Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light.

Thiohydantoin and quinolone derivatives have attracted researchers' attention because of a broad spectrum of their medical applications. The aim of our research was to synthesize and analyze the antimicrobial properties of novel 2-thiohydantoin and 2-quinolone derivatives. For this purpose, two series of hybrid compounds were synthesized. Both series consisted of 2-thiohydantoin core and 2-quinolone derivative ring, however one of them was enriched with an acetic acid group at N3 atom in 2-thiohydantoin core. Antibacterial properties of these compounds were examined against bacteria: Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antimicrobial assay was carried out using a serial dilution method to obtain the MIC. The influence of blue light irradiation on the tested compounds was investigated. The relative yield of singlet oxygen (1O2*, 1Δg) generation upon excitation with 420 nm was determined by a comparative method, employing perinaphthenone (PN) as a standard. Antimicrobial properties were also investigated after blue light irradiation of the suspensions of the hybrids and bacteria placed in microtitrate plates. Preliminary results confirmed that some of the hybrid compounds showed bacteriostatic activity to the reference Gram-positive bacterial strains and a few of them were bacteriostatic towards Gram-negative bacteria, as well. Blue light activation enhanced bacteriostatic effect of the tested compounds.

Validation of exophthalmos magnetic resonance imaging measurements in patients with Graves' orbitopathy, compared to ophthalmometry results.

Purpose: Although assessment of the orbital structures using magnetic resonance imaging (MRI) is well described in the literature, there is no consensus as to which measurement method is the most useful in exophthalmos assessment. The aim of the study was to correlate 2 MRI methods of exophthalmos measurement with exophthalmometry results and to determine a proper technique of exophthalmos measurement. Material and methods: Fifty-four patients (108 orbits) with exophthalmos in the course of Graves' orbitopathy were enrolled in the study. Two measurements on axial T2W orbital MRI images were performed by 2 independent radiologists: the distance from the interzygomatic line to the anterior surface of the globe (AD) and the distance from the interzygomatic line to the posterior sclera (PD). Within 4 weeks, an exophthalmometry was performed by an ophthalmologist using a Hertel exophthalmometer. The inter-observer variation was assessed using the Pearson correlation coefficient. Values were presented as mean and standard deviation, and the differences in values were explored with Student's t-test. Results: The mean AD measured on MRI by the first observer was 20.6 ± 3 mm, and 20.6 ± 2.9 mm by the second observer. PD values were 2.9 ± 2.8 mm and 3.4 ± 2.8 mm, respectively. The mean exophthalmometry result was 21 ± 3.3 mm. The correlation was very high between observers for AD measurements (r = 0.98, p = 0.01) and high for PD measurements (r = 0.95, p = 0.01). AD measurements on MRI and exophthalmometry results were strongly correlated (r = 0.9, p = 0.01). Conclusions: The AD measurement has better reproducibility and is directly correlated with Hertel exophthalmometry. This method could be sufficient in routine practice.

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

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

Products of Docosahexaenoate Oxidation as Contributors to Photosensitising Properties of Retinal Lipofuscin.

Retinal lipofuscin which accumulates with age in the retinal pigment epithelium (RPE) is subjected to daily exposures to high fluxes of visible light and exhibits potent photosensitising properties; however, the molecules responsible for its photoreactivity remain unknown. Here, we demonstrate that autooxidation of docosahexaenoate (DHE) leads to the formation of products absorbing, in addition to UVB and UVA light, also visible light. The products of DHE oxidation exhibit potent photosensitising properties similar to photosensitising properties of lipofuscin, including generation of an excited triplet state with similar characteristics as the lipofuscin triplet state, and photosensitised formation of singlet oxygen and superoxide. The quantum yields of singlet oxygen and superoxide generation by oxidised DHE photoexcited with visible light are 2.4- and 3.6-fold higher, respectively, than for lipofuscin, which is consistent with the fact that lipofuscin contains some chromophores which do contribute to the absorption of light but not so much to its photosensitising properties. Importantly, the wavelength dependence of photooxidation induced by DHE oxidation products normalised to equal numbers of incident photons is also similar to that of lipofuscin-it steeply increases with decreasing wavelength. Altogether, our results demonstrate that products of DHE oxidation include potent photosensitiser(s) which are likely to contribute to lipofuscin photoreactivity.

[Endoscopic decompression of orbit in Graves' orbitopathy]. / Endoskopowa dekompresja oczodolu w orbitopatii tarczycowej.

Graves' orbitopathy (GO) is an extrathyroidal manifestation of Graves' disease (GD). The majority of patients has mild form of the disease, with no need of additional treatment. A few percent of patients can have a severe or very severe course of disease. In severe forms of GO there might occur considerable exophthalmos complicated in some cases with corneal ulceration or pressure on optic nerve leading to neuropathy (DON, dysthyroid optic neuropathy). In therapy of severe forms of GO different types of treatment are used depending on diagnosis and activity of disease. The pharmacological (among the others very high doses of intravenous methylprednisolone) and surgery treatment (orbit decompression) are used. The orbital decompression is a procedure performed in order to decrease the intraorbital pressure by removing part of its bony borders in cases with excessive mass in orbit. For decades many external approaches have been used. With the progress of the endoscopic techniques the endoscopic orbit decompression has become the first line treatment. The lack of facial incisions is connected with many benefits for patients. In our article endoscopic decompression technique in GO was described, as well as available medical literature concerning this technique and its outcomes was performed.

Women with inflammatory bowel diseases have a suboptimal cervical cancer screening rate and are not aware of the recommended human papilloma virus vaccine.

The aim of the study was to assess the self-reported cervical cancer screening rate among patients with inflammatory bowel diseases (IBD) and patient attitude towards human papilloma virus (HPV) vaccination. A self-designed survey was conducted in hospitalized IBD patients. The survey comprised demographic data, questions regarding cervical smear test frequency and vaccinations recommended for an IBD patient. Randomly, patients completed the survey with a physician present to determine question comprehension. In order to provide test-retest reliability a group of 10 patients completed it twice. Survey data from 150 IBD patients (mean age: 36 years, SD ± 13; mean IBD duration: 10 years, SD ± 6.5) were analyzed. Fifteen percent of the patients reported irregular cervical testing and 15% do not remember when having had a previous cervical testing performed. Only 69% of the patients undergo testing regularly; 30% annually, 32% every 2-3 years; 7% every 5 years. The mean age of patients tested regularly was 22 years, vs. 32 years tested irregularly (p < .001). Only 10% of women claimed that HPV vaccine is recommended for an IBD patient. There is a low adherence to the recommendations regarding cervical cancer screening and prophylaxis. Better multi-disciplinary cooperation between patients and physicians is required to improve patient education and outcomes.

Immobilization and detection of platelet-derived extracellular vesicles on functionalized silicon substrate: cytometric and spectrometric approach.

Among the various biomarkers that are used to diagnose or monitor disease, extracellular vesicles (EVs) represent one of the most promising targets in the development of new therapeutic strategies and the application of new diagnostic methods. The detection of circulating platelet-derived microvesicles (PMVs) is a considerable challenge for laboratory diagnostics, especially in the preliminary phase of a disease. In this study, we present a multistep approach to immobilizing and detecting PMVs in biological samples (microvesicles generated from activated platelets and human platelet-poor plasma) on functionalized silicon substrate. We describe the application of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and spectroscopic ellipsometry methods to the detection of immobilized PMVs in the context of a novel imaging flow cytometry (ISX) technique and atomic force microscopy (AFM). This novel approach allowed us to confirm the presence of the abundant microvesicle phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) on a surface with immobilized PMVs. Phosphatidylcholine groups (C5H12N+; C5H15PNO4+) were also detected. Moreover, we were able to show that ellipsometry permitted the immobilization of PMVs on a functionalized surface to be evaluated. The sensitivity of the ISX technique depends on the size and refractive index of the analyzed microvesicles. Graphical abstract Human platelets activated with thrombin (in concentration 1IU/mL) generate population of PMVs (platelet derived microvesicles), which can be detected and enumerated with fluorescent-label method (imaging cytometry). Alternatively, PMVs can be immobilized on the modified silicon substrate which is functionalized with a specific IgM murine monoclonal antibody against human glycoprotein IIb/IIIa complex (PAC-1). Immobilized PMVs can be subjected to label-free analyses by means ellipsometry, atomic force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS).

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Parathyroid adenoma diagnosed on the basis of a giant cell tumor of parieto-occipital region and multifocal bone injuries.

Brown tumors are rare skeletal manifestations of hyperparathyroidism (HPT) that may mimic cancer metastases. Histopathologically, they are difficult to differentiate from other giant cell lesions. A case is presented of 41-year-old woman with giant cell tumor in parieto-occipital region with injury of external bone lamina, growing into the skull cavity. The mass was suspected of being neoplastic. Numerous osteolytic lesions in the skull skeleton and multifocal bone injuries were observed, also. Elevation in calcium (5.91 mEq/L) and parathormone (1188 ng/mL) concentrations and hypercalciuria (52 mEq/24 h) suggested the diagnosis of HPT initially manifesting as a brown tumor of the skull. Further exploration confirmed the existence of parathyroid adenoma as a cause of the disease. The key treatment for the condition was surgical excision of the adenoma followed by the normalization of parathyroid function and significant reduction in size of skull tumor and other lesions.

Primary hyperparathyroidism presenting as a giant cell tumor of the jaws.

OBJECTIVE: Giant cell tumors of the maxillofacial skeleton are uncommon, they are usually late manifestation of primary hyperparathyroidism. A series of five clinical cases in four women and one man presenting as the giant cell lesions in the maxilla and/or mandible are discussed. METHODS: Biopsy of the lesions, biochemical and hormonal analyses, densitometry and parathyroid scintigraphy were carried out. RESULTS: Biopsy of the lesions showed giant cell tumor of bone. The medical history and laboratory analyses showed primary hyperparathyroidism. Bone density loss was documented and scintigraphy revealed the presence of parathyroid adenomas in four cases. Surgical treatment of hyperparathyroidism, and in the second step - after 6-12 months - the subsequent excision of residual brown tumors in all cases was performed. CONCLUSIONS: One should have in mind that osteolytic bone lesions may be due to metabolic disease of the bone. Accurate diagnosis enabling the proper treatment should be carried out, avoiding unnecessary harm to the patients.

Differences in Chronic Low-Grade Inflammation and Metabolic Disturbances between VDR Genotypes in an Ethnically Homogenous Postmenopausal Female Population from Poland.

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50-60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

Structural Impact of Selected Retinoids on Model Photoreceptor Membranes.

Photoreceptor membranes have a unique lipid composition. They contain a high level of polyunsaturated fatty acids including the most unsaturated fatty acid in nature, docosahexaenoic acid (22:6), and are enriched in phosphatidylethanolamines. The phospholipid composition and cholesterol content of the subcellular components of photoreceptor outer segments enables to divide photoreceptor membranes into three types: plasma membranes, young disc membranes, and old disc membranes. A high degree of lipid unsaturation, extended exposure to intensive irradiation, and high respiratory demands make these membranes sensitive to oxidative stress and lipid peroxidation. Moreover, all-trans retinal (AtRAL), which is a photoreactive product of visual pigment bleaching, accumulates transiently inside these membranes, where its concentration may reach a phototoxic level. An elevated concentration of AtRAL leads to accelerated formation and accumulation of bisretinoid condensation products such as A2E or AtRAL dimers. However, a possible structural impact of these retinoids on the photoreceptor-membrane properties has not yet been studied. In this work we focused just on this aspect. The changes induced by retinoids, although noticeable, seem not to be significant enough to be physiologically relevant. This is, however, an positive conclusion because it can be assumed that accumulation of AtRAL in photoreceptor membranes will not affect the transduction of visual signals and will not disturb the interaction of proteins engaged in this process.

CD8+CD28-lymphocytes in peripheral blood and serum concentrations of soluble interleukin 6 receptor are increased in patients with Graves' orbitopathy and correlate with disease activity.

BACKGROUND: The extrathyroid, orbital manifestation of Graves' disease (GD)--Graves' orbitopathy (GO)--presents a difficult clinical problem. The immunological status of GO patients is still under investigation. The aim of this study was to assess the serum concentration of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R), and CD8+CD28- lymphocytes in GO patients and to evaluate if these parameters were associated with disease activity. PATIENTS: Thirty-nine patients (29 women and 10 men, aged 24-71, mean 50.18) with newly diagnosed GD were enrolled in the study. Active GO was diagnosed in 20 patients. The control group included 12 healthy individuals. METHODS: Serum concentrations of IL-6 and sIL-6R were estimated by ELISA. Percentages of CD8+CD28- lymphocytes in peripheral blood were assessed by flow cytometry. RESULTS: Mean serum IL-6 and sIL-6R concentrations were significantly higher in all GD patients and in GO and non-GO patients than in normal controls. In all GD patients and the non-GO group, serum IL-6 and sIL-6R concentrations were significantly reduced after efficient treatment. In GO patients, only serum sIL-6R concentration was significantly lower after efficient treatment. In all GD patients, the mean percentage of CD8+CD28- lymphocytes was significantly lower after efficient treatment. In GO patients, the mean percentage of CD8+CD28- lymphocytes was significantly higher than in the non-GO group or in normals. Moreover, in the GO group, the mean percentage of CD8+CD28- lymphocytes was significantly lower after treatment. CONCLUSION: Our results have shown that CD8+CD28- lymphocyte percentage in peripheral blood and serum concentration of sIL-6R are increased in GO patients and correlate with disease activity.

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

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

Multiplex analysis of age-related protein and lipid modifications in human Bruch's membrane.

Aging of the human retina is characterized by progressive pathology, which can lead to vision loss. This progression is believed to involve reactive metabolic intermediates reacting with constituents of Bruch's membrane, significantly altering its physiochemical nature and function. We aimed to replace a myriad of techniques following these changes with one, Raman spectroscopy. We used multiplexed Raman spectroscopy to analyze the age-related changes in 7 proteins, 3 lipids, and 8 advanced glycation/lipoxidation endproducts (AGEs/ALEs) in 63 postmortem human donors. We provided an important database for Raman spectra from a broad range of AGEs and ALEs, each with a characteristic fingerprint. Many of these adducts were shown for the first time in human Bruch's membrane and are significantly associated with aging. The study also introduced the previously unreported up-regulation of heme during aging of Bruch's membrane, which is associated with AGE/ALE formation. Selection of donors ranged from ages 32 to 92 yr. We demonstrated that Raman spectroscopy can identify and quantify age-related changes in a single nondestructive measurement, with potential to measure age-related changes in vivo. We present the first directly recorded evidence of the key role of heme in AGE/ALE formation.

Comparison of photodynamic efficiency of cholesterol, selected cholesterol esters, metabolites and oxidation products on lipid peroxidation processes.

Cholesterol (Ch) is one of the most important components of biological membranes, which has a significant impact on their biophysical properties. As a key component of lipid membranes, Ch along with other unsaturated lipids present in a biological membrane undergoes oxidation reaction during oxidative stress. Cholesterol oxidation products, cholesteryl esters and metabolites are also localise in lipid membranes, where they may modify membrane properties. In this work the impact of cholesterol, selected cholesteryl esters, cholesterol oxidation products and metabolites on lipid peroxidation induced by photodynamic action has been studied using EPR oximetry and direct detection of singlet oxygen phosphorescence at 1270 nm. The obtained rate constants values of interaction of selected lipids and sterols with singlet oxygen indicate that the tested compounds are not efficient singlet oxygen quenchers. Nevertheless, the presence of sterols modifies to different extend the oxygen photoconsumption rate in peroxidisable liposomes.

Relationships between Vitamin D and Selected Cytokines and Hemogram Parameters in Professional Football Players-Pilot Study.

Vitamin D affects both innate and adaptive immunity. Most of the effects of vitamin D on innate immunity are anti-inflammatory. In monocytes/macrophages, vitamin D suppresses the production of the inflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-8. Therefore, the aim of our study was to investigate the relationship between 25(OH)D concentration and selected cytokines-IL-6, TNF-α, and IL-1ß, which are hemogram parameters for professional football players. We enrolled 41 Polish premier league soccer players. The mean age, career duration, and VO2max were, respectively: 22.7 ± 5.3 years, 14.7 ± 4.5 years, and 55.8 ± 4.0 mL/kg/min. Serum levels of 25(OH)D were measured by electrochemiluminescence (ECLIA) using the Elecsys system (Roche, Switzerland). Serum levels of IL-6, IL-1ß, and TNF-α were measured by ELISA (R&D Systems, Minneapolis). Blood count with smear was measured on a Sysmex XT-4000i analyzer (Sysmex Corporation, Japan). Our study showed decreased serum 25(OH)D levels in 78% of the professional players. We found a significant negative correlation between 25(OH)D levels and TNF-α and LYMPH (%). The results also demonstrated a statistically significant positive correlation between vitamin D levels and NEUTH (%), NEUTH (tys/µL), and EOS (tys/µL). Based on the results of our study, we concluded that football players from Poland are not protected against vitamin D insufficiency in winter months. Moreover, vitamin D deficiency may be associated with an increased pro-inflammatory risk in well-trained athletes.

Tauroursodeoxycholic Acid (TUDCA)-Lipid Interactions and Antioxidant Properties of TUDCA Studied in Model of Photoreceptor Membranes.

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid containing taurine conjugated with the ursodeoxycholic acid (UDCA), has been known and used from ancient times as a therapeutic compound in traditional Chinese medicine. TUDCA has recently been gaining significant interest as a neuroprotective agent, also exploited in the visual disorders. Among several mechanisms of TUDCA's protective action, its antioxidant activity and stabilizing effect on mitochondrial and plasma membranes are considered. In this work we investigated antioxidant activity of TUDCA and its impact on structural properties of model membranes of different composition using electron paramagnetic resonance spectroscopy and the spin labeling technique. Localization of TUDCA molecules in a pure POPC bilayer has been studied using a molecular dynamics simulation (MD). The obtained results indicate that TUDCA is not an efficient singlet oxygen (1O2 (1Δg)) quencher, and the determined rate constant of its interaction with 1O2 (1Δg) is only 1.9 × 105 M-1s-1. However, in lipid oxidation process induced by a Fenton reaction, TUDCA reveals substantial antioxidant activity significantly decreasing the rate of oxygen consumption in the system studied. In addition, TUDCA induces slight, but noticeable changes in the polarity and fluidity of the investigated model membranes. The results of performed MD simulation correspond very well with the experimental results.

Analysis of photoreactivity and phototoxicity of riboflavin's analogue 3MeTARF.

Recent studies focus on usage of blue light of λ = 450 nm in combination with photosensitizers to treat surface skin disorders, including cancers. In search of convenient therapeutic factor we studied riboflavin analogue 3-methyl-tetraacetylriboflavin (3MeTARF) as potential sensitizer. Riboflavin (Rfl) itself, non -toxic in the darkness, upon absorption of UVA and blue light, may act as photosensitizer. However, Rfl efficiency is limited due to its susceptibility to photodecomposition. Riboflavin's acetylated analogue, 3MeTARF, bears substituents in ribose chain, which inhibit intramolecular processes leading to degradation. Upon excitation, this compound, reveals higher photochemical resistance, remaining a good singlet oxygen generator. Thus, being more stable as the sensitizer, might be much more efficient in photodynamic processes. The objective of undertaken study was to elucidate mechanisms of 3MeTARF photoreactivity under the irradiation with blue light in comparison to its mater compound, riboflavin. We approached this goal by using spectroscopic methods, like direct singlet oxygen phosphorescence detection at 1270 nm, EPR spin trapping and oximetry. Additionally, we tested both riboflavin and 3MeTARF phototoxicity against melanoma cells (WM115) and we studied mechanism of photodynamic cell death, as well. Moreover, 3MeTARF induces apoptosis in melanoma cells at ten times lower concentration than riboflavin itself. Our studies confirmed that 3MeTARF remains stable upon blue light activation and is more efficient photosensitizer than Rfl.

[The difficulties in differential diagnosis of primary aldosteronism subtypes in women with strokes at a young age]. / Trudnosci w diagnostyce róznicowej podtypów pierwotnego aldosteronizmu u kobiety z udarami mózgowymi w mlodym wieku.

In patients with primary aldosteronism (PA), it is fundamental to distinguish between subtypes that benefit from different treatment. The authors describe difficulties in differential diagnosis in a case of 46 year old women with PA and two strokes in the past. Based on high plasma and urine aldosterone concentration, low plasma renin activity (PRA), very high aldosterone/PRA ratio and unilateral macroadenoma detected in computed tomography, aldosterone producing adenoma was diagnosed and the patient was performed unilateral adrenalectomy. Despite the surgical treatment the patient still presented with clinical and biochemical PA symptoms. Moreover, histological examination suggested adrenal hyperplasia, and laboratory tests were typical for glucocorticoid-remediable aldosteronism. Unfortunately, we didn't find a chimeric CYP 11beta1/CYP 11beta2 gene. Finally, bilateral adrenal hyperplasia was diagnosed and medical treatment with aldosterone antagonist was initiated.