A hormone complex of FABP4 and nucleoside kinases regulates islet function.

The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis1,2. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4)3. Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans4-7, no mechanism of action has yet been described8-10. Here we show that hormonal FABP4 forms a functional hormone complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK) to regulate extracellular ATP and ADP levels. We identify a substantial effect of this hormone on beta cells and given the central role of beta-cell function in both the control of lipolysis and development of diabetes, postulate that hormonal FABP4 is a key regulator of an adipose-beta-cell endocrine axis. Antibody-mediated targeting of this hormone complex improves metabolic outcomes, enhances beta-cell function and preserves beta-cell integrity to prevent both type 1 and type 2 diabetes. Thus, the FABP4-ADK-NDPK complex, Fabkin, represents a previously unknown hormone and mechanism of action that integrates energy status with the function of metabolic organs, and represents a promising target against metabolic disease.

An easy and practical method for toric intraocular lens implantation: marking corneal astigmatic axis at slit-lamp.

The objective of this study was to present a practical method of marking the corneal astigmatic axis for the patient sitting at the slit-lamp before toric intraocular lens (IOL) implantation. Eighteen eyes of 18 patients, who underwent uncomplicated phacoemulsification, with an implantation of Acrysof toric IOL were included. We marked the astigmatic axis while the patient sitting at the slit-lamp before surgery. The patient was asked to look at a distant target at head height with the fellow eye. Using the rotator switch, the slit light of the slit-lamp was just turned on to the steep astigmatic meridian in the orthograde position. Then, two tips of the astigmatic meridian were marked with a marking pen, where the slit light crossed at the limbus 180° away. Preoperative corneal and postoperative refractive astigmatism values were compared. Uncorrected and corrected postoperative visual acuities (UDVA and BCVA) and IOL rotations at early and late periods were noted. The mean age and mean follow-up were 63.6 ± 14.6 years and 9.4 ± 5.3 months (range 3-16 months), respectively. Mean postoperative UDVA and BCVA at Snellen chart were 0.62 ± 0.21 and 0.82 ± 0.13, respectively. Mean preoperative keratometric and mean postoperative refractive astigmatism values were 2.48 ± 0.87 D and 0.66 ± 0.48 D, respectively. Reduction of astigmatism was significant (p < 0.01). The mean rotation at 1 week and that at last follow-up were 2.1° ± 3.1° and 2.3° ± 3.0°, respectively. Marking corneal astigmatic axis at slit-lamp is a simple and effective method in toric intraocular lens implantation. Surgeon does not need additional instrument except a slit-lamp and a marking pen, and can complete the marking task in just one setting.

Measurements of central corneal thickness and endothelial parameters with three different non-contact specular microscopy devices.

We aimed to compare the measurements of central corneal thickness (CCT) and endothelial parameters with three different non-contact specular microscopy (SM) devices. Fifteen eyes of 15 healthy individuals (6 males; 9 females) were enrolled in the study. Mean age was 37.93 ± 15.13 years. Endothelial parameters and CCT were measured with Nidek CEM-530, Topcon SP-3000P, and Tomey EM-3000 SM devices by the same physician. Endothelial parameters included endothelial cell count (ECC), maximum, minimum, and average endothelial cell size. and hexagonality ratio. There were no statistically significant differences in ECC, CTT, and average endothelial size (AES) between the devices (p > 0.05). The measurement of maximum endothelial size (MES) was different between Nidek SM and Topcon SM devices (p = 0.001), but there was no difference in MES between Nidek SM and Tomey SM (p = 0.058), and between Topcon SM and Tomey SM (p = 0.081). There was no difference in minimum endothelial size (MinES) between Nidek SM and Topcon SM (p = 0.794); however, there was a significant difference in MinES between Tomey SM and Nidek SM (p < 0.001), and between Tomey SM and Topcon SM (p < 0.001). Comparison of hexagonality ratio showed statistically significant difference between the devices (p < 0.001). No significant differences in the measurements of ECC, CCT, and AES were detected between different SM devices, whereas a statistically significant difference in hexagonality ratio was detected between the devices. These devices should not be used alternatively in the endothelial morphology assessment in patient's follow-up.

Reproducibility and repeatability of central corneal thickness measurement in healthy eyes using four different optical devices.

AIM: The aim of the study is to compare the measurements of central corneal thickness (CCT) performed by two examiners with four different methods at different times inter- and intra-individually. METHODS: Thirty healthy people were included in the study. In these measurements, an optical low-coherence reflectometry (OLCR), an optic coherence tomography (OCT), a specular microscopy (SM), and a corneal topography (CT) were used. Two examiners performed the measurements in a consecutive manner. After 1-7 days of the first measurements, the second measurements were performed again consecutively. The mean of three measurements was taken in each session for all devices. RESULTS: In OCT measurements, there was a significant difference between two examiners in both sessions (p < 0.001), while no significant differences were found between two examiners in first and second sessions in SM, CT, and OLCR measurements. When each examiner's measurements were compared to two sessions, there were no significant differences (p > 0.05, for all) except the SM measurements of the first examiner (p = 0.041). When the first measurements of two examiners were compared, the smallest values were of OCT. At the first session of two examiners, there was a significant difference between OCT and CT measurements, and between OCT and OLCR (p < 0.001, p = 0.002 for the first examiner and p < 0.001 for the second examiner, respectively). CONCLUSION: Our study showed that CCT measurements made by CT and OLCR methods were almost same and highly correlated for both the examiners' measurements. CCTs measured by OCT were on average 30 µm thinner than CT and OLCR.

Retinal nerve fibre layer, ganglion cell layer and choroid thinning in migraine with aura.

BACKGROUND: The aim of this study was to investigate the thickness of the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and choroid thickness (CT) in patients who have migraines, with and without aura, using spectral optical coherence tomography (OCT). METHODS: Forty-five patients who had migraines without aura (Group 1), 45 patients who had migraines with aura (Group 2), and 30 healthy participants (control group) were included in the study. Spectral OCT was used to measure the RNFL, GCL and CT values for all patients. RESULTS: The mean age of Group 1, Group 2, and the control group was 34.6 ± 4.3, 32.8 ± 4.9, and 31.8 ± 4.6 years, respectively. The mean attack frequency was 3.6/month in Group 1 and 3.7/month in Group 2. The mean age among the groups (p = 0.27) and number of attacks in migraine patients (p = 0.73) were not significantly different. There was significant thinning in the RNFL and GCL in Group 2 (p < 0.05, p < 0.001 respectively), while there were no significant differences in RNFL and GCL measurements between Group 1 and the control group (p > 0.05). All groups were significantly different from one another with respect to CT, with the most thinning observed in Group 2 (p < 0.001). When all migraine patients (without grouping) were compared with the control group, there were significant differences on all parameters: RNFL thickness, GCC thickness and CT (p < 0.05). CONCLUSIONS: RNFL and GCL were significantly thinner in the migraine patients with aura as compared with both the migraine patients without aura and the control subjects. In migraine, both with aura and without aura, patients' choroid thinning should be considered when evaluating ophthalmological findings.

Targeting Cleavage of C-Terminal Fragment of Cytoskeletal Filamin A in Cancers.

Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted by two hinge regions between repeats 15-16 and 23-24. Cleavage of these hinge regions produces a naturally occurring C-terminal 90 kDa fragment of FLNA (FLNACT) that physically interacts with multiple proteins with diverse functions. This cleavage leads to actin cytoskeleton remodeling, which in turn contributes to cellular signaling, nucleocytoplasmic shuttling of transcriptional factors and nuclear receptors, and regulation of their transcriptional activities that are important for initiation and progression of cancers. Therefore, recent studies have proposed blocking FLNA cleavage as a means of cancer therapy. Here, we update how FLNA cleavage has been targeted by different approaches and their potential implications for future treatment of human cancers.

Cloning, expression, purification, crystallization and preliminary X-ray analysis of NodS N-methyltransferase from Bradyrhizobium japonicum WM9.

The Nod factor (NF) is a rhizobial signal molecule that is involved in recognition of a legume host and the formation of root and stem nodules. Some unique enzymes are involved in the biosynthesis of NF, which is a variously but specifically substituted lipochitooligosaccharide. One of these enzymes is NodS, an N-methyltransferase that methylates end-deacetylated chitooligosaccharide substrates. In the methylation reaction, NodS uses S-adenosyl-L-methionine (SAM) as a methyl donor. To date, no structural information is available about NodS from any rhizobium. X-ray crystallographic studies of the NodS protein from Bradyrhizobium japonicum WM9, which infects the legumes lupin and serradella, have been undertaken. The nodS gene was cloned and the recombinant protein was expressed in Escherichia coli cells using natural amino acids and as an SeMet derivative. NodS without ligands was crystallized in the presence of PEG 3350 and MgCl(2). The protein was also crystallized in complex with S-adenosyl-L-homocysteine (SAH) in the presence of PEG 8000 and MgCl(2). SAH is produced from SAM as a byproduct of the methylation reaction. The crystals of apo NodS are tetragonal and diffracted X-rays to 2.42 A resolution. The NodS-SAH complex crystallizes in an orthorhombic space group and the crystals diffracted X-rays to 1.85 A resolution.

Arcuate keratotomy on post-keratoplasty astigmatism is unpredictable and frequently needs repeat procedures to increase its success rate.

PURPOSE: To evaluate the effectiveness and predictability of arcuate keratotomy (AK) for post-keratoplasty astigmatism and to present the complications and rate of repeat procedures. METHODS: Sixteen eyes from 14 patients were included. Paired 70-80° arc length AKs centred on the steep axis were carried out 0.5 mm within the graft-host junction. The depth of the AKs was set at approximately 80-90% of the depth of the cornea, based on a topographic pachymeter at the incision location. The outcome measures included preoperative and postoperative topographic astigmatism, uncorrected and corrected visual acuity, surgical complications and repeat procedures. RESULTS: In 12 of the 16 eyes (75%), at least one additional surgical procedure was required to obtain the desired result: suturing for overcorrection or wound gape in six eyes (38%), lengthening of the incisions for undercorrection in four eyes (25%) and additional AKs for marked astigmatic axis displacement in three eyes (19%). The mean preoperative astigmatism was 10.45±3.82 dioptres (D); the postoperative astigmatism at the last visit was 2.99±1.14 D (in a mean follow-up of 17.6±5.55 months). The efficacy index was 0.83 and the safety index was 1.68. CONCLUSIONS: In treatment of post-keratoplasty astigmatism, AK does not have a good predictability. Additional procedures such as lengthening of the AK incisions for undercorrection or using compression sutures for overcorrection with significantly gaping wounds are frequently required to improve the final outcome.

Toxic anterior segment syndrome following deep anterior lamellar keratoplasty.

We present the case of a 31-year-old patient with toxic anterior segment syndrome (TASS) that developed after undergoing deep anterior lamellar keratoplasty (DALK). She had keratoconus, and despite wearing hard contact lenses for many years in the left eye, her vision had deteriorated; therefore, DALK was performed on this eye. The preoperative visual acuity (VA) was finger counting at 3 m. Routine DALK was performed using the "big-bubble" technique. The corneal entry incision was hydrated at the end of the surgery, which was terminated by air injection into the anterior chamber. On postoperative day 1, VA was at the level of hand movements, and the cornea was edematous. Topical high-dose dexamethasone and oral steroids were initiated considering the diagnosis of TASS. Subsequently, the patient's VA increased, and the corneal edema decreased. We believe that the use of re-sterilized cannulas may have been the likely cause of TASS. Although DALK can be performed without interfering with the anterior chamber, one should keep in mind that TASS may occur in response to the solution used to hydrate the incision site and the air injected into the anterior chamber.

Periorbital discoid lupus: a rare localization in a patient with systemic lupus erythematosus.

A 40-year-old female patient with a 5-year history of systemic lupus erythematosus was referred to our policlinic with complaints of erythema, atrophy, and telangiectasia on the upper eyelids for 8 months. No associated mucocutaneous lesion was present. Biopsy taken by our ophthalmology department revealed discoid lupus erythematosus. Topical tacrolimus was augmented to the systemic therapeutic regimen of the patient, which consisted of continuous antimalarial treatment and intermittent corticosteroid drugs. We observed no remission in spite of the 6-month supervised therapy. Periorbital discoid lupus erythematosus is very unusual and should be considered in the differential diagnosis of erythematous lesions of the periorbital area..

Evaluation of ocular findings in patients with vitiligo.

In this study, we aimed to investigate ocular manifestations in patients with vitiligo. Sixty-one patients with vitiligo were included in the study. From the patients who referred for examination to the dermatology and ophthalmology clinic, 57 patients without any systemic disease were taken as the control group. In both groups, otorefractometry, keratometry, visual acuity test, intraocular pressure measurement, anterior segment, and fundus examinations of the eye with slit lamp, Schirmer test, and perimetry were carried out. The mean age was 24.54 ± 11.90 years and 23.03 ± 8.72 years in the patients and control group, respectively. The mean Schirmer test results were as follows: 16.74 ± 9.11 mm and 17.64 ± 9.41 mm for the right and left eyes of the patients, and 21.96 ± 12.51 mm and 23.42 ± 12.51 mm for the right and left eyes of controls, respectively. Of the patients, 36 eyes showed lenticular findings. However, only 12 eyes of the controls have some lenticular findings. Twenty-nine eyes in the vitiligo group and four in the controls showed some fundus findings. When the two groups were compared with each other, there was a statistically significant difference between them in terms of Schirmer test results, lens, and fundus findings (P < 0.05 for all). However, there was no significant difference in terms of age, gender, visual acuity, refraction, keratometry, intraocular pressure, perimetry, and corneal findings (P > 0.05 for all). Patients with vitiligo may have more lenticular and retinal findings than normal. They can be more prone to dry eye syndrome as well.

Ocular findings in patients with alopecia areata.

OBJECTIVES: This study investigated ocular findings in patients with alopecia. METHODS: A total of 42 patients with alopecia (31 male, 11 female; 84 eyes) and 45 healthy individuals (28 male, 17 female; 90 eyes) were enrolled in the study. Of the patients with alopecia, 34 had alopecia areata, seven had alopecia universalis, and one had ophiasis alopecia. Seven patients had eyebrow involvement and seven had eyelash involvement. Autorefractometry, keratometry, visual acuity, central corneal thickness and intraocular pressure (IOP) measurements, bilateral anterior and posterior segment examinations, Schirmer's tests, and visual field examinations were performed in both groups. RESULTS: The mean ± standard deviation age of the subjects was 25.21 ± 10.88 years in the alopecia group and 28.24 ± 9.31 years in the control group. Lens abnormalities were observed in 35 eyes in the alopecia group and in 11 eyes in the control group (P < 0.05). Posterior segment abnormalities were seen in 29 eyes in the alopecia group and four eyes in the control group (P < 0.05). There were no statistically significant differences in age, sex, visual acuity, refractive error, keratometric findings, IOP, central corneal thickness, perimetry, or Schirmer's test results between the alopecia and control groups (P > 0.05). CONCLUSIONS: Patients with alopecia may have more lenticular and retinal findings than normal individuals, but those findings do not interfere with visual acuity. Close surveillance for the early onset of cataract formation is important in patients with alopecia.

Plasmalogen phospholipids protect internodal myelin from oxidative damage.

Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin.

Topical anesthesia for cataract surgery: the patients' perspective.

Purpose. To evaluate the analgesic efficacy of 0.5% propacaine hydrochloride as topical anesthesia during phacoemulsification surgery. Methods. Intraoperative pain intensity was assessed using a 5-category verbal rating scale during each of three surgical stages. Pain scores from each surgical stage and total pain scores were compared for the factors of patient age, gender, cataract laterality, and type. Results. In comparison of cataract type subgroups, the mean total pain scores and mean stage 2 pain scores in both white mature cataract (WMC) and corticonuclear plus posterior subcapsular cataract (CN + PSC) groups were significantly higher than in the PSC-only (PSC) group (P < 0.05). Conclusion. Phacoemulsification with topical anesthesia is not a completely painless procedure. Pain intensity varies with cataract type and stage of surgery.

The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan.

PURPOSE: We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 µg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS: The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS: Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.

Comparison of the effect of W-shaped and linear skin incisions on scar visibility in bilateral external dacryocystorhinostomy.

BACKGROUND: The aim of this study was to compare the effect of W-shaped skin (WS) and linear skin (LS) incisions on cutaneous scar tissue formation in patients who have undergone bilateral external dacryocystorhinostomy. METHODS: Sixteen patients (14 females and two males) with acquired bilateral nasolacrimal duct obstruction were included in this prospective, interventional comparative study. LS incision was applied to one side and WS skin incision to the other side. The skin incisions were assessed 6 months after each procedure by the patients themselves and by two ophthalmologists who were unaware of the skin incision shape and side. Scar tissue that was not recognized under the same light conditions and in the same room from a 100 cm distance was recorded as grade 1. Minimally visible scar tissue was assessed as grade 2, moderately visible scar tissue as grade 3, and easily visible scar tissue as grade 4. RESULTS: The mean scar assessment scores recorded by the first ophthalmologist were 2.50±0.82 for the LS group and 1.25±0.45 for the WS group (P<0.001). The second ophthalmologist's assessment scores were 2.25±0.86 for the LS group and 1.25±0.45 for the WS group (P<0.001). The mean patient self-assessment score for the incision scars was 2.44±1.03 for the LS group and 1.56±0.73 for the WS group (P<0.001). CONCLUSION: Compared with LS incision, WS incision resulted in less cutaneous scar tissue formation in patients who have undergone bilateral external dacryocystorhinostomy.