The factors that determine the manifestation of uremic poisoning during the development of chronic kidney failure

To specify factors determining the intensity of uremic intoxication, 86 patients with chronic glomerulonephritis were examined without regard for exacerbation at different stages of chronic renal failure. Microcolumn gel chromatography was used to measure the content of medium-size molecules in the blood serum, urine, gastric and intestinal juice of the patients and 22 mongrel dogs before and after bilateral nephrectomy. It has been established that as the mass of acting nephrons decreases, the content of "medium-size" molecules in the blood serum and intestinal juice rises, being unchanged in gastric juice. At the same time the urinary clearance of the given group of substances declines. It is assumed that in stage I chronic renal failure, enhancement of the excretion of "medium-size" molecules in the proximal third of the small intestine is made for by hyperfiltration of intact nephrons. The appearance of the clinical symptomatology in stage II and III chronic renal failure is determined by intensification of absorption of uremic toxins by the intestine, associated with a fall of their urinary clearance. The necessity of early administration of the low-protein diet combined with enterosorbents is stressed.     

Study of drying process of diacetone-2-keto-L-gulonic acid hydrate as an object for process management

Pharmaceutical Chemistry Journal -     

Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.     

Crotoxin acceptor protein isolated from Torpedo electric organ: binding properties to crotoxin by surface plasmon resonance.

Crotoxin, a potent neurotoxin from the South American rattlesnake Crotalus durissus terrificus, is a heterodimeric phospholipase A(2) (EC 3.1.1.4), which blocks the release of acetylcholine from peripheral neurons. We previously have suggested the existence of a 48 kDa crotoxin-binding protein in the presynaptic membranes of the electric organ of Torpedo marmorata. Here, we report the purification and characterization of this protein that we called the crotoxin acceptor protein from Torpedo (CAPT). The membranes of electric organs from Torpedo were solubilized with a detergent (4% (w/v) Triton X-100) and CAPT was isolated by affinity chromatography on a crotoxin column. SDS-PAGE showed that the purified protein was homogeneous and cross-linking studies with radioiodinated crotoxin confirmed that it had retained its toxin-binding properties. The purified CAPT has similar molecular mass as crocalbin, a crotoxin-binding protein isolated from porcine brains, yet anti-crocalbin antiserum failed to recognize CAPT. Surface plasmon resonance biosensor technology was used to measure the specific interaction between crotoxin and solubilized CAPT. Using this method, it was possible to follow CAPT throughout the purification procedure. As well, an apparent dissociation constant (K(d)(app)) of 3.4 nM was calculated for the interaction of pure CAPT and crotoxin from the dissociation rate constant (k(off)=1.2 x 10(-2)s(-1)) and the association rate constant (k(on)=3.5 x 10(6)M(-1)s(-1)).     

The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task

The study examined the effects of modulation of dopamine D2 receptors-mediated neurotransmission in the rat's prefrontal cortex (PFC) on storage and executive components of working memory. Rats were trained on delayed (delay interval, 3 s) and non-delayed choice in a U-maze. The prominence of proactive interference was evaluated by sorting errors in a current trial on the basis of animal reactions in a preceding trial. The erroneous runs to the same arm of the maze as in the previous trial were identified as the repetitions (RE) and the erroneous runs to the other arm in comparison with the previous trial were classified as alternations (AE). The bilateral microinfusion of D2 agonists PPHT (0.004 microg, 0.04 microg, 0.4 microg/1 microl) into medial wall of the PFC produced a dose-dependent increase in the error rate of the delayed-response task and did not influence non-delayed choice. In delay condition PPHT enhanced the perseverative tendencies (the rate of RE was significantly higher than the rate of AE), in non-delayed choice the erroneous performance was mainly represented by AE. In contrast, the infusion of D2-receptor antagonist sulpiride (0.03 microg, 0.3 microg, 3 microg/1 microl) increased the accuracy of delayed choice and changed the mode of intertrial dependence-rats made significantly more AE than RE. The results are discussed in terms of the involvement of D2 receptor dependent transmission of the PFC in different cognitive processes related to the delayed performance in U-maze (within-trial short-term storage of information versus dynamic control of between-trials working memory processing).     

Naja melanoleuca cobra venom contains two forms of complement-depleting factor (CVF)

Two forms of complement-depleting cobra venom factor (CVFm1 and CVFm2), possessing molecular masses of 142.6 kDa (CVFm1) and 143.1 kDa (CVFm2), according to MALDI mass-spectrometry, were isolated from the Naja melanoleuca cobra venom. As shown by polyacrylamide gel electrophoresis in the presence of SDS, both forms similarly to factor from the Naja kaouthia cobra venom (CVFk) consist of three polypeptide chains with molecular masses of about 70, 50, and 30 kDa, the two large subunits being glycosylated. As determined by MALDI mass-spectrometry, 30 kDa subunits of CVFm1 and CVFm2 have considerably different finger-prints of tryptic digests that suggests differences in their amino acid sequences. A study of activity in vivo has shown no significant differences in C3 consumption by CVFm1, CVFm2 and CVFk in mouse blood. However, as shown by an immunoassay method, they differ in their ability to activate the complement system via C3 conversion, the ratio of these activities for CVFm1:CVFm2:CVFk being 2.5:1.6:1. Kinetic studies using a hemolytic test showed that complement depletion by CVFm1 is faster than that by CVFm2. Thus, for the first time the presence in a single venom of two forms of CVF differing by both amino acid sequence and biological activity has been shown.     

A Feasibility Study of High-Entropy Alloy Coating Deposition by Detonation Spraying Combined with Laser Melting

In this work, a new two-stage approach to the deposition of high-entropy alloy coatings is proposed. At the first stage, a composite precursor coating is formed by detonation spraying of the metal powder mixtures. At the second stage, the precursor coating is re-melted by a laser, and the formation of multi-component solid solution phases can be expected upon solidification. The feasibility of the proposed approach was validated using three different mixtures of Fe, Ni, Cu, Co and Al powders. It was shown that detonation spraying allows forming composite coatings with a uniform distribution of the lamellae of different metals. The results of the structural analysis of the laser-treated coatings suggest that complete alloying occurred in the melt and face-centered cubic solid solutions formed in the coatings upon cooling.     

Transmission of Diverse Variants of Strawberry Viruses Is Governed by a Vector Species

Advances in high-throughput sequencing methods have boosted the discovery of multistrain viral infections in diverse plant systems. This phenomenon appears to be pervasive for certain viral species. However, our knowledge of the transmission aspects leading to the establishment of such mixed infections is limited. Recently, we reported a mixed infection of a single strawberry plant with strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). While SCV and StrV-1 are represented by two and three molecular variants, respectively, SmoV has three different RNA1 and RNA2 segments. In this study, we focus on virus acquisition by individual adult aphids of the Aphis gossypii, Aphis forbesi and Chaetosiphon fragaefolii species. Single-aphid transmission trials are performed under experimental conditions. Both different viruses and individual virus strains show varying performances in single aphid acquisition. The obtained data suggests that numerous individual transmission events lead to the establishment of multistrain infections. These data will be important for the development of epidemiological models in plant virology.