. Plasma cortisol was significantly increased at thehighest exposure concentration (0.75 mg/L). Plasma Na + was significantly elevated at exposure concentrations of 0.3, 0.5, 0.65, and 0.75 mg/L. Gill Na +/K +-ATPase activitywas significantly reduced at exposure concentrations of 0.65 mg/L and 0.75 mg/L. The use of the seawater challenge to demonstrate sublethal physiological stress and impaired osmoregulatory capacity in coho salmon smolts is relevant to salmonid life history in terms of the animal's transition from freshwater to seawater during its seaward migration. [ABSTRACT FROM AUTHOR]