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Biomedical subjects

T Cichocki

Publications and source records attributed to T Cichocki.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice.

BACKGROUND: Recent reports point to an important role of leukotrienes in atherogenesis. Leukotrienes are produced by 5-lipoxygenase co-operating with five lipoxygenase activating protein (FLAP). We hypothesized that MK-886, an inhibitor of FLAP, could attenuate the development of atherosclerosis in the atherogenic apolipoprotein E/low density lipoprotein receptor (apoE/LDLR) double knockout (DKO) mouse model. MATERIALS AND METHODS: Female apoE/LDLR-DKO mice at the age of 8 weeks were put on Western diet. The experimental group (n = 10) received the same diet as the control group (n = 10), but mixed with MK-886 (Merck, Rahway, NJ) at a dose of 4 microg per 100 mg of body-weight per day. At age 6 months the mice were sacrificed under anaesthesia. RESULTS: Measured by the en face method, the percentage of area occupied by lesions in aortas in the control group was 25.15 +/- 2.9%, whereas in the MK-886-treated group it was 11.16 +/- 0.7% (P < 0.05). Lesion area measured by cross-section of aortic roots was 455,494 +/- 29,564 microm(2) in the control group versus 263,042 +/- 20,736 microm(2) in the MK-886-treated group (P < 0.05). The MK-886 did not change the plasma cholesterol lipoprotein profile as compared with the control mice. Finally, we show that MK-886 may increase plaque stability by decreasing the macrophage content as well as increasing the collagen and smooth-muscle cell content. CONCLUSIONS: Our results show for the first time that inhibition of FLAP by MK-886 reduces development of atherosclerosis in gene-targeted apoE/LDLR-DKO mice.

5-Lipoxygenase-Activating Proteins↗
PubMed2000

Development of the innervation of long bones: expression of the growth-associated protein 43.

It has been known from clinical and experimental observations that the peripheral nervous system is involved in the development of long bones. Expression of growth-associated protein 43 (GAP-43/B-50) was found in axonal growth cones during embryonic and postnatal ontogeny as well as in regenerating axons after nerve injury. The aim of the present study was to examine the occurrence of growing nerve fibers in rat tibia from gestational day 16 (GD 16) to postnatal day 28 (PD28). An indirect immunoenzymatic reaction using antibodies raised against GAP-43 was applied to detect outgrowing nerve fibers penetrating into the developing bone. On GD 16 and GD 17 no GAP-43-immunoreactive (IR) fibers were observed in the close vicinity of bone rudiments. On GD19 GAP-43-IR fibers were scarcely present within the periosteum of the central portion of the diaphysis. In the perichondrium surrounding the proximal epiphysis, nerve fibers were first detected around birth. From PD1 onward, numerous fibers were seen in the fibrous buds of the perichondrium at the epi-metaphyseal junction (Ranvier's grooves), some of them being adjacent to the blood vessels. Nerve fibers penetrating into the bone and located in the bone marrow, predominantly associated with blood vessels, were first observed on GD21 and their number increased with further development. They were initially located in the central portion of the diaphysis and later extended towards the metaphyses. On PD4 an increased number of GAP-43-IR fibers appeared in the perichondrium of proximal and distal epiphyses. In the fibrous strands penetrating into the epiphyses and in the secondary ossification centers, nerve fibers were first observed on PD10. From PD14 onward the pattern of tibial innervation remained unchanged but the intensity of GAP-43 immunostaining visibly decreased. The present study demonstrates that developing long bones of rat hindlimbs are supplied by growing nerve fibers immunoreactive for GAP-43 from GD 19 onward. Time and location of their appearance were at least partially correlated with known events taking place during long bone development, e.g. formation of primary and secondary ossification centers. Decreased expression of GAP-43 immunoreactivity in later developmental stages is believed to reflect nerve fiber maturation.

Aging↗
PubMed1998

[Calcification of allogenic aortic heart valves].

The material used for the studies consisted of allogenic aortic valves (AAV) collected from 14 individuals. The necessity of AAV replacement arose from growing circulation insufficiency and AAV dysfunction. The aim the study was the determination of the elemental composition and crystallographic structure of the inorganic deposits in AAV. Moreover, the results of the physicochemical investigations were correlated with clinical data (age of the patient, time between valve replacement surgeries, endomyocarditis, number of infections during last 12 months, arterial hypertension and disturbance of the lipid balance) and with echocardiographic examinations (cusp mineralization and perforation, vegetation, systolic and diastolic dimensions of the left ventricle, maximal and average gradient through allograft valve as well as range of the recoil wave to left ventricle). It was found that mineralization of the AAV cusps was a time-dependent process and took place predominantly at the surface of the cusp. The elemental composition and crystallographic data revealed that the inorganic deposits in AAV were composed of hydroxyapatite crystals. However, the presence of other calcium salts was also found. The development of the mineralization process in AAV does not correlate with endomyocarditis, arterial hypertension and the disturbance of the lipid balance. Probably, endomyocarditis and arterial hypertension induce the pathologic alternations of AAV independently from the mineralization process. The echocardiographic estimations of the pathomorphologic changes of the aortic valve cups are not always consistent with the results of the physicochemical studies.

Adult↗
PubMed1992

Calcification of the aortic wall in hypercalcemic rabbits.

The mineralization process was investigated in the aortic wall of hypercalcemic rabbits. The elevated calcium level in serum was induced by intramuscular injection of vitamin D3. The animals were killed at different times of the experiment (max. 246 d). The freeze-dried tissue homogenates were used for elemental composition studies by means of proton induced X-ray emission (PIXE) and atomic absorption spectroscopy. The structural information was obtained from infrared (IR) and X-ray diffraction (XRD) spectra. Moreover, the ascending part of the aortic arch was separated and used for micro-PIXE (PIXE in combination with proton microprobe) and histochemical examinations. It was found that hypercalcemia (blood serum Ca content elevated by about 20%) induced calcification of the aortic wall. The mineral phase within the aortic wall consisted of Ca-P salts. The Ca/P ratio continuously increased during the experiment and approached 2 after 246 d of the vitamin D3 treatment. The IR and XRD studies made possible the identification of the complex phase composition of the samples. The hydroxyapatite crystals were detected after 196 days, however, in earlier phases of the experiment, amorphous calcium phosphate, dicalcium phosphate dihydrate and octacalcium phosphate were also observed. On the basis of the data obtained, the mechanism of the precipitation and growth of inorganic deposits in the tunica media of the aortic wall was discussed.

Animals↗
PubMed1991

Calcification of aortic wall in cholesterol-fed rabbits.

Development of the mineralization process in the course of atherogenesis was studied using the cholesterol-fed rabbit model. The aorta samples were investigated by means of proton and electron microprobes, infrared spectroscopy and X-ray diffraction as well as selected histochemical staining. Blood serum was analysed every 2 weeks to determine the content of cholesterol, triglycerides, inorganic phosphorus, ionized calcium, elemental composition as well as activity of alkaline phosphatase. It was found that the administered diet did not disturb the calcium and phosphorus homeostasis. Histochemical findings confirmed the formation of lipid-rich lesions blocking the lumen of the vessel. The dystrophic calcification was observed only in the atheroma, while in the tunica media a slight mineralization similar to that found in controls was observed after 210 days of the diet. In the atheroma the only phase detected was a defective hydroxyapatite. The perfection of the crystals, as well as the diameter of the deposits, increased during the course of the diet reaching about 2 microns after 210 days. The crystals were not contaminated with carbonate groups regardless of the duration of the diet.

Animals↗
PubMed1990

Intramembranaceous ossification analyses by a proton microprobe.

The proton induced X-ray emission method in combination with a proton microprobe was applied to study the intramembranaceous ossification. As material sections of mouse embryo skulls from the 17th and 19th day of gestation were used. The morphology of the sample was examined by routine histochemical procedure performed on the sections adjacent to that irradiated by the proton microprobe. The measurements were made in line scan and raster scan mode. The concentrations of P, S, Cl, K, Ca, Fe and Zn were determined at each irradiated point. The average element concentrations were calculated for four parts of each section (bone, cartilage, mesenchymal tissue close to the bone and mesenchymal tissue in other places). The distributions of Ca and P (less markedly than Ca) concentrations almost exclusively correlate with localization of the bone while S, Cl and K concentrations show preference to the cartilage. The amount of inorganic material in flat bones of the 17-day embryo amounts to 14% of the dry mass. The material is characterized by a Ca/P ratio of about 1.6. In the embryo 2 days older the amount of the inorganic phase is practically the same (15%) while the Ca/P ratio approaches 2. This suggests the presence of the precursor phase in the flat bone calcification. It is possible that octacalcium phosphate (Ca/P ratio equals to 1.72) is formed at the onset of the flat bone mineralization which transforms rapidly (in 2 days) to a more stable mineral (defective hydroxyapatite).

Animals↗
PubMed1990

Peroxidase activity in peritoneal macrophages of patients with terminal renal failure treated by intermittent peritoneal dialysis.

Peroxidase activity was assessed cytochemically in macrophages from peritoneal dialysate of 50 patients with terminal renal failure treated by intermittent peritoneal dialysis. In 22 patients cells were harvested for the second time after development of peritonitis as the complication of the treatment. The obtained results were compared with those of the control group consisting of 30 patients with normal renal function. Patients treated with peritoneal dialysis showed both in complication-free period and during the course of peritonitis significantly higher peroxidase activity in macrophages as revealed by the semiquantitative score test. In the course of peritonitis, peroxidase activity in macrophages was significantly lower than in complication-free period. Electron-microscopic cytochemistry demonstrated that in macrophages obtained from both control and dialyzed patients the peroxidase activity was located exclusively in cytoplasmic granules, suggesting a similarity of the studied cells and exudative macrophages.

Adolescent↗
PubMed1990

Developing an artificial fallopian tube: successful in vitro trials in mice.

This report describes the design and testing of an artificial fallopian tube for the treatment of tubal infertility. Within the device, mouse eggs incubated with sperm were fertilized and a microinfusion pump was used to transport the fertilized ova through the tube. Normal offspring resulted from transfer of the developing embryos into pseudopregnant recipients. These results provide encouraging evidence that an artificial fallopian tube warrants further investigation as a potential alternative to in vitro fertilization.

Animals↗
PubMed1989

The analysis of mineral deposits and proteoglycans content in the cartilage of mouse trachea using PIXE in combination with proton microprobe.

The tracheal cartilage of mature mice have been investigated using PIXE (proton induced X-ray emission) in combination with a proton microprobe on snap frozen cryosectioned material. The localization and quantitative measurements of P, S, Cl, K, Ca, Fe, and Zn concentrations as well as direct and indirect assessment of glycosaminoglycans by measurement of S content and measurement of bound colloidal iron at pH = 1.8 has been performed. Adjacent sections were stained with the Hale method in Müller modifications and the v. Koss method for sulphated mucins and inorganic deposits respectively. It has been found that hyaline cartilage in trachea contains mineral deposits and that P + Ca amounts up to 22% of cartilage dry mass. The Ca/P ratio approaches 2 what indicates hydroxyapatite type crystals. The cartilage contains substantial amounts of S reflecting the presence of sulphate groups. It was found that the cartilage binds also colloidal iron at low pH. There is a good correlation between places with high amount of bound colloidal iron assessed by PIXE and places showing strong Prussian Blue staining. The Fe/S ratio was, however, much lower in the cartilage than in other tissues what indicates that the colloidal iron method does not give quantitative results. There were no regions showing substantial decrease in Fe/S ratio which we found previously as typical for degenerating and calcifying growth plate cartilage. This may be connected with a relatively low degree of calcification degree of the tracheal cartilage.

Animals↗
PubMed1989

Changes in activity of selected lysosomal enzymes in peritoneal macrophages of renal failure patients on peritoneal dialysis.

Activity of acid phosphatase (AP), beta-glucuronidase (GR), N-acetyl-beta-D-glucosaminidase (GZ), and peroxidase (P) was assessed using a semiquantitative cytochemical method in peritoneal macrophages of 30 patients with end-stage renal failure treated by intermittent peritoneal dialysis and of 30 control patients with normal renal function. The dialysed patients showed a significantly higher activity of GR and P at the beginning of the treatment as compared with the respective activities observed in the control group and a further significant rise of these activities after 4 months of dialysis. Activity of AP at the beginning of the treatment was insignificantly lower than in the control group and the difference became significant at the end of the investigated period. There was no significant difference between the dialysed patients and the control group in the activity of GZ assessed at the beginning of the dialytic treatment and after 4 months of dialysis. A significant decrease in that activity was, however, observed in the course of dialysis.

Acetylglucosaminidase↗
PubMed1988

Measurement of colloidal iron binding at low pH in cartilage using the proton microprobe.

Quantitative micro-PIXE analysis was performed on mouse embryo epiphyseal cartilage and on the rib cartilage of mature animals after incubation of sections with colloidal iron at pH 1.8. The iron content as well as that of sulphur and phosphorus and Fe/S, Fe/P ratios were determined. It was found that colloidal iron content was higher in the cartilage than in other tissues. The cartilage also displayed the highest content of sulphur. The Fe/S ratio was however not constant, being highest in the degeneration zone close to the mineralization front, where the binding of iron was strongest while the amount of sulphur decreased. This indicates that factors other than number of sulphate groups influence the binding of positively charged molecules to glycosaminoglycans. This is confirmed by differences in the results obtained for embryonic and mature rib cartilage.

Aging↗
PubMed1988

Investigation of inorganic deposits in selected organic matrices.

Inorganic deposits in the wall of human and animal arteries and in experimental tumor (Morris hepatoma 7777) were examined using proton induced X-ray emission (PIXE) and PIXE in combination with proton microprobe (micro-PIXE) techniques. The sections adjacent to the irradiated ones part were submitted to histological investigations and one part of the material was additionally investigated by infrared (IR) spectroscopy. For identification of mineral deposits, the micro-PIXE method appeared the most sensitive. The mineral deposits were detected in the artery samples, even in those without visible morphological changes, as well as in tumor samples. The deposites showed different localization and composition, depending on age and type of vessel. There were also differences between human and animal arteries. IR spectroscopy revealed the presence of carbonate apatite within the artery samples from old individuals. Matching of histological observations with data obtained by micro-PIXE method allows a better correlation of morphological and analytical results.

Animals↗
PubMed1985

Elemental composition of the human atherosclerotic artery wall.

The elemental composition of the human atherosclerotic popliteal artery was examined using the proton-induced X-ray-emission (PIXE) method. The application of a narrow proton beam (3 X 10 micron 2) enabled us to determine not only the concentrations of Cl, K, Ca, Fe, Cu, Zn, Br and Pb, but also their localization in different artery-wall regions. The highest mean concentrations of Cl, K, Zn and Br were found in the tunica media. In the investigated sections the distribution of Ca and Fe varied: sometimes, these elements were prevalent in the tunica intima, whereas in other cases, the highest concentrations were observed in the tunica media or tunica adventitia. The concentration profiles of each element were characterized by many sharp, narrow peaks. The highest concentrations of Ca and Fe showed such high levels that only one explanation is possible, i.e. the presence of crystals. The correlation of Ca peaks with those of Zn and Fe is discussed. The usefulness of the micro-PIXE method for the investigation of biomedical materials is also considered.

Aged↗
PubMed1985

Leucine aminopeptidase of neutrophils and lymphocytes in patients with cancer.

The leucine aminopeptidase activity has been determined by using the cytochemical method of Burston and Folk in peripheral blood neutrophils and lymphocytes of 45 patients with various malignancies. Lung cancer, carcinoma of the stomach and cancer of the colon was diagnosed in 24, 16, and 5 patients, respectively. Patients with metastases showed a significantly higher activity of the enzyme if compared with that in the control group of healthy subjects and patients without metastases. The percentage of enzyme-positive lymphocytes was elevated significantly in patients with metastases whereas a total percentage of lymphocytes with regard to differential leukocyte count was diminished both in patients with and without metastases. The absolute count of neutrophils was elevated both in patients with and without metastases. The authors discuss the significance of their observation with regard to the antitumor cytotoxic effect of neutrophils and lymphocytes.

Colonic Neoplasms↗