The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we ...evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.
The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage.
The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities.
Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.
► Sulfur concrete samples are made of modified secondary sulfur, sand, and fillers. ► Durability of sulfur concrete is investigated in 10% HCl, 20% H
2SO
4 and 3% NaCl. ► Compressive strength loss is ...higher for samples treated by HCl compared to H
2SO
4. ► Compressive strength loss is negligible after treatment in NaCl. ► Apparent porosity increase is in agreement with compressive strength loss.
Durability of sulfur concrete with different fillers, as well as Portland cement concrete, was tested in the solutions of HCl, H
2SO
4, and NaCl. Regarding mass changes, in the solutions of HCl and H
2SO
4 sulfur concrete with talc and fly ash exhibited higher durability, while in NaCl samples with alumina and microsilica were better. The type of filler did not affect durability regarding compressive strength. Strength loss was higher in the solution of HCl comparing to H
2SO
4, while negligible in NaCl which is in accordance with apparent porosity increase. Portland cement concrete after two months lost 20% of mass.
Titanium dioxide is a photocatalyst, known not only for its ability to oxidize organic contaminants, but also for its antimicrobial properties. In this article, significant enhancement of the ...antimicrobial activity of TiO2 (up to 32 times) was demonstrated after its activation by ball milling. The antimicrobial activity was analyzed for one fungal and 13 bacterial ATCC strains using the microdilution method and recording the minimum inhibitory concentration (MIC) values. In order to further investigate the correlation between the mechanical activation of TiO2 and its antimicrobial activity, the structure, morphology and phase composition of the material were studied by means of Electron Microscopy, X‐ray diffraction and nitrogen adsorption‐desorption measurements. UV‐Vis diffuse reflectance spectra were recorded and the Kubelka‐Munk function was applied to convert reflectance into the equivalent band gap energy (Eg) and, consequently, to investigate changes in the Eg value. X‐ray photoelectron spectroscopy was used to analyze the influence of mechanical activation on the Ti 2p and O 1s spectra. The presented results are expected to enable the development of more sustainable and effective advanced TiO2‐based materials with antimicrobial properties that could be used in numerous green technology applications.
In order to predict service life of the sulfur–polymer composite, the samples were subjected to the induced destruction using 10% hydrochloric acid solution. Control specimens were prepared using ...Portland cement binder. Sulfur–polymer composite showed limited mechanical strength and mass loss, while physico-mechanical properties of Portland cement composite regressed rapidly. The Image Pro Plus software was used for surface destruction monitoring. The simulations for composites were applied to the previously reported model for predicting the mechanical strength degradation during durability testing, based on the image analysis results. The results proved that the time gradient of structural change was useful for quantification of service life, therefore it can be accepted as a parameter that represents service life.
During chronic tonsillitis, the relationship between proliferation and apoptosis of lymphocytes in tonsillar follicles can be disturbed, which gives rise to attenuation of tonsil immunocompetence and ...diminishing its contribution in systemic immunity. In this study, we have quantified the cells expressing the markers of proliferation and apoptosis in the follicles of the palatine tonsil. Six tonsils from patients aged 10-29 years with hypertrophic tonsillitis and five tonsils from patients aged 18-22 years with recurrent tonsillitis were studied. The sections of paraffin blocks of tonsillar tissue were stained by the immunohistochemical LSAB/HRP method with the utilisation of antibodies for: Ki-67 antigen-cell marker of proliferation; Bcl-2 and survivin anti-apoptotic factors and Fas/CD95, caspase-3 and Bax pro-apoptotic factors. The size of lymphoid follicles, i.e. mean follicle area and number of lymphoid follicle immunopositive cells per mm2 of a slice area, i.e. numerical areal density were determined by the quantitative image analysis. The localisation of Ki-67, Bcl-2, survivin, Fas/CD95, caspase-3 and Bax- immunopositive cells inside the palatine tonsil was similar in both types of tonsillitis. The number of Ki-67 immunopositive cells was significantly (p < 0.01) larger in the tonsils with hypertrophic tonsillitis (14681.4 ± 1460.5) in comparison to those with recurrent tonsillitis (12491.4 ± 2321.6), although the number of survivin and caspase-3 immunopositive cells was significantly (p < 0.05) larger in recurrent tonsillitis (survivin, 406.9 ± 98.4; caspase-3, 350.4 ± 119.4) when compared to those with hypertrophic tonsillitis (survivin, 117.4 ± 14.5; caspase-3, 210 ± 24). Our results show that the rate of the proliferation and apoptosis of follicular lymphocytes is different in various types of tonsillitis. This suggests that the immunological potential of the palatine tonsil varies in patients with hypertrophic and recurrent tonsillitis, which in practice poses a dilemma over the choice of conservative or surgical treatment.
Abstract
Titanium dioxide is a photocatalyst, known not only for its ability to oxidize organic contaminants, but also for its antimicrobial properties. In this article, significant enhancement of ...the antimicrobial activity of TiO
2
(up to 32 times) was demonstrated after its activation by ball milling. The antimicrobial activity was analyzed for one fungal and 13 bacterial ATCC strains using the microdilution method and recording the minimum inhibitory concentration (MIC) values. In order to further investigate the correlation between the mechanical activation of TiO
2
and its antimicrobial activity, the structure, morphology and phase composition of the material were studied by means of Electron Microscopy, X‐ray diffraction and nitrogen adsorption‐desorption measurements. UV‐Vis diffuse reflectance spectra were recorded and the Kubelka‐Munk function was applied to convert reflectance into the equivalent band gap energy (
E
g
) and, consequently, to investigate changes in the
E
g
value. X‐ray photoelectron spectroscopy was used to analyze the influence of mechanical activation on the Ti 2p and O 1s spectra. The presented results are expected to enable the development of more sustainable and effective advanced TiO
2
‐based materials with antimicrobial properties that could be used in numerous green technology applications.
Palatine tonsils represent the first place of contact for a variety of antigenic substances present in air and food. Upon antigen stimulation, the interactions between T and B lymphocytes in the ...tonsil are known to depend on the expression of different co-stimulatory molecules, including proteolytic ectoenzymes. Dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN), as T lymphocyte co-stimulatory molecules, participate in the regulation of the immune response during inflammation.
In this study, the serum and lymphocyte enzymatic activity of DPP IV and APN was investigated in 32 patients, 13 with recurrent tonsillitis (RT) and 19 with tonsillar hypertrophy (TH), before and one month after tonsillectomy. The enzymatic activity of DPP IV and APN in tonsillar lymphocytes and serum was determined kinetically at 37 degrees C using Gly-Pro-p-nitroanilide (for DPP IV) and Ala-p-nitroanilide (for APN) as chromogenic substrates.
Significantly higher serum DPP IV and APN activities (P<0.001) were found in TH patients compared with those with RT before tonsillectomy. DPP IV activity in TH patients was also elevated compared with the control of the same age (P<0.001), whereas the activity of APN was the same as the control group. The activity of both enzymes was the same as of controls after tonsillectomy. In addition, the results show that DPP IV and APN activities in serum decrease significantly with age. Tonsillar lymphocytes demonstrated a wide range of DPP IV and APN activities without significant differences between the investigated groups.
An increased serum DPP IV activity was observed in TH patients compared with both RT patients and controls before tonsillectomy. After tonsillectomy, all activities were similar. The results suggest that serum DPP IV activity may have potential as a diagnostic marker for patients with TH.
Patients with end-stage renal disease (ESKD) present an immunodeficiency state paradoxically exacerbated by hemodialysis (HD) and associated with signs of T-cell activation. B cells are also ...activated in uremia, and this activation could be altered by erythropoietin therapy in HD patients. In this study, the effects of human recombinant erythropoietin (rHu-EPO) and 1-alpha-D3 treatments on lymphocyte immunomodulatory enzymes, aminopeptidase N (APN), and 5'-nucleotidase activity in patients on HD were investigated in hemodialysis patients before and after two-month treatment with s.c. rHu-EPO (15 patients, 2000-3000 U three times weekly) or oral 1-alpha-D3 (14 patients, 2 microg three times weekly).
A two-month EPO treatment of 15 HD patients produced a rise in hemoglobin from 6.51 +/- 0.18 to 9.69 +/- 0.14 g/dL. Basal lymphocyte APN activity in HD patients was not significantly different from the level in healthy controls. Treatment of patients with rHu-EPO increased unstimulated lymphocyte APN activity to values significantly higher than those before treatment (p<0.05). A two-month pulse oral 1-alpha-D3 treatment of 14 HD patients increased hematocrit by 21% and raised hemoglobin from 7.11 +/- 0.32 to 8.80 +/- 0.39 g/dL. Unstimulated and Con A-stimulated lymphocyte APN activity after pulse oral 1-alpha-D3 was significantly increased (p<0.01 and p<0.05, respectively) from the pretreatment levels. In HD patients lymphocyte basal, Con A-, and PMA-stimulated 5'-nucleotidase activity was significantly higher (p<0.05) than it was in healthy controls. The two-month treatment with rHu-EPO or pulse oral 1-alpha D3 did not change the level of lymphocyte 5'-nucleotidase in these patients.
This study demonstrated that a two-month treatment of HD patients with rHu-EPO or pulse oral 1-alpha D3 significantly increases activity of lymphocyte APN, important for cleavage of peptides and small proteins, which accumulate in the blood of ESKD patients. In HD patients lymphocyte ecto-5'-nucleotidase activity was significantly higher than that in healthy controls and was not changed after a two-month treatment with rHu-EPO or pulse oral 1-alpha D3. We speculate that oxidative stress activates 5'-nucleotidase and production of adenosine by lymphocytes of HD patients.
Rhabdomyolysis may account for about 10% of all cases of acute renal failure (ARF). This study was performed to explore the protective influence of proanthocyanidins from seeds of grape in an ...experimental model of myoglobinuric ARF. Rats were injected with 50% glycerol (8 mL Kg, im) followed immediately and daily in the next three days by ip proanthocyanidins (20 mg kg) or saline. After 96 h rats were sacrificed and kidney morphology, kidney cortex peptidase activities, and malondialdehyde (MDA) content were determined. A moderate renal failure was produced by glycerol injection with blood urea of 31.8 ± 11.0 vs. 7.68 ± 0.24 mmol L, and serum creatinine of 153.6 ± 38.2 vs. 39.6 ± 9.0 μmol L, in glycerol-induced ARF vs. control rats, respectively. Rats that received proanthocyanidins in addition to glycerol had significantly lower (p < 0.01) blood urea and serum creatinine levels compared to those receiving glycerol alone. These functional differences between the glycerol and glycerol plus proanthocianidins groups were also confirmed histologically. Kidney cortex dipeptidylpeptidase IV (DPP IV) activity was not significantly changed in glycerol-induced ARF, however, markedly increased after proanthocyanidins treatment. Kidney cortex malondialdehyde content was found significantly increased in glycerol-induced ARF over control level, and was markedly reduced by proanthocyanidin treatment. Taken together, these results provide strong evidence for the protective role of proanthocyanidins from seeds of grape in glycerol-induced ARF. The effect is probably due to the antioxidant activity of proanthocyanidins and to increased expression of kidney cortex DPP IV with effective degradation of TNF-α. This may provide therapeutic opportunities of preventing and or treating myoglobinuric ARF in humans.
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