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    Diagnosis of autoimmune bullous dermatoses: Comparative analysis of immunohistochemical staining using C4d, C3d, IgG, and IgG4 in lesional tissues and perilesional frozen skin samples
    (Elsevier Science Inc, 2024) Karabag, Sevil; Zorlu, Ozge
    Immunohistochemical staining with immunoglobulins and complements may aid the diagnosis of patients whose clinical and histological findings are consistent with autoimmune bullous dermatoses (AIBD). We aimed to investigate the diagnostic value of immunohistochemical markers in lesional biopsy and perilesional frozen samples in AIBD. We included 136 cases from whom lesional biopsies and perilesional samples for direct immunofluorescence (DIF) examination were collected with a preliminary diagnosis of AIBD between January 2019 and January 2023. All diagnoses were reconfirmed by evaluating the clinical, histopathological, and serological findings and DIF results (C3, IgG, IgA, or IgM positivity compatible with the clinical diagnosis) altogether, although DIF results were considered a priority. After confirming the diagnoses, the samples were categorized as AIBD or the others. The perilesional tissues obtained for DIF simultaneously with skin biopsy and stored at-80 degrees C were thawed, and FFPE tissues were prepared. We performed immunohistochemical staining (C4d, C3d, IgG, and IgG4) on FFPE tissues of both lesional and perilesional samples. Strong, linear, or granular staining patterns at the dermoepidermal junction or the intraepidermal blistering space were considered positive in line with the diagnosis of the case. Cases other than AIBD were used as negative control tissues to assess the specificity of immunohistochemical markers. Of the 136 cases, 52 were diagnosed with AIBD. In lesional samples, the sensitivity of C4d, C3d, IgG, and IgG4 was 80.6 %, 69.4 %, 75 %, and 5.7 % with corresponding specificity of 100 %, 98.7 %, 89.6 %, and 97.4 %, respectively in pemphigoid diseases compared to a sensitivity of 18.2 %, 9.1 %, 70 %, and 9.1 % and specificity of 98.7 %, 100 %, 89.6 %, and 97.4 %, respectively in pemphigus diseases. In frozen samples, we detected expression in a limited number of cases. The sensitivity of C4d, C3d, IgG, and IgG4 was 8.7 %, 2.2 %, 19.4 %, and 2.2 %, with corresponding specificity of 100 %, 100 %, 98.5 %, and 98.6, respectively. There was a none to slight concordance rate between the IHC results of lesional tissues and perilesional frozen samples. Kappa coefficients for C4d, C3d, IgG, and IgG4 were 0.120 (P P = 0.029), 0.111 (P P = 0.050), 0.203 (P P = 0.003), and- 0.15 (P P = 0.846), respectively. Immunohistochemical staining with C4d, C3d, IgG, and IgG4 on biopsy samples collected from lesions may guide the diagnosis of AIBD, thereby eliminating the need for an additional biopsy and accelerating the diagnostic process.
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    Digital Skin Ulceration and Acro-Osteolysis: A Rare Presentation of Severe Carpal Tunnel Syndrome
    (Wolters Kluwer Medknow Publications, 2022) Zorlu, Ozge; Karabag, Sevil
    [Abstract Not Available]
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    EZH2 expression in the skin of developing human fetuses and adults: a comparative study
    (Cukurova Univ, Fac Medicine, 2023) Zorlu, Ozge; Karabag, Sevil; Erdogan, Kivilcim Eren; Kussever, Evin; Aslan, Ilke Ozer
    Purpose: In animals, the appropriate levels of Enhancer of zeste homolog 2 (EZH2), a well-established epigenetic regulator, are essential for the embryonic development of skin and appendages. We aimed to explore the EZH2 expression patterns in the skin of human fetuses and compare them with adults.Materials and Methods: We performed EZH2 immunohistochemical staining in skin samples from the scalp region of 67 fetuses and from the farthest surgical margin of the lip wedge resection, where no lesions were found, of 23 adults. EZH2 scores were evaluated according to the literature.Results: Epidermal (r = - 0.528), dermal (rs = - 0.509), and hair follicle (r = - 0.576) EZH2 scores were inversely correlated with gestational age. Epidermal and hair follicle EZH2 scores were significantly higher in adults compared to fetuses. There were significant and positive correlations between epidermal, dermal, and hair follicle EZH2 scores among fetuses and adults.Conclusion: Lower levels of EZH2 may be necessary for final cutaneous differentiation and maturation before birth. Our findings may have a therapeutic impact on cutaneous disorders with differentiation defects, chronic wounds, and alopecias.
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    Histopathological and histomorphometric investigation of the effects of different irrigation solutions on Achilles tendon healing in rats
    (Turkish Joint Diseases Foundation, 2023) Dincel, Yaşar Mahsut; Can, Erdem; Karabag, Sevil
    Objectives: This study aimed to examine the effect of irrigation fluids containing povidone-iodine (PVP-I), rifampicin (RF), and chlorhexidine gluconate (CHG) used during surgery on healing on a rat Achilles tendon model. Materials and methods: Twenty-eight male Sprague-Dawley rats (range, 300 to 400 g) were used in the experiment carried out between November 2022 and December 2022. The rats were divided into PVP-I, RF, CHG, and control groups, with seven rats in each group. Following the tenotomy and repair of the right Achilles tendon, the surgical site was irrigated using PVP-I, RF, CHG, or normal saline (the control group) for 2 min. All rats were sacrificed on the 21st postoperative day. The samples were evaluated histomorphometrically using the scoring system modified by Svensson, Soslowsky, and Cook and histopathologically using the Bonar and Movin classifications. Results: The RF group gave better results in all three scoring systems compared to the control, PVP-I, and CHG groups (p=0.008, p=0.002, and p=0.006, respectively). Cellularity, rounding, and tenocyte morphology showed a significant difference in favor of the RF group (p=0.004). While the distribution of ground substance glycosaminoglycans showed a significant difference in favor of the RF group, there was no significant difference among the other groups (p=0.22). Conclusion: Irrigation solutions containing PVP-I, RF, or CHG show no negative effect on Achilles tendon healing. Moreover, the findings suggest that RF irrigation can accelerate the healing process. © 2024, All right reserved by the Turkish Joint Diseases Foundation This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes (http://creativecommons.org/licenses/by-nc/4.0/).
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    Immunoexpression Patterns of Adhesion Molecules (E-cadherin, ?-catenin, CD56) and Cytokeratins (CK19, CK20, HMWCK, CAM5.2) During Hair Development in Human Fetuses Compared With Adults
    (Lippincott Williams & Wilkins, 2024) Zorlu, Ozge; Karabag, Sevil; Erdogan, Kivilcim E.; Aksin, Merve; Ustun, Batuhan
    Abnormalities in the expression of cytokeratins or adhesion molecules have been associated with hair disorders. The expression patterns of these molecules in the hair follicles of developing human fetuses are not obvious. We aimed to investigate the expression patterns of some cytokeratins and adhesion molecules in the hair follicle of human fetuses and compared them with adults. Forty-eight fetuses of >16 gestational weeks and 22 adult cases with total excisions of benign nevi or cysts were enrolled. The skin samples were taken from both the scalp and back of the fetuses. The histopathologically normal skin areas were evaluated in adults. CK19, CK20, CAM5.2, high-molecular-weight cytokeratin, E-cadherin, beta-catenin, and CD56 immunohistochemical stainings were performed. In the fetus group, the staining scores declined in the third trimester but elevated and reached the highest level in adults, except for CD56, which did not stain any adult samples. All stainings were mostly observed in the outer root sheath, except CD56 that stained the perifollicular dermal sheath only in fetuses. E-cadherin, beta-catenin, and high-molecular-weight cytokeratin strongly and diffusely stained all adult samples. CAM5.2 and CK19 scores were correlated in fetuses (scalp scores: r(s) = 0.405, P = 0.004; back scores: r(s) = 0.422, P = 0.003) and adults (back scores: r(s) = 0.562, P = 0.046). CD56 negativity indicated the immune-privilege feature of adult hair follicles. As CK19, CAM5.2 may be used to find the regions of stem cells or transient amplifying cells.
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    The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair
    (Turkish Joint Diseases Foundation, 2024) Can, Erdem; Dincel, Yasar Mahsut; Karabulut, Derya; Karabag, Sevil; Arslan, Yunus Ziya
    Objectives: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. Materials and methods: Forty-eight adult male SpragueDawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15(th) (early period) or 30(th) (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15(th) and 30(th) days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. Results: Histopathologically, there were no significant differences among the groups on the 15 th day. However, on the 30 th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). Conclusion: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.