Cushing's syndrome is associated with altered adipokine profile.

Introduction: Adipokines are signaling molecules involved in the integration of metabolism. Changes in their concentrations were observed in obesity, metabolic syndrome, diabetes mellitus and cardiovascular diseases, as well as endocrine disorders. Cushing's syndrome is associated with metabolic dysregulation, but the significance of adipokines in this entity and related complications is largely unknown. The aim of our study was to determine the concentrations of adipokines: fetuin A, fatty acid binding protein 4 (FABP4) and retinol binding protein 4 (RBP4) in Cushing's syndrome and to assess their relation to established cardiovascular and diabetes risk markers. Methods: We examined 21 subjects with Cushing's syndrome and 24 healthy controls in a cross-sectional manner. Venous blood samples were analysed for adipokines, cortisol, adrenocorticotrophin, glucose, insulin, glycated haemoglobin (HbA1c), triglycerides, cholesterol fractions, thyrotropin and free thyroid hormones concentrations. Patients' body mass index (BMI) was evaluated, homeostatic model assessment-insulin resistance and Systematic Coronary Risk Evaluation (SCORE) were calculated. Results: We found that the concentration of fetuin A was lower, while FABP4 and RBP4 concentrations were higher in Cushing's syndrome compared to controls [156.4 ± 60.0 µg/ml vs 260.7 ± 49.6 µg/ml; 79.8 (35.2-156.1) ng/ml vs 27.9 (17.1-36.7) ng/ml and 34 (30-37.7) mg/l vs 25.8 (23.6-27.7) mg/l, respectively]. Fetuin A correlated inversely, while FABP4 and RBP4 positively, with the concentrations of urinary free cortisol and adrenocorticotrophin. Fetuin A was positively related to LDL-cholesterol, and negatively to SCORE and HbA1c. FABP4 was associated positively with BMI, HbA1c and triglycerides, while RBP4 correlated positively with triglycerides and systolic blood pressure. Conclusions: Adipokines' concentrations change in hypercortisolism. Further research is needed to ascertain whether adipokines are involved in the development of metabolic complications accompanying Cushing's syndrome or secondarily reflect metabolic dysregulation.

Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation.

Signalling between the tissues integrating synthesis, transformation and utilization of energy substrates and their regulatory hormonal axes play a substantial role in the development of metabolic disorders. Interactions between cytokines, particularly liver derived hepatokines and adipokines, secreted from adipose tissue, constitute one of major areas of current research devoted to metabolic dysregulation. The thyroid exerts crucial influence on the maintenance of basal metabolic rate, thermogenesis, carbohydrate and lipid metabolism, while its dysfunction promotes the development of metabolic disorders. In this review, we discuss the interplay between three adipokines: fatty acid binding protein type 4, fetuin-A, retinol binding protein type 4 and thyroid hormones, that shed a new light onto mechanisms underlying atherosclerosis, cardiovascular complications, obesity, insulin resistance and diabetes accompanying thyroid dysfunction. Furthermore, we summarize clinical findings on those cytokines in the course of thyroid disorders.

APTES-Modified SBA-15 as a Non-Toxic Carrier for Phenylbutazone.

Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, 1H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone.

Improved solubility of lornoxicam by inclusion into SBA-15: Comparison of loading methods.

An increasing proportion of new medicinal substances are poorly soluble in water. Adsorption on mesoporous silicas increases their bioavailability when administered orally. Loading method determines adsorption either on the surface in crystalline state or inside the mesopores in amorphus form. The aim of this study was to compare two methods (adsorption equilibrium and solvent evaporation) of lornoxicam adsorption on SBA-15 and APTES-modified SBA-15 in terms of drug adsorption site. Additionally, we investigated the drug release profiles at different pH and cytotoxicity of the analysed mesoporous materials. The materials were characterized by a number of physicochemical techniques including X-ray diffraction, nitrogen adsorption/desorption techniques, differential scanning calorimetry, thermogravimetric analysis, scanning and transmission electron microscopy, infrared spectroscopy and 1H NMR. Lornoxicam was loaded on the studied materials and released in the media (HCl pH 1.2, phosphate buffers pH 6.8 and 7.4). The cytotoxicity assays of APTES-modified SBA-15 were performed on CaCo-2 human colon cancer cell line. We proved that adsorption equilibrium method is a more advantageous method of loading. It ensures drug adsorption in an amorphous state inside the mesopores. The solvent evaporation method, despite a greater amount of loaded drug, results in drug adsorption in a crystalline state on the silica surface. In drug release studies a greater amount of lornoxicam is released from modified materials compared to crystalline lornoxicam. Cytotoxicity study proved the safety of APTES-modified silica. We concluded that APTES-modified SBA-15 is applicable as an effective and non-toxic carrier for the poorly soluble drug lornoxicam. The adsorption equilibrium method should be the preferred loading method. It enables the adsorption of sparingly soluble substances inside the mesoproes and enhances bioavailability of oral pharmaceutical forms.

Presenting symptoms and endocrine dysfunction in Rathke cleft cysts - a two-centre experience.

INTRODUCTION: Rathke cleft cysts (RCC) arise as developmental abnormalities of the pituitary gland and are usually diagnosed incidentally. However, they may present with headaches, visual impairment, or pituitary dysfunction. Rathke cleft cysts are poorly described in the Polish literature. We aimed to characterize presenting symptoms, associated endocrine dysfunction, and concomitant disorders in the Polish population of patients with RCC. MATERIAL AND METHODS: We performed a retrospective analysis of medical records of 102 patients diagnosed with RCC between 2006 and 2021 at Heliodor Swiecicki Clinical Hospital in Poznan and Independent Public Clinical Hospital No. 4 in Lublin. RESULTS: The cohort was 72% female, with a mean age of 43 years. The median maximal cyst diameter was 7 mm. The majority of subjects were overweight or obese and presented lipid profile or glucose disturbances. Common presenting symptoms included headache, vertigo, and visual impairment. Less frequently we observed sexual dysfunction, irregular menses, galactorrhoea, or fatigue. Hormonal abnormalities were identified in 30% of patients, with hyperprolactinaemia being the commonest endocrinopathy (23%). Pituitary function in patients with RCC did not correlate with cyst size. Both concomitant pituitary adenomas and pineal cysts were diagnosed in 3% of patients. A considerable proportion of subjects were diagnosed with Hashimoto's thyroiditis and multinodular goitre. CONCLUSIONS: RCCs occur mostly in females and may result in a variety of symptoms and hormonal dysfunction. Patients require a full clinical and endocrine evaluation regardless of the cyst diameter. We report a substantial co-occurrence of RCC and metabolic disorders and primary thyroid diseases, which requires further investigation.

Modification of the Release of Poorly Soluble Sulindac with the APTES-Modified SBA-15 Mesoporous Silica.

The effectiveness of oral drug administration is related to the solubility of a drug in the gastrointestinal tract and its ability to penetrate the biological membranes. As most new drugs are poorly soluble in water, there is a need to develop novel drug carriers that improve the dissolution rate and increase bioavailability. The aim of this study was to analyze the modification of sulindac release profiles in various pH levels with two APTES ((3-aminopropyl)triethoxysilane)-modified SBA-15 (Santa Barbara Amorphous-15) silicas differing in 3-aminopropyl group content. Furthermore, we investigated the cytotoxicity of the analyzed molecules. The materials were characterized by differential scanning calorimetry, powder X-ray diffraction, scanning and transmission electron microscopy, proton nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Sulindac loaded on the SBA-15 was released in the hydrochloric acidic medium (pH 1.2) and phosphate buffers (pH 5.8, 6.8, and 7.4). The cytotoxicity studies were performed on Caco-2 cell line. The APTES-modified SBA-15 with a lower adsorption capacity towards sulindac released the drug in a less favorable manner. However, both analyzed materials improved the dissolution rate in acidic pH, as compared to crystalline sulindac. Moreover, the SBA-15, both before and after drug adsorption, exhibited insignificant cytotoxicity towards Caco-2 cells. The presented study evidenced that SBA-15 could serve as a non-toxic drug delivery system that enhances the dissolution rate of sulindac and improves its bioavailability.

IgG4 as a Biomarker in Graves' Orbitopathy.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory disorder associated with fibrosis and abundant tissue lymphoplasmacytic infiltrations. It typically affects the pancreas, the salivary glands, and the retroperitoneal space. However, it might also involve multiple other organs, including the orbit and the thyroid. Recent studies have suggested that IgG4 plays a role in the pathophysiology of autoimmune thyroid diseases. This ultimately led to the establishment of new clinical entities called IgG4-related thyroid disease and thyroid disease with an elevation of IgG4. The aim of this paper is to describe the pathophysiological, histopathological, and clinical features of Graves' Disease (GD) and Graves' Orbitopathy (GO) with elevated IgG4 levels. Multiple studies have demonstrated higher IgG4 serum concentrations in GD patients than in healthy euthyroid controls. Depending on the studied population, elevated serum IgG4 levels occur in 6.4-23% (average: 10.3%) of all patients with GD, 8.3-37.5% (average: 17.6%) of patients with GO, and 0-9.8% (average: 5.4%) of patients with GD without GO, while GO patients comprise 37.5-100% (average: 65.8%) of all GD patients with elevated IgG4 levels. Characteristic features of GD with elevated IgG4 levels include lower echogenicity of the thyroid gland on ultrasound examination, peripheral blood eosinophilia, higher prevalence of orbitopathy, and better response to antithyroid drugs with a tendency to develop hypothyroidism when compared to patients with GD and normal levels of IgG4. Typical signs of GO accompanied by increased concentration of IgG4 include younger age at diagnosis, and more severe course of the disease with a higher Clinical Activity Score (CAS).. We strongly recommend considering the diagnosis of GO with elevated IgG4 in patients with an established diagnosis of GD, elevated serum IgG4 levels, and clinical features of ophthalmic disease overlapping with those of IgG4-related orbital disease.

Changes in complete blood count parameters influenced by endocrine disorders.

Complete blood count is one of the most common diagnostic methods used in everyday practice. Hormonal status is known to affect blood count parameters. The aim of this study is to summarize changes in blood count that may indicate endocrine disorders, based on a literature review. Red cell parameters deteriorate in thyroid disorders including autoimmune thyroiditis and tend to resolve with appropriate treatment implementation. The most frequent form of anaemia associated with thyroid dysfunction is normocytic anaemia. Macrocytic anaemia is more typical of autoimmune thyroiditis-induced hypothyroidism, while microcytic anaemia is more common in hyperthyroidism. Unexplained anaemia or an increase in red cell distribution width should prompt the investigation of thyroid disorders. Cushing's disease may manifest as an increase in white blood cells and platelets. In the blood smear, neutrophilia is often present, while lymphocytes and eosinophils may be within the lower normal range. Hypercortisolism may induce both hyperaemia and anaemia. In hypopituitarism, a decrease in red blood cell count, haemoglobin, haematocrit, and platelets is observed. Acromegaly may be accompanied by an increase in mean corpuscular volume of erythrocytes. Testosterone deficiency is manifested by a decrease in red cell parameters, whereas hyperandrogenism may lead to polycythaemia. In polycystic ovary syndrome an increase in white blood cell count reflects an underlying inflammatory state. Complete blood count analysis is an easily available and cost-effective additional tool in the diagnosis and treatment monitoring of endocrine disorders.

Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People.

Different forms of physical activity-endurance, resistance or dynamic power-stimulate cytokine release from various tissues to the bloodstream. Receptors for exercise-induced cytokines are present in muscle tissue, adipose tissue, liver, brain, bones, cardiovascular system, immune system, pancreas, and skin. They have autocrine, paracrine and endocrine activities. Many of them regulate the myocyte growth and differentiation necessary for muscle hypertrophy and myogenesis. They also modify energy homeostasis, lipid, carbohydrate, and protein metabolism, regulate inflammation and exchange information (crosstalk) between remote organs. So far, interleukin 6 and irisin have been the best studied exercise-induced cytokines. However, many more can be grouped into myokines, hepatokines and adipomyokines. This review focuses on the less known exercise-induced cytokines such as myostatin, follistatin, decorin, brain-derived neurotrophic factor, fibroblast growth factor 21 and interleukin 15, and their relation to various forms of exercise, i.e., acute vs. chronic, regular training in healthy people.

Correlates of inconsistent condom use and drug use among men having sex with men in Poland: a cross-sectional study.

The number of new human immunodeficiency virus (HIV) diagnoses is rising in many parts of Europe. We sought to evaluate the rising prevalence of new HIV diagnoses in Poland, where the majority of newly-diagnosed HIV cases are men having sex with men (MSM). This study aims to measure the prevalence of condom use and drug use and to identify risk factors for contracting sexually transmitted infections (STIs) among MSM in Poland by distributing an anonymous online survey aimed toward MSM. Among the 1438 participants who completed valid surveys, those with low education level and greater than 100 prior sexual partners showed the highest odds for inconsistent condom use (adjusted odds ratio [aOR] 3.027, 2.044, respectively). Participants who identified themselves as heterosexuals, with multiple sexual partners and living in big cities showed the highest odds for drug use (aOR 4.869, 3.305, 1.720, respectively). This study identifies groups at the highest risk of HIV/STIs and provides valuable information for public health experts to develop targeted STI prevention campaigns.

Preoperative blood morphology and incidence of acute kidney injury after on-pump coronary artery bypass grafting - a single-center preliminary report.

INTRODUCTION: Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) performed in cardiopulmonary bypass (CPB) may complicate the postoperative course and has a negative impact on outcome. In some cases, postoperative AKI develops in spite of normal baseline creatinine concentration and estimated glomerular filtration rate (eGFR). AIM: To examine whether there is any association between the preoperative blood morphology and incidence of post-operative AKI. MATERIAL AND METHODS: The study involved 62 consecutive patients with the mean age of 64.0 ±7.4 years who underwent CABG in CPB. Before surgery, blood morphology and biochemistry were analyzed. Patients with eGFR below 60 ml/min/1.73 m2 were excluded. After the operation, parameters of renal function were checked systematically. Acute kidney injury was defined according to the Acute Kidney Injury Network (AKIN) classification. RESULTS: Twenty-one (33.9%) patients presented AKI (group AKI), although in the majority of them (n = 16) it was temporary and medical management was enough to cure AKI. Only in 1 (1.6%) case was renal replacement therapy necessary. In group AKI, patients' preoperative hemoglobin concentration (8.46 ±0.72 mM/l), red blood cell count (4.51 ±0.39 × 1012/l) and hematocrit (0.40 ±0.04) were significantly lower (p < 0.05) than in group C (9.07 ±0.57 mM/l; 4.78 ±0.36 × 1012/l; 0.43 ±0.03, respectively). Interestingly, the baseline parameters of renal function were comparable between groups. CONCLUSIONS: Hemoglobin concentration and red blood cell counts close to the lower limit of the normal range may enable identification of patients at risk of AKI early after CABG in CPB among individuals with normal preoperative biochemical parameters of renal function.