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Introduction: Osteoporosis is the most common metabolic bone disease. Vitamin D deficiency, often associated with osteoporosis and other bone tissue disorders, is spread worldwide. Among other factors, obesity seems to be a major cause of the growing hypovitaminosis D. The aim of the study was to assess the correlation between body mass index (BMI) and vitamin D concentrations in postmenopausal women diagnosed with osteoporosis. Materials and Methods: Sixty-nine women with postmenopausal osteoporosis were included in the study. Dual-energy X-ray absorptiometry and vitamin D measures were performed in all patients. Three groups, BMI- dependent, were distinguished: normal weight, overweight and obesity group. Results: Vitamin D deficiency was found in all women with postmenopausal osteoporosis. There was no correlation between BMI and vitamin D level. Conclusions: Vitamin D deficiency is frequent in the population of patients diagnosed with postmenopausal osteoporosis, regardless of their BMI.

Introduction: Despite considerable progress in knowledge, ischaemic stroke is still a disease that causes serious clinical problems. A role in its pathogenesis can be attributed to i.a. adipose tissue hormones. The aim of this paper is to assess the blood levels of selected adipocytokines in patients during the acute phase of ischaemic stroke as compared to healthy persons, and an attempt to indicate a correlation between their blood concentrations and the level of stroke severity and its outcomes. Material and methods: The study included 46 patients with fresh ischaemic stroke (27 females, 19 males, average age 67.6 years). All patients had a CT scan of the head, their neurological condition was assessed using a stroke severity scale, and their blood levels of resistin, chemerin, and visfatin were tested. The control group consisted of 32 patients (16 females, 16 males, average age 64.1 years) who had never suffered cerebrovascular diseases. Results: Elevated levels of both resistin and chemerin were found in the group of patients with ischaemic stroke (9.17 ± 2.95 ng/mL vs. 6.55 ± 2.01 ng/mL for resistin and 265.0 ± 59.3 ng/mL vs. 191.0 ± 43.6 ng/mL for chemerin). It was also found that the blood concentration of chemerin was higher in females than in males with stroke. However, no difference was found in visfatin blood concentration between the group with ischaemic stroke and the control group (1.65 ± 1.09 ng/mL vs. 1.5 ± 1.39 ng/mL). Conclusions: Higher resistin and chemerin blood concentrations significantly increase the risk of ischaemic stroke. The level of stroke severity at the moment of its occurrence and during its course do not depend on the concentrations of adipocytokines under analysis.

This is a review considering atypical manifestations of granulomatosis with polyangiitis (GPA). Virtually any organ can be affected, and in some patients, GPA can manifest unusually. Since thoracic involvement of GPA often predominates, the first who might be expected to establish a diagnosis are pulmonary specialists. We would like to familiarize pulmonary specialists with several extra-ELK (E: ear-nose-throat; L: lung; K: kidney) involvements of the disease. We describe sites rarely affected by GPA like the breast, skeletal system, orbit and eye, heart and vessels, central nervous system, urogenital system as well as endocrine and gastrointestinal tract involvement.

Prostate cancer is the most commonly diagnosed cancer among men in the world and in Poland it is the second cause of death in men suffering from cancer. Recent evidence suggests that obesity is associated with prostate cancer. Increased BMI correlates with aggressive disease and with higher risk of recurrence and mortality in prostate cancer patients. Obesity can promote the progression of prostate cancer through endocrine disturbances, mainly in sex steroids, through chronic inflammation resulting in altered production of adipokines, peripheral insulin resistance with hyperinsulinemia and oxidative stress. Diagnosis of metabolic syndrome can be used in the global assessment of prognosis in patients with prostate cancer. The aim of the paper is to present current state of knowledge about connections between obesity, metabolic syndrome, sex steroids and adipokines in men with prostate cancer.

Prostate cancer is one of the most frequent cancers in men. Although several treatment options exist, their clinical effectiveness is still not satisfactory. One the possible reason of such situation might be the presence of myeloid-derived suppressor cells (MDSC) and their pro-turnorigenic activity. MDSC possess irnmunosuppressive ability and in many studies were shown to support tumor development and progression. In this study we addressed the question whether commonly used therapies of prostate cancer affect the level of MDSC populations in the patients' blood. We compared the level of granulocytic (Gr-MDSC), monocytic (Mo-MDSC) and early stage MDSC (eMDSC) in the blood of patients at different clinical stage and different tumor grading scores, who underwent either surgery or hormonal therapy alone or were given a combined treatment, including e.g. radiotherapy. The obtained results showed that the level of Gr-MDSC was significantly lower in all treated patients comparing to untreated group. On the other hand, surgery or hormonal therapy alone did not affect the level of Mo-MDSC. These results were independent of the PSA level, the tumor grading and clinical stage of the patients. In conclusion, we suggest that Mo-MDSC should be considered as a potential therapy target in the course of prostate cancer treatment to enhance its anti-tumor effectiveness.

Introduction: Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. Material and methods: The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18–24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. Results: The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. Conclusions: Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

Background Histoplasmosis is a mycosis caused by soil-based fungus Histoplasma capsulatum endemic in the USA, Latin America, Africa and South-East Asia. The disease is usually self-resolving, but exposure to a large inoculum or accompanying immune deficiencies may result in severe illness. Symptoms are unspecific with fever, cough and malaise as the most common. Thus, this is a case of disease which is difficult to diagnose and very rare in Europe. As a result, it is usually not suspected in elderly patients with cough and dyspnea. Case presentation This is a case of a 78-year-old patient, admitted to our department due to respiratory failure, cough, shortness of breath, fever and weight loss with no response to antibiotics administered before the admission. Chest CT revealed numerous reticular and nodular infiltrations with distribution in all lobes. The cytopathology of BAL showed small parts of mycelium and numerous oval spores. Considering clinical presentation and history of travel to Mexico before onset of disease, pulmonary histoplasmosis was diagnosed. After introduction of antifungal treatment rapid improvement was achieved in terms of both clinical picture and respiratory function. Conclusions Since the risk of Histoplasma exposure in Europe is minimal, patients, who present with dyspnea, fever and malaise are not primarily considered for diagnosis of histoplasmosis. However, taking into account increasing popularity of travelling, also by elderly or patients with impaired immunity, histoplasmosis should be included into differential diagnosis.

Human oral and gut microbiomes are crucial for maintenance of homeostasis in the human body. Porphyromonas gingivalis, the key etiologic agent of chronic periodontitis, can cause dysbiosis in the mouth and gut, which results in local and systemic infectious inflammatory diseases. Our previous work resulted in extensive biochemical and functional characterization of one of the major P. gingivalis heme acquisition systems (Hmu), with the leading role played by the HmuY hemophore-like protein. We continued our studies on the homologous heme acquisition protein (Bvu) expressed by Bacteroides vulgatus, the dominant species of the gut microbiome. Results from spectrophotometric experiments showed that Bvu binds heme preferentially under reducing conditions using Met145 and Met172 as heme iron-coordinating ligands. Bvu captures heme bound to human serum albumin and only under reducing conditions. Importantly, HmuY is able to sequester heme complexed to Bvu. This is the first study demonstrating that B. vulgatus expresses a heme-binding hemophore-like protein, thus increasing the number of members of a novel HmuY-like family. Data gained in this study confirm the importance of HmuY in the context of P. gingivalis survival in regard to its ability to cause dysbiosis also in the gut microbiome.

The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8+ and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.

Colorectal cancer (CRC) remains one of the most common malignancies diagnosed worldwide. The pathogenesis of CRC is complex and involves, among others, accumulation of genetic predispositions and epigenetic factors, dietary habits, alterations in gut microbiota, and lack of physical activity. A growing body of evidence suggests that immune cells play different roles in CRC, comprising both pro- and anti-tumorigenic functions. Immunosuppression observed during cancer development and progression is a result of the orchestration of many cell types, including myeloid-derived suppressor cells (MDSCs). MDSCs, along with other cells, stimulate tumor growth, angiogenesis, and formation of metastases. This article focuses on MDSCs in relation to their role in the initiation and progression of CRC. Possible forms of immunotherapies targeting MDSCs in CRC are also discussed.

Background Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. Methods This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. Results A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75–30) months and from diagnosis to start of pirfenidone treatment was 6 (2–23) months. Patients were followed on treatment for a median of 17 (12–22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient’s own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was −20 ml (−200–100) and during the second year was −120 ml (−340–30). Over a study period, 33 patients (10.75%) died. Conclusions The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

Mechanisms linking obesity and prostate cancer (PC) include increased insulin signaling, persistent inflammation, and altered adipocytokines secretion. Previous studies indicated that omentin may play a potential role in cancerogenesis of different sites, including the prostate. In this study, we focused on the hormonal and metabolic characteristics of men recruited for prostate biopsy. We evaluated serum concentrations of adipocytokines and sex steroids where concentrations are related to the adiposity: omentin, leptin, testosterone, estradiol, and sex hormone-binding globulin (SHBG). Aim: The aim of the study was to assess the concentration of serum omentin in men with PC. We also investigated relationships between omentin, leptin, sex steroids, SHBG, age, and metabolic syndrome (MS). Methods: Our study was conducted on 72 patients with PC and 65 men with benign prostate hyperplasia (BPH). Both groups were compared for body mass index. Results: Comparing men with PC to subjects with BPH there were significantly higher serum concentrations of omentin, estradiol, and prostate specific antigen (PSA) in the former. Estradiol/testosterone ratio, which is a marker of testosterone to estradiol conversion, was also significantly higher in the PC group. MS was diagnosed in 47 men with PC and in 30 men with BPH, the prevalence was significantly higher in the PC group. When the subjects with PC were subdivided into two subgroups, the serum omentin did not differ between those with MS and without MS. In the overall sample serum, omentin was positively associated with age, SHBG, and leptin. A positive correlation was also found between omentin and estradiol/testosterone ratio, and negatively with testosterone/SHBG ratio. Positive correlations were noted between age and SHBG, PSA and estradiol/testosterone ratio. In our study, a drop of total testosterone and testosterone/SHBG ratio, due to age, was also demonstrated. Conclusions: In patients with prostate cancer, serum omentin may be a diagnostic indicator. Omentin levels do not correlate with estradiol or testosterone concentrations but they are related to the testosterone/SHBG ratio. Omentin is not associated with an increased likelihood of having metabolic syndrome in men with prostate cancer.

Introduction: This document presents the Guideliness of the Polish Respiratory Society (PTChP, Polskie Towarzystwo Chorób Płuc) for diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), developed by agroup of Polish experts. Material and methods: The recommendations were developed in the form of answers to previously formulated questions concer-ning everyday diagnostic and therapeutic challenges. They were developed based on acurrent literature review using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: We formulated 28 recommendations for diagnosis (8), pharmacological treatment (12) as well as non-pharma-cological and palliative therapy (8). The experts suggest that surgical lung biopsy (SLB) not be performed in patients with the probable usual interstitial pneumonia (UIP) pattern, with an appropriate clinical context and unanimous opinion of a multidisciplinary team. The experts recommend using antifibrotic agents in IPF patients and suggest their use irrespective of the degree of functional impairment. As regards non-pharmacological and palliative treatment, strong re-commendations were formulated regarding pulmonary rehabilitation, oxygen therapy (in patients with chronic respiratory failure), preventive vaccinations as well as referring IPF patients to transplant centres. Table 1 presents an aggregate list of recommendations. Conclusions: The Polish Respiratory Society Working Group developed Guideliness for IPF diagnosis and treatment.

For 40 years many studies have been conducted to verify the connection between serum uric acid concentration and cardiovascular diseases, such as myocardial infarction. Unfortunately, it remains unclear which form of uric acid – prooxidant or antioxidant – could be a predictive marker of cardiovascular disease, especially in patients after myocardial infarction. It is well-known that uric acid is an organic compound and the water-soluble final product of purine catabolism, which is catalysed by xanthine oxidoreductase and excreted by kidneys. An increased concentration of UA in human plasma leads to diseases like tumours, renal disorders, atherosclerosis, hypertension, diabetes, metabolic syndrome, polycythaemia vera, haemolytic anaemias, ischemia, oxidative stress, and rare genetic disorders connected with UA degradation. Epidemiological studies have shown that UA might be a marker of oxidative stress, progression of inflammation, or renal disease. A fortiori, it is possible that could also be a predictor for short/long-term survival of patients with CVD. Evidence provided by multiple studies is controversial and mutually exclusive. Among 71 studies the most of them found an independent association between SUA and CVD risk. Some of those studies confirm that CVD risk is higher in women who had elevated SUA levels. On the other hand, many studies reached the opposite conclusion and did not find any relationship between SUA and CVD mortality and morbidity.

Introduction: The aim of this study was to assess the therapeutic effect and the safety of pre surgical treatment with long-acting octreotide in patients with acromegaly. Material and methods: This project was conducted in 25 centres across Poland as a non interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide (Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18–86 years (51.3 ± 13.4). Results: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. Conclusion: In conclusion, we have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with longacting somatostatin analogues in acromegaly patients.

Polyphenols include flavonoids, phenolic acids, tannins and lignans which are known to have antioxidant, UV protection and antimicrobial properties. Among them the most commonly investigated are flavonoids and phenolic acids, which, due to their plant origin, may interact with the plant cell wall (PCW) components, specifically with its polysaccharides. Knowledge concerning the nature of the interactions between these components may be used in the production of functional food or in the development of food packaging materials with additional properties. The content of polyphenols in such products is responsible for their colour and taste, and may also act as a natural preservative. On the other hand, the PCW components may have protective role of polyphenols which has impact on their release in the human digestive system. Therefore, this review is an attempt to summarize the current state of knowledge that emerged after 2017 concerning the interaction of PCW components with polyphenols, with a particular focus on hemicellulose and pectin.

The relationships between thyroid cancer and obesity are not fully understood. Adipokines, proinflammatory cytokines, and vitamin D may mediate these associations. In this study, we estimated serum concentrations of leptin, adiponectin, chemerin, interleukin-6 (IL-6), and vitamin D in patients with papillary thyroid cancer (PTC). We searched for associations between the adipokines, IL-6, vitamin D, anthropometric parameters, and TNM AJCC/UICC 2017 classification in 177 patients diagnosed with PTC (151 women and 26 men). Normal weight patients were predominantly classified as clinical stage I. The prevalence of stages higher than I was significantly higher in PTC patients with BMI ≥ 25 or with metabolic syndrome. Using logistic regression waist circumference ≥ 88 cm in women and ≥102 cm in men, upper tertiles of IL-6 and leptin were associated with a higher clinical stage. There were no differences in the prevalence of microcarcinomas in analyzed groups (BMI ≥ 25 versus BMI

Introduction Transient hypogammaglobulinaemia of infancy (THI) is a primary immunodeficiency characterised by low levels of immunoglobulin G (often with concomitant decrease of IgA and sometimes also of IgM) with still unknown exact reason. A delayed normalisation of the immunoglobulin level in THI may be associated with a transiently elevated number of regulatory T cells (Treg). Although in cancer and chronic inflammation it was shown that the level of Treg cells can be increased by myeloid-derived suppressor cells (MDSCs), until now no studies have been performed in the context of the role of MDSCs in THI and their correlation with Treg cells. Consequently, we aimed to determine the occurrence of MDSCs in the peripheral blood of children with THI and correlate their level with the level of Treg cells. Material and methods Flow cytometry analyses of Mo-MDSCs and Gr-MDSCs, characterised as HLA-DR-CD11b+CD15-CD14+ and HLA-DR-CD11b+CD15+CD14-, respectively, and Treg (CD4+CD25+Foxp3+) cells were performed. Results The proportion of Mo-MDSCs and Gr-MDSCs was significantly higher in the group of THI patients with elevated level of Treg cells (from the 95% confidence interval level of healthy controls). The cells with Mo-MDSC and Gr-MDSC characteristics positively correlated with the level of Treg cells. Moreover, children with a higher proportion of circulating Treg cells, and thereby higher level of MDSCs, showed delayed normalisation of IgG level and recovery. Conclusions These findings show for the first time that MDSCs may be involved in the pathomechanism of THI, probably acting through the induction of Treg cells.

Breast cancer is the most common cancer of women—it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.

Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer-tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358-368.

Introduction: The recent studies demonstrated that obese heart failure patients have better prognosis — “obesity paradox”. The aim of the study was to evaluate the relationship between body mass index (BMI), leptin and adiponectin concentrations and prognosis in patients with heart failure due to non ischeamic dilated cardiomyopathy (NIDCM). Material and methods: 128 patients with NIDCM were included and followed-up for three years. Leptin and adiponectin were measured at baseline using commercially available ELISA tests. Clinical data, routine laboratory parameters, NT–proBNP were assessed as risk factors for reaching the study endpoints: urgent heart transplantation (B), death (C), or combined endpoint death or urgent heart transplantation (D). Results: Patient with adverse outcome had lower BMI and higher NT-proBNP concentration. Leptin was significantly elevated in group C and adiponectin was higher in groups B and D than in survived patients. Patients with leptin concentration below median or with adiponectin concentration above median were more often transplanted in three years follow-up (p = 0.029, p = 0.022, respectively). The cumulative probability of death was greater in patients with concentration of leptin above median (p = 0.024). In the multivariable Cox proportional hazards analyses, increasing leptin and lower BMI were predictors of death. Adiponectin was associated with higher risk of heart transplantation. Both an inverse association of BMI and positive association of leptin and adiponectin with combined endpoint were discovered. Further adjustment to established risk factors abolished association between combined endpoint and BMI, and modestly attenuate with adiponectin and leptin concentration. Conclusion: Evaluation of adiponectin and leptin concentrations was more useful than BMI in prediction of unfavourable outcome in patients with NIDCM. (Endokrynol Pol 2017; 68 (1): 26–34)

SummaryOral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.

This study was undertaken in order to estimate the effect of in vitro propagation on antioxidant activity in strawberry. Results of this research exhibited differences between conventionally and in vitro propagated plants in respect of all traits analyzed. In spite of the decrease in range and mean content of vitamin C and polyphenols as well as antioxidant activity, the genetic gain expressed as percent of mean was higher in microplants regarding phenolics, flavonoids and antioxidant activity in contrast to conventional plants (22.39-20.83, 21.79-15.61, 9.52-3.39; resp.). Correlation and path coefficients showed changes of antioxidants inter-relations between micropropagated and conventional plants. Phenolics and vitamin C correlated positively with antioxidant activity in all genotypes. The highest positive direct effect on antioxidant activity was observed via vitamin C in microplants (0.705), while in conventional plants via phenolics (0.834). Flavonoids affected directly and positively antioxidant activity in microplants (0.103) and negatively in conventional plants (-0.143).

Surgical procedure has immense impact on the immune balance. However, little is known about perioperative changes in T regulatory and Th17 lymphocyte subpopulations in patients undergoing colorectal resection. Patients with resectable colon cancer were enrolled in the study. Blood samples were obtained on two occasions, i.e. before the procedure and two days after the surgery. We also recruited a control group of young, healthy individuals. Lymphocyte subpopulations were analyzed with the use of flow cytometry. Investigated subpopulations consisted of total lymphocyte count, CD4+, CD8+, T regulatory Foxp3+ (Tregs), Th17 lymphocytes and white blood cell (WBC) count. There were significant differences in immune cell levels before and after the surgery. Reduction was recorded in the CD4+, CD8+, Tregs and total lymphocyte counts (p=0.002, p=0.01, p=0.008 and p=0.001, respectively). Increase was observed in total WBC and Th17 cells, however, Th17 lymphocytes did not reach statistical significance (p=0.01 and p=0.5, respectively). In conclusion, surgical intervention caused changes in all lymphocyte subpopulations investigated in patients undergoing surgery for colorectal cancer. However, it seemed to be an effect of perioperative trauma. Further studies are needed to investigate the impact of surgical intervention on lymphocyte subpopulations., Kirurški zahvat ima golem učinak na ravnotežu imunog sustava. Međutim, malo se zna o perioperacijskim promjenama u subpopulacijama T regulatornih i Th17 limfocita u bolesnika podvrgnutih resekciji kolorektuma. U istraživanje su bili uključeni bolesnici s resektabilnim karcinomom kolona. Uzorci krvi prikupljeni su dva puta: prije zahvata i dva dana nakon operacije. Uključena je bila i kontrolna skupina sastavljena od mladih i zdravih osoba. Subpopulacije limfocita analizirane su protočnom citometrijom. Istraživane su sljedeće subpopulacije: ukupan broj limfocita, CD4+, CD8+, T regulatorni Foxp3+ (Tregs), Th17 i bijela krvna slika. Utvrđene su značajne razlike u razinama imuno stanica prije i nakon operacije. Snižene razine zabilježene su za CD4+, CD8+, Tregs i ukupni broj limfocita (p=0,002, p=0,01, p=0,008 odnosno p=0,001). Povišenje je zapaženo za bijelu krvnu sliku i Th17 stanice, međutim, Th17 limfociti nisu postigli statističku značajnost (p=0,01 odnosno p=0,5). Zaključujemo da je kirurški zahvat uzrokovao promjene u svim istraživanim subpopulacijama limfocita kod bolesnika podvrgnutih operaciji kolorektalnog karcinoma. Međutim, čini se da je to bio učinak perioperacijske traume. Potrebna su daljnja istraživanja kako bi se ispitao utjecaj kirurškog zahvata na subpopulacije limfocita.

Introduction. Nowadays, due to the “morphine effect”, the screening of methods that provide quick and effective platelet inhibition with oral P2Y12 inhibitors administrated simultaneously with morphine in patients with acute coronary syndromes are extensively investigated by numerous scientists. Metoclopramide, which stimulates the motility of gastrointestinal tract, may become a potential method of overcoming the negative morphine effect. The present study was designed to demonstrate the influence of metoclopramide administration on the pharmacokinetic and pharmacodynamic profile of ticagrelor between patients with unstable angina pectoris treated with morphine and crushed ticagrelor. Methods/design. A study was designed as a phase IV, single-centre, randomized, investigator-initiated, parallel-group, open-label, interventional trial. Patients will be randomized in a 1:1 manner into two arms: 1) patients treated with a combination of crushed ticagrelor and morphine and 2) patients treated with a combination of crushed ticagrelor followed by morphine and metoclopramide. Blood sample collection will be scheduled directly before the administration of ticagrelor loading dose and 15, 30, 45, 60, 120, 180, 240, and 360 minutes after the loading dose. Pharmacokinetic and pharmacodynamic assessment of ticagrelor and its active metabolite will be evaluated in all pre-defined time points. Discussion. The current study is, to our knowledge, the first one to provide data on the influence of metoclopramide in patients with acute coronary syndromes, who received intravenous opioid analgesia. It is expected to contribute to the development of contemporary knowledge on the treatment of patients presenting with acute coronary syndromes, and should enable clinicians to implement strategies of quick platelet inhibition.

BACKGROUND Genome-wide and allelic association studies have shown the contribution of CHRNA5-A3-B4 nicotinic receptor subunit gene cluster within chromosome 15 to nicotine dependence (ND). While an association between several single-nucleotide polymorphisms (SNPs) at that locus and smoking quantity (cigarettes per day; CPD) has been well recognized, there are some inconsistencies in demonstrating the influence of these SNPs on other ND phenotypes. This uncertainty motivated us to examine the association of 3 selected SNPs (CHRNA3 rs1051730, rs6495308, and CHRNA5 rs55853898) with ND in an isolated population of Kashubians from Poland. MATERIAL AND METHODS The study sample consisted of 788 current daily smokers. ND was assessed by CPD, the Fagerstrom Test for Nicotine Dependence (FTND), its brief version - Heavy Smoking Index (HSI), and time to first cigarette after waking (TTF). The correlation between studied SNPs and dichotomized values of ND measures was assessed in the regression analysis. Bonferroni corrected p-value of 0.017 was set for a type 1 error. RESULTS We found a robust association between risk allele A of rs1051730 and CPD >10 (odds ratio (OR)=1.77, 95% confidence interval (CI): 1.20-2.59, p=0.004), and a weak association, which did not survive correction for multiple testing, with FTND ³4. No associations between studied SNPs and HSI or TTF were demonstrated. CONCLUSIONS Our findings confirm that rs1051730 influences ND phenotype, as defined by CPD.

Introduction Many clinicians consider chronic gastritis to be equivalent to Helicobacter pylori infection. However, it is known that there are numerous other causes of the condition. Aim Determination of the incidence of gastritis in patients with dyspepsia referred for diagnostic endoscopy of the upper part of the digestive tract, identification of the parts of the stomach most frequently affected by the inflammation, as well as the impact of an insufficient number of collected samples on the correct diagnosis. Material and methods Upper gastrointestinal endoscopy due to dyspepsia was performed in 110 patients. In the course of gastroscopy two biopsy specimens were collected for histopathological examination and towards H. pylori infection from the lesser and greater curvature in the antrum 3 cm from the pyloric sphincter, in the body - 4 cm proximally to the stomach angular incisure on the lesser curvature, and in the middle of the greater curvature, as well as in the subcardiac region on the side of the lesser and greater curvature. Results In patients with dyspepsia H. pylori-negative chronic gastritis is more common than gastritis with accompanying H. pylori infection. Collection of too small a number of biopsy specimens results in failure to detect inflammatory changes and/or H. pylori infection, which may be limited to one part of the stomach. Biopsy specimens of gastric mucosa should be collected in compliance with the assumptions of the Sydney System. Helicobacter pylori infection in people with dyspepsia is now being reported more rarely than in the past (36%). Conclusions In patients with dyspepsia chronic H. pylori-negative gastritis is more common than gastritis with an accompanying H. pylori infection. Helicobacter pylori infection is not always equivalent to the presence of chronic gastritis.

Introduction Expiratory central airway collapse is defined by excessive inward bulging of either tracheobronchial posterior membrane or cartilage. The former is called excessive dynamic airway collapse (EDAC), and the latter, depending on the site of collapse, tracheomalacia, bronchomalacia or tracheobronchomalacia. Due to their non-specific symptoms and lack of awareness amongst clinicians they tend to be mislabeled as common obstructive lung disorders, or complicate their course undetected. Particular controversies refer to EDAC sometimes considered just as a symptom of obstructive lung disease and not a separate entity. Nonetheless, a growing body of evidence indicates that EDAC might be present in patients without apparent obstructive lung disease or it might be an independent risk factor in chronic obstructive pulmonary disease or asthma patients. Patient concerns Patient #1 was admitted because of idiopathic chronic cough whereas patient #2 was admitted for differential diagnosis of dyspnea of uncertain etiology. In both patients symptoms were unresponsive to bronchodilators and inhaled corticosteroids. Findings and diagnosis In both patients an excess collapse of tracheobronchial posterior membrane was detected during bronchoscopy; in patient #1, of right main bronchus and right upper lobe bronchus and in patient #2 of right upper lobe bronchus and both main bronchi. Excess central airway collapse in patient #2 was also visualized on expiratory chest CT. In patient #1 spirometry did not reveal obturation, whereas in patient #2 only mild, irreversible, obstruction was revealed, disproportionate to patients significant breathlessness. Interventions Both patients were treated with N-acetylcysteine and adjustable positive expiratory pressure valves. Outcomes Due to aforementioned treatment chronic cough in patient #1 subsided almost completely whereas patient's #2 dyspnea improved significantly. Conclusions In presented cases EDAC was an unexpected finding, even though, it firmly corresponded with reported symptoms. Treatment modification led to improvement of patients quality of life.

Introduction: The prevalence of metabolic syndrome increases after menopause; however, the role of concomitant subclinical hypothyroidism has not been completely elucidated. The aim of the study was to identify associations between thyrotropin, immune status, inflammation, and metabolic syndrome in postmenopausal women. The specific goals were: to assess thyrotropin (TSH) and interleukin-6 (IL-6) concentrations in the serum of subclinical hypothyroid postmenopausal women with and without metabolic syndrome and compare them with euthyroid controls; to test whether immune status is related to metabolic syndrome in postmenopausal women and determine the role of IL-6; to examine the relationships between TSH and different features of metabolic syndrome: insulin resistance, waist circumferences, waist-to-hip ratio (WHR), BMI, metabolic parameters (triglycerides, total cholesterol and high-density lipoprotein cholesterol), and inflammatory cytokines (IL-6). Material and methods: Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mL > TSH ≥ 4.5 uIU/mL, normal fT4), and 258 women were in euthyreosis (TSH 0.35–4.5 uIU/mL, normal fT4); both groups were matched by age. Anthropometric measurements were conducted (BMI, waist circumference, WHR) and blood pressure was measured. In all subjects the following were assessed in serum: lipid profile, glucose, insulin, TSH, fT4, thyroid antibodies (T-Abs) — TPO-Abs, TG-Abs, and IL-6 concentrations. Results: The prevalence of metabolic syndrome was 49.12% in subclinical hypothyroid women and 46.89% in euthyroid women. However, the proportion of subjects with one or two abnormalities was significantly higher in the subclinical hypothyroid group (45.61%) than in the euthyroid group (32.17%). When we compared subclinical hypothyroid women with and without metabolic syndrome, subjects with metabolic syndrome had higher BMI, abdominal circumferences, WHR, and HOMA-I. They presented higher systolic and diastolic blood pressure. Serum concentrations of cholesterol, triglycerides, fasting glucose, IL-6, TSH, T-Abs were also higher and serum cHDL was lower. There were no significant differences in fT4 concentrations. A similar comparison was made for euthyroid women with and without metabolic syndrome. Higher BMI, waist circumference, WHR, HOMA-I, and systolic blood pressure were observed in subjects with metabolic syndrome. Serum concentrations of TSH, triglycerides, glucose, and IL-6 were also higher, but the concentration of cHDL was significantly lower. There were no significant differences in fT4, T-Abs, cholesterol levels, and diastolic pressure. When we compared euthyroid women T-Abs (+) and T-Abs (–), the prevalence of metabolic syndrome was similar (48.68% vs. 46.15%). There were no differences in BMI, waist circumference, WHR, lipid profile, glucose, and HOMA-I, fT4. However, thyroid autoimmunity was associated with elevated TSH and IL-6 levels. When we analysed subclinical hypothyroid women with and without thyroid autoimmunity, there were no significant differences in glucose and lipid profile. However, Hashimoto`s subjects were more obese, had higher waist circumference, WHR, HOMA-I, and higher prevalence of metabolic syndrome. Serum concentrations of TSH and IL-6 were also higher and fT4 was lower. Among all of the women, serum TSH concentration was significantly correlated with BMI, waist circumference, WHR, systolic blood pressure, cholesterol, triglycerides, and TPO-Abs. When the variables of subjects with upper quartile of TSH were compared with lower quartile of TSH, we found significantly higher BMI, waist circumference, WHR, increased concentration of IL-6, cholesterol, triglycerides, and T-Abs, and concentrations of cHDL and fT4 were lower. OR for metabolic syndrome in subjects with upper quartile TSH vs. lower quartile was 1.35 (95% confidence interval [CI] 1.10–1.60). Conclusions: Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role. (Endokrynol Pol 2015; 66 (5): 394–403)

Introduction Graves’ disease is the most common cause of hyperthyroidism, and orbitopathy is the most frequent extrathyroidal manifestation of Graves’ disease. The aims of this study were as follows: (1) to evaluate the serum concentration of HGF and IL-8 in the blood of newly diagnosed Graves’ disease patients with the first episode of active GO and healthy controls; (2) to estimate the influence of the thyroid function (euthyreosis vs. hyperthyreosis) on HGF and IL-8 blood levels in patients with active GO; (3) to evaluate the influence of intravenous (i.v.) methylprednisolone (MP) pulse therapy and additional oral MP treatment on HGF and IL-8 blood levels in patients with active GO. Patients and methods Thirty-nine Graves’ disease patients with the first episode of clinically active GO (Group A) were enrolled in the study. To estimate the influence of the thyroid function on serum concentrations of the studied proangiogenic factors, Group A was divided into Group A I (n = 18) in euthyroid and Group A II (n = 21) in hyperthyroid stage of Graves’ disease in moderate-to-severe stage of GO. The control group consisted of 20 healthy volunteers age- and sex-matched to the GO group. Concentrations of the studied proangiogenic factors in serum samples were measured by an enzyme-linked immunosorbent assay before (Group A) and after (Group A1) intensive pulse i.v.MP treatment and 1 month after the end of additional oral MP treatment (Group A2). Results We found a significant increase in serum concentrations of studied factors in the GO group before immunosuppressive therapy when compared with the control group and decrease after i.v.MP treatment. One month after the end of additional oral MP treatment (Group A2), serum concentrations of HGF and IL-8 still decreased and no significant difference was observed in HGF and IL-8 concentrations when compared with the control group. We did not find the difference in serum concentration of the studied proangiogenic factors between patients in euthyroid and hyperthyroid stage of Graves’ disease before MP therapy. Conclusions Serum HGF and IL-8 concentrations are elevated in Graves’ disease patients with active Graves’ orbitopathy as compared to the healthy control group. Successful management of active Graves’ orbitopathy with glucocorticoids is associated with a decrease in HGF and IL-8 serum concentrations.

Introduction: Chronic liver disease caused by HBV and HCV infections, due to its great prevalence and serious medical consequences, is at the present time a significant clinical problem. An impaired liver function can provoke severe disturbances in calcium and phosphorus homeostasis, and consequently in the bone metabolism resulting in hepatic osteodystrophy. The aim of this study was to determine whether there are significant differences in bone mineral density (BMD) and/or circadian levels of hormones connected with bone metabolism and bone turnover markers in patients with chronic viral hepatitis. Material and methods: Circadian levels (AUC, area under the curve) of GH, IGF-I, IGFBP-3, osteocalcin (BGLAP), C-terminal telopeptide of type I collagen (ICTP), PTH, 25(OH)D, total calcium and total phosporus were measured in the blood of members of the study group (n = 80). BMD was assessed using the dual-energy X-ray absorptiometry method of the L2-L4 lumbar spine. Data was compared to that of healthy individuals (n = 40). Results: BMD (1.05 g/cm3 vs. 1.20 g/cm3), total calcium concentration (2.20 mmol/L vs. 2.45 mmol/L), total phosphorus concentration (1.06 mmol/L vs. 1.33 mmol/L), IGF-I (AUC 3,982.32 ng/mL vs. 5,167.61 ng/mL), IGFBP-3 (AUC 725.09 ng/L vs. 944.35 ng/L), 25(OH)D (AUC 356.35 ng/mL vs. 767.53 ng/mL) and BGLAP (AUC 161.39 ng/L vs. 298 ng/L) were lower in the study group. GH (AUC 88.3 ng/mL vs. 48.04 ng/mL), iPTH (AUC 1,201.94 pg/mL vs. 711.73 pg/mL) and ICTP (AUC 104.30 μg/L vs. 54.49 μg/L) were higher in patients with hepatitis. Positive correlations were noted between bone mineral density and IGF-I, IGFBP-3, and BGLAP levels. Conclusions: Chronic viral hepatitis causes a decrease in bone mineral density. Impaired liver function disrupts homeostasis of the calcium– vitamin D–parathyroid hormone axis and provokes secondary hyperparathyroidism. Chronic viral hepatitis induces a decrease in the synthesis of IGF-I and IGFBP-3 and an increase in GH secretion. Hepatic osteodystrophy is probably caused by both changes in calciotropic hormones as well as in the somatotropin hormone axis.

Tobacco smoking is the single most important modifiable factor in increased morbidity and premature mortality. Numerous factors—including genetics, personality, and environment—affect the development and persistence of tobacco addiction, and knowledge regarding these factors could improve smoking cessation rates. This study compared personality traits between never, former, and current smokers, using the Five-Factor Model of Personality in a country with a turbulent smoking reduction process.: In this cross-sectional study, 909 Polish adults completed the Revised Neuroticism-Extraversion-Openness Personality Inventory. Our results showed that current smokers’ scores for extraversion, one of the five global dimensions of personality, were higher relative to never smokers. Neuroticism, openness to experience, agreeableness, and conscientiousness did not differ significantly according to smoking status. Facet analysis, which described each dimension in detail, showed that current smokers’ activity and excitement seeking (facets of extraversion) scores were higher relative to those of never and former smokers. In turn, current smokers’ dutifulness and deliberation (facets of conscientiousness) scores were lower than those found in former and never smokers. Never smokers scored the highest in self-consciousness (a facet of neuroticism) and compliance (a component of agreeableness). The study conducted among Polish individuals showed variation in personality traits according to their smoking status; however, this variation differed from that reported in countries in which efforts to reduce smoking had begun earlier relative to Poland. Knowledge regarding personality traits could be useful in designing smoking prevention and cessation programs tailored to individuals’ needs.

Wstep: Pierwsza cześc pracy dotyczy ludzi zdrowych — dostarcza dane o stezeniach TGFβ1 i VEGF we krwi (z podzialem i bez podzialu na plec), ich wartości punktowe (godz. 8), średniodobowe stezenie (MDC), pole pod krzywą (AUC; calkowite dobowe wydzielanie), rytm okolodobowy. Druga cześc pracy dotyczy orbitopatii Gravesa (GO). Celem pracy bylo: 1) określenie fizjologicznego wzoru wydzielania TGFβ1 i VEGF; 2) porownanie okolodobowych surowiczych stezen TGFβ1 i VEGF u chorych z nowo rozpoznaną nadczynnością tarczycy i aktywną fazą GO oraz u ludzi zdrowych (H); 3) ocena wplywu wysokodawkowej dozylnej pulsacyjnej terapii metyloprednizolonem (MP) na stezenia TGFβ1 i VEGF we krwi chorych z GO. Material i metody: Przebadano 22 zdrowych (H); 16 pacjentow z nadczynnością tarczycy i GO leczonych MP (6 g/14 dni) obserwowanych okulistycznie. Krew pobierano przed i po 2 tygodniach terapii MP. Stezenia TGFβ1 i VEGF oznaczono metodą ELISA. Wyniki: Nie stwierdzono roznic w stezeniu TGFβ1 i VEGF we krwi miedzy zdrowymi kobietami i zdrowymi mezczyznami — dalszym analizom poddawano wiec grupe zdrowych (H) skladającą sie z kobiet i mezczyzn. Krew pobierano przed i po 2 tygodniach terapii MP. Choc wykazanie braku rytmow okolodobowych stezen TGFβ1 i VEGF we krwi umozliwia zastosowanie ich oceny punktowej to jednak stwierdzono, ze bardziej precyzyjną jest ocena MDC i AUC. Nie wykazano roznicy w TGFβ1 MDC/AUC miedzy GO i H. VEGF MDC/ AUC byly wyzsze u GO niz u H. MP zwiekszyl TGFβ1 MDC/AUC, tym samym u GO po MP, TGFβ1 MDC/AUC byly tez wyzsze niz u H. Nie stwierdzono roznicy w VEGF MDC/AUC podczas MP. MP byl skuteczny u 15/16 chorych. Wnioski: 1. Terapia MP zwieksza MDC i AUC TGFβ1. Skutecznośc MP u chorych z aktywną fazą GO moze byc związana z jego wplywem na stezenia TGFβ1 we krwi, co sugeruje istnienie nieznanego dotąd mechanizmu dzialania glikokortykosteroidow polegającego na zwiekszaniu wydzielania TGFβ1. 2. Podwyzszone stezenia VEGF we krwi u chorych z nadczynnością tarczycy i aktywną fazą GO mogą byc odzwierciedleniem dlugotrwalego procesu autoimmunologicznego w tkankach oczodolu i tarczycy oraz nasilonej angiogenezy w gruczole tarczowym. (Endokrynol Pol 2014; 65 (5): 349–356)

Introduction: Thyroid orbitopathy (TO) is the most frequent extrathyroid manifestation of Graves’ disease. The aim of this study was to evaluate the serum concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth Factor-AA (PDGF-AA) in the blood of patients with active OT before and after immunosuppressive therapy. Patients and Methods: The study was performed in group of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I) and hyperthyroid (n=21, Group A II) stage of Graves’ disease in moderate or severe stage of TO. Control group consist of 20 healthy age-matched control subjects. Concentration of studied proangiogenic factors in serum samples were measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and after (group A1) intensive pulse methylprednisolone treatment and one month after the end of additional oral methylprednisolone treatment (Group A2). Results: We have found significant increased serum levels of VEGF in patients with TO (reg­ardless to treatment) when compared with control group (542.4±328.1 pg/ml vs. 94.6±55.3 pg/ml, p=0.0002) and increased serum levels of ­PDGF-AA in patients before treatment (3 173.6±1 480.3 pg/ml) in comparison with controls (1 768.9±520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2 325.9±1 456.8 pg/ml). One month after the end of additional oral methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased and were was not significant difference with value in control group (1 853.1±795.4 vs. 1 769.9±520.0 pg/ml, p=0.99). Serum concentration of VEGF was still significantly higher compared with control. We have not observed difference in serum concentration of studied proangiogenic factors between patients in euthyroid or hyperthyroid stage of Graves’ disease. Conclusions: Results of the present study confirm the fact that angiogenesis could play a role in pathogenesis of thyroid orbitopathy.

Fragaria vesca (wild strawberry) belongs to the Rosaceae family. Besides the leaves (Fragariae folium) and roots (Fragariae radix), the aromatic fruits (Fragariae fructus) of wild strawberry are also herbal materials used in medicine. The aim of this study was to compare the value of phytochemical and antioxidant activity of wild strawberry fruits (Fragaria vesca L.). The fruits were analyzed regarding their secondary metabolites contents (flavonoids, sum of phenolic acids, tannins, anthocyanins, DPPH), depending on the origin of the raw material (from natural habitats vs. cultivation). According to the obtained results, raw material originating from natural habitats contained significantly more flavonoids (0.559 mg∙g -1 ), compared to fruits harvested from cultivation (0.472 mg∙g -1 , on average). Mean concentration of phenolic acids ranged from 1.648 mg∙g -1 – 2.348 mg∙g -1 , although the wild form was characterized by higher levels of examined substances. Tannins are an important fraction of phenolic compounds; their content in studied fruits ranged from 2.2% (from cultivation) – 3.0% (from natural habitats). When comparing the average contents of anthocyanins in the studied materials, it was revealed that remarkably more of these compounds were recorded in wild strawberry fruits harvested from natural habitats vs. those from cultivations: 132 mg∙100 g -1 vs. 90 mg∙100 g -1 . A difference was indicated with respect to the ability of DPPH radical

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechow near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013-2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed.

Smoking is still considered to be mainly a male problem. However, it is estimated that there are approximately 250 million women worldwide who smoke cigarettes and millions more women who use smokeless tobacco products. This article addresses the many facets of tobacco use among women. The aim of the paper is to increase recognition among clinicians and researchers of the specific characteristics of female tobacco use. Together with providing epidemiological data on the distribution of tobacco use among women and data from population-based analyses on sociocultural factors that influence it, the article presents tobacco use during pregnancy as a particularly important public health problem. Further, the article points out sex-related differences (ie, physiological, psychological, or behavioral) between male and female tobacco use. A special focus is on the important role of ovarian hormones. Adverse effects of tobacco use to women and their children as well as tobacco-related morbidities and comorbidities are presented, and women’s greater susceptibility to tobacco constituents as compared to men is stressed. Awareness of these differences can contribute to improvement of the effectiveness of smoking cessation programs addressed both to the specific female population and to an individual smoking woman.

Objective The aim of our prospective study was to assess the health-related quality of life (HRQOL) of children with mitral valve prolapse (MVP) and the impact of clinical symptoms on HRQOL. Methods Sixty-seven patients with primary MVP aged 8–18 years were studied and compared with 31 healthy children. All children completed the polish version of KIDSCREEN-27. For searching occurrence and frequency of 18 clinical symptoms, authors’ questionnaire was used. Results The statistically significant difference was found only for one from five searching dimensions of HRQOL—physical well-being. In the remaining studied aspects of HRQOL, no statistically significant differences were found in comparison with the healthy children. The statistically significant moderate correlation between the number and frequency of clinical symptoms and physical well-being was found. Conclusions In children with MVP, the lower self-assessment is observed mainly in evaluation of their health and own physical activity. The remaining studied dimensions of HRQOL are comparable with the healthy children. However, within the population of children suffering from MVP, the frequency of clinical symptoms impact upon the different HRQOL dimensions. Thus, MVP represents a heterogeneous population. Whether there are impairments of HRQOL largely depend on the severity and frequency of clinical symptoms.

Background: Insect venom allergy (IVA) is present in 1–3% of the population. A group of patients with high specific IgE do not react to stings. In contrast, a proportion of patients with IVA have low specific IgE levels. These findings indicate that factors other than specific IgE may also be involved in IVA. Dysfunction of the renin-angiotensin system (RAS) has been described as a potential factor in IVA. The objective of this study was to determine the prevalence of angiotensin AGT p.M235T and angiotensin-converting enzyme ACE I/D, I/I, D/D gene polymorphisms in patients with IVA and to relate the presence of these gene variants to the course of IVA and the safety of treatment. Methods: A total of 107 patients with IVA and 113 controls were studied. AGT p.M235T and ACE (ID, I/I, D/D) gene polymorphisms were examined, and angiotensin I levels were measured by immunoassay. Results: The frequency of the AGT MM M235T variant was significantly higher in IVA patients (29.9%) than in controls (17%, p = 0.02). The presence of the MM M235T genotype increased the risk of grade IV reactions (odds ratio = 2.5 and 95% confidence interval 1.04–6.08). There were no differences in the prevalence of the ACE I/D polymorphism and angiotensin I levels between control groups and patients with different grades of anaphylactic reactions or patients with side effects of venom immunotherapy. Conclusion: The AGT M235T MM variant may be responsible for severe anaphylactic reactions to insect venom allergens in some patients.

The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 +/- 123.57 U/l) when compared with control (312.04 +/- 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 +/- 79.87 micromol/l) when compared with group 1 (522.79 +/- 167.56 micromol/l) and control (529.80 +/- 81.99 micromol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 +/- 22.56 U/g protein) when compared with control (45.22 +/- 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 +/- 2.47 mg/l) when compared with group 1 (1.75 +/- 1.01 mg/l) and control (0.57 +/- 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)or =4] and with inactive TAO (24 patients, CAS4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CASor =4 and patients with a CAS4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p0.001).Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.