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Lupus erythematosus is an autoimmune connective tissue disorder showing a broad spectrum of clinical manifestations.

Erythema multiforme (EM) is an acute immune-mediated disease with multifactor etiology, which presents with symmetric target-like lesions on the skin. Probably the most common etiological factor of EM is viral infections, particularly herpes simplex virus (HSV). Herpes-associated erythema multiforme (HAEM) is an acute exudative dermatosis, caused mostly by HSV-1 and much rarely by HSV-2. A 44-year-old female patient with herpes associated erythema multiforme was consulted with initial appearance of typical target lesions on the dorsal surface of both hands, after long history of labial herpes episodes. The diagnostic algorithm included routine laboratory tests, histological examination and serologic test for HSV-1 and 2. Our first choice of treatment was acyclovir 5 x 200 mg/24 h and dexamethasone 4 mg/24 h, however due to increased anxiety and tachycardia reported by patient the corticosteroid therapy was discontinued and promethazine was initiated. The patient responded well to the therapeutic regimen and at the follow-up visit was in clinical remission. In conclusion, the diagnosis of HAEM is mainly clinical, when the patient develops target lesions and coexisting HSV infection is detected.

Graham-Little-Piccardi-Lassueur syndrome (GLPLS) is a rare syndrome characterized by the triad of cicatricial alopecia of the scalp, non-cicatricial alopecia of the axilla and groin and follicular lichen planus eruptions on the trunk and extremities. GLPLS is considered to be a variant of lichen planopilaris. We report two cases that have fulfilled all of the criteria for GLPLS. The first case was a 71-year-old woman, admitted to the Department of Dermatology for pruritic perifollicullar erythema and scaling of the scalp, cicatricial scalp alopecia and hair loss of the axilla and pubic region for five months. Subsequently, follicular hyperkeratotic eruptions and hyperpigmented macules on the skin of the chest and abdomen appeared. The second case was a 48-year-old man with pruritic follicular papules on the face, trunk and extremities for four months. All of the laboratory examinations in both patients were within normal limits. No alternation in the general condition of the patients was observed. Histological examinations in both patients confirmed the diagnosis GLPLS. The patients were treated with systemic and local corticosteroid resulting in marked improvement of the skin lesions; however, cicatricial scalp alopecia showed no response to the treatment.

Neurofibromatosis type I is an autosomal dominant genetic disorder with an incidence of about 1 in 3000 births. Apart from the typical skin involvement NF1 may affect multiple organs with ocular, neurological, skeletal and cardiovascular manifestations. We present a case of a 38-year-old man with multiple café-au-lait macules and hundreds of neurofibromas disseminated on the trunk and extremities dating from childhood. To establish the diagnosis and to exclude any complications we performed multiple examinations, including skin biopsy, laboratory investigations, ophthalmologic assessment, consultations with a neurologist, internist and orthopedist, etc. The treatment of cutaneous NF1 is mainly symptomatic. Surgical excision aims to achieve cosmetic results. Recently novel and perspective conservative therapies have been investigated. In order to ensure better outcome for the patients with NF1 long-term multi-disciplinary approach is advised.

The group of congenital limb overgrowth syndromes associated with vascular malformations include various disorders, often with variable clinical expression. Klippel-Trenaunay syndrome is the most common syndrome in this group, compared to other similar disorders such as Proteus, Parkes-Weber, Sturge-Weber, Cobb, Maffucii and CLOVES syndromes. We present a case of a 55-year-old male who presented with swelling, pain, heaviness, numbness and increased local temperature, involving the right upper extremity and the right side of the chest wall and associated with a livid erythema. The patient had several comorbidities including arterial hypertension and ischemic heart disease. He also had a family history of diabetes mellitus. A multidisciplinary team-based treatment approach, including physicians with expertise in various medical and surgical specialties was applied with the patient being “the unifying focus” of all these experts and their efforts. A personal approach tailored to the patient’s preferences was the key to a successful treatment.

The aim of the study was to develop a molecular diagnosis protocol of monocytic ehrlichiosis and granulocytic anaplasmosis in dogs by conventional polymerase chain reaction (PCR) and to compare the results from PCR and a rapid serological test. One hundred and six blood samples from dogs were tested by the rapid serological test SNAP 4Dx Plus (IDEXX Laboratories, Westbrook, ME) and by conventional PCR. Sixty-two of them (58.49%) were positive for antibodies to Ehrlichia canis/Ehrlichia ewingii and 14 (13.21%) for antibodies to Anaplasma phagocytophilum/Anaplasma platys. In 24 (22.64%) blood samples, antibodies against both pathogens were simultaneously detected. Six (5.66%) samples were seronegative. Fourty-six of the 106 tested samples (43.4%) were positive for a 345 bp segment of the ribosomal gene of family Anaplasmataceae. In 28 of them the presence of a 444 bp fragment of the ankA gene of A. phagocytophilum was detected, and in 26: a 409 bp fragment of the gene of E. canis. Nine samples were simultaneously positive for genetic sequences of E. canis and A. phagocytophilum. The target DNA fragments specific for the two studied pathogens were not detected in one of the Anaplasmataceae-positive samples. In the remaining 60 cases (56.6%), the presence of a 345 bp segment of the ribosomal gene was not detected. In the present study, the DNA of E. canis and of A. phagocytophilum was detected for the first time in Bulgarian dogs by the conventional PCR. [ABSTRACT FROM AUTHOR]

The changes in cognitive functions that occur with aging and in various pathological conditions are a subject of growing interest. Experimental and clinical data justify the hypothesis about the influence the immune system exerts on cognitive processes. The balance between pro-inflammatory and anti-inflammatory cytokines has been established as a necessary factor for normal cognitive functioning. Cytokine production is under strong genetic control and various single nucleotide polymorphisms (SNPs) in cytokine genes have been described. As cytokine SNPs have been demonstrated to affect the gene expression or the functional activity of the immune protein this logically led to the suggestion about the role of these polymorphisms in cognitive functioning. Studies exploring the association between different genetic variants of cytokine gene polymorphisms and cognitive abilities in healthy subjects and in demented patients show divergent results. The review of relevant literature suggests that SNPs implement their effect on cognition in large interactions with each other, as well as with many other factors, some of which still remain to be identified. This article summarizes the contemporary knowledge about the correlations between SNPs in cytokine genes and cognitive status in humans. Further research is needed to determine the precise role and the molecular mechanisms of action of the SNPs in cognitive processes.

PURPOSE: Atopic dermatitis (AD) is an immune-mediated disease which usually begins during the childhood. The major regulators of Th1/Th2 balance are cytokines and T-regulatory cells. The aim of the present study was to compare gene expression profiles in children and adults with AD. METHODS: Total RNA was isolated from blood samples of 19 AD patients composed of 6 children and 13 adult AD patients. We analyzed the gene expression of IL12A, IL12B, IL23A, IL10 and Foxp3 mRNA in patients' blood, by quantitative real-time PCR. Relative quantitative evaluation of mRNAs was performed by the comparative ΔΔCt method. RESULTS: The gene expression, on mRNA level, of all investigated genes was higher in children than in adult AD patients. However, the major result from this study is that IL12A (RQ=4.14; p=0.0029), IL23A (RQ=3.53; p=0.006), and Foxp3 (RQ=3.51;p=0.023) mRNAs are significantly increased in children's blood compared to adult AD patients, in contrast to IL12B and IL10 mRNAs. CONCLUSION: On the basis of these preliminary results, we could conclude that the altered Th1/Th2 cytokine balance in AD depends on the age of patients. Our results demonstrated that IL- 12p70, IL-23 and Treg cells could play different roles in pathogenesis of atopic dermatitis in younger compared to older ages. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of type 1 diabetes (T1D), as an autoimmune and multifactorial disease, depends on both environmental and genetic factors.Methods: This study investigates the distribution of the 3'UTR polymorphism of IL12B in 51 diabetic Bulgarian children stratified by age of diagnosis and its influence on IL-12p40 serum levels. The quantity of serum IL-12p40 was detected by ELISA and the genotyping was performed by PCR-RFLP.Results: Significantly-higher frequency of C allele was observed in patients diagnosed at greater than 12 years of age (0.50) compared with patients with early onset of T1D (0.22 and 0.25) and controls (0.24). Strongly-elevated serum IL-12p40 was observed in patients (245.6 +/- 100 pg/mL) than in healthy children (58.5 +/- 17.3pg/mL; p=0.0001) and adults (72.2 +/- 31 pg/mL; p=0.0001), independently of 3'UTR polymorphism in IL12B and age of diagnosis.Conclusion: Our data suggests that 3'UTR polymorphism in IL12B was not associated with Ti D susceptibility or IL-12p40 serum level, but carrying of variant allele may contribute to late onset of disease. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients’ quality of life, independently from the course and phase of the disease.

Background. Psoriasis impairs the quality of life (QoL) of patients as is in such severe diseases as cardiac failure or some malignant diseases. The aim of the study was to assess the QoL of Bulgarian psoriasis patients and its dynamics after different treatment approaches. Material and methods. The study was conducted in 93 patients (55 men and 38 women), mean age 45 years. The patients were divided in 3 groups: group of patients with psoriasis placata and group of patients with psoriasis palmoplantaris, both undergoing combined climatotherapy and a control group of patients with psoriasis placata undergoing Narrow Band Ultraviolet B phototherapy (NB UVB). The combined climatotherapy was performed in the "Tuzlata" rehabilitation hospital, Balchik, Bulgaria and included thalassotherapy, peloidotherapy and balneotherapy. We used the Dermatology Quality of Life Index (DQLI) questionnaire to assess the QoL of the patients before and after the treatment. Results. The improvement of the QoL in patients with psoriasis placata undergoing combined climatotherapy was statistically higher compared to the patients undergoing NB UVB phototherapy. The improvement in the QoL of the patients with psoriasis placata undergoing combined climatotherapy was statistically significant compared to the patients with psoriasis palmoplantaris undergoing the same treatment. There was no statistically significant difference in the improvement of the QoL between the patients with and without comorbidities. Conclusion. Our results suggest that the combined climatotherapy has better beneficial effect on the QoL of the patients with psoriasis. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the association between serum levels of IL-12p40 and IL-10 and progression of the colorectal cancer (CRC). An association between severity of CRC and serum levels of investigated cytokines was observed. IL-12p40 was in the highest level in stage-I (423.6±224.7pg/ml) compared to more severe stages. In the opposite direction were the data for immunosuppressive cytokine, IL-10. Patients with stage-IV had the highest level of IL-10 (36.02±9.5pg/ml). On the basis of our results we could conclude that IL-12p40 and IL-10 serum levels were inversely associated with tumour progression. More severe stages of CRC are characterized by low IL-12p40 and high IL-10 serum levels. [ABSTRACT FROM AUTHOR]

Infection of dogs with the tick-borne rickettsiae Ehrlichia and Anaplasma provokes an immune response mediating the pathology and bacterial resistance. IL-10 is the main anti-inflammatory cytokine and plays a multifaceted role in host protection. The study aimed to investigate circulating IL-10 in 32 dogs naturally infected with A. phagocytophilum and E. canis , identified by PCR positivity, and 33 PCR-negative animals which tested positive for antibodies against these pathogens, as well as 22 healthy animals. The highest quantity of IL-10, measured by ELISA, was observed among dogs positive simultaneously for anti- E. canis and anti-A. phagocytophilum IgG antibodies, followed by dogs positive for anti- E. canis only. The concentration of IL-10 in PCR-positive dogs was almost three and a half times higher than that measured in the control group (77.09 ± 23.61 pg./mL vs. 21.55 ± 4.61 pg./mL; p = 0.0015) and five times higher than the concentration of interleukin in PCR-negative animals (77.09 ± 23.61 pg./mL vs. 14.86 ± 3.01 pg./mL; p = 0.000016). The highest level of IL-10 was observed in PCR-positive dogs with mixed infection (120.54 ± 44.18), followed by the level in PCR-positive dogs for E. canis only (78.81 ± 16.92). The lowest level of IL-10 was observed in PCR-positive dogs for A. phagocytophilum only (56.32 ± 12.68). We may suggest that infection with E. canis and A. phagocytophilum stimulates the IL-10 production in dogs, which may facilitate specific antibody responses.

We aimed to investigate the expression of pro-inflammatory cytokine genes TNFA , IL6 , IL12B , IL23 , IL18 and immunoregulatory genes FOXP3 , TGFB1 , and IL10 in the peripheral blood of patients with rheumatoid arthritis (RA) at messenger ribonucleic acid (mRNA) level. The total RNA was isolated from peripheral blood samples. Real-time quantitative PCR was used to perform TaqMan-based assays to quantify mRNAs from 8 target genes. IL23A was upregulated (1.7-fold), whereas IL6 (5-fold), FOXP3 (4-fold), and IL12B (2.56-fold) were downregulated in patients compared to controls. In addition, we found a strong positive correlation between the expression of FOXP3 and TNFA and a moderate correlation between FOXP3 and TGFB1. These data showed the imbalance of the T helper (Th) 1/Th17/ T regulatory (Treg) axis at a systemic level in RA. In cases with active disease, the IL10 gene expression was approximately 2-fold higher; in contrast, the expression of FOXP3 was significantly decreased (3.38-fold). The main part of patients with higher disease activity expressed upregulation of IL10 and downregulation of TNFA . Different disease activity cohorts could be separated based on IL10 , TNFA and IL12B expression combinations. In conclusion, our results showed that active disease is associated with an elevated IL10 and lower TNFA mRNA level in peripheral blood cells of RA patients.

The aim of the study was to determine prevalence of Anaplasmataceae -infected ticks in the Black Sea Coast and the Pleven regions of Bulgaria. A total of 350 ticks from different tick species were collected. Two hundred fifty-five ticks were removed from dogs in the Black Sea Coast region, and 95 Ixodes ricinus ticks were collected by flagging vegetation with a white flannel cloth in two areas in the region of Pleven. After the DNA isolation of the ticks, a genus-specific polymerase chain reaction (PCR) was performed to identify Anaplasmataceae. Second PCRs were performed with species-specific primers to identify Ehrlichia canis ( E. canis ) and Anaplasma phagocytophilum ( A. phagocytophilum ). The results showed that 26.9% of the Ixodes ricinus ticks were infected with Anaplasmataceae in the Black Sea Coast region and 36.8% in the Pleven region. The infection with E. canis was detected in 35.7% and A. phagocytophilum in 25.0% of positive ticks from the Black Sea Coast region. In the Pleven region, 22.9% of ticks were positive for E. canis , while 42.9% were positive for A. phagocytophilum . The molecular identification of E. canis in ticks collected from Bulgaria was performed for the first time. In conclusion, the present study revealed a higher prevalence of ticks infected with Anaplasmataceae , particularly A. phagocytophilum , in the Pleven region than in the Black Sea Coast region.

Acquiring adequate sensory information and using it to provide motor control are important issues in the process of creating walking robots. The objective of this article is to present control algorithms for the optimization of the walking cycle of an innovative walking robot named "Big Foot". The construction of the robot is based on minimalist design principles-only two motors are used, with which Big Foot can walk and even overcome obstacles. It is equipped with different types of sensors, with some of them providing information necessary for the realization of an optimized walk cycle. We examine two laws of motion-sinusoidal and polynomial-where we compare the results with constant angular velocity motion. Both proposed laws try to find balance between minimizing shock loads and maximizing walking speed for a given motor power. Experimental results are derived with the help of a 3D-printed working prototype of the robot, with the correct realization of the laws of motion being ensured by the use of a PD controller receiving data from motor encoders and tactile sensors. The experimental results validate the proposed laws of motion and the results can be applied to other walking robots with similar construction.

In our study, we focused on the role of the immunosuppressive cytokines TGF-β1 and IL-10 in RA and, in particular, the influence of the IL10 -1082 A/G (rs1800896) and TGFB1 -509C/T (rs1800469) promoter polymorphisms on their levels as a prerequisite for RA and disease activity clinical features. We found significantly higher IL-10 and lower TGF-β1 serum levels in women with RA than in controls. Patients who carried the -1082AA and AG genotypes had significantly higher levels of lnIL-10 compared to GG in contrast to healthy women carrying the same genotypes. The heterozygous -1082AG genotype was less frequent in RA cases (45.4%) than in healthy women (56.1%) and could be a protective factor for RA development (over-dominant model, OR = 0.66 95% CI 0.38-1.57). In addition, RA patients carrying the heterozygous -1082AG genotype were less likely to be anti-CCP positive than those carrying the homozygous AA/GG genotypes (37.1% vs. 62.9%; OR = 0.495. 95% CI 0.238-1.029, p = 0.058). There was no association between TGFB1 -509C/T SNP and susceptibility to RA and no relation between systemic TGF-β1 levels and rs1800469 genotypes. In conclusion, the IL10-1082 genotypes affect the serum levels of IL-10 in women with RA in a different way from that in healthy women and appear to play a role in the genetic predisposition and autoantibody production in the Bulgarian population.

Aortoiliac occlusive disease (AIOD) is non-inflammatory obstructive vasculopathy commonly affecting patients with advanced atherosclerosis, diabetes mellitus, or elevated cholesterol levels, and subjects with other risk factors such as cigarette smoking.Two Caucasian patients (a 55-year-old woman and a 56-year-old man), with ulcerous cutaneous lesions of AIOD are reported. In both cases, medical history comprises initial lower limb claudication, multiple painful ulcers along the legs and absence of superficial femoral artery pulse. Severe obstruction of both infrarenal aorta and iliac arteries on the left side was demonstrated by contrast angiography and Doppler ultrasonography.The evolution of the disease showed some characteristic findings, including pyoderma gangrenosum-like ulcerations as the initial cutaneous manifestation of AIOD, multiple painful ulcers along the lower extremities, and aorto-iliac occlusive disease due to atherosclerosis.Early diagnosis and surgical reconstruction of vessels in patients with AIOD improved quality of life and limb salvage rates., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the naked eye. Recently, it gained popularity for evaluation of inflammatory skin conditions. In the field of connective tissue diseases, dermoscopy has been used mainly as a simple and accessible substitute of nailfold capillaroscopy., Objectives: The aim of the present study is to expand the application of dermoscopy in patients with dermatomyositis (DM) beyond the usual nailfold examination. A clinico-dermoscopic correlation between clinical signs of skin affection and dermoscopic features is also suggested., Methods: A total of 29 patients with DM were enrolled in this descriptive prospective study, conducted over a 3-year period. Dermoscopy was performed by a DermLite DL1 dermatoscope on polarization mode, attached to One Plus 3T camera. The following skin lesions were examined: periungual affection, scalp DM, Gottron papules, palmar papules, poikiloderma and auricular changes., Results: Dermoscopy detected predominantly advanced nail fold capillary changes - giant capillaries (79%), microhemorrhages (46%) and avascular areas (25%). The most prevalent trichoscopic features were enlarged tortuous capillaries (64%), interfollicular scales (50%) and peripilar casts and tufting (36%). Among the other skin lesions assessed in this study - Gottron papules were present in 20 patients, poikiloderma in 11, palmar papules in 4 and auricular lesions in 4 patients., Conclusions: The use of dermoscopy for clinical evaluation of skin lesions in DM enhances diagnostic accuracy and elucidates poorly known characteristics of the disease., Competing Interests: Competing interests: None., (©2022 Pozharashka et al.)

We aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04-175.3] vs 4.64 pg/ml [2.95-13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients' subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients., (© 2021. The Author(s).)

Background: The connection between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is well-established, as persistent intestinal inflammation plays a substantial role in both disorders. Cytokines may further influence the inflammation and the carcinogenesis process., Aim: To compare cytokine patterns of active IBD patients with early and advanced CRC., Methods: Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior, in colon specimens, as mRNA biomarkers, and their serum protein levels., Results: We found a significant difference between higher gene expression of FoxP3 , TGFb1 , IL-10 , and IL-23 , and approximately equal level of IL-6 in CRC patients in comparison with IBD patients. After stratification of CRC patients, we found a significant difference in FoxP3 , IL-10 , IL-23 , and IL-17A mRNA in early cases compared to IBD, and IL-23 alone in advanced CRC. The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients., Conclusion: Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes ( TGFb1, IL-10, IL-23 , and transcription factor FoxP3 ) is a crucial primarily for CRC development. The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

It is widely known that sporadic colorectal cancer (CRC) is age-related diseases with higher incidence rate among men. Transforming growth factor-β1 (TGF-β1) is a major immune regulatory cytokine with a great impact and dual role in gastrointestinal carcinogenesis. In this context, the aim of the study was to explore the role of circulating TGF-β1 and the -509C/T functional promoter polymorphism (rs1800469) within the TGF-β1 gene (TGFB1) in the susceptibility, progression, and prognosis of CRC among Bulgarian male and female patients. Patients with sporadic CRC and healthy controls were genotyped by polymerase-chain reaction-restriction fragment length polymorphism. Serum TGF-β1 levels before and after curative surgery were determined by ELISA. Total RNA was extracted from paired tumor, normal mucosa and distant metastasis samples and was used for quantitative detection of TGFB1 mRNA by TaqMan qPCR.We observed that TGF-β1 serum levels depend on the -509C/T genotype in combination with gender. TGF-β1 serum levels in CRC patients were decreased compared to controls, but statistical significance was reached only for men. In the stratified analysis by gender and genotype, a significant association was found for the CC genotype. Overall, our results indicate that the -509C allele increased the cancer risk, particularly for advanced stages (OR = 1.477; p = 0.029). The results from the relative mRNA quantification showed a significant upregulation of TGFB1 in distant metastases compared to primary tumor tissues and higher TGFB1 mRNA levels in men (RQ = 4.959; p = 0.022). In conclusion, we present data that diminished circulating TGF-β1 due to the CC genotype could be a possible risk factor for tumor susceptibility and progression. This association is more pronounced in males than in females. Colorectal cancer tissue expression of TGFB1 gene mRNA correlates with tumor progression and metastasis., Competing Interests: The authors have declared that no competing interests exist.

Aim of the Study: The ability of immune cells in peripheral blood to produce certain cytokines affects tumour-elicited inflammation. The aim of this study was to investigate the gene expression of interleukin 12A (IL-12A), IL-12B, IL-23A, IL-10, IL-6, transforming growth factor β (TGF-β), HDAC3, and iNOS in peripheral blood mononuclear cells (PBMC) from colorectal cancer (CRC) patients., Material and Methods: The venous blood for PBMC isolation was collected preoperatively and 10 days after surgery, from CRC patients. After isolation of total RNA and synthesis of cDNA, quantitative real-time PCR assays were performed., Results: Our results demonstrated that among investigated cytokine genes IL-10 and TGF-β were significantly upregulated in patients with CRC compared to the control group, while the expression of IL-23 mRNA was significantly decreased in CRC patients. We observed significantly increased mRNA levels in CRC patients' PBMC before surgery for IL-10 and TGF-β compared to both postoperative and control groups. We also found a significant upregulation of iNOS in early compared to advanced CRC., Conclusions: Based on the results we can assume that PBMC gene expression programming in CRC patients drives local differentiation of Th cells towards Treg instead of the Th1 anti-tumour subpopulation.

Colorectal cancer (CRC) development is strongly associated with innate immune mechanisms and intestinal inflammation. The aim of the study was to investigate the pre-operative serum levels of TNF-α and its correlation with cancer progression and survival in CRC patients taking into account the genotype of -308G/A promoter polymorphism in TNF-α gene (rs1800629). TNF-α -308G/A genotypes of 119 CRC cases and 177 no CRC controls were determined by restriction fragment length polymorphism assay (RFLP-PCR). TNF-α serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Although no significant differences in allele and genotype frequencies between CRC and controls were observed, it should be noted that the minor allele-A and its homozygous genotype were overrepresented among CRC. In addition, allele-A was more frequent in early CRC patients compared to advanced cases. TNF-α serum level was significantly higher in CRC patients than in controls (36.1 ± 8.4 pg/mL vs. 18.66 ± 11 pg/mL; p = 0.0000001). In the subgroup analysis by tumour-node-metastasis stages, the highest TNF-α level was found in stage IV (42.7 ± 12.5 pg/mL) and was significantly elevated compared to earlier stages of CRC and controls. The survival rate of CRC patients with low TNF-α serum level, estimated as median survival, was significantly higher than that of patients with high levels of TNF-α (38.4 vs. 7.761 months; log rank test p = 0.00015) In conclusion, we can affirm that TNF-α affects tumour development along with disease progression which has an impact on the survival of CRC.

Introduction: Polyamines - putrescine, spermidine and spermine are polycationic compounds ubiquitous for all living organisms. They are essential for the cell growth and differentiation, the control of cell cycle progress, apoptosis, and cancerogenesis. Accumulated scientific evidence suggests the central role of polyamines in the process of keratinocytic proliferation, differentiation, and regulation., Objective: To elucidate the polyamine metabolic changes that occur in benign keratinocytic proliferation. Fifty eight patients were enrolled in the study, 31 with plaque-form of psoriasis vulgaris, which had been referred to as a model of benign keratinocytic proliferation, and 27-healthy controls., Materials and Methods: An original, innovative chromatographic method was used to detect the levels of putrescine, spermidine, and spermine in all skin samples., Results: Were significantly proven (P < 0.05). No difference was found between the polyamines levels of non-lesional psoriatic skin and healthy controls. Psoriatic lesions showed a two-time higher concentration of all polyamines in lesional, compared to non-lesional skin. Spermine had the highest concentration and highest proliferation trend, which demonstrated the importance of propylamine synthesis in the pathogenesis of psoriasis. Spermine highest concentrations suggested the leading role of adenosine methionine decarboxylase (AMDC) in the pathogenesis of benign keratinocytic proliferations., Conclusions: Non-lesional skin in psoriatic patients did not show latent changes in polyamine metabolism. Psoriatic lesions demontrated two-time higher levels of the most essential biogenic polyamines compared to healthy controls. The highest level of spermine proved the crucial role of AMDC in the polyamine metabolism changes in psoriasis. Future therapeutic approaches should be focused on reduction of exogenic spermine intake, utilizing new spermine blockers, and synthesis of AMDC inhibitors.

Perforating necrobiosis lipoidica is a very rare clinical variant which consists of degeneration and transepidermal elimination of the collagen with few cases reported in the literature. In two-thirds of the patients it associates with diabetes, with no relation with the glucose control. We present a 42-year-old female patient with a 7-year history of diabetes on insulin therapy, referred to our clinic with a 3-year history of multiple asymptomatic firm plaques disseminated on the upper and lower extremities. The clinical and histological findings proved the diagnosis of perforating necrobiosis lipoidica.

Introduction: Polyamines (putrescine, spermidine, and spermine) are polycationic compounds that play a central role in keratinocytic proliferation, differentiation, and regulation. The objective was to elucidate the polyamine metabolic changes that occur in various benign and neoplastic skin proliferations., Methods: The study included 58 patients: 31 with the plaque form of psoriasis vulgaris and 27 with non-melanoma skin tumors. The levels of putrescine, spermidine, and spermine were detected in lesional and non-lesional skin samples., Results: Findings were representative (p < 0.05). Psoriatic lesions showed a twofold elevation of all polyamines in lesional skin compared to non-lesional skin. Spermine had the highest concentration, which suggested a leading position of propylamine synthesis in psoriatic pathogenesis. Results on the polyamine metabolism of basal cell carcinoma represented basic characteristics similar to those of psoriasis. Conversely, squamous-cell carcinoma lesions showed the highest concentration of putrescine, suggesting a crucial role of spermidine-spermine acetyltransferase in their pathogenesis., Discussion: Our findings showed different polyamine metabolic changes in lesions from benign and neoplastic keratinocytic proliferations. Basal-cell carcinoma polyamine metabolism revealed a closer relationship to psoriasis than to squamous-cell carcinoma, which might explain its long-term benign course and non-metastatic nature.

Keratosis palmoplantaris varians of Wachters is a rare autosomal dominant disorder. A 17-year-old boy with characteristic clinical and histopathologic findings of 10 years' duration is described. He displayed yellowish patchy and linear hyperkeratoses of the palms and nummular keratoses on the soles that were symmetrical and often confluent, specifically on the pressure points. Because there was no family history of a similar pattern, he probably represented an isolated case in his family. The typical clinical presentation, differential diagnosis, and classification of hereditary palmoplantar keratoses are discussed.

Introduction: Cytokines have been suggested to both modulate anti-tumor responses and promote tumor growth., Materials and Methods: We analyzed the expression of pro-inflammatory IL-12p35, IL-12p40, IL-23p19, anti-inflammatory IL-10, antiapoptotic factor survivin, and transcription factors-RelA, c-Jun, and Foxp3 mRNA in patients' blood, colon carcinoma tissue, and in normal mucosal tissue by real-time polymerase chain reaction. The quantity determination of serum IL-12p40, IL-23, and IL-10 was performed by enzyme-linked immunosorbent assay., Results: We observed significantly higher levels in patients for all three analyzed cytokines, with IL-23 concentration change being the highest. We detected the greatest upregulation of IL-23p19, Foxp3 and survivin mRNA in colorectal carcinomas than normal mucosa. A statistically significant upregulation of IL-12p40, IL-10, and c-Jun mRNA but not for IL-12p35 and RelA mRNA in tumor tissue comparing to normal tissue was also established., Conclusions: In conclusion, we show a characteristic gene expression profile combining markers associated with inhibition of anti-tumor immune response (Foxp3, IL-10), inhibition of apoptosis (survivin), and induction of the cytokines with protumoral activity as IL-12p40 and IL-23p19 (IL-23) in the colorectal tumor tissue but not in peripheral blood of patients.

Background and Aims: Etiologically, the sporadic colorectal cancer (CRC) is a complex and multifactorial disease that is linked to both exogenic and endogenic factors. Accumulating evidence indicates that susceptibility to cancers, including CRC, is mediated by genetically determined differences in the effectiveness of detoxification of potential carcinogens. A member of the glutathione-S-transferase (GST) family, GSTP1, is an important candidate for involvement in susceptibility to carcinogen-associated CRC. An A-->G transition in exon 5 of the GSTP1 gene resulting in Ile(105)Val amino acid substitution has been identified. This change leads to alteration in catalytic efficiency of variant enzyme. The aim of the current study was to evaluate the influence of Ile(105)Val GSTP1 polymorphism on susceptibility to CRC., Materials and Methods: The GSTP1 genotyping was conducted in a case-control study of 80 ethnic Bulgarian CRC patients and 126 unaffected controls using polymerase chain reaction restriction fragment length polymorphism method., Results: A statistically significant case-control difference in genotype frequencies was observed: 0.69 vs 0.54 for Ile/Ile, 0.22 vs 0.39 for Ile/Val, and 0.09 vs 0.07 for Val/Val (p = 0.049). The odds ratio (OR) for Val/Val was close to 1 (0.96, 95%CI: 0.35-2.66, p = 0.942), whereas the OR for Ile/Val was significantly lower, 0.45 (95%CI: 0.24-0.86, p = 0.016), compared to the referent Ile/Ile genotype. Although a prevalence of the GSTP1 variant allele-containing genotypes (Ile/Val or Val/Val) was found in controls than in patients (OR = 0.53, 95%CI: 0.30-0.96, p = 0.035), the allele frequencies did not show significant difference between cases and controls (p = 0.127)., Conclusions: Based on the obtained protective effect of Ile/Val GSTP1 genotype, we could suggest that Ile(105)Val GSTP1 polymorphism may play some role in susceptibility to CRC.