M. Akif Çiftçioğlu

Nitrotyrosine formation and apoptosis in rat models of ocular injury.

This study was performed to examine inducible nitric oxide synthase (NOS-2) expression, nitrotyrosine formation and apoptosis in rats with elevated intraocular pressure (IOP) and/or ocular inflammation. Ocular inflammation was induced via injection of intra-vitreal lipopolysaccharide (LPS) while IOP was elevated by episcleral vessel cauterization. Animals were randomized to one of the following conditions: elevated IOP, LPS, elevated IOP+LPS, and control. Immunohistochemical staining and western blot analysis of retinal lysates revealed NOS-2 and nitrotyrosine immunoreactivity in all disease groups. NOS-2 expression and protein nitration was significantly greater in rats with elevated IOP+LPS compared to elevated IOP, LPS, and control groups. Nitrite levels in the retina affirmed significantly increased levels of nitric oxide generation in LPS-treated rats with elevated IOP (346 ± 23.8 μM) vs LPS-treated, elevated IOP and control groups (195.6 ± 12.6, 130 ± 2.5 and 76.6 ± 15.6 μM, respectively). Retinal TUNEL staining showed apoptosis in all diseased groups. Percent of apoptotic cells was significantly greater in the elevated IOP+LPS group compared to LPS-treated or elevated IOP groups. Presented data illustrates that both elevated IOP and ocular inflammation augment NOS-2 expression, retinal protein nitration and apoptosis in rats.

Diagnosis and Demarcation of Skin Malignancy Using Elastic Light Single-Scattering Spectroscopy: A Pilot Study

BACKGROUND Elastic light single‐scattering spectroscopy (ELSSS) is a noninvasive and real‐time technique that has been used to differentiate tumors from surrounding nontumor tissue in animal models and humans. OBJECTIVE To investigate potential application of ELSSS as an adjunctive tool for noninvasive, in vivo, real‐time differentiation of malignant and benign skin lesions and to detect positive surgical margins of excised biopsy samples. METHODS In vivo spectroscopic measurements were performed on 28 lesions in 23 patients. The distribution of the lesions was as follows: nine basal cell carcinoma (BCC), four melanoma, two squamous cell carcinoma (SCC), and 13 benign lesions. Intraoperative margin assessments were performed on the 28 biopsy samples using ELSSS. RESULTS The sign of the spectral slopes was positive for benign and negative for malignant tissues. It was used as a discrimination parameter between malignant and benign lesions with a sensitivity and specificity of 87% and 85%, respectively. Sensitivity and specificity of the system in detecting positive surgical margins on 14 excised biopsy samples were 80% and 90%, respectively. CONCLUSION ELSSS has the potential for use as an adjunctive tool to reduce the number of negative biopsies and to detect positive surgical margins in real time.

Differentiation of melanoma from non-cancerous tissue in an animal model using elastic light single-scattering spectroscopy.

Cutaneous melanoma is the most serious form of skin cancer and is curable only if it is detected early. The most effective treatment for the melanoma is surgical excision of the lesion. Traditionally, wide margins of excision have been used for effective treatment, but are not always desirable due to increased risk of infection and esthetic reasons. Besides, safe surgical margins of the lesion are not always correlated well with the size of the lesions. We have previously developed a system using elastic light single-scattering spectroscopy to differentiate cancerous tissue from non-cancerous tissue and tested it in vitro. The goal of this study was, therefore, to determine the effectiveness of this system ex vivo by using a mouse model of melanoma. First, a melanoma cell line; B16F10 were injected subcutaneously at right mid flank region of C57BL6 mice (n=5) and allowed to develop for two weeks. Tumors were dissected and spectra were taken on tumor tissue and on normal looking skin tissue that was 10 mm distant from the incision. Since these tumors become markedly necrotic in the middle, spectra of necrotic area was also taken. Slopes of the spectra were positive taken on non-cancerous skin tissues that were later verified by histological examination. On the other hand, it gave negative slopes on melanomas. Increased sizes of the nuclei correlated with the negative slope while smaller nuclei found in non-cancerous tissue gave positive slope. Spectrum taken from necrotic area differed from both cancerous and non-cancerous tissue such that it gave a U-shaped spectrum. These results demonstrate that elastic light single-scattering spectroscopy system can differentiate cancerous tissue from non-cancerous and has potential to be used intraoperatively to determine the surgical margins.

A case of erythema elevatum diutinum associated with breast carcinoma.

A 53‐year‐old woman diagnosed with invasive ductal‐type breast carcinoma was referred to our clinic with red–purple lesions on the hands and legs. She had neither pruritus nor pain. The first lesion developed on the dorsal hand. In the following days, new lesions appeared on the extensor surface of the legs. The patient had been treated with modified radical mastectomy and three courses of cyclophosphamide, adriamycin, and fluorouracil chemotherapy.

Apoptotic and Proliferative Index after Alpha-1-Adrenoceptor Antagonist and/or Finasteride Treatment in Benign Prostatic Hyperplasia

Introduction: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of α1-adrenoceptor antagonist (α1-ARA), 5-α reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. Material and Methods: A total of 49 male patients with BPH (mean age: 66.5 years) treated with α1-ARA and/or finasteride were retrospectively evaluated. Patients treated with α1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and α1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. Results: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. α1- ARA, α1-ARA vs. finasteride + α1-ARA and finasteride + α1-ARA vs. finasteride groups. While α1-ARA was more effective than finasteride on stromal apoptosis, α1-ARA-induced stromal apoptosis was not significantly different from α1-ARA plus finasteirde treatment. Conclusion: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and α1-ARA is not superior to α1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation.

An unusual presentation of immunodeficiency with hyper-IgM.

Abstract: Hyper‐IgM syndrome is a rare immunodeficiency disease characterized by markedly decreased serum IgG, IgA, and IgE levels but normal or elevated IgM levels. The most common clinical signs are infections, cirrhosis, arthritis, malignancies, and mucosal ulcers. Approximately two‐thirds of patients have chronic neutropenia associated with oral and perirectal ulcers. We report a 14‐month‐old girl with hyper‐IgM syndrome who has recurrent cutaneous ulcers restricted to the diaper area.

Detecting Skin Malignancy Using Elastic Light Scattering Spectroscopy

We have used elastic light scattering spectroscopy to differentiate between malign and benign skin lesions. The system consists of a UV spectrometer, a single optical fiber probe and a laptop. The single optical fiber probe was used for both delivery and detection of white light to tissue and from the tissue. The single optical fiber probe received singly scattered photons rather than diffused photons in tissue. Therefore, the spectra are correlated with morphological differences of the cells. It has been shown that spectra of malign skin lesions are different than spectra of benign skin lesions. While slopes of the spectra taken on benign lesions or normal skin tissues were positive, slopes of the spectra taken on malign skin lesions tissues were negative. In vivo experiments were conducted on 20 lesions from 18 patients (11 men with mean age of 68 ± 9 years and 7 women with mean age of 52 ± 20 years) applied to the Department of Dermatology and Venerology. Before the biopsy, spectra were taken on the lesion and adjacent (approximately 1 cm distant) normal-appearing skin. Spectra of the normal skin were used as a control group. The spectra were correlated to the pathology results with sensitivity and specificity of 82% and 89%, respectively. Due to small diameter of fiber probe and limited number of sampling (15), some positive cases are missed, which is lowered the sensitivity of the system. The results are promising and could suggest that the system may be able to detect malignant skin lesion non-invasively and in real time.

Elastic light single-scattering spectroscopy for detection of dysplastic tissues

Elastic light single-scattering spectroscopy (ELSSS) system has been developed and tested in diagnosis of cancerous tissues of different organs. ELSSS system consists of a miniature visible light spectrometer, a single fiber optical probe, a halogen tungsten light source and a laptop. Measurements were performed on excised brain, skin, cervix and prostate tumor specimens and surrounding normal tissues. Single fiber optical probe with a core diameter of 100 μm was used to deliver white light to and from tissue. Single optical fiber probe mostly detects singly scattered light from tissue rather than diffused light. Therefore, measured spectra are sensitive to size of scatters in tissue such as cells, nuclei, mitochondria and other organelles of cells. Usually, nuclei of tumor cells are larger than nuclei of normal cells. Therefore, spectrum of singly scattered light of tumor tissue is different than normal tissue. The spectral slopes were shown to be positive for normal brain, skin and prostate and cervix tissues and negative for the tumors of the same tissues. Signs of the spectral slopes were used as a discrimination parameter to differentiate tumor from normal tissues for the three organ tissues. Sensitivity and specificity of the system in differentiation between tumors from normal tissues were 93% and %100 for brain, 87% and 85% for skin, 93.7% and 46.1% for cervix and 98% and 100% for prostate.

Single Optical Fiber Probe Spectroscopy for Detection of Dysplastic Tissues

A single optical fiber probe with a core diameter of 100 μm was used to deliver visible light to tissue and from tissue to a spectrometer to diagnose cancerous tissues of different organs. Measurements were performed on brain, skin, cervix and prostate tumor specimens and surrounding normal tissues ex-vivo. The spectral slopes were positive for normal tissues and negative for the tumors. Signs of the spectral slopes were used as a discrimination parameter to differentiate tumor from normal tissues for the four organ tissues. Sensitivity and specificity of the system in differentiation between tumors from normal tissues were 93% and %100 for brain, 87% and 85% for skin, 93.7% and 46.1% for cervix and 98% and 100% for prostate respectively.