Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Use-Long-term Follow-up of First Tuberous Sclerosis Complex Patient Treated De Novo With Sirolimus After Kidney Transplantation: A Case Report.

Mammalian target of rapamycin inhibitors (mTORI) are increasingly used in the treatment of tuberous sclerosis complex (TSC) and as immunosuppressants after organ transplantation. In TSC patients, mTORI are the treatment of choice after kidney transplantation. It is still under debate if benefits from long-term mTORI use will not be limited by side effects. MATERIALS AND METHODS: We report long-term follow-up data of the first TSC patient after kidney transplantation treated with sirolimus de novo. In 2005, a female patient was transplanted with a kidney graft after bilateral nephrectomy due to angiomyolipoma. Initial immunosuppressive treatment consisted of antithymocyte globulin, methylprednisolone, tacrolimus, and, due to TSC diagnosis, sirolimus. Creatinine level at discharge was 1.2 mg/dL. RESULTS: Long-term mTORI use resulted in skin lesion regression (angiofibromas, "confetti" skin lesions, shagreen patch) and disease stabilization in brain, abdominal, and chest magnetic resonance imaging/computed tomography scans. Pulmonary function tests showed improvement in restriction and slow deterioration in obstruction and diffusion parameters. Sirolimus related adverse reactions were hyperlipidemia and hypertriglyceridemia and respiratory and urinary tract infections. No gastrointestinal or hematologic symptoms occurred. Sirolimus concentrations ranged between 1.7 and 8.2 ng/mL (mean 4.01 ± 2.09 ng/mL). Since 2009 proteinuria and slow increase in creatinine level have been observed. No biopsy was performed to establish etiology and potential association with mTORI. In 2017 creatinine level was 2.2 mg/dL. CONCLUSION: The case of the patient confirms clinical effectiveness and acceptable safety of long-term mTORI treatment. Long-term mTORI use requires meticulous patient observation to optimize dosage, achieve immunosuppressive effect, and improve TSC manifestations with minimal side effects.

Intensify production, transform biomass to energy and novel goods and protect soils in Europe-A vision how to mobilize marginal lands.

The rapid increase of the world population constantly demands more food production from agricultural soils. This causes conflicts, since at the same time strong interest arises on novel bio-based products from agriculture, and new perspectives for rural landscapes with their valuable ecosystem services. Agriculture is in transition to fulfill these demands. In many countries, conventional farming, influenced by post-war food requirements, has largely been transformed into integrated and sustainable farming. However, since it is estimated that agricultural production systems will have to produce food for a global population that might amount to 9.1 billion by 2050 and over 10 billion by the end of the century, we will require an even smarter use of the available land, including fallow and derelict sites. One of the biggest challenges is to reverse non-sustainable management and land degradation. Innovative technologies and principles have to be applied to characterize marginal lands, explore options for remediation and re-establish productivity. With view to the heterogeneity of agricultural lands, it is more than logical to apply specific crop management and production practices according to soil conditions. Cross-fertilizing with conservation agriculture, such a novel approach will provide (1) increased resource use efficiency by producing more with less (ensuring food security), (2) improved product quality, (3) ameliorated nutritional status in food and feed products, (4) increased sustainability, (5) product traceability and (6) minimized negative environmental impacts notably on biodiversity and ecological functions. A sustainable strategy for future agriculture should concentrate on production of food and fodder, before utilizing bulk fractions for emerging bio-based products and convert residual stage products to compost, biochar and bioenergy. The present position paper discusses recent developments to indicate how to unlock the potentials of marginal land.

Influence of narrowband ultraviolet B phototherapy on serum tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in patients with psoriasis.

Psoriasis is characterized by keratinocyte resistance to apoptosis. We recently demonstrated an increase in serum tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in patients after topical treatment for psoriasis. We decided to verify whether narrowband ultraviolet B (NB-UVB) has a similar effect. Serum concentration of TWEAK was estimated in patients with exacerbated plaque psoriasis treated with NB-UVB. Baseline TWEAK levels were similar in patients with psoriasis and healthy controls, and Psoriasis Area and Severity Index (PASI) correlated inversely with TWEAK levels. Treatment with NB-UVB caused a significant reduction in PASI and concurrent increase in serum TWEAK. This finding may be due to increased expression of TWEAK receptor in psoriatic skin, which has been reported previously, with consequent binding of excess soluble TWEAK during treatment and subsequent release after treatment. Severity of plaque psoriasis and its improvement after NB-UVB treatment may be associated with TWEAK concentrations. The importance of our findings remains to be established.

SPR imaging biosensor for determination of laminin-5 as a potential cancer marker in biological material.

A new method for the selective determination of laminin-5 concentration using a biosensor and surface plasmon resonance imaging (SPRI) technique is presented. A biosensor based on the specific interaction of laminin-5 with rabbit polyclonal antibody was constructed. The analytically useful dynamic response range of the biosensor is between 0.014 and 0.1 ng mL(-1). The detection limit is 4 pg mL(-1). The potential influence of interferences on the SPRI signal was investigated, and the high selectivity of the biosensor was confirmed. In order to demonstrate the potential application of the biosensor, laminin-5 concentration in blood plasma was determined. The results were compared with the laminin-5 concentration obtained by the commercial enzyme-linked immunosorbent assay (ELISA) kit. A comparison of results from healthy donors obtained by SPRI measurement and ELISA indicates that they are close and shows good agreement with the data reported in the literature. The plasma samples of bladder cancer patients gave higher concentration measured with specific biosensor than by ELISA assay. The study shows the clear difference in concentration of laminin-5 in healthy humans and patients with bladder cancer. Extensive clinical studies using the newly developed method can result in an increase in the use of laminin-5 as a potential cancer marker.

The progressive reduction in the ovarian reserve in young women after anticancer treatment.

Anticancer treatment can disturb gonadal function and deplete the primordial follicle pool, leading to premature menopause. We made a prospective analysis of serum hormone levels in young female cancer survivors who had been treated during childhood and adolescence. Serum anti-Müllerian hormone (AMH) as a marker of ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after bone marrow transplantation, and in 34 healthy controls. The group of survivors was divided according to the risk of gonadotoxicity into the low risk and median risk group (LR+MR), and into the high risk (HR) group. The measurements were repeated after 5 years. In the HR group, AMH levels were significantly lower than in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first examination fell progressively after 5 years (p=0.03), whereas elevated FSH values (p=0.053) increased (p=0.001). Unchanged LH values in the first measurement rose in the second one (p=0.001). In the LR+MR group, the levels of AMH and FSH were normal (compared to the control) at baseline, but after 5 years serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate that anticancer treatment during childhood and adolescence is associated with a serious, progressive risk of ovarian failure. It is necessary to inform female cancer survivors, especially the high risk patients, about the risk of premature menopause.

Evaluation of the influence of ozonotherapy on the clinical parameters and MMP levels in patients with chronic and aggressive periodontitis.

PURPOSE: A comparison of the clinical status and salivary MMP levels after SRP alone or with ozonotherapy in patients with aggressive and chronic periodontitis. MATERIAL/METHODS: The study was performed in 52 generally healthy subjects with chronic or aggressive periodontitis. Group CP-S consisted of 12 patients with chronic periodontitis, who underwent scaling and root planing (SRP). In group CP-O there were 25 patients with chronic periodontitis who additionaly to SRP underwent ozonotherapy. The same therapy was performed in group AP, containing 15 patients with aggressive periodontitis. Plaque index, approximal plaque index, bleeding on probing, sulcus bleeding index, probing pocket depth and clinical attachment loss were measured at baseline, at two weeks and two months post-therapy. The levels of MMP-1, MMP-8 and MMP-9 were estimated in non-stimulated saliva with an ELISA method. RESULTS: All the clinical parameters assessed in the study groups were reduced after treatment. SRP with additional ozonotherapy provided an increase in MMP levels in patients with chronic periodontitis and a reduction in MMP levels in patients with aggressive periodontitis. CONCLUSIONS: SRP followed by ozonotherapy does not lead to further improvement in clinical periodontal parameters in patients with AP and CP.

Relationship between metabolic parameters and thyroid hormones and the level of gastric peptides in children with autoimmune thyroid diseases.

Overweight and diseases connected with it are increasing problems in children and adults. We often observe change of weight in thyroid disease. It is emphasized that changes in hormones such as peptide levels are in close relationship with regulation of body mass: ghrelin increases appetite and in effect increases body mass, but obestatin decreases appetite and weight. The aim of the study was to analyze the relationship between lipid-carbohydrate metabolism parameters and thyroid hormones and the level of gastric peptides (ghrelin and obestatin) in young patients with Graves' disease, Hashimoto's thyroiditis and in children with simple goiter. The study group formed 78 patients suffering from Graves' disease (29 girls and 2 boys; aged from 6 to 21 - mean 15,2 yrs) and Hashimoto's thyroiditis (29 girls and 3 boys; aged from 9 to 18--mean 14.5 yrs). The control group consisted of children with simple goiter--13 girls and 2 boys; aged from 9 to 18 --mean 14.8 yrs. In all patients, ghrelin and obestatin levels were analyzed by the RIA method (Phoenix Pharmaceuticals, USA). In children and adolescents with untreated Graves' disease we found higher levels of insulin and HOMA-IR index compared to the group of children with simple goiter (34 +/- 8 microIU/mL vs 15 +/- 5; p < 0.03; 7.3 +/- 1.2 vs 3 +/- 0.3, p < 0.03). No significant correlations were observed of gastric hormones with antithyroid antibodies, lipids or h-CRP in patients with untreated hyperthyroidism and subclinical hypothyroidism. Positive correlation was noted of insulin and glucose levels and HOMA-IR index with ghrelin level in children with newly diagnosed Graves' disease (r = 0.109, p < 0.045; r = 0.176, p < 0.036; r = 0.174, p < 0.037). The correlation was also positive between obestatin level and HOMA-IR index in children with subclinical hypothyroidism in the course of Hashimoto's thyroiditis (r = 0.497, p < 0.011). We also examined the relationship between BMI, thyroid hormones and the level of gastric peptides. In untreated GD patients, ghrelin level exhibited a significant negative correlation with fT3 and fT4 (r = -0.38, p < 0.041; r = -0.459, p < 0.012) and positive with TSH (r = 0.38, p < 0.041) and BMI (r = 0.8, p < 0.01). In conclusion, we suggest that the disturbances in carbohydrate parameters in thyroid diseases have an essential effect on change of hormone-controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in Subclinical hypothyroidism).

The evaluation of lysozyme concentration and peroxidase activity in non-stimulated saliva of patients infected with HIV.

PURPOSE: The aim of the study was the comparison of lysozyme concentration and peroxidase activity in mixed, non-stimulated saliva of HIV-positive patients and healthy subjects. MATERIAL AND METHODS: The study was carried out in the group of 37 patients infected with HIV. The control group comprised of non-infected individuals, counterpart of the examined group. Mixed non-stimulated saliva, collected using expectoration method in the amount of 3-5 ml 2 hours after meal, was used for the study. Saliva samples were centrifuged, divided into portions 200 microl each, and stored at -80 degrees C. Peroxidase activity was determined using the method by Mansson-Rahemtull et al. Lysozyme concentrations were determined with the use of radial immunodiffusion method, ready-made kits (Human NL Nanorid plate--The Binding Site Ltd., UK). RESULTS: Higher concentrations of lysozyme as well as peroxidase activity were observed in the group of patients with HIV as compared to the control group, and they were 35.08 microg/ml, 46.74 IU/1, 21.3 microg/ml, 37.73 IU/l, respectively. The difference was statistically significant only in case of peroxidase activity. CONCLUSIONS: 1. HIV infection triggers immune mechanisms, that are manifested by the increase in salivary enzymes responsible for local non-specific resistance. 2. The immunological resistance decrease, manifested by the drop of the absolute number of CD4 lymphocytes T, is compensated by the increase in lysozyme concentration and peroxidase activity in non-stimulated saliva of HIV-positive patients.

The saliva immunology mechanisms and periodontal status in HIV infected subjects.

PURPOSE: The aim of this study was the evaluation of connection between parodontium determined by using GI and PBI indexes and specific immunity status and non-specific in HIV infected group and in control group. MATERIAL AND METHODS: The study was carried out in the group of 37 patients infected with HIV. Mixed non-stimulated saliva was used for the study. Peroxidase activity was determined using the method by Mansson-Rahemtull. Lysozyme and A, G, M antibodies concentrations were determined with the use of radial immunodiffusion method. The concentration of lactoferrin was determined by using ELISA method. The clinical state of parodontium estimated by means of GI and PBI evaluating quality changes in the gum. RESULTS: Deterioration of the immunological status of subjects was accompanied by the increase of the values of GI and PBI. The strong negative correlation between GI and PBI and the concentration of lactoferrin and positive activity of the peroxidase in the whole examined population was determined. In the infected group the correlation between the status of gingiva expressed by GI and concentration or activity of examined enzymes and immunoglobulins was not ascertained. CONCLUSIONS: 1. HIV infection is connected to worsening of paradontium status expressed by values of GI and PBI indexes. 2. Paradontium status correlated positively with immunological status of HIV positive subjects. 3. In HIV infected group, no connection between number of IgA, IgG, IgM, concentration of lysozyme, lactoferrin, activity of peroxidase and paradontium status was observed.

[Nitrate and nitrite content in potatoes from ecological and conventional farms]. / Azotany i azotyny w ziemniakach z gospodarstw ekologicznych i konwencjonalnych.

The aim of this investigation was to determine nitrate and nitrite content in potatoes from ecological and conventional farms. The influence of variety on nitrate and nitrite content was also evaluated. Vegetables and potatoes from ecological cultures are supposed to contain less nitrates and nitrites and on this basis could have been advised for children, sick and people in special physiological stages. Nitrite content was determined colorimetrically, with sulfanilic acid, nitrate content was determined following reduction of nitrites by means of metallic cadmium. The results showed significantly lower nitrate content in potatoes from ecological farms, and almost twice higher in those from conventional farms. The nitrite content showed no differentiation in conventional and ecological farms. Within three varieties of potatoes (sokól, bryza, ania) significantly highest content of nitrate was determined in bryza. Considering low nitrate level potatoes from ecological farms could be advised for children and sick people, but for the complete safety evaluation also content of other contaminants (i.e. heavy metals) have to be assessed.