Predictors of subclinical systemic sclerosis primary heart involvement characterised by microvasculopathy and myocardial fibrosis.

OBJECTIVES: SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI. METHODS: A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured. RESULTS: Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6-2.4) vs 3 (2-3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P < 0.001]. Presence of late gadolinium enhancement and higher ECV was associated with skin score [odds ratio (OR) = 1.115, P = 0.048; R2 = 0.353, P = 0.004], and ECV and myocardial perfusion reserve was associated with the presence of digital ulcers at multivariate analysis (R2 = 0.353, P < 0.001; R2 = 0.238, P = 0.011). High-sensitivity troponin I was significantly higher in patients with late gadolinium enhancement, and N-terminal pro-brain natriuretic peptide was associated with ECV (P < 0.05). CONCLUSION: Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.

Incidental significant arrhythmia in scleroderma associates with cardiac magnetic resonance measure of fibrosis and hs-TnI and NT-proBNP.

OBJECTIVES: To screen for significant arrhythmias with an implantable loop recorder (ILR) in patients with SSc and no known cardiovascular disease, and identify associated disease phenotype, blood and cardiovascular magnetic resonance (CMR) biomarkers. METHODS: Twenty patients with SSc with no history of primary SSc heart disease, traditional cardiovascular disease, diabetes or maximum one traditional cardiovascular risk factor underwent clinical assessment, contrast-enhanced CMR and ILR insertion. RESULTS: ILR data were available for 19 patients: 63% female, mean (s.d.) age of 53 (12) years, 32% diffuse SSc. Eight patients had significant arrhythmias over 3 years: one complete heart block, two non-sustained ventricular tachycardia [all three dcSSc, two anti-topoisomerase antibodies (Scl70) positive, three interstitial lung disease and two previous digital ulceration] and five atrial arrhythmias of which four were with limited SSc. These required interventions with one permanent pacemaker implantation, four anti-arrhythmic pharmacotherapy, one anticoagulation.Patients with significant arrhythmia had higher baseline high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide [mean difference (95% CI) 117 (-11, 245) and 92 (-30, 215) ng/l, respectively], and CMR-extracellular volume [mean (s.d.) 32 (2) vs 29 (4)%]. Late gadolinium enhancement was observed in five patients, only one with significant arrhythmia. CONCLUSION: This first ILR study identified potentially life-threatening arrhythmias in asymptomatic SSc patients attributable to a primary SSc heart disease. Disease phenotype, CMR-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening. Future studies can inform a risk model and provide insights into SSc-associated arrhythmia pathogenesis.

[Serum free light chains for monitoring systemic lupus erythematosus activity].

OBJECTIVE: Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease leading to chronic inflammation of numerous tissues and organs. The search for clinically useful markers of its activity is ongoing. At present, it is suggested that serum free light chains (FLC) may be useful in assessing SLE activity. The aim of study: To investigate the relationship between serum levels of free light chains (FLC) and the activity of SLE. PATIENTS AND METHODS: Material and methods: Eighty-four SLE patients (75 female; 9 men) aged 34.9±11.8 years, with the disease duration of 6.2±5.2 years, were included. The disease activity was assessed by: circulating C3 and C4 complement components levels, anti-double-stranded DNA (anti-DNA), SLEDAI-2K scale and levels of FLC. We also assessed the relationship between levels of FLC and clinical manifestations of SLE. RESULTS: Results: Median serum levels of FLC κ and FLC λ were 25.9 ± 15.6mg/L and 21.2 ± 9.4 mg/L in SLE pts, respectively. Serum levels of FLC κ were positive in 60 SLE pts (71.4%) and FLC λ in 20 SLE pts (23.8%). The significant correlations were found between levels of FLC κ, FLC λ and of anti-dsDNA (p=0.01; r=0.27); (p=0.001; r=0.35), C3 complement (p<0.02; r= -0.25); (p<0.004; r= -0.31), C4 complement (p<0.04; r= -0.22); (p<0.006; r= -0.3) and SLEDAI -2K (p<0.009; r=0.28); (p<0.001; r=0.35). The SLE pts with arthritis / myositis and hematologic symptoms had significantly higher FLC levels than those without. CONCLUSION: Conclusion: Measurement of serum levels of FLC can help in the periodical assessment of the disease activity in SLE pts.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.

OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values. RESULTS: Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007). CONCLUSION: When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX. TRIAL REGISTRATION: EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

[The involvement of galectin-3 in heart failure]. / Rola galektyny-3 w niewydolnosci serca.

Hart failure (HF) accounts for numerous serious problems: medical, social and financial. HF affects 2-3% adult population and its frequency increases with age. Despite advances in laboratory diagnostics of HR the use of biochemical markers remains limited. Currently, only natriuretic peptides, especially type B natriuretic peptides (BNP) and N-terminal fragment of pro-BNP (NT-proBNP) have been fully approved biomarkers employed in diagnosing HF. The concentration of those peptides fluctuates and largely depends on age, gender, renal function, day/night rhythm and volemia which reflects hemodynamic state rather than hart abnormal structure. As the application of natriuretic peptides is limited in certain groups of patients, it is necessary to search for other more stable biomarkers. Recent investigations have suggested galectin-3 (gal-3) to be a new promising cardiological marker. Gal-3 belongs to a family of lectins that demonstrate binding specificity for ß-galactoside which are produced by activated macrophages. Its operative path involves stimulation of cardiac fibroblasts and collagen production which can result in pathological remodeling of the myocardium structure. Numerous research found substantially increased gal-3 level in patients with chronic HF disregarding the etiology of disease. Moreover, some clinical studies have proved that increased gal-3 concentration is a factor of poor prognosis and predicative of death due to any reason in patients with HF. Contrary to natriuretic peptides, gal-3 is hemodynamically stable which is an additional asset of gal-3 as a marker of myocardial fibrosis.The article presents current state of research into gal-3 involvement in HF pathogenesis and possible use of gal-3 as a diagnostic marker of HF.

Nutritional responsiveness affects novel neutrophil parameters and reduces in-hospital mortality and costs in elective cancer oesophagectomy - a single centre, prospective, observational study.

INTRODUCTION: Malnutrition in surgical patients remains a common issue affecting the perioperative period. Oesophageal cancer is a disease associated with one of the highest malnutrition rates. Assessment of patient nutritional status remains a challenge due to limited validated tools. Novel parameters to identify malnourished patients and the effectiveness of preoperative nutritional intervention might improve treatment results in the perioperative period. MATERIAL AND METHODS: This was a prospective, observational, single-centre study of patients scheduled for elective oesophagectomy. The primary aim of this study was to establish the correlation between neutrophil reactivity intensity (NEUT-RI) and neutrophil granularity intensity (NEUT-GI) and patients' nutritional status. We divided patients into nutritional responders (R group) and nutritional non-responders (NR group) defined as regaining at least 25% of the maximum preoperative body weight loss during the preoperative period. RESULTS: The R group had significantly shorter intensive care unit (ICU) stays: 5.5 (4-8) vs. 13 (7-31) days ( P = 0.01). It resulted in a lower cost of ICU stays in the R group: 4775.2 (3938.9-7640.7) vs. 12255.8 (7787.6-49108.7) euro in the NR group ( P = 0.01). Between the R group and the NR group, we observed statistically significant differences in both preoperative NEUT-RI (48.6 vs. 53.4, P = 0.03) and NEUT-GI (154.6 vs. 159.3, P = 0.02). Apart from the T grade, the only preoperative factor associated with reduced mortality was the nutritional responsiveness: 11.1% vs. 71.4% ( P = 0.008). CONCLUSIONS: Preoperative nutritional responsiveness affects neutrophil intensity indexes and reduces in-hospital mortality and costs associated with hospital stay. Further research is required to determine the correlation between novel neutrophil parameters and patients' nutritional status.

Comparative analysis of adiponectin isoform distribution in pregnant women with gestational diabetes mellitus and after delivery.

OBJECTIVE: To evaluate the distribution of circulating adiponectin isoforms in pregnant women with gestational diabetes mellitus (GDM) and compare isoform distribution changes 12 months after delivery. DESIGN CROSS-SECTIONAL STUDY SETTING: University Hospital. POPULATION: Sixty-four consecutive pregnant women who underwent routine prenatal tests for GDM between 24 and 28 weeks of gestation. The study group included 36 women diagnosed with GDM, 30 of whom underwent re-testing for diabetes 12 months after delivery. The control group included 28 healthy pregnant women. METHODS: Quantitative determination of total adiponectin and its isoforms in serum was performed with the multimeric adiponectin enzyme-linked immunosorbent assay. RESULTS: Total adiponectin concentration in women with GDM was significantly lower than in women without GDM. Among adiponectin isoforms, significantly lower concentrations of multimers and trimers in women with GDM were found in comparison to controls, while the concentration of hexamers did not differ between the groups. After delivery, a significant increase in total adiponectin and in the concentration of multimers and trimers was found in women with history of GDM. Additionally, we found that multimers and hexamers were negatively correlated with body mass index before and during gestation, as well as after delivery, and middle molecular weight isoforms in gestation were negatively correlated with birthweight. CONCLUSIONS: Hypoadiponectinemia during GDM was characterized by a significant, reversible decrease in multimeric levels; thus this isoform seems to function in a cohesive way with total adiponectin. Negative correlations of adiponectin isomers with body mass index indicate that there is a possibility to normalize total adiponectin and prevent GDM.

The influence of selenium compounds of different structure on morphology, blood biochemistry and phagocytic capability of granulocytes in rats.

BACKGROUND: Selenium belongs to important microelements. Numerous studies have revealed relationships between its deficiency and occurrence of diverse illnesses, but the question of the proper form and dose of Se-supplementation still remains unsolved. OBJECTIVE: In the present study the influence of different selenium compounds on blood morphology and biochemistry as well as on phagocytic capacity of granulocytes and NBT test in rats was investigated. MATERIAL AND METHODS: Adolescent male Wistar rats were divided into four groups (ten animals each): I--control, received saline; II--received sodium selenite Na2SeO3; III--received selenoorganic compound A of chain structure 4-(o-tolyl-)-selenosemicarbazide of 2-chlorobenzoic acid; IV--received selenoorganic compound B of cyclic structure 3-(2-chlorobenzoylamino-)-2-(o-tolylimino-)-4-methyl-4-selenazoline. The administration was performed by stomach tube at a dose of 5 x 10(-4) mg Se g(-1) b.w. once a day for 10 days. RESULTS: Selenium compounds treatment decreased haematocrit. Erythrocytes number was unchanged in all groups receiving Se vs. control, whereas leucocytes number was depressed in groups II and IV. Haemoglobin was significantly decreased in group III. White blood count was altered in groups II and III, where all parameters were markedly decreased except for lymphocytes in group III and remained unchanged in group IV. The outcomes regarding selenium effect on biochemistry parameters of blood showed that urea remained unchanged, glucose was statistically decreased in groups II and III, whereas cholesterol was significantly diminished in group II and increased in group III vs. control. Results concerning phagocytosis and NBT test displayed that % of positive cells were decreased in groups II and III, whereas remained unaltered in group IV vs. control. CONCLUSIONS: As cyclic selenoorganic compound B did not cause many significant changes of the studied parameters it may be suggested that after further researches it could be taken into account as a possible selenium supplement.

Assessment of Immune Cell Activation in Pemphigus.

(1) Background: Pemphigus is a blistering autoimmune disease of the skin and/or mucous membranes, characterised by the presence of specific autoantibodies directed against structural proteins of the human skin. Recent reports indicate that new haematological parameters, termed Extended Inflammation Parameters (EIP), can be used to assess the activation of immune cells during active inflammation. These include parameters assessing both neutrophil activation (NEUT-RI, NEUT-GI) and the number of activated lymphocytes (RE-LYMP). The aim of this study was to investigate the relationship between changes in NEUT-RI, NEUT-GI and RE-LYMP and the disease activity in patients with pemphigus. (2) Results: The study involved 32 patients with diagnosed different types of pemphigus. Neutrophil activation parameters (NEUT-RI and NEUT-GI) and lymphocytes (RE-LYMP) were significantly higher in these patients compared to the parameters in healthy participants (respectively p = 0.0127, p = 0.0011 and p = 0.0033). The increased quantity of activated lymphocytes (RE-LYMP) also correlated significantly with the extent of skin and/or mucosal lesions in patients assessed by the PDAI scale (p < 0.02). (3) Conclusions: The NEUT-RI, NEUT-GI and RE-LYMP parameters proved to be appropriate markers of inflammation severity in pemphigus, also in relation to local lesions, which was not possible with the inflammation markers (CRP, ESR) used so far on a routine basis.

Extended Inflammation Parameters (EIP) as Markers of Immune System Cell Activation in Psoriasis.

Psoriasis is an inflammatory, autoimmune disease that affects approximately 2% of the population. The inflammation in psoriasis can be systemic, so despite a predominantly cutaneous manifestation, it also affects the internal organs. The diagnosis and monitoring of the disease are based on the clinical picture. To assess the disorders of other organs, additional tests need to be performed. Recently, the examination of blood morphology has been enriched with modern haematological parameters, i.e., Extended Inflammation Parameters (EIP), which include RE-LYMPH (activated lymphocytes), AS-LYMPH (antibody-producing B lymphocytes), and NEUT-RI and NEUT-GI (activated neutrophils). In the study, higher values of new haematological parameters were observed in individuals with psoriasis than in healthy controls. A higher EIP value was noted in the group of individuals with plaque psoriasis than in the group of individuals with psoriatic arthritis. Implementation of these parameters into routine laboratory analysis will likely make it possible to estimate the severity of the inflammation and improve its assessment.

Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers.

OBJECTIVES: To explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI). METHODS: Patients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction. RESULTS: Seventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073). CONCLUSION: These data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.

Carotid artery volumetric measures associate with clinical ten-year cardiovascular (CV) risk scores and individual traditional CV risk factors in rheumatoid arthritis; a carotid-MRI feasibility study.

BACKGROUND: Common carotid artery intima-media thickness (CIMT), as measured by ultrasound, has utility in stratification of the accelerated cardiovascular risk seen in rheumatoid arthritis (RA); however, the technique has limitations. Carotid magnetic resonance imaging (MRI) is emerging as a useful research tool in the general population, but has yet to be applied in RA populations. Our objectives were to describe the utility of carotid artery MRI (carotid-MRI) in patients with RA in comparison to healthy controls and to describe the association with RA disease phenotype. METHODS: Sixty-four patients with RA and no history of cardiovascular (CV) disease/diabetes mellitus were assessed for RA and CV profile, including homeostasis model assessment-estimated insulin resistance (HOMA-IR) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All underwent carotid-MRI (3 T), and were compared to 24 healthy controls. Univariable analysis (UVA) and multivariable linear regression models (MVA) were used to determine associations between disease phenotype and carotid-MRI measures. RESULTS: There were no significant differences in carotid arterial wall measurements between patients with RA and controls. Wall and luminal volume correlated with 10-year CV risk scores (adjusted as per 2017 European League Against Rheumatism (EULAR) guidance); rho = 0.33 (p = 0.012) and rho = 0.35 (p = 0.008), respectively, for Joint British Societies-2 risk score. In UVA, carotid-MRI volumetric measures predominantly were associated with traditional CV risk factors including age, ever-smoking and HOMA-IR (p < 0.05). Lower body mass index was associated with wall maximum thickness (r = - 0.25 p = 0.026). In MVA, age was independently associated with wall volume (B 1.13 (95% CI 0.32, 1.93), p = 0.007) and luminal volume (B 3.69 (95% CI 0.55, 6.83, p = 0.022), and RA disease duration was associated with luminal volume (B 3.88 (95% CI 0.80, 6.97), p = 0.015). CONCLUSIONS: This study demonstrates the utility of carotid-MRI in RA, reporting an association between three-dimensional measures in particular and CV risk scores, individual traditional CV risk factors and RA disease duration. Carotid-MRI in RA is a promising research tool in the investigation of CVD.

Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis.

OBJECTIVE: Psoriasis and depression may have common mechanisms, such as systemic inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin D3 deficiency. Among men with psoriasis, this study examined whether depression severity was associated with serum concentrations of different metabolic and inflammatory markers. METHODS: The study included 85 men with psoriasis (mean age ± standard deviation [SD], 47 ± 14 years) and 65 men without psoriasis (mean age ± SD, 44 ± 13 years). In both groups, we measured the body mass index; blood pressure; and serum concentrations of lipids, uric acid, lipase, interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants completed the Beck Depression Inventory. Other variables analyzed included psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body surface area affected by psoriatic lesions. RESULTS: Compared with controls, patients with psoriasis had significantly greater depression severity, higher body mass indices, and higher serum concentrations of total cholesterol and interleukins 6 and 18; moreover, they had significantly lower serum 25-hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index, the percentage of body surface area affected by psoriatic lesions, and interleukin-18 concentration. In patients with psoriasis, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not correlate significantly with the serum concentrations of interleukin 6 and cortisol. CONCLUSIONS: High concentrations of interleukin 18 and low concentrations of 25-hydroxyvitamin D3 may be associated with depression severity in men with psoriasis. Thus, further studies should examine whether effective anti-inflammatory treatments or vitamin D3 supplementation can improve depression outcomes in these patients.

The New TLC Method for Separation and Determination of Multicomponent Mixtures of Plant Extracts.

The new mode of two-dimensional gradient thin layer chromatography (MGD-2D TLC) has been presented. Short distance development of sample in the first dimension leads to formation of the preconcentrated narrow zones. They are consecutively separated in the second dimension with the mobile phase gradient in several steps of development until the eluent reaches the further end of the chromatographic plate. The use of the above-mentioned technique allows isolating and then identifying the compounds of various polarity from the multicomponent mixture. The practical application of two-dimensional gradient thin layer chromatography has been performed for isolation of the two plant (Juniperus and Thymus) oils components as the examples of test mixtures. The experiments have been carried out with the use of silica gel plates as well as a normal phase condition. The results of solute separation with isocratic one-dimensional thin layer chromatography system have been compared with those of two-dimensional gradient system. It has been observed that application of the latter mode leads to almost triplicated number of zones in comparison with the former one. It is purposeful to apply the proposed mode to control the purity of the dominant component or components of the mixture.

Trichophyton mentagrophytes-associated Majocchi's granuloma treated with cryotherapy.

We here report the case of a woman with dermatophytosis of the thighs due to Trichophyton mentagrophytes where an unusual clinical picture posed considerable diagnostic and therapeutic problems. She presented numerous skin lesions located on the dorsolateral face of the left thigh and the medial surface of the right calf. The initial lesions consisted of small itchy pustules that evolved to exfoliation after scratching. Results of histopathologic examination ofa skin biopsy were consistent with dermatophytosis, although the negativity of PAS staining did not allow confirmation of this diagnosis. Direct microscopic examination with 10% KOH was negative; however, skin cultures on BioMerieux media revealed Tr. Mentagrophytes. Following the diagnosis of Trichophyton infection, the patient was treated with a combination of isoconazole nitrate and difluocortolone valerate. After therapy, both direct microscopic mycologic examination and culture on BioMerieux medium were negative; however, the lesions persisted, assuming a completely different aspect. Cryotherapy with liquid nitrogen was started. This led to a spectacular improvement: the surface of the skin became almost normal, merely showing slight discoloration. An unusual clinical presentation and non-responsiveness to treatment should prompt revision of the primary diagnosis. A negative result of direct microscopy should not exclude the diagnosis of dermatophytosis. Cryotherapy should be considered in cases that do not respond to conventional antifungal medication.

The effect of ursolic and oleanolic acids on human skin fibroblast cells.

In this article, we look at how ursolic and oleanolic acids can be used for the purpose of quality control of natural products used in dermatocosmetology as well as of various other therapeutic preparations. Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenes and they are constituents of many medicinal herbs. In this study, we analyzed the cytotoxic and anti-proliferative activity of OA and UA against normal human skin fibroblasts (HSF). Additionally, the scavenging activity of free radicals of both acids was analyzed. The sensitivity of cells to OA and UA activity was determined using a standard spectrophotometric (MTT) assay. The free radical scavenging activity of OA and UA was measured using the DPPH• test. The F-actin cytoskeletal proteins organization was analyzed using TRITC-phalloidine fluorescent staining. The cytotoxic activity of the analyzed acids was determined using Neutral Red (NR) uptake assay. Of the two isomeric compounds, UA showed a higher cytotoxic activity against HSF cells than did OA. Our investigations showed that OA, in view of its non-toxic nature, may be used as a supplementary factor for dermal preparations.

Effect of infliximab on the levels of TNF-alpha and TGF-beta in the whole blood cultures of irradiated patients.

TGF-beta is supposed to be the major cytokine responsible for post-radiation fibrosis of healthy tissues and actively modifies post-radiation changes. The growth of TGF-beta level induces the expression of collagen synthesis gene which triggers off the production of fibrosis of hyaline membranes. The main purpose of this study was to discover the way and methods of reducing post-radiation damage of normal tissues and provide an adequate scientific justification for using Infliximab as an effective radio protector in the neoplasm radiotherapy. A group of 97 patients were subjected to the experiment. Randomly selected patients were assigned to 3 groups according to the radiation exposure. The samples of whole blood were suspended in RPMI 1640 growth medium standardized according to the number of leukocytes. Two milliliters of whole blood was taken from each patient immediately before irradiation and 100 microl sample of the blood was placed in wells with 0.8 mg/ml of Infliximab or without the preparation. TGF-beta levels in blood culture without cA2 before irradiation showed continuous rise from 3978 to 8950 pg/ml at the 96th h. In the post irradiated group without cA2, a continuous growth was recorded till the 48th h (from 4758 to 13324 pg/ml at the 24th h) and then a slight decline to 11950 pg/ml at 96th h, respectively. In the cultures with cA2, TGF-beta levels before irradiation showed also the peak value at the 48th h (from 4050 to 7340 pg/ml at the 48th h) and then started to go down (6500 pg/ml at the 72nd h and 5720 pg/ml at the 96th h). In the post-irradiated group, during the first 6 hours, there was a growth from 4717 pg/ml to 7462 pg/ml, and then a paradoxical increase to 16885 pg/ml at the 12th h. From the 12th h the values started to decrease to 6895 pg/ml at the 96th h. The obtained results confirmed the hypothesis of decreasing the TGF-beta expression by inactivating TNF-alpha with a monoclonal antibody (Infliximab) in the patients' whole blood culture in vitro. These observations are a good starting point for further experiments in vitro and in vivo, whose main objective is to reduce post radiation fibrosis.

Comparison of selenium distribution in mice organs after the supplementation with inorganic and organic selenium compound selenosemicarbazide.

Studies on selenium organ content and its function in living organisms just like studies on other elements provide interesting results although their interpretation is not always clear. The aim of our study was to determine the concentration and distribution of selenium in several organs and tissues in mice after supplementation with our newly synthesized organic compound of selenium selenosemicarbazide (4-o-tolyl-selenosemicarbazide of o-chlorobenzoic acid) as compared to the effects of the supplementation with inorganic compounds. SWISS mice were fed with both types of compounds at the dose of 10(-3) g Se per kg for the period of 10 days. The concentrations of selenium in brains of mice treated with selenocarbazide and sodium selenite were higher than in controls (38.04 micrograms g-1 and 32.00 micrograms g-1 vs. 26.18 micrograms g-1). There was a statistically significant increase in the selenium contents in lungs after supplementation with selenosemicarbazide and sodium selenite (11.81 micrograms g-1 and 6.79 micrograms g-1 vs. 1.75 micrograms g-1 in controls). We found a statistically insignificant increase in selenium contents in intercostal muscles after supplementation with inorganic selenium compounds and a statistically significant increase after the supplementation with selenosemicarbazide (10.13 micrograms g-1; 14.21 micrograms g-1 and 28.84 micrograms g-1, respectively). Our investigations lead to a conclusion that 4-o-tolyl-seleno-semicarbazide of o-chlorobenzoic acid, an organic selenium compound may be more easily absorbed than inorganic sodium IV selenite.