Chronic pelvic allodynia is mediated by CCL2 through mast cells in an experimental autoimmune cystitis model.

The cause of chronic pelvic pain in interstitial cystitis/painful bladder syndrome (IC/PBS) remains unclear; autoimmunity is a possible etiology. We have recently shown that injection of a single immunogenic peptide of uroplakin 3A (UPK3A 65-84) induces experimental autoimmune cystitis (EAC) in female BALB/cJ mice that is unique among experimental models in accurately reflecting both the urinary symptoms and pelvic pain of IC/PBS. The aim of this project was to identify the roles of mast cells and mast cell chemoattractant/activator monocyte chemoattractant protein-1 [chemokine (C-C motif) ligand 2 (CCL2)] in the allodynia in this model. We immunized 6- to 8-wk-old female BALB/cJ mice with UPK3A 65-84 peptide and, 5-40 days later, observed increased responses to stimulation of the suprapubic abdominal and hindpaw surfaces with von Frey monofilaments compared with mice injected with adjuvant alone. Suprapubic and hindpaw tactile allodynia responses by EAC mice were blocked by instillation of lidocaine into the bladder but not by lidocaine in the uterus, confirming the bladder as the source of the hypersensitivity. Markedly increased numbers of activated mast cells and expression of CCL2 were found in the bladder after immunization with UPK3A 65-84. Hypersensitive responses were inhibited by mast cell stabilizer cromolyn sodium and antagonists of histamine receptors 1 and 2. Furthermore, BALB/cJ mice with deletion of the Ccl2 or chemokine (C-C motif) receptor 2 gene exhibited markedly reduced allodynia and accumulation of mast cells after UPK3A 65-84 immunization. These results show that UPK3A 65-84 immunization causes chronic visceral allodynia and suggest that it is mediated by CCL2-driven mast cell accumulation in the bladder.

Matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2, and transforming growth factor beta 1 in the aqueous humor and serum of patients with pseudoexfoliation syndrome.

PURPOSE: The aim of the study reported in this article was to determine the presence and quantitative differences of matrix metalloproteinase-2 (MMP-2), its tissue inhibitor (TIMP-2) and transforming growth factor beta 1 (TGF-ß1) in the aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome. METHODS: Aqueous humor and serum samples were collected from 32 patients with PEX syndrome (with and without glaucoma) and a control group, who underwent routine cataract surgery. Levels of MMP-2, TIMP-2, and TGF-ß1 were determined by specific immunoassays (enzyme-linked immunosorbent assay). RESULTS: MMP-2, TIMP-2, and TGF-ß1 were identified in aqueous humor and serum samples from all groups of patients. The aqueous and serum samples of MMP-2, TIMP-2, and TGF-ß1 showed no significant differences between PEX syndrome and control groups. Serum levels of MMP-2, TIMP-2, and TGF-ß1 were statistically greater than their aqueous levels (P<0.05), except for TIMP-2 levels in the control group. CONCLUSION: No statistically significant difference among mean MMP-2, TIMP-2, and TGF-ß1 levels in both aqueous humor and serum samples was found between patients with PEX syndrome and the control group. It is important to simultaneously evaluate serum and aqueous samples from patients with PEX syndrome, which is related to an impaired blood-aqueous barrier.

Stem cell homing factor, CCL7, expression in mouse models of stress urinary incontinence.

OBJECTIVES: Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7) In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence using VD and pudendal nerve transection (PNT). METHODS: Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT, anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An analysis of variance model was used to compare the relative expression of CCL7 in each group. RESULTS: Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (P < 0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD, or anesthesia groups compared with the controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in the VD, PNT, and sham PNT (P < 0.01 in all) groups after 24 hours compared with the control group. CONCLUSIONS: This study demonstrates overexpression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 overexpression. The overexpression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.

Uroplakin peptide-specific autoimmunity initiates interstitial cystitis/painful bladder syndrome in mice.

The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) is enigmatic. Autoimmunity and impaired urothelium might lead the underlying pathology. A major shortcoming in IC/PBS research has been the lack of an appropriate animal model. In this study, we show that the bladder specific uroplakin 3A-derived immunogenic peptide UPK3A 65-84, which contains the binding motif for IA(d) MHC class II molecules expressed in BALB/c mice, is capable of inducing experimental autoimmune cystitis in female mice of that strain. A highly antigen-specific recall proliferative response of lymph node cells to UPK3A 65-84 was observed, characterized by selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype, including enhanced production of interferon γ and interleukin-2. T cell infiltration of the bladder and bladder-specific increased gene expression of inflammatory cytokines were observed. Either active immunization with UPK3A 65-84 or adoptive transfer of peptide-activated CD4+ T cells induced all of the predominant IC/PBS phenotypic characteristics, including increased micturition frequency, decreased urine output per micturition, and increased pelvic pain responses to stimulation with von Frey filaments. Our study demonstrates the creation of a more specific experimental autoimmune cystitis model that is the first inducible model for IC/PBS that manifests all of the major symptoms of this debilitating condition.

A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide.

The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. Eight-week-old mice were immunized subcutaneously with prostate-specific peptides in an emulsion of complete Freund's adjuvant. Mice were euthanized 10 days after immunization, and lymph node cells were isolated and assessed for recall proliferation to each peptide. P25 99-118 was the most immunogenic peptide. T-cell and B-cell immunity and serum levels of C-reactive protein and nitrate/nitrite levels were evaluated over a 9-wk period. Morphometric studies of prostate, 24-h micturition frequencies, and urine volume per void were evaluated. Tactile referred hyperalgesia was measured using von Frey filaments to the pelvic region. The unpaired Student's t-test was used to analyze differences between EAP and control groups. Prostates from p25 99-118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1ß, not observed in control mice. Compared with controls, p25 99-118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99-118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments.

Glaucoma after penetrating keratoplasty: incidence, risk factors, and management.

Purpose. To report the incidence and risk factors for postkeratoplasty glaucoma (PKG), as well as its management. Subjects and Methods. 122 eyes, (43% with pseudophakic and aphakic bullous keratopathy (PABK)) which underwent penetrating keratoplasty (PK), were analyzed. Results. The rate of PKG development was 34% within 39 months of follow-up. PABK, corneal perforations, keratitis, and previous high intraocular pressure (PHIOP) were high risk factors for PKG. Glaucoma was controlled medically in 62% of PKG cases. Surgery (Ex-PRESS shunt in 63%) and diode laser cyclophotocoagulation were applied in others (38%). The rate of postoperative complications and graft survival was similar in eyes with and without PKG. Conclusion. PHIOP, preoperative diagnoses other than keratoconus, and corneal dystrophies were highly associated with PKG. Ex-PRESS shunts were effective in refractory PKG. If glaucoma is controlled, it is possible to obtain similar rates of graft survival and postoperative complications in eyes with and without PKG.

Long-term results of bare sclera, limbal-conjunctival autograft and amniotic membrane graft techniques in primary pterygium excisions.

PURPOSE: To compare the long-term follow-up results of the bare sclera technique (BST), limbal-conjunctival autograft technique (LCAT) and amniotic membrane graft technique (AMGT) in primary pterygium excisions. MATERIALS AND METHODS: In this study, 48 eyes of 48 patients who underwent pterygium surgery using BST (group 1), 63 eyes of 63 patients who underwent pterygium surgery using LCAT (group 2) and 52 eyes of 52 patients who underwent pterygium surgery using AMGT (group 3) were compared with respect to corneal epithelialization, recurrence and complication of the procedures. The mean ages of the groups were 47.88 +/- 14.21 years in group 1, 49.63 +/- 14.42 years in group 2 and 47.92 +/- 15.52 years in group 3. Patients were followed up to 72.39 +/- 11.03 months in group 1, 69.91 +/- 12.41 months in group 2 and 61.43 +/- 9.83 months in group 3. RESULTS: Postoperative corneal epithelialization was completed in 5.62 +/- 1.74 days in group 1, 4.33 +/- 0.91 days in group 2 and 4.79 +/- 1.39 days in group 3. Corneal epithelialization time was earlier in group 2 than in groups 1 (p < 0.01) and 3 (p < 0.05). Recurrences were detected in 19 eyes (39.58%) in group 1, 11 eyes (14.29%) in group 2 and 12 eyes (23.08%) in group 3. The recurrence rate was significantly lower in group 2 than in groups 1 and 3 (p < 0.001). Postoperative complications were not seen in any of the groups. Graft retraction and necrosis were not detected in the LCAT and AMGT groups during the follow-up period. CONCLUSIONS: LCAT was found to be a more effective procedure than BST and AMGT, with decreased recurrence rates after pterygium excision. Limbal-conjunctival autograft seems to be a useful treatment in pterygium surgery due to higher success rates and lower recurrence rates. Amniotic membrane grafts may be an alternative surgical technique for pterygium treatment for patients with or without glaucoma who might need glaucoma surgery in the future.

[Cystic echinococcosis in Turkey from 2001-2005]. / Türkiye'de 2001-2005 Yillari Arasinda Kistik Ekinokokkozis.

Cystic echinococcosis (CE) caused by the metacestode form of Echinococcus granulosus is a major public health problem especially in animal-raising regions of the world. In the present study, CE cases were determined during 2001-2005 by investigating different hospital and health directorship documents and Health Ministry documents, retrospectively. Our results show that there were 2534 (13.13%) cases in the Marmara region; 2114 (16.94%), in the Aegean region; 2578 (16.09%), Mediterranean region; 5404 (38.57%), in the Middle Anatolian region; 428 (5.70%), in the Black Sea region; 844 (6.80%), in the eastern Anatolian region; and 887 (2.75%), in the southeastern Anatolian region making a total of 14,789 CE cases. Finally, it has been determined that the patients were hospitalized for a total of 149,464 days.

Treatment of intracameral fibrinous membranes with tissue plasminogen activator.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of intracameral tissue plasminogen activator (tPA) in the treatment of severe fibrinous membranes that do not respond to anti-inflammatory treatment. PATIENTS AND METHODS: In this technique, 0.1 mL of aqueous was aspirated, followed by injection of 0.1 mL (25 microg) of tPA into the anterior chamber in 15 patients with severe fibrinous membranes that developed after pars plana vitrectomy (n = 6), cataract extraction (n = 4), combined cataract and glaucoma surgery (n = 2), trabeculectomy (n = 1), and endophthalmitis (n = 2). The clearance of fibrinous membranes and changes in visual acuity and in intraocular pressure were observed. RESULTS: Patients were treated 2 to 10 days postoperatively (mean, 5.6 +/- 0.57 days). Complete fibrinolysis was observed in all cases. The mean time for clearance of fibrin was 7.73 +/- 2.73 hours. A temporary increase in intraocular pressure was noted in two cases. CONCLUSION: In this technique, intracameral injection of 25 microg of tPA is both effective and safe in the treatment of severe fibrinous membranes that do not respond to anti-inflammatory treatment.

The effect of N-acetyl serotonin on ultraviolet-radiation-induced cataracts in rats.

AIMS: To investigate the effects of ultraviolet radiation (UVR) on cataract development in rat lenses and whether or not N-acetyl serotonin has an effect on changes in these lenses. MATERIAL AND METHODS: The study was performed using 5 groups of Sprague-Dawley albino rats, with each group consisting of 15 rats. The 5th group being the control group did not receive any applications, whilst the other 4 groups received a daily dose of 0.2 J/cm(2)/day UVR (305 nm wavelength) for 60 days. A dose of 4 mg/kg/0.1 ml N-acetyl serotonin was injected intraperitoneally to group 1 and group 2 every day and on alternate days, respectively. Group 3 received an intraperitoneal injection of 0.1 ml phosphate buffer solution every day, whilst group 4 received no injection. On the 60th day, an intracardiac withdrawal of blood was performed, after the rats had been anesthetized with ether. Following the withdrawal of blood, the rats were killed using a high dose of ether and their eyes were enucleated. The lens fresh weights, plasma malondialdehyde (P-MDA), erythrocyte glutathione peroxidase (E-GSHPx), erythrocyte glutathione reductase, blood reduced glutathione (B-RGSH), erythrocyte catalase (E-CAT), lenticular malondialdehyde, lenticular superoxide dismutase (L-SOD), lenticular glutathione peroxidase (L-GSHPx) and lenticular glutathione (L-GSH) levels were all assessed. RESULTS: The lens fresh weights were determined to be lower in group 1 and in the control group in comparison with the other groups (p < 0.01). Whilst the P-MDA level was found to be lower (p < 0.001), the E-GSHPx level was higher (p < 0.01) in the control group than in the other groups. The E-GSHPx level was higher in groups 1 and 2 than in groups 3 and 4 (p < 0.01). The B-RGSH level was higher in the control group than in the other groups (p < 0.001). The E-CAT level was higher in both the control group and group 1 than in groups 2, 3 and 4 (p < 0.01), whilst it was higher in group 2 when compared to groups 3 and 4 (p < 0.01). The L-SOD levels were found to be higher in the control group and group 1 than in groups 2, 3 and 4 (p < 0.001). Whilst the L-GSHPx levels were determined to be higher only in the control group (p < 0.001), the L-GSH levels were higher in the control group and group 1 than in the other groups (p < 0.001). CONCLUSIONS: In recent years, the depletion of the atmospheric ozone layer has resulted in the penetration of more UVR to the earth, which causes various effects on different tissues of organisms. N-acetyl serotonin, a melatonin precursor, may well be effective in the prevention of the negative effects induced by the UVR upon the lens tissue, in which case the capability of melatonin to capture free radicals as well as its antioxidative properties should be taken into consideration.

Results of autografting of marginal conjunctiva in pterygium excision.

PURPOSE: To investigate and compare the efficiency of autografting of marginal conjunctiva (autograft of marginal conjunctiva technique, AMCT) and the bare sclera technique (BST) in pterygium excision. MATERIALS AND METHODS: In this study, 51 eyes of 51 patients who underwent pterygium surgery using the AMCT (group 1) were compared to 45 eyes of 45 patients who underwent pterygium excision using the BST (group 2), with regard to epithelialisation, recurrence and complication of the procedures. Patients were followed up for 15.37 +/- 12.01 months in group 1 and for 18.57 +/- 10.42 months in group 2. RESULTS: Postoperative epithelialisation was completed in 4.34 +/- 1.27 days in group 1 and in 5.61 +/- 1.71 days in group 2. Epithelialisation was completed earlier in group 1 than group 2 (p < 0.05). Recurrences were detected in 7 eyes (13.73%) of group 1 and in 17 eyes (37.78%) of group 2. The difference between the groups was statistically significant (p < 0.01). No postoperative complications were seen in either of the groups. CONCLUSIONS: The AMCT was found to be a more efficient procedure than the BST. Autografting of marginal conjunctiva may be a useful alternative treatment in pterygium surgery due to higher success and lower recurrence rates.