Raynaud's phenomenon and endothelial dysfunction in end-stage renal disease patients treated with hemodialysis

BACKGROUND/AIMS: Steal syndrome is a well-known complication of arteriovenous shunt placement. Increased frequency of Raynaud's phenomenon (RP) especially concerning shunt limb is reported among hemodialysis (HD) patients. The aim of the study was to assess the relation of impairment of peripheral circulation diagnosed with cold stress test (CST) and thermography to the AV shunt location and markers of endothelial dysfunction in HD patients. METHODS: The study group comprised 21 patients (6 male, 15 female, mean age 32.6 +/- 15.0 years) treated with HD for a mean of 69 +/- 54 months. 10 healthy individuals (4 male, 6 female, mean age 38.6 +/- 14.7 years) served as controls. The diagnosis of RP was made upon the results of thermographic measurements during CST. Von Willebrand factor activity and antigen, endothelin-1 and plasma total homocysteine (tHcy) were measured in all subjects. RESULTS: RP was found significantly more often in HD patients than in controls: 11/21 vs. 1/10 (p = 0.04). RP occurred in both hands in 7/11 (64%) patients. tHcy was higher in HD patients than in the controls (31.7 +/- 13.9 vs. 10.9 +/- 3.2 microg/l, p < 0.0001). tHcy and von Willebrand factor antigen were significantly higher in the RP-positive than RP-negative patients or controls. CONCLUSION: Small vessel dysfunction diagnosed as positive RP is a frequent finding in HD patients. It seems that endothelial injury rather than AV shunt steal syndrome is responsible for development of RP in HD patients.     

Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type

A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.     

Biological activity of synthetic analogs of laminin active sequences: YIGSR,RGD, SIKVAV

The invasion of malignant cells through the basement membrane is a critical step in local infiltration and metastasis. Adhesion and invasion of malignant cells may be modulated by their receptor mediated binding to the basement membrane glycoprotein-laminin. Laminin consists of the sequences with anticancer and antimetastatic activity. Its peptide fragment YIGSR is known to inhibit the experimental metastases of several tumors. This sequence and a tripeptide RGD of laminin inhibits both angiogenesis and tumor growth. In contrary, the sequence SIKVAV initiates angiogenesis and tumor progression. Moreover, laminin plays also other functions in human organism. One of them is the influence on platelet aggregation and thrombogenesis.     

Bilateral aggressive malignant granulosa cell tumour with essentially different immunophenotypes in primary and metastatic lesions comprising predominantly sarcomatoid and fibrothecomatous patterns – looking for prognostic markers: a case report

We present an unusual case of a young woman with rare bilateral, very aggressive ovarian granulosa cell tumour (GCT), comprised of granulosa, sarcomatoid and fibrothecomatous fields with significantly different immunostaining of primary and metastatic tumours showing stronger WT1, Bcl2, fascin and EGFR expression in metastases. Despite radical surgery and chemotherapy the tumour recurred rapidly and the patient died 16 months later. Such results clearly demonstrate the usefulness of immunostaining for the above markers as prognostic/predictive factors and the need for careful assessment of the immunoprofile of both primary and metastatic tumours, which can be useful for therapy and follow-up planning in GCT cases.     

Wtórne nowotwory u chorych z nadpłytkowością samoistną leczonych w Klinice Hematoonkologii i Transplantacji Szpiku UM w Lublinie

ET is a relatively indolent disease, but a shorter survival of patients has been observed. Previously the main risk factors for reduced survival time were advanced age and the history of thrombotic complications. Recently the other cause of reduced survival is put on – secondary nonhematological neoplasms.     

T lymphocytes as a target of histamine action

Histamine is one of the most important biogenic amines in medicine and biology but its role in allergy, autoimmune and neoplastic diseases has not yet been fully defined. The last few years have brought many discoveries concerning important modulatory effects of histamine and its receptors on basic mechanisms of the immunological processes. The role of histamine H1 and H2 receptors in immunomodulation has been established. The immunomodulatory function of a newly described histamine H4 receptor has been revealed. One of the most important modulatory effects of histamine currently studied is its influence on T lymphocyte differentiation and function. Our present knowledge suggests that histamine may have a wider influence on various immunological processes than is now accepted; therefore, we need further studies to fully clarify the role of histamine and its receptors. This knowledge can bring new therapeutic solutions in allergies, autoimmune diseases and malignancies.     

Proteolysis on the body surface of pyrethroid-sensitive and resistant Varroa destructor

The aim of this work was to determine the activity of proteases and protease inhibitors sampled from the body surface of tau-fluvalinate-sensitive and resistant V. destructor. Proteins were isolated from the tau-fluvalinate-sensitive and resistant mites, while mites untreated with tau-fluvalinate constituted the control. Subsequently, the following methodology was applied: protein concentration assay by the Lowry method — as modified by Schacterle and Pollack; assay of proteolytic activity in relation to various substrates (gelatine, haemoglobin, ovoalbumin, albumin, cytochrome C, casein) by the modified Anson method; identification of proteolytic activity in relation to diagnostic inhibitors of proteolytic enzymes (pepstatin A, PMSF, iodoacetamide, o-phenantrolin), using the Lee and Lin method; identification of acidic, neutral and basic protease activities by means of the modified Anson method; electrophoretic analysis of proteins in a polyacrylamide gel for protease detection with the Laemmli method and for protease inhibitor detection with the Felicioli method. The highest value of protein concentration was found in the tau-fluvalinate-sensitive V. destructor, while the highest activity levels of acidic, neutral and alkaline proteases were observed in the tau-fluvalinate-resistant mites. Aspartic, serine, thiolic and metallic proteases were found in the drug-resistant and drug-sensitive Varroa mites. The control samples were found to contain aspartic and serine proteases. In an acidic and alkaline environment, the results revealed a complete loss of inhibitor activities in the in vitro analyses and electrophoresis. Serine protease inhibitor activities (at pH 7.0) were high, especially in the group of tau-fluvalinate-resistant mites.