Acute and 28-day repeated dose toxicity evaluations of cold pressed Pinus halepensis Mill. seed oil in mice and rats.

Pinus halepensis Mill. seed (Pinaceae), popularly known as 'Zgougou', is widely consumed in the Mediterranean countries and used traditionally in the treatment of some diseases such as bronchitis, rheumatism, infection, and inflammation. The present study aimed to evaluate the oral safety of cold pressed oil of Pinus halepensis Mill. seeds (COPHS) by acute and 28-day repeated dose toxicities studies in Wistar mice and rats, respectively. In the acute toxicity study, oral administration of COPHS to mice did not provoke mortality or any toxic signs at doses up to 5000 mg/kg bw. After administration of COPHS at doses of 250, 500, and 1000 mg/kg bw/day for 28 days, no abnormal changes were observed in body weight, water intake, food consumption, organ weight, blood haematological, serum biochemistry parameters, and histology profile. Furthermore, there was no animal death or any symptom of toxicity in any group during sub-acute toxicity test period. Our findings demonstrate that COPHS is relatively non-toxic and has a large safety margin (>5000 mg/kg). The results of the present research provide basic reference data for food consumption and for future in vivo screening of biological and pharmacological properties of cold pressed oil of Pinus halepensis Mill. seeds.

Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants.

PURPOSE: To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. METHODS: Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture. RESULTS: Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal-Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or tertiary outgrowths was not distinguishable from each other. The percentage of dye-excluding cells present within this zone and the capacity of the explant epithelial outgrowth of the regenerated peripheral corneal zone were also on par with those of the donor corneas. The Krt3-negative cells that characterize the basal epithelial layer of the normal limbus could not be found in any regenerated cornea from the primary to tertiary outgrowths. CONCLUSIONS: Our results demonstrate that in rabbits post-primary explant outgrowths retain the capacity for LSCD recovery found in primary explants.

Scleral Contact Lens to Preserve a Corneal Graft in Chronic Lagophthalmos.

Facial burns involving the periorbital region may lead to cicatricial ectropion and lagophthalmos, causing severe exposure keratopathy and eventually blindness if uncorrected. In these patients, it is critical to provide aesthetic and functional surgical correction to protect the ocular surface from chronic desiccation in addition to visual rehabilitation. Conventional methods may not be sufficient to provide visual rehabilitation in complex cases. Scleral lenses can be a multipurpose alternative for these patients. Herein, we present the challenging case of a patient who developed cicatricial lagophthalmos and exposure keratopathy after facial transplantation due to gasoline burns and received a scleral contact lens for visual rehabilitation.

Embedded Episcleral Foreign Body Mimicking Nodular Anterior Scleritis.

A 56-year-old man was referred to our clinic for unilateral nodular scleritis unresponsive to systemic corticosteroids. A localized, nodular hyperemia on the nasal bulbar conjunctiva surrounding a central cyst-like lesion together with vascular engorgement was observed on slit-lamp examination of the left eye. No abnormal fundoscopic findings were noted. Surgical exploration revealed an embedded episcleral brown colored, soft to touch, splinter-like organic foreign body (FB) which was confirmed by the histopathological examination. Nodular hyperemia resolved during the postoperative follow-up period, and mild scar tissue accompanied by scleral thinning developed in the left nasal bulbar conjunctiva. Ocular injury associated with FBs may cause significant ocular morbidity depending on the nature and location of the FB. Severe visual disability may occur if left untreated. Subconjunctival FBs are rare and may present with a clinical picture mimicking episcleritis or scleritis. History of trauma involving a FB should always be assessed for an accurate differential diagnosis and appropriate management of patients with anterior scleritis.

Isolation and characterization of nettle (Urtica dioica L.) seed proteins: Conversion of underutilized by-products of the edible oil industry into food emulsifiers.

This study aimed to upcycle a byproduct of the edible oil industry, cold-pressed nettle seed meal (CPNSM), into a plant-based emulsifier, thereby increasing the sustainability of the food system. The protein content of the nettle seed protein (NSP) powder was 48.3% with glutamic acid (16.6%), asparagine (10.7%), and arginine (9.7%) being the major amino acids. NSPs had a denaturation temperature of 66.6 °C and an isoelectric point of pH 4.3. They could be used as emulsifiers to form highly viscous coarse corn oil-in-water emulsions (10% oil, 4% NSP). Nevertheless, 10-fold diluted emulsions exhibited rapid creaming under different pH (2-9), salt (0-500 mM NaCl) and temperature (>40 °C) conditions, but they were relatively stable to aggregation. Our findings suggest that NSPs could be used as emulsifiers in highly viscous or gelled foods, like dressings, sauces, egg, cheese, or meat analogs.

Hormone replacement therapy: relation to homocysteine and prooxidant-antioxidant status in healthy postmenopausal women.

OBJECTIVES: Studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). DESIGN AND METHODS: In this study, the effects of HRT were investigated on plasma total homocysteine (tHcy) and the oxidant-antioxidant status in postmenopausal women. 35 of postmenopausal receiving (2 mg estrodiol valerate + 1 mg cyproterone acetate) HRT group, the remaining 25 received orally placebo (NHRT group). RESULTS: There was no significant change in plasma tHcy levels between HRT and NHRT groups. Malondialdehyde (MDA) and total thiol (t-SH) correlated significantly with tHcy (0.388 and 0.478, respectively) content, and there was a significant negative correlation between E2 level and glutathione transferase (GST) activity (-0.425) in HRT group. Superoxide dismutase (SOD) and HDL-C correlated significantly with t-SH level (0.339 and 0.336, respectively) in plasma after HRT. CONCLUSION: Our results show that HRT is beneficial in the protection against oxidative damage, and prevents atherosclerotic complications.

Clinical Performance of Samfilcon A Contact Lenses in Intensive Digital Device Users: A Multicenter, Prospective Clinical Study.

INTRODUCTION: To evaluate patient satisfaction with samfilcon A contact lenses (CLs) in intensive digital device users with myopia and to compare patient satisfaction with samfilcon A lenses to prior experience with senofilcon A or lotrafilcon B CLs. METHODS: This was a comparative, prospective, national study conducted at 14 centers in Turkey. Subjects were adults aged 18 and 45 years with myopia (range -0.25 D to -6.00 D) who spend a minimum of 3 hours viewing digital devices (e.g., computer, smartphone). A subgroup of patients were habitual lens wearers (senofilcon A or lotrafilcon B lens wear for at least 6 months prior to enrollment). The primary assessment was patient satisfaction with samfilcon A lenses (0-100 Likert scale). Secondary assessments included patient satisfaction with samfilcon A lenses compared to patients' habitual lenses, investigator satisfaction with samfilcon A lenses and investigator-evaluated slit lamp examination findings. RESULTS: Samfilcon A lenses were given high overall ratings from both patients and investigators, with a low incidence of ocular symptoms. Overall, patients were highly satisfied with samfilcon A lenses for comfort, vision and overall performance, and stated that they would consider wearing these lenses in the future. Among habitual senofilcon A or lotrafilcon B lens wearers, samfilcon A lenses were rated significantly better than the habitual lenses in regard to comfort, vision and overall performance. Investigator assessments were also highly favorable, both at initial fit and after 4 weeks of follow-up, with no significant findings noted on slit lamp examination. CONCLUSION: Samfilcon A lenses were rated highly by investigators in regard to fit, handling and slit lamp findings, and by novice and habitual lens wearers in regard to comfort, vision and overall performance. These results support the use of samfilcon A lenses among digital device users who seek day-long comfort and good visual acuity.

Sympathetic ophthalmia following vitreoretinal surgery.

The objective is to discuss the characteristics of three patients who developed sympathetic ophthalmia following vitreoretinal surgery. The first case was a 29-year-old man who underwent placement of an encircling band, pars plana vitrectomy, foreign body removal, endolaser photocoagulation, transscleral cryotherapy, and silicone oil injection due to a retained foreign body 3 months after a corneoscleral rupture repair. He experienced visual loss in the fellow eye 2 months after the vitrectomy. An extensive exudative detachment was detected in the fellow eye. Sympathetic ophthalmia was diagnosed and systemic steroids together with azathioprine were initiated. The injured eye was enucleated as there was no useful vision. The other two cases were operated for rhegmatogenous retinal detachments. One underwent placement of an encircling band, pars plana vitrectomy, silicone oil injection, and endolaser photocoagulation with good anatomic outcome. However, 4 months later, the fellow eye experienced severe visual loss with disc swelling and hyperemia and exudative retinal detachment. Systemic steroid was sufficient to reverse the process and the visual acuity recovered. The other case underwent placement of an encircling band, subretinal fluid drainage, SF(6) injection and 360 degrees indirect laser photocoagulation. Two years later, he noted a sudden visual decrease in the fellow eye in which we detected a Harada-like extensive exudative detachment. Systemic steroid without immunosuppressive therapy rendered regression of the detachment and recovery of good visual acuity. Sympathetic ophthalmia may occur following vitreoretinal surgery either for trauma-related problems or rhegmatogenous retinal detachment. Since it may present with relatively mild anterior segment findings and mainly posterior segment involvement; any visual disturbance in the fellow eye of a patient with a history of perforating trauma or vitreoretinal surgery should be thoroughly evaluated for sympathetic ophthalmia.

Association of genetic variants in Methylenetetrahydrofolate Reductase and Paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease.

BACKGROUND: The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD). METHODS: The study included 235 patients with CAD and 268 healthy control subjects. RESULTS: LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively. CONCLUSION: Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Identification of Acanthamoeba genotype T4 and Paravahlkampfia sp. from two clinical samples.

In this study, two free-living amoebae strains, Acanthamoeba genotype T4 and Paravahlkampfia sp., which were isolated from keratitis cases are presented. While the Acanthamoeba strain was isolated as a single agent, the Paravahlkampfia strain was found together with herpes simplex virus. Neither of the patients were contact lens wearers, but they did have a history of minor corneal trauma. Amoebae were detected on non-nutrient agar covered with Escherichia coli. Based on PCR-amplified 18S rRNA-gene analysis the first isolate was identified as Acanthamoeba genotype T4 and the second as Paravahlkampfia sp. In thermotolerance tests, the maximum temperature at which trophozoites continued to divide was determined as 37 degrees C for this Acanthamoeba strain and 35 degrees C for the Paravahlkampfia strain. To the best of our knowledge, the Acanthamoeba strain described herein is the second molecularly identified Acanthamoeba strain in an Acanthamoeba keratitis patient in Turkey. However, the Paravahlkampfia isolate is believed to be the first strain that has been isolated from a keratitis patient and has been molecularly differentiated from Vahlkampfia.

Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives.

We investigated the effect of polymorphic variants of c.1298A>C (Glu429Ala) and c.677C>T (Ala222Val) in methylenetetrahydrofolate (MTHFR) gene on the total homocysteine (tHcy), folate and B12 levels in patients with bipolar disorder, first-degree relatives of patients, and controls. The c.677C>T and c.1298A>C polymorphisms in MTHFR were determined by polymerase chain reaction-restriction fragment length polymorphism in 197 bipolar patients, 278 relatives and 238 controls. tHcy and folate and vitamin B12 levels were measured by Fluorescence Polarization Immunoassay and Electrochemiluminescence, respectively. The tHcy was significantly increased in patients and relatives. In contrast, folate and B12 were significantly lower in patients and relatives. Gender was not considered as a significant determinant in the multivariate analysis. Genotypes of c.1298A>C and c.677C>T were correlated with tHcy, folate and B12. Patients and relatives carrying TT and/or AA and AC genotypes had elevated tHcy and reduced folate and B12 levels. High tHcy but low folate and vitamin B12 levels may be a risk factor for development of bipolar disorder.

Effect of diode laser cyclophotocoagulation on the anterior segment: an Orbscan Study.

PURPOSE: To evaluate the effect of transscleral contact diode laser cyclophotocoagulation (TCDLC) on corneal topography, central corneal thickness (CCT), and anterior-chamber depth (ACD). METHODS: The Orbscan II system was used to determine the changes in corneal topography, CCT, and ACD before and after TCDLC in 25 eyes of 24 patients. RESULTS: Mean prelaser astigmatism was 4.51 +/- 1.81, 4.64 +/- 3.47, and 5.40 +/- 3.04 D at central and 3- and 5-mm zones, respectively. Mean postlaser astigmatism was 4.54 +/- 2.59, 4.75 +/- 3.33, and 5.57 +/- 3.12 D at central and 3- and 5-mm zones at 10 days and 3.99 +/- 2.01, 4.05 +/- 2.20, 5.52 +/- 4.60 D at 1 month, respectively, showing no statistically significant difference. Prelaser CCT was 540.72 +/- 103.48 microm. Postlaser CCT was 617.08 +/- 86.35 microm at 10 days and 569.88 +/- 70.36 microm at 1 month. CCT was significantly thicker at 10 days compared with prelaser CCT, whereas CCT at 1 month was not statistically different. ACD showed a nonsignificant decrease after TCDLC from 3.77 +/- 0.81 to 3.38 +/- 0.85 mm at 10 days and 3.58 +/- 0.78 mm at 1 month. CONCLUSIONS: TCDLC does not alter corneal topography or ACD significantly. However, CCT increases during the 10 days after TCDLC and returns to normal at 1 month, which might be related to the inflammation induced by cyclophotocoagulation. Increased CCT may lead to artificially high intraocular pressure measurements within the first 4 weeks after surgery.

Conjunctival involvement in chronic recurrent multifocal osteomyelitis.

PURPOSE: To report a case of chronic recurrent multifocal osteomyelitis (CRMO) with conjunctival involvement. METHODS: Retrospective chart review. RESULTS: A 10-year-old girl who complained of fatigue and debilitating pain in both hips and legs for >1 year had recurrent episodes of redness and discharge in both eyes with little response to different topical medications. The diagnosis of CRMO was confirmed with the help of magnetic resonance imaging, bone scan, and bone biopsy results. She had moderate hyperemia and multiple discrete salmon-colored lesions in both palpebral and fornical conjunctivae. Biopsy revealed chronic inflammatory infiltration composed predominantly of lymphocytes forming a follicular pattern. Conjunctival lesions worsened during relapses of skeletal symptoms, improved during remission, and resolved shortly after the initiation of oral prednisolone therapy. No recurrence was observed during 16 months of follow-up. CONCLUSIONS: Salmon-colored conjunctival lesions may accompany CRMO and respond favorably to systemic steroid therapy.

Combined impact of matrix metalloproteinase-3 and paraoxonase 1 55/192 gene variants on coronary artery disease in Turkish patients.

BACKGROUND: We investigated the association of matrix metalloproteinase-3 (MMP-3) and paraoxonase 1 (PON1) 55/192 polymorphisms with coronary artery disease (CAD) and the number of diseased vessels in patients with CAD. MATERIAL/METHODS: One hundred thirty-nine CAD patients and 119 healthy control subjects were included in the study. Genotypes for PON1 55/192 and MMP-3 5A/6A polymorphisms were determined by restriction fragment length polymorphism. RESULTS: Although distributions of the RR genotype of PON1 192 and the 5A5A genotype of MMP-3 were more frequent in patients, frequencies of the QQ genotype of PON1 192, the MM genotype of PON1 55, and the 6A6A genotype of MMP-3 were significantly lower in patients compared with healthy control subjects. The combined genotypes of RR/LL and/or 5A5A are increased the risk of CAD when compared with subjects who possess neither the MMP-3 5A5A nor the PON1 RR/LL genotype. While the MMP-3 5A/6A genetic variants were not associated with the number of diseased vessels, PON1 55/192 variants were associated with the number of diseased vessels. CONCLUSIONS: The combined PON1 55/192 and MMP-3 5A/6A genetic variants are associated with CAD; PON1 seems to be connected with the number of diseased vessels, and hypertension and hyperlipidemia are related with PON1 192 and MMP-3 in CAD patients.

Unilateral acute retinal necrosis initially presenting with painful orbitopathy.

Painful orbital inflammation and scleritis-like clinical appearance can be the initial manifestation of acute retinal necrosis. We report a 25-year-old woman who first presented with painful orbitopathy that eventually developed into unilateral acute retinal necrosis with typical fundus appearance. Our case illustrates the importance of careful fundus examination in cases presenting with painful orbital inflammation.

Transscleral fixation of a black diaphragm intraocular lens in severely traumatized eyes requiring vitreoretinal surgery.

The records of 4 eyes of 4 patients who had transscleral fixation of black diaphragm intraocular lenses (IOLs) after vitreoretinal surgery due to complications of severe perforating trauma were retrospectively reviewed. The transscleral fixation was performed 4 to 13 months after the vitreoretinal surgery. All patients reported a subjective decrease in glare and photophobia, with improved visual acuity in 2 eyes during a mean follow-up of 3 years. Cystoid macular edema was noted in 1 eye and transitory intraocular pressure elevation due to intraocular silicone oil in 1 eye. Severe perforating eye injury is frequently associated with extensive iris defects and lenticular and vitreoretinal complications. Although visual acuity may not be the primary concern in these eyes, favorable visual rehabilitation can be achieved following proper management of the retinal complications and transscleral fixation of black diaphragm IOLs to overcome glare and photophobia.

Topical steroids in the management of Churg-Strauss syndrome involving the conjunctiva.

PURPOSE: To discuss a case of Churg-Strauss syndrome that developed bilateral conjunctival involvement while recovering from miliary tuberculosis. METHODS: Case report and literature review. RESULTS: A 22-year-old man who was on oral prednisolone for Churg-Strauss syndrome since 2002 contracted miliary tuberculosis in June 2004. The diagnosis was confirmed by liver biopsy. Ophthalmologic examination was within reference limits except for bilateral multifocal choroiditis. A combined therapy of rifampicin, ethambutol, streptomycin, and morphazinamide was started on June 24, 2004. Complete recovery was achieved, and the antituberculosis therapy was terminated in June 2005. The patient noted redness and pain in both eyes a month later. He had bilateral irregular, pink-yellow, gravel-like infiltrations involving the bulbar conjunctiva. Biopsy revealed granulomas with central fibrinoid necrosis, histiocytes, and eosinophils, suggestive of conjunctival involvement of Churg-Strauss syndrome. Topical dexamethasone 0.1% drops were started 4 times per day and tapered gradually. Lesions totally regressed within 2 months. No recurrence was noted during a follow-up of 11 months. CONCLUSIONS: Churg-Strauss syndrome may rarely involve the conjunctiva, and conjunctival lesions respond favorably to topical steroids.

The effect of scleral buckling surgery on corneal astigmatism, corneal thickness, and anterior chamber depth.

PURPOSE: To evaluate the effect of scleral buckling surgery on corneal topography, corneal thickness, and anterior chamber depth. METHODS: Thirty-two eyes of 32 patients who underwent encircling buckling surgery for rhegmatogenous retinal detachment were included in the study. Fellow eyes comprised the control group. Orbscan II topography system was used to determine the changes in corneal topography, corneal thickness, and anterior chamber depth before surgery and 1 week, 1 month, and 3 months after surgery. Statistical analyses used in the study were independent t test, paired t test, one way analysis of variance, and correlation analyses. RESULTS: Postoperatively, mean central corneal astigmatism at 1 week, 1 month, and 3 months was 4.3 +/- 2.0 diopters (D), 3.3 +/- 1.6 D, and 3.1 +/- 1.0 D, respectively. The change between 1 week and 3 months was statistically significant. Central cornea was thickened at the first postoperative week. The thickness gradually decreased to the preoperative levels at 3 months. Anterior chamber depth decreased, and the anterior chamber remained shallow after the surgery. The comparison between preoperative (2.94 +/- 0.6 mm) and postoperative anterior chamber depth was statistically significant at 1 week (2.57 +/- 0.7 mm), 1 month (2.83 +/- 0.7 mm), and 3 months (2.73 +/- 0.6 mm). CONCLUSIONS: Corneal changes after scleral buckling surgery were mild to moderate and the cornea almost resumed its preoperative parameters in 3 months' time. However, the anterior chamber remained shallow during 3 months of follow-up.

Successful management of aniridic ocular surface disease with long-term bandage contact lens wear.

PURPOSE: To present an aniridic patient with failed penetrating keratoplasties OU (PK) who underwent successful repeat PK OD, which has remained clear for 4 years with continuous bandage lens (BCL) wear. METHODS: A 73-year-old aniridic woman who had a failed PK complicated by ocular surface disease refused limbal stem cell transplantation and underwent repeat PK in her right eye. The immediate postoperative course was uneventful except for mild irregularity of the graft epithelium. Two months postoperatively, she presented with an epithelial defect along the inferotemporal graft margin adjacent to an exposed, loose interrupted suture. The suture was removed, and although the initial epithelial defect healed, she suffered recurrent episodes of epithelial breakdown and generalized whorl epitheliopathy. A BCL was inserted and rendered prompt healing of the graft epithelium, which has remained smooth and intact for 4 years. RESULTS: The graft remains thin and clear with a smooth and intact epithelial surface beneath the BCL and no signs of limbal stem-cell deficiency. CONCLUSION: Long-term BCL wear provided good corneal transplant surface protection in an aniridic patient with recurrent epithelial breakdown, thereby sparing the need for limbal stem cell transplantation and the use of potentially toxic systemic immunosuppressive therapy. Meticulous follow-up is required to monitor contact lens loss and epithelial breakdown as well as signs of secondary infectious keratitis.