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In the inbred SHR/OlaIpcv rat colony, we identified males with small testicles and inability to reproduce. By selectively breeding their parents, we revealed the infertility to segregate as an autosomal recessive Mendelian character. No other phenotype was observed in males, and females were completely normal. By linkage using a backcross with Brown Norway strain, we mapped the locus to a 1.2Mbp segment on chromosome 7, harboring 35 genes. Sequencing of candidate genes revealed a G to A substitution in a canonical ‘AG’ splice site of intron 37 inSbf1(SET binding factor 1, alias myotubularin-related protein 5). This leads to either skipping exon 38 or shifting splicing one base downstream, invariantly resulting in frameshift, premature stop codon and truncation of the protein. Western blotting using two anti-Sbf1 antibodies revealed absence of the full-length protein in the mutant testis. Testicles of the mutant males were significantly smaller compared with SHR from 4weeks, peaked at 84% wild-type weight at 6weeks and declined afterward to 28%, reflecting massive germ cell loss. Histological examination revealed lower germ cell number; latest observed germ cell stage were round spermatids, resulting in the absence of sperm in the epididymis (azoospermia). SBF1 is a member of a phosphatase family lacking the catalytical activity. It probably modulates the activity of a phosphoinositol phosphatase MTMR2. Human homozygotes or compound heterozygotes for missenseSBF1mutations exhibit Charcot–Marie–Tooth disease (manifested mainly as progressive neuropathy), while a single mouse knockout reported in the literature identified male infertility as the only phenotype manifestation.

Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA.Methods.PGRN levels were evaluated in patients with RA (n=47) and OA (n=42) and healthy controls (n=41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied.Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1±100.2and221.5±102.5versus128.1±34.7 ng/mL;P<0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5±275.3versus241.4±165.2 ng/mL;P=0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r=0.327,P=0.049) and HAQ score (r=0.323,P=0.032), while synovial fluid PGRN correlated only with HAQ (r=0.310,P=0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies.Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.

Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects.To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity.Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28).Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p0.02), and DAS28 (r=0.44, p0.05), but not with selected (adipo) cytokines.The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.

We studied the effect of peroxisome proliferator-activated receptor-α (PPAR-α) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-α agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-α activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.

Analysis of one case of vulvar extramammary Paget´s disease (EMPD) and associated well differentiated endometrial adenocarcinoma.Desing: A case report.On this case report we present current theoretical knowledge about EMPD, difficulty of diagnostics, treatment and dispensarization the patients with this rare intraepithelial non-squamous neoplasia. We report a rare case of a 62 years old female patient with extramammary Paget´s disease of vulva and associated well differentiated endometrial adenocarcinoma.EMPD is a rare intraephitelial non-squamous neoplasia, which represents less then 1% vulvar tumors. Predominantly it affects white women between 60 and 80 years of age. EMPD occurs in cutaneous areas bearing apocrine glands - vulva, perineum, perianal area, axilla, penis, scrotum and rarely region of tights or buttocks. It is characterized microscopically by the presence of specific tumor cells called Paget´s cells - atypical large cells with pale clear cytoplasm and large round nuclei.extramammary Paget´s disease, EMPD, Paget´s cells, vulvectomy, imiquimod 5%, photodynamic therapy, imunotherapy, radiotherapy.

Kolevska J., R. Husnik, V. Brunclik, V. Mandys, Z. Vernerova, P. Schanilec, L. Barto‰ova, M. Svoboda:A Case of Canine Insulinoma . Acta Vet. Brno 2004, 73: 353-358. The paper reports on a ten-year-old German Shepherd presented with a history of episodic weakness and convulsions after exercise. The patient showed status epilepticus upon presentation. Glucose concentrations repeatedly determined by glucometer were below detection threshold. After intravenous administration of glucose the condition always temporarily improved, however after 1‐2 hours the situation reverted. Insulinoma was diagnosed on the basis of parallel determination of hypoglycaemia (glucose 3.3 mmol⋅l -1 ) and hyperinsulinaemia (2.398 pmol⋅l -1 ). A poor prognosis was stated and the owner decided for euthanasia. Necropsy revealed a tumour of pancreas. Subsequent pathological, immunohistochemical and electron microscopic examinations confirmed the diagnosis of insulinoma.

The clinical course and therapy of mantle cell lymphoma (MCL) are heterogeneous and often unsatisfactory. Prognostic factors are needed to stratify the patients. Microvessel density (MVD) has prognostic significance in some malignancies. There is little information about the vasculature of MCL, although some antiangiogenic drugs are in use. We studied MVD using systematic uniform random sampling and unbiased counting frames in immunohistochemical reactions with anti-CD34 antibody in pre-therapeutic extramedullary MCL samples of 177 patients. We analyzed the relationship of MVD to overall survival (OS) and progression-free survival (PFS), as well as to proliferative activity (Ki-67), mantle cell lymphoma prognostic index (MIPI), morphological variant, pattern of growth, and localization. MVD varied widely: range 54.6-503.6 vessels/mm(2), median 158.2 vessels/mm(2). Higher MVD was associated with bone marrow infiltration at the time of diagnosis (P = 0.001). High MVD was associated with significantly worse OS (P = 0.04) only in patients treated with non-intensive (conventional) therapy. MVD correlated positively with MIPI scores but not with the proliferation, morphological variant, growth pattern, or localization. Univariate analysis identified a prognostic influence of morphological variant, MIPI, and proliferative activity on OS and PFS and a prognostic influence of bone marrow infiltration at the time of diagnosis on PFS. Multivariate analysis showed prognostic influence of MIPI and proliferative activity on OS and PFS only. In conclusion, this is the first clinicopathological study of MVD of MCL with long-term follow-up showing negative prognostic trends of high MVD in MCL and positive correlation of MVD and MIPI.

Retroviruses are known to integrate in the host cell genome as proviruses, and therefore they are prone to cell-mediated control at the transcriptional and posttranscriptional levels. This plays an important role especially after retrovirus heterotransmission to foreign species, but also to differentiated cells. In addition to host cell-mediated blocks in provirus expression, also so far undefined host specificities, deciding upon the pathogenic manifestation of retrovirus heterotransmission, are in play. In this respect, we discuss especially the occurrence of wasting disease and immunodeficiency syndrome, which we established also in avian species using avian leukosis virus subgroup C (ALV-C) inoculated in mid-embryogenesis in duck or chicken embryos. The problem of provirus downregulation in foreign species or in differentiated cells has been in the recent years approached experimentally. From a series of observations it became apparent that provirus downregulation is mediated by its methylation, especially in the region of proviral enhancer-promoter located in long terminal repeats (LTR). Several strategies have been devised in order to protect the provirus from methylation using LTR modification and/or introducing in the LTR sequence motifs acting as antimethylation tags. In such a way the expression of retroviruses and vectors in foreign species, as well as in differentiated cells, has been significantly improved. The complexity of the mechanisms involved in provirus downregulation and further possibilities to modulate it are discussed.

Proviral DNA load and expression of avian leukosis viruses of subgroup C (ALV-C) in ducks infected in mid embryogenesis were studied using quantitative PCR, RT-PCR, in situ hybridization employing ALV-specific riboprobe, and immunohistochemistry. A group of long-term surviving, non-reviremic ducks was selected for the study and compared to control reviremic animals in order to obtain information about persisting retroviruses in different duck tissues. A widespread distribution of proviruses in the tested tissues was found, but the proviral load was significantly lower in non-reviremic in comparison to reviremic animals. The only exception were brain and blood cells, in which no significant difference in the quantity of integrated proviruses was found between both categories of ducks, thus indicating an exceptional position of the brain and blood cells among all tested tissues. Contrary to reviremic, the proviruses were not transcribed in non-reviremic ducks, with the exception of brain and thymus. In the majority of non-reviremic ducks viral RNA was revealed in the brain, but no infectious virus could be recovered from this tissue. The opposite situation was observed in the thymus, where infectious virus was recovered but viral RNA remained below the detection limit of the assay. As revealed by in situ analysis, infected cells were either disseminated or focally distributed in tissues. From the long-term follow up of ALV-C in intraembryonally infected ducks we conclude that this model is suitable for the study of retrovirus persistence accompained both by the presence and absence of reviremias. The possible consequences of transmission and long-term persistence of retroviruses in the heterologous host for retroviral evolution are discussed.

Objective To assess the expression of the novel adipokine Fatty Acid Binding Protein-4 (FABP4) in synovial tissues, serum and the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationships among FABP4, disease activity and metabolic status. Methods FABP4 levels were measured in the serum and synovial fluid of 40 patients with RA and 40 control patients with OA. The disease activity score (DAS28), C-reactive protein (CRP) levels and serum lipids were assessed in patients with RA. Immunohistochemical analysis and confocal microscopy were used to study the expression and cell-specific distribution of FABP4 in synovial tissues. Results The age, sex and body mass index (BMI) adjusted levels of FABP4 were significantly higher in the serum ( p = 0.001) and synovial fluid ( p = 0.005) of patients with RA when compared to OA patients. FABP4 levels were higher in females than in males and correlated positively with body mass index (BMI) in patients with RA. Independent of confounders, FABP4 levels correlated with total cholesterol and LDL cholesterol in patients with RA, but not in OA patients. FABP4 levels were not affected by disease activity. Furthermore, the increased expression of FABP4 that was otherwise restricted to synovial fibroblasts, macrophages and B-cells was noted in RA patients at levels higher than that observed in OA patients. Conclusions The observed elevation of FABP4 levels in RA patients and the positive correlation of the adipokine to cholesterol suggest that FABP4 may represent a potential link between RA and the increased risk of atherosclerotic changes.

To evaluate risk factors for development of recurrent disease in borderline ovarian tumors.Retrospective study of 10-years single institution population.Dept. of Gynecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague.59 consecutive cases of borderline ovarian tumors (BOT) were analyzed for age, histopathological type, DNA ploidy, stage, presence of invasive and non-invasive peritoneal implants, type of surgical procedure, residual disease, adjuvant therapy, recurrence and long-time prognosis of the patients.Median follow-up was 47 months (range 1-144). There were 5 (8.5%) patients with DNA aneuploid tumors in the study group; 4 of them were younger than 50 years, 4 of them were early stage serous BOT; no one recur so far. No death of disease was described in the whole study group; only 2 patients (3.4%) developed recurrent disease - both were young patients after conservative surgery for serous diploid stage I/II BOT. Conservative surgery was the only significant factor for recurrence in univariate analysis (p = 0.0159) in our setting.DNA ploidy was not proved to be prognostic factor in borderline ovarian tumors in our study group. The only significant risk factor for development of recurrent disease was conservative surgery, with no influence on overall survival.

To develop guideline for primary surgical treatment of endometrial carcinoma.Review, consensus of expert group.Dept. of Gynaecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague.A retrospective review of published data, analysis of statistic data from Czech Republic, consensus among proposers and opponents.The guideline recognizes endometrial carcinoma patients based on their risk and recommends type of surgical treatment for certain group. It emphasizes the importance of centralized oncogynaecological treatment. Surgical staging remains the basic principle for treatment of endometrial carcinoma patients. The aim of pre-operative diagnostics is to estimate the extent of the disease--"interim staging", that can be different from definitive histopathological staging. Based on risk factors patients are divided into low or high risk group. Standard procedure for low risk patients is hysterectomy and bilateral salpingoophorectomy. It is advisable to use peroperative biopsy in these patients that can shift the patient to high risk group. High risk patients are recommended for hysterectomy, bilateral salpingoophorectomy, and systematic aortopelvic lymphadenectomy. The guideline contains recommendation for young patients wishing to preserve their fertility, for cases of inadequate surgery and for follow-up.Guideline for treatment of endometrial carcinoma is recommendation for clinicians and other subjects who participate on the process of the diagnostics/treatment of endometrial carcinoma patients. All points of the guideline were discussed and voted about by all participants of expert group.

Post-traumatic splenic pseudocysts are rare condition and comprise more than 75% of non-parasitic cysts. They result from subcapsular or intraparenchymatous hematoma, by its liquefaction and creation of the fibrous peripheral capsula. Splenic pseudocysts have no epithelial lining, its diameter could be more than 15 cm and are mostly symptomatic.A female, 53 years old, was admitted to the Clinic of surgery with blunt pains in the left hypochondrium after falling on the left side of body 6 months ago. Ultrasonography and CT scan reveal posttraumatic pseudocyst of the spleen, 156 x 135 x 148 mm in diameter. The splenic parenchyma was reduced to 15 mm dorso-caudal. Extirpation of the pseudocyst and splenectomy during laparotomy was performed with healing per primam. The patient was discharged 6 day after surgery.Posttraumatic splenic pseudocysts are good diagnosed in CT scan. Giant pseudocysts and psuedocysts in splenic hilus require surgical resection. Spleen parenchyma preserving operations, currently recommended in small cysts, reduce the risk of early and late septic complications, particularly overwhelming postsplenectomy sepsis. Partial splenectomy offers a definitive treatment of a splenic cyst while preserving splenic functions. Miniinvasive surgery as a percutaneous drainage and laparoscopic fenestration have an unacceptably high rate of failure.

Experimental model of 5/6 nephrectomy or the remnant kidney model represents one of the most used animal models of progressive renal failure by reduced nephron number, best-characterized in rats. The reduction of renal mass is achieved by either infarction or surgical excision of both poles, with removal of the contralateral kidney. It enables to investigate the influence of pharmacological, nutritive and other factors on functional and morphological renal parameters. 5/6 nephrectomy produced by infarction is characterised by high plasma renin levels. By contrast, reduction of an equivalent amount of renal parenchyma by surgical excision does not result in the development of hypertension and plasma renin activity is normal to low. The initially normal remnant nephrons undergo compensatory functional and structural adaptations. Simultaneous glomerular hypertension is one of the main factors responsible for the development of renal injury. Morphologicaly progressive focal segmental to global glomerulosclerosis is present, accompanied clinically by increasing proteinuria and deteriorating renal function.

Fibrillary glomerulonephritis (FGN) is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic hematuria, nephrotic syndrome or decreased kidney function. Around one half of patients develop chronic renal failure in the course of several years. The diagnosis of fibrillary glomerulonephritis is to be established only basing on the results of renal biopsy. Pathognomonic is the electron-microscopic examination, evidencing fibrillar deposits in mesangium and in basal membranes of glomeruli. Fibrils are similar to those seen at amyloidosis, however, with larger diameter, non-linear deposition and do not stain with Congo red or thioflavin T. Immunofluorescency test usually shows the presence of IgG, namely the subclasses IgG4, C3 and kappa and lambda of light immunoglobulin chains. The presented case report describes clinical and laboratory findings at a patient suffering from nephrotic syndrome. Results of renal biopsy and detailed histological examinations concluded the diagnosis as fibrillary glomerulonephritis. The patient was treated with a combination of prednisone (1 mg/kg/24 hrs) with cyclophosphamide (2 mg/kg/24 hrs) for six months. This led to a decrease of proteinuria from the initial value of 5.38 g/24 hours to 1.88 g/24 hours, as well as to a partial remission of nephritic syndrome. Glomerular filtration, evaluated using endogenous creatinine clearance, remained within limits of normal values throughout the follow-up, with the value of 2.6 ml/s after the treatment.

We have studied the pathogenic changes in Khaki Campbell ducks injected in mid embryogenesis with ALV subgroup C virus td daPR-C derived from a molecular clone. The employed duck flock was shown to be highly genetically homogeneous and was controlled for the absence of current infections. Clear symptoms of wasting disease, which appeared since one week post hatching, represented the early consequence of the virus infection. They were manifested by decreased body weight, including clear involution of thymic tissue and pronounced anaemia. Microscopically, thymuses of infected animals displayed lymphatic depletion, clearly visible in the lobular cortex. Similarly, in the bursa Fabricii follicles, a marked reduction of the cortical layer and a decrease in folicullar centres was revealed. A decrease in the antibody response correlated with bursa Fabricii atrophy. The clear signs of anaemia were confirmed by haematological measurements, red blood cell count, haematocrit value and haemoglobin included. On the basis of these and additional observations we propose that inoculation of duck embryos provides a suitable model for analysis of the wasting disease produced by ALV-C.

An overview concerning different types of kidney involvement associated with monoclonal gammapathy (MG) is given, focused on light-chain deposition disease (LCDD). Pathophysiologic basis of LCDD remains in the light-chain tissue deposition (resp. in tissue deposition of immunoglobulin's stable domain). This mechanism is typical for monoclonal immunoglobulin's overproduction as found in MG. Clinical picture of LCDD reflects multiorgan character of disorder, while renal lesions rank among the most frequent, serious and best documented ones. Clinical data referring to a group of six patients, treated in our nephrologic department are presented. Diagnosis of LCDD was established on basis of the renal biopsy finding. Renal functions were decreased at the time of diagnosis in all patients, whereas haemodialysis treatment was started in one patient. On conclusion therapeutic possibilities of LCDD are discussed, in which number symptomatic therapy of renal failure is combined with corticosteroids therapy and cytostatic therapy; prognosis of most patients remains serious.

A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.

Chest pains are related to coronary disease, and to several other disorders, among which the most commons are the oesophageal diseases. The aim of the work was the identification of the reflux oesophagitis in patients with chest pain and normal selective coronary angiogram.In the examined group 65 patients (42 females, 23 males) of the average age 55.2 years were included. All of them underwent endoscopic investigation with biopsy from the terminal part of the oesophagus. Endoscopy picture was evaluated according Savary-Miller classification. Biopsy samples were histologically examined and evaluated according our proper classification of the reflux oesophagitis (1st degree: mild, 2nd degree: medium, 3rd degree: heavy, 4th degree: ulcerous). Endoscopical finding was normal in 59 patients (90.8%), reflux oesophagitis of the 1st degree in 2 patients (3.1%) 2nd degree in one patient (1.5%), 3rd degree in 2 patients (3.1%), 4th degree in one patient (1.5%). Histological changes which can be included into the picture of so called microscopic oesophagitis were found in 49 patients (75.4%). The rest of patients had the histology picture normal.In 75.4% of patients with chest pain and negative selective coronary angiogram histological examination revealed structural changes corresponding with oesophagitis, mostly of the mild type.

Increased permeability of glomerular capillary wall in adriamycin nephropathy may be mediated by increased generation of free radicals and possibly also by the non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors may reduce proteinuria, possibly due to the decrease of intraglomerular pressure and increased permselectivity of the glomerular capillary wall. These effects may be partly mediated by the inhibition of the degradation of kinins. It is not clear if newly available angiotensin II antagonists have the same antiproteinuric and renoprotective effects.We compared the effect of an ACE inhibitor (enalapril, 0.4 mg/kg bw i.p. daily for 3 weeks) and angiotensin II antagonist (losartan, 2 mg/kg bw in the same way) on experimental nephrotic syndrome induced in rats by the administration of adriamycin (5 mg/kg bw i.v. in a single dose). To elucidate the potential differences between these two drugs we also measured total malondialdehyde in blood and urinary excretion some eicosanoids and their metabolites (TxB2, 6-keto-PGF1alfa, bicyclo-PGE2 and 8-isoprostane). Proteinuria increased in adriamycin treated rats after 3 weeks from 0.18 +/- 0.01 to 0.44 +/- 0.14 g/mmol creat, p0.01. This increase was not prevented by losartan (increase from 0.18 +/- 0.12 to 0.50 +/- 0.11 g/mmol creat, p0.05), but tended to be partly blunted by enalapril (increase from 0.20 +/- 0.10 to only 0.32 +/- 0.08 g/mmol creat, p0.05). Similarly there was no increase of serum cholesterol, only in enalapril treated rats. On the other hand, both losartan (1.27 +/- 0.13 vs. 1.91 +/- 0.30 mumol/l, p0.05) and enalapril (0.93 +/- 0.06 mumol/l, p0.001) prevented adriamycin induced increase of total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treated by losartan compared to controls. Enalapril induced increase of urinary excretion of bicyclo-PGE2 (4.32 +/- 0.62 vs. 1.66 +/- 0.81 ng/mmol creat, p0.001) was possibly mediated by kinins. There was no significant difference in the urinary excretion of other eicosanoids between different groups, but proteinuria correlated positively with urinary excretion of 8-isoprostane (p0.01). Proteinuric rats had also significantly higher urinary excretion of 8-isoprostane than non-proteinuric rats (44.8 +/- 7.1 vs. 26.7 +/- 3.4 ng/mmol. creat, p0.05).Our data suggest that proteinuria in adriamycin nephropathy may mainly depend on free radical generation and the formation of 8-isoprostane. Haemodynamic parameters (glomerular pressure) do not seem to be so important. The mild antiproteinuric effect of enalapril may suggest a contributory role of the inhibition of kinin degradation in this model of nephrotic syndrome.

A case report of a young patient (born in 1980) with a 2-year history of chronic ulcerative proctocolitis was described. Checking colonoscopy 6 months from the beginning of disease showed multiple and even confluent polypoid lesions in transverse gut starting from hepatic flexure in addition to diffuse inflammatory rectosigmoideal changes. Biopsy found only colic mucosa without any tumorous structures. Five months later the patient's state got worse accompanied instantly by vomiting, weight loss and malabsorption symptoms. A duodenocolic fistula was supposed according to gastroduodenoscopy and biopsy. Because of progressive suffering of the patient colectomy with ileoduodenoanastomosis and ileosigmoidoanastomosis was performed. Polypous lesions were observed from the blind gut up to descendent colon and a transversoduodenal fistula was proved. The removed part of gut was completely changed into a dense network of elongated polypous lesions. In microscopy, bigger polyps showed an inner stromal part often with bands of smooth muscle cells covered by nearly normal gut mucosa. Smaller polyps were formed by hypertrophic gut mucosa only. At the base of polyps, a stagnation of gut contents was found as well as ulcerous defects of various depth. Macroscopy and microscopy of polypoid lesions formed by non-neoplastic gut mucosa were those of so called bizzare ("giant") inflammatory polyposis of the gut. Up to now the patient's clinical picture and local finding in the stump of resected gut have been typical for chronic ulcerous colitis and polypous lesions were not revealed by checking investigations.

Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process.We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R).Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.

A case of a rare skin adnexal tumour, aggressive digital papillary adenoma was described. The tumour had a characteristic forefinger localization, showed microscopical cystopapillary pattern combined with more solid and partly cribriform structures. Tumour cells were represented by lighter cuboid and darker smaller spindle elements. In immunohistology, the tumour cells were positive for epithelial markers (CK, EMA), minority of them showed S 100 protein positivity. Basal cells along the collagenous stroma tissue were strongly actin positive. The light microscopical picture was complemented by electron microscopy for the sake of a more detailed description of tumour cells.

The involution of Wolffian duct in female rat fetuses from 15 to 21 days of gestation was studied in electron microscope. The female Wolffian duct stopped its differentiation on day 17 and the onset of duct regression was found in 18 days old fetuses. The involution was accompanied by degeneration and disintegration of epithelial cells, removal of basal lamina and elimination of altered cells into periductal mesenchyme. Although the mechanism of programmed cell death contributed to the WD regression the findings of non-altered epithelial cells supported the opinion of possible migration of some WD cells into the mesenchymal cell compartment.

The structural differentiation of the Müllerian ducts of both sexes was studied in rat fetuses from 15 to 21 days of gestation. Differences between the male and female Müllerian ducts were observed from the 17th day onward. The epithelium of male Müllerian duct lost its regular arrangement, the increased lysosomal activity and disintegration of some cells was found. The involution of the male duct was accompanied by the condensation of the surrounding mesenchyme with the participation of macrophages. The female Müllerian duct was lined with simple columnar epithelium; its pattern remained indifferent until birth. The apical migration of centrioles and solitary cilia formation belonged to the typical findings from the 18th day. Neither ciliated cells nor multiple centriole replication were observed in oviductal segment of Müllerian duct.

The horns of bicornic uterus in the rat develop from the middle parts of Müllerian ducts. Female rat fetuses for this study were taken on 16-21 days of gestation. On the 16th prenatal day the uterine part of Müllerian duct was short, lined with a columnar epithelium and basal lamina around the duct was incomplete. During further development the duct enlarged, epithelial cells became taller and basement membrane was formed. Until birth the epithelium remained relatively indifferent as far as the periductal mesenchyme. Contrary to the animals with a long gestational period and human, the differentiation of uterine wall including uterine mucosa in the rat takes place after birth.

Submicroscopic examination of rat oviducts in the early postnatal period showed that the character of the epithelium remained relatively indifferent up to the 6th day. Typical findings in this phase include an apical migration of the centrioles, with subsequent formation of solitary cilia; ciliated cells were an isolated occurrence. Ciliogenesis in the rat oviductal epithelium starts between the 8th and the 10th day. A continuous kinociliary apparatus is formed on the basis of centriole replication. The first secretory and peg cells appear towards the end of the second week.

We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat – dominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR-Dca compared with SHR (P1.2-fold difference in expression between SHR and SHR-Dca. Tumor necrosis factor was the most significant upstream regulator and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR-Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR-Dca strain, decreases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney.

Acute liver failure (ALF) is a clinical condition with very high mortality rate. Its pathophysiological background is still poorly understood, which necessitates a search for optimal experimental ALF models with features resembling those of the human disorder. Taking into consideration reproducibility of induction of ALF, adequate animal size, cost of animals, the required time gap between insult and death of animals (“therapeutic window”), potential risk to investigator and other aspects, administration of thioacetamide (TAA) in rats is currently most recommended. However, the fundamental details of this ALF model have not yet been evaluated. This prompted us to investigate, first, the course of ALF as induced by intraperitoneal TAA at doses increasing from 175 to 700 mg/kg BW per day. The animals’ survival rate, plasma alanine and aspartate aminotransferase activities, and bilirubin and ammonia levels were determined over the follow-up period. Second, we examined whether Wistar and Lewis rats exhibit any differences in the course of ALF induced by different TAA doses. We found that the optimal dose for ALF induction in rats is 350 mg.kg-1 i.p., given as a single injection. Wistar rats proved more susceptible to the development of TAA-induced ALF compared with Lewis rats. Collectively, our present findings provide a sound methodological background for experimental studies aimed at evaluation of pathophysiology and development of new approaches in the therapy of ALF.

Serum levels of adiponectin were measured in patients with benign prostatic hyperplasia and prostate cancer of pT2 and pT3 stage. Adiponectin ELISA assay, immunohistochemistry, and selected metabolic and biochemical parameters measurement was performed in 25 patients with benign prostatic hyperplasia and 43 with prostate cancer (17 patients with organ-confined and 26 patients with locally advanced disease). Serum adiponectin levels did not differ between prostate benign hyperplasia and cancer clinical stage T2, but was significantly higher in pT3 relative to pT2 group (14.51±4.92 vs. 21.41±8.12, P = 0.003). Tissue immunohistochemistry showed enhanced staining in neoplastic prostate glands and intraepithelial neoplasia relative to benign prostatic hyperplasia without distinction between disease grade and stage. Serum adiponectin levels are higher in locally advanced relative to organ-confined prostate cancer and may thus serve as an auxiliary marker providing further improvement for discrimination between pT2 and pT3 stages.