Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

BACKGROUND: Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. METHODS AND RESULTS: Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). CONCLUSION: The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study.

Morphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.

Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid.

INTRODUCTION: Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. AIM: To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. MATERIAL AND METHODS: Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0-3 scale. RESULTS: Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). CONCLUSIONS: The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.

Biochemical and histopathologic assessment of effects of acitretin on epiphyseal growth plate in rats.

INTRODUCTION: Acitretin is a commonly used retinoid in dermatology. Although there are generally known side effects, the effects on the epiphyseal plaque and bone metabolism are not clear in the literature. AIM: To histopathologically investigate the effects on the epiphyseal plate and assess variations in bone metabolism caused by acitretin. MATERIAL AND METHODS: Three groups were formed with 10 rats in each group. The 1st group (n = 10, 5 male, 5 female) were administered 10 mg/kg/day oral acitretin solution and the 2nd group (n = 10, 5 male, 5 female) were administered 3 mg/kg/day oral acitretin solution. The control group were given normal standard feed and water. Rats were sacrificed at the end of 4 weeks. The proximal tibias were excised and histopathologically and immunohistochemically assessed. Biochemical assessment was also carried out. RESULTS: Staining with haematoxylin-eosin found reductions in the epiphyseal plate in the 1st and 2nd group compared to the control group, though this situation was not statistically significant. Immunohistochemical studies did not encounter Type II collagen in the epiphyseal bone, proliferative zone and hypertrophic zone in the control group, low dose acitretin solution group and high dose acitretin solution group. Type II collagen was not observed in osteoids and osteoblasts. Type I collagen was not observed in the hypertrophic zone and proliferative zone of any group. CONCLUSIONS: Our data show that though acitretin caused degeneration of the epiphyseal plate, it did not cause clear thinning and we identified no significant variations in bone metabolism markers.

Protective effect of aerobic exercise on the vocal folds against cigarette smoke exposure.

PURPOSE: Laryngeal pathologies due to cigarette smoking vary among individuals, whereas some smokers remain disease free. These differences can be explained by multiple factors among individuals. In this context, an animal study was designed to determine if there is any protective effect of aerobic exercise against the detrimental effects of cigarette smoke on laryngeal tissues. METHODS: A total of 24 male Wistar albino rats were divided into three groups of eight animals each: control (no smoke exposure), smoking (smoke exposure), and exercise (smoke exposure and exercise) groups. Histopathological (light and electron microscopy) and immunohistochemical (GSTA1, CYP1A1, CYP2E1) evaluations of the vocal folds were performed at the end of experimental period. RESULTS: Exercise group revealed statistically significant decrease in edema (p = 0.03) and inflammatory cell infiltration (p = 0.02) compared to smoking group. In electron microscopic evaluation; cytoplasmic vacuoles were also present in exercise group, but were smaller than smoking group. Edema and swollen mitochondria were also less prominent in exercise group. Condensed chromatin material in the periphery of nucleus was observed only in few cells in exercise group, and observed in more cells in smoking group. GSTA1 expression was higher (p = 0.047) and CYP1A1 expression was lower (p = 0.01) in exercise group than smoking group. CONCLUSIONS: Our results indicate that aerobic exercise has a protective role on the larynx against the damaging effect of cigarette smoke. Smokers who exercise regularly may be at a lower risk of cigarette smoke-related laryngeal diseases, as compared with those who do not exercise.

Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients.

OBJECTIVE: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. SUBJECTS AND METHODS: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016-2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. RESULTS: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP-1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. CONCLUSION: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

Expression of Sigma-Class Glutathione-S-Transferase in Fetal and Pediatric Filum Terminale Samples: A Comparative Study.

Background and objectives: The pathophysiology of tethered cord syndrome (TCS) in children is not well elucidated. An inelastic filum terminale (FT) is the main factor underlying the stretching of the spinal cord in TCS. Our study aimed to investigate the expression of glutathione-S-transferase (GST) in children and fetal FT samples in order to understand the relationship between this enzyme expression and the development of TCS. Materials and Methods: FT samples were obtained from ten children with TCS (Group 1) and histological and immunohistochemical examinations were performed. For comparison, FT samples from fifteen normal human fetuses (Group 2) were also analyzed using the same techniques. Statistical comparison was made using a Chi-square test. Results: Positive GST-sigma expression was detected in eight (80%) of 10 samples in Group 1. The positive GST-sigma expression was less frequent in nine (60%) of 15 samples from Group 2. No statistically significant difference was detected between the two groups (p = 0.197). Conclusions: Decreased FT elasticity in TCS may be associated with increased GST expression in FT. More prospective studies are needed to clarify the mechanism of the GST-TCS relationship in children.

Evaluation of oxidative stress via protein expression of glutathione S-transferase and cytochrome p450 (CYP450) isoenzymes in psoriasis vulgaris patients treated with methotrexate.

INTRODUCTION: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products. AIM: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process. MATERIAL AND METHODS: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15 mg/week of MTX for minimum 12 weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. RESULTS: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05, respectively). In the psoriasis patients, GSTO1 expression was similar the control group. CYP1B1 and CYP2E1 expressions were significantly higher in the pre-treatment and post-treatment psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05; p < 0.05, respectively). CONCLUSION: We found a significant increase in the tissue levels of, either expression of GST, or CYP, which has important role in drug metabolism and oxidative stress. MTX treatment resulted in marked clinical improvement, yet we found that MTX did not have any significant effect on these parameters. CYP2E1 is especially the most important enzyme for MTX metabolism since it is the primarily responsible of the toxic metabolism of various drugs. The other experimental studies involving greater number of patients and other different drug are needed to enlighten the role of oxidant and antioxidant systems and the other possible mechanisms for the pathogenesis of psoriasis.

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris.

BACKGROUND: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. METHODS: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. RESULTS: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). CONCLUSIONS: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

Comparison of TLR-2, TLR-4, and antimicrobial peptide levels in different lesions of acne vulgaris.

CONTEXT: Recent studies have shown that tolls like receptors (TLRs) and antimicrobial peptides (hBD-1, cathelicidin) play an important role in the pathogenesis of acne vulgaris (AV). OBJECTIVE: To evaluate and report the expression of TLR-2, TLR-4, hBD-1 and cathelicidin in different regions of skin in AV. PARTICIPANTS: This study was performed in 80 patients with AV and a control group of 20 healthy individuals. MATERIAL AND METHODS: Skin biopsies were performed from 20 papular, 20 pustular, 20 comedonal and 20 nodular lesions of patients and 20 healthy volunteers. Expression levels of TLR-2, TLR-4, hBD-1 and cathelicidin in four separate areas (epidermis, dermis, inflammation region and skin appendages) were evaluated by immunohistochemical method. Further, these parameters were compared between different skin lesions. RESULTS: A significant difference was found between the levels of staining of TLR-2, TLR-4 and hBD-1 from the epidermis, inflammation region, dermis and skin appendages (p < 0.05). Levels of cathelicidin were different in only the inflammation region (p < 0.05). The level of TLR-2 in the epidermis with nodules was lower than the papules and comedones (p < 0.05). Levels of TLR-2 in the inflammation and dermis of the cases with papules were significantly higher when compared to pustules (p < 0.05). The levels of staining of TLR-4 in the dermis with comedones were significantly lower compared to the cases with papules (p < 005). The level of hBD-1 in the epidermis region of comedones was significantly higher compared to nodules (p < 0.05). The expression of cathelicidin in the inflammation region of comedones was significantly low (p < 0.05). CONCLUSION: It is thought that TLR-2, TLR-4, hBD-1 and cathelicidin play an important role in the pathogenesis of AV and in the development of different acne types. We think that, better results could be obtained in treatment of AV with different treatment options targeted in regulation of TLR-2, TLR-4, hBD-1 and cathelicidin release.

The effect of CYP1A1 and GSTP1 isozymes on the occurrence of aortic aneurysms.

BACKGROUND: Aortic aneurysms are vascular diseases that are associated with high mortality and morbidity. Cytochrome P450 CYP1A1 and glutathione S-transferase (GSTP1) isozymes were searched and compared with the patients who had experienced aortic surgery due to aortic aneurysm and atherosclerotic patients without aneurysm to find the relation of the oxidative stress with the aneurysms. MATERIALS AND METHODS: Study group consisted of the patients with the diagnosis of aortic aneurysm (group I, n: 12) and control group who were operated for coronary bypass surgery: preoperatively drug users (group II, n: 21) and nonusers (group III, n: 15). Paraffin sections (4 µm thick) of aortic biopsy materials were stained with hematoxylin and eosine, CYP1A1 and GSTP1 immunohistochemical markers. The specimens were evaluated using light microscopy at 40- to 400-fold magnification. RESULTS: The expressions of CYP1A1 and GSTP1 isozymes were found statistically significantly higher in the patients who have an aortic aneurysm than both the control groups (p < 0.05). There was no significant association between protein expressions, drugs and duration of usage, patient's demographic variables, and smoking (p > 0.05). CONCLUSIONS: In this pioneering study, CYP1A1 and GSTP1 isozymes are related with the aneurysms. The strategy that prevents the oxidative stress for the patients who had aortic aneurysms could be a valuable choice of searching to effect the aneurysmal progression.

Expression Levels of Glutathione S-Transferase and Cytochrome P450 Isoenzymes in Nasal Polyp Tissue.

Nasal polyps are benign sinonasal masses composed of eosinophils and extracellular edema. Pathogenesis of the polyp formation is unclear but several studies strongly suggest a correlation with infection, inflammation and allergy conditions. Our aim is to investigate the potential link between allergy and nasal polyp in tissue level. Nasal polyp group included 60 patients whose diagnosis was confirmed with biopsy and the control group included 38 healthy patients. Tissue sample of the control group was taken from inferior turbinate mucosa under local anesthesia and nasal polyp tissue was collected from functional endoscopic sinus surgery. The glutathione S-transferase (GST) and cytochrome P450 (CYP) isoenzyme expressions of the tissue samples were investigated under light microscopy and graded by a senior pathologist. GSTP1 protein expression was significantly higher in tissue samples from nasal polyp group compared to that of control group (p < 0.05). However, CYP1A1, GSTM1 and GSTA1 isoenzymes were not different between the two groups (p > 0.05). We have found that GSTP1 isoenzyme was elevated in nasal polyp tissue compared to the control. The increase in protein expression of GSTP1 might have occured as a tissue response to the increased oxidative stress thus suggesting a role of GSTP1 in polyp formation.

Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells.

BACKGROUND AIMS: The types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-α and transforming growth factor (TGF)-ß1 in anastomosed facial nerves that had been treated with or without MSC. METHODS: In seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 18-20, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays. RESULTS: MSC application significantly increased CNTF, PDGF-α, LIF, TGF-ß1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant. CONCLUSIONS: These results suggest that MSC increases expression of CNTF, PDGF-α, LIF,TGF-ß1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors.

Glutathione S-transferase expression in benign and malignant eyelid tumors.

Eyelid tumors commonly originate from the skin and its appendages. Environmental toxins and oxidants affect eyelid carcinogenesis. Glutathione S-transferases (GST) are antioxidants that participate in pathogenesis. We investigated GST levels in malignant and benign eyelid tumors in otherwise healthy individuals. We used 57 malignant eyelid biopsies, benign eyelid biopsies, and tissue removed during blepharoplasty and entropion operations culled from pathology archives. Specimens were divided into three groups: malignant lesions, benign lesions and controls consisting of eyelid tissue removed during routine blepharoplasty and entropion surgery. Specimens were immunostained for seven GST (GST-A, GST-P, GST-Z, GST-S, GST-K, GST-O, GST-T) and the intensity of staining was quantified. In the malignant group, GST-O and GST-P staining was less intense than for the control group. In the benign group, the GST-P level was less than for the control group. We found no significant difference between the intensity of staining in malignant and benign groups. Our findings suggest that GST-O and GST-P enzymes may play significant roles in eyelid carcinogenesis.

Tissue expression of glutathione S transferase isoenzymes in vitiligo.

The association of glutathione S-transferase (GST) enzymes with vitiligo is inconclusive. To evaluate tissue expressions of GST isoenzymes in vitiligo patients and to compare these expressions with healthy controls, we used 26 active depigmented patches on the trunk of vitiligo patients and 20 healthy sex and age matched controls. Punch biopsies were taken from the lesioned or normal skin. Tissue expression of GST isoenzymes were analyzed immunohistochemically. Tissue expression of GSTT1, GSTA1 and GSTP1 was significantly higher in the patient group than controls. Tissue expression of GSTM1 was not significantly different between the two groups. The increased tissue expression of GSTT1, GSTA1 and GSTP1 may represent a response to excess free radical formation in vitiligo and may support the role of oxidative stress in the pathogenesis of vitiligo.

Chemoresistance in Malignant Intracranial Tumors: Longer Survival with Negative MDR1 Expression.

AIM: To analyze the Glutathione S-transferase (GST)-P, GST-M, cytochrome p450 (CYP)1-A1, CYP1-B1, and multidrug resistance (MDR)-1 expressions in malignant intracranial tumor (ICT)s, and to elicit their role on patient survival. MATERIAL AND METHODS: GST-P, GST-M, CYP1-A1, CYP1-B1, and MDR-1 expressions were analyzed using immunostaining in 149 samples from 141 patients with preoperative ICT diagnosis. The case characteristics were reviewed, and the enzyme expressions were equated based on the age, gender, and tumor type. Then, 77 of 141 patients with malignant ICT and complete medical records postoperative were also investigated in detail for the relationship between the diagnosis, enzyme expression, and overall survival. RESULTS: The average age was 49.44 years, with 83 (58.45%) male patients. Among the 77 malignant ICTs, 38 (49.3%) and 29 were glial tumors and metastases, respectively, with a 13.35-month overall survival. Patients with metastatic tumor have approximately threefold higher GSTP level than those with glial tumors. MDR-1 expression was approximately twofold higher in > 60-year-old patients. No statistically significant association was found between patients? smoking behaviors, alcohol consumption, and overall survival. Only MDR-1 expression was correlated with overall survival. Better overall survival was observed in patients with a negative MDR-1 expression than those with a positive one. CONCLUSION: MDR-1 is an important indicator of survival in malignant intracranial tumor patients. Longer survival is associated with negative MDR-1 expression.

Protective Effect of Aerobic Exercise on the Nasal Mucosa of Rats Against the Histopathologic Changes in Cigarette Smoke Exposure.

INTRODUCTION: Smoking is a public health problem that has been proven to have adverse effects on human health. Aerobic exercise has positive effects on the human body, especially on the respiratory system. OBJECTIVE: The aim of this experimental animal model study was to determine whether regular aerobic exercise has a protective effect against the harmful effects of cigarette smoke on the nasal mucosa of rats. METHODS: A total of 24 male Wistar albino rats were randomly separated into 3 groups of 8: group 1 (cigarette smoking), group 2 (cigarette smoking and exercise), and group 3 (control group). At the end of the experiment period, histopathological (light and electron microscopy) and immunohistochemical (GSTA 1, CYP1A1, and CYP2E1) evaluations were made of the nasal mucosa of the animals. RESULTS: Goblet cell loss and basal membrane thickening were significantly lower in group 2 and group 3 compared to group 1. In the electron microscope evaluation, the inflammatory expressions of the goblet cells were observed in a very small area in group 2. In group 1, these were distributed over large areas between the mucosal cells. There was seen to be significant swelling of the mitochondria in group 1 compared to the other groups. No statistically significant difference was determined between the groups with respect to GSTA1, CYP2E1, and CYP1A1 scores (P > .05). CONCLUSION: The results of this study showed that regular aerobic exercise has a protective effect against the harmful effects of smoking on the nasal mucosa of rats.

Effects of Different Doses of Systemic Isotretinoin on Eyes: A Histopathological and Immunohistochemical Study in Rats.

PURPOSE: To evaluate ocular side effects associated with systemic isotretinoin histopathologically. METHODS: In this multicenter study, a total of 15 male and 15 female rats were randomly divided into 3 equal groups according to the oral dose of isotretinoin they were administered: 0 mg/kg/d (group A), 7.5 mg/kg/d (group B), and 15 mg/kg/d (group C). Biopsy specimens were taken from the globe conjunctiva, cornea, and eyelid conjunctiva. Expression levels of human beta-defensin-1, human beta-defensin-2, toll-like receptor (TLR)-2, and TLR-4 were evaluated by immunohistochemical methods. RESULTS: The number of goblet cells in eyelid conjunctiva was significantly lower in group B than that in group A and group C (P = 0.002). The sizes of meibomian gland acini were significantly smaller in group B and group C than those in group A (P < 0.001). Fibrosis of eyelid conjunctiva was significantly higher in group C and group B than that in group A (P = 0.002). The levels of staining of TLR-4 in the cornea with group B were significantly lower compared with group C (P = 0.035). CONCLUSIONS: Our study suggests that isotretinoin in the early period affects eyelid conjunctiva and meibomian glands without affecting the globe conjunctiva and cornea. Occurrence of the initial symptoms of isotretinoin on the eyelids, especially on the meibomian glands, suggests that the symptoms of patients occur because of evaporative dry eye.

Alteration of tissue expression of human beta defensin-1 and human beta defensin-2 in psoriasis vulgaris following phototherapy.

We compared the expression profiles of antimicrobial peptides (AMPs) in psoriatic skin before and after narrow band ultraviolet B (nb-UVB) phototherapy and compared the levels to healthy controls. We studied 15 male and 12 female patients with psoriasis vulgaris, and 11 female and nine male control individuals. The patient group was treated with 24-36 sessions of nb-UVB phototherapy. Immunohistochemical staining for human beta defensin 1 (hBD-1) and human beta defensin 2 (hBD-2) expression of lesioned and control skin was performed prior to and following phototherapy. After phototherapy, the psoriatic area and severity index (PASI) decreased significantly in the treated patients compared to controls. The hBD-1 level was significantly higher in psoriasis patients than healthy controls. We found no statistically significant difference in hBD-1 and hBD 2 levels before and after phototherapy in the patient group. Although hBD-1 plays a role in psoriasis, levels of human beta defensin 1 and 2 are not affected significantly by phototherapy.

Expressions of glutathione S-transferase alpha, mu, pi, and theta in the skin samples of patients with acne rosacea.

BACKGROUND: Data point to the importance of oxidative stress in rosacea. Glutathione S-transferases (GSTs) have substantial roles in a wide variety of oxidative stress-related conditions. AIM: To evaluate the immunohistochemical staining characteristics of GST alpha (GSTA), mu (GSTM), pi (GSTP), and theta (GSTT) in patients with rosacea. PATIENTS/METHODS: The study included 23 women and 7 men with rosacea (mean ± SD age 49 ± 11 year) and 15 healthy control subjects (10 women, 5 men; mean ± SD age 47.86 ± 10.88 year). For each patient, the average disease duration, disease subtype, ocular involvement, and severity score were recorded. A 3-mm punch biopsy was taken from the facial skin of each patient and control. Expression of GST isoenzymes was analyzed immunohistochemically. RESULTS: Expressions of GSTM1, GSTP1, and GSTT1 were significantly elevated in patients with rosacea compared to those in the control group (P = .0001, P = .0002, P < .0001, respectively). In the rosacea group, GSTT1 expression was significantly stronger than GSTP1 and GSTA1 expressions (P = .019, P < .0001, respectively). There were no significant associations between expressions of GST isoenzymes and gender, age, average duration of illness, disease subtype, ocular involvement, or severity score in the patient group (all P > .05). CONCLUSIONS: In rosacea, the significant increase of GSTT1, GSTP1, and GSTM1 expressions might result from activation of GST as an outcome of extreme free radical generation from triggered neutrophils or ultraviolet vulnerability. These findings support the relevance of oxidant stress in the pathogenesis of rosacea.