[A case of the cerebral vasculitis at the late stage of Kawasaki disease].

A description of the clinical observation of the child at the late stage of Kawasaki disease is presented. In our observation, an aneurysm of the circumflex branch of the left coronary artery was discovered on the echocardiography of the child. MRI results of the brain with vascular program revealed a picture of vasculitis, fusiform expansion of the A1 segment of the right anterior cerebral artery, M1 segment of the left middle cerebral artery. Systemic vasculitis was diagnosed at the late stage of disease. This case shows the importance of better awareness of pediatricians, cardiologists, neurologists about Kawasaki disease, its manifestations at the early stage and possible long-term complications, as well as modern approaches to treatment.

[The clinical picture, diagnostic and treatment of the acute iliopsoitis].

The treatment results of the acute iliopsoitis in 29 patients were analyzed. The right side inflammation was observed more frequently (n=17). The most common infectious agent was the Staphylococcus aureus. The source of the inflammation was septic lesions of the lower body, whereas the perdisposal factors were considered to be the diabetes mellitus, drug abuse and immunodeficiency. The cardinal diagnostic sign of the acute iliopsoitis proved to be the psoas-symptom. The main diagnostic instruments were the ultrasound investigation, CT and MRI. 1 patient was successfully treated conservatively, though the rest 28 demanded surgical opening and drainage of m. iliopsoas. The lethality rate was 3,4%. 96,6% of the treated patients were successfully cured.

[Prophylaxis of acute postoperative gastroduodenal ulcers at the patients with colorectal cancer].

Effective method for prophylaxis of acute postoperative gastric ulcers and erosions was developed. The core of this method is ozone therapy in preoperative period. Intensity of blood serum and erythrocytes chemiluminescence and ATPase activity of erythrocytes were studied at 86 patients with colorectal cancer before surgery and at 1st and 4th days of postoperative period. It was demonstrated that preoperative ozone therapy promoted normalization of free radical reactions and ATPase activity at postoperative period.

[Foreign bodies of appendix and caecum complicated with acute appendicitis].

Twelve patients with exogenous foreign bodies (small chicken and fish bones, portion of wire, nail, cherry stone, piece of glass) of appendix (8) or adjacent zone of caecum (4) were treated. Based on experience of treatment of these patients authors analyze pathogenesis of appendicitis associated with foreign bodies, and other aspects of this problem.

[The activity of adenosinetriphosphatase of erythrocytes in peripheral blood of patients with colorectal cancer].

We studied the activity of whole ATPase, Mg2+ -ATPase and Na+, K+ -ATPase of peripheral blood erythrocytes in 68 patients with colorectal cancer before surgery and immediately after it and found such activity to be reduced. The low activity of Na+, K+ -ATPase of peripheral blood erythrocyte was shown as possible for use in prognosticating acute postoperative erosive-ulcerous lesions of the gastric tunic. Ozone therapy, if undertaken preoperatively, restores the ATPase activity.

Endothelin receptor antagonist TAK-044 arrests and reverses the development of carbon tetrachloride induced cirrhosis in rats.

BACKGROUND AND AIMS: Hepatic concentrations of the powerful vasoconstrictor and fibrogen endothelin 1 (ET-1) and its receptors increase in human and experimental cirrhosis, suggesting a major role for ET-1 in the pathology of chronic liver disease. We investigated whether ET-1 receptor antagonism, after the development of fibrosis and cirrhosis, arrests/reverses the progression of chronic liver disease. METHODS: Chronic liver injury was induced in rats by carbon tetrachloride (CCl(4)) treatment (0.15 ml/kg intraperitoneally twice a week) in conjunction with phenobarbital in drinking water (0.4 g/l) for four (group 1: fibrosis) and eight (group 2: cirrhosis) weeks. Rat were then treated concurrently with the ET-1 receptor antagonist TAK-044 (10 mg/kg/day) and CCl(4)/phenobarbital for a further four weeks. RESULTS: Histopathological examination revealed significant arrest of progression to cirrhosis in group 1 and reversal of cirrhosis in group 2 rats. TAK-044 treatment caused significant amelioration of portal hypertension, systemic hypotension, and liver injury (reduced activities of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), and improved hepatic synthetic capacity (increased serum albumin concentration) in both groups of rats relative to vehicle treated rats. TAK-044 treatment reduced collagen synthesis, as evidenced by decreased hepatic hydroxyproline content, mRNA expression of collagen-alpha type I, and tissue inhibitors of matrix metalloproteinases 1 and 2, and mRNA and protein expression of a potent fibrogenic cytokine, transforming growth factor beta1. CONCLUSIONS: The results emphasise the role of ET-1 in the development of cirrhosis and strongly suggest that blockade of its actions can be a rational therapy for chronic liver disease and its complications.

Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis.

BACKGROUND AND AIMS: The liver is a major site for the synthesis and actions of platelet activating factor (PAF), a potent hepatic vasoconstrictor and systemic vasodilator. As PAF is implicated in portal hypertension and hyperdynamic circulation associated with liver cirrhosis, we characterised changes in the hepatic PAF system in experimental cirrhosis. METHODS: In rats made cirrhotic by carbon tetrachloride (CCl(4)) administration for eight weeks, we determined hepatic levels of PAF and its cognate receptor, and the effects of PAF and PAF antagonist (BN52021) on portal and arterial pressure. RESULTS: Compared with control rats, cirrhotic rats had higher hepatic PAF levels, higher apparent hepatic efflux of PAF, and higher PAF levels in arterial blood (p<0.01, p<0.01, p<0.05, respectively). Relative to controls, cirrhotic livers had elevated hepatic PAF receptors (by mRNA and protein levels and [(3)H]PAF binding), higher (p<0.01) baseline hepatic portal pressure, and an augmented (p = 0.03) portal pressure response to PAF infusion (1 microg/kg). Portal infusion of BN52021 (5 mg/kg) showed that elevated endogenous PAF was responsible for 23% of the cirrhotic portal pressure increase but made no contribution to systemic hypotension. Finally, increased PAF receptor density was observed in the contractile perisinusoidal stellate cells isolated from cirrhotic livers relative to those from control livers. CONCLUSIONS: In cirrhosis, increased hepatic release of PAF elevates systemic PAF; in combination with upregulated hepatic PAF receptors in stellate cells, this contributes to portal hypertension.

Time course of gene expression after plasmid DNA gene transfer to the liver.

BACKGROUND: High levels of expression in hepatocytes can be achieved after intraportal delivery of plasmid DNA vectors with up to 10% of all liver cells transfected. CMV promoter-driven expression is very high on Day 1 after injection, but is diminished strongly by Day 2. Expression slowly declines after 1 week. We describe experiments aimed at elucidating the reasons for this rapid decline in transgene expression. METHODS: Histological methods were used to determine the presence and extent of liver damage and hepatocyte proliferation. Viral and liver-specific promoters were tested to study promoter shut-off, Southern blotting was performed to determine the loss of the pDNA vector over time, and several mouse models were used to study the host immunological response. RESULTS: pDNA is lost rapidly early after injection, but remains at a relatively stable copy number after Day 4. Southern blotting experiments showed that plasmid DNA could be detected for at least 12 weeks after injection (0.2 copies per genome). The early rapid decline of expression is promoter dependent. A liver-specific albumin promoter resulted in similar levels of expression on Days 1 and 7, suggesting that promoter inactivation may be responsible for the instability of CMV promoter-driven expression. The slow decline in expression levels after 1 week appears to be the result of an immune response directed against the expressed transgene. Expression was much prolonged in immunosuppressed, immunodeficient, or antigen-tolerized mice. CONCLUSION: The present data suggest that if promoter inactivation can be overcome, intravascular delivery of plasmid DNA could be a highly efficient, simple and non-toxic liver gene therapy approach. Intravascular delivery of pDNA allows for the rapid screening of novel expression vectors in vivo.

Interleukin-17 antagonism inhibits acute but not chronic vascular rejection.

BACKGROUND: Blocking the action of interleukin (IL) 17 with an IL-17 receptor (R):Fc fusion protein inhibits T-cell proliferative responses to alloantigens and prolongs vascularized heart graft survival. In this study, we examined whether IL-17 antagonism could suppress the development of chronic rejection. METHODS: A 0.6-cm section of C57BL10 (H2b) thoracic aorta was transplanted to recipient C3H (H2k) abdominal aorta. IL-17R:Fc or control human immunoglobulin G was administered i.p. (500 microg/day) from days 0 to 6 or from days 0 to 29. Mice were killed on days 7 or 30. Grafts were examined histologically and stained for alpha-smooth muscle actin (alpha-smA). Antidonor mixed leukocyte reaction, cytotoxic T cell, and alloantibody responses were quantified. RESULTS: On day 7, control grafts showed mononuclear cell (MNC) infiltration, pronounced endothelial damage, and apoptosis of intimal and medial cell compartments. By day 30, there was concentric intimal thickening, accumulation of alpha-smA+ cells, and collagen deposition. Patchy destruction of the elastic membranes and loss of alpha-smA expression in media were evident. IL-17R:Fc for 6 days decreased MNC infiltration in the intimal and medial compartments at day 7. The endothelium was preserved (completely or partially) in all grafts. The medial compartment showed normal alpha-smA expression. Irrespective of IL-17R:Fc treatment for either 6 days or continuously, allografts harvested at day 30 showed circumferential intimal thickening, with accumulation of alpha-smA+ cells and collagen deposition. There was no effect on circulating alloantibody levels. CONCLUSIONS: These findings support a role for IL-17 in the immunopathogenesis of acute vascular rejection and demonstrate the potential of IL-17 antagonism for therapy. By contrast, IL-17 antagonism does not appear to prevent ensuing chronic graft vascular disease, in particular neointimal formation.

Enhanced synthesis and reduced metabolism of endothelin-1 (ET-1) by hepatocytes--an important mechanism of increased endogenous levels of ET-1 in liver cirrhosis.

BACKGROUND/AIMS: Hepatic concentration of endothelin-1 (ET-1) is increased in human and experimental liver cirrhosis. Because of its potent actions in the liver, ET-1 has been suggested to play an important role in the pathophysiology of cirrhosis. Since hepatocytes are the major cell type to metabolize ET-1, we investigated whether their reduced capacity to degrade ET-1 is a mechanism of its elevated levels in cirrhosis. METHODS: The expression of ET-1 receptors, ET-1 and endothelin converting enzyme (ECE), and metabolism of ET-1 and ECE activity were compared in hepatocytes isolated from control and carbon tetrachloride-induced cirrhotic rats. RESULTS: ET-1 receptor density and receptor-mediated internalization of ET-1 were significantly increased in cirrhotic hepatocytes relative to the control cells. However, compared to control hepatocytes, metabolism of ET-1 by the cirrhotic cells was reduced significantly. Interestingly, hepatocytes were found to contain preproET-1 mRNA, ECE-1 mRNA and ET-1. PreproET-1 mRNA and ET-1 levels were increased in cirrhotic hepatocytes but their ECE mRNA and ECE activity were not altered. CONCLUSIONS: These results provide the first evidence that hepatocytes have the ability to synthesize ET-1 and demonstrate that decreased metabolism and enhanced synthesis, of ET-1 in hepatocytes are an important mechanism of its elevated levels in cirrhosis.

Interleukin-12 and Flt3 ligand differentially promote dendropoiesis in vivo.

Interleukin-12 (IL-12) and Flt3 ligand (FL) regulate hematopoiesis by stimulating proliferation, differentiation and migration of progenitor and/or stem cells. In this study, we evaluated the in vivo effect of IL-12 alone or in combination with FL on dendritic cell (DC) generation and accumulation in murine spleen, lymph node, thymus, liver, and tumor tissues. Both cytokines induced accumulation of functional DC in lymphoid and non-lymphoid tissues. IL-12 promoted predominantly myeloid dendropoiesis, while FL induced both myeloid and lymphoid dendropoiesis. Combination treatment resulted in a dramatic increase in CD86+, and particularly, NLDC-145+ cells within the liver, which was largely due to cell proliferation. Combination therapy also revealed the ability of FL to protect bone marrow cell populations from IL-12-induced depletion in vivo. In vitro, we found a significant FL-induced up-regulation of IL-12 production by DC at both mRNA and protein levels. Thus, our study suggests that (i) the antitumor activity of IL-12 may, at least in part, be mediated by the stimulation of dendropoiesis and (ii) IL-12 might contribute to the antitumor activity of FL. Furthermore, induction of DC generation in vivo by a combination of IL-12 and FL might become a new approach for immunotherapy of cancer.

[Foreign bodies of the rectum]. / Inorodnye tela priamoi kishki.

During the 22 years period there were 26 patients (23 men and 3 women) aged from 18 to 71 with foreign bodies in the rectum introduced through the anal canal. The main causes of the appearance of foreign bodies in the rectum were anal masturbation (in 12 patients) and forced introduction of the objects by other people (in 10 patients). Among the foreign bodies prevailing were plastic and glass bottles, cucumbers and carrots, wooden and rubber objects in the from of the phallus. Typical were large sizes of the most objects introduced (the diametrical size more than 6 cm and the length more than 15 cm) which was responsible for the development of complications and made the removal difficult. The symptoms of the presence of foreign bodies in the rectum were determined as well as the optimum methods of diagnosis. A classification of rectal foreign bodies is proposed for the solution of medico-tactical tasks. The transcanal removal of the foreign bodies was fulfilled in 23 patients. The standardized technique of the transcanal removal of the objects is thought by the authors to include 10 principal propositions. Open operative interventions (removal of the foreign body, suturing the rupture, drainage of the abdominal cavity or of the perirectal space, sigmostomy) were performed in 4 patients with penetrating injuries of the rectum wall. The results of the treatment including removal of all foreign bodies were good, without lethal outcomes.

Comparative analysis of dendritic cell density and total number in commonly transplanted organs: morphometric estimation in normal mice.

Dendritic cells (DC) are considered to be the major cell type responsible for induction of primary immune responses. While they have been shown to play a critical role in eliciting allosensitization via the direct pathway, there is evidence that maturational and/or activational heterogeneity between DC in different donor organs may be crucial to allograft outcome. Despite such an important perceived role for DC, no accurate estimates of their number in commonly transplanted organs have been reported. Therefore, leukocytes and DC were visualized and enumerated in cryostat sections of normal mouse (C57BL/10, B10.BR, C3H) liver, heart, kidney and pancreas by immunohistochemistry (CD45 and MHC class II staining, respectively). Total immunopositive cell number and MHC class II+ cell density (C57BL/10 mice only) were estimated using established morphometric techniques--the fractionator and disector principles, respectively. Liver contained considerably more leukocytes (approximately 5-20 x 10(6)) and DC (approximately 1-3 x 10(6)) than the other organs examined (pancreas: approximately 0.6 x 10(6) and approximately 0.35 x 10(6); heart: approximately 0.8 x 10(6) and approximately 0.4 x 10(6); kidney approximately 1.2 x 10(6) and 0.65 x 10(6), respectively). In liver, DC comprised a lower proportion of all leukocytes (approximately 15-25%) than in the other parenchymal organs examined (approximately 40-60%). Comparatively, DC density in C57BL/10 mice was heart > kidney > pancreas >> liver (approximately 6.6 x 10(6), 5 x 10(6), 4.5 x 10(6) and 1.1 x 10(6) cells/cm3, respectively). When compared to previously published data on allograft survival, the results indicate that the absolute number of MHC class II+ DC present in a donor organ is a poor predictor of graft outcome. Survival of solid organ allografts is more closely related to the density of the donor DC network within the graft.

Hypogonadism precedes liver feminization in chronic alcohol-fed male rats.

Men who chronically abuse alcohol may display a spectrum of endocrine abnormalities including hypogonadism and feminization, with elevated serum estradiol and low serum testosterone. We examined factors that may result in disruption of hepatic sex hormone homeostasis in alcohol-fed male rats and possible consequences of such changes. Rats were fed alcohol-containing or isocaloric diets for 30, 60, and 90 days. In alcohol-fed rats, serum testosterone levels and hepatic activity of 2 androgen-dependent estrogen metabolizing enzymes were reduced (P <.05) at all times, as was activity of androgen receptor. There was also a significant early and progressive decrease in testes/body ratio in alcohol-fed rats. Compared with this early decrease in testosterone-related parameters, there was a significant increase in serum estrogen levels (at 30 and 90 days, 132% and 168% of control values, respectively). An increase in serum ceruloplasmin, an estrogen-responsive liver protein, was apparent at 60 and 90 days, but not at 30 days of alcohol exposure, suggesting that hypogonadism precedes liver feminization. Hepatic estrogen receptor activity was decreased in alcohol-fed rats at 60 and 90 days, the latter despite elevated serum estrogen levels. Hepatic aromatase was slightly increased in alcohol-fed rats, an elevation probably not sufficient to account for observed increases in serum estrogen. Taken together, these data suggest that (1) alcohol induces profound reduction of serum testosterone, resulting in loss of androgen-regulated hepatic functions such as estrogen-metabolizing enzyme activity and activity of androgen receptors; and (2) such alcohol-induced hypogonadism precedes changes in hepatic sex hormone homeostasis and subsequent feminization.

Differential regulation of epidermal and dermal dendritic cells by IL-12 and Flt3 ligand.

An abrogation of the decline in epidermal Langerhans cell numbers above melanoma might significantly improve the efficacy of immunotherapy for melanoma treatment. Systemic Flt3 ligand (FL) administration in mice induced a significant increase in mature dendritic cells (DC) within the skin, preferentially in the dermis, whereas IL-12 promoted a significant increase of immature DC preferentially in the epidermis. Both effects were abrogated in IL-12 knockout mice. Thus, IL-12 could promote FL-induced accumulation of skin DC. The involvement of FL and IL-12 in the regulation of DC accumulation within the skin may contribute, at least in part, to the stimulation of antimelanoma immunity by FL- and IL-12-based immunotherapies. Moreover, FL and IL-12 could be used for selective in vivo generation of DC in either epidermis or dermis for experimental and clinical purposes.

[Surgical policy in gastrointestinal tract foreign bodies]. / Khirurgicheskaia taktika pri inorodnikh telakh zheludochno-kishechnogo trakta.

66 patients (45 males and 21 females) who have swallowed 157 foreign bodies (fragments of wire, nails, needles, hafts of spoons, et were treated). If the objects were located in the stomach and the duodenum in the absence of complications endoscopic method of treatment was preferable, with the help of which 31 objects were successfully removed and the terms of treatment were significantly decreased. Conservative treatment (diet rich in fiber and protective substances, barium sulfate administration) resulted in elimination of 58 objects by vias naturals, 53 from which were not more that 8 cm long. Evacuation of the foreign bodies was carried out only during the first 3 weeks after the swallowing. Operative treatment was carried out in 21 patients, in whom 68 foreign bodies were extracted. An urgent operation in the first 6 hours in complications due to foreign bodies (perforation, incarceration, gastrointestinal bleeding) was carried out in 13 patients. An urgent operation in terms from 6 to 24 hours of hospitalization was carried out in 6 patients with large (more that 8 cm) swallowed objects, conglomerates and bunches of foreign bodies. Early removal of these objects prevented development of complications. Elective operation was carried out in failure of conservative treatment as was in 2 patients. No lethality was registered.

A fresh look at augmenter of liver regeneration in rats.

Augmenter of liver regeneration (ALR) is a hepatotrophic protein originally identified by bioassay in regenerating rat and canine livers following partial hepatectomy and in the hyperplastic livers of weanling rats, but not in resting adult livers. The ALR gene and gene product were subsequently described, but little is known about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dissemination of the peptide. To obtain this information in rats, we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent assay (ELISA). ALR concentrations were then determined in intact livers of unaltered weanling and adult rats; in regenerating residual liver after partial hepatectomy; in cultured hepatocytes and nonparenchymal cells (NPCs); and in culture medium and serum. ALR in the various liver cells was localized with immunohistochemistry. In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. The hepatocyte was the predominant liver cell in which ALR was synthesized and stored; the cultured hepatocytes secreted ALR into the medium in a time-dependent fashion. Contrary to previous belief, the ALR peptide and ALR mRNA were present in comparable concentrations in the hepatocytes of both weanling and resting adult livers, as well as in cultured hepatocytes. A further unexpected finding was that hepatic ALR levels decreased for 12 hours after 70% hepatectomy in adult rats and then rose with no corresponding change in mRNA transcripts. In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereafter. Thus, ALR appears to be constitutively expressed in hepatocytes in an inactive form, and released from the cells in an active form by unknown means in response to partial hepatectomy and under other circumstances of liver maturation (as in weanling rats) or regeneration.