RAGE and HMGB1 Expression in Orbital Tissue Microenvironment in Graves' Ophthalmopathy.

Graves' ophthalmopathy (GO) is a chronic autoimmune inflammatory disorder involving orbital tissues. A receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 (HMGB1) protein trigger inflammation and cell proliferation and are involved in the pathogenesis of various chronic inflammatory diseases. This study was aimed to evaluate RAGE and HMGB1 expression in GO to determine its potential clinical significance. To the best of our knowledge, this is the first study showing RAGE and HMGB1 expression in orbital tissue using immunohistochemistry. Sections of orbital adipose tissue obtained from patients diagnosed with GO (23 patients; 36 orbits) and normal controls (NC) (15 patients; 15 orbits) were analyzed by immunohistochemistry for RAGE and HMGB1 expression. Expression profiles were then correlated with clinical data of the study group. RAGE and HMGB1 expression were elevated in GO patients in comparison with NC (p = 0.001 and p = 0.02, respectively). We observed a correlation between RAGE expression and occurrence of dysthyroid optic neuropathy (DON) (p = 0.05) and levels of TSH Receptor Antibodies (TRAb) (p = 0.01). Overexpression of RAGE and HMGB1 might be associated with GO pathogenesis. In addition, RAGE and HMGB1 proteins may be considered as promising therapeutic targets, but this requires further research.

Morphea and antithyroid antibodies.

INTRODUCTION: Morphea, also known as localized scleroderma, is an autoimmune skin disease which is characterized by excessive accumulation of collagen that leads to the thickening of the dermis and subcutaneous tissue. There is an unclear relationship between morphea and other autoimmune diseases, especially related to the thyroid gland. AIM: To determine the occurrence of increased antithyroid antibodies in patients with morphea in relation to the clinical manifestations of the disease. MATERIAL AND METHODS: Forty-two Caucasian patients with different forms of morphea were included into the study. To determine the thyroid status, thyrotropin (TSH), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab) were evaluated with the use of the electrochemiluminescence method and TSH receptor autoantibodies (TRAb) - with the use of the radioimmunoassay method. RESULTS: Increased levels of antithyroid antibodies were observed in 6 cases in relation to TPO-Ab (14.3%), in 4 cases in relation to of Tg-Ab (9.5%) and in 1 patient in relation to TRAb (2.3%). There was no difference in the level of antithyroid antibodies between circumscribed and generalized forms of morphea. CONCLUSIONS: Although morphea is an autoimmune disease, it does not seem to be associated with increased prevalence of positive antithyroid antibodies. We conclude that there is no need to perform routine laboratory tests for thyroid disorders in patients with morphea.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.

BACKGROUND: The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane. METHODS: The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. RESULTS: The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia. CONCLUSIONS: GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

Itching sensation in psoriatic patients and its relation to body mass index and IL-17 and IL-31 concentrations.

INTRODUCTION: According to available data, pruritus is a common symptom of psoriasis, however its characteristics and pathogenesis are not clearly understood. AIM: The main aim of this study was to assess itching sensation among patients suffering from psoriasis, including its incidence and severity. All factors triggering and worsening pruritic symptoms were also carefully analyzed. The authors assessed the relationship of itch with body mass index (BMI) and severity of disease. Moreover, serum levels of interleukin 17 (IL-17) and IL-31 were analyzed in relation to Psoriasis Activity and Severity Index, BMI and severity of pruritus. MATERIAL AND METHODS: The study group consisted of 60 patients with plaque-type psoriasis. Analysis of impact of pruritus on the quality of life and worsening factors was based on the questionnaire. The severity of pruritus was assessed with the use of two independent scales. Serum IL-17 and IL-31 levels were measured in 30 patients suffering from psoriasis and in 10 healthy controls using immunoassay tests. RESULTS: 88.3% of analyzed patients complained of itch and the most common factor which exacerbated pruritus was stress (39.6%). Pruritus in psoriasis was independent of gender, illness duration and extent of skin lesions. The average intensity of pruritus was assessed as moderate and did not correlate significantly with BMI level, IL-17 and IL-31. CONCLUSIONS: Since the pathogenesis of pruritus in psoriasis is not fully understood, further investigation in this area needs to be conducted. Pruritus may be considered as a characteristic feature of psoriasis and, besides the skin lesions, should be a target in dermatological treatment to improve patient's quality of life.

Anti-Müllerian hormone concentration as a biomarker of pregnancy success or failure.

OBJECTIVE: This study was conducted to determine serum anti-Müllerian hormone (AMH) concentration influence on pregnancy outcome. STUDY DESIGN: In this study we investigated sixty one infertile women (aged 27 to 44 years) who were diagnosed and treated between 2011 and 2013. We determine ovarian reserve measured by AMH concentration. Patients were divided in three groups according to their serum AMH concentration (<1 ng/ml; 1-2.5 ng/ml; >2.5 ng/ml respectively). We investigated the relationship between clinical pregnancy rate and AMH concentration. In addition, anti-thyroid antibodies (anti-TG and/or anti-TPO) positivity and insulin concentration were correlated with AMH level and pregnancy outcome in the study groups. RESULTS: We found no statistical differences between AMH concentration regarding number of pregnancies (42.3%; 41.1 %; 38.9% respectively in study groups; p>0.05). The miscarriage rate was highest in women with AMH>2.5 ng/mL (27.3%, 0%, 86% respectively in study groups; p>0.05). We found that anti-thyroid positivity is more frequent in women with lower AMH concentration (23.1%; 11.7%; 5.5% respectively; p>0.05) and patients with lower serum AMH had higher serum insulin concentration (p<0.05). CONCLUSIONS: It seems that AMH concentration might not reflect oocyte quality and the chance of pregnancy, but increased AMH concentration may be associated with negative pregnancy outcome. Moreover, it cannot be excluded that presence of anti-thyroid antibodies and increased insulin serum concentration may be connected to diminished ovarian reserve measured by AMH concentration.

Physical activity and body composition, body physique, and quality of life in premenopausal breast cancer patients during endocrine therapy--a feasibility study.

UNLABELLED: Endocrine therapy (ET) is a common method of treatment in breast cancer patients; however, its negative impact on body composition, body physique (physical body shape/measurements), and quality of life (QoL) remains controversial. Previous studies have shown physical exercise can have a positive effect on QoL in breast cancer patients, especially premenopausal subjects. OBJECTIVE: In this feasibility study, we sought to assess the impact that physical exercise had on body composition and QoL in premenopausal breast cancer patients undergoing ET, and to determine the appropriateness of further testing of this intervention in this patient group. MATERIAL AND METHODS: This study involved 41 premenopausal female breast cancer patients before and after six, 12, and 18 months of ET. Aerobic training began in the 6th month and resistance training was added in the 12th month. Body composition was evaluated using dual-energy x-ray absorptiometry (DXA) scans, body physique was evaluated using anthropometric measurement techniques, and QoL was evaluated using questionnaires from the European Organization for Research and Treatment of Cancer. RESULTS: The initial period of ET with no exercise resulted in a reduction in fat-free body mass (FFBM), an increase in fat body mass (FBM), and a decline in QoL scores. Adding aerobic training resulted in a reduction of FBM and percentage of android fat, and improved QoL scores. The introduction of resistance training further reduced percentage of android and gynoid fat, increased FFBM, and further improved QoL scores. CONCLUSION: ET negatively impacts body composition, body physique, and QoL of premenopausal breast cancer patients. This feasibility study shows that physical activity may improve QoL and reduce adverse effects of ET on body composition and body physique, indicating appropriateness for further investigation on the use of exercise programs in premenopausal breast cancer patients to improve the outcomes of therapy.

Exercise tolerance in breast cancer patients during radiotherapy after aerobic training.

AIM OF THE STUDY: In spite of the introduction of dose constraints based on patient individual assessment techniques for radiation therapy (RT), some side effects from the heart and lungs are observed. Regular physical exercises improve efficiency, which was confirmed in clinical trials. The aim of this study was to evaluate endurance exercise tolerance and the impact of aerobic training (AT) on selected clinical parameters in breast cancer patients during RT. MATERIAL AND METHODS: This study involved 46 women with breast cancer who were irradiated using conformal technique (3DCRT) to a total dose of 50 Gray during a 5-week course of RT. In this period 25 patients (group A) simultaneously performed AT, and the rest of the patients, without rehabilitation (group B), undertook irregular physical activity on their own. The exercise tolerance was assessed through the 6-minute walk test (6MWT) using: oxygen saturation (SO2), heart rate (HR), blood pressure (BP), 6-minute walk distance (6MWD) and dyspnea scale. RESULTS: After AT in group A, a statistically significant (p < 0.05) decrease was observed in average diastolic BP before 6MWT and in HR parameters before and after 6MWT (p > 0.05), and 6MWD was increased (p < 0.05). In group B, after RT, an increase (p < 0.05) in HR was observed after the test as well as dyspnea. Oxygen saturation in both groups was not significantly changed. CONCLUSIONS: The results of our study showed that regular AT after just 6 weeks caused an improvement in exercise tolerance parameters with a substantial decline in dyspnea in breast cancer patients receiving RT.

Transforming growth factor-ß1 in plaque morphea.

INTRODUCTION: Morphea (localized scleroderma) is a rare cutaneous disease characterized by skin fibrosis of unknown pathogenesis. Transforming growth factor-ß (TGF-ß) is a potent profibrotic factor. The role of TGF-ß in morphea remains unclear. AIM: The goal of this study was to estimate the expression level of TGF-ß1 in skin and peripheral blood mononuclear cells as well as the plasma levels of TGF-ß1 in plaque morphea (MEP). MATERIAL AND METHODS: The study involved 20 MEP patients. Three control groups were involved: 1 - plasma: 36 healthy volunteers; 2 - PBMC: 47 healthy volunteers; 3 - skin biopsies: 13 samples collected during mastectomy (breast cancer was not skin involved). The analysis of TGF-ß1 plasma levels was performed with the use an adequate ELISA kit, while real-time polymerase chain reaction was employed for the expression of TGF-ß1 in peripheral blood mononuclear cells (PBMC) and skin. RESULTS: In our study we have not detected differences in TGF-ß 1 expression in PBMC, skin, nor in plasma levels of TGF-ß1 between MEP patients and healthy controls, regardless of disease activity and its duration. CONCLUSIONS: The results of our study contradict the claim of the substantial role of TGF-ß1 in the most common morphea subtype - MEP.

Effect of Herbal Feed Additives on Goat Milk Volatile Flavor Compounds.

The aim of this study is to investigate the effects of herbal supplements administered to goats on sensory quality and volatile flavor compounds in their milk. The experiment was conducted on sixty Polish white improved goats randomly allocated into five feeding groups (four experimental and one control) of twelve goats each. The trial lasted 12 weeks. The experimental animals received supplements containing a mixture of seven or nine different species of herbs at 20 or 40 g/animal/day. The control group received feed without any herbal supplements. Milk obtained from experimental and control groups of animals was characterized by a low content of aroma compounds, with only 11 chemical compounds being identified. Decanoic methyl ester, methylo 2-heptanone and methylo-butanoic methyl ester had the highest share in the total variability of the tested aroma compounds (PCA). During the sensory evaluation, the smell and taste of most of the samples were similar (p > 0.05). However, the addition of herbal feed supplements lowered the concentration of Caproic acid (C6:0), Caprylic acid (C8:0) and Capric acid (C10:0), which caused a significant reduction in the goaty smell of milk. The obtained results indicate that the studied herbal supplements can reduce the intensity of goaty smell and allow goat milk production without modification of other sensory features.

17ß Hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma.

OBJECTIVE: 17ß-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in the growth and progression of this tumor. METHODS: Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined. RESULTS: HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogeneous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown. CONCLUSION: HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression.

The Influence of the Accelerated Aging Process on the Compressive Strength of Wood Treated with Components of a Salt Fire Retardant.

This paper presents the results of research on the influence of the components of salt flame retardants on the compressive strength of wood depending on the time of accelerated aging. The effect of the agent was assessed on the basis of the change in the strength of treated wood compared to that of untreated wood. In addition, a statistical analysis of the obtained results was used to determine which of the components most significantly affect the changes in the compressive strength of wood along the fibers, and to what extent. It was found that extending the aging process time in the case of control and boric acid-protected samples did not significantly change the strength properties. It has also been found that some compounds contained in fire retardant have an antagonistic effect related to the compressive strength of wood.

Influence of Impregnation with Modified Starch of a Paper Core on Bending of Wood-Based Honeycomb Panels in Changing Climatic Conditions.

The main objective of the study was to determine the effect of impregnation of the paper core with acetylated starch on the mechanical properties and absorbed energy in the three-point bending test of wood-based honeycomb panels under varying temperatures and relative air humidity conditions. Nearly six hundred beams in various combinations, three types of facings, three core cells geometries, and two paper thicknesses were tested. The experiment results and their statistical analysis prove a significant relationship between the impregnation of paper with modified starch and mechanical properties. The most effective in absorbing energy, the honeycomb panels, consisted of a core with a wall thickness of 0.25 mm and a particleboard facing.

Treatment Results of Endoscopic Transnasal Orbital Decompression for Graves' Orbitopathy-A Single-Center Retrospective Analysis in 28 Orbits of 16 Patients.

Graves' orbitopathy (GO) is an extrathyroidal manifestation of Graves' disease (GD), which can be associated with corneal ulcerations or optic neuropathy in severe forms. Transnasal endoscopic orbital decompression (TEOD) is a surgical procedure performed in order to decrease the intraorbital pressure by removing part of its bony borders in cases with excessive mass in orbit. The aim of this study was to present the results and evaluate the efficacy of TEOD for GO. The retrospective study included 28 orbits (16 patients) who underwent TEOD from 2017 to 2020. Outcome was evaluated based on visual acuity improvement, clinical activity score (CAS) decrease, proptosis, and intraocular pressure (IOP) reduction. A preoperative best-corrected visual acuity (BCVA) increased from 0.69 ± 0.385 (mean ± standard deviation) to 0.74 ± 0.332 (p = 0.17) postoperatively. CAS decreased in 15 orbits postoperatively. Proptosis decreased from 22.89 ± 1.873 mm to 21.25 ± 2.053 mm (p < 0.05). IOP decreased from a preoperative 16.11 ± 3.93 mmHg to 14.40 ± 3.27 mmHg (p < 0.05) postoperatively. In addition, postoperative relief of exposure keratitis was observed. The analysis of development of iatrogenic diplopia revealed increasing in degree of diplopia. TEOD shows rare complications, but significant improvements in BCVA, CAS, proptosis, and IOP.

[Costs of population cervical cancer screening program in Poland between 2007-2009]. / Koszty funkcjonowania polskiego populacyjnego programu profilaktyki i wczesnego wykrywania raka szyjki macicy w latach 2007-2009.

BACKGROUND: Screening programs may contribute to decreasing the mortality rate in a given population and their main target, in case of cervical cancer; is to find and to cure preclinical stages of this malignancy. Regularly repeated tests in defined time intervals can diagnose the illness at its early stages but the results come with a high cost. Population program of early detection of cervical cancer has been conducted since 2007 and is run by the Central Coordinating Center and 16 regional centers. Funds for promotional, educational, monitoring and medical activities are obtained from the National Health Service. AIM: The aim of this study was to present the cost-effectiveness of the Program between 2007 and 2009. MATERIAL AND METHODS: The material for the analysis was obtained from the SIMP system, where all the data about women participating in the Program are implemented. The analysis of the cervical carcinoma treatment and procedure costs was made on the basis of the National Health Service estimates. The number of new cervical carcinoma cases was calculated with the help of the newly introduced system code--C53. RESULTS: Between 2007 and 2009 the cost of one cytological smear was similar in all regions (about 10 PLN). The highest costs were noted in Lubuski and Swietokrzyski regions. The costs of promotional and educational activities amounted up to 4.5 million PLN. A single cervical smear test cost for one woman has increased in the analyzed years from 3.95 up to 7.34 PLN. The total cost of one woman cytological examination--medical and non-medical elements--was more than 60 PLN. In 2009, 622 new cases of cervical cancer were found thanks to the Program. The cost of one case of cervical cancer diagnosis was 15 000 PLN. The total costs of all cases of cervical cancer in 2009 was 45.5 million PLN. CONCLUSIONS: The situation calls for creating new and effective tools for monitoring medical, epidemiological and financial parameters of the Program. Otherwise, the estimates of the health and social impact of the Program will fail to be plausible. Increased attendance at the Program will only marginally lower the costs of the tests. Not to mention, that different means and solutions regarding cervical cancer prevention need to be suggested due to the fact that Polish population does not yet seem to have developed the habit of taking preventive tests.

[Attendance rate in the Polish Cervical Cancer Screening Program in the years 2007-2009]. / Uczestnictwo kobiet w Populacyjnym Programie profilaktyki i Wczesnego Wykrywania Raka Szyjki Macicy w latach 2007-2009.

BACKGROUND: In Poland in 2007, according to the National Cancer Registry 3431 women were diagnosed with cervical cancer and 1907 died. To change the unfavorable epidemiologic situation, in 2005 the Ministry of Health (MH), the National Health Fund (NHF) and the Polish Gynecological Society following WHO/IARC guidelines developed a National Population-Based Cervical Cancer Screening Program. Its implementation and roll-out started in 2006. The target population are women aged 25 to 59 insured in the National Health Fund. A Pap test is done with a three-year interval, free of charge. The system is based on personal invitations sent by regular post. Invitation to screening is supported by a social educational campaign "Choose Life" run under one slogan and logo across the whole country The NHF data base enables identification of women to screen. Pap smears are collected by gynecologists and since 2008 also by midwives trained and certified by the Program National Coordinating Center Pap test results are reported in the Bethesda 2001 system. The Screening Program has its system of quality assurance and control and is supported by a specially designed computer data base called SIMP (System of Information Monitoring in Prophylaxis) with online access to all records. In addition to organized, population-based screening there is also opportunistic screening in Poland practiced either by private gynecological practices or by some units that cooperate with the National Health Fund, but do Pap tests as an element of comprehensive gynecological examination. Those smears are not registered in the SIMP. AIM: Our aim was analysis of attendance rate in the Cervical Cancer Screening Program in the years 2007-2009. We also investigated correlation between screening coverage and invitation sending schedule, as well as between coverage and screening accessibility determined by the number of gynaecological practices where Pap smears are collected. MATERIAL AND METHODS: Attendance rate in the Screening Program was evaluated for the years 2007, 2008 and 2009. The analysis included screening coverage in all voivodeships in the 12 months of the year as well as the number of gynaecological practices participating in the Program. In addition, the place of residence of screening attenders (urban/rural area) was taken into account. For the analysis the SIMP (System of Information Monitoring in Prophylaxis) data were used. Statistical analysis was performed using Statistica 9.0 software. P-values < 0.05 were considered statistically significant. RESULTS: The target population in the years 2007-2009 was 9,727,842 women. Personal invitations were sent to 99.7% of them. Pap Smears were collected from 24.14% of the target women (in 2007--21.25%; in 2008--24.39%; in 2009--26.77%). We noted that the number of 1400 gynecological practices participating in the Program was the minimal value to observe a significant increase in the number of Pap smears collected (p = 0.000). Polish women do not attend screening in the winter months. However when a batch of invitations was sent in the spring or summer months, within two following months we could observe an increase in the number of Pap smears collected (p = 0.000). There are significant differences in the screening uptake in particular regions of Poland (a stable trend). Compared to urban women, rural women participate in the screening more often (p = 0.003). CONCLUSION: All Pap test results including opportunistic screening should be registered in the SIMP In the regions where particularly low attendance rates were observed, an intensive promotional campaign should be run to encourage participation in the screening. Also, sending a repeated invitation to non-compliers should be considered. The currently unfavorable schedule of invitation sending should be changed. According to the analysis performed, invitations should be more effective if sent on a regular basis (in small but regular batches), more intensively in the summer and spring months. In the winter season it would probably be better to focus on an extensive media campaign followed by sending a large number of personal invitations.

High-frequency ultrasonography in objective evaluation of the efficacy of PUVA and UVA 1 phototherapy in mycosis fungoides.

The aim of the present study was to assess the effectiveness of UVA1 and PUVA therapy in treating patients with mycosis fungoides (MF) and to evaluate high-frequency ultrasonography (HF-USG) to monitor the clinical response of these patients. A total of 18 patients diagnosed with MF (stages I-IIA) underwent phototherapy, either UVA1 (6 cases) or PUVA (12 cases). Clinical response was evaluated according to modified Severity Weighted Assessment Tool (mSWAT) criteria and HF-USG (20 MHz). In the PUVA group, 50% of patients (6/12) achieved complete remission (CR) versus 33% (2/6) of patients in the UVA1 group. Before treatment, all subjects (100%) presented a subepidermal low echogenic band (SLEB) on HF-USG in the lesional skin. After phototherapy, the SLEB decreased significantly in all cases, with complete disappearance in 66% of cases. SLEB thickness was associated with disease severity and was wider in stage IIA patients than in stage IA and IB. These findings demonstrate that skin ultrasonography can be used to monitor treatment response in these patients. Moreover, HF-USG can quantify response, thus providing an objective measure of response that closely corresponds to scoring systems such as mSWAT used in routine clinical practice.

The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia.

Propofol (2,6-diisopropylphenol) is one of the safest and most commonly used anaesthetic agents for intravenous general anaesthesia. However, in clinical practice, a large inter-individual variability in response to propofol is observed. To limit the risk of adverse effects, pharmacogenetic investigations are recommended. The aim of our study was to verify the impact of genetic changes c.516G>T in the CYP2B6, c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes on the individual propofol pharmacokinetic profile in the Polish patients undergoing general anaesthesia. Eighty-five patients from the Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poland, anaesthetised with propofol for surgery, were enrolled in the study. We have genotyped CYP2B6, UGT1A9 and CYP2C9 polymorphisms with the use of pyrosequencing. HPLC measurements of propofol plasma concentration were applied for a pharmacokinetic analysis of the anaesthetic. We identified poor (20), intermediate (42) and rapid (23) metabolisers of propofol, which constituted 24%, 49% and 27% of the group, respectively. Homozygotes c.516 T/T in the CYP2B6 gene were statistically more often found in the rapid metabolisers group (p < 0.05). However, polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol. The mean propofol retention time (MRT) correlated with the patient's body mass index (BMI) (p < 0.05). From all the analysed changes, only polymorphism c.516G>T in the CYP2B6 gene and BMI affect the metabolism rate of propofol and may play an important role in the optimisation of propofol anaesthesia.

Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia.

The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insufficient. The aim of our study was to determine genetic predictors of variable pharmacokinetics and pharmacodynamics of propofol within selected 9 genes coding for propofol biotransformation enzymes, receptors and transporters. Our studies are the first extensive pharmaocgenetics research of propofol using high throughput sequencing technology. After the design and optimization of long range PCR-based next-generation sequencing experiment, we screened promoter and coding sequences of all genes analyzed among 87 Polish patients undergoing general anaesthesia with propofol. Initially we found that two variants, c.516 G > T in the CYP2B6 gene and c.2677 T > G in the ABCB1 gene, significantly correlate with propofol's metabolic profile, however after Bonferroni correction the P-values were not statistically significant. Our results suggest, that variants within the CYP2B6 and ABCB1 genes correlate stronger with propofol's metabolic profile compared to other 7 genes. CYP2B6 and ABCB1 variants can play a potentially important role in response to this anaesthetic and they are promising object for further studies.

Clinical and neurophysiological evaluation of persistent sensory disturbances in breast cancer women after mastectomy with or without radiotherapy.

PURPOSE: Breast cancer surgery or radiotherapy (RT) are potential causes of persistent pain syndrome. It remains to be clarified whether numbness or pain reported by patients after mastectomy and RT are conditioned by changes in nerve transmission. The aim of this study was to examine the potential relationship between subjective sensory complications and neurophysiological examinations in breast cancer survivors with post-mastectomy pain syndrome. METHODS: Sixty breast cancer survivors (30 patients only after mastectomy - group A; and 30 after mastectomy with RT - group B) complaining of pain and sensory disturbances in the brachial plexus area and 20 healthy women (group C) were studied with regard to sensory perception and pain intensity using the Visual Analogue Scale and electroneurography (ENG). RESULTS: There was a statistically significant decrease in the amplitudes in SCV recordings following stimulation of the ulnar (p = 0.04) and lateral cutaneous antebrachii nerves (p = 0.02) in group B in comparison to group C. Additionally, a significant decrease in the amplitude and conduction velocity parameters was detected in the sensory fibers of the median and medial cutaneous antebrachii nerves in group A (p = 0.00 and p = 0.02, respectively) in comparison to group C. CONCLUSIONS: The results of this pilot study suggest persistent post-mastectomy pain syndrome sometimes appears as a result of nerve injury in course of breast cancer surgery and RT. Therefore studies in nerve conduction may be added to the comprehensive patient assessment used in planning breast cancer patients' rehabilitation after oncological treatment has finished.

High motility group box 1 (HMGB1) protein and its receptor for advanced glycation end products (RAGE) expression in chronic rhinosinusitis without nasal polyps.

INTRODUCTION: Chronic rhinosinusitis (CRS) affects 14% of the world population. The high motility group box 1 (HMGB1) protein triggers inflammation, cell proliferation and cell survival through its receptor for advanced glycation end products (RAGE) upon release from stressed or necrotic cells. The aim of the study was to analyze the expression and function of HMGB1 and RAGE in CRS, providing more information about HMGB1 signaling pathway in CRS, to determine its potential clinical significance. MATERIAL AND METHODS: Thirty-seven patients with CRS and 26 normal controls (NC) were enrolled in this study. Classification of disease severity using the SNOT-20 questionnaire, nasal endoscopy, CT scan, assessment of allergy status, microbiological and cytological analysis was performed in patients. Fresh sinus mucosa samples were obtained and analyzed by immunohistochemistry for HMGB1 and RAGE expression in epithelial cells. ELISA assay was performed to evaluate the concentration of HMGB1 in the patients' sera. RESULTS: No differences were found in HMGB1 immunoexpression between CRS patients and NC, however there was a highly significant difference in RAGE immunoexpression between both groups. There was a correlation between RAGE expression and number of tissue-infiltrating lymphocytes. Further, RAGE expression positively correlated with disease severity and a positive history for allergies. CONCLUSIONS: Interaction of HMGB1 and RAGE might be relevant to CRS pathomechanisms leading to sinus mucosa hyperproliferation. CRS pathogenesis might be especially related to the RAGE overexpression correlated with disease severity and allergy.