National Medical Research Center of Surgery named after A. Vishnevsky

// Anna V. Kudryavtseva 1,2 , George S. Krasnov 1 , Alexey A. Dmitriev 1 , Boris Y. Alekseev 2 , Olga L. Kardymon 1 , Asiya F. Sadritdinova 1,2 , Maria S. Fedorova 1 , Anatoly V. Pokrovsky 3 , Nataliya V. Melnikova 1 , Andrey D. Kaprin 2 , Alexey A. Moskalev 1,4 and Anastasiya V. Snezhkina 1 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia 3 A.V. Vishnevsky Institute of Surgery, Moscow, Russia 4 Moscow Institute of Physics and Technology, Dolgoprudny, Russia Correspondence to: Anna V. Kudryavtseva, email: // Keywords : oxidative stress, mitochondrial dysfunction, ROS, aging, cancer, Gerotarget Received : November 23, 2015 Accepted : May 28, 2016 Published : June 05, 2016 Abstract Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.

Evolution has created a large family of different classes of voltage-gated Ca2+ channels and a variety of additional splice variants with different inactivation properties. Inactivation controls the amount of Ca2+ entry during an action potential and is, therefore, believed to play an important role in tissue-specific Ca2+ signalling. Furthermore, mutations in a neuronal Ca2+ channel (Ca(v)2.1) that are associated with the aetiology of neurological disorders such as familial hemiplegic migraine and ataxia cause significant changes in the process of channel inactivation. Ca2+ channels of a given subtype may inactivate by three different conformational changes: a fast and a slow voltage-dependent inactivation process and in some channel types by an additional Ca2+-dependent inactivation mechanism. Inactivation kinetics of Ca2+ channels are determined by the intrinsic properties of their pore-forming alpha1-subunits and by interactions with other channel subunits. This review focuses on structural determinants of Ca2+ channel inactivation in different parts of Ca2+ channel alpha1-subunits, including pore-forming transmembrane segments and loops, intracellular domain linkers and the carboxyl terminus. Inactivation is also affected by the interaction of the alpha1-subunits with auxiliary beta-subunits and intracellular regulator proteins. The evidence shows that pore-forming S6 segments and conformational changes in extra- (pore loop) and intracellular linkers connected to pore-forming segments may play a principal role in the modulation of Ca2+ channel inactivation. Structural concepts of Ca2+ channel inactivation are discussed.

The role of channel inactivation in the molecular mechanism of calcium (Ca 2+ ) channel block by phenylalkylamines (PAA) was analyzed by designing mutant Ca 2+ channels that carry the high affinity determinants of the PAA receptor site [Hockerman, G. H., Johnson, B. D., Scheuer, T., and Catterall, W. A. (1995) J. Biol. Chem. 270, 22119–22122] but inactivate at different rates. Use-dependent block by PAAs was studied after expressing the mutant Ca 2+ channels in Xenopus oocytes. Substitution of single putative pore-orientated amino acids in segment IIIS6 by alanine (F-1499-A, F-1500-A, F-1510-A, I-1514-A, and F-1515-A) gradually slowed channel inactivation and simultaneously reduced inhibition of barium currents (I Ba ) by (−)D600 upon depolarization by 100 ms steps at 0.1 Hz. This apparent reduction in drug sensitivity was only evident if test pulses were applied at a low frequency of 0.1 Hz and almost disappeared at the frequency of 1 Hz. (−)D600 slowed I Ba recovery after maintained membrane depolarization (1–3 sec) to a comparable extent in all channel constructs. A drug-induced delay in the onset of I Ba recovery from inactivation suggests that PAAs promote the transition to a deep inactivated channel conformation. These findings indicate that apparent PAA sensitivity of Ca 2+ channels is not only defined by drug interaction with its receptor site but also crucially dependent on intrinsic gating properties of the channel molecule. A molecular model for PAA-Ca 2+ channel interaction that accounts for the relationship between drug induced inactivation and channel block by PAA is proposed.

Aim . Optimal revascularization strategy in multivessel (MV) coronary artery disease (CAD) eligible for percutaneous management (PCI) and surgery remains unresolved. We evaluated, in a randomized clinical trial, residual myocardial ischemia (RI) and clinical outcomes of MV-CAD revascularization using coronary artery bypass grafting (CABG), hybrid coronary revascularization (HCR), or MV-PCI. Methods . Consecutive MV-CAD patients ( n = 155) were randomized (1 : 1 : 1) to conventional CABG (LIMA-LAD plus venous grafts) or HCR (MIDCAB LIMA-LAD followed by PCI for remaining vessels) or MV-PCI (everolimus-eluting CoCr stents) under Heart Team agreement on equal technical and clinical feasibility of each strategy. SPECT at 12 months (primary endpoint of RI that the trial was powered for; a measure of revascularization midterm efficacy and an independent predictor of long-term prognosis) preceded routine angiographic control. Results . Data are given, respectively, for the CABG, HCR, and MV-PCI arms. Incomplete revascularization rate was 8.0% vs. 7.7% vs. 5.7% (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.71</mml:mn></mml:mrow></mml:math>). Hospital stay was 13.8 vs. 13.5 vs. 4.5 days (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>), and sick-leave duration was 23 vs. 16 vs. 8 weeks (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>). At 12 months, RI was 5 (2, 9)% vs. 5 (3, 7)% vs. 6 (3, 10)% (median; Q1, Q3) with noninferiority <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi></mml:math> values of 0.0006 (HCR vs. CABG) and 0.016 (MV-PCI vs. CABG). Rates of angiographic graft stenosis/occlusion or in-segment restenosis were 20.4% vs. 8.2% vs. 5.9% (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). Clinical target vessel/graft failure occurred in 12.0% vs. 11.5% vs. 11.3% (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.62</mml:mn></mml:mrow></mml:math>). Major adverse cardiac and cerebral event (MACCE) rate was similar (12% vs. 13.4% vs. 13.2%; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.83</mml:mn></mml:mrow></mml:math>). Conclusion . In this first randomized controlled study comparing CABG, HCR, and MV-PCI, residual myocardial ischemia and MACCE were similar at 12 months. There was no midterm indication of any added value of HCR. Hospital stay and sick-leave duration were shortest with MV-PCI. While longer-term follow-up is warranted, these findings may impact patient and physician choices and healthcare resources utilization. This trial is registered with NCT01699048 .

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC. RESULTS: Using CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types. CONCLUSIONS: We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.

CONTEXT: It is important to recognize arterial variants in the preoperative planning of extended pancreatic resections. The absence of surgical confirmation of radiological data is a limitation of the majority of angiographic or CT-angiographic studies of celiac and mesenteric arterial anatomy. OBJECTIVE: The purpose of this study was to test the accuracy of CT angiography in delineating the arterial architecture by comparing the resultant 3D images with findings at surgery and determining the frequency of different celiac and mesenteric arterial anatomy variants. METHODS: Abdominal CT angiographies of 350 patients were performed on a 64- and 256-MDCT scanner prior to major pancreatic or hepatobiliary surgery. Variants of celiac and mesenteric arterial anatomy were documented as 3D reconstructions. Radiological data were compared to operative photographs during extended pancreaticoduodenectomies and extended distal pancreatectomies in 59 cases. RESULTS: Only 197 patients (56.3%) had the classic arterial anatomy identified at CT angiography. The most common variants were a replaced or accessory right hepatic artery originating from the superior mesenteric artery (62 cases, 17.7%) and a replaced or accessory left hepatic artery (43 cases, 12.3%) originating from the left gastric artery. According to a comparison with operative photographs, CT angiography demonstrated 100% accuracy in identifying celiac and mesenteric arterial anatomy variants, stenoses, obstructions and aneurysms of the celiac and mesenteric branches, including those which were hemodynamically significant and which influence the choice and sequence of operative procedures. CONCLUSION: The celiac and mesenteric arterial anatomy variants are fairly common and are of great significance in planning extended pancreatic resections. Radiological findings were fully corroborated by operative data, which means that CT angiography is a reliable tool for identifying celiac and mesenteric arterial anatomy aberrations and arterial lesions.

BACKGROUND: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma. However, the mechanism of action of HKs in the promotion of tumor growth remains unclear. RESULTS: The purpose of the present study was to investigate the effect of silencing of hexokinase genes (HK1, HK2, and HK3) in colorectal cancer (HT-29, SW 480, HCT-15, RKO, and HCT 116) and melanoma (MDA-MB-435S and SK-MEL-28) cell lines using short hairpin RNA (shRNA) lentiviral vectors. shRNA lentiviral plasmid vectors pLSLP-HK1, pLSLP-HK2, and pLSLP-HK3 were constructed and then transfected separately or co-transfected into the cells. HK2 inactivation was associated with increased expression of HK1 in colorectal cancer cell lines pointing to the compensation effect. Simultaneous attenuation of HK1 and HK2 levels led to decreased cell viability. Co-transfection with shRNA vectors against HK1, HK2, and HK3 mRNAs resulted in a rapid cell death via apoptosis. CONCLUSIONS: We have demonstrated that simultaneous inactivation of HK1 and HK2 was sufficient to decrease proliferation and viability of melanoma and colorectal cancer cells. Our results suggest that HK1 and HK2 could be the key therapeutic targets for reducing aerobic glycolysis in examined cancers.

Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient's age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary.

// Svetlana O. Zhikrivetskaya 1,* , Anastasiya V. Snezhkina 1,* , Andrew R. Zaretsky 2 , Boris Y. Alekseev 3 , Anatoly V. Pokrovsky 4 , Alexander L. Golovyuk 4 , Nataliya V. Melnikova 1 , Oleg A. Stepanov 1,3 , Dmitry V. Kalinin 4 , Alexey A. Moskalev 1 , George S. Krasnov 1 , Alexey A. Dmitriev 1 and Anna V. Kudryavtseva 1,3 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 M.M. Shemyakin - Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia 3 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia 4 A.V. Vishnevsky Institute of Surgery, Moscow, Russia * These authors have contributed equally to this work Correspondence to: Anna V. Kudryavtseva, email: // Keywords : paragangliomas, pheochromocytomas, molecular markers, germline and somatic mutations, signaling pathways Received : August 02, 2016 Accepted : January 23, 2017 Published : February 08, 2017 Abstract Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 25&ndash;30% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics.

beta-subunit modulation of slow inactivation of class A calcium (Ca2+) channels was studied with two-microlectrode voltage clamp after expression of the alpha1A- (BI-2) together with beta1a-, beta2a-, beta3- or beta4-subunits in Xenopus oocytes. On- and off-rates of slow inactivation were estimated from the kinetics of recovery from slow inactivation. Ca2+ channels with an alpha1A/beta-subunit composition inducing the slower rate of fast inactivation displayed the faster rate of slow inactivation. The corresponding order of slow inactivation time constants (tau[onset]) was: alpha1A/beta2a, 33 +/- 3 s; alpha1A/beta4, 42 +/- 4 s; alpha1A/beta1a, 59 +/- 4 s; alpha1A/beta3, 67 +/- 5 s (n >= 7). Recovery of class A Ca2+ channels from slow inactivation was voltage dependent and accelerated at hyperpolarized voltages. At a given holding potential recovery kinetics were not significantly modulated by different beta-subunits. Two mutations in segment IIIS6 (IF1612/1613AA) slowed fast inactivation and accelerated the onset of slow inactivation in the resulting mutant (alpha1A/IF-AA/beta3) in a similar manner as coexpression of the beta2a-subunit. Recovery from slow inactivation was slightly slowed in the double mutant. Our data suggest that class A Ca2+ channels enter the 'slow inactivated' state more willingly from the open than from the 'fast inactivated' state. The rate of slow inactivation is, therefore, indirectly modulated by different beta-subunits. Fast and slow inactivation in class A Ca2+ channels appears to represent structurally independent conformational changes. Fast inactivation is not a prerequisite for slow inactivation.

BACKGROUND: The term "paraduodenal pancreatitis" (PP) was proposed as a synonym for duodenal dystrophy (DD) and groove pancreatitis, but it is still unclear what organ PP originates from and how to treat it properly. OBJECTIVE: To assess the results of different types of treatment for PP. METHOD: Prospective analysis of 62 cases of PP (2004-2013) with histopathology of 40 specimens was performed; clinical presentation was assessed and the results of treatment were recorded. RESULTS: Preoperative diagnosis was correct in all the cases except one (1.9%). Patients presented with abdominal pain (100%), weight loss (76%), vomiting (30%), and jaundice (18%). CT, MRI, and endoUS were the most useful diagnostic modalities. Ten patients were treated conservatively, 24 underwent pancreaticoduodenectomies (PD), pancreatico- and cystoenterostomies (8), Nakao procedures (5), duodenum-preserving pancreatic head resections (5), and 10 pancreas-preserving duodenal resections (PPDR) without mortality. Full pain control was achieved after PPRDs in 83%, after PDs in 85%, and after PPPH resections and draining procedures in 18% of cases. Diabetes mellitus developed thrice after PD. CONCLUSIONS: PD is the main surgical option for PP treatment at present; early diagnosis makes PPDR the treatment of choice for PP; efficacy of PPDR for DD treatment provides proof that so-called PP is an entity of duodenal, but not "paraduodenal," origin.

Aim Despite the regular heart damage in patients with coronavirus pneumonia caused by SARS-Cov-2, a possibility of developing lymphocytic myocarditis as a part of COVID-19 remains unsubstantiated. The aim of this study was to demonstrate a possibility of lymphocytic myocarditis and to study its morphological features in patients with the novel coronavirus infection (COVID-19) with a severe course.Material and methods Postmortem data were studied for 5 elderly patients (74.8±4.4 years; 3 men and 2 women) with the novel coronavirus infection and bilateral, severe polysegmental pneumonia (stage 3-4 by computed tomography). COVID-19 was diagnosed based on the typical clinical presentation and positive polymerase chain reaction test in nasopharyngeal swabs. All patients were treated in different hospitals repurposed for the treatment of patients with COVID-19. A standard histological study was performed with hematoxylin and eosin, toluidine blue, and van Gieson staining. Serial paraffin slices were studied immunohistochemically with antibodies to CD3, СD68, CD20, perforin, and toll-like receptors (TLR) 4 and 9.Results In none of the cases, myocarditis was suspected clinically, added to the diagnosis or indicated as a possible cause of death. IHD and acute myocardial infarction were mentioned as error diagnoses not confirmed by the postmortem examination. The morphological examination of the heart identified signs of lymphocytic myocarditis consistent with Dallas criteria for this diagnosis. Myocardial infiltrate was characterized in detail, and a combined inflammatory damage of endocardium and pericardium was described. The immunohistochemical study with cell infiltrate typing confirmed the presence of CD3-positive Т lymphocytes and the increased expression of TLR-4. A picture of coronaritis, including that with microvascular thrombosis, was found in all cases.Conclusion A possibility for development of lymphocytic viral myocarditis in COVID-19 was confirmed morphologically and immunohistochemically. Specific features of myocarditis in COVID-19 include the presence of coronaritis and a possible combination of myocarditis with lymphocytic endo- and pericarditis.

Presented herein is the authors' experience gained in employing a method of prosthetic repair of the internal carotid artery in patients suffering from atherosclerotic stenosis. Special attention is paid to intraoperative factors having led to arterial prosthetic reconstruction. Also analysed are the remote results of treatment in 81 of 97 operated patients. The mean duration of follow-up amounted to 28 +/- 3 months. All the patients in the remote period were subjected to colour duplex scanning of the reconstructed tone and that of the contralateral internal carotid artery (ICA), immediately followed by assessing the neurological status. Two patients were found to have developed single transient ischaemic attacks, with their grafts remaining patent. A further three patients had developed thrombosis of the graft, with restenosis of the anastomosis zone being revealed in four patients more. All complications were symptom-free. The obtained findings showed that, taking into consideration the remote results and in certain indications, prosthetic repair of carotid arteries is an efficient method of treatment for atherosclerotic lesions of the ICA and in this relation is at least not inferior to the conventional techniques of carotid endarterectomy.

BACKGROUND: Stromal cells are a functionally important component of human carcinomas. The aim of this study was to obtain and characterise primary cultures of stromal cells from human carcinomas and the corresponding surrounding normal tissue. METHODS: Primary stromal cell cultures from tumours of lung, oesophagus and pancreas were obtained using a mild tissue dissociation method and a medium for culturing mesenchymal cells. Immunofluorescence staining and western blotting were used to analyse the expression of differentiation markers and selected known oncoproteins in the cell cultures obtained. RESULTS: A panel of stromal primary cultures was prepared from different human tumours and from matched normal cancer-free tissues. The in vitro proliferative potential of tumour-associated fibroblasts was shown to be higher than that of matched normal stromal cells. A mutational analysis of the TP53 and KRAS2 genes in a number of stromal cultures did not reveal known mutations in most cells of the cultures studied. Western blot analysis showed that stromal cells of lung tumours were characterised by a statistically significantly lower expression level of the p16 protein as compared with that in normal lung stromal cells. An important finding of our study was that, according to immunofluorescence assay, a fraction of fibroblast-like vimentin-positive cells in some tumour and normal stromal cell cultures expressed an epithelial marker - cytokeratins. CONCLUSIONS: Proliferating stromal cells from the carcinomas studied proved to be genetically normal cells with altered expression profiles of some genes involved in carcinogenesis, as compared with normal stromal cells. Epithelial-mesenchymal transition may lead to the emergence of transdifferentiated fibroblast-like cells in tumour stroma and in the tumour-surrounding tissue.

The guideline presents modern classification, diagnostic algorithms and protocols of complex treatment of various forms of diabetic foot syndrome. The recommendations are intended for use by a wide range of professionals involved in the treatment of patients with this pathology.

A comparative study was performed of the caseinolytic, necrolytic and fibrinolytic activities of a crab collagenase product prepared from the hepatopancreas of the king crab (Paralithodes camtschatica) and four enzyme preparations (trypsin/chymotrypsin and protease complexes isolated from Aspergillus terricola, Carica papaya and pseudomonodaceae). This paper reports an in vitro investigation, an in vivo study with rats and a clinical evaluation. It was found that crab collagenase has the highest proteolytic activity measured with respect to fibrin clot and necrotic eschar in vitro although its caseinolytic activity is the lowest. A clinical trial involving 21 patients with leg ulcers confirmed the clinical efficiency of crab collagenase compared with trypsin/chymotrypsin. The results suggest that crab collagenase is useful in wound debridement.

A new method to isolate adult cardiocytes with pronase in the presence of 250 microM free calcium was developed. Ultrastructural and electrophysiological properties of these cells were investigated. It is shown that by this method normal calcium-tolerant cells can be obtained.

The study of postburn scar contractures in various locations has revealed four contracture variables: edge, medial, strip, and total. Following the surgical treatment of more than 2000 patients with such contractures, a trapezeplasty flap method has been worked out and applied since 1979. This method allows one to make up for deficient scar tissue of the same shape. Flaps are cut out of sheets of a fold with the maximum use of undamaged skin in adjacent sections. They move toward each other and merge with adjacent sides into a state of tension. This surgery is based on use of the reserve on the width of the surface of a fold and the high tension of skin with pressure on underlying tissue. The extended skin grows quickly, the tension disappears, and the scars dissolve. For each contracture type, there are trapeze-flap variables either in pure form or in combination with the transposition of split-thickness skin with a flap to create a flexible joint zone. The trapezeplasty flap method can be used to treat all edge, medial, strip, and total contractures of joints whose natural position is adduction, the shoulder joint, and contractures between fingers. Skin-fat or skin-fascia trapeze flaps prevent the relapse of contracture and make the weakened scars softer, which, as a rule, ensures a good functional and aesthetic result.

BACKGROUND AND OBJECTIVES: The compatibility of an ABO blood group independently applicable plasma, Uniplas, was explored in liver resection because patients undergoing liver resection frequently require the transfusion of plasma to compensate for blood loss and/or clotting factors. MATERIALS AND METHODS: One-hundred and twenty two patients undergoing elective liver resection were enrolled; 81 patients required plasma transfusion, while 41 did not. Of those in need of plasma, 58 were blood group A, B or AB, and 23 were blood group O. Patients were monitored up to day 7 postoperatively for signs of haemolysis and haemostasis, and viral markers were assessed at baseline and 3 weeks postoperatively. RESULTS: Uniplas transfusions of up to 50.7 ml/kg body weight were given per treatment episode, without signs of haemolysis caused by transfusion. A total of 94/99 patients (95%) were negative in the direct antiglobulin test throughout the study. Two patients, one transfused with Uniplas, the other not, had a positive direct antiglobulin test result at baseline, while three of 64 patients transfused with Uniplas demonstrated a change from having negative to intermittently positive direct antiglobulin test results without concurrent signs of haemolysis. International normalized ratio, activated partial thromboplastin time and protein C levels were maintained by transfusion of plasma (>/= 20 ml/kg body weight). No patient underwent seroconversion for human immunodeficiency virus, hepatitis B virus or hepatitis C virus. Positivity for hepatitis A virus (HAV) immunoglobulin G (IgG) in 11 patients from the Uniplas group (who tested HAV immunoglobulin M negative), together with an apparent seroconversion for parvovirus B19 seen in two patients who received Uniplas, indicated passively transferred IgG antibodies. CONCLUSIONS: No haemolysis was observed as a result of Uniplas transfusions up to 50.7 ml/kg body weight per treatment episode in patients undergoing liver resection. Moreover, transfusion (>/= 20 ml/kg body weight of Uniplas) maintained acceptable levels of international normalized ratio, activated partial thromboplastin time and protein C.

Abstract The kinetic specificity of polyethylene terephthalate (PET) degradation in a living body was investigated. The polyethylene terephthalate net implanted subcutaneously in the backs of rabbits and dogs usually degrades from the surface very slowly. The time of complete degradation of PET fibers in both dogs and humans amounts to 30 ± 7 yr. The time for loss of 50% of the initial filament strength under similar conditions is 10 ± 2 yr. An equation for promotion of changes in the mechanical properties of polyethylene terephthalate fibers in living animals and humans has been derived.