Evaluation of the Antioxidant, Cytoprotective and Antityrosinase Effects of Schisandra chinensis Extracts and Their Applicability in Skin Care Product.

Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.

Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn's disease naive to anti-TNF agents.

INTRODUCTION: Objective assessment of Crohn's disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. AIM: To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment. MATERIAL AND METHODS: Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically. RESULTS: The median time of follow-up was 29 months (interquartile range - IQR: 14-46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35-97%) sensitivity and 72% (IQR: 46-90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing). CONCLUSIONS: Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.

[The use of methotrexate in an inflammatory bowel diseases based on the review of the current literature].

M ethotrexate (MTX) as an immunomodulatory drug has numerous applications in autoimmune diseases. Autoimmune patomechanism is one of the factors responsible for development of inflammatory bowel diseases (IBD). MTX is an alternative therapy in the treatment of IBD. Over the past several years clinical trials has confirmed the efficacy of MTX in the treatment of Crohn's disease (CD). Data concerning use of MTX in ulcerative colitis (UC) are not as numerous as in the CD. Currently, MTX is recommended for the induction treatment and maintenance therapy in CD patients, especially in steroid-dependent patients, disease refractory to corticosteroids, no improvement after treatment with azathioprine and 6-mercaptopurine, or in case of intolerance to these drugs. Preferred route of administration in the treatment of CD is parenteral supply. Contraception is indicated during MTX treatment since it's teratogenic.

Comparison of PAHs uptake by selected Monocotyledones and Dicotyledones from municipal and industrial sewage sludge.

The study was focused on two goals: (i) the confirmation of the existence of a general relation between the content of polycyclic aromatic hydrocarbons (PAHs) in sewage sludge and in plants growing in it, regardless of the type and content of sewage sludge, and (ii) if so, the answer to the question whether the uptake of PAHs by plants depends on their type. To realize the set aims, the contents of PAHs in four differentiated plant species were measured, two belonging to the Monocotyledones and two belonging to Dicotyledones group, growing in municipal and industrial sewage sludge in two locations. All the investigations were carried out during the period of 3 years. The results clearly demonstrated that the uptake of PAHs by a plant depended on polyaromatic hydrocarbon concentration in the sewage sludge. The relation between accumulation coefficient of PAHs in plant material vs. the content of PAH in sewage sludge was of exponential character. The results indicate that in case of four- and five-ring PAHs, the root uptake mechanism from soil solution occurs, regardless of the type and origin of sewage sludge and the type of plant. For three-ring PAHs, we can assume for Monocotyledones that the root uptake mechanism occurs because we observe a significant correlation between the content of fluorene, phenanthrene, and anthracene in plant material and in the sewage sludge. For Dicotyledones, the correlation is insignificant, and in this case probably two mechanisms occur-the uptake by roots and by leaves.

Osteoprotegerin, s-RANKL, and selected interleukins in the pathology of bone metabolism in patients with Crohn's disease.

INTRODUCTION: Crohn's disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known. AIM: Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD. MATERIAL AND METHODS: Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2-L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1ß, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected. RESULTS: The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1ß concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2-L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2-L4. CONCLUSIONS: The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1ß, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG.

Diagnostic importance of faecal markers in long-term monitoring of anti-TNF-α therapy in primary responders with Crohn's disease.

INTRODUCTION: Monitoring the response to biological treatment in Crohn's disease (CD) is a very important element of the therapeutic optimisation. AIM: To evaluate the usefulness of measuring calprotectin, lactoferrin, and myeloperoxidase in stool as markers of long-term clinical and endoscopic response to anti-tumour necrosis factor α (anti-TNF) treatment in CD. MATERIAL AND METHODS: The studied group consisted of 35 CD patients treated with anti-TNF-α antibodies. Clinical activity was evaluated using Crohn's Disease Activity Index (CDAI), and the exacerbation of endoscopic changes was evaluated using a Simple Endoscopic Score for Crohn's Disease (SES-CD). The concentration of calprotectin, lactoferrin, and myeloperoxidase was measured using the ELISA method. All measurements were performed three times - before, after 3 months, and after a year of therapy. RESULTS: During anti-TNF treatment the concentrations of all measured faecal markers decreased significantly in relation to baseline values. We observed a significant correlation at all time-points: before the therapy, after 3 months, and 12 months after starting the therapy, between the concentration of calprotectin and SES-CD, calprotectin and CDAI, as well as between lactoferrin and SES-CD, and lactoferrin and CDAI. Myeloperoxidase correlated with both SES-CD and CDAI only after 1 year of treatment. CONCLUSIONS: Faecal calprotectin and lactoferrin are valuable markers of clinical and endoscopic activity of CD in patients treated with anti-TNF antibodies. They are useful in monitoring the response to treatment. The usefulness of myeloperoxidase in this respect remains controversial.

The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases.

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

Association of serum VEGF with clinical response to anti-TNFα therapy for Crohn's disease.

Down-regulation of immune-mediated angiogenesis seems to be an important mechanism in anti-tumor necrosis factor α (anti-TNFα) therapy for Crohn's disease (CD). However, it remains to be established whether the baseline pro-angiogenic activity as reflected by the level of vascular endothelial growth factor (VEGF) could be of predictive value for successful clinical outcome of such treatment. Here, the levels of serum VEGF and other crucial angiogenesis-regulating peptides were assessed before and after induction anti-TNFα therapy in CD patients, and in age- and sex-matched healthy controls. Clinical, endoscopic, and biochemical activity of CD was estimated in parallel. CD patients were divided into two subgroups, depending on baseline VEGF levels: a "low-VEGF" subgroup with VEGF levels similar to those detected in healthy people, and a "high-VEGF" subgroup with VEGF levels significantly increased. VEGF levels were found to significantly correlate with CD clinical activity. Compared to the "low-VEGF" subgroup, the reduction in CD clinical activity as assessed by Crohn's Disease Activity Index was significantly greater in "high-VEGF" patients both in absolute numbers, and as a percentage of pre-treatment values. Accordingly, the fraction of patients who did not respond adequately to treatment was significantly greater in the "low-VEGF" group. These data indicate that VEGF may serve as an additional marker of CD activity and that baseline VEGF levels can be helpful in predicting the efficacy of anti-TNFα therapy.

The diagnostic usefulness of fecal lactoferrin in the assessment of Crohn's disease activity.

BACKGROUND: Diagnosis and monitoring of Crohn's disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce. AIMS: To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity. METHODS: The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohn's Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores. RESULTS: Median FL concentration was 84.14 (IQR: 36.4-302.9) µg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 µg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%. CONCLUSIONS: FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD.

The influence of anti-TNF therapy on the magnetic resonance enterographic parameters of Crohn's disease activity.

PURPOSE: Magnetic resonance enterography (MRE) is a useful tool in assessing the transmural and extraintestinal lesions in Crohn's disease (CD). However, the influence of anti-tumor necrosis factor (anti-TNF) therapy on MRE features of CD severity remains unknown. The purpose of the study was to assess the short- and long-term changes in MRE features of CD activity in relation to CD clinical course in patients treated with anti-TNF antibodies. METHODS: The influence on the most important parameters of CD activity seen in MRE was assessed retrospectively using a validated score. Patients were treated with anti-TNF agents and the clinical, laboratory, and MRE CD activity was estimated at baseline, after the induction therapy and after 1 year of treatment. RESULTS: 71 patients were enrolled in a study. The change in CD clinical activity correlated significantly with fluctuations in MRE activity score (P < 0.0001, r = 0.5 for induction; P = 0.004, r = 0.7 for maintenance anti-TNF therapy, respectively). Bowel wall thickening, mesenteric lymphadenopathy, and fat wrapping with vascular proliferation were MRE parameters which changed significantly both after the induction and maintenance treatment in patients responding to the therapy. The change in MRE activity score was mostly pronounced during the first 3 months of treatment, when compared to the continuation of the therapy till week 52-54 (-6 points vs. -2 points, respectively; P = 0.0008). CONCLUSIONS: Transmural and extraintestinal healing seen in MRE correlates with changes in CD clinical activity during anti-TNF therapy, thus MRE seems to be a useful tool in monitoring the efficacy of biological agents.

Is faecal calprotectin equally useful in all Crohn's disease locations? A prospective, comparative study.

INTRODUCTION: There are data suggesting that the diagnostic usefulness of faecal calprotectin (FC) may vary depending on the Crohn's disease (CD) location. The aim of the study was to compare the diagnostic usefulness of FC in CD patients with different disease locations. MATERIAL AND METHODS: We prospectively enrolled 120 CD patients in the study. Disease activity was assessed by using Crohn's Disease Activity Index (CDAI), biochemical markers, and endoscopic and radiographic methods. Faecal calprotectin concentration was assessed in single stool samples by using the ELISA method. RESULTS: Among all patients, 54 (45%) had ileocolonic CD location, 44 (36.5%) had isolated small bowel location, and 22 (18.5%) had colonic CD location. FC correlated significantly with C-reactive protein concentration and endoscopic and radiographic activity among patients with isolated small bowel CD (p = 0.03, r = 0.32; p < 0.0001, r = 0.78; p = 0.03, r = 0.35; respectively) and with C-reactive protein and endoscopic activity in isolated colonic CD (p = 0.0009, r = 0.7; p = 0.0002, r = 0.78; respectively). CDAI and inflammatory biochemical markers did not correlate with endoscopic and radiographic assessment in small bowel CD. In patients with ileocolonic CD, FC correlated significantly with endoscopy (p = 0.006, r = 0.5), radiographic assessment (p = 0.04, r = 0.3), CDAI (p = 0.0006, r = 0.5) and the majority of biochemical markers. CONCLUSIONS: Faecal calprotectin is a useful diagnostic marker in all CD patients. Although its usefulness in small bowel CD seems to be the lowest, it should be utilized particularly in this disease location because of the lack of other reliable, non-invasive diagnostic methods.

Magnetic resonance enterographic predictors of one-year outcome in ileal and ileocolonic Crohn's disease treated with anti-tumor necrosis factor antibodies.

The aim of the study was to assess the role of magnetic resonance enterography (MRE) in predicting one-year efficacy of anti-tumor necrosis factor antibodies--infliximab (IFX), adalimumab (ADA) in Crohn's disease (CD) patients primarily responding to therapy. We performed retrospective analysis among 61 CD patients who had undergone a successful IFX/ADA induction therapy and were treated with maintenance doses. All patients underwent MRE at week 0. We assessed which MRE features were predictive for steroid-free remission at week 52, and which were associated with a secondary loss of response. 44 patients were in steroid-free remission at week 52, 17--were secondary non-responders. The ROC curve showed that bowel thickening with contrast enhancement analyzed together at week 0 were associated with steroid-free remission at week 52 (p = 0.01; AUC 0.67). Bowel stenosis with or without prestenotic dilatation [OR 5.8 (95% CI 1.4-25) and 2.4 (95% CI 1.2 - 5) respectively; p = 0.01] and the presence of intra-abdominal fistulas [OR 1.4 (95% CI 1.1-2); p=0.004] were related to secondary non-response. A high baseline inflammatory activity detected by MRE predicts one-year response in CD after IFX/ADA. In case of bowel stenosis, intra-abdominal fistulas, other therapeutic options should be considered.

The relation between polyaromatic hydrocarbon concentration in sewage sludge and its uptake by plants: Phragmites communis, Polygonum persicaria and Bidens tripartita.

The aim of the study was to define the relationship between the concentration of PAHs in sewage sludge at a particular location and their amount in various plant materials growing on it. The credibility of the results is enhanced by the fact that sewage sludge from two separate sewage-treatment plants were selected for their influence on the content of PAHs in three plant species growing on them. The investigations were carried out for a period of three years. The results demonstrated unequivocally that the uptake of PAHs by a plant depended on polyaromatic hydrocarbon concentration in the sewage sludge. The correlation between accumulation coefficient of PAH in a plant and the content of the same PAH in the sewage sludge had for three-, four- and five-ring hydrocarbons an exponential character and for six-ring hydrocarbons was of a linear character. The accumulation coefficients calculated for three-ring aromatics were several times higher than for four-ring PAHs; further the coefficient values calculated for five-ring PAHs were several times lower than for four-ring hydrocarbons. Finally, the accumulation coefficient values of six-ring PAHs were the lowest in the series of studied polyaromatic hydrocarbons.

Association between disease duration and usefulness of fecal calprotectin measurement in patients with Crohn's disease.

INTRODUCTION: Fecal calprotectin is a useful diagnostic marker in the assessment of Crohn's disease (CD) activity. However, the clinical picture of CD is diverse and its phenotypes change with disease duration: in the early phase, an inflammatory activity dominates and, with time, an increasing percentage of patients develop strictures and fistulas. OBJECTIVES:  The aim of the study was to assess whether disease duration affects the diagnostic utility of fecal calprotectin measurement in patients with CD. PATIENTS AND METHODS:  A total of 150 patients with CD were prospectively enrolled into the study. CD activity was assessed by magnetic resonance enterography by calculating the Simple Enterographic Activity Score for Crohn's Disease. Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES­CD). The blood levels of inflammatory markers and the fecal calprotectin concentration were assessed using an enzyme­linked immunosorbent assay. Patients were divided into 2 subgroups depending on CD duration: less than 10 years and 10 years or longer from the diagnosis. RESULTS:  Patients with longer disease duration had lower inflammatory CD activity assessed by biochemical, endoscopic, and radiographic tests. Fecal calprotectin showed a tendency for lower concentrations in this subgroup (106.5 ±93.2 mg/l vs. 135.7 ±128.8 mg/l; P >0.05). A stricturing or penetrating CD phenotype was observed significantly more often in patients with long­lasting CD (P <0.04). Nevertheless, in both study subgroups, fecal calprotectin was significantly correlated with SES­CD, C­reactive protein levels, and platelet count. CONCLUSIONS:  Disease duration and time­dependent changes of the CD phenotype do not affect the diagnostic utility of the fecal calprotectin measurement. Reliability of this noninvasive biochemical method in the assessment of disease activity is similar in all patients with CD; therefore, it may be used independently of the time from diagnosis.

Factors influencing the clinical course of popliteal artery aneurysm.

BACKGROUND: The literature concerning the threshold for intervention in asymptomatic popliteal aneurysm is inconsistent. The purpose of this study was to identify factors related to the clinical course of popliteal aneurysms. MATERIAL/METHODS: We analyzed the influence of patients' age and sex, diameter of the aneurysm, atherosclerotic risk factors, use of antiplatelet medications and statins, lipid profile, and the presence of other aneurysms on the symptoms and status of the popliteal aneurysm (patent or thrombosed). RESULTS: Of 86 cases of popliteal aneurysms in 61 patients, 18 were asymptomatic, 22 were associated with intermittent claudication, 26 with acute limb ischemia, 10 with critical limb ischemia, and 10 with nonischemic symptoms. There was a trend of borderline statistical significance for smaller diameter in asymptomatic popliteal aneurysms. It was not possible to discriminate between cases with and without limb-threatening symptoms, or patent versus thrombosed popliteal aneurysm based on the diameter of the aneurysm. The 58 cases with hypercholesterolemia less frequently presented with limb-threatening symptoms (32.8%) compared with the 28 patients without hypercholesterolemia (60.7%, P=.02), and more often had patent aneurysms (55.2% versus 28.6%, P=.04). Patients with patent popliteal aneurysms were younger (P=.047) and were more frequently on statins (30% versus 12.5%, P=.063). CONCLUSIONS: Expectations regarding clinical course and indications for intervention in popliteal aneurysm should not be based on its diameter. Statins may have a beneficial influence on the clinical course of popliteal aneurysms, but further investigations are required.