Oxidative stress and metabolic biomarkers in patients with Psoriasis.

Background: Psoriasis is an autoinflammatory disease that affects not only skin but multiple organs thus being associated with many comorbidities. Oxidative stress and inflammation play the major role in the pathogenesis of this disease. Studies that examined by-products of oxidative stress in psoriasis show discrepant results. Hence, we aimed to examine the oxidative stress, inflammation and metabolic markers and to explore their potential relationship with disease severity in patients with psoriasis. Methods: This case-control study comprised of 35 patients with psoriasis and 35 age, sex and body mass index-matched healthy controls. Metabolic and oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), and catalase (CAT)] were measured. The principal component analysis (PCA) was employed to reduce the number of measured variables into smaller number of factors. PCA factors were subsequently used in logistic regression analysis for severe psoriasis prediction.

Comparative Analysis of Redox Homeostasis Biomarkers in Patients with Psoriasis and Atopic Dermatitis.

Aim: There are no studies regarding comparative analysis of serum biomarkers of oxidative stress in patients with psoriasis (PsO) and atopic dermatitis (AD). We aimed to compare the serum redox homeostasis parameters in patients with PsO vs. AD in an attempt to find the sensitive and specific oxidative stress biomarker that could best reflect the existence of one of these disease entities. Methods: Forty patients with PsO and forty patients with AD were consecutively included in this cross-sectional study. Parameters of redox homeostasis, i.e., pro-oxidants [malondialdehyde (MDA) and advanced oxidation protein products (AOPP)] and antioxidants [catalase (CAT) and superoxide dismutase (SOD)] were determined. Results: There was no difference in oxidative stress biomarkers between the PsO and AD group, except for higher CAT activity in the AD group (p < 0.001). Among all examined redox homeostasis biomarkers, ROC analysis showed that only CAT exhibited good diagnostic accuracy (AUC = 0.719) in the discrimination of patients with PsO vs. AD, with 0.436 U/L as the cut-off value of CAT activity. Conclusions: The CAT exhibited good diagnostic accuracy in the discrimination of patients with AD from those with PsO. The obtained results could suggest the importance of the use of antioxidants as a potential therapeutic strategy in the treatment of these two skin inflammatory diseases.

Comparative Study of Hematological Parameters and Biomarkers of Immunity and Inflammation in Patients with Psoriasis and Atopic Dermatitis.

Background and Objectives: There are no studies regarding comparative analysis of hematological parameters in patients with psoriasis (PsO) and atopic dermatitis (AD), whereas studies examining serum biomarkers of immunity and inflammation in these entities are scarce and contradictory. We aimed to compare such parameters in patients with PsO and AD. Materials and Methods: Patients with PsO (n = 40) and AD (n = 40) were consecutively included in this cross-sectional study. Hematological parameters and biomarkers of immunity and inflammation (interferon-gamma (IFN-γ), interleukine (IL)-22 and C-reactive protein (CRP)) were determined. Results: While the mean corpuscular volume (MCV) was higher in the PsO group vs. the AD group (p < 0.05), there was no difference in the other examined parameters between groups. A higher neutrophil-to-lymphocyte ratio (NLR) was found in patients with AD > 50 years vs. patients with PsO of similar age (p < 0.05). Higher IL-22 levels were found in patients with AD < 50 years vs. patients with PsO of similar age (p < 0.05). Lower IL-22 levels were found in patients with AD > 50 years vs. patients with AD < 50 years (p < 0.05). Patients with PsO and with comorbidities had lower platelets (PLT), plateletcrit (PCT) and platelet-to-lymphocyte ratio (PLR), whereas lymphocytes, red cell distribution width-to-PLT ratio (RPR) and mean platelet volume/PLT ratio (MPR) were higher vs. PsO patients without comorbidities. Patients with AD and with comorbidities had lower PCT and PLR, whereas RPR was higher vs. AD patients without comorbidities. Conclusions: A higher pro-inflammatory state (i.e., higher NLR and IL-22) was found in AD vs. PsO in age-specific groups. A higher pro-inflammatory state (i.e., as reflected by platelet indexes) was found in both diseases with comorbidities.

Cutaneous Manifestations of Tuberous Sclerosis.

Dear Editor, Tuberous sclerosis (TS) is an autosomal dominant multisystem disease, which occurs due to genetically determined hyperplasia of ectodermal and mesodermal cells. Clinical manifestations present on the skin and in the nervous system, kidneys, heart, and other organs. Recent studies estimate the incidence of TS at 1/6000 to 1/10,000 live births, and a prevalence in the general population of approximately 1 in 20,000 (1). There are two different genetic loci responsible for TS: 9q34 (TSC1-hamartin) and 16p13.3 (TSC2-tuberin) (2). Cutaneous manifestations occur in about 96% of patients (3). Neurological disorders occur in 50% of patients in the form of seizures and motor and psychomotor symptomatology (4). A 19-year-old male patient was hospitalized for clinical and diagnostic evaluation in February 2016 year in Clinic for Nephrology, Clinical Center of Montenegro, Podgorica, Montenegro. Polycystic kidney changes were verified by ultrasound when the patient was three years old, with the presence of several calcified nodules in lateral ventricles and supraventricularly in the brain as well as the existence of several hypopigmented maculae on the skin. During the last hospitalization in February 2016, the following tests were performed: cranial magnet resonance imaging (MRI) findings showed the existence of visible changes in the signal in the form of ectopic tuber tissue in the region of the cortex and subcortical white matter of the brain, but without neurological and psychomotor abnormalities; ultrasound of the urinary tract showed that both kidneys were enlarged with multiple cysts, with dominant cysts at the lower pole of the right kidney with a size of 55 mm and at the upper pole of the left kidney, approximately 40 mm. Reduced functional capacity of kidneys was found on dynamic scintigraphy, slightly more in the left kidney (41%) compared with the right (59%). Electroencephalography, X-ray of the lungs and heart, and echocardiography were also performed, but without any pathological findings. Dermatological examination found numerous fibroma up to 0.5 cm in diameter, the largest located nasolabially, periorally, and on the chin skin (Figure 1) at the age of seven, whereas a fibroma and several white maculae were present from birth on the skin of the forehead. They were now also present on the skin of the trunk and on the upper and lower extremities (Figure 2), accompanied by surrounding minor changes in the form of confetti-like maculae. A subungual fibroma was present on the third finger of the right hand. Collagen nevus (shagreen patch) (5), i.e. a subepidermal fibrosis as a mildly elevated, palm-sized area is also characteristic of TS, which is described in literature, in most cases in the lumbosacral region. In our case, such a fibrosis about 3 cm in diameter, and with the consistency of an orange peel, was discovered on the right shoulder. Subungual fibromas (Koenen tumors) (6), which can develop in adolescence, were present in our patient on the third finger of the right hand. The diagnosis of TS was established based on genetic testing, physical examination, ultrasound-verified polycystic kidney disease and reduced global renal functions, intracranial MRI, many hypomelanotic changes, and angiofibromas found with dermatological examination (7). There is no specific therapeutic approach for TS, and the treatment is symptomatic. Angiofibromas of the skin can be removed by dermabrasion or laser. Recent data show a good therapeutic effect of applying 0.1% rapamycin (8), which leads to a reduction of angiofibromas in patients with TS. On dermatological follow up after five weeks of application of tacrolimus, angiofibromas of the face were in regression. Some studies suggest the simultaneous topical applications of both of those drugs (9). In adolescents and adults of reproductive age, genetic counseling is recommended (10).

Morphometric analysis of the human anterior pituitary's folliculostellate cells during the aging process.

Folliculostellate cells represent non-endocrine cells of the anterior pituitary which influence the function of the endocrine cells via paracrine action. Though there is a lack of literature data on their presence during human aging, the aim of this research was to perform the quantification of anterior pituitary folliculostellate cells by the application of immunohistochemical and morphometric methods. The material for the study consisted of 15 anterior pituitaries taken from cadavers at routine autopsy. Their tissue was processed by standard histological procedure and the obtained histological slices were stained by S100 polyclonal antibody. Digital images of stained histological sections were analyzed by morphometric method with ImageJ system. The volume density of S100 positive cells was measured for each case. Results of morphometric and statistical analysis showed a significantly positive correlation between folliculostellate cell volume density and the age of the evaluated cases. Linear regression additionally showed that the age significantly predicts folliculostellate cells volume density in our sample. Further, all cases were classified into three age groups and One Way ANOVA showed that the volume density of folliculostellate cells was significantly higher only in the third age group in relation to the first and the second group, respectively. Volume densities of the first and the second age groups were not significantly different. So, the results of our study pointed to the conclusion that folliculostellate cells presence generally increases with age, but this increase is significant only in the oldest cases and might represent the modality of successful anterior pituitary aging.

[Patterns of lipofuscin accumulation in ganglionic nerve cells of superior cervical ganglion in humans].

BACKGROUND/AIM: Considering available literature lipofuscin is a classical age pigment of postmitotic cells, and a consistently recognized phenomenon in humans and animals. Lipofuscin accumulation is characteristic for nerve cells that are postmitotic. This research was focused on lipofuscin accumulation in ganglionic cells (GC) (postganglionic sympathetic cell bodies) of superior cervical ganglion in humans during ageing. METHODS: We analysed 30 ganglions from cadavers ranging from 20 to over 80 years of age. As material the tissue samples were used from the middle portion of the ganglion, which was separated from the surrounding tissue by the method of macrodissection. The tissue samples were routinely fixed in 10% neutral formalin and embedded in paraffin for classical histological analysis, then three consecutive (successive) sections 5 microm thick were made and stained with hematoxylin and eosin method (HE), silver impregnation technique by Masson Fontana and trichrome stain by Florantin. RESULTS: Immersion microscopy was used to analyse patterns of lipofuscin accumulation during ageing making possible to distinguish diffuse type (lipofuscin granules were irregularly distributed and non-confluent), unipolar type (lipofuscin granules were grouped at the end of the cell), bipolar type (lipofuscin granules were concentrated at the two opposite ends of a cell with the nucleus in between at the center of a cell), annular type (lipofuscin granules were in the shape of a complete or incomplete ring around the nucleus) and a cell completely filled with lipofuscin (two subtypes distinguishing, one with visible a nucleus, and the other with invisible one). Even at the age of 20 there were cells with lipofuscin granules accumulated in diffuse way, but in smaller numbers; the GC without lipofuscin were dominant. Growing older, especially above 60 years, all of the above mentioned patterns of lipofuscin accumulation were present with the evident increase in cells completely filled with lipofuscin, but cells without lipofuscin were also present even in the oldest persons. CONCLUSION: Lipofuscin is present in all periods of ageing with a different intensity of accumulation. GC without the pigment, diffusely distributed, as well as very rare cells with a unipolar type of lipofuscin distribution are characteristic for the age of 20-60 years. In the age above 60 years, except the cells without pigment and diffuse accumulation type, there are also bipolar and annular types and forms in which cells are completely filled with lipofuscin granules.

[Anatomohistological characteristics of Meckel's diverticulum in human fetuses].

BACKGROUND/AIM: Meckel's diverticulum (MD) is the most frequent anomaly of the small intestine. It appears after incomplete obliteration of the omphalomesenteric or viteline duct which normaly obliterates and disappears by the 9th week of gestation. The majority of MD do not give rise to any clinical symptoms and are encounted either incidentally, at examination or intervention, or due to complications which may occur (obstruction, hemorrhagy, rupture), and are described in many clinical reports. The aim of the study was to find out the incidence of MD in fetuses when the development of the alimentary tract is already finished. METHODS: The investigation was performed on 150 human fetuses of different sex and gastational age, using microdissection method. The cases with MD were photographed, described, their positions and dimensions were registered. The samples of MD taken for histological investigation were dyed with hematoksilin eosin method. RESULTS: Meckel's diverticulum was found in five fatuses (three male and two female); in one case the fibrous band was found. All of them were located on animesenteric margine of the small intestine at the average distance of 92.5 mm from the ileocecal junction. They were of different shape and dimensions, but of the normal constitution of the small intestine. CONCLUSION: The incidence of MD was 3.3%, and 4% of all the anomalies of the intestines connected to the disappearance of the viteline duct. It was more frequent in the male, located on antimesenteric margine of the small intestine, at the destination which highly correlated to the age of the fetus. Meckel's diverticule were of different shapes and dimensions but of the typical constitution of the small intestine.