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Background: Although the iron is an essential element for the physiological functions of cells, tissues and organs, it is also an important inductor of reactive oxygen species (ROS)., Material and Methods: Three groups of human spleen with autoimmune thrombocytopenia (AITP), hereditary spherocytosis (HS) and reference samples stained by haematoxylin and eosin, Perls' reaction for nonheme Fe(III) iron and Alcian blue for glycoconjugates detection were studied., Results: Positive Perls' reaction in both AITP and HS groups was seen. Higher positivity in the HS than in AITP group was observed. HS group showed a higher amount of acidic glycoconjugates deposits than AITP group. Iron overload in HS and AITP leads to overproduction of ROS., Conclusion: We suggest that acidic glycoconjugates deposits are involved in antioxidant defence by elimination and restriction of iron as a ROS inducer (Fig. 4, Ref. 19).

Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum of different states and diseases. Mixed or polyclonal cryoglobulins can be seen in patients with autoimmune disorders, chronic infections and lymphoproliferative disorders. Monoclonal cryoglobulins are often revealed in patients with multiple myeloma or Waldenström's macroglobulinemia. Cryoglobulinemia is in most cases asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels. In this report, we describe a case of a patient presented with gangrene of almost all fingers and toes, who was finally diagnosed and treated as cryoglobulinemic vasculitis due to multiple myeloma.

In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a significant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. In this study treatment of adjuvant arthritis in rats with Detralex, methotrexate, and their combination were evaluated. Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, and whole-body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. Long-term prophylactic treatment with low-dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of bone mineral density in AA rats was significantly lower only in the group treated with the combination of Detralex and methotrexate. Our results indicate that Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAME-induced hypertension.

Objectives: The acute toxicity of magnetic nanoparticles was effectively lowered by their encapsulation with poly(D,L lactide). In relation to the idea to use magnetic nanoparticles in development of new delivery systems suitable for targeted drug administration, the toxicological profile of five types of magnetic fluids was assessed in mice., Methods: The nanoprecipitation method was used to prepare magnetic fluids containing nanoparticles of Fe(3)O(4) encapsulated with biodegradable substances. The acute toxicity testing was performed according to OECD Test Guideline 425. In the pilot distribution study a special staining method was examined for the detection of Fe ions in body tissues of mice after intravenous administration of magnetic fluids., Results: The p.o. LD(50) values were greater than 2,000.0 mg/kg of body weight and i.v. LD(50) values were in the range of 231.7-558.9 mg/kg of body weight., Conclusions: Of the magnetic nanoparticles tested, those encapsulated with poly(D,L lactide) were the most prospective for further in vivo testing.

1. The role of oxidative stress, and accordingly uncontrolled reactive oxygen species generation/action, have been widely documented in a number of different neuronal pathologies. However, the concept of pharmacological interventions in prevention and therapy of oxidative stress-related diseases has not found adequate application in clinical practice. This may be due to the insufficient efficacy of drugs available, their unsuitable pharmacokinetics, side effects, toxicity, etc. 2. Based on stobadine, (--)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole, a well-known antioxidant, free radical scavenger, and neuroprotectant, it was attempted to develop new stobadine derivatives with improved pharmacodynamic and toxicity profiles, on applying molecular design, synthesis and adequate tests. Stobadine molecule was modified mostly by electron donating substitution on the benzene ring and by alkoxycarbonyl substitution at N-2 position. A total of >70 derivatives were prepared. 3. In a mice model of head trauma, some of the new stobadine derivatives administered i.v. immediately after the trauma, significantly improved sensomotoric outcome in the animals assessed 1 h later. Accordingly, decrease in brain edema was proved histologically as well as by brain wet weight assessment. 4. Putative neuroprotective action of the compounds was confirmed on rat hippocampal slices exposed to reversible 6 min hypoxia/low glucose by analysis of synaptic transmission in CA1 region neurons. Irreversible impairment of neurotransmission resulting from the hypoxia was significantly reduced by the presence of SMe1EC2, one of the new compounds, in concentration range 0.03-10.0x10(-6) mol l(-1). Both the neuroprotective and antioxidant effect of the compound closely resembled those of stobadine, melatonin, 21-aminosteroids, alpha-phenyl-tert-butylnitrone and others, all well-established antioxidants, except the range of effective concentrations was by 1-2 orders lower in SMe1EC2. 5. A remarkable antioxidant efficacy was observed in the new compounds in rat brain homogenates exposed to iron/ascorbate system by protection of lipids and creatine kinase against the oxidative impairment. A link between the neuroprotective and antioxidant/ scavenger properties in the compounds can be assumed. 6. Acute toxicity of some of the new pyridoindoles was diminished compared to stobadine. That might be due to the virtually full elimination of stobadine's undesired alpha (1)-adrenolytic activity attained by appropriate modifications of its molecule. 7. The new pyridoindoles extend the range of available neuroprotectants interfering with oxidative stress in neuronal tissue.

Classification of thyroid tumours and their variants is described with special respect to some recent findings on somatic mutations characteristics which are associated with individual types of malignity. Special attention is paid to the interrelations between thyroid nodules and malignity and predictive risk factors are listed.

Objective: Red wine polyphenols have been reported to possess beneficial properties for preventing cardiovascular diseases but their effects on hemodynamic and functional cardiovascular changes during inhibition of nitric oxide (NO) synthesis have not been elucidated., Design: The effects of the red wine polyphenols, Provinols, on arterial hypertension as well as left ventricular (LV) hypertrophy, myocardial fibrosis and vascular remodeling were investigated in rats during chronic inhibition of nitric oxide synthase (NOS) activity. Rats were divided into four groups: a control group, a group treated with N-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg per day), a group receiving Provinols (40 mg/kg per day) alone or Provinols plus L-NAME., Results: Provinols markedly reduced the increase in both blood pressure and protein synthesis in the heart and aorta caused by chronic inhibition of NO synthesis. Provinols reduced myocardial fibrosis even though it did not affect LV hypertrophy. In addition, Provinols prevented aortic thickening and corrected the augmented reactivity of the aorta to norepinephrine and the attenuated endothelium-dependent relaxation to acetylcholine in NO-deficient rats. These alterations were associated with an increase of NOS activity, a moderate enhancement of endothelial NOS expression and a reduction of oxidative stress in the LV and aorta., Conclusion: Our results provide evidence that Provinols partially prevents L-NAME-induced hypertension, cardiovascular remodeling and vascular dysfunction via the increase of NO-synthase activity and prevention of oxidative stress. Thus, the beneficial effects of plant polyphenols in prevention of hypertension may result from their complex influence on the NO balance in the cardiovascular system.

Histopathological evaluation of the mammary gland tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU), and treated with either CpG oligodeoxynucleotides (CpG-ODN) and/or 13-cis retinoic acid has been performed in this work. Since, the treatment of animals with CpG-ODN induced a significant decrease of tumour burden and volume in comparison with MNU treated control group (Macejova et al. 2001), it was of high impact to compare histological appearance of tumours in different experimental groups (MNU, CpG-ODN, 13-cis retinoic acid, CpG-ODN plus 13-cis retinoic acid). We have found reduced number of carcinomas with necroses in the CpG motifs treated group when compared to animals treated with MNU only. From the histological point of view the treatment with the CpG-ODN may have some protective effect. Carcinoma patterns proportion in the group treated with CpG-ODN was found to be different in comparison with other experimental groups. Treatment of rats with CpG-ODN had no apparent effect on invasiveness of developed carcinomas.

Authors describe in the case report a development of the primary hemochromatosis. At the time of the diagnosis in 1979 from organ complication the liver fibrosis and secondary diabetes mellitus were presented. Patient was treated with the venepunctions and with desferoxamine. In the 1998 the primary hepatocellular tumor was found and resected. Instead of the chemotherapy occurred the progression of the disease with multiple metastases and liver insufficiency and 66-years old patient died 19 months after surgery in the 20th year of the disease.

The effects of the red wine polyphenolic compounds (Provinol) on hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular remodeling were investigated after chronic inhibition of nitric oxide (NO) synthase by administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats. Rats were divided into four groups: a control group, a group treated for 4 wk with L-NAME (40 mg x kg(-1) x day(-1)), and two groups treated with L-NAME followed by 3 wk of either spontaneous recovery or recovery with Provinol treatment (40 mg x kg(-1) x day(-1)). Administration of Provinol produced a greater readiness of the decrease in blood pressure than that in the spontaneous recovery group. Provinol significantly depressed myocardial fibrosis and expedited the decrease in aortic cross-sectional area, the increase in endothelium-dependent relaxation, and the decrease in contraction of the aorta. These effects of Provinol were associated with a greater increase of NO synthase activity in the left ventricle and the aorta. The present study provides evidence that Provinol accelerates the regression of blood pressure and improves structural and functional cardiovascular changes produced by chronic inhibition of NO synthesis.

The effects of pleuran, beta-1,3 glucan isolated from Pleurotus ostreatus, were studied in a model of acute colitis induced by intracolonic administration of acetic acid. There was a reduction of the colonic damage score, colonic wet weight and wet/dry weight ratio 48 h after single luminal 2% pleuran suspension pretreatment. Similar results were obtained after repeated intraperitoneal administration of pleuran in doses of 30 and 100 mg/kg. Pleuran given orally as a 10% food component over 4 weeks was effective in reducing the extent of mucosal damage, but did not prevent the increase of myeloperoxidase in the injured colonic segment. In the segment without macroscopic evidence of inflammation, myeloperoxidase activity was significantly lower as documented by histological examination. The results indicate a possible role of this immunomodulator in the treatment of ulcerative colitis.

Familial occurrence of malignant carcinoid is rare (about 3%). Authors describe occurrence of the malignant carcinoid in two brothers. In the older one the diagnosis was estimated in 1991. He had multiple intestinal carcinoid tumor with multiple liver metastases histological type III by Soga classification. Patient is intermittently treated with somatostatin analogue--lanreotid and with interferon alfa. By this therapy the disease is stabile. In the younger of brothers the diagnosis was estimated in 1999. The disease had rapid progression and in ten months patient died despite of the therapy. Definitive diagnosis was a malignant neuroendocrine tumor of pancreas-mixed low differentiated carcinoid with calcitonin overproduction. (Fig. 4, Ref. 15.)

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.

In the normal female and male breast epithelial structures any prostate-specific antigen (PSA) immunohistochemical positivity was observed. Variable PSA expression, which often borders the positivity, was observed in membranes of adipocytes of fat tissue and in the endothelium of small vessels in a female and a male breast. Based on these initial observations, tissue of the normal breast, male or female, can not be considered to be the principal source of PSA.

Thromboangiitis obliterans or Winiwarter-Buerger's disease is a primary systemic vasculitis of an unknown etiology, which affects medium-sized arteries and veins mainly in the lower and upper extremities, causing multiple segmental arterial occlusions especially in young male smokers. The aim of our study is to compare the knowledge on the etiology, epidemiology, clinical presentation, diagnostic and therapeutic possibilities in the time of Leo Buerger (90 years ago) and now. Between 1994 and 1998, 26 patients (19 men and 7 women) were investigated with clinical suspicion for Winiwarter-Buerger's disease. Laboratory and arteriographic investigation revealed typical signs for this disease in 22 of them. To the most common clinical signs or symptoms belong smoking and the onset of the disease before the age of 50 years (in 95.5%), intermittent claudication (in 72.7%), rest pain and ischaemic ulcers or gangrenes in the fingers (in 68.2%). In slightly more than half of the patients migrating superficial thrombophlebitis was present and similarly in one half of the patients Raynaud's phenomenon was found. In conclusion--What has changed from the times of Leo Buerger? 1. Prevalence of TAO increased in women. 2. Older patients (more than 40 years old) are being diagnosed. 3. Upperextremity involvement is more frequently present. 4. Diagnosis of TAO is being more proper, especially due to up-to-date diagnostic methods, like digital subtraction angiography. 5. The treatment is more effective, amputation number is decreased. And what has not changed? Similarly like Leo Buerger we do not known the precise etiology of the disease. Ceasation of smoking has still the most important therapeutic procedure. The clinical course of the disease is individual and in spite of the treatment is the clinical course unpredictable. (Tab. 5, Ref. 47.)

Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered NG-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. A does of 40 mg/kg/day increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heart/body weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14C]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14C]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with focal myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular medial proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO.

Present possibilities of morphometric analysis of the spleen have been studied. We have compared possibilities provided by stereological calculation and by computer image analysators a) Telemet II (Tesla, Piestany) and b) CUE-2 GALAI (Israel). In both latter cases equidensitometric evaluation and image processing methods were used. Stereological calculations are not technically demanding but time consuming. Computer image processing on the base of equidensitometric measurements is more effective that stereological calculations. The difference between used equipments is based on access to appropriate microscopic and computer technique and software equipment.