[The kinetic parameters of retainment and release of deposited in human tissue structures calcium].

The analysis of retainment and release kinetics of deposited in tissue structures calcium was made in the hypercalcemic conditions in 28 healthy volunteers (22 males and 6 females) of the age of 33 ± 6.5 years via drip infusion (Groups 1, 2) and in 9 individuals (3 males and 6 females) in 12 trials via stream infusion (Group 3). By the end of each hour after the termination of calcium infusion the amount of calcium retained in tissues was calculated (Mtis./kg); the parameters of its binding (specific buffer volume--ß3 sp, association constant--Ka, number of binding centers--n) were established using the Langmuir and Scetchard coordinates. The Group 1 volunteers (n = = 12) showed a section of positive cooperativity (a direct regression on Sketchard coordinates, Hill coefficient 3.36 ± 1.63) and 2 sections of the consecutive calcium separation from one set of noninteracting centers. 5 volunteers of Group 2 and 8 volunteers of Group 3 demonstrated a slight calcium delivery to tissues after 1 hour of observation which then followed for 2 volunteers of Group 2 and for 2 volunteers of Group 3. Other volunteers of Groups 2 and 3 showed a release of tissue-deposited calcium via the mechanism of the consecutive separation from one set of noninteracting centers with ßsp 3 times less and Ka 7 times higher than with the calcium infusion. The excretion of calcium in urine was the highest in Group 1 and the lowest in Group 3. The [Ca2+] and Mtis./kg values were normalized in Groups 1 and 2 the next morning and in Group 3 after 2-3 hours of observation. An assumption was made about the relationship between the tissue and kidney [Ca2+] normalizing mechanisms with hypercalcemia.

[Kinetic parameters of calcium binding to tissue structures in human acute hypercalcaemia].

Calcium binding kinetic by tissue structures was analysed in 19 health volunteers (13 men and 6 women) of the age group of 33 +/- 6.5 under conditions of acute hypercalcaemia followed by a drip i.v. infusion of calcium gluconate over 2.5 hours. At the end of each 30-minute period the calcium amount retained by tissue structures was recorded and the kinetic parameters of calcium binding were determined according to Langmuir and Scatchard. In all volunteers there was a segment of binding isotherm with positive cooperativity (direct regression in Scatchard) with analogous buffer capacity (beta) for calcium in Langmuir (0.58 +/- 0.24 L kg). One half of volunteers demonstrated cooperativity at [Ca++] 1.3-1.5, while another--at [Ca++] 1.0-1.3 mmol/L which corresponded to the differences in the association constant (Ka) and the number of interactive sites (n) with [Ca++] 1 mmol/L. Additionally, two segments of binding isotherm were detected with the successive binding of calcium to one set of noninteractive sites with similar kinetic parameters of calcium binding (beta, K(a), n). Four different curves of calcium binding in healthy volunteers were established. This study may serve as the basis for a functional diagnostic test of disorders of the tissue calcium-binding properties in different pathological conditions.

[The dynamics of biochemical markers of remodelling of bone tissue after liver transplantation].

The sample of 45 recipients (30 females and 15 males) after orthotopic transplantation of liver was examined thrice in dynamics. Three groups were formed according the resulted values of T-criterion of bone mineral density in the area of lumbar vertebrae. The bone mineral density of group A was considered as osteoporosis, of group B as osteopenia and of group C as physiologic norm. In early period (1-4 months) after orthotopic transplantation of liver gross disorders of bone metabolism were established in all recipients independently of the degree of bone mass loss. In distant period (up to 32 months) after orthotopic transplantation of liver the bone losses decreased entailing full normalization of bone metabolism in 37% of recipients with osteoporosis, 82% with osteopenia and 91% with normal bone mineral density.

[Level of aminoterminal type 1 procollagen propeptide--the bone formation marker--in the sera of healthy males].

The biochemical bone formation marker aminoterminal type 1 procollagen propeptide (total P1NP) was determined in 91 serum samples from healthy male donors aged 19 to 60 years, by using an "Elecsys Total P1NP" kit of reagents ("Roche-Diagnostics", Germany) on an "Elecsys 2010" electric chemiluminescence analyzer ("Roche-Hitachi", Japan). A relationship was found between the serum concentration of total P1NP and the age of the examined males. At the age of 19-20 years, the content of the propeptide is highest, at the age of 21-24 years, it decreased by 1.5-2 times, by the age of 30 years, there is its moderate decrease, which is then followed by its stabilization. The detected age-related changes reflect accelerated bone metabolism in young males during formation of the bone mass peak. The findings may be used as references in measuring male total P1NP on Elecsys automatic analyzers.

[Biochemical markers of bone formation in hemodialysis and after allotransplantation of cadaveric kidney].

AIM: To ascertain informative value of estimation of bone forming markers in patients on chronic hemodyalisis (CHD) and recipients of cadaveric kidney (CK). MATERIAL AND METHODS: Parathyroid hormone (PTH), beta-crosslaps (CTX), osteocalcin (OC), amino-terminal procollagen propeptide 1 (PINP), bone alkaline phosphatase (BAP), bone mineral density (BMD) were determined in 152 patients on CHD (89 males and 63 females aged 49 +/- 13 years) and 195 CK recipients (106 males and 89 females aged 42 +/- 12 years) 30 +/- 38 months after kidney transplantation. RESULTS: PTH, CTX and BAP determination specifies skeletal disease (secondary hyperparathyroidism or adynamic bone disease) in CHD patients. In patients with CK recipients osteoporosis differed from osteopenia by higher levels of PTH, CTX, OC in the absence of any differences in BAP, PINP. All bone forming markers were lower than CTX showing suppression of bone forming. Bone fractures in CK recipients' anamnesis were associated with OC and BAP decrease in men and low border of normal OC in women. Determination of bone formation and resorption markers in patients on CHD and CK recipients is of great clinical importance.

[The peculiarities of bone exchange disorder and its regulation in men after long terms following orthotopic heart transplantation and cadaveric kidney transplantation].

The study found bone exchange disorder manifested by accelerated bone resorption, retarded bone formation, and the loss of the bone mineral density (BMD) of the axial and peripheral skeleton in 19 men (39 observations) 66 +/- 44 months following orthotopic heart transplantation (OTHT) and in 92 men 45 +/- 28 months after cadaveric kidney transplantation. An accelerated bone resorption, more pronounced in cadaveric kidney (CK) recipients, is associated with hyperparathyroidism (HPT) and renal dysfunction, while bone formation retardation is associated with a decrease in insulin-like growth factor-1 level. An increase in osteoprotegerin level is of compensatory character. The prominence of HPT depends on the degree of renal dysfunction; in CK recipients it also depends on the degree of the reduction in the levels of biologically active testosterone and estradiol. Reduction in BMD of the peripheral skeleton after OTHT are associated with the degree of renal dysfunction and a decrease in free testosterone index; after CK transplantation it is associated with HPT, the cumulative dose of glucocorticoids, reduction in the levels of biologically active testosterone and estradiol, as well as sex-hormone binding globulin (SHBG); reduction in spine BMD is only associated with SHBG.

[Biochemical markers of bone metabolism and bone tissue losses after allotransplantation of the cadaveric kidney: a cross-sectional].

The biochemical markers of bone metabolism (osteocalcin (OC), C- and N-terminal procollagen I propeptides (PICP) and PINP), bone alkaline phosphatase (BALP), deoxypyridinoline (DPD), beta-crosslaps (beta-CL), bone acid phosphatase (BAP), osteoprotegerin (OPG), insulin-like growth factor I (IGF-I), and parathyroid hormone (PTH)), daily urinary calcium excretion (DUCE) (intestinal calcium absorption), and lumbar and hip bone mineral density (BMD) were determined in 195 patients (78 females and 74 males with normal function of the grafted kidney and 11 females and 31 males with chronic renal failure (CRF) 40 +/- 33 months after renal transplantation (RT). All RT recipients received triple immunosuppressive therapy (cyclosporin, prednisolone, and azathioprine). All groups showed a significant increase in resorption markers and a moderate increase in bone formation markers (except BALP), which suggested bone remodeling dissociation, as well as elevated levels of PTH and OPG and decreased DUCE and BMD in the vertebral column and hip. Increased bone metabolism and decreased intestinal calcium absorption were largely pronounced in CRF. In the majority of recipients, the BMD reduction in the vertebral column and hip was moderate (osteopenia) and only in male recipients with CRF, axial osteopenia was concurrent with peripheral osteoporosis. The main predictor of accelerated bone metabolism and BMD losses following RT was hyperparathyroidism mainly caused by decreased renal graft function. Decreased IGF-I may be a cause of bone remodeling dissociation after RT/ and the increase in OPG seems to be compensatory, which suppresses bone resorption and reduces bone losses.

[The calcium-binding properties of the plasma proteins from patients with aseptic necrosis of bone following a cadaveric kidney allograft]. / Kal'tsiisviazyvaiushchie svoistva plazmennykh belkov u bol'nykh s asepticheskimi nekrozami kostei posle allotransplantatsii trupnoi pochki.

Calcium-binding properties of plasma proteins in hypo- and hypercalcaemia, induced in vitro, were studied at late posttransplantation periods in 15 recipients of cadaveric kidney, 8 of whom showed aseptic necrosis (AN) of the femur heard. Immunosuppression included prednisolone and azathioprine with analogous mean monthly doses in all recipients. Langmuir and Scatchard analysis revealed lowering of specific and total buffer capacity of plasma proteins (beta SP., beta pr) in hypercalcemia only in AN recipients at the expense of decreased Na and increased Ka during calcium binding by independent protein sites.

[A method of calculating complexed calcium in patients with in-vitro simulated hypo- and hypercalcemia]. / Metod rascheta kompleksirovannogo kal'tsiia u bol'nykh pri modeliruemoi in vitro gipo- i giperkal'tsiemii.

Assessment of plasma protein calcium-binding capacity in disease involves measurements of Ca fractions in native plasma and its samples after in vitro stimulation of hypo- and hypercalcemia; such measurements include multiple and labor-consuming anaerobic ultrafiltration procedures. Values of Ca bound to plasma complexons and effective constants of their associations with Ca were experimentally assessed in 20 normal subjects, 7 patients before and 20 ones after kidney transplantation with the use of ultrafiltration. A method for estimation of integrated calcium in a sample lot has been developed, based on a single experimental value of integrated calcium in native plasma and the mean association constant in health. Experimental and estimated values of liganded Ca were in good correlation, this confirming the rightfulness of clinical use of the suggested method. This method essentially simplifies assessment of plasma proteins Ca-binding properties and requires lesser blood volumes.

[The functional characteristics of the calcium-regulating systems and the calcium content of the blood following a cadaveric kidney allograft]. / Osobennosti funktsional'nogo sostoianiia kal'tsiireguliruiushchikh sistem i soderzhanie kal'tsiia v krovi posle allotransplantatsii trupnoi pochki.

Total plasma calcium (Ca), Ca renal reabsorption, Ca tissue transport, parathyroid hormones and calcitonin were measured in fasting 30 recipients of a renal allotransplant, 95 healthy subjects, 9 primary hyperparathyroidism patients, 12 patients with bronchial asthma and exogenic hypercorticism. Total Ca proved normal in 26 but lowered in 4 recipients. Canalicular Ca reabsorption got enhanced in 17 recipients with high parathormone levels in 10 of them. Normal Ca reabsorption was registered in 13 recipients through parathormone elevated in 6 of them. Tissue Ca binding enhanced in its high reabsorption in the transplant. The binding did not depend either on parathormone secretion intensity or cyclosporin A treatment, being partially determined by steroid therapy. When investigated under Ca intravenous drop infusion in 20 recipients and 14 healthy subjects, Ca tissue binding confirmed its physiochemical nature and revealed in one third of the recipients impaired buffer capacity of the tissues as well as Ca retention and release rates. The impairment was related neither to changes in the basal level nor with secretion fluctuations of parathormone and calcitonin. Increased tissue Ca binding accounts for the absence of hypercalcemia in renal transplantation.

[Calcium-binding properties of tissue proteins after kidney allotransplantation]. / Kal'tsiisviazyvaiushchie svoistva tkanevykh belkov posle allotransplantatsii pochki.

The kinetics of calcium binding to tissue substrates in hypercalcaemia, induced by intravenous constant rate infusion of calcium gluconate were studied in 19 patients after renal transplantation and in 14 healthy volunteers. Langmuir, Scatchard and Hill analysis revealed the positive cooperative mechanism of calcium binding to tissue in all patients and in healthy volunteers. These results provide indirect evidence of binding of calcium to tissue proteins. The significant decrease of the values of specific buffer capacity of tissue proteins, pool of exchangeable calcium and also the effective Ka were observed in 37% of patients. These changes are proposed to play a role in the pathological calcification of vessels and soft tissues in patients after renal transplantation.

[Use of the equipment for hemodialysis in the diagnosis of calcium metabolism disorders in terminal chronic renal failure]. / Ispol'zovanie apparatury dlia gemodializa v diagnostike narushenii obmena kal'tsiia pri terminal'noi khronicheskoi pochechnoi nedostatochnosti.

As many as 18 patients with terminal chronic renal failure were treated by program hemodialysis. The initial concentration of ionized calcium in those patients' blood plasma amounted to 1.06 +/- 0.22 mmol/l. To assess function of the systems counteracting hypocalcemia, use was made of a session of hemodialysis against calcium-free dialysate. 2/3 of the patients demonstrated satisfactory function of the homeostatic system, maintained by a high secretion of PTH and involvement into regulation processes of the extraplasmic system marked by higher buffer capacities and a large pool of metabolism-capable calcium and apparently localized in the skeleton. In 1/3 of the patients, homeostatic function turned out to be dramatically impaired, which was provoked by inhibition of the secretory capacity of the parathyroid glands and manifested clinically by low tolerance to calcium losses and osteomalacia.

[The mechanisms of the disorder of calcium homeostasis in terminal kidney failure and the allotransplantation of a cadaver kidney]. / Mekhanizmy narusheniia gomeostaza kal'tsiia pri terminal'noi pochechnoi nedostatochnosti i allotransplantatsii trupnoi pochki.

Overall 34 patients with terminal renal failure (TRF) and 81 recipients of the allotransplanted cadaveric kidney (ACK) were examined. It has been established in in-vitro experiments with modulated by additions of EDTA to the plasma and CaCl2 hypo- and hypercalcemia that the magnitude of bound calcium (standardized at the concentration of ionized calcium-Ca++1 mmol/l) decreased in the blood plasma in 65 and 61% of cases. Besides protein-bound calcium dropped in 94 and 91% of cases; the total buffer capacity of the plasma and buffer capacity of proteins fell in 59 and 87% of cases in TRF and ACK, respectively. The rise of the Ca++ content on an empty stomach seen in 21 out of 99 patients with TRF and in 42 out of 98 recipients of the ACK was caused by a decrease of calcium binding in the blood plasma, not made for by the fall of calcium supply to the blood because of "tertiary" hyperparathyroidism. Hypocalcemia detected in 38% of TRF patients was consequence to the rise of calcium binding not made for by the increased calcium supply to the blood provoked by bone resistance to parathyroid hormone.

[The calcium-binding properties of plasma proteins following the allograft of a cadaveric kidney]. / Kal'tsiisviazyvaiushchie svoistva plazmennykh belkov posle allotransplantatsii trupnoi pochki.

The kinetics of calcium binding to plasma proteins in hypo- and hypercalcaemia, induced in vitro, were studied in 60 patients after renal transplantation. Langmuir and Scatchard analysis revealed the normal binding of calcium to plasma proteins in 10 patients (cooperative mechanism of calcium-protein interaction in hypocalcaemic state and existence of one or several sets of calcium binding independent sites in hypercalcaemic state). Cooperative binding with the decreased values of effective Ka, effective n. molar binding ratio (CaPr/A) and specific buffer capacity (beta sp.) were observed in 1/3 patients. Cooperative mechanism of calcium-proteins interaction has not been observed in more than 1/2 patients and the values of n. CaPr/A, beta sp, decreased in most of the patients. The observed changes may be caused by a proteins metabolism deterioration and may result in deterioration of calcium homeostasis.

[Results of test-bed and clinical trials of DIP-03-02 dialyzers manufactured by the West German firm Frezenius using polysulfone hollow fibers]. / Rezul'taty stendovykh i klinicheskikh ispytanii kapilliarnykh dializatorov DIP-03-02 proizvodsta firmy "Frezenius" (FRG) na osnove polykh volokon iz polisul'fona.

The authors provide the results of the clinical trial of the dialyzers DIP-03-02 manufactured by the USSR in cooperation with the FRG (Frezenius Company). In accordance with clearances of low-, medium- and high-molecular compounds as well as with the ultrafiltration characteristics, DIP-03-02 are similar to the modern capillary dialyzers from hollow fibers on the basis of cellulose membranes with an analogous surface. During manufacture of the dialyzers DIP-03-02, the polysulfone membrane possessing low permeability for liquid was obtained for the first time. The tentative data on biocompatibility (the complement activation test) are positive.