[Correlation adaptometry as a method of renal assessment and rganismic interaction with closed kidney injury].

INTRODUCTION: The kidney concussion causes damage to intraorganic angioarchitectonics, microcirculatory disorders, as a consequence - a decrease in functional capabilities of the organ, affecting inter-system interrelationships in the organism. PURPOSE OF THE STUDY: to evaluate the interaction of renal functions and hemodynamic homeostasis by the method of correlation adaptometry in groups of victims after closed kidney injury with different areas of organ damage. MATERIALS AND METHODS: The study involved 114 patients with isolated comotional kidney injury Grade I-III, with the involvement of the 1st organ segment - 30 (26.0%), 2 segments - 26 (22.8%), 3 segments - 58 (51.2%). A radionuclide study was performed, the parameters of hemodynamic homeostasis were determined, and the functional stress index (IFN) was calculated. The assessment of the contingency of the analyzed parameters was carried out on the basis of correlation analysis, and the degree of connectivity of the parameters was estimated using the correlation graph. RESULTS: It was found that with an increase in the number of damaged segments of the kidney, the main physiological parameters of the organ regress together with an increase in functional deficit. Vector decrease of functional capabilities of the organism by IFN was noted: from satisfactory adaptation (when kidney segment 1 was injured); through tension of adaptation mechanisms (2 segments); to unsatisfactory adaptation (3 segments), when homeostasis was preserved with significant tension of regulatory systems. The correlation graph was recorded at the level of 11,96 and 11,57 in trauma of the 1st and 2nd segments of the kidney. In case of damage to 3 segments of the organ, the weight of the correlation graph increases - 16,97, which indicates pronounced structural and functional maladaptive disorders in the activity of the organ. CONCLUSION: assessment of the conjugacy of indicators of renal and organism interaction, indicates the greatest tension of the reserves of functional potential of the organism in case of damage of 3 segments of the kidney.

[Mechanical kidney injury what urologists miss in medical records].

The article provides a brief description of the main terms and concepts of kidney damage used in forensic medicine and urology, with a list of requirements for the description and formation of a clinical diagnosis when maintaining primary medical documentation. The importance of a unified approach in objective interpretation in the expert assessment of kidney injuries is substantiated.

[The closed injury of a kidney and posttraumatic arterial hypertension: condition of study of a problem].

The article summarizes the worlds information on the history of the study, classification, management tactics of patients with closed kidney injury, analysis of the development of post-traumatic arterial hypertension (AH). In a research of renovascular and renoparenchymal mechanisms of a syndrome of AG there is no consensus of dependence on severity of injury of a kidney, a type of treatment, about the temporary period between getting injured and emergence of a complication that defines relevance of further studying.

[Cluster analysis of the main parameters of homeostasis with kidney injury].

INTRODUCTION: Damage to the structure of the kidney in blunt trauma leads to disruption of angioarchitectonics and microcirculation. OBJECTIVE: to establish the dependence of renal function and circulatory system on the severity of injury and the type of blunt renal trauma. MATERIALS AND METHODS: The clinical and laboratory homeostasis tests were carried out in 127 patients with the kidney parenchyma contusion and ruptures in the nearest posttraumatic period. RESULTS: Five factors and five clusters of signs were revealed. Tissue level reactions predominate in case of contusion injury of less than half of the organ. Trauma of more than half of the kidney and parenchyma rupture involve the circulatory system in the response reaction. CONCLUSION: the volume/area and type of damage are predictors in the level of the functional response of the organism - organ or organismal.

[The application of superselective embolization of renal vessels in case of bleeding after percutaneous nephro- lithotomy].

BACKGROUND: Bleeding, injures to surrounding organs and pleura are serious complications of percutaneous nephrolithotripsy. The inefficiency of hemostatic therapy is an indication for superselective embolization of the renal vessels. This technique demonstrates the high efficiency in case of postoperative bleeding. AIM: To develop a treatment algorithm and to evaluate an efficiency of superselective embolization of the renal vessels, based on the results of treatment of postoperative complications, which are associated with bleeding. MATERIALS AND METHODS: A retrospective analysis of 1375 patients treated from January 2011 to December 2018 for large (over 1.5 cm) and staghorn renal stones was performed. A number of patients had various complications in the early postoperative period, which were graded according to the Clavien-Dindo classification, including bleeding due to intraoperative damage to renal vessels, which required additional interventions. The treatment strategy was based on the assessment of volume and severity of blood loss as well as the hemodynamic stability. RESULTS: Based on the severity of bleeding and hemodynamic stability, the treatment algorithm was developed. The analysis of the results of superselective embolization of renal arteries demonstrates the high effectiveness of this technique in case of postoperative bleeding. CONCLUSION: Superselective embolization is an effective method of hemostasis in case of postoperative bleeding. The proposed algorithm allows for early coordination of therapeutic measures depending on the severity of bleeding and the patients condition in order to evaluate the risk of continued bleeding and the determine the optimal treatment strategy.

A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

BACKGROUND: Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity. METHODS: BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade ≥3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade ≥3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported. RESULTS: A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade ≥3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%. CONCLUSIONS: Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757].

Inhibition of family II pyrophosphatases by analogs of pyrophosphate and phosphate.

Imidodiphosphate (the pyrophosphate analog containing a nitrogen atom in the bridge position instead of oxygen) is a potent inhibitor of family II pyrophosphatases from Streptococcus mutans and Streptococcus gordonii (inhibition constant Ki approximately 10 microM), which is slowly hydrolyzed by these enzymes with a catalytic constant of approximately 1 min(-1). Diphosphonates with different substituents at the bridge carbon atom are much less effective (Ki = 1-6 mM). The value of Ki for sulfate (a phosphate analog) is only 12 mM. The inhibitory effect of the pyrophosphate analogs exhibits only a weak dependence on the nature of the metal ion (Mn, Mg, or Co) bound in the active site.

Determination of Mn(II) and Co(II) with Arsenazo III.

Complex formation between Arsenazo III and Mn2+ and Co2+ at equilibrium has been investigated at pH 7.2, and the stoichiometry and stability of the complexes have been determined. The data indicate that Arsenazo III is suitable for determination of Mn2+ and Co2+ on the micromolar scale. The dissociation constants of the phosphate complexes of Mn2+ and Co2+ at pH 7.2 were estimated with Arsenazo III as 3.6 and 10 mM, respectively.

Fluoride effects along the reaction pathway of pyrophosphatase: evidence for a second enzyme.pyrophosphate intermediate.

The fluoride ion is a potent and specific inhibitor of cytoplasmic pyrophosphatase (PPase). Fluoride action on yeast PPase during PP(i) hydrolysis involves rapid and slow phases, the latter being only slowly reversible [Smirnova, I. N., and Baykov, A. A. (1983) Biokhimiya 48, 1643-1653]. A similar behavior is observed during yeast PPase catalyzed PP(i) synthesis. The amount of enzyme.PP(i) complex formed from solution P(i) exhibits a rapid drop upon addition of fluoride, followed, at pH 7.2, by a slow increase to nearly 100% of the total enzyme. The slow reaction results in enzyme inactivation, which is not immediately reversed by dilution. These data show that fluoride binds to an enzyme.PP(i) intermediate during the slow phase and to an enzyme.P(i) intermediate during the rapid phase of the inhibition. In Escherichia coli PPase, the enzyme.PP(i) intermediate binds F(-) rapidly, explaining the lack of time dependence in the inhibition of this enzyme. The enzyme.PP(i) intermediate formed during PP(i) hydrolysis binds fluoride much faster (yeast PPase) or tighter (E. coli PPase) than the similar complex existing at equilibrium with P(i). It is concluded that PPase catalysis involves two enzyme.PP(i) intermediates, of which only one (immediately following PP(i) addition and predominating at acidic pH) can bind fluoride. Simulation experiments have indicated that interconversion of the enzyme.PP(i) intermediates is a partially rate-limiting step in the direction of hydrolysis and an exclusively rate-limiting step in the direction of synthesis.

The electrophilic and leaving group phosphates in the catalytic mechanism of yeast pyrophosphatase.

Binding of pyrophosphate or two phosphate molecules to the pyrophosphatase (PPase) active site occurs at two subsites, P1 and P2. Mutations at P2 subsite residues (Y93F and K56R) caused a much greater decrease in phosphate binding affinity of yeast PPase in the presence of Mn(2+) or Co(2+) than mutations at P1 subsite residues (R78K and K193R). Phosphate binding was estimated in these experiments from the inhibition of ATP hydrolysis at a sub-K(m) concentration of ATP. Tight phosphate binding required four Mn(2+) ions/active site. These data identify P2 as the high affinity subsite and P1 as the low affinity subsite, the difference in the affinities being at least 250-fold. The time course of five "isotopomers" of phosphate that have from zero to four (18)O during [(18)O]P(i)-[(16)O]H(2)O oxygen exchange indicated that the phosphate containing added water is released after the leaving group phosphate during pyrophosphate hydrolysis. These findings provide support for the structure-based mechanism in which pyrophosphate hydrolysis involves water attack on the phosphorus atom located at the P2 subsite of PPase.