Anna Wojas-Pelc

Topical taurine bromamine, a new candidate in the treatment of moderate inflammatory acne vulgaris – A pilot study

Taurine bromamine (TauBr), the product of taurine and hypobromous acid (HOBr), exerts anti-inflammatory and antibacterial properties. Recently we have shown that Propionibacterium acnes, a potential pathogenic agent of acne, is extremely sensitive to TauBr. As topical antibiotics are associated with the emergence of resistant bacteria, TauBr seems to be a good candidate for topical therapy for acne vulgaris. In our double blind investigation, the efficacy and safety of 3.5 mM TauBr cream was evaluated. 1% Clindamycin gel (Clindacin T), one of the most common topical agents in the treatment of acne vulgaris, was used as a control. Forty patients with mild to moderate inflammatory facial acne vulgaris were randomly treated with either TauBr or clindamycin for 6 weeks, twice-a-day. More than 80% of the patients markedly improved with both treatments, without any adverse effects observed. Both TauBr and clindamycin produced a significant reduction in inflammatory skin lesion counts (papules/ pustules). After 6 weeks, comparable reductions of acne lesions, 65% and 68%, were observed in the TauBr and clindamycin groups, respectively. In conclusion, these data support our concept that TauBr can be used as a topical agent in the treatment of acne vulgaris, especially in patients who have already developed antibiotic resistance.

What is a role of haeme oxygenase-1 in psoriasis? Current concepts of pathogenesis

The skin is constantly exposed to endogenous and environmental pro‐oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro‐oxidant agents, show strong expression of ROS‐detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO‐1, constitutive HO‐2 and HO‐3) is the rate‐limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO‐1 is a stress‐responsive protein whose expression is induced by various oxidative agents. HO‐1 is known for its cytoprotective, antioxidant and anti‐inflammatory properties. Interestingly, a strong overexpression of HO‐1 was observed in psoriatic skin. However, the role of HO‐1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO‐1 in skin inflammation to show the relationships between HO‐1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO‐1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions.

Cyclin D1 and D3 expression in melanocytic skin lesions

Cyclins, cyclin-dependent kinases, as well as proteins cooperating with them are responsible for cell cycle regulation which is crucial for normal development, injury repair, and tumorigenesis. D-type cyclins regulate G1 cell cycle progression by enhancing the activities of cyclin-dependent kinases, and their expression is frequently altered in tumors. Disturbances in cyclin expression were also reported in melanocytic skin lesions. The objective of the study was to evaluate the expression of cyclins D1 and D3 in common, dysplastic, and malignant melanocytic skin lesions. Forty-eight melanocytic skin lesions including common nevi (10), dysplastic nevi (24), and melanomas (14) were diagnosed by dermoscopy and excised. Expression of cyclin D1 and D3 was detected by immunohistochemistry and quantified as percentage of immunostained cell nuclei in each sample. In normal skin, expression of cyclins D1 and D3 was not detected. The mean percentage of cyclin D1-positive nuclei was 7.75% for melanoma samples, 5% for dysplastic nevi samples, and 0.34% for common nevi samples. For cyclin D3, the respective values were 17.8, 6.4, and 1.8%. Statistically significant differences in cyclin D1 expression were observed between melanomas and common nevi as well as between dysplastic and common nevi (pxa0=xa00.0001), but not between melanomas and dysplastic nevi. Cyclin D3 expression revealed significant differences between all investigated lesion types (pxa0=xa00.0000). The mean cyclin D1 and D3 scores of melanomas with Breslow thickness <1xa0mm and >1xa0mm were not significantly different. G1/S abnormalities are crucial for the progression of malignant melanoma, and enhanced cyclin D1 and D3 expression leading to increased melanocyte proliferation is observed in both melanoma and dysplastic nevi. In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type.

The role of focal infections in the pathogenesis of psoriasis and chronic urticaria.

Introduction The Focal Infection Theory, originally presented at the beginning of the 20th century, postulates that systemic diseases can be caused by microorganisms that arise from the focus of infection. Foci of infections have been described as sinuses, adenoids, tonsils, teeth, genitourinary tract, gall bladder and kidneys. A focus of infection is defined as the area that can occur in any part of the body, contains a pathogen (microorganism) and is usually asymptomatic. There are discordant opinions about the role of focal infections in the pathogenesis of psoriasis and urticaria. Aim To establish whether there is a higher incidence of focal infections in patients with chronic urticaria and psoriasis. Material and methods We retrospectively reviewed 129 patients with a history of psoriasis and chronic urticaria: 58 women and 71 men treated in the Department of Dermatology of the Jagiellonian University Medical College in Krakow. Results In the analyzed group, 11 patients had a dental consultation, 58 – laryngological consultation and 29 women had a gynecological consultation. The most common examples of focal infection were tonsillitis, upper respiratory tract infections, sinusitis, dental caries and genitourinary tract infections. Aggravating factors were similar to previously described. Conclusions A high incidence of focal infections in patients with psoriasis and urticaria suggests that infections may play a significant role in the pathogenesis of these skin disorders. Treatment of infection foci may play the key role in the remission of skin changes.

Association of CSF glucose concentration with neurosyphilis diagnosis

The most specific criterion for diagnosing neurosyphilis is a reactive CSF VDRL. Unfortunately, there are in Europe, including Poland small number of specialized laboratories for serological diagnosis of syphilis. Thus, CSF serology results are obtained with delay. Therefore, the decision on recommended therapy for neurosyphilis is taken on the basis of CSF basic tests. In this paper we attempt to determine the utility of CSF glucose concentration and its cut-off values in prediction of asymptomatic neurosyphilis. CSF and blood were collected from 55 HIV-uninfected patients with syphilis of unknown duration. Patients with neurosyphilis (14.5%) were characterized by higher CSF pleocytosis (p<0.0001), elevated CSF protein concentration (p<0.05) and lower CSF glucose concentration (p<0.0001). Multivariate regression analysis identified CSF pleocytosis and CSF glucose concentration as the two independent predictors of reactive CSF VDRL (p<0.0001). In the selected group of patients with CSF pleocytosis ≥5/µL (n=25) CSF glucose concentration ≤2.72 mmol/L was associated with 100% sensitivity (95%CI: 63–100%) and 100% specificity (95%CI: 75.3–100%) for reactive CSF VDRL. CSF glucose concentration may be particularly useful as a predictive marker of neurosyphilis in HIV uninfected patients with syphilis of unknown duration with CSF plecytosis ≥5/µL.

Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma

The aim of this study was to compare the expressions of mRNA for metalloproteinases (MMP-2 and MMP-9) and type IV collagen in two different histological types of basal-cell carcinoma (BCCs; nodular and infiltrative) and in normal tissues from the tumor interface. The study included biopsy specimens of the skin involved with BCC and normal skin adjacent the lesion. The expressions of mRNA for MMP-2, MMP-9 and type IV collagen were determined by means of RT-PCR (Reverse transcription polymerase chain reaction). The level of type IV collagen mRNA in nodular and infiltrative BCCs turned out to be significantly lower, and the expressions of MMP-2 and MMP-9 mRNA significantly higher than in normal tissues adjacent to these tumors. The expression of mRNA for MMP-9 but not for MMP-2 was significantly higher in infiltrative BCCs than in the nodular BCCs. In turn, normal tissues adjacent to nodular BCCs showed significantly higher levels of mRNA for MMP-2 and significantly lower levels of type IV collagen mRNA than the normal tissues from the interface of infiltrative BCCs. The findings suggest that MMP-2 and MMP-9 could be used as prognostic factors of BCCs.

Suspicion of pulmonary embolism during treatment of pemphigoid gestationis

Pemphigoid gestationis (PG), first described in 1872 by Laws Milton, is a rare autoimmune bullous disease of pregnancy and puerperium. Pemphigoid gestationis has been estimated to occur in 1: 50 000 pregnancies and usually presents in the second or third trimester with exacerbation after partum. This disease is caused by circulating IgG1 immunoglobulin against hemidesmosomal protein bullous pemphigoid BP180 (BPAG2) type XVII collagen and less frequently BP230. We present a case of pemphigoid gestationis in primigravida with complications during treatment due to the suspicion of pulmonary embolism.

Utility of antitreponemal IgM testing in the diagnosis of early and repeat syphilis among HIV-infected and non-infected patients

Until now only non-treponemal tests (e.g. rapid plasma reagin [RPR]) have been used to monitor syphilis activity (e.g. distinguishing between treated, untreated and repeat disease) and efficacy of treatment. However, they usually require manual operation and are less specific than treponemal tests. The aim of the current study was to evaluate the use of the antitreponemal IgM testing in the diagnosis of early and repeat syphilis in HIV-infected and non-infected patients. One hundred and seventeen patients with early syphilis were included in this prospective study. RPR and anti-Treponema pallidum-IgM (TP-IgM) tests were conducted at onset and at three-month intervals during 24-month follow-up after initial treatment. In 31 of 117 syphilitic patients the co-occurrence of HIV infection was diagnosed. A positive TP-IgM test was present in 78.6% of patients with newly-diagnosed primary syphilis, 95.8% with secondary and 57.9% with early latent syphilis, but only in 38.5% patients with syphilis reinfection. There was a significant correlation between primary and secondary syphilis, higher baseline RPR titre and the pre-treatment IgM test reactivity. Regardless of the syphilis stage, HIV-seropositive individuals were more frequently positive for TP-IgM, both during the first onset of the disease (90.3%), and reinfection (71.4%), as compared to the HIV-seronegative group (71.4% and 0%, respectively, Pu2009<u20090.03). TP-IgM seroreversion was observed in 115 out of 117 patients studied (98.3%) during follow-up (mean time to seroreversion 6.9 months). The time to TP-IgM seroreversion after treatment was significantly shorter in patients with early symptomatic syphilis (mean 4.9 months) when compared to early latent syphilis (7.7 months, Pu2009<u20090.05). A negative TP-IgM test was found in approximately 20% and 40% of individuals with primary and early latent syphilis, respectively. The value of IgM testing in the diagnosis of syphilis reinfection is doubtful.

The PCOS Patients differ in Lipid Profile According to their Phenotypes

Polycystic ovary syndrome (PCOS) affects 4-18% of women of reproductive age. The number of reports exploring the lipid profiles among PCOS patients and number of studied patients are limited. The aim of our study was to assess the lipid profile separately in lean and non-lean women with polycystic ovary syndrome divided according to hyperandrogenemia, defined as free androgen index (FAI)≥5. The second aim was to compare the lipid profiles among lean and non-lean PCOS patients with respect to hyperandrogenemia and regularity of menstruation cycles. We evaluated 232 patients from Department of Endocrinological Gynecology, Jagiellonian University Medical College in Krakow diagnosed with PCOS. The population consisted of 166 lean and 66 non-lean women. We observed higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C) in lean patients with FAI<5 than in lean patients with FAI≥5. There were no differences in lipid profile between non-lean patients with FAI≥5 and non-lean patients with FAI<5. Among lean patients higher total cholesterol levels were observed in those with irregular menstruation cycles and FAI<5 than in patients with FAI≥5 and regular cycles. There were no differences in lipid profiles between four phenotypes among non-lean PCOS patients.nnnCONCLUSIONSnThe results of our study showed differences in lipid profile between lean PCOS patients according to their phenotype based on androgens level. This effect was abandoned by fat tissue mass in non-lean ones. Further studies should be conducted to explore these associations.

Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features

Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC). A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001). The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001). Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC) compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.