JAK2 mutation status, hemostatic risk factors and thrombophilic factors in essential thrombocythemia (ET) patients

The recently discovered JAK2 V617F point mutation, found in 50–60% of ET patients, has been reported to be associated with a higher risk of thrombotic events. In this study, we explored if JAK2 V617F mutation, or coexisting thrombophilic and hemostatic risk factors, contributed to these complications. We examined 32 patients with ET, and looked for pathogenetic JAK2 V617F mutation and prothrombotic genes mutations: factor V Leiden, prothrombin and MTHFR. We also evaluated plasma levels of fibrinogen, factors VIII and XII, AT, protein C, protein S and serum level of homocysteine. Urokinase concentration was assessed in patients’ plasma as well as platelet lysates. There was no difference in the number of thrombotic complications between ET patients with and without JAK2 mutation. However, we found a number of thrombophilic and hemostatic risk factors that could contribute to thrombotic complications in ET patients. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 267–271

The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders

Understanding the neurochemical basis for cognitive function is one of the major goals of neuroscience, with a potential impact on the diagnosis, prevention and treatment of a range of psychiatric and neurological disorders. In this review, the focus will be on a biochemical pathway that remains under-recognised in its implications for brain function, even though it can be responsible for moderating the activity of two neurotransmitters fundamentally involved in cognition – glutamate and acetylcholine. Since this pathway – the kynurenine pathway of tryptophan metabolism - is induced by immunological activation and stress it also stands in an unique position to mediate the effects of environmental factors on cognition and behaviour. Targetting the pathway for new drug development could, therefore, be of value not only for the treatment of existing psychiatric conditions, but also for preventing the development of cognitive disorders in response to environmental pressures

Secondary malignancy in patients with essential thrombocythemia – case reports

Nadpłytkowość samoistna (ET; essential thrombocythemia) należy do przewlekłych chorób mieloproliferacyjnych i ma na ogół mało agresywny przebieg, jednak czas przeżycia chorych jest krótszy w porównaniu z ogólną populacją. Do niedawna za główne przyczyny skrócenia czasu życia chorych uznawano zaawansowany wiek i przebyte epizody zakrzepowe. Obecnie coraz więcej uwagi zwraca się na inny powód, jakim jest rozwój u tych chorych wtórnych nowotworów niehematologicznych.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

Mild hyperhomocysteinemia in patients with essential thrombocythemia (ET) and its relation with MTHFR gene mutation and folic acid concentration

In this study we assessed homocysteine level in 106 patients with ET – 80 females and 26 males, mean age 54 (23–82) and in 20 healthy persons – 6 males and 14 females, mean age 41 (31–54). We also searched for a relation between homocysteine level and MTHFR gene mutation as well as vitamin B12 and folic acid concentration. Median homocysteine serum level was higher in ET patients than in control group. Elevated homocysteine level primarily stems from folic acid deficiency rather than from the presence of MTHFR gene mutation. Median folic acid level was lower in ET patients presenting thrombotic and bleeding complications than in ET patient without vascular episodes. We concluded that folic acid substitution may not only prevent hyperhomocysteinemia but also the development of vascular complications in ET patients

Spermatozoa injuries estimation by the method of extracellular activity determination of enzymes as exemplified by the value of young boar semen

Целью труда было определение связи между активностью энзимов в плазме семени 6-месячных хрячков и его качеством выраженным количественными параметрами и показателями микроскопной оценки в рамках трех породных групп: крупной белой польской породы (32 головы), породы дюрок (29 голов) и многопородных помесей (22 головы) содержимых в Гибридизационном центре Павливице. Биохимическая оценка семени была выражена активностью энзимов в его плазме (AspAT, ALAT, LDH и АР). Среди анализируемых биохимических тастов плазмы семени, свидетельствующих о степени повреждения сперматозоидов, не был найден универсальный тест, который смог бы касаться хотя бы одного параметра количественной и микроскопной оценки для всех исследуемых породных групп. Характерными и специфическими представляются высокие коэффициенты корреляции для связи между активностью AspAT и ALAT в плазме семени с одной стороны и движением массы сперматозоидов (r = -0,57** , -0,67**) и общим числом сперматозоидов в эякуляте (r = -0,45* и -0,75**) и между активностью LDH и концентрацией и процентом живых сперматовоидов (r = -0,67** и -0,61**) с другой стороны для хрячков породы дюрок, семя которых характеризовалось самыми низкими значениями в проведенной оценке. Была получена прямая эависимость между активностью LDH и процентов живых сперматозоидов (r = 54*) в рамках помесных храчков. Рост процента сперматозоидов с основании изменениями связан с пониженной активностью LDH в плазме семени (r = -0,40*).The aim of the work was to find the relationship between the activity of enzymes in the semen plasma of the 6-month boars and its value expressed in terms of quantitative parameters and microscopic estimation indices within the framework of three breed groups: Polish Large White (32 heads), Duroc (29 heads) and polybred hybrids (22 heads) at the Hybridization Centre of Pawłowice. The biochemical assessment of the semen was expressed in terms of activity of enzymes in its plasma (AspAT, AlAT, LDH and Ap). In analyzed biochemical tests of the semen plasma concerning the spermatozoid injury degree no universal test, which could concern at least one parameter of the quantitative and microscopic estimation for all breed groups, has been found. Characteristic and specific seem to be the obtained high coefficients of correlation for the relationship between the AspAT and AlAT activity in the semen plasma, spermatouoa mass movement (r = -0.57**, -0.67**) and total number of spermatozoa in the ejaculate (r = -0.45* and -0.75**) on the one hand and the AlAT activity and concentration and per cent of living spermatozoa (r = -0.67** and -0.61**) for the Duroc boars, the semen of which appeared to be the worst in the ejaculate, on the other. A simple relationship between the LDK activity and the per cent of living spermatozoa (r = 54*) within the group of hybrid boars has been obtained. Increase of the per cent of spermatozoa with basic changes is connected with a lowered LDH activity in the semen plasma (r = -0.40*)

Beneficial impact of cathelicidin on hypersensitivity pneumonitis treatment-In vivo studies.

Cathelicidin (CRAMP) is a defence peptide with a wide range of biological responses including antimicrobial, immunomodulatory and wound healing. Due to its original properties the usefulness of CRAMP in the treatment of pulmonary fibrosis was assessed in a murine model of hypersensitivity pneumonitis (HP). The studies were conducted on mouse strain C57BL/6J exposed to a saline extract of Pantoea agglomerans cells (HP inducer). Cathelicidin was administered in the form of an aerosol during and after HP development. Changes in the composition of immune cell populations (NK cells, macrophages, lymphocytes: Tc, Th, Treg, B), were monitored in lung tissue by flow cytometry. Extracellular matrix deposition (collagens, hydroxyproline), the concentration of cytokines involved in inflammatory and the fibrosis process (IFNγ, TNFα, TGFβ1, IL1β, IL4, IL5, IL10, IL12α, IL13) were examined in lung homogenates by the ELISA method. Alterations in lung tissue morphology were examined in mouse lung sections stained with haematoxylin and eosin as well as Masson trichrome dyes. The performed studies revealed that cathelicidin did not cause any negative changes in lung morphology/structure, immune cell composition or cytokines production. At the same time, CRAMP attenuated the immune reaction induced by mice chronic exposure to P. agglomerans and inhibited hydroxyproline and collagen deposition in the lung tissue of mice treated with bacteria extract. The beneficial effect of CRAMP on HP treatment was associated with restoring the balance in quantity of immune cells, cytokines production and synthesis of extracellular matrix components. The presented study suggests the usefulness of cathelicidin in preventing lung fibrosis; however, cathelicidin was not able to reverse pathological changes completely