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ABSTRACT: The dried blood spot (DBS) specimens have been successfully employed for the large-scale diagnostics of α1-antitrypsin (AAT) deficiency as an easy to collect and transport alternative to plasma/serum. In the present study we propose a fast, efficient, and cost effective protocol of DNA extraction from dried blood spot (DBS) samples that provides sufficient quantity and quality of DNA and effectively eliminates any natural PCR inhibitors, allowing for successful AAT genotyping by real-time PCR and direct sequencing. DNA extracted from 84 DBS samples from chronic obstructive pulmonary disease patients was genotyped for AAT deficiency variants by real-time PCR. The results of DBS AAT genotyping were validated by serum IEF phenotyping and AAT concentration measurement. The proposed protocol allowed successful DNA extraction from all analyzed DBS samples. Both quantity and quality of DNA were sufficient for further real-time PCR and, if necessary, for genetic sequence analysis. A 100% concordance between AAT DBS genotypes and serum phenotypes in positive detection of two major deficiency S- and Z- alleles was achieved. Both assays, DBS AAT genotyping by real-time PCR and serum AAT phenotyping by IEF, positively identified PI*S and PI*Z allele in 8 out of the 84 (9.5%) and 16 out of 84 (19.0%) patients, respectively. In conclusion, the proposed protocol noticeably reduces the costs and the hand-on-time of DBS samples preparation providing genomic DNA of sufficient quantity and quality for further real-time PCR or genetic sequence analysis. Consequently, it is ideally suited for large-scale AAT deficiency screening programs and should be method of choice.
Advances in experimental medicine and biology 01/2013; 756:29-37. · 1.09 Impact Factor
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J Gibka,
A Wasiutyński,
E Skopińska-Rózewska,
A K Siwicki, J Chorostowska-Wynimko,
E Sommer,
M Mazurkiewicz,
M Gliński,
H Skurzak,
R Wójcik,
L Jung
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ABSTRACT: The in vivo effects of some derivatives of aliphatic ketones (2-undecanone, 3-undecanone, 4-undecanone and their derivatives) on L-1 sarcoma tumor angiogenesis and VEGF content were studied in Balb/c mice. Mice that inhaled 10% solution of 3-undecanone(3-on) or 1% solution of 2-undecanone propylene acetal (Acpr2) for 3 days after tumor cells implantation, presented lower neovascular response measured by tumor-induced cutaneous angiogenesis test (TIA) and lower tumor VEGF content in 5-days tumors, than non-inhaled controls. Other substances presented various effects on tumor VEGF concentration and angiogenesis. Histological examination of lesions collected from mice inhaled Acpr2, or non-inhaled controls, revealed small diffused areas of necrosis in the former group. In both groups, slight to moderate inflammatory infiltrations were seen at the tumor's margin. In Acpr2 group, there were less small blood vessels at tumor's margin than in the control group.
Polish journal of veterinary sciences 01/2010; 13(1):105-15. · 0.56 Impact Factor
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ABSTRACT: Free-circulating DNA is present in minute amounts in plasma of healthy individuals, whereas increased levels are found in a number of malignant pathologies including non-small cell lung cancer (NSCLC). The objective of this research was the evaluation of the plasma DNA quantification capacity to distinguish between healthy subjects and non-small cell lung cancer (NSCLC) patients.
Plasma samples were collected prospectively from 16 healthy volunteers and 30 untreated NSCLC patients (I-IIIA). Subsequently, free-circulating DNA extraction and quantitative real-time PCR analysis were performed.
The values of plasma DNA concentration ranged from 0.9 up to 7.0 ng/ml in healthy individuals and from 1.5 up to 50 ng/ml in NSCLC patients before treatment. Cancer group showed several-fold higher mean free-circulating DNA concentration than that present in healthy subjects (mean 12.00 vs. 2.65 ng/ml; P<0.001). A greater variability of plasma DNA concentrations was observed in NSCLC patients than in controls (SD 14.50 vs. 2.02, respectively). The area under the ROC curve was 0.87 (95% CI, 0.744 to 0.954, P<0.001).
Non-small cell lung cancer is associated with elevated levels of cell-free DNA in plasma with respect to healthy controls. Real-time PCR method proved its utility in effective free-circulating DNA detection and quantification.
European journal of medical research 12/2009; 14 Suppl 4:237-40. · 1.13 Impact Factor
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ABSTRACT: While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce.
The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-beta, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). - Material and methods: Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day before surgery and 3 days after.
TGF-beta serum concentrations were significantly lower after both chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent significant up-regulation after surgery (P<0.001). Interestingly, post-surgery serum VEGF strongly correlated with TGF-beta concentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1 concentrations at any of three evaluated time-points.
Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.
European journal of medical research 12/2009; 14 Suppl 4:42-4. · 1.13 Impact Factor
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ABSTRACT: In the last decade numerous reports demonstrated that free-circulating DNA in plasma/serum samples might be a promising biomarker in a number of pathologies, including cancer. Thus, choosing the reliable and efficient method of plasma DNA quantification would be an essential step prior to any clinical evaluation of cell-free DNA measurement in cancer patients. The aim of present study was to compare two highly-sensitive DNA quantification methods in regard to their applicability and effectiveness in monitoring the cell-free DNA level in the blood of patients with resectable non-small cell lung cancer. Plasma samples collected from 10 patients before any treatment, after neoadjuvant therapy and subsequent surgery, were used for DNA quantification by direct fluorescent PicoGreen staining and by real-time qPCR in SYBR Green and TaqMan probe approach using beta-actin gene as the amplifying target. The PicoGreen method demonstrated a high level of correlation with both the SYBR Green (r=0.87, P<0.0001) and TaqMan probe approach (r=0.94, P<0.0001). The total DNA content, determined by PicoGreen, proved to be several-fold higher than the amplifiable DNA amount measured by real-time qPCR. Consequently, intercalating fluorochromes, like PicoGreen, might serve as a rapid, accurate, and inexpensive alternative to real-time qPCR for routine dsDNA quantification and multicenter standardization.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2008; 59 Suppl 6:675-81. · 2.27 Impact Factor
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ABSTRACT: Induced sputum is a useful non-invasive method for the assessment of airway and parenchymal lung diseases. This study aimed to compare induced sputum and bronchoalveolar lavage fluid (BALF) cellular composition and T-lymphocyte subpopulations in patients with interstitial lung disease. We evaluated 33 patients: 15 with sarcoidosis, 11 with hypersensitivity pneumonitis, and 7 with idiopathic pulmonary fibrosis. The percentage of macrophages was significantly lower in induced sputum than in BALF in sarcoidosis (P=0.005), and the percentage of neutrophils was higher in induced sputum than in BALF in sarcoidosis (P=0.001) and hypersensitivity pneumonitis (P=0.006). A significant correlation was found between the BALF and induced sputum CD4+, CD8+ subsets and the CD4+/CD8+ ratio in both the whole patient group (r(s)=0.80, r(s)=0.88, r(s)=0.88, P<0.001, respectively) and in the 3 subgroups. A strong correlation of the T-lymphocyte subsets in induced sputum and BALF in patients with interstitial lung disease shows that induced sputum may be a non-invasive surrogate for certain parameters in BALF in these patients.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2008; 59 Suppl 6:645-57. · 2.27 Impact Factor
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ABSTRACT: Leptin is believed to play a significant role in the pathogenesis of obstructive sleep apnea syndrome (OSAS) as well as progression of OSAS-related obesity. It is also known that other factors such as gender and diurnal variations in serum strongly affect the measurement results making repeated blood sampling necessary for leptin precise monitoring. Since renal metabolism and urine secretion are the main elimination mechanism for leptin, in this study we evaluated urine relevance for leptin secretion monitoring. Serum and urine (collected during the day and overnight) sampled from 169 OSAS patients and 41 controls were assayed by immunoenzymatic method specific for human leptin. Only 5 (17%) controls and 10 (5.8%) OSAS patients had undetectable urine leptin. We observed significant relationships between serum and urinary leptin in both day-time (r=0.656, P<0.001) and night-time (r=0.518, P<0.001) samples and between day and night-time urine leptin (r=0.811, P<0.001). Significance values did not alter when urinary leptin levels were expressed as the ratio to urinary creatinine. Gender-related differences in leptin concentrations were present both in serum (P<0.001) and overnight urine (P<0.01) in the OSAS group. However, mean night-time urine leptin was lower in the OSAS patients (P<0.05) and their subgroups stratified according to disease severity (P<0.01), while serum leptin levels were comparable in both groups. We conclude that assaying leptin in urine by immunoenzymatic method is a reliable and useful non-invasive alternative for its serum measurement. However, night-time urine leptin levels better reflect differences in its turnover due to gender and OSAS severity.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2007; 58 Suppl 5(Pt 1):105-15. · 2.27 Impact Factor
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ABSTRACT: Recent evidence suggests that theophylline, apart from bronchodilatation, derives its therapeutic activity in asthma from anti-inflammatory effects. Free oxygen radicals play important role in the perpetuation of inflammatory processes underlying bronchoconstriction and airway hyperresponsiveness in asthmatics. In our previous studies, we have analyzed the immunomodulatory effects of theophylline on human monocyte metabolic activity and showed that theophylline in doses of 5-20 microg/ml inhibited the process of zymosan-induced activation, decreasing total and maximum O2- production. The aim of present study was to analyze the mechanism of theophylline action on human monocytes. Therefore, the effects of papaverine--a phosphodiesterase inhibitor, LAS 31025--selective phosphodiesterase IV inhibitor, 8-phenyltheophylline--A1 and A2 adenosine receptors antagonist, and 8-cyclopenthyl-1, 3 dipropylxanthine--selective A1 receptor antagonist on O2- release were assessed. Adenosine receptor antagonist exerted no influence, while papaverine and LAS 31025 suppressed spontaneous, zymosan-induced total and maximum O2- production. The suppressant effect was concentration-dependent. We conclude that theophylline in therapeutic and subtherapeutic concentrations suppresses human monocyte metabolic activity via phosphodiesterase inhibition.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2007; 58 Suppl 5(Pt 1):95-103. · 2.27 Impact Factor
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ABSTRACT: Pulmonary sarcoidosis may progress to fibrosis in some patients, so that close monitoring of its activity is essential for recommending clinical strategy. Examination of airway inflammatory markers in bronchoalveolar lavage (BAL) is one of the methods applied to assess the disease severity. Recently, the expired breath condensate (EBC) has become another source of cytokines and mediators. In sarcoidosis, except for NO and oxidative stress markers, no other mediators have yet been estimated in the exhaled air. In the present study we attempted to answer the question of whether airway inflammatory markers in pulmonary sarcoidosis patients might be assessable in EBC and to what extend these markers might reflect the disease activity in the lungs IL-6, TNF-alpha, PAI-1, and IGF-1 were measured by Elisa method in EBC and BALF samples from 9 patients with newly-diagnosed pulmonary sarcoidosis. TNF-alpha, IGF-1, and PAI-1 levels in EBC and BAL samples were comparable and closely positively correlated [TNF-alpha (r=0.79, P<0.001), IGF-1 (r=0.94, P<0.001), and PAI-1 (r=0.81, P<0.001)]. In contrast, IL-6 concentration in EBC was significantly lower compared with that in BALF, while the correlation between both materials was negative (r=-0.47, P<0.05). An important distinction in IL-6 performance, which might explain this inconsistency, is its tendency to form more complex molecular forms of a higher weight than that of other cytokines. Our study shows that EBC reflects cytokine production in the lung as effectively as BALF, providing that the characteristics of proteins evaluated allow their easy transfer into the exhaled air. Further studies are required before accepting EBC samples as an equivalent to BALF.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 09/2006; 57 Suppl 4:335-40. · 2.27 Impact Factor
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ABSTRACT: Diabetic retinopathy is the leading cause of adult vision loss and blindness. The most important contributors to the development of diabetic retinopathy are hyperglycemia and hypoxemia that lead to increased vasopermeability, endothelial cell proliferation, and pathological neovascularization. In our previous studies, close relationship between proangiogenic activity of sera from type 2 diabetes mellitus patients (DM2) with background retinopathy, assessed in the in vivo serum-induced mouse cutaneous test (SIA), and VEGF and IL-18 serum concentration were observed. Moreover, it was clearly shown that IGF-1 might play an important role in the negative regulation of neoangiogenesis induced by DM2 patients' sera by diminishing the VEGF stimulatory effect. To confirm the observed phenomenon we evaluated the effect of DM2 patients' sera on the in vitro proliferative activity of human endothelial cells, which is critical for the sprouting and generation of new blood capillaries. Endothelial proliferative activity was significantly higher in the presence of sera from DM2 patients than from healthy controls (P<0.001), as estimated by the MTT test. Moreover, the examined sera from DM2 patients were characterized by increased IL-18 (P<0.05), diminished IGF-1 (P<0.02), and unchanged VEGF levels compared with those in controls. In conclusion, the present study showed a strong stimulatory effect of DM2 patients' sera on the proliferation of endothelial cells, which, along with the findings of our previous studies, proves that the described phenomenon is universal and valid for both animal and human endothelium.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 09/2005; 56 Suppl 4:65-70. · 2.27 Impact Factor
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ABSTRACT: It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 09/2005; 56 Suppl 4:71-7. · 2.27 Impact Factor
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ABSTRACT: Sarcoidosis is a chronic inflammatory multiorgan disease of unknown origin. Our previous study demonstrated a significant correlation between the relative count of non CD4(+), non CD8(+) lymphocytes in bronchoalveolar lavage of active sarcoidosis patients and proangiogenic activity of BAL homogenates. The aim of the present study was to evaluate in a group of 40 patients with active sarcoidosis the possible relationship between the intensity of alveolitis, particularly the non CD4(+), non CD8(+) lymphocyte subset, and other parameters characterizing the level of pulmonary (lung function tests) and extrapulmonary (spleen longitudinal dimension) disease activity. We found that the relative count of non CD4(+), non CD8(+) lymphocytes in BAL correlated positively with spleen size (r=0.50, P<0.01) and negatively with static compliance (r=0.43, P<0.05). We concluded that the lymphocytes belonging to the non CD4(+)non CD8(+) subset participate in the inflammatory process in sarcoidosis. However, more detailed phenotypic and functional characteristics of this cellular population are needed.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 10/2004; 55 Suppl 3:41-7. · 2.27 Impact Factor
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ABSTRACT: Plasminogen activator inhibitor type-1 (PAI-1), the primary regulator of plasminogen activator - urokinase (uPA) plays a crucial role in the cell adhesion and migration and in angiogenesis. We had previously demonstrated that PAI-1 - endothelial cell interplay is critical for the formation of new blood vessels and the process is mostly conducted via uPA- anti-proteinase interaction. In the present study we wished to further examine the role of PAI-1 in the sprout formation, representing the first step of new capillary vessels development by evaluating the effect of PAI-1 on the sprout area. We addressed the issue by assessing the influence of cysteine-mutated PAI-1 proteins characterized by a prolonged half-life time (hD beta T - T(1/2)= 63.59 h and beta T-T(1/2)= 6931.47 h), and therefore more stable anti-uPA activity, on the appearance of newly formed sprouts. We found that both CysPAI-1 proteins significantly diminished the mean sprout area in a concentration-dependent fashion. The inhibitory effect present in the two examined endothelial cells systems of different origin and functional characteristics - human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HLMVEC) cultures - was noticeably greater for HLMVEC -high urokinase-producers. Moreover, the inhibition rate was significantly greater for the beta T mutant than that for the hD beta T PAI-1 mutant in all examined doses (P<0.002), proving a key role of anti-proteinase activity for this effect. We concluded that, apart from the total sprout length, as it had repeatedly been demonstrated before, also affects the sprout area in the in vitro sprout formation angiogenesis assay. This effect was achieved mainly via PAI-1's antiproteinase activity.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 10/2004; 55 Suppl 3:49-56. · 2.27 Impact Factor
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ABSTRACT: Caffeine and its active derivative, theobromine, are probably the most frequently ingested pharmacologically active substances. Considering their uninhibited transport via the placental barrier as well as immature enzymatic activities and metabolic pathways in embryos and infants resulting in the longer half-life of methyloxanthines and their accumulation, unrestrained uptake of these substances might result in noticeably more pronounced biological effects during pregnancy and the postnatal period. Our previous studies have shown that methyloxanthines are significant inhibitors of angiogenic growth factors production and angiogenesis itself. We have hypothesized that increased uptake of these substances might affect embryonal angiogenesis and, later in the postnatal period, maturation and functional activity of the offspring's immune system. The study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day during pregnancy and lactation. On day 18 of pregnancy the number and weight of embryos were assessed as was their tissue angiogenic activity, using the cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and spleen were weighed together with the trunk, and tail and limb length were measured. Six weeks after birth the splenocytes' mitogen-induced activity and their ability to induce graft-versus-host reaction as well as the humoral response to SRBC antigen were evaluated. Content of theobromine in the embryos' tissue was estimated by high liquid performance chromatography (HPLC). Theobromine feeding resulted in significant inhibition of embryo growth as assessed by their weight and decreased angiogenic activity of their tissue. The theobromine content in embryo tissue from treated groups was higher than in the controls, and the difference was close to significant. In the postnatal period the discrepancies in the treated 4-week-old group's development were also observed in the significantly shorter limbs in comparison to the controls. Moreover in the treated group of 6-week-old sucklings, considerable variations in the immune system's functional activity were registered as far as cellular and immune response were concerned. Respectively, the splenocytes' mitogen-induced proliferative activity was significantly suppressed while the graft-versus-host reaction was up-regulated, and the serum antibodies titer was elevated in correspondence to the observed spleen enlargement. We concluded that a theobromine-enriched diet affects progeny development in both prenatal and postnatal periods. Consequently, particular attention should be paid to the reduction of theobromine consumption, and most probably that of other methyloxanthines, during pregnancy and lactation.
International journal of tissue reactions 02/2004; 26(1-2):53-60.
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ABSTRACT: Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.
Polish journal of veterinary sciences 02/2003; 6(3 Suppl):54-6. · 0.56 Impact Factor
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ABSTRACT: We previously reported the inhibitory effect of various methyloxantines and phenolic compounds on tumor-induced angiogenesis and the production of angiogenic growth factors. The aim of the present work was to evaluate the effect of chocolate (CH), food containing substantial amounts of methyloxantine theobromine and polyphenols (mainly catechins), given to mice during pregnancy and the lactation period, on weight of organs, length of limbs, and bone vascular endothelial growth factor (VEGF) concentration (tested by ELISA), in 4-week old offspring. The study was performed on 2-month old Balb/c mice fed during pregnancy and lactation 400 mg of CH daily. Content of polyphenols (catechines) and theobromine in the chocolate was estimated by high liquid perforance chromatography (HPLC). Concentration of VEGF was tested by ELISA. Feeding pregnant mice chocolate produced the following effects: decrease of relative length of limbs and thigh bones in 4-week old progeny and decrease in VEGF content of offspring femoral bones. Conclusion: attention should be paid to possible unwanted effects of catechine- and methyloxantine-rich food and beverages during pregnancy and lactation. 200 mg of chocolate per mouse corresponds to 100 g per person.
Polish journal of veterinary sciences 02/2003; 6(3 Suppl):57-9. · 0.56 Impact Factor
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ABSTRACT: Investigations on immune suppression and reconstitution of immune functions dependent on the presence of physiological microflora allow us to conclude that symbiotic microorganisms such as Lactobacillus sp. are essential for adequate activity of the defense system in humans. In addition to their beneficial influence on the intestinal microbial balance, these microorganisms exert a variety of immunomodulatory effects on the host immune system. On the other hand, immunostimulatory animal-derived substances rich in alkylglycerols have been shown to enhance lactic acid bacteria proliferation. Therefore, the aim of the present study was to evaluate the effects on murine humoral response of the combined administration of lyophilized combination of three lactic acid bacteria: L. acidophilus, L. bulgaricus and Bifidobacterium bifidum together with alkylglycerol-rich shark liver oil. The lactic acid bacteria mixture induced markedly stronger enhancement of the humoral response than alkylglycerols did. A significant synergistic stimulatory effect of lactic acid bacteria and alkylglycerols was observed in both treatment schedules: post- as well as in preimmunization with sheep red blood cells. However, their concomitant administration exerted stronger immunomodulatory effect than did the alternative route of treatment.
International journal of tissue reactions 02/2001; 23(3):81-7.
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J Chorostowska-Wynimko
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ABSTRACT: Theophylline has been used in the treatment of obstructive pulmonary diseases since 30s. However, its mechanism of action is still poorly defined. Up to now, its several different actions on the cellular levels are known or hypothesised including most important--inhibition of phosphodiesterase isoenzymes and antagonism of adenosine, as well as enhancement of catecholamine secretion and modulation of calcium ions fluxes. Author reviews all of the proposed theories, outlining existing arguments for and against.
Postȩpy higieny i medycyny doświadczalnej 02/2000; 54(6):867-77.
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ABSTRACT: Isoniazid (INH), antituberculous drug with immunomodulatory properties, have been described as lupus-like syndrome inducer. The development of autoimmunological phenomena results from immunoregulatory disturbances. The goal of this work was to determine the influence of INH on selected parameters of the immune response in vivo and in vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary humoral response and cellular response was evaluated. Drug dose was 25 mg/kg. In vitro (using peripheral blood of volunteers) the influence of INH on mitogen induced proliferation, metabolic activity of granulocytes and production of angiogenic cytokines by diverse subpopulation of mononuclear cells was examined. The concentrations tested were 0.5 mg/ml, 5 mg/ml and 50 mg/ml. No effect of INH could be demonstrated on the production anti-SRBC antibodies nor on the cellular response in mice. In vitro INH added to the cell cultures increased PHA and ConA stimulated proliferation. The chemiluminescence of human granulocytes increased in the presence of INH. Drug enhanced production of angiogenic cytokines by human lymphocytes CD4+ and suppressed angiogenic activity of CD8+ cells. The results suggest that INH has strong immunomodulatory properties which may explain its involvement in pathogenesis of lupus-like disease.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 02/2000; 7(43):27-30.
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J Chorostowska-Wynimko
Pneumonologia i alergologia polska: organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruzlicy i Chorob Pluc 02/2000; 68(9-10):463-70.
