[Cardiooncology: Current Aspects of Prevention of Anthracycline Toxicity].

Anthracyclines including doxorubicin, epirubicin, daunorubicin, aclarubicin are extensively used as chemotherapeutic agents for treatment of hematological and other malignancies. In cancer therapy anthracyclines are often used in combinations with other chemotherapeutic drugs and agents for molecularly targeted therapy. Anthracyclines are effective and powerful antineoplastic drugs with wide spectrum of application but active use of preparations of this group is limited because of such side effects as cardiotoxicity, myelotoxicity, thromboembolism, alopecia, etc. Cardiotoxicity is the most severe side effect of anthracycline administration. Clinical studies have shown that it is progressive and irreversible. Therefore, early detection and prevention of anthracycline cardiotoxicity has become an important trend in cardiology.

[G(i) proteins in regulation of water permeability of the rat kidney collecting tube epithelium cell membrane].

Principal mechanism of the transepithelial water permeability increase in the kidney collecting ducts in response to vasopressin involves insertion of aquaporin 2 (AQP2) into the apical membrane. Previously we have shown that water permeability of the basolateral membrane also may be increased with stimulation of V2-receptors. It is known that inhibition of G(i)-proteins with pertussis toxin blocks redistribution of AQP2 into the apical membrane following the application of vasopressin or forskolin. The aim of the present study was to investigate potential involvement of G(i)-proteins in regulation of basolateral membrane water permeability. Effect of pertussis toxin on the ability of desmopressin to increase the basolateral membrane osmotic water permeability was investigated, and the expression of Galpha(i)2 and Galpha(i)3 genes under normal conditions and after 2 days of water deprivation were evaluated. We demonstrated that dehydration leds to a 30% increase of Galpha(i)3 mRNA content while the Galpha(i)2 mRNA level remains unchanged. In control experiments, basolateral membrane water permeability increased in response to desmopressin from 59.2 +/- 6.61 to 70.6 +/- 9.2 microm/s (p < 0.05, paired t-test). Pertussis toxin completely blocked this reaction (53.5 +/- 5.18 vs 50.1 +/- 6.50 microm/s, respectively). We conclude that G(i)-proteins participate in the mechanism of the basolateral membrane water permeability increase in response to stimulation of V2-receptors. Clarification of the G(i)-proteins role in this process requires further investigation, but most likely they are involved in regulation of aquaporin transport and insertion into the cell membrane.

[Calciumdependent mechanisms in vasopressin regulation of osmotic water permeability in the mouse kidney collecting duct cells].

In the study, the role of PKC and Ca++ in vasopressin regulation of the plasma membrane water permeability was studied in the cells of the mouse kidney collecting duct. Coefficient of osmotic water permeability of total cell surface (Pf) was calculated from the initial rate of cell swelling following the osmotic shock caused by changing the medium osmolarity from isotonic to hypotonic (300 mOsm to 200 mOsm). Desmopressin (dDAVP 1 nM) increased the Pf in hydrated mice from 168.4 +/- 11.8 microm/s up to 231.3 +/- 14.7 microm/s. The Ca++ chelator BAPTA prevented the desmopressin-induced increase in water permeability. Inhibition of PKC (Ro-31-8220 0.1 microM) also abolished the desmopressin-stimulated increase of plasma membrane water permeability, whereas inhibitor of PKC alone did not suppress the stimulation of the water permeability by db-cAMP. The PKC activity and calciumdependent second messengers seem to be important for regulation of water permeability by vasopressin.

[Reconstructive jejuno-gastroplasty in the treatment of operated stomach disease].

The results of treatment of 205 patients with operated stomach disease were analyzed. Conservative therapy was effective in 71.7% patients. Surgical treatment was used in 58 (28.3%) patients. Reoperation was performed less than a year after primary surgery in 5.2% patients, 1 to 3 years later -- in 41.4%, 3 to 5 years -- in 36.2%, more than 5 years later - in 17.2% patients. Early after operation complications were observed in 24.1% patients. Clinical and device examinations demonstrate that surgical reconstruction significantly reduces intensity of pathological symptoms in all the patients.

[Role of Ca2+ and aquaporin-2 in regulation of basolateral water permeability of collecting ducts in the rat kidney].

The role of AQP2,3 and intracellular calcium in vasopressin-induced increase in the water permeability of the basolateral cell membrane in microdissected rat kidney OMCD was studied. It was shown that increase in the water permeability of the basolateral membranes correlated with increase in the content of AQP2 and AQP3 in the membrane fraction isolated from outer kidney medulla. Preliminary loading of cells with BAPTA-AM which binds intracellular Ca2+ abolished the increase in the water permeability and prevented the rise of the AQP2 content in response to dDAVP. BAPTA was ineffective to block the enhancement of AQP2 content in membrane fraction in presence of dDAVP. These results suggest that the increase in intracellular calcium activity and the enhanced content of AQP2 in plasma membrane are important for the antidiuretic effect of dDAVP.

[Method of treatment of reflux-esophagitis after gastrectomy].

A new method of treatment of reflux-esophagitis developed for patients after gastrectomy has a distinctive moment: the formation of a restraining mechanism in the field of esophago-gastric anastomosis, without opening the intestinal tube lumen. The carried on trials of clinical application of the method have shown its high effectiveness for prophylactics ofjejuno-esophageal reflux both in the early and distant terms after operation. The method of operating was given a patent of the Russian Federation.

[Water permeability of the OMCD and IMCD cells' basolateral membrane under the conditions of dehydration and dDAVP action]. / Vodnaia pronitsaemost' bazolateral'noi membrany kletok sobiratel'nykh trubok naruzhnogo i vnutrennego mozgovogo veshchestva pochki krys v usloviiakh degidrtatsii pri deistvii desmopressina.

Water permeability of the basolateral membrane was estimated in isolated fragments of OMCD or IMCD in the Wistar rats. Apical surface of the fragments was blocked with oil injected into the lumen. Apparent water permeability coefficient (Pf) was measured by the rate of epithelium swelling following transition from hypertonic to isotonic medium (600 mOsm to 300 mOsm). Water deprivation caused significant increase in the Pf value in OMCD and IMCD fragments. Desmopressin (10(-8) M) increased water permeability in hydrated rats both in OMCD and IMCD. Mercury chloride decreased the Pf and abolished the effect of desmopressin in reversible manner. Estimation of aquaporins 2, 3, 4 mRNA content in the renal medulla was performed by semi-quantitative RT-PCR. Content of AQP4 and AQP2 mRNA in dehydrated animals was significantly higher than in hydrated ones both in outer medulla and inner medulla. Expression of AQP3 increased during dehydration only in the inner medulla. The findings reveal that water permeability of OMCD and IMCD can be increased by physiological stimuli, e.g. water deprivation. The activation of gene expression of the key elements of vasopressin signal system seems to contribute to this reaction.

[Vasopressin-dependent water permeability of the basolateral membrane of the kidney outer medullary collecting duct in postnatal ontogenesis in rats]. / Vazopressinzavisimaia vodnaia pronitsaemost' bazolateral'noi poverkhnosti sobiratel'nykh trubok naruzhnogo mozgovogo veshchestva pochki krysy v postnatal'nom ontogeneze.

Kidneys of new-born animals are resistant to arginine vasopressin (AVP). The ability of the hormone to regulate water permeability of the collecting duct can be seen from weaning period, probably due to the maturation of the intracellular signaling pathway. The purpose of the present work was to investigate the effect of V2 receptor agonist dDAVP on the water permeability of OMCD basolateral membrane in 10-, 22- and 60-day old Wistar rats. We also estimated ontogenetic gene expression of AQP2, AQP3, AQP4 and V2 receptor. Osmotic water permeability (Pf) of the basolateral membrane of microdissected OMCD was measured under control conditions and after incubation with the agonist V2 receptor desmopressin (dDAVP; 10(-7) M). Water permeability in 10- and 22-day old rats under control conditions were significantly higher than in adults. Desmopressin stimulated significant increase of this parameter in 22-day old pups (Pf = = 125 +/- 4.85; Pf = 174 +/- 8.2 microns/s, p < 0.001) and adult rats (Pf = 100.5 +/- 7.38; Pf = 178.8 +/- 9.54 microns/s, p < 0.001). Osmotic water permeability of the OMCD basolateral membrane in 10-day old rats does not depend on dDAVP (Pf = 172.5 +/- 23.8; Pf = 164.8 +/- 34 microns/s). With the RT-PCR, we observed a gradual increase of AQP2 and V2 receptor genes expression during postnatal ontogenesis. The gene expression of AQP3 and AQP4 remained unchanged during postnatal ontogenesis. In general, the water permeability of the OMCD basolateral membrane of rats can be stimulated by AVP since the 22nd day of postnatal life. The water permeability of the OMCD basolateral membrane under control conditions gradually decreased during postnatal development, while gene expression of AQP3 and AQP4 was unchanged. The mechanism of this decrease remains to be established.

Effect of dDAVP on basolateral cell surface water permeability in the outer medullary collecting duct.

We report a novel approach for assessing the volume of living cells which allows quantitative, high-resolution characterization of dynamic changes in cell volume while retaining the cell functionality. The aim of this study was to evaluate the short-term effect of vasopressin on basolateral cell surface water permeability in the outer medullary collecting duct (OMCD). The permeability of the basolateral cell membrane was determined in the tubules where the apical membrane was blocked with oil injected into the lumen. The apparent coefficient of water permeability (Pf) was evaluated by measuring the cell swelling after the step from hypertonic to isotonic medium (600 mosm to 300 mosm). Desmopressin (dDAVP) induced an increase of the basolateral Pf from 113.7+/-8.5 microm/s in control cells to 186.6+/-11.4 mum/s in micro-dissected fragments of the OMCD incubated in vitro (10(-7) M dDAVP, 30 min at 37 degrees C) (P<0.05). Mercury caused pronounced inhibition of basolateral water permeability (26.0+/-6.9 microm/s; P<0.05). The effect of mercury (1.0 mM HgCl2) was reversible: after washing the fragments with PBS for 20 min, Pf values were restored to the control levels (125.0+/-9.5 microm/s). The results of the study indicate the existence of a mechanism controlling the osmotic water permeability of the basolateral cell membrane in the OMCD epithelium.

[Effect of dehydration and dDAVP on water permeability of basolateral membranes of epithelial cells in the kidney collecting tubules]. / Vliianie degidratatsii i dDAVP na pronitsaemost' dlia vody bazolateral'noi membrany kletok épiteliia sobiratel'nykh trubok pochki.

Water permeability of the outer medullary collecting duct's (OMCD) basolateral membrane was determined in vitro in the tubules isolated from hyperhydrated or dehydrated Wistar rats. Oil was injected into the lumen to block apical membrane water permeability. OMCD fragments underwent a hypoosmic shock (600/300 mOsm) and epithelial cells volume increased ad recorded with a digital camera. The latter's rate was used to calculate apparent water permeability of the membrane (Pf). Treatment of the tubules with Hg2Cl2 suppressed the water permeability. Water deprivation and dDAVP induced an increase in the basolateral water permeability. The data obtained suggest that the water permeability of the OMCD basolateral membrane may be stimulated by vasopressin and water deprivation.

The state of cholinergic structures in forebrain of bulbectomized mice.

The effects of bulbectomy on the state of basal forebrain cholinergic structures and spatial memory in Morris water maze were studied. Immunostaining with polyclonal antibodies to choline acetyltransferase AB144P revealed decreased density of immunoreactive cells in the horizontal limb of the diagonal band of Broca (55% of control), basal magnocellular preoptic nucleus (58.9%), and the caudate nucleus-putamen complex (68.2%). No significant changes in the vertical limb of the diagonal band of Broca and globus pallidus were observed. These findings and published data allow us to assume that pathology of the olfactory bulb can underlie memory impairment during Alzheimer's disease associated with dysfunction of acetylcholine-synthesizing structures in the forebrain.

[Modified water maze for studying spatial memory of rats]. / Modifitsirovannyi vodnyi labirint dlia issledovaniia prostranstvennoi pamiati krys.

A method for evaluation of impairments of spatial memory in rats is put forward. Sensitivity of the advanced method based on the principles of Morris' water maze was compared with that of the classic prototype. Efficiency of the advanced method was assessed by dose- and time-dependent effects of agroclavine on the spatial memory of rats. Agroclavine (10 micrograms/kg) was shown to produce spatial memory impairment in rats. The obtained results also indicate that the modernized maze is more sensitive in revealing impairments of the spatial memory in rats than the classic water maze.

Two new diterpenoids, sarcophytins B and C, from the Indian Ocean soft coral Sarcophyton species.

Two new diterpenoids, sarcophytins B and C (1, 2), and the previously known sarcophytin (4) have been isolated from the Indian Ocean soft coral Sarcophyton sp. Structures of 1 and 2 were established by spectral data and supported by X-ray analysis of 1.

Partial recovery of in vivo function by improved incubation conditions of isolated renal proximal tubule. II. Change of Na-HCO3 cotransport stoichiometry and of response to acetazolamide.

In the preceding publication we reported that some transport properties of proximal tubules perfused in vitro differ from those of tubules perfused in vivo, and that the in vivo function can be largely recuperated by improved metabolic substrate supply and stimulation with norepinephrine (NE). Since we have previously observed that the basolateral Na-HCO3-cotransporter operates with an overall stoichiometric ratio of q approximately 3 HCO3- :1 Na+ in vivo, but with q approximately 2 HCO3- :1 Na+ in vitro and that it responds differently in both cases to acetazolamide (ACZ), we have now tested whether the cotransporter can regain its in vivo function in vitro if the incubation conditions are improved. Cell membrane potentials (Vb) and cell pH (pHi) were measured with microelectrodes and microfluorimetric techniques on isolated S2 segments of rabbit proximal tubule and the instantaneous Vb response to a 2:1 reduction of bath HCO3- or Na+ concentration was determined. (DeltaVb)HCO3 and (deltaVb)Na averaged 13.1 +/- 0.9 mV (SEM) and 6.9 +/- 0.5 mV in D-glucose-containing control HCO3-Ringer solution and decreased respectively to 10.1 +/- 0.5 mV and 3.8 +/- 0.2 mV (n = 8) after incubation in tissue culture medium and NE (10(-5) mmol/l). These data imply that q increased from 1.9 to 2.7. Concomitantly the tubules became susceptible to ACZ (1 mmol/l), which reduced (deltaVb)HCO3 in control conditions only to 94.6 +/- 1.2% but under improved incubation conditions to 64.5 +/- 2.4%. As verified in voltage divider measurements the latter reduction was not caused by activation of a basolateral K+ conductance. The results indicate that improved incubation conditions can at least partially revert cotransport function towards that of the in vivo state. The effect of ACZ may be explained if in the improved state 1 CO32- + 1 HCO3- + 1 Na+ are cotransported, in which case inhibition of carbonic anhydrase (CA) may cause a CO32-/pH disequilibrium to develop in the basal labyrinth which impedes the cotransport. Under conventional incubation conditions, however, when only 2 HCO3- + 1 Na+ are cotransported no such disequilibrium should develop irrespective of whether CA is active or inhibited.

[Role of vasopressin and aldosterone in the mechanism of osmoregulating reaction]. / Rol' vazopressina i al'dosterona v mekhanizme osmoreguliruiushchei reaktsii.

Possible mechanisms responsible for a natriuretic response to NaCl hypertonic solution (515 mmol/l) digestively administered were studied in chronic experiments on Wistar and Brattleboro rats with continuously implanted urinary bladder catheters. The administration of the solution resulted in rapid antidiuresis and marked natriuresis though the plasma levels of N+ remained unchanged throughout the experiment. Natriuresis did not differ in the Brattleboro and Wistar rats. The time course of blood aldosterone was examined in experiments on Wistar rats. There was its double statistically significant decrease. It is suggested that in addition to secretion of hypophyseal neuropeptides there are additional reflex mechanisms that modulate natriuresis in osmotic irritation of the liver and that these mechanisms may trigger a decrease in plasma aldosterone levels.

[Leukinferon in the comprehensive therapy of sepsis in newborns]. / Ispol'zovanie leikinferona v kompleksnom lechenii sepsisa novorozhdennykh.

Leukinferon was used in adoptive immunotherapy of sepsis in risk group newborns by activation of the donor leukocyte suspension in combination with etiotropic, antitoxic and other agents of chemotherapy. It accelerated the recovery at the average of 7 days in comparison with the control (the routine treatment). The favourable time course of the major immunological indices such as leukocytosis and absolute and relative counts of lymphocytes mainly due to correction of the T-lymphocyte count, NBT and LII impaired by the pathological process was recorded at the average 4 days earlier against the control. By the end of the treatment normalization of the above mentioned indices proved to be more complete. Neither complications of the septic process nor side effects of the immunotherapy were observed.

Determination of molecular-weight distribution and average molecular weights of block copolymers by gel-permeation chromatography.

The problem of preparation of a block copolymer of precise molecular-weight distribution (MWD) and with heterogeneous composition on the basis of gel-permeation chromatography (GPC) data has been investigated. It has been shown that in MWD calculations the distribution f(p) of the composition p in individual GPC fractions should be taken into account. The type of the f(p) functions can be simultaneously established by an independent method, such as use of adsorption-column or thin-layer chromatography sensitive to the composition of the copolymer. It has also been shown that the actual f(p) may be replaced by a corresponding piecewise distribution, of simple form, without decrease in the precision of calculation of the MWD and average molecular weights of most known block copolymers.

Peculiarities in gel permeation chromatography of flexible-chain polymers on macroporous swelling sorbents.

In gel permeation chromatography on macroporous swelling sorbents, deviations from the Benoit principle of universal calibration were observed. It is suggested that these are caused by different degrees of thermodynamic compatibility of the eluted polymers with the sorbent matrix.