Lymphogranuloma venereum: an emerging problem in Poland.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease that increases in incidence, particularly in more developed countries worldwide. LGV is caused by Chlamydia trachomatis serovars/genovars L1-3, including their subvariants, and in Europe mostly affects men who have sex with men (MSM). It can be asymptomatic but has now emerged as a frequent cause of severe proctitis/proctocolitis, especially in MSM. LGV has often been misdiagnosed as C. trachomatis serovars/genovars D-K infection. It is essential with accurate diagnosis that ensures appropriate treatment and protects the patient from complications and sequelae as well as from the consequences of misdiagnosis, e.g. as inflammatory bowel disease or cancer. We present a systematic review of LGV and two new LGV cases diagnosed in Poland.

Correction to: Multiresistant Neisseria gonorrhoeae: a new threat in second decade of the XXI century.

The article "Multiresistant Neisseria gonorrhoeae: a new threat in second decade of the XXI century", written by Beata Mlynarczyk­Bonikowska, Anna Majewska, Magdalena Malejczyk, Grazyna Mlynarczyk, Slawomir Majewski was originally published electronically on the publisher's internet portal (currently SpringerLink) on December 04, 2019 without open access.

Multiresistant Neisseria gonorrhoeae: a new threat in second decade of the XXI century.

Neisseria gonorrhoeae is an etiologic agent of gonorrhoea, one of the most common sexually transmitted diseases caused by bacteria. For many years, infections caused by N. gonorrhoeae were considered to be relatively easy to treat; however, resistance has emerged successively to all therapeutic agents used in treatment of the disease, e.g., penicillin, ciprofloxacin or azithromycin. Currently, the global problem is the emergence and a threat of spread of N. gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESC), such as injectable ceftriaxone and oral-used cefixime. Especially, dangerous are multi-resistant strains resistant simultaneously to ESC and azithromycin. Three strains with high-level resistance to azithromycin and resistant to ESC were first time isolated in 2018. Moreover, in 2018, the first ESBL was described in N. gonorrhoeae and that makes the threat of appearing the ESBL mechanism of resistance in N. gonorrhoeae more real, even though the strain was sensitive to ceftriaxone. Molecular typing revealed that variants resistant to ESC occurred also among strains belonging to epidemic clonal complex CC1 (genogroup G1407) distinguished in NG-MAST typing system. The G1407 genogroup, in particular the ST1407 sequence type, is currently dominant in most European countries. The presence of different mechanisms of drug resistance significantly affects clinical practice and force changes in treatment regimens and introduction of new drugs.

Polymetastatic testicular cancer turns out to be secondary syphilis: a case report.

Syphilis is a sexually transmissible infection, with increasing rates of infection worldwide. The differential diagnosis of syphilis should include various diseases, not excluding cancer. Making the right diagnosis can protect the patient against life-threatening complications and the repercussions of a misdiagnosis, as in the present case (orchidectomy).

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part I. Prophylaxis, topical treatment and phototherapy.

Atopic dermatitis is a chronic and recurrent inflammatory dermatosis with concomitant intensive pruritus, and is diagnosed both in children and adults. Atopic dermatitis-patients are predisposed to have bacterial, viral and fungal skin infections; they also suffer from an increased risk of developing food allergies (especially, at an infantile age), allergic rhinitis, or bronchial asthma (a so-called atopic march). Currently, an increasing atopic dermatitis incidence constitutes a serious medical problem that regards not only dermatology and allergology, but also paediatrics, and family medicine. The basis for atopic dermatitis treatment and prophylaxis is restoration of epidermal barrier functions by means of tailored emollients. Atopic dermatitis therapies should effectively eliminate clinical symptoms of the disease, prevent exacerbations as well as complications, and improve patients' quality of life.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part II. Systemic treatment and new therapeutic methods.

The treatment goal in atopic dermatitis is eliminating clinical symptoms of the disease, preventing exacerbations and complications, as well as improving patients' quality of life. In cases of severe atopic dermatitis and lack of response it is recommended to introduce systemic therapy. Patients ofter require multi-specialist consultations, and occasionally hospitalization. It is not recommended to use acupuncture, acupressure, bioresonance, homeopathy, or Chinese herbs in the treatment of atopic dermatitis.

Identification of C/EBPα as a novel target of the HPV8 E6 protein regulating miR-203 in human keratinocytes.

Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions. We provide evidence that CCAAT/enhancer-binding protein α (C/EBPα), a differentiation-regulating transcription factor and suppressor of UV-induced skin carcinogenesis, directly binds the miR-203 gene within its hairpin region and thereby induces miR-203 transcription. Our data further demonstrate that the HPV8 E6 protein significantly suppresses this novel C/EBPα/mir-203-pathway. As a consequence, the miR-203 target ΔNp63α, a proliferation-inducing transcription factor, is up-regulated, while the differentiation factor involucrin is suppressed. HPV8 E6 specifically down-regulates C/EBPα but not C/EBPß expression at the transcriptional level. As shown in knock-down experiments, C/EBPα is regulated by the acetyltransferase p300, a well-described target of cutaneous E6 proteins. Notably, p300 bound significantly less to the C/EBPα regulatory region in HPV8 E6 expressing keratinocytes than in control cells as demonstrated by chromatin immunoprecipitation. In situ analysis confirmed congruent suprabasal expression patterns of C/EBPα and miR-203 in non-lesional skin of EV-patients. In HPV8-positive EV-lesions both factors are potently down-regulated in vivo further supporting our in vitro data. In conclusion our study has unraveled a novel p300/C/EBPα/mir-203-dependent mechanism, by which the cutaneous HPV8 E6 protein may expand p63-positive cells in the epidermis of EV-patients and disturbs fundamental keratinocyte functions. This may drive HPV-mediated pathogenesis and may potentially also pave the way for skin carcinogenesis in EV-patients.

Antibiotic resistance and NG-MAST sequence types of Neisseria gonorrhoeae isolates in Poland compared to the world.

Gonorrhoea is one of the most common sexually transmitted infections and in 2012, the World Health Organization estimated about 78 million of new global urogenital cases among adults per year. The main concern during the latest decade has been the emergence and spread of multidrug-resistant strains of Neisseria gonorrhoeae. Resistance has emerged internationally to the extended-spectrum cephalosporins, ceftriaxone and cefixime, which are the last remaining options for empiric first-line monotherapy of gonorrhoea. In Poland, the levels of resistance to ciprofloxacin, benzylpenicillin and tetracycline are high, and the prevalence of azithromycin resistance has increased. However, no resistance to ceftriaxone has been identified. The currently spread multidrug-resistant strains frequently represent epidemic clones. The present paper reviews and describes the antimicrobial resistance and N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence types of N. gonorrhoeae strains spreading in Poland compared to the world.

The levels of epithelial anchor proteins ß-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8.

Infection with viruses of the genus Betapapillomavirus, ß-human papillomaviruses (ß-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins ß-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that ß-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of ß-catenin was elevated, no signs of ß-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of ß-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that ß-catenin and ZO-1 are direct targets of E7 of the oncogenic ß-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.

Dominating types of penicillinase-plasmids in Neisseria gonorrhoeae strains isolated in 2010-2012 in Warsaw.

INTRODUCTION: The reason of Neisseria gonorrhoeae resistance to penicillin is often production of TEM beta-lactamases encoded by plasmids. The most common types of the plasmid are Africa, Asia and Toronto/Rio. Another reason of resistance can be mutations in bacterial chromosome. The aim of the study was to investigate the types of plasmids occurring in in Neisseria gonorrhoeae strains isolated in 2010-2012 in Warsaw. MATERIAL AND METHODS: From 218 isolated in 2010, 2011 and at the beginning of 2012 from patients of Medical University in Warsaw we selected 12 strains producing beta- lactamase (penicillinase producing N. gonorrhoeae, PPNG). d B-tests to investigate bacterial sensitivity to penicillin and cefiriaxon. The types of plasmids were determined with PCR. RESULTS: The Beta-lactamases were encoded by Toronto/Rio (41,7%), Asia (33,3%) and Africa (25,0%) plasmids. All the strains were resistant to penicillin (MIC 2-8 mg/L) and sensitive to ceftriaxon (MIC 0,004-0,032 mg/L). CONCLUSIONS: All of the investigate PPNG strains were penicillin resistant and ceftriaxon sensitive. The dominating type of the penicillinase plasmid was Toronto/Rio.

The occurrence of herpes simplex viruses 1 and 2 in skin and mucosal lesions in patients with suspicion of genital herpes.

INTRODUCTION: Infection with herpes simplex viruses 1 and 2 (HSV 1 and 2 or Human herpesvirus HHV) are one of the most common infections in human. Real time PCR is a sensitive and specific method for diagnostics of HHV infections. The aim of the study was to investigate the occurrence of HHV 1 and HHV 2 DNA in patient with clinical symptoms suggesting HHV infection. METHODS: We used real time PCR to investigate swabs from genital and perianal lesions from 74 patients of the Department of Dermatology and Venereology Medical University Warsaw and of gynecological outpatient clinics in Warsaw 40 women and 34 men. RESULTS: The results were positive for HHV 2 in 25 cases (34%), for HHV 1 in 19 cases (26%) and for both viruses in 20 cases (27%). 10 samples were negative for both viruses. CONCLUSIONS: The results confirm that the main cause of symptomatic genital herpes is HHV 2, however the percentage of HHV 1 and specially of mixed HHV 1/HHV 2 infections was unexpectedly high.

The role of antimicrobial peptides in chronic inflammatory skin diseases.

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases.

The EVER genes - the genetic etiology of carcinogenesis in epidermodysplasia verruciformis and a possible role in non-epidermodysplasia verruciformis patients.

In recent years, the two adjacent novel EVER1 and EVER2 genes have been identified, whose mutations are responsible for the development of epidermodysplasia verruciformis (EV). Epidermodysplasia verruciformis is a rare, autosomal recessive genodermatosis associated with increased risk of skin carcinoma. Up to now 7 mutations in the EVER1 gene and 5 mutations in the EVER2 gene have been identified only in EV. It was also determined that the EVER genes belong to a novel gene family, the transmembrane channel-like (TMC) family, and are responsible for properly functioning zinc homeostasis. These observations have given new insights into EV pathogenesis.

Plasmid-mediated resistance to tetracyclines among Neisseria gonorrhoeae strains isolated in Poland between 2012 and 2013.

INTRODUCTION: One of two main mechanisms of resistance in tetracycline-resistant Neisseria gonorrhoeae (TRNG) is associated with the presence of TetM protein responsible for actively blocking of the tetracycline target site in the 30S ribosomal subunit. This mechanism is encoded by conjugative plasmids. The second mechanism is chromosomal in nature and due to mutations in specific genes. AIM: To determine the incidence and type of tetM determinants in TRNG strains isolated from patients presenting with gonorrhea infection to the Dermatology and Venereology Clinic in Warsaw in 2012-2013. MATERIAL AND METHODS: Tetracycline and doxycycline susceptibility was determined by E-Tests. The presence and type of the tetM gene were determined by polymerase chain reaction. RESULTS: Tetracycline resistance was detected in 50.8% of the evaluated strains. The TRNG strains containing the tetM plasmid constituted 13.8% of all the evaluated strains. Dutch type tetM constituted 12.3% and American type tetM 1.5% of all the evaluated strains. In the remaining TRNG strains, resistance to tetracyclines was presumably chromosome-encoded. The minimal inhibitory concentration (MIC) of tetracycline ranged from 0.25 to 32.0 mg/l, MIC50 = 2.0 mg/l, MIC90 = 32.0 mg/l. The MIC of doxycycline ranged from 0.25 to 32.0 mg/l, MIC50 = 4.0 mg/l, MIC90 = 16.0 mg/l. CONCLUSIONS: Unlike most of European countries, in 2012-2013 in Poland, the Dutch type tetM was found to be much more common than the American type. Minimal inhibitory concentration values of tetracycline and doxycycline were similar, with doxycycline exhibiting a somewhat lower effectiveness in vitro than tetracycline towards chromosome-mediated tetracycline resistant strains of N. gonorrhoeae.

Human papillomavirus vaccine trials and tribulations: Clinical perspectives.

Human papillomavirus (HPV) affects hundreds of millions of people worldwide and is associated with both benign and malignant neoplasms in men and women. It is a double-stranded DNA virus with an icosahedral capsid. Forty HPV types are known to infect mucosal keratinocytes. If not cured by the immune system, the infection can lead to genital warts, mucosal dysplasia, or cancer. The most common oncogenic types are 16 and 18. The vaccine to prevent HPV and its associated morbidity and mortality has existed since 2006. Several variations protect against an increasing number of HPV types. The recommended vaccination age is before sexual exposure; administration of the vaccine to children has been controversial. This continuing medical education review evaluates the current HPV vaccines available to clinicians. Part I focuses on the debate over who should be vaccinated, at what age, and in which populations.

Human papillomavirus vaccine trials and tribulations: Vaccine efficacy.

As of December 2014, there were 3 approved vaccines for human papillomavirus (HPV): bivalent Cervarix (GlaxoSmithKline, New York, NY), quadrivalent Gardasil (Merck and Co, Kenilworth, NJ), and 9-valent Gardasil-9 (Merck and Co). The average cost per dose is $120, with a recommended 3-dose course. The quadrivalent vaccine is the most widely administered worldwide. As with the bivalent and 9-valent vaccines, the vaccine is considered safe, although concerns have been raised. In addition to immunization against the targeted HPV types, there is evidence that there is cross protection against other types of HPV. This continuing medical education review evaluates the differences in vaccines that are currently on the market; part II focuses on the cost-effectiveness of vaccination, the HPV vaccination programs currently instituted around the globe, efficacy, and safety.

In vivo and ex vivo evaluation of cosmetic properties of seedcakes.

The seedcakes are a potential source of natural bioactive substances: antioxidants, protein, and carbohydrates. Thus, they may scavenge free radicals and have an effect on the stratum corneum hydration and epidermal barrier function. The aim of the study was to evaluate the in vivo and ex vivo properties of emulsions with the seedcake extracts using the pH meter, corneometer, tewameter, methyl nicotinate model of micro-inflammation in human skin, and tape stripping of the stratum corneum. The in vivo and ex vivo studies showed that the emulsions with Oenothera biennis, Borago officinalis, and Nigella sativa seedcake extracts have anti-inflammatory and antioxidant activity. The 6-week topical application of the emulsions with the B. officinalis and N. sativa seedcakes significantly reduced skin irritation and influenced the improvement of the skin hydration and epidermal barrier function compared with placebo. The seedcakes due to their antioxidant and anti-inflammatory activities have potential application in anti-aging, moisturizing, mitigating, and protective cosmetics.

Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction.

Autoimmune diseases are chronic, destructive diseases that can cause functional disability and multiple organ failure. Despite significant advances in the range of therapeutic agents, especially biologicals, limitations of the routes of administration, requirement for frequent long-term dosing and inadequate targeting options often lead to suboptimal effects, systemic adverse reactions and patient non-compliance. Nanotechnology offers promising strategies to improve and optimize autoimmune disease treatment with the ability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we focus on nanomedicine-based delivery strategies of biological immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis and type 1 diabetes. This comprehensive review details the concepts and clinical potential of novel nanomedicine approaches for inducing immunosuppression and immunological tolerance in autoimmune diseases in order to modulate aberrant and pathologic immune responses. FROM THE CLINICAL EDITOR: The treatment of autoimmune diseases remains a significant challenge. The authors here provided a comprehensive review, focusing on the current status and potential of nanomedicine-based delivery strategies of immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type 1 diabetes.

Influence of polyphenols on the physiological processes in the skin.

In the last decade antioxidants from a group of polyphenols have been proposed as one of the most effective functional ingredients of anti-ageing properties that counteract the effects of oxidative damage to the skin. It has been shown that the use of polyphenols affects skin protection and mitigates inflammatory conditions of the skin. Numerous studies have confirmed that polyphenols by neutralizing free radicals, antioxidant activity and by their ability to chelate ions of transition metals can effectively reduce the level of nonprotein inflammatory mediators. The biological activity of polyphenols in the skin is primarily determined by their physicochemical properties and the ability to overcome the epidermal barrier as they try to reach appropriate receptors. This study reviews literature on the effects of polyphenols relating to the physiological processes in the skin and role of the major plant polyphenols in cosmetology and dermatology.

[Susceptibility of Neisseria gonorrhoeae strains isolated in Poland in 2012-2013 to spectinomycin]. / Wrazliwosc na spektynomycyne szczepów Neisseria gonorrheae izolowanych w Polsce w latach 2012-2013.

INTRODUCTION: A rapid growth of the antibiotic resistance among Neisseria gonorrhoeae strains was recently observed in many countries. The common resistance or decreased susceptibility to penicillin, tetracyclines, ciprofloxacin, azithromycin as well as emergence of the first strains resistant to ceftriakson and cefixim is a cause of an anxiety worldwide. Spectinomycin may constitute an alternative therapy of gonorrhoea except of pharyngeal infection. METHODS: The susceptibility to spectinomycin of 65 N. gonorrhoeae strains isolated in the second half of 2012 and the first half of 2013 in Dermatology and Venereology Clinic in Warsaw was investigated. The E-Tests (bioMerieux) were performed and the results (sensitive or resistant) were interpreted according to EUCAST and CLSI recommendations. RESULTS: The MIC (Minimal inhibitory concentration) values of spectinomycin for the investigated strains ranged from 4,0 mg/L to 32 mg/L, MIC50=16,0 mg/L and MIC=90=16,0 mg/L. It was shown that 100% of the strains was sensitive to spectinomycin according to EUCAST as well CLSI tables. CONCLUSIONS: High susceptibility of the investigated strains to spectinomycin suggests that the drug can be used in the therapy of the resistant gonorrhoea in monotherapy or combined with other drugs.