Динаміка та аналіз виробничого травматизму та професійних захворювань в Україні

Кожного року в Україні на виробництві травмується понад 10 тис. людей, з них гине понад 600 осіб. Оптимістична, на перший погляд, статистика, за якою травматизм на виробництві за роки незалежності України зменшився в десять разів, виявляється не такою вже й оптимістичною, коли аналізуються конкретні цифри

Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is associated with a significant polyuria and natriuesis as well as increased plasma aldosterone and anti-diuretic hormone arginine vasopressin (AVP). This study aimed to determine whether diabetic kidneys compensate for the urinary sodium and water losses by increasing apical targeting of epithelial sodium channel (ENaC) subunits and aquaporin-2 (AQP2) in the collecting duct, in addition to the previously observed changes in ENaC subunit protein expression in different kidney zones. METHODS: Female rats were investigated 2 weeks after induction of DM by streptozotocin administration. Kidneys were examined by immunohistochemisty and semiquantitative immunoblotting. RESULTS: We demonstrated that the protein expression of renal AQP2, Ser-256 phosphorylated AQP2, AQP3, beta- and gamma-ENaC (but not alpha-ENaC) increased consistently with an increased AVP response. In contrast, there were no significant changes in the relative apical targeting of beta-, gamma- and alpha-ENaC, and the shift in the molecular weight of gamma-ENaC from 85 kDa to 70 kDa was not observed despite increased plasma aldosterone levels. These results were supported by changes in the functional data showing increased solute-free water reabsorption, increased fractional excretion of sodium and an unchanged ratio of potassium to sodium in the urine. CONCLUSIONS: The data demonstrate that diabetic kidneys have a reduced sensitivity to the anti-natriuretic action of elevated plasma aldosterone levels with no relative increase in ENaC subunit apical targeting, whereas there is increased expression of beta- and gamma-ENaC, which alone may play a role in the increased sodium reabsorption in the kidney in DM

PCA score scatter and loading plots of metabolites quantification through targeted profiling of plasma at 4 weeks (A, B) and 8 (C, D), respectively.

<p>The loading plots were produced from the score plots which showed a significant differentiation between the two groups. CKD, chronic kidney disease.</p

¹H chemical shift and relative concentrations of metabolites observed in plasma from CKD and sham-operated groups.

<p>Letters in parentheses denote the peak multiplicities: s, singlet; d, double; t, triplet; dd, doublet of doublet; m, multiplets and br, broad; The fold change ratio indicates the ratio of relative concentrations between CKD and sham-operated groups; Statistical analysis was performed by Mann-Whitney test and Welch's t-test to assess the statistical significance between CKD vs. sham-operated groups; *, **, *** indicate bonferroni corrected <i>P</i><0.05, <0.01, and <0.001, respectively.</p

A diagram for the changes in plasma metabolites in CKD.

<p>The metabolite profiles of plasma in rats with CKD showed significantly increased levels of lactate, pyruvate, acetoacetate, β-hydroxybutyrate, glutamine, glutamate, and citrate. Metabolic acidosis is commonly complicated in CKD, due to both decreased net acid excretion and impaired regeneration of bicarbonate. This could change the citrate reabsorption in renal tubular cells, which metabolism generates HCO₃^– ions producing an alkalinizing effect. Moreover, increased protein breakdown and insensitivity to epinephrine in muscle in CKD could induce the increases of alanine, glutamate, and glutamine in plasma.</p

Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots and permutation tests of PLS-DA obtained from the ¹H NMR spectra of plasma at 4 weeks (A, C, E) or 8 weeks (B, D, F) after 5/6 nephrectomy and sham operation, demonstrating a clear differentiation between the two groups.

<p>CKD, chronic kidney disease.</p

Orthogonal partial least-squares discriminant analysis (OPLS-DA) score and coefficient loading plots derived from the ¹H NMR spectra derived from plasma at 4 weeks (A, C) or 8 weeks (B, D) after 5/6 nephrectomy and sham operation.

<p>The OPLS-DA coefficient loading plot shows a significant difference in the metabolite levels between the two groups. 1, VLDL/LDL CH₃; 2, β-hydroxybutyrate; 3, VLDL/LDL (CH₂)_n; 4, Alanine; 5, Lipid CH₂CH₂C = O; 6, Lipid CH₂CH₂C = C; 7, Arginine; 8, Acetate; 9, N-acetylglycoproteins; 10, Methionine; 11, Lipid CH₂C = O; 12, Acetoacetate; 13, Glutamine/Glutamate; 14, Citrate; 15, Trimethylamine (TMA); 16, Choline; 17, Trimethylamine-N-oxide (TMAO); 18, O-phosphocholine; 19, Glucose/Maltose; 20, Lactate; 21, Urea; and 22, Formate. CKD, chronic kidney disease.</p

Quantification of changes of plasma metabolites in rats with CKD at 4 weeks and 8 weeks after 5/6 nephrectomy, respectively.

<p>*, **, *** indicate bonferroni corrected <i>P</i><0.05, <0.01, and <0.001, respectively.</p

Changes of renal functions.

<p>n, number of rats; BW, body weight; RK, right kidney in sham-operated control rats and remnant kidney in CKD rats; p-osm, plasma osmolality; p-Na, plasma sodium, p-K, plasma potassium, p-urea nitrogen, plasma urea nitrogen; p-Creat, plasma creatinine. *<i>P</i><0.05.</p

Representative 600 MHz ¹H nuclear magnetic resonance (NMR) spectra of plasma obtained from 5/6 nephrectomized CKD rats and sham-operated control rats at 4 weeks (A) or 8 weeks (B) after 5/6 nephrectomy and sham operation.

<p>1, VLDL/LDL CH₃; 2, Leucine/Isoleucine; 3, Valine; 4, β-hydroxybutyrate; 5, VLDL/LDL (CH₂)_n; 6, Alanine; 7, Lipid CH₂CH₂C = O; 8, Lipid CH₂CH₂C = C; 9, Arginine; 10, Acetate; 11, N-acetylglycoproteins; 12, Glutamine; 13, Methionine; 14, Lipid CH₂C = O; 15, Acetoacetate; 16, Pyruvate; 17, Glutamate/Glutamine; 18, Citrate; 19, Dimethylamine (DMA); 20, Trimethylamine (TMA); 21, Creatinine; 22, Choline; 23, Trimethylamine-N-oxide (TMAO); 24, O-phosphocholine; 25, Myo-inositol; 26, Glycine; 27, Glucose/Maltose; 28, Lactate; 29, Urea; and 30, Formate. CKD, chronic kidney disease.</p