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Objective: Meglumine antimoniate (Glucantime®) and Sodium stibogluconate (Pentostam®) are used for the treatment of cutaneous leismaniasis in Turkey. There is a reported resistance to these drugs in recent years. The aim of the present study was to compare the in vitro sensitivities of resistant Leishmania isolates against Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin and Sodium Stibogluconate. Methods: Five Leishmania isolates of patients with cutaneous leishmaniasis, who showed no clinical recovery despite two consecutive meglumine antimoniate treatments, which were stored in the Parasite Bank in Manisa Celal Bayar University Medical Faculty were selected. They were genotyped with Real-Time PCR using specific primers and probes to ITS1 region. Drug resistance levels of each Leishmania isolate were analysed for Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin, and Sodium Stibogluconate at concentrations of 500, 250, 125, 50, 25 μg/mL with XTT method and hemocytometer. Results: It was observed that the resistant Leishmania tropica isolates showed no resistance to Amphotericin B, and were sensitive to Miltefosine, Sodium Stibogluconate, Paromomycin and Meglumin Antimonate, respectively. In addition, Leishmania tropica (MHOM/AZ/1974/SAF-K27) isolate of the control group could stay viable in none of the drug concentrations of five agents in the study. Conclusion: It was determined that none of the selected resistant L. tropica isolates showed resistance to Amphotericin B and that was also shown statistically (p

Amaç: Leishmaniasis, Dünya Sağlık Örgütü’nün ihmal edilen hastalıklar sıralamasında sıtmadan sonra dünyada en fazla ölüme sebep olan ikinci paraziter hastalıktır. Kutanöz leishmaniasis (KL), Leishmaniasis’in en yaygın görülen formu olup, çatışma ve çevresel faktörlerden dolayı, insidansı artmakta olan az sayıdaki bulaşıcı hastalıklardan biri olarak bilinmektedir. KL iki ana gruba ayrılabilir: Akut KL (AKL) ve kronik KL (KKL). Bu çalışmada, oral yol ile kullanılan bir alkilfosfolipid analoğu olan miltefosinin, standart tedavide kullanılan beş değerli antimon bileşiklerine göre tedavi etkinliğinin in vitro olarak karşılaştırılması amaçlanmıştır. Yöntemler: Çalışmada, daha önce 5 KKL hastasından elde edilen hasta örnekleri kullanılmıştır. Bu izolatlara internal transcribed spacer-1 problu gerçek zamanlı polimeraz zincir reaksiyonu testi uygulanarak genotipleme yapılmıştır. Genotipleme sonrası, meglumin antimoniat (MA) ve miltefosine karşı etkinliklerini değerlendirmek amacıyla in vitro ilaç etkinliği testleri uygulanmıştır. MA ve miltefosinden hazırlanan seri sulandırımlar (512, 256, 128, 64, 32, 16, 8 ve 4 µg/mL) RPMI 1640 besiyeri (%15 FCS eklenmiş) içinde 96’lık düz tabanlı hücre kültürü plaklarında 100 µL olarak hazırlanmış ve 48 saat boyunca 24 °C’lik etüvlerde enkübe edilmiştir. İlaçların Leishmania spp. promastigotları üzerindeki etkisi, 24. ve 48. saatlerde, hemositometri lamında sayılarak ve XTT hücre canlılık testi ile değerlendirilmiştir. Bulgular: Tüm örnekler L. tropica olarak genotiplenmiştir. İlk 24 saat sonunda yapılan hemositometri ve XTT testleri sonucunda, miltefosin ve MA’ın tam leishmanisidal etki gösterdiği minimum konsantrasyon sırasıyla 128 µg/mL ve 256 µg/mL olarak saptanmıştır. Kırk sekizinci saatteki incelemede, miltefosin ve MA’nın minimum etkin konsantrasyonu 32 µg/mL ve 64 µg/mL olarak izlenmiştir. Hemositometri ile sayım ve XTT yöntemi sonuçları korelasyon göstermektedir. Sonuç: Literatürde, KKL hasta örneklerinde miltefosin etkinliğinin değerlendirildiği bir çalışma bulunmamaktadır. Bu özel hasta grubunda karşılaşılan tedavi zorluklarının giderilmesi için daha fazla çalışma yapılması gerekmektedir. Elde ettiğimiz sonuçlara göre, miltefosinin KKL tedavisinde etkili bir ajan olduğu görülmüş ve miltefosin ile yapılacak klinik çalışmaların değerli veriler sunacağı sonucuna varılmıştır. Objective: Leishmaniasis is the second deadliest parasitic disease in the World Health Organisation’s list of neglected diseases, following malaria. Cutaneous leishmaniasis (CL) is the most common form of the disease and it is one of the few communicable diseases with increasing incidence rates owing to factors like armed conflicts and climate change. CL can be divided into two major groups: Acute CL (ACL) and chronic CL (CCL). The aim of this study was to compare the in vitro efficacy of miltefosine and pentavalent antimony compounds in the CCL patient samples. Methods: Five isolates previously isolated from 5 CCL patients were included in this study. Genotyping is performed using internal transcribed spacer 1 (ITS 1) gene region real-time PCR. In vitro drug efficacy tests were applied to determine their activity against meglumine antimoniate (MA) and miltefosine. Serial dilutions (512, 256, 128, 64, 32, 16, 8 and 4 µg/mL) prepared from MA and miltefosine were prepared in 96-well flat-bottom cell culture plates and incubated at 24 °C for 48 hours. The efficacy of the drug on Leishmania spp. promastigotes after 24 and 48 hours was evaluated by hemocytometer slide and XTT cell viability test. Results: All of the samples were genotyped as L. tropica. Evaluation of 24 and 48 hours showed, 128 µg/mL and 256 µg/mL and 32 µg/mL and 64 µg/ mL concentrations of miltefosine and MA were enough to kill all the promastigotes respectively. The results of the hemocytometer slide and XTT were consistent. Conclusion: There are no studies investigating the in vitro efficacy of miltefosine with the CCL patient group. To overcome the treatment challenges experienced in this special patient group, more studies are needed. According to our results, it is concluded that miltefosine is efficient for the treatment of CCL and further clinical studies with miltefosine will reveal valuable data.

World Health Organization reported that approximately one billion people are at risk in endemic areas, one million cases of cutaneous leishmaniasis (CL) and approximately 300,000 cases of visceral leishmaniasis (VL) were reported per year in the last five years. the number of deaths due to VL is reported to be approximately 20,000 per year. Approximately 2500 cases/year have been reported as CL, caused by Leishmania tropica and Leishmania infantum, in Turkey. the significant increase observed in many cities mainly in the provinces of Mediterranean and Aegean regions in cases and foci in recent years, suggests that there may be an increase in this infections in the following years as well. in Turkey, the causative agent of CL is L.tropica and meglumine antimoniate is used in the treatment of CL. We aimed to determine antimony resistance genes specific for L.tropica by comparing the gene and protein expressions of antimony-resistant and non-resistant L.tropica strains. Ltropica isolates obtained from 3 CL patients without antimonate resistance from Aegean, Mediterranean and Southeastern regions of Turkey were provided to transform into 3 resistant isolates against meglumine antimony in the laboratory conditions. Gene expression alterations by microarray method; protein profiles by two-dimensional gel electrophoresis (2D-PAGE) and relevant proteins by MALDI-TOF/TOF MS of these isolates were accomplished and compared. L.tropica isolates from 10 CL patients who did not respond to antimony therapy were analyzed for resistance to antimonial compounds and quantitative real-time polymerase chain reaction was performed to detect the expression of genes responsible for resistance development. Moreover, differences in protein expression levels in isolates with and without antimony resistance were determined by comparing protein profiles and identification of proteins with different expression levels was carried out. Enolase, elongation factor-2, heat shock protein 70, tripanthione reductase, protein kinase C and metallo-peptidase proteins have been shown to play roles in L.tropica isolates developing resistance to antimonial compounds and similar expression changes have also been demonstrated in naturally resistant isolates from patients. in conclusion, it was revealed that L.tropica strains in our country may gain resistance to meglumine antimoniate in a short time. It is foreseen that if the patients living in our country or entering the country are treated inadequately and incompletely, there may be new, resistant leishmaniasis foci that may increase the number of resistant strains and cases rapidly.

Amaç: Bu çalışmada, gerçek zamanlı polimeraz zincir reaksiyonu yöntemi ile parazitin sitokrom b gen bölgesi kullanılarak leishmaniasis etkeninin (Leishmania donovani, Leishmania major, Leishmania tropica ve Leishmania infantum) tür tayininin belirlenmesi için primer ve probların dizayn edilmesi amaçlanmıştır. Yöntem: Manisa Celal Bayar Üniversitesi Tıp Fakültesi Parazit Bankası’nda kriyoprezervasyonu yapılarak sıvı azot tankında saklanmış olan Leishmania suşları uygun koşullarda canlandırılarak besiyerlerine aktarılmış ve ticari kit ile DNA izolasyonları yapılmıştır. Elde edilen DNA’lara Leishmania’nın yeni tasarladığımız sitokrom b gen bölgesi primer ve prob adayları ve kontrol için daha önce kullandığımız internal transcribed spacer-1 gen bölgesine özgü tasarlanan primer ve problar kullanılarak gerçek zamanlı polimeraz zincir reaksiyonu erime analizleri uygulanmıştır. Bulgular: Yeni tasarlanan sitokrom b gen bölgesi primer ve probları ile Leishmania tropica, Leishmania major, Leishmania infantum, Leishmania donovani, Leishmania aethiopica ve Leishmania infantum/donovani hibrit türlerinin genotiplendiği saptanmıştır. Sonuç: Yeni Dünya leishmaniasis etkenleri olan Leishmania brazilensis ve Leishmania amazonensis dışında, Eski Dünya leishmaniasis etkeni olan Leishmania tropica, Leishmania major, Leishmania infantum, Leishmania donovani, Leishmania aethiopica ve Leishmania infantum/ donovani hibritinin yeni tasarlanan sitokrom b gen bölgesi primer ve probları kullanılarak başarı- lı bir şekilde genotiplendirildiği görülmüştür, Objective: In this study, it was aimed to design primers and probes to identify Leishmania species (Leishmania donovani, Leishmania major, Leishmania tropica and Leishmania infantum) through Real Time Polymerase Chain Reaction using the cytochrome b gene region. Method: The Leishmania strains, which have been cryopreserved and stored in liquid nitrogen in the Parasite Bank of Manisa Celal Bayar University, were transferred to culture media after being revived under the appropriate conditions and their DNA isolations were conducted using a commercial kit. Real Time Polymerase Chain Reaction melting analyses were conducted for the extracted DNA by utilizing both the candidate primers and probes of cytochrome b gene region, newly designed for Leishmania, and the primers and probes, designed for internal transcribed spacer-1 gene region we had previously used for control. Results: Leishmania tropica, Leishmania major, Leishmania infantum, Leishmania donovani, Leishmania aethiopica and Leishmania infantum/donovani hybrid species were managed to be genotyped succesfully using the primers and probes of the newly designed cytochrome b gene region. Conclusion: It has been observed that Old World Leishmania species (Leishmania tropica, Leishmania major, Leishmania infantum, Leishmania donovani, Leishmania aethiopica and Leishmania infantum/donovani hybrid), rather than New World Leishmania species (Leishmania brazilensis and Leishmania amazonensis), were successfully genotyped by the primers and probes of the newly designed cytochrome b gene region.

WOS: 000413524200001, PubMed ID: 29252169, Pemphigus is a group of rare and life-threatening autoimmune blistering diseases of the skin and mucous membranes. Although they occur worldwide, their incidence shows wide geographical variation, and prospective data on the epidemiology of pemphigus are very limited. Objective of this work is to evaluate the incidence and epidemiological and clinical features of patients with pemphigus in Turkey. All patients newly diagnosed with pemphigus between June 2013 and June 2014 were prospectively enrolled in 33 dermatology departments in 20 different provinces from all seven regions of Turkey. Disease parameters including demography and clinical findings were recorded. A total of 220 patients were diagnosed with pemphigus during the 1-year period, with an annual incidence of 4.7 per million people in Turkey. Patients were predominantly women, with a male to female ratio of 1:1.41. The mean age at onset was 48.9 years. Pemphigus vulgaris (PV) was the commonest clinical subtype (n= 192; 87.3%), followed by pemphigus foliaceus (n= 21; 9.6%). The most common clinical subtype of PV was the mucocutaneous type (n= 83; 43.2%). The mean Pemphigus Disease Area Index was 28.14 +/- 22.21 (mean +/- Standard Deviation). The incidence rate of pemphigus in Turkey is similar to the countries of South-East Europe, higher than those reported for the Central and Northern European countries and lower than the countries around the Mediterranean Sea and Iran. Pemphigus is more frequent in middle-aged people and is more common in women. The most frequent subtype was PV, with a 9-fold higher incidence than pemphigus foliaceus.

WOS: 000428835600005, PubMed ID: 29642829, Leishmaniasis is a vector-borne zoonotic disease that shows different clinical features like cutaneous, mucocutaneous, visceral and viscerotropic forms. The protocols used in the treatment of leishmaniasis are toxic and have many limitations during administration. One of the limitations of treatment is the resistance against the protocols in practice. There is also a need to define new treatment options especially for resistant patients. Ex-vivo models using primary cell cultures may be a good source for evaluating new drug options in patients with antimony resistance, in addition to in-vitro and in-vivo studies. In this study, it was aimed to define a new ex-vivo culture model to evaluate treatment options in patients with cutaneous leishmaniasis who did not respond to treatment. In our experimental model of ex-vivo infection, Leishmania tropica promastigotes isolated from a case previously diagnosed with cutaneous leishmaniasis were used. The primary astroglial cell culture used for the ex-vivo model was prepared from 2-3 days old neonatal Sprague Dawley rat brains under sterile conditions by the modification McCarthy's method. The astroglia cells, which reached sufficient density, were infected with antimony resistant L.tropica promastigotes. After 24 hours of incubation, the supernatant on the cells were collected, the cell culture plate was dried at room temperature, then fixed with methyl alcohol and stained with Giemsa to search for L.tropica amastigotes. Amastigotes were intensely observed in glia cells in primary cell cultures infected with L.tropica promastigotes. No promastigotes were seen on Giemsa stained preparations of the precipitates prepared from the bottom sediment after the centrifugation of the liquid medium removed from the infected plates. In this study, promastigotes from a cutaneous leishmaniasis patient unable to respond to pentavalent antimony therapy were shown to infect rat glia cells and converted to amastigote form. This amastigote glial cell model, as far as we know, is the first model in the literature produced by L.tropica. The occurrence of L.tropica amastigote forms in glia cells may be indicative of the ability of Leishmania species to infect the central nervous system. The central nervous system may be an area for the Leishmania amastigotes to escape from the immune system in cases of leishmaniasis without a treatment response. Our study is important because it is the first study to show the infection of glia cells with L.tropica amastigotes.

Objectives: Lichen planus is an immunologic disease mediated by lymphocytes in which T lymphocytes target at basal cells. It is believed that TNF-α that is released from T lymphocytes and keratinocytes plays a key role in the starting and progression of lichen planus by inducing apoptosis. MHC Class-I antigens on basal keratinocytes and interleukin-2 (IL-2) and IFN-gamma (γ) that are produced from CD4+ T cells stimulate the apoptosis of keratinocytes in lichen planus. The aim of this study was to measured the IL-2 and TNF-α levels in peripheral blood from patients with Lichen planus. Materials and methods: A total of 26 lichen planus patients (18 females, 8 males) that applied to the dermatology policlinics in Dicle University Hosspital between 2004 and 2006 and a healthy control group were included in the study. Serum IL-2 and TNF-α levels were measured by using Immulate 1000 solid phase and two-site chemiluminescent immunometric assay method. The results of patients and control group were compared. Results: Level of IL-2 (1172.615 ± 774.967) and TNF-α (13.361 ± 5.638) were higher in lichen planus to compared controls. IL-2 and TNF-α levels in the patient group were found to be significantly high statistically compared to health control group, respectively p=0.004 and p, Amaç: Liken planus T lenfositlerin bazal hücreleri hedef aldığı lenfosit aracılı immünolojik bir hastalıktır. T lenfositlerinden ve keratinositlerden salınan TNF-α\'nın apoptozisi indükleyerek liken planusun başlangıç ve progresyonunda anahtar rolü oynadığı düşünülmektedir. Bazal keratinositlerin üzerindeki MHC Class-I antijenler ve CD4+ T hücrelerinden üretilen IL-2 ve IFN-gamma (γ) liken planusta keratinositlerin apoptozisini tetiklemektedir. Bizim çalışmamızın amacı liken planuslu hastaların periferik kanlarındaki İL-2 ve TNF-α seviyelerini saptamaktır. Gereç ve yöntem: Dicle Üniversitesi Tıp Fakültesi Dermatoloji polikliniğine 2004-2006 yılları arasında başvuran 26 liken planuslu hasta (18 kadın, 8 erkek) ve sağlıklı kontrol grubu çalışmaya alındı. Serum IL-2 ve TNF-α seviyeleri Immulate 1000 solid faz ve two-site chemiluminescent immunometric assay yöntemi kullanılarak ölçüldü. Hasta ve kontrol grubunun sonuçları istatistiksel olarak karşılaştırıldı. Bulgular: IL-2 (1172,615 ± 774,967) ve TNF-α (13.361 ± 5,638) seviyeleri liken planuslu hastalarda kontrollere göre daha yüksek saptandı. Hasta grubunda IL-2 ve TNF-α seviyeleri, sağlıklı kontrollere göre istatistiksel olarak anlamlı derecede yüksek bulundu (sırasıyla p=0.004 ve p

Lichen planus is a benign, inflammatory and itchy dermatosis that is incurred by skin, skin extensions and mucosa. Lichen planus rarely show palmoplantar involvement. Since stratum corneum in palmoplantar lichen planus is extremely thick, lesions can be yellow colored instead of the purple colored papules that are classic lesions. Clinically, it might be confused with psoriasis, secondary syphilis, verruca vulgaris, hyperkeratotic eczema, palmoplantar keratodermas, hyperkeratotic type tinea pedis and xanthomas. In this report, four lichen planus cases were presented who represented palmoplantar involvement., Liken planus deri, deri eklentileri ve mukozayı tutan selim, yangısal ve kaşıntılı bir dermatozdur. Liken planus nadiren palmoplanter tutulum gösterir. Plamoplanter liken planusda stratum corneum çok kalın olduğu için bu bölgedeki lezyonlar klasik erguvani görünüm yerine sarı renkte olabilir. Klinik olarak psoriasis, sekonder sifiliz, siğil, hiperkeratotik egzema, palmoplanter keratoderma, hiperkeratotik tinea pedis ve ksantomalar ile karıştırılabilir. Bu raporda, palmoplantar tutulum gösteren dört liken planus olgusu sunulmuştur.

Amaç: Anabilim Dalı'mızda pilomatrikoma tanısı alan 32 olgunun histolojik ve klinik özelliklerini gözden geçirmeyi amaçladık. Materyal ve Metot: Bu çalışmada, 1984-1999 yılları arasında Dide Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı 'nda pilomatrikoma tanısı alan 32 olgu sunuldu. Bulgular: Ortalama yaşı 27.43 olup, olguların çoğunluğu üçüncü dekaddaydı. Olgulardan birinde perforasyon izlendi. Histopatolojik olarak pilomatrikomanın en önemli özelliği hayalet hücreleridir. Baş, boyun ve üst ekstremitelerin en sık yerleşim yeri olduğunu izledik. Sonuç: KUnik olarak pilomatrikoma diğer lezyonlarla kolaylıkla karışabilmektedir. Anahtar kelimeler: Deri, pilomatrikoma, kalsifiye epitelioma, malherbe, Objectives: The purpose of this study is to review the clinical and histologic features of pilomatricomas diagnosed in our department. Materials and Methods: In this study, 32 patients with pilomatricoma diagnosed at Pathology Department of Dide University Medical Faculty, during the period 1984-1999 are presented. Findings: The mean age was 27.43 years and the majority of the cases occurred in the third decade of life. One of our cases was perforating pilomatricoma. Histopathologically, the most important feature of pilomatricoma was shadow cells (ghost cells). We observed that the most common sites were head, neck and upper limb. Conclusions: Pilomatricoma can be easily confused clinically with other lesions. Key words: Skin, pilomatricoma, calcifying epithelioma ofmalherbe

Background: Leishmaniasis is a protozoan disease caused by more than twenty Leishmania species which are transmitted by infected phlebotomine sandflies to humans. Leishmaniasis include multiple clinical syndromes such as visceral , mucosal and cutaneous forms. Cutaneous Leishmaniasis (CL) is the most common and endemic form in southeastern Turkey. Purpose: CL can be caused by L. major, L. tropica, L. mexicana and L. amazonensis. Microscopy remains to be the standard diagnostic method because of its cheapness, ease of application and high specificity . Microscopic examination of smears, parasite culture and serological tests are performed for diagnosis. Recently several molecular methods, especially those based on the Polymerase chain reaction (PCR) have been developed for identification of Leishmania species. Method: In this study, 150 smear samples taken from patients with clinical findings of CL were studied by PCR- RFLP (restriction fragment length polymorphism) Results: Leishmania tropica was detected in 128 smear sample. L. tropica was found to be the most common species causing CL in southeastern Turkey. Conclusion: Identification of Leishmania species is important because different types may require different treatments. Determining the common species in the region may lead to develop treatment protocols.

Pemfigus nadir görülen, kronik seyirli, hayatı tehdit eden otoimmün bir hastalıktır. Bu retrospektif çalışmanın amacı Dicle Üniversitesi Tıp Fakültesi Dermatoloji kliniğinde tedavi edilen pemfiguslu hastalarda seyir ve prognozu değerlendirmektir. Kliniğimizde Temmuz 1994 - Ocak 2004 tarihleri arasında pemfigus tanısı ile düzenli izlenmiş 42 hastanın tıbbi kayıtları retrospektif olarak incelendi. Bu hastaların 38\'i metilprednizolon ve azathioprin kombinasyonu ile, 4\'ü ise sadece metilprednizolon ile tedavi edilmişti. Başlangıç dozları metilprednisolon için günlük 80-300 mg, azathioprin için 100-150 mg arasında değişiyordu. Metilprednisolon ve azathioprin kombinasyonu ile tedavi edilen 5 olguda remisyon sağlanamamıştı. Hastaların 5\'i ölmüştü. Ölen hastaların tümü pemfigus vulgaris hastaları idi. Dört hastada ölümün nedeni hastalıkla veya tedavi ile ilişkili idi. Yirmi dokuz hastanın 4 ay ile 8 yıl arasında değişen sürelerden beri tedavisiz remisyonda oldukları saptandı., Pemphigus is a rare, chronic and life-threating autoimmune disease. The objective of this retrospective study was to evaluate the course and prognosis of pemphigus patients treated in our clinics. Medical records of 42 patients followed up regularly, and diagnosed at the Department of Dermatology, Faculty of Medicine, University of Dicle, from July 1994 to January 2004 were reviewed retrospectively. Of 42 patients with pemphigus, 38 had been treated with combination of methylprednisolone and azathioprine. Four patients had been treated with methylprednisolone alone. The initial doses ranged from 80 to 300 mg of methylprednisolone and 100-150 mg of azathioprine daily. No remission was obtained in 5 cases treated with combined therapy of methylprednisolone and azathioprine. Of 42 patients, 5 died during the study period. All of the patients who died were those patients with pemphigus vulgaris. In 4 patients, death occurred due to reasons related to the disease or treatment. Twenty nine patients were in complete remission with no therapy for duration varying between 4 months and 8 years.