ДИНАМИКА ИНСУЛИНОПОДОБНОГО ФАКТОРА РОСТА 1 (ИФР-1) ПРИ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ ДЕТЯМ ОТ ДОНОРА, НЕ СОВМЕСТИМОГО ПО ГРУППЕ КРОВИ

It is shown that liver transplantation (LT) from donor with incompatible blood type (AB0i) may be effective and safe, but the impact of such operation upon the various systems of the body has not been investigated yet. Insulinlike growth factor-1 (IGF-1) is synthesized in the liver and mediates the action of growth hormone. The level of IGF-1 is a marker of the processes of cell proliferation and tissue regeneration. Aim. To evaluate levels of IGF-1 in children-recipients with liver transplant from AB0i (incompatible) and AB0c (compatible) donors.Materials and methods. 140 children aged 3 to 36 (19,5 ± 16,5 months) with congenital diseases of the hepatobiliar system, 58 of them boys, were surveyed. All patients underwent transplantation of left lateral liver sector from living related donors: 111 children were transplanted with fragment of the liver from AB0c donors, 29 – from AB0i donors; in 10 children with AB0i liver before and/or after LT operation anti-group antibodies (anti-A/B) were revealed. The concentration of IGF-1 was determined by ELISA using specifi c kits (Immunodiagnostic System, USA) in samples of blood plasma, which were received up to a month and a year after a liver transplant.Results. Average level of IGF-1 21,0 ± 29,5 μg/l in patients before LT was signifi cantly lower than in healthy children (52,2 ± 26,3 μg/l, p < 0,001) and did not vary in children, having received later a piece of liver from a compatible (AB0c) donor and from donor AB0i (23,5 ± 30,9 and 21,2 ± 23,2 μg/l respectively, p = 0,70). In patients with anti-A/B prior to surgery average level of IGF-1 was not different from that of the patients without antibodies (32,6 ± 27,6 and 22,3 ± 29,6 μg/l respectively, p = 0,4). One month after LT level of IGF-1 has increased both in the general group, and in patients with AB0c and AV0i liver (92,1 ± 77,8 and 131,2 ± 106,7 μg/l respectively, p = 0,09). The level of IGF-1 was not varied in the group with antibodies (152,5 + 150,4 μg/l) and without them (95,9 ± 77,0 μg/l). A year after LT the average level of IGF-1 in recipients of AV0c and AV0i liver was not varied and was signifi cantly higher than before LT (82,0 + 60,7 and 91,2 ± 77,8 μg/l, p < 0,005 and p = 0,03 respectively). The content of IGF-1 in patients with anti-A/B and without them (104,7 ± 67,5 and 84,7 ± 63,7 μg/l respectively) also did not differ.Conclusion: the results of our studies have shown that restoration of the level of IGF-1 is not dependent on transplantation of compatible or incompatible blood type liver, as well as on the availability of anti-group antibodies.Показано, что трансплантация печени (ТП) от не совместимого по группе крови (АВ0н) донора может быть эффективной и безопасной, однако вопросы, связанные с эффектом такой операции на различные системы организма, не исследованы. Инсулиноподобный фактор роста 1 (ИФР-1) синтезируется в печени и опосредует действие гормона роста, его уровень является маркером процессов пролиферации и регенерации тканей.Цель: исследовать динамику уровня ИФР-1 у детей – реципиентов печени при трансплантации от родственного совместимого и не совместимого по группе крови донора.Материалы и методы. Обследовано 140 детей с врожденными заболеваниями гепатобилиарной системы в возрасте от 3 до 36 (19,5 ± 16,5) месяцев, из них 58 мальчиков. Всем пациентам была проведена трансплантация левого латерального сектора печени от живого родственного донора: 111 детям был пересажен фрагмент печени от АВ0с донора, 29 – от АВ0н донора; у 10 детей с АВ0н ТП до и/или после операции обнаруживались антигрупповые антитела (анти-А/В). Концентрацию ИФР-1 определяли методом ИФА в образцах плазмы крови.Результаты. Средний уровень ИФР-1 21,0 ± 29,5 мкг/л у пациентов до ТП был достоверно ниже, чем у здоровых детей (52,2 ± 26,3 мкг/л, p < 0,001), и не различался у детей, позднее получивших фрагмент печени от совместимого (АВ0с) и от АВ0н донора (23,5 ± 30,9 и 21,2 ± 23,2 мкг/л соответственно, p = 0,70). У пациентов с анти-А/В до операции средний уровень ИФР-1 не отличался от такового у пациентов без антител (32,6 ± 27,6 и 22,3 ± 29,6 мкг/л соответственно, р = 0,4). Через месяц после ТП уровень ИФР-1 повысился как в общей группе, так и у пациентов с АВ0с и АВ0н ТП (92,1 ± 77,8 мкг/л и 131,2 ± 106,7 мкг/л соответственно, р = 0,09). Уровень ИФР-1 не различался в группе с антителами (152,5 ± 150,4 мкг/л) и без них (95,9 ± 77,0 мкг/л). Через год после ТП средний уровень ИФР-1 у реципиентов АВ0с и АВ0н печени не различался и был достоверно выше, чем до ТП (82,0 ± 60,7 и 91,2 ± 77,8 мкг/л, р < 0,005 и р = 0,03 соответственно). Содержание ИФР-1 у пациентов с анти-А/В и без них (104,7 ± 67,5 мкг/л и 84,7 ± 63,7 мкг/л соответственно) также не отличалось.Заключение. Результаты исследования показали, что восстановление уровня ИФР-1 не зависит от того, был ли донор фрагмента печени совместимым по системе АВ0 или нет и содержались ли у реципиента в крови антигрупповые антитела до трансплантации

Approximation of the relief and calculation of top-corrections in the framework of the method of linear integral representations

Linear problems of gravimetry and magnitometry were considered so far either as problems of finding solutions of linear integral equations or as problems of finding integral operators values. But in this case infinite-dimensional constructions appear, which are practically unimplemented. Problem statements adequate to real geophysical practice appear within the boundaries of linear integral concepts method which general methodology and constructive bases were elaborated by V. N. Strakhov. In this method finiteness and proximity of available information on the studied potential fields (gravity, magnetic, thermal et al.) and on lay of land are taken into account initially. Analytical approximations of the relief allow to produce digital models of the locality and to calculate with their help topographic corrections

DYNAMICS OF INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) IN CHILDREN AFTER AB0-INCOMPATIBLE LIVER TRANSPLANTATION

It is shown that liver transplantation (LT) from donor with incompatible blood type (AB0i) may be effective and safe, but the impact of such operation upon the various systems of the body has not been investigated yet. Insulinlike growth factor-1 (IGF-1) is synthesized in the liver and mediates the action of growth hormone. The level of IGF-1 is a marker of the processes of cell proliferation and tissue regeneration. Aim. To evaluate levels of IGF-1 in children-recipients with liver transplant from AB0i (incompatible) and AB0c (compatible) donors.Materials and methods. 140 children aged 3 to 36 (19,5 ± 16,5 months) with congenital diseases of the hepatobiliar system, 58 of them boys, were surveyed. All patients underwent transplantation of left lateral liver sector from living related donors: 111 children were transplanted with fragment of the liver from AB0c donors, 29 – from AB0i donors; in 10 children with AB0i liver before and/or after LT operation anti-group antibodies (anti-A/B) were revealed. The concentration of IGF-1 was determined by ELISA using specifi c kits (Immunodiagnostic System, USA) in samples of blood plasma, which were received up to a month and a year after a liver transplant.Results. Average level of IGF-1 21,0 ± 29,5 μg/l in patients before LT was signifi cantly lower than in healthy children (52,2 ± 26,3 μg/l, p < 0,001) and did not vary in children, having received later a piece of liver from a compatible (AB0c) donor and from donor AB0i (23,5 ± 30,9 and 21,2 ± 23,2 μg/l respectively, p = 0,70). In patients with anti-A/B prior to surgery average level of IGF-1 was not different from that of the patients without antibodies (32,6 ± 27,6 and 22,3 ± 29,6 μg/l respectively, p = 0,4). One month after LT level of IGF-1 has increased both in the general group, and in patients with AB0c and AV0i liver (92,1 ± 77,8 and 131,2 ± 106,7 μg/l respectively, p = 0,09). The level of IGF-1 was not varied in the group with antibodies (152,5 + 150,4 μg/l) and without them (95,9 ± 77,0 μg/l). A year after LT the average level of IGF-1 in recipients of AV0c and AV0i liver was not varied and was signifi cantly higher than before LT (82,0 + 60,7 and 91,2 ± 77,8 μg/l, p < 0,005 and p = 0,03 respectively). The content of IGF-1 in patients with anti-A/B and without them (104,7 ± 67,5 and 84,7 ± 63,7 μg/l respectively) also did not differ.Conclusion: the results of our studies have shown that restoration of the level of IGF-1 is not dependent on transplantation of compatible or incompatible blood type liver, as well as on the availability of anti-group antibodies

"Splenism" - the function of spleen, as the organ conducting the interrelation of the circulatory system and hematopoiesis

On Wistar rats splenic involvement into the regulation of erythropoiesis was studied. Splenomegaly was reproduced for this both by ligation of splenic veins and transfusion of suspension of washed erythrocytes that leaded to the pronounced increase in the size of the spleen which has reserved the part of erythrocytes. It has been shown that in both cases the inhibition of erythropoiesis takes place due to the appearance of the active inhibitor in plasma: the injection of such plasma reduces the hematopoietic activity of intact rats-recipients. It is assumed that the inhibitor depresses the formation of blood by reducing the production of erythropoietin by the kidneys. We believe that the inhibiting effect is caused by serotonin, which concentration in blood plasma was increased. The inhibiting effect of serotonin is evidenced by its increase in those layers of the kidneys, which are structures that synthesize erythropoietin. Indirect confi rmation of serotonin’s participation in the inhibition of hematopoiesis may be the clinical data about decreased platelet count, which are apparently destroyed in the spleen (platelets contain a lot of serotonin), in patients with splenomegaly. We have shown that if you deprive the spleen of the possibility to deposit the excess of transfused red blood cells by preliminary sheathing it with capron, the appearance of erythropoiesis inhibitory factor (serotonin) doesn’t happen. Thus, we believe that the normal activation of the spleen (hypersplenism) takes place in case of secondary splenomegaly in patients with the cirrhosis of the liver, it consists in the regulation of erythropoiesis through its function of depositary. And we propose to call this function of normal spleen «splenism»

Спленізм – функція селезінки як органа, що здійснює взаємозв’язок систем кровообігу і кровотворення

The term “hypersplenism” has long been entrenched firmly in clinical practice; it is defined as the enlargement of the spleen (splenomegaly), as a consequence of difficulties of blood outflow from the spleen, accompanied by the development of pancytopenia. Most frequently and "clean" such - secondary splenomegaly develops as a result of difficulties of blood outflow in the liver cirrhosis (in 30-50% of patients) (12). In this case, the phenomenon of hypersplenism, which manifests itself in pancytopenia, is observed in more than half of these patients (11, 18, 19, 20). However, the mechanism of anemia needs to be clarified, as a rule the emphasis is only on blood cell destruction in the congestive spleen or blood loss from the varicose veins. (14, 16, 18).Previously we (5) had found that in most of the 25 studied patients with secondary splenomegaly (cirrhosis and splenic vein thrombophlebitis) potent inhibitor of blood was detected in serum. Splenectomy led to the disappearance of the inhibitor and the activation of erythropoiesis.Materials and methods. The experiments were performed on Wistar rats, weighing 200-250 g; several models of experiments were involved. Splenomegaly was created either by ligation of splenic vein or intraperitoneal infusion of 80% saline suspension of washed red blood cells (3.5 ml/100 g body weight). In part of this group of animals spleen was tightly sheathed with capron a week before transfusion of red blood cells in order to deprive of the opportunity to deposit the excess of red blood cells. Red blood cells count, hemoglobin level and concentration of reticulocytes were studied in the dynamics. We determined the concentration of serotonin in blood and kidneys.Results and Discussion. Ligation of the splenic veins as well as deposition of the part of the transfused red blood cells in it, as evidenced by the almost two-fold increase of its mass (from 1.0-1.2 g to 2.0-2.5 g), led to the weakening of erythropoiesis. The inhibition of erythropoiesis is evidenced by the sharp decrease of the concentration of young red cells - reticulocytes and the gradual reduction of erythrocytes. Transfusion of large number of red blood cells results in the same effect.In plasma of these animals there is an active factor, which leads to inhibition of erythropoiesis. This can be concluded on the basis of the fact that the introduction of the blood serum of these animals resulted in inhibition of blood in recipients: as evidenced by the reduction in the concentration of reticulocytes. In contrast, the reproduction of erythrocytosis against the deprivation of spleen’s possibility to deposit the excess of red blood cells, in spite of the decrease in the activity of erythropoiesis, did not lead to the appearance of active inhibitor of erythropoiesis in the blood of these animals: after the introduction of serum erythropoietic activity of the recipient did not change (the concentration of reticulocytes count remained at the level of the control animals). Polyglobulia itself leads to the reduced formation of erythropoiesis stimulator - erythropoietin.Thus, we have found that enlargement of the spleen (splenomegaly), both after ligation of its veins and when depositing excess of erythrocytes in case of erythrocytosis, leads to anemia due to the formation of the active inhibitor. We believe that the active inhibitor exerts its effect through inhibition of the formation of erythropoietin in the kidney rather than by direct blocking of the bone marrow. Such inhibitor is serotonin, as its blood level increased with splenomegaly. In patients with splenomegaly source of serotonin is apparently the destruction of platelets. Increased serotonin level was found in those parts of kidneys, which are the structures that synthesize erythropoietin. Removal of the spleen leads to the significant reduction of serotonin level both in blood and kidneys.Conclusions:1. Pancytopenia develops in patients with congestive splenomegaly, it is caused not only by the destruction of blood cells, but also by active suppression of hemopoiesis.2. Serotonin is apparently the erythropoiesis depressing factor; its high concentration in the blood is detected in case of blood stagnation in the spleen.3. Hyperserotoninemia inhibits the production of erythropoietin in kidneys despite the presence of anemia. 4. Polycythemia in rats, which spleen is deprived of the possibility to deposit the blood excess, does not lead to the appearance of the inhibitor of erythropoietin.5. Spleen, performing the function of depositary, provides the connection of the circulatory system and blood formation. Taking part in deposition of excess of red blood cells in the circulatory system, spleen blocks the formation of erythropoietin, thereby reducing the formation of red blood cells. This functional mechanism of the spleen could be called "splenism". And the excessive increase of this function leads to the pathology - hypersplenism.На крысах линии Вистар изучали участие селезенки в регуляции эритропоэза. Для этого спленомегалию вызывали двумя путями: перевязкой вен селезенки и переливанием взвеси отмытых эритроцитов, что приводило к выраженному увеличению размеров селезенки, депонировавшей часть эритроцитов. Отмечено, что в обоих случаях происходит угнетение эритропоэза за счет появления в плазме крови активного ингибитора: введение такой плазмы приводит к снижению активности кроветворения интактных крыс-реципиентов. Предполагается, что данный ингибитор угнетает кроветворение путем снижения образования эритропоэтина почками. Считаем, что этот ингибирующий эффект обусловлен серотонином, концентрация которого в плазме крови повышалась. Об ингибирующем влиянии серотонина свидетельствует его увеличение в тех слоях почек, в которых располагаются структуры, синтезирующие эритропоэтин. Косвенным подтверждением участия серотонина в угнетении кроветворения могут быть и клинические данные о наличии у больных спленомегалией сниженного количества тромбоцитов, которые, по-видимому, разрушаются в селезенке (а в тромбоцитах содержится много серотонина). Показано, что если лишить селезенку возможности депонировать излишки перелитых эритроцитов путем предварительного плотного обшивания ее капроном, появление угнетающего эритропоэз фактора (серотонина) не происходит. Считаем, что при вторичной спленомегалии у больных циррозом печени происходит активация нормальной функции селезенки (гиперспленизм), заключающаяся в регуляции эритропоэза через депонирующую функцию. Именно эту функцию нормальной селезенки предлагаем назвать спленизмом.На щурах лінії Вістар вивчали участь селезінки в регуляції еритропоезу. Для цього відтворювали спленомегалію двома шляхами: перев’язкою вен селезінки і переливанням суспензії відмитих еритроцитів, що призводило до вираженого збільшення розмірів селезінки, яка депонувала частину еритроцитів. Спостережено, що в обох випадках відбувається пригнічення еритропоезу за рахунок появи в плазмі крові активного інгібітора: введення такої плазми призводить до зниження активності кровотворення інтактних щурів-реципієнтів. Передбачається, що цей інгібітор пригнічує кровотворення шляхом зниження утворення еритропоетину нирками. Вважаємо, що цей інгібуючий ефект зумовлений серотоніном, концентрація якого в плазмі крові підвищувалась. Про інгібуючий вплив серотоніну свідчить його збільшення у тих шарах нирок, де розташовуються структури, що синтезують еритропоетин. Опосередкованим підтвердженням участі серотоніну в пригніченні кровотворення можуть бути клінічні дані про наявність у хворих на спленомегалію зниженої кількості тромбоцитів, які, ймовірно, руйнуються в селезінці (а в тромбоцитах міститься багато серотоніну). Доведено, якщо позбавити селезінку можливості депонувати надлишки перелитих еритроцитів шляхом попереднього щільного обшивання її капроном, то фактор, що пригнічує еритропоез (серотоніну), не з’являється. Вважаємо, що при вторинній спленомегалії у хворих на цироз печінки відбувається активація нормальної функції селезінки (гіперспленізм), що полягає в регуляції еритропоезу завдяки депонуючій функції. Саме цю функцію нормальної селезінки пропонуємо називати спленізмом