The role of viruses in human carcinogenesis

Procjenjuje se da virusne infekcije pridonose nastanku 15 – 20 % svih malignih tumora ljudi. Kao obligatorni intracelularni paraziti, virusi kodiraju proteine koji reprogramiraju signalne puteve odgovorne za kontrolu proliferacije, diferencijacije, smrti stanice, genomskog integriteta, kao i prepoznavanja od strane imunološkog sustava. Virusni sustavi podržavaju koncept da je za razvoj tumora potrebna akumulacija međusobno povezanih događaja. Virusi koji su do sada prihvaćeni kao etiološki čimbenici ljudskih malignoma uključuju hepatitis B virus, Epstein-Barr virus, humani papiloma virus, virus leukemije ljudskih T-stanica, hepatitis C virus, te još nekoliko ljudskih onkogenih virusa. Obično protekne niz godina od infekcije do razvoja tumora i većina inficiranih osoba ne razvije rak, iako imunološki kompromitirane osobe pokazuju veći rizik za nastanak tumora povezanih s virusima. Malo je vjerojatno da je virus sam dovoljan da transformira normalnu stanicu u tumorsku. Vjerojatnija je mogućnost da kombinirano djelovanje virusnih proteina i mutacije staničnih gena zajedno vode tumorogenezi.It is estimated that viral infections contribute to 15-20 % of all human cancers. As obligatory intracellular parasites, viruses encode proteins which reprogramme host cellular signalling pathways which in turn control proliferation, differentiation, cell death, genomic integrity, and recognition by the immune system. Viral systems support the concept that cancer development occurs by accumulation of multiple cooperating events. Viruses are now accepted as etiologic factors of human cancer, and include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus and hepatitis C virus, plus several candidate human cancer viruses. Many years may pass between initial infection and tumor appearance. Most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. It is unlikely that a tumor virus is sufficient to convert a normal cell to a tumor cell. Rather, a combination of the action of viral proteins and cellular gene mutation cooperate to drive tumorogenesis

Perioral dermatitis as a consequence of prolonged use of topical corticosteroids

Cilj: Perioralni dermatitis je kronična ekcematoidna i papulopustulozna upalna dermatoza kože lica od koje najčešće obolijevaju žene mlađe i srednje dobi. Etiopatogeneza je nepoznata, a od mogućih etioloških čimbenika u obzir dolaze dugotrajna uporaba topičkih kortikosteroida, kozmetičkih preparata na bazi petrolata i parafina, infektivni uzročnici, hormoni, gastrointestinalni poremećaj, neurogena upala i emocionalni stres. Prikaz slučaja: Prikazana je 49-godišnja žena s izrazitim eritemom kože lica, edemom kapaka te brojnim grupiranim papulama i papulopustulama na koži lica, uz brojne subjektivne simptome. Bolesnica je samoinicijativno duže od godinu dana na licu primjenjivala potentni kortikosteroidni pripravak. Rasprava i zaključak: Prikaz slučaja govori u prilog hipotezi o važnoj ulozi topičkih kortikosteroida u patogenezi perioralnog dermatitisa. U radu je prikazan i pregled recentne literature o etiologiji, patogenezi i liječenju bolesti.Aim: Perioral dermatitis is a chronic papulopustular and eczematous facial dermatitis which predominantly affects young to middle aged women. The etiology of perioral dermatitis is unknown, and possible etiological factors include long time use of topical corticosteroids, cosmetics with petrolatum or paraffin base, microbiological factors, hormonal factors, gastrointestinal disturbances, neurogenic inflammation and emotional stress. Case report: A 49-year-old woman presented with expressive facial skin erythema, edema of the eyelids, a number of grouped papules and papulopustules on the face, accompanied with a number of subjective symptoms. Patient used potent corticosteroid preparations on the face for more than a year. Discussion and conclusion: The case supports the hypothesis that topical corticosteroids have an important role of in the pathogenesis of perioral dermatitis. This paper presents an overview of recent literature on the etiology, pathogenesis and treatment of the disease

Human Hair Follicle: An Update on Biology and Perspectives in Hair Growth Disorders Treatment

The Hair Follicle (HF) is a vital component of mammalian skin and represents a unique, highly regenerative system that undergoes phases of rapid growth, regression, and resting periods. The hair cycling is of profound clinical relevance since majority of the hair growth disorders occur as a result of cycle changes. The influence of many molecules governing the formation of HF has been investigated and many of important cycle mediators have been identified. Cellular and molecular events during cycling are controlled by a network of sequential activation of autocrine, paracrine and endocrine signaling pathways. This implies variations in the expression or activity of the Wnt family molecules, Fibroblast Growth Factor (FGF), Transforming Growth Factor β (TGF-β), Hedgehog pathway, β-Catenin pathway, noggin, transcription factor Stat3, Epidermal Growth Factor (EGF), Insulin Growth Factor-1 (IGF- 1), Vascular Endothelial Growth Factor (VEGF), Thyrotropin Releasing Hormone (TRH), Polyamine, Spermidine, Neurotrophins (NT3, NT4), prolactin, retinoids, Bone Morphogenetic Protein 4 (BMP4), cathepsin L, 17-β estradiol, dihydrotestosterone and many others. Despite considerable progress in this area, the key elements of cycle control have not been identified. Therefore, for the most common hair disorders several agents are available, even none of these is curative or preventive. The one of the prime challenges of hair research is a better understanding of the molecular controls of hair cycling and developing drug which would effectively manipulate the cycle. Future therapy strategies will be based on new and better knowledge about the HF biology. Until than, alopecia areata, telogen effluvium and androgenetic alopecia, will remain unsolved medical problems

TREATMENT OF ALOPECIA AREATA: MODERN PRINCIPLES AND PERSPECTIVES

Alopecija areata (AA) česta je bolest koja se očituje neožiljnim gubitkom dlake na vlasištu i/ili tijelu. Folikul dlake u alopeciji areati nije nepovratno uništen, stoga potencijal za ponovni rast kose ostaje. Budući da je etiopatogeneza nepoznata, liječenje AA je simptomatsko i usmjereno na zaustavljanje aktivnosti bolesti. Limfociti oko dlačnog folikula, povišena razina autoprotutijela, poremećaj citokina te udruženost s drugim autoimunosnim bolestima, podupiru hipotezu da je AA organ-specifična autoimunosna bolest. Nova su istraživanja stoga usmjerena na razvoj lijekova koji bi imunomodulatornim ili imunosupresivnim djelovanjem potaknuli rast dlake. Proučavanje utjecaja novih bioloških lijekova na rast kose, kao i razvoj genske terapije u tijeku su. U radu će biti raspravljeni suvremeni principi i dostupne metode liječenja alopecije areate.Alopecia areata (AA) is a frequent disease with nonscarring hair loss on the scalp and/or body. Hair follicle in alopecia areata is not irreversibly destroyed, so potential for hair regrowth remains. Considering unknown etiopathogenesis, treatment of AA is symptomatic and directed toward halting disease activity. Lymphocytic inflammatory infiltrate around hair follicle, increased levels of autoantibodies, cytokine abnormalities and increased prevalence of autoimmune comorbidities, support the hypothesis of AA as an organ-specific autoimmune disorder. Therefore, investigations are directed toward new immunomodulatory or immunosupresive drugs with induction effect on hair growth. New biologic drugs and their influence on hair growth as well as genetic therapy for alopecia areata are currently under investigation. Contemporary principles in therapy of alopecia areata and treatments available will be discussed in this article

TREATMENT OF ALOPECIA AREATA: MODERN PRINCIPLES AND PERSPECTIVES

Alopecija areata (AA) česta je bolest koja se očituje neožiljnim gubitkom dlake na vlasištu i/ili tijelu. Folikul dlake u alopeciji areati nije nepovratno uništen, stoga potencijal za ponovni rast kose ostaje. Budući da je etiopatogeneza nepoznata, liječenje AA je simptomatsko i usmjereno na zaustavljanje aktivnosti bolesti. Limfociti oko dlačnog folikula, povišena razina autoprotutijela, poremećaj citokina te udruženost s drugim autoimunosnim bolestima, podupiru hipotezu da je AA organ-specifična autoimunosna bolest. Nova su istraživanja stoga usmjerena na razvoj lijekova koji bi imunomodulatornim ili imunosupresivnim djelovanjem potaknuli rast dlake. Proučavanje utjecaja novih bioloških lijekova na rast kose, kao i razvoj genske terapije u tijeku su. U radu će biti raspravljeni suvremeni principi i dostupne metode liječenja alopecije areate.Alopecia areata (AA) is a frequent disease with nonscarring hair loss on the scalp and/or body. Hair follicle in alopecia areata is not irreversibly destroyed, so potential for hair regrowth remains. Considering unknown etiopathogenesis, treatment of AA is symptomatic and directed toward halting disease activity. Lymphocytic inflammatory infiltrate around hair follicle, increased levels of autoantibodies, cytokine abnormalities and increased prevalence of autoimmune comorbidities, support the hypothesis of AA as an organ-specific autoimmune disorder. Therefore, investigations are directed toward new immunomodulatory or immunosupresive drugs with induction effect on hair growth. New biologic drugs and their influence on hair growth as well as genetic therapy for alopecia areata are currently under investigation. Contemporary principles in therapy of alopecia areata and treatments available will be discussed in this article

Alopecia areata – clinical spectrum, histology and treatment

Alopecija areata neožiljni je upalni gubitak dlake na vlasištu i/ili tijelu, nepoznate etiopatogeneze. Najčešće zahvaćeno mjesto je vlasište. Histopatologija se očituje povećanim brojem katagenih i telogenih folikula te nazočnošću upalnog limfocitnog infiltrata u peribulbarnoj regiji. U liječenju alopecije areate najčešće se primjenjuju kortikosteroidi. U radu je opisana klinička i patohistološka slika uz suvremene metode liječenja alopecije areate.Alopecia areata is a nonscarring, inflammatory hair loss on the scalp, and/or body. Etiology and pathogenesis are still unknown. The most common affected site is the scalp. Histopathology is characterized by an increased number of the catagen and telogen follicles along with the presence of inflammatory lymphocytic infiltrate in the peribulbar region. Corticosteroids are the most popular drugs for the treatment of this disease. Clinical features, histological data as well as modern treatment options will be discussed in this article

Alopecia areata – clinical spectrum, histology and treatment

Alopecija areata neožiljni je upalni gubitak dlake na vlasištu i/ili tijelu, nepoznate etiopatogeneze. Najčešće zahvaćeno mjesto je vlasište. Histopatologija se očituje povećanim brojem katagenih i telogenih folikula te nazočnošću upalnog limfocitnog infiltrata u peribulbarnoj regiji. U liječenju alopecije areate najčešće se primjenjuju kortikosteroidi. U radu je opisana klinička i patohistološka slika uz suvremene metode liječenja alopecije areate.Alopecia areata is a nonscarring, inflammatory hair loss on the scalp, and/or body. Etiology and pathogenesis are still unknown. The most common affected site is the scalp. Histopathology is characterized by an increased number of the catagen and telogen follicles along with the presence of inflammatory lymphocytic infiltrate in the peribulbar region. Corticosteroids are the most popular drugs for the treatment of this disease. Clinical features, histological data as well as modern treatment options will be discussed in this article