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Purpose: To identify visually significant spectral-domain optical coherence tomography (SD-OCT) features of epiretinal membranes (ERM) in patients with uveitis., Design: Retrospective cohort and cross-sectional study., Methods: Eighty consecutive eyes with uveitis and SD-OCT-documented ERM were included. Clinical data were collected at the time of diagnosis of ERM and at the final visit. SD-OCT images at the last visit were evaluated to identify fovea and ERM configuration and structural changes. Changes of 10% and 20% in central subfield thickness between initial and last SD-OCT were calculated and correlated with visual acuity (VA). An ERM thickness map was created using validated SD-OCT grading software., Results: VA improved significantly in eyes with more than 12 months of follow-up (P = .03). Although inflammation activity and medical treatment methods were no different in eyes with more or less than 12 months of follow-up, 16 eyes in the subset with longer follow-up underwent cataract extraction and intraocular lens implantation. Kaplan-Meier analysis demonstrated few vision losses during the follow-up period. Change in central subfield thickness did not correlate with VA. Foveal center involvement (P < .001), focal attachment of the ERM (P = .003), and foveal inner segment and outer segment junction disruption (P = .006) were associated independently with lower VA. ERM was thinner in eyes with 20/40 or better VA (4.6 ± 0.6 μm) compared with eyes with VA of less than 20/200 (P = .02). Longer duration of ERM was associated with thicker ERM (P < .05)., Conclusions: In most eyes with uveitis and ERM, VA remains stable if ocular inflammation and comorbidities are addressed appropriately., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes of pars plana vitrectomy (PPV) and intravitreal phacoemulsification in patients with dropped nuclei/nuclear fragments following complicated cataract surgery., Methods: In this retrospective case series, charts of patients who had undergone PPV and intravitreal phacoemulsification for removal of dislocated nuclei/lens fragments were reviewed. After standard PPV, a conventional phacoemulsification probe with an amputated sleeve was used for grasping and emulsifying the nucleus/nuclear fragments in mid/anterior vitreous cavity. Pre- and postoperative visual acuity, and intra- and postoperative complications were recorded., Results: A total of 22 patients with mean age of 71.1±8.2 years were studied. Mean interval between complicated cataract surgery and PPV was 26.6±36.5 (range: 0-120) days. Patients were followed for a mean of 105.5±57.5 days. Preoperatively, best corrected visual acuity was 2.4±0.6 logMAR which was improved to 1.4±0.6 logMAR at final follow-up (P<0.001). Intraoperative complications included iatrogenic peripheral retinal breaks in three eyes. Postoperative complications consisted of epiretinal membrane formation in one eye, hypotony in one eye, and medically-controlled glaucoma in 2 eyes., Conclusion: In this series, PPV and intravitreal phacoemulsification using a conventional phacoemulsification probe in patients with dropped nuclei/nuclear fragments following complicated cataract surgery resulted in visual improvement without any complications directly attributable to the probe.

Background/purpose: The prevalence of obesity and overweight among children and adolescents is increasing rapidly. The present research was performed to determine the influence of a ''behavior modification'' program on body mass index (BMI) in obese public high school students in Iran., Methods: In this study, 152 adolescence and their parents were selected from 12 high schools of Khorram Abad from 2004 to 2006, and they were randomly assigned to either the intervention or the control groups. The "behavior modification" interventional program consisted of nutritional education, modifying dietary habits, teaching exercise programs, teaching nutritional facts to the parents, and performing exercises 3 days a week. The height and weight as well as waist, hip, and wrist circumferences of the participants were measured before and after implementing the interventional program. BMI and waist to hip ratio (WHR) were calculated. The adolescents and parents completed a nutrition knowledge questionnaire. Adolescents also completed the Beck's Depression Questionnaire., Results: Adolescent's mean weight, BMI, and waist and hip circumferences decreased significantly after implementing the interventional program, in the intervention group (p≤0.001). In addition, the students' and parents' nutrition knowledge increased in the intervention group after implementing the interventional program (p<0.046). The symptoms of depression decreased and the frequency of students without symptoms of depression increased in the case group, but it did not reveal a statistically significant difference between case and control groups., Conclusion: The ''behavior modification'' interventional program is effective in reducing BMI in obese students, and therefore, school principals and planners can play an important role in controlling obesity by implementing this program via the students, their parents, and the school staff., (Copyright © 2012. Published by Elsevier B.V.)

Background: Oocyte maturation and subsequent in vitro production (IVP) of embryos are affected by diverse groups of chemicals in maturation medium which are needed for successful mammalian oocyte maturation during which the dramatic cytoplasmic and nuclear reprogramming events take place. This study was designed to evaluate the effects of protein source (fetal bovine serum, FBS, and bovine serum albumin, BSA) as well as two different maturation media during in vitro maturation of ovine oocytes on subsequent embryo development., Methods: Cumulus oocyte complexes were recovered from ovaries obtained from slaughter house and cultured for 24 hr in either TCM-199 or SOFaa maturation medium supplemented with 10% (v/v) FBS or 0.8% (w/v) BSA. Data were analyzed by one-way ANOVA using Sigma Stat (Ver. 2). A p-value smaller than 0.05 was considered statistically significant., Results: The proportions of cleavage and total blastocyst (evaluated on days 3 and 6, respectively) were significantly higher in FBS than BSA supplemented groups, though no differences were observed between the two used different maturation media. The cryotolerance of blastocysts was negatively influenced by the presence of FBS rather than BSA during IVM. The quality of produced embryos, however, was affected neither by the source of macromolecules nor the maturation medium in terms of hatching rate, total blastocyst cells and inner cell mass/total cell ratio., Conclusion: The rate of oocyte development was improved by the presence of FBS, though the cryosurvival of resulting blastocysts was negatively influenced by the presence of the serum during in vitro production of sheep oocytes.

Insulin regulates glucose uptake into fat and skeletal muscle cells by modulating the translocation of GLUT4 between the cell surface and interior. We investigated a role for cortactin, a cortical actin binding protein, in the actin filament organization and translocation of GLUT4 in Chinese hamster ovary (CHO-GLUT4myc) and L6-GLUT4myc myotube cells. Overexpression of wild-type cortactin enhanced insulin-stimulated GLUT4myc translocation but did not alter actin fiber formation. Conversely, cortactin mutants lacking the Src homology 3 (SH3) domain inhibited insulin-stimulated formation of actin stress fibers and GLUT4 translocation similar to the actin depolymerizing agent cytochalasin D. Wortmannin, genistein, and a PP1 analog completely blocked insulin-induced Akt phosphorylation, formation of actin stress fibers, and GLUT4 translocation indicating the involvement of both PI3-K/Akt and the Src family of kinases. The effect of these inhibitors was even more pronounced in the presence of overexpressed cortactin suggesting that the same pathways are involved. Knockdown of cortactin by siRNA did not inhibit insulin-induced Akt phosphorylation but completely inhibited actin stress fiber formation and glucose uptake. These results suggest that the actin binding protein cortactin is required for actin stress fiber formation in muscle cells and that this process is absolutely required for translocation of GLUT4-containing vesicles to the plasma membrane.

Objective: Obsessive-compulsive disorder (OCD) is one of the chronic anxiety disorders that interfere with routine individual life, occupational and social functions. There is controversy about the first choice of treatment for OCD between medication and psychotherapy., Aim: the aim was to investigate the efficacy of eye movement desensitization and reprocessing (EMDR) compared with medication by citalopram in treatment of OCD., Methods: This randomized controlled trial was carried out on 90 OCD patients that randomly were assigned into two groups. They either received therapeutic sessions of EMDR or citalopram during 12 weeks. Both groups blindly were evaluated by the Yale-Brown scale before and after the trial period., Results: Pretreatment average Yale-Brown score of citalopram group was about 25.26 as well as 24.83 in EMDR group. The after treatment scores were 19.06 and 13.6, respectively. There was significant difference between the mean Yale-Brown scores of the two groups after treatment and EMDR was more effective than citalopram in improvement of OCD signs., Conclusion: It is concluded that although both therapeutic methods (EMDR and Citalopram) had significant effect in improving obsessive signs but it seems that in short term EMRD has better effect in improvement of final outcome of OCD.

Objective: To investigate different varicocele hemodynamic patterns (shunt type vs. stop type) as predictors of new-onset testicular hypotrophy or recurrence after varicocelectomy., Design: Prospective clinical study., Setting: Department of pediatric urology, children's hospital medical center., Patient(s): Seventy-four children and adolescents with varicocele., Intervention(s): Based on ultrasound findings, patients were classified into shunt-type or stop-type varicocele groups. All patients with stop-type varicocele and testicular volume discrepancy of ≥20% underwent retroperitoneal varicocelectomy and internal spermatic vein ligation. Patients with shunt-type varicocele and ≥20% testicular asymmetry were randomly divided to undergo either retroperitoneal varicocelectomy (ligation of internal spermatic vein) or inguinal varicocelectomy with ligation of both internal and external spermatic veins. Patients with testicular volume discrepancy of <20% were put on conservative management., Main Outcome Measure(s): Occurrence of new-onset asymmetry among untreated patients and recurrence rate among operated patients., Result(s): Patients with shunt-type varicocele who did not undergo surgery revealed a higher risk of developing asymmetry during follow-up (odds ratio 10.5). Ligation of both internal and external spermatic veins in shunt-type patients was associated with significantly decreased rate of recurrence (6.3%) compared with retroperitoneal approach (30.8%)., Conclusion(s): Shunt-type varicocele is associated with a higher risk of testicular hypotrophy among untreated patients. In addition, recurrence rate in shunt-type patients who underwent inguinal varicocelectomy was lower compared with retroperitoneal approach., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the effect of intravitreal injection of erythropoietin for the treatment of non-arteritic anterior ischaemic optic neuropathy (NAION)., Methods: In this prospective interventional case series, 31 eyes of 31 patients with NAION were included. Patients received intravitreal injection of 2000 unit (0.2 cm³) of erythropoietin within 1 month of the onset of the disease. Visual acuity and visual field were recorded before injections and 1 week, 1 month, 3 months and 6 months after the injections., Results: The mean duration of symptoms before injections was 11.2 ± 5.5 days. Six months after injections, visual acuity improved in 27 eyes (87%), and 17 eyes (54.8%) had ≥ 3 lines of visual improvement. The mean preinjection visual acuity was 1.01 ± 0.88 logMAR and 0.58 ± 0.58 logMAR (p<0.001) at last follow-up. Visual acuity improvement occurred in 61.2% of patients within the first month. It followed a biphasic pattern in which there was continuous improvement up to 3 months and then started to deteriorate, although it remained significantly better than baseline until the last follow-up. No patient lost any lines of visual acuity compared with the baseline values. The mean of mean deviations of visual field was -19.6 ± 5.7 dB at baseline and -18.6 ± 6.3 dB (p = 0.6) at last follow-up., Conclusions: Intravitreal injection of erythropoietin may be safe and effective in the treatment of NAION. The effect may last for a few months and then decline.

The objective of this study was to determine the effects of various methods of sperm pre-treatment on male pronuclear (MPN) formation and subsequent development of ovine embryos derived from in vitro-matured oocytes and intracytoplasmic sperm injection (ICSI). The effect of treatment of injected oocytes with dithiothreitol (DTT) on embryo development was also assessed. In Exp. 1, the injected oocytes with non-treated sperm were activated with three different procedures. The cleavage and blastocyst rates in those activated with DTT was lower (p<0.05) than those activated with either ionomycin (Io) +6-dimethylaminopurine (6-DMAP) or DTT + I + 6-DMAP. In Exp. 2, the effects of sperm pre-incubated with DTT, sodium dodecyl sulphate (SDS) or DTT + SDS as well as two-time frozen/thawed sperm (without cryoprotectant) on MPN formation and oocyte activation were examined. The non-treated sperm served as controls. The MPN formation in DTT + SDS group was higher (p<0.05) than other groups except for freeze-thaw group. No difference in the rate of activated ICSI oocytes was observed among groups. In Exp. 3, the effect of pre-treatment of sperm on subsequent development of ICSI embryos and blastocyst cell numbers were examined. The rates of cleavage and blastocyst formation as well as the blastocyst cell numbers were similar among the pre-treated and control groups. In conclusion, pre-treatment of sperm with DTT + SDS positively affected MPN formation, although the subsequent development capacity of the resulting embryos remained limited. Moreover, DTT was not effective on oocyte activation compared with Io + 6-DMAP after ICSI., (© 2010 Blackwell Verlag GmbH.)

The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ∼200 bacilli to guinea pig lungs. Choroidal tuberculous granulomas showed reduced oxygen tension, as evidenced by staining with the hypoxia-specific probe pimonidazole, and expression of vascular endothelial growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day 56 after infection. This model may be useful in further elucidating the pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis and assessment of antituberculosis treatment responses in the eye.

Purpose: To evaluate outcomes of intravitreal injection of bevacizumab for the treatment of severe retinopathy of prematurity (ROP) associated with vitreous or retinal hemorrhages (VH or RH)., Methods: This is a prospective interventional case-series. Fourteen eyes of eight premature infants with severe ROP associated with vitreous or retinal hemorrhage were consecutively included. In eight eyes, VH and/or RH precluding complete laser ablation developed at the time of laser treatment. In six eyes, VH developed early after laser ablation. All participants underwent intravitreal injection of 0.625 mg (0.025 ml) bevacizumab immediately after diagnosis of VH or RH. Follow-up examinations were performed at days 1, 3, 7, and 14, and 1, 2 and 3 months after injection. Main outcome measure was the absence of unfavorable structural outcomes., Results: Mean gestational age was 27.6 weeks (range, 26-29 weeks) and mean birth weight was 1047 g (range, 780-1500 g). Mean gestational age at the time of injection was 35.4 weeks (range, 32-38 weeks). In all eyes, plus disease disappeared completely within 2 weeks and VH and/or RH was absorbed at last follow-up. None of the eyes developed unfavorable structural outcomes. No eyes needed additional injection or laser treatment. No major systemic or ocular complications were observed., Conclusion: In this small series of patients, intravitreal injection of bevacizumab was effective for treatment of severe retinopathy of prematurity associated with vitreous or retinal hemorrhage.

Background: Various drugs have been suggested for treatment of Borderline Personality Disorder (BPD)-a disabling disease affecting two percent of the general population. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult., Subjects and Methods: This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. This study is a clinical trial. 120 males and females were chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily) and Sertraline (50-100 mg daily) therapy. The SCL-90 questionnaire was filled by all participants before treatment and at the 4th, 8th and 12th weeks of treatment., Results: According to this clinical trial, Olanzapine and Sertraline are effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationships and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy., Conclusion: As result of this study it appears that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are recommended for these patients.

The effects of the age of cell donor animal on in vitro development of ovine nuclear transfer (NT) embryos were investigated. Somatic donor cells were obtained from two different sources: (1) adult cells (adult fibroblast cells; AFC and adult cumulus cells; ACC); and (2) fetal fibroblasts (40-day-old; FFC-40 and 65-day-old; FFC-65). The fibroblast cell lines were used for NT procedures within 4-13 subpassages. While the cumulus cells were used as non-cultured (fresh) cells. The in vitro matured abattoir-derived oocytes were considered as recipients. No differences in the rates of fusion (75.7, 77.7, 76.3 and 86.7%) and cleavage (80.1, 84.3, 77.8 and 74%) were detected among couplets reconstructed with FFC-40, FFC-65, AFC and ACC, respectively. Blastocyst formation rate of those oocytes reconstructed with FFC-40 was higher (18%; p < 0.001) than those reconstructed with FFC-65 (13%) and AFC (10.9) and comparable with those reconstructed with ACC (17.5%). When the effect of passage number was analysed within groups (FFC-40, FFC-65 and AFC) there were no significant differences in fusion, cleavage and blastocyst rates between reconstructed oocytes. The present study demonstrates that the fetal and adult fibroblasts as well as fresh cumulus cells are comparable in their ability to attain cell fusion and embryonic cleavage. Moreover, the blastocyst formation rate is influenced by the age of the donor animal and the fresh cumulus cells have similar remodelling potential to that of fetal fibroblasts in term of blastocyst formation rate.

Euphorbia tirucalli (Euphorbiaceae family) an environmental risk factor for Burkitt's lymphoma also has pharmacological activities. In the northeast of region in Brazil its latex is used as an antimicrobial, antiparasitic in the treatment of coughs, rheumatism, cancer and other disease as folk treatment. The prevalent constituents of this plant latex are diterpenes from the Inganen types (ingenol esters) as well as the tigliane (phorbol esters). Scientifically, there is not any data till now about anticancer effects of the Euphorbia tirucalli Linn., since the Ingenol esters have already presented tumor-promoting ability. Microtubules (MTs), and cytoskeletal proteins are essential in eukaryotic cells for a variety of functions, such as cellular transport, cell motility and mitosis. Single Inganen in cytoplasm can interact with these proteins and affect on their crucial functions. In this study, we showed the effects of Inganen on MT organization using ultraviolet spectrophotometer and fluorometry. The fluorescent spectroscopy showed a significant tubulin conformational change at the presence of Inganen which decrease polymerization of tubulin as well as the ultraviolet spectroscopy results. The aim of this study is to find the potential function of Inganen for treatment of cancer in cells and human organs.

This study was conducted to evaluate the effects of developmental stage of in vitro produced (IVP) ovine embryos and the type of vitrification procedure used on embryo cryotolerance. The IVP embryos were vitrified at five different developmental stages: 4-, 8- and 16-cell, morula, and blastocyst. For each stage, half of the embryos were vitrified in either 30 microl 3.4M glycerol+4.6M ethylene glycol in straw (method 1) or in <0.1 microl 2.7 M ethylene glycol+2.1 M Me(2)SO+0.5M sucrose placed on the inner surface of a straw (method 2) of vitrification solution, based on two different procedures. After warming embryo viability was determined by assessing the rates of re-expansion, survival, and blastocyst formation. The quality of surviving embryos was evaluated by their hatching rate and blastocyst cell numbers. In both vitrification methods, embryo survival progressively increased as the developmental stage progressed. In method 1 few of the early cleavage stage embryos (4-, 8- and 16-cell) could reach to the blastocyst stage following warming. There was no significant difference in blastocyst cell numbers (total, ICM, and trophectoderm cells) or hatching rate of blastocysts derived from vitrified embryos at different developmental stages. The number of dead cells in vitrified blastocysts in method 1 was higher than for non-vitrified blastocysts (P<0.05). The number of apoptotic cells in vitrified blastocysts was higher than for non-vitrified counterparts (P<0.05). In conclusion, both the developmental stage of IVP ovine embryos and the method of vitrification have a significant effect on the viability and developmental competence of sheep embryos., (Copyright 2009 Elsevier Inc. All rights reserved.)

Improvements on embryo micromanipulation techniques led to the use of embryo biopsy in commercial embryo transfer programs for genetic analysis of preimplantation bovine embryos. The aim of this study was to evaluate the quality of bovine blastocyst derived from embryos biopsied at different pre-compacted morulae stages by assessment of cryosurvivability of the resulting blastocysts. The in vitro produced bovine embryos were subjected to biopsy at days 2, 3, and 4 post-insemination with different cell numbers (4 to 16-cells). Embryo cell biopsy was carried out in a 100 µl drop of H-SOF following pronase drilling by aspiration of one blastomere. The biopsied embryos were then cultured in SOFaaBSA co-cultured with oviduct cells-monolayer until blastocyst formation. The blastocysts were cryopreserved at room temperature after exposure of equilibration (glycerol 1.4 M for 5 min and then glycerol 1.4 M and ethylene glycol 3.6 M for 5 min) and vitrification solutions (3.4 M glycerol and 4.6 M ethylene glycol). The blastocysts were loaded into the center of 0.25 ml straws separated by air bubbles from 2 columns of sucrose 0.5 M and plunged immediately into liquid nitrogen. There was no significant difference in cryosurvivability of vitrified-warmed blastocysts derived form biopsied embryos at different pre-compacted morula stages. The quality of biopsy derived blastocysts was identical to that of non-biopsy derived ones in terms of post vitrifcation survival and hatching rates. In conclusion there was no preference between different times of embryo biopsy at precompacted morula stages in term of cryosurvivability of biopsy derived bovine blastocysts.

Purpose: To evaluate the effect of intra-silicone injection of bevacizumab for the treatment of neovascular glaucoma (NVG) after vitrectomy for advanced proliferative diabetic retinopathy., Methods: Bevacizumab was injected into the silicone oil in five pseudophakic eyes of five patients with NVG. The iris neovascularization (INV) and NVG had developed 1.5-4 months after vitrectomy and silicone oil tamponade. The main outcome measures were regression of INV, intraocular pressure and visual acuity., Results: In all eyes, INV regressed and intraocular pressure was controlled within 7 days. Visual acuity improved in all eyes. In one patient, INV and NVG recurred 10 weeks after the injection and was successfully treated with a repeat intra-silicone bevacizumab injection., Conclusion: Intra-silicone injection of bevacizumab is effective in the treatment of patients with INV and NVG after vitrectomy for advanced proliferative diabetic retinopathy.

The vitreoretinal interface is involved in a wide range of vitreoretinal disorders and separation of the posterior vitreous face from the retinal surface is an essential part of vitrectomy surgeries. A diverse range of enzymatic and non-enzymatic agents are being studied as an adjunct before or during vitrectomy to facilitate the induction of posterior vitreous detachment. There is a significant body of knowledge in the literature about different vitreolytic agents under investigation for a variety of pathologies involving the vitreoretinal interface which will be summarized in this review.

This study was designed to evaluate the effect of in vitro culture system on bovine blastocyst yield and quality after vitrification. In Experiment 1, IVM/IVF zygotes were allocated to three culture conditions: (I) Oviductal cells-SOF (OCM-SOF); (II) Oviductal cells-TCM (OCM-TCM); and (III) SOF for 8 days. There was no significant difference between blastocyst rates among groups. In Experiment 2, the IVP-blastocysts in three above culture conditions were vitrified within groups segregated according to age (Day 7 and 8) and blastocoelic cavity size (early and expanded blastocysts). A trend of higher survival rate was obtained in vitrified/warmed early blastocysts compared with expanded ones, so that the difference in OCM-TCM group was significant (P<0.001). Higher survival and hatching rates (P<0.001) were obtained in OCM-SOF and OCM-TCM groups (co-culture) compared with SOF group and the age of blastocyst had no effect on post-thaw survival and hatching rates. In Experiment 3, after staining of blastocysts, in fresh blastocysts the highest number of trophectoderm cells was observed in OCM-TCM group and the number of inner cell mass (ICM) was higher in co-culture groups than SOF group (P<0.001). In vitrified/warmed blastocysts the number of ICM and trophectoderm cells in co-culture groups was higher than SOF group (P<0.001) except for the ICM of expanded blastocysts. In conclusion, in our culture conditions, the blastocyst yield is not influenced by culture system, while the cryotolerance of IVP-blastocysts is positively influenced by the presence of somatic cells. Moreover, the expanded blastocysts are more susceptible to cryoinjury than early blastocysts.

The aim of this study was to compare the effect of time of parthenogenetic activation (22 hr versus 27 hr after In Vitro Maturation-IVM) on in vitro development of ovine oocytes using either single (Ionomycin 5 µM for 5 min or Ethanol 7% for 7 min) or combined (ionomycin and ethanol with 6-DMAP 2 mM for 3 hr) activation treatments. The abattoir-derived in vitro matured activated oocytes were cultured in modified synthetic oviductal fluid and assessed for the cleavage, blastocyst, and hatching rates. The single-activated oocytes had a reduction in cleavage, blastocyst and hatching rates compared to the combined-activated oocytes (except for the cleavage at 27 hr). In single-treated groups the rates of cleavage and blastocyst were increased as the maturation time was extended from 22 hr to 27 hr. The numbers of total cells and Inner Cell Mass (ICM), though insignificant, were greater in combined-treated groups compared to the single treatment. The number of ICM in Eth + 6-DMAP group activated at 27 hr was lower than 22 hr. Nonetheless, irrespective of the activation protocol, development to the blastocyst stage, the numbers of total cell, ICM, and cell allocation (ICM/total cells) were significantly lower in parthenogenetic than fertilized embryos. In conclusion, though the cleavage and blastocyst rates in single-treated groups were positively influenced by the extension of duration of IVM (27 hr), there was a trend of decreased numbers of total cells and ICM in slightly aged oocytes. Moreover, developmental potential of ovine parthenotes, especially in young oocytes, was improved by the addition of 6-DMAP to the activation regimen.

Purpose: To evaluate the use of preoperative intravitreal bevacizumab (IVB) injection in patients undergoing pars plana vitrectomy for complications of proliferative diabetic retinopathy (PDR)., Methods: In this prospective surgeon-masked randomized clinical trial, 40 eyes of 40 diabetic patients who were candidates for vitrectomy were randomly assigned to receive 2.5 mg IVB 3-5 days before operation (injected group) or no injection before operation (noninjected group). A preoperative complexity score (CS) was recorded. Best-corrected visual acuity, number of endodiathermy applications, backflush needle applications, duration of surgery, and postoperative vitreous hemorrhage were recorded., Results: Twenty-two patients with a CS of 6+/-0.95 in the injected group and 18 patients with a CS of 5.7+/-1.1 in the noninjected group (p=0.3) were studied. Postoperative visual acuities were significantly better than preoperative visual acuities. Preoperative and 3-month postoperative visual acuities were the same for both groups; however, in the last follow-up examinations (mean 7+/- 3.6 months) the injected group had better visual acuities than the noninjected group (1.1+/-0.4 and 1.4+/-0.3 logMAR, respectively, p=0.006). Mean surgical time was 62+/-57.3 minutes in the injected group vs 95.5+/-36 minutes in the noninjected group (p=0.03): endodiathermy applications 6.0+/-4.3 vs 11.0+/-5.8 (p=0.004), backflush cannula applications 11.0+/-7.2 vs 18.1+/-7.8 (p=0.004). In non-silicone-filled eyes, no patient in the injected group developed significant postoperative vitreous hemorrhage obscuring the fundus details, while 7 eyes of noninjected eyes had this complication (p=0.01)., Conclusions: IVB injection before vitrectomy for PDR facilitates the surgery, and may decrease the rate of postoperative vitreous hemorrhage and improve the visual acuity results of the operation.

Background/aims: Retinoblastoma is a highly malignant eye tumour in children with different survival rates across the world. The aims of this study are to determine the globe and patient survival in children with retinoblastoma in a major referral centre in Iran., Methods: 156 eyes of 105 consecutive patients with retinoblastoma were enrolled from 2001 to 2007. All demographic data, family history, presenting symptoms, duration of symptoms, ocular findings and treatment modalities that were used for the patients were collected. For patient survival, event was defined as death and for globe survival as enucleation., Results: The mean age at diagnosis was 28.5 months (unilateral 27.4 months; bilateral 30 months). Five patients had a positive family history. Fifty-two per cent of the cases were unilateral, and 48% were bilateral. The most common presenting sign was leucocoria (64.8%) followed by strabismus (28.2%). Enucleation was done primarily for 75.9% of unilateral cases and 34.3% of bilateral cases. Secondary enucleation was necessary in 5.6% and 7.8% of unilateral and bilaterally involved eyes respectively. Sixty-nine (44.2%) of 156 eyes were salvaged by different globe preserving modalities (unilateral 18.5%; bilateral 57.9%). The Kaplan-Meier survival estimate for globe preservation according to International Classification of Retinoblastoma (ICRB) was 100% for group A eyes, 93.5% for group B, 86.7% for group C, 57.1% for group D and 0% for group E eyes. Kaplan-Meier estimates for patients survival were 100% at 1 year, 94.8% at 3 years and 83.1% at 5 years., Conclusion: Progress in methods of treatment, early detection of the disease and prompt referral to specialised centres have led to improved outcomes for patients with retinoblastoma in terms of globe and patients' survival rates even in developing countries.

Background: Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (K(ATP)) channels and may help to restore vascular tone in patients with vasodilatory shock. In the present study, we investigated whether extracellular acidification modifies the inhibition of vascular K(ATP) channels by AVP., Methods: We used a cell-attached patch-clamp configuration to investigate the effects of extracellular pH (pH(o)) on AVP-K(ATP) channel interaction in rat aortic smooth muscle cells., Results: Bath application of AVP significantly inhibited extracellular acidification (pH(o) = 6.5)-induced K(ATP) channel activity in a concentration-dependent manner, with an half-maximal inhibitory concentration (IC50) value of 16.8 pM. Furthermore, bath application of AVP significantly inhibited pinacidil-induced K(ATP) channel activity at mild (pH(o) = 7.0) and severe (pH(o) = 6.5) extracellular acidification, with IC50 values of 266.7 and 21.4 pM, respectively, but failed to significantly inhibit at normal pH (pH(o) = 7.4) or under alkalosis (pH(o) = 9.0). Augmentation of AVP inhibition of vascular K(ATP) channels during extracellular acidification was eliminated by pretreatment with OPC-21268, a specific blocker of the V1 receptor, but not by a V2 blocker, OPC-31260. AVP-induced inhibition was also suppressed by pretreatment with a protein kinase C inhibitor, calphostin C., Conclusions: Our results suggest that AVP inhibits extracellular acidification-induced vascular K(ATP) channel activity, and that the inhibitory effects of AVP on vascular K(ATP) channels are enhanced by extracellular acidification via the V1 receptor-protein kinase C cell-signaling pathway. The potent inhibition of vascular K(ATP) channels by AVP under acidic conditions may make it suitable for management of vasodilatory shock.

Background: Recent evidence indicates that vascular adenosine triphosphate-sensitive potassium (K(ATP)) channels in vascular smooth muscle cells are critical in the regulation of vascular tonus under both physiologic and pathophysiologic conditions. Studies of the interaction of volatile anesthetics with vascular K(ATP) channels have been limited. In the current study, the authors investigated the molecular mechanism of isoflurane's action on vascular K(ATP) channels., Methods: Electrophysiologic experiments were performed using cell-attached and inside-out patch clamp techniques to monitor native vascular K(ATP) channels, and recombinant K(ATP) channels comprised of inwardly rectifying potassium channel subunits (Kir6.1) and the sulfonylurea receptor (SUR2B). Isometric tension experiments were performed in rat thoracic aortic rings without endothelium., Results: Application of isoflurane (0.5 mM) to the bath solution during cell-attached recordings induced a significant increase in K(ATP) channel activity, which was greatly reduced by pretreatment with a selective inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). In inside-out patches, isoflurane did not activate K(ATP) channels. Isoflurane significantly activated wild-type recombinant SUR2B/Kir6.1 in cell-attached patches. Isoflurane-induced activation of wild-type channels was diminished in the PKA-insensitive mutant SUR2B-T633A/Kir6.1, SUR2B-S1465A/Kir6.1, and SUR2B/Kir6.1-S385A. In addition, the authors demonstrated that isoflurane-induced PKA activation was associated with isoflurane-induced decreases in isometric tension in the rat aorta., Conclusion: These results indicate that isoflurane activates K(ATP) channels via PKA activation. PKA-dependent vasodilation induced by isoflurane also was observed in isometric tension experiments. Analysis of expressed vascular-type K(ATP) channels suggested that PKA-mediated phosphorylation of both Kir6.1 and SUR2B subunits plays a pivotal role in isoflurane-induced vascular K(ATP) channel activation.

Background: The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity., Methods: In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2DeltaC36 channels), and (4) mutant Kir6.2DeltaC36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2DeltaC36-K185Q channels)., Results: Etomidate (> or = 10 m), but not midazolam (up to 10 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10 m; maximum inhibitory concentration: 1.22 x 10 m). Etomidate (> or = 3 x 10 m), but not midazolam (up to 10 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10 m and 1.52 x 10 m, respectively. Etomidate (10 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2DeltaC36 channels, and Kir6.2DeltaC36-K185Q channels with equivalent potency., Conclusions: Clinical concentrations of etomidate, but not midazolam, inhibit the KATP channel activity in vascular smooth muscle cells. The inhibition is presumably through its effects on the Kir6.0 subunit, but not on the SUR subunit, with the binding site different from adenosine triphosphate at the amino acid level.

There is crosstalk in intracellular signaling between Angiotensin II (Ang II) and insulin. We hypothesized that the underlying mechanism might be related to changes in cytoskeleton. In the presence of 100 nM of Ang II, insulin-induced glucose uptake was decreased and insulin-induced actin filament organization was inhibited. PKC inhibitors, including GF109203x and p38MAPK inhibitor (SB203580) neither improved insulin-induced actin reorganization nor glucose uptake. In contrast, the Ang II-induced inhibition of glucose uptake and actin filament disorganization was reversed by 10 micromol ERK 1/2 MAPK inhibitor (PD98059). Pretreatment of Ang II increased ERK1/2 phosphorylation and inhibited insulin-induced Akt phosphorylation. The effect of Ang II on ERK1/2 phosphorylation was blocked by Ang II type 1 receptor antagonists, RNH6270 and PD98059 but not by SB203580 or Guanosine-5'-O-(2-ThioDiphosphate), a G-protein inhibitor. We next tested the effect of broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM6001) on Ang II-inhibition of insulin signaling pathway. GM6001 did not improve Ang II-induced actin filament disorganization and did not inhibit ERK1/2 phosphorylation. From these data in L6 myotube, we conclude that Ang II negatively regulates the insulin signal not through MMP signaling pathway but specifically through MMP-independent ERK1/2 activation pathway, providing an alternative molecular mechanism for angiotensin-induced insulin resistance.