78 Публикации о гигантских (более 5 см) псевдоаневризмах (ПА) гастродуоденальной арте рии (ГДА) ограничиваются небольшими сериями наблюдений, которые показывают сложность выбо ра эффективного метода лечения [1–6]. Приводим наше наблюдение. Больной А., 57 лет, злоупотребляющий алкоголем, был госпитализирован в клинику с жалобами на слабость, тошноту, боль в животе. За месяц до госпитализации лечился по поводу хронического панкреатита (ХП), псевдокисты головки поджелудочной железы. В связи со сдавлением псевдокистой общего желчного протока и развитием механической желтухи ему была наложена пункционная холецистостома под ультразвуковым (УЗ) наведением. В анамнезе неоднократно отмечались признаки мелены. В момент госпитализации при наличии анемии (Нb 81 г/л) пациент был гемодинамически стабильным. Кли ни ческих признаков активного кровотечения не было. При эзофаго гастродуоденоскопии с осмотром большого и малого сосочков двенадцатиперстной кишки не обнаружено признаков кровотечения. При чрескожной допплеровской сонографии была выявлена псевдокиста головки поджелудочной железы размерами 7×6 см с активным артериальным кровотоком в ее полости, при компьютерной томографии (КТ) с болюсным контрастированием в области головки идентифицировано овальной формы образование размером 73×48×65 мм с признаками экстравазации контраста из гастродуоденальной артерии (рис. 1). В срочном порядке под местной анестезией выполнена диагностическая селективная ангиография ветвей чревного ствола и суперселективная ангиография © Коллектив авторов, 2018 УДК 616.37-002.2-06:616.136.41-007.64-07-089.27 DOI: 10.24884/0042-4625-2018-177-2-78-80

Aim. To study the nature of peripancreatic lesions and its course in patients with AP without CT-signs of pancreatic necrosis. Material and Methods. We had analyzed the treatment of 38 patients with AP in whom contrast-enhanced CT did not reveal disorders of contrast accumulation by pancreatic tissue. Peripancreatic changes were assessed by presence of inhomogeneous acute necrotic collections and homogeneous acute peripancreatic fluid collections. Balthazar (2002) and K. Ishikawa et al. (2006) classification was used to estimate prevalence of parapancreatitis. Results. Acute necrotic collections were revealed in 15 patients. Balthazar index was 3.7 ± 0.1, K. Ishikawa index — 2.46 ± 0.45 on the left side and 0.86 ± 0.4 on the right side (p 0.05). Patients were discharged after 34 ± 5 days. Acute peripancreatic fluid collections were in 23 patients. Balthazar index was 2.5 ± 0.2, the gradation by Japanese classification — 1.3 ± 0.2 on the left side and 0.8 ± 0.2 on the right side. Conservative treatment was applied in 22 (96%) patients, 1 patient was exposed to percutaneous puncture. All patients were discharged after 16 ± 1 day. Conclusion. Our data evidence the importance to identify acute necrotic collections in the absence of pancreatic necrosis as a marker of peripancreatic necrosis. 33% of these patients required surgery due to infection. Classification of parapancreatitis by Kazuo Ishikawa reflects parapancreatitis development and its localization more precisely than Balthazar index.

Aim . To analyze the effect of growing liver biological set on viability and proliferative activity of various cellular cultures in vitro. Material and Methods. The biological combination is an extract from the growing liver obtained by using of original technique. We have assessed extract’s effect on the following cellular lines: hepatic carcinoma Huh7, L-fibroblasts of mice, murine bone marrow mesenchymal stem cells. Viability and proliferative activity were assessed by staining the cells with trypan blue and visual counting of cells under phase contrast microscopy. Result. Biological combination from neonatal piglet’s growing liver dose-dependently protects hepatocyte-like cells from deprivation of fetal serum and stimulates cellular growth in presence of serum. High concentrations of HRS do not lead to growth arrest of the Huh7 cells. At the same time, it is a cytostatic (or cytotoxic) for murine L- fibroblasts. Limited protective effect of the combination on the deprivation of serum when exposed to bone marrow stem cells was revealed. Conclusion. Our data show that the extract may be considered as an important regulator of reparative regeneration of liver with protective and/or stimulating effect on mesenchymal stem and hepatic-like cells and cytostatic effect on fibroblasts. So, further trials are necessary.

The lack of acceptable pharmacological approaches for restoration of the injured liver is associated with complex of mechanisms involved in hepatic regeneration and with difficulty of the target selection. The aim of this research was to study the hepatoprotective function of the extract from both the growing and regenerating liver containing a natural set of factors crucial for the hepatic restoration. Extracts from both regenerating liver of rats after 70% hepatic resection and the growing liver of neonatal pigs were obtained using own original technique. The set of resultant extracts was named as the hepatic regeneration set (HRS). HRS fractionation was carried out using the Toyopearl HW-50S sorbent. The efficiency of HRS and its fractions was estimated using a model of the mouse liver thioacetamide injury and monitoring hepatic enzyme activity in blood serum. The activities of AST and ALT in intact animals were 50 U/l and 80 U/l, respectively; after thioacetamide administration they increased to 2059±212 U/l and 4280±440 E/l, respectively (p<0.05). Treatment of injured animals with HRS from the rat regenerating liver resulted in a significant decrease of transaminase activities to 924±148 U/l (AST; p<0.05) and 1633±308 U/l (ALT; p<0.05). A similar effect was observed after treatment with HRS from the neonatal pig liver: the AST decreased to 937±138 U/l (p<0.05), while ALT activity decreased to 1710±237 U/l (p<0.05). HRs fractionation resulted in identification two active fractions characterized by much higher (8-29) hepatotropic effect that that of the whole extract. These fractions contained peptide/protein components with the range of molecular mass of 3-60 kDa (fraction 1) and 3-25 kDa (fraction 2a). Fraction 1 also contained some polynucleotides in fraction 1. Subsequent studies of these fractions exceeding the hepatotropic effect of original HRS is clearly needed to identify their individual components by immunochromatography methods, ELISA, MRM mass spectrometry and quantitative PCR.

Tankyrase, one of the NAD+ ADP-ribosyltransferases, is a target for drugs developed for their anticancer and other pharmacological activities. We designed an assay for estimation of the inhibition or activation of the enzyme in preclinical studies. In mice, the highest specific activity of tankyrase was observed in thymus, spleen, pancreas, and bone marrow. In murine liver, tankyrase is active in ontogenesis and during reparative regeneration; however, the basal activity is hardly detectable in normal liver and most of other organs of adult animals. We suggest that tankyrase is a part of the tissue growth and repair machinery, while its age-dependent inhibition, when an organism stops growing, turns on phenoptosis.

Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.

The goal of this work was to study the expression of tumor necrosis factor alpha (TNFalpha), sphingomyelin cycle activation, and lipid peroxidation (LPO) processes after the removal of a cholestatic factor in the liver subjected to different durations of cholestasis. Restored bile flow after a 9-day hepatic cholestasis normalized sphingomyelinase (SMase) activity and levels of TNFalpha and LPO products. The removal of a cholestatic factor after a 12-day cholestasis did not normalize the studied parameters: SMase activity and the levels of TNFalpha and LPO products remained much higher compared to control. A significant positive correlation between TNFalpha expression, SMase activity, and LPO rate has been revealed. The obtained data indicate that hepatocyte apoptosis after bile outflow restoration in late cholestasis can be due to the activation of the sphingomyelin cycle, LPO, and TNFalpha expression. The synergistic interaction can sharply increase the proapoptotic capacity of each of these factors since TNFalpha activates SMase and LPO, SMase activity depends on the LPO rate, while ceramide, an SMase-produced secondary messenger of apoptosis, can induce oxidative stress.

Changes in sphingomyelinase activity, tumor necrosis factor α expression, and level of lipid peroxidation products in the course of development of cholestatic liver injury have been studied. The same type phase shifts in the analyzed parameters were observed, which included a marked decrease at the early stages of cholestasis (days 3–6) and a pronounced increase at the later stages (days 12–16), i.e., under the conditions of developed pathology. There was a significant positive linear correlation between tumor necrosis factor α expression, sphingomyelinase activity, and lipid peroxidation intensity in cholestatic injury. We propose that detected changes may reflect the balance between the effects of the two major bile components—bilirubin, which is accumulated in the liver at the early stages of cholestasis, and bile acids, whose influence dominates at the later stages of pathologic process. Our results indicate that tumor necrosis factor α overexpression, sphingomyelin cycle activation, and lipid peroxidation intensification may cause apoptosis of hepatocytes at the late stages of cholestasis.

Indirect immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men. The intensity of expression was maximum in secondary liver cancer, high in obstructive jaundice of different etiology, and less pronounced in cholelithiasis. The expression of prolactin receptors in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice of different etiology. Cells of secondary tumors were characterized by low expression, while distant hepatocytes most intensively expressed prolactin receptors.

The signal transduction pathways triggering apoptotic mechanisms after ischemia/reperfusion may involve TNF-α secretion, ceramide generation, and initiation of lipid peroxidation. In the present study involvement of the TNF-α, sphingomyelin cycle, and lipid peroxidation in the initiation of apoptosis induced in liver cells by ischemia and reperfusion was investigated. Wistar rats were subjected to total liver ischemia (for 15, 30 min, and 1 h) followed by subsequent reperfusion. Ischemia caused sharp decrease of neutral sphingomyelinase activity. Activity of acidic sphingomyelinase initially decreased (during 15-30 min ischemia) but then increased (after 1 h of ischemic injury). Reperfusion of the ischemic lobe of the liver caused increase in neutral sphingomyelinase activity and decrease in acidic sphingomyelinase activity. A small amount of TNF-α detected by immunoblotting analysis was accumulated in the ischemic area of liver rapidly and the content of this cytokine dramatically increased after the reperfusion. TNF-α is known to induce free radical production. We found that the accumulation of TNF and increase of sphingomyelinase activity during the development of ischemic/reperfusion injury coincided with increase in content of lipid peroxidation products (conjugated dienes) and DNA degradation detected by gel electrophoresis. Recently it was shown that superoxide radicals are used as signaling molecules within the sphingomyelin pathway. This suggests the existence of cross-talk between the oxidation system and the sphingomyelin cycle in cells, which may have important implications for the initial phase and subsequent development of post-ischemic injury.

The relationship between energy metabolism in the remaining liver tissue after 60% hepatectomy and the activity of low-molecular-weight thermostable hepatocyte growth factor was studied in rats. The energy status of the liver was markedly reduced 6 h and to a greater degree 12 h after the operation, judging from the levels of ATP, ADP, AMP, and energy potential. The energy status improved (energy potential increased to 95% of the initial level) 24–72 h after the operation. This coincided with a decrease in hexokinase and phosphofructokinase activities and an increase in glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase activities, indicating suppressed glycolysis and activation of the Krebs' cycle. High activity of low-molecular-weight thermostable hepatocyte growth factor was detected 24–72 h after resection of the liver (with maximum activity after 48 h). The activity of the hepatocyte growth factor increased if the range of energy potential surpassed the level sufficient for maintaining protein production, which is an energy-consuming process, but lower than the normal level.

A new surgical method of treating patients with unstable insulin-dependent diabetes (IDD) has been developed-that of surgically shunting pancreatic blood into the systemic blood flow with the purpose of creating a more optimal interaction of subcutaneously administered insulin and pancreas-secreted glucagon. The long term results of the operation depend on the patency of a splenorenal anastomosis. This has been studied by following up 137 patients over periods from half a year to three years. Anastomotic patency was determined by renal and splenic venography and celiacy arteriography, which revealed a patent anastomosis in 114 patients, and an obliterated one in 23. Patients with patent anastomoses showed a lowering of glycosylated hemoglobin (HbA lc ) from 13.3±0.03% to 9.3±0.6%, p<0.05, a decrease of the injected insulin dose from 0.97±0.04 to 0.72±0.03 U/ kg, p<0.05, disappearance or considerable abatement of pain in the lower extremities, and of hypoglycemia. Improvement of clinical status was accompanied by an increase of glucagon in the systemic blood stream from 60.8±10.1 to 91.5±9.4 pg/ml, p<0.05, a rise of tissue oxygen pressure, PO 2 , from 49.2±2.4 to 58.1±1.9 mm Hg, p<0.05. In patients with oblivious anastomoses postoperative HbA lc levels did not change from preoperative values: 12.9±0.4% and 12.8±0.7%, p<0.05, respectively; the insulin dose remained the same-0.91 ±0.07 U/kg and 0.85±0.07 U/kg, p<0.05, no rise of the systemic blood glucagon content was noted, and former complaints continued. The suggested method is not an alternative for insulin therapy, but considerably enhances its potential.

Protein content was measured using ponceau S stain in "protein-free" urine (as shown by clinical analysis with sulfosalicylic acid) of 34 patients with insulin-dependent diabetes mellitus. In 15 patients (group 1) protein levels did not differ from those in healthy subjects. In 19 patients (group 2) protein levels surpassed the normal value by 3.6 times, on an average (p < 0.001). Measurements of urinary albumin revealed microalbuminuria in group 2 and normo-albuminuria in group 1. The data indicate that protein measured with the use of ponceau S stain in group 2 patients is not a false-positive result, but reflects the presence of proteins of plasma origin in the urine. Hence, measurements of urinary protein with the use of ponceau S stain may be used for identification of early stages of diabetic nephropathy.

Erythrocytes of patients with insulin-dependent diabetes mellitus contained two forms of aldose reductase a and b (EC No. 1.1.1.21) (the key enzyme in the sorbitol pathway of glucose utilization) as compared with those of healthy donors in whom the form b of the enzyme was only found. The aldose reductase a exhibited a higher maximal rate (Vmax = 16.7 +/- 3.2 IU/D280) and a lower substrate affinity (Km = 6.5 = 19 mM) than the enzyme b, Vmax = 43.8 +/- 0.6 IU/D280, Km = 3.0 = 4.0 mM, respectively. More severe development of the disease was observed in the patients whose erythrocytes contained only aldose reductase a (HbA1c = 14.56 +/- 0.69%) as compared with those in whom the enzyme a and b were found (HbA1c = 11.5 +/- 0.4%). Kinetic parameters of the enzyme showed that aldose reductase a may be active in hyperglycemia of diabetes mellitus, thus contributing to intensification of the sorbitol pathway in these patients.

When Hb AIc was estimated by affinity chromatography where boron phenyl-agarose was used as a sorbent, the highest rate of Hb AIc binding with the sorbent was detected at pH 8.5-9.0 while the maximal elution of the protein occurred at 0.3-0.5 M concentration of sorbitol used as an eluent. Content of Hb AIc, estimated in 56 patients with insulin-dependent diabetes mellitus, constituted 12.3 +/- 0.4%, while in 20 healthy volunteers it was equal to 5.4 +/- 0.2%, which are consistent with the literature data obtained by other methods. At the same time, the data of Hb AIc estimation by means of affinity chromatography correlated exactly with the results of ion exchange chromatography (r = 0.98), thus corroborating the validity of the procedure used. Only the stable ketoamine fraction of Hb AIc was found to interact with boron phenyl-agarose.