Bio-adhesive polymers containing liposomes for DED treatment

Dry eye disease (DED) is a prevalent and multifactorial pathology of the ocular surface affecting 5-50% of the world’s population.1 The disease is characterized by a loss of homeostasis of the tear film and it may manifest with ocular symptoms such as dryness and burning.2,3 Tear hyperosmolarity and tear film instability constitute the core mechanisms in DED pathophysiology.4 Recently, neutrophil extracellular traps (NETs) have also been postulated to play a role in the pathogenesis of the disease.5,6 Artificial tears constitute the first-line therapy for mild dry eye.7 Nonetheless, most of these ophthalmic formulations in the market supplement only the aqueous phase of the tear film, providing primarily symptomatic relief. Furthermore, artificial tears have drawbacks such as short ocular residence time.8Objectives and ResultsObjective-1: Development of artificial tear formulations containing novel components, with suitable physicochemical properties, optimum tolerance, and extended ocular residence time. Liposomes were utilized to replenish the lipids of the tear film and bioadhesive and/or in situ gelling polymers (hydroxypropyl methylcellulose and/or gellan gum, respectively) to extend the ocular residence time of the formulations. In addition, antioxidants (vitamins A, C, and E), osmoprotectants (levocarnitine and trehalose), or antidessicants (trehalose) were incorporated into the formulations for their potential beneficial effects in DED treatment. The neutral to slightly alkaline pH (7.0–7.6), surface tension (44.6–48.7 mN/m), viscosity (3.6–12.1 mPa.s), slight hypotonicity (222.7–272.7 mOsm/L), and liposome size (191.0–200.1 nm) exhibited by the formulations in the physicochemical characterization were considered suitable for topical ophthalmic administration. Formulations containing gellan gum produced viscoelastic gels with shear-thinning properties and suitable viscosities (2.8–3.0 mPa.s). In vivo tolerance studies (in rabbits) showed that the formulations resulted well tolerated. Objective-2: Development of novel tools to evaluate the efficacy of the artificial tear formulations. An in vivo dry eye model and an ex vivo dry eye model were developed. Dry eye was induced in rabbits with topical administration of the preservative benzalkonium chloride (BAK) at 0.1% for 15 days. Dry eye signs including corneal damage, goblet cell loss, and impairments in the conjunctival epithelium were observed in animals after the BAK treatment. Furthermore, a complete ex vivo porcine anterior eye model (Aston Biological Anterior Eye Model) was optimized by adjusting the irrigation frequency of the eyes with a tear analogue. Objective-3: Efficacy studies of the novel artificial tear formulations. Preliminary studies. Preliminary efficacy studies of one of the novel formulations, composed of an in situ gelling polymer (gellan gum 0.25%), a bioadhesive polymer (hydroxypropyl methylcellulose 0.12%), osmoprotectants (levocarnitine 0.4% and trehalose 1.68%), an antioxidant (vitamin C 0.01%), electrolytes (sodium chloride 0.05% and potassium chloride 0.05%), and borates (boric acid 0.84% and sodium tetraborate anhydrous 0.08%), were performed in the previously mentioned in vivo and ex vivo DED models, over a period of 21 days and 18 hours, respectively. In the in vivo model, the treatment with the artificial tear promoted significant improvements in the cornea and the conjunctiva at 7 days after continued treatment (significantly reduced fluorescein and cytological scores compared with baseline). In the ex vivo model, the formulation improved the ocular surface with two instillations after 18 hours, though the small sample size did not allow statistical analysis. Objective-4: Assessment of the effects of the novel artificial tear formulations on NET formation as a proof of concept. Excessive amounts and impaired clearance of NETs have been observed on the ocular surface of DED patients and linked with the pathogenesis of the disease.5,6 Effects of the novel artificial tear formulations on NET formation (NETosis) were assessed in neutrophils. The formulations did not increase NET formation in unstimulated neutrophils, demonstrating an optimal tolerance. Furthermore, in neutrophils stimulated with a NETosis inducing agent, all of the formulations reduced NET formation significantly.Conclusions1. All of the novel artificial tear formulations developed in this thesis, containing different combinations of liposomes (made up of phosphatidylcholine and cholesterol), a bioadhesive polymer (hydroxypropyl methylcellulose), an in situ gelling polymer (gellan gum), osmoprotectants (levocarnitine and trehalose), antioxidants (vitamins A, C, and E), and other formulation excipients (fructose, electrolytes, and borates) demonstrate suitable physicochemical properties for topical ophthalmic administration and are well tolerated in rabbits.2. Incorporation of gellan gum at 0.25% with electrolytes created artificial tears with in situ gelling properties, capable of producing viscoelastic gels that suggest an extended ocular residence time of the ophthalmic formulations.3. Twice-daily topical ophthalmic administration of the preservative benzalkonium chloride at 0.1% for 15 days induces significant alterations on the ocular surface of rabbits that are indicative of dry eye disease. The experimental dry eye model can be used as a platform to evaluate the efficacy of artificial tears.4. According to the preliminary efficacy studies performed in the in vivo dry eye model, the novel artificial tear containing the in situ gelling polymer gellan gum (0.25%), the bioadhesive polymer hydroxypropyl methylcellulose (0.12%), the osmoprotectants levocarnitine (0.4%) and trehalose (1.68%), the antioxidant vitamin C (0.01%), borates (boric acid 0.84% and sodium tetraborate anhydrous 0.08%), and electrolytes (sodium chloride 0.05% and potassium chloride 0.05%) may be beneficial in DED treatment

Bio-adhesive polymers containing liposomes for DED treatment

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Farmacia Galénica y Tecnología Alimentaria, leída el 28-06-2019La enfermedad de ojo seco (EOS) se considera una patología multifactorial que cursa con sequedad o quemazón de la superficie ocular con una prevalencia comprendida entre el 5 y el 50% de la población mundial. La hiperosmolaridad y la inestabilidad de la película lagrimal constituyen los mecanismos principales dela fisiopatología del EOS. Recientemente se ha postulado que las trampas extracelulares de neutrófilos (NET) están involucrados en la patogénesis de la enfermedad...Dry eye disease (DED) is a prevalent and multifactorial pathology of the ocular surface affecting 5-50% of the world’s population. The disease is characterized by a loss of homeostasis of the tear film and it may manifest with ocular symptoms such as dryness and burning. Tear hyperosmolarity and tear film instability constitute the core mechanisms in DED pathophysiology. Recently, neutrophilextracellular traps (NETs) have also been postulated to play a role in the pathogenesis of the disease..Fac. de FarmaciaTRUEunpu

Türk hastalarda epilepsi cerrahisinden sonra yaşam kalitesi ve maliyet analizi

Objectives: The aim of this study was to evaluate postoperative changes in terms of seizure frequency, antiepileptic drug (AED) consumption and quality of life, and in parallel with this, to determine the changes in AED and healthcare costs after surgery. Methods: Twenty-four patients who underwent epilepsy surgery with medically intractable epilepsy were included in the study. Demographic features, seizure frequency and number of AEDs were obtained, and the Short Form Health Survey (SF-36) was administered pre- and postoperatively. Financial records were accessed via the university hospital database and the central network database of the national social security administration. Results: ATLE or lesionectomy was carried out in 24 patients. During the mean follow-up period of 24 months, 67% of patients achieved Class 1 and 2 seizure control and a significant reduction in the number of AEDs (p<0.005). On the SF-36, the general perception of health and role limitations due to emotional problems significantly improved postoperatively. The cost analysis revealed a significant reduction in AED and healthcare costs due to epilepsy in patients who underwent surgery (p<0.005). Conclusion: Surgical interventions for medically intractable epilepsy are effective in seizure control and have a notable beneficial effect on quality of life as well as healthcare costs. These medical and economic benefits of epilepsy surgery should encourage Turkish neurologists to refer patients to comprehensive epilepsy centers

Ownership and Corporate Social Responsibility:"The power of the female touch"

Using a sample of 26,029 firm-year observations over the period 2002–2017 from 4,479 firms and 44 countries, we examine the relationship between ownership concentration and corporate social responsibility by focusing on the mediating role of board gender diversity and the moderating role of family shareholding. We find that ownership concentration negatively affects corporate social responsibility, and the board gender diversity partially mediates this negative effect. Our results indicate that the mediating effect of board gender diversity leads to a 10.65 percent decrease in the impact of ownership concentration on corporate social responsibility. Furthermore, moderated path analysis indicates that family shareholding weakens the direct effect of ownership concentration on board gender diversity and its indirect effect on corporate social responsibility. In post hoc analysis, we also document that the effect of gender diversity on the board is more prevalent in high gender-egalitarian societies where women are more involved in decision-making. Our study addresses the strategic role of female board members in increasing firms' respect for corporate social responsibility, especially in family-controlled firms. Thus, our results may provide insights to regulators and policymakers to enhance firms’ corporate social practices by encouraging women’s participation on corporate boards

Türkiye'de subklinik mastitisli pırlak koyunlardan izole edilen stafilokoklarda metisilin direnç ve panton-valentine lökosidin genlerinin prevalansı

This study aimed to investigate the presence of mecA and pvl genes in 47 Staphylococci previously isolated from 464 half-udder milk samples belong to 235 Pirlak sheep screening for subclinical mastitis. The species from Pirlak sheep used in the present study included: 13 S. aureus, 13 S. epidermidis, six S. xylosus, five S. chromogenes, three S. simulans, three S. hyicus, two S. warneri, one S. lentus and one S. saprophyticus. A total of 10 strains (21.3%) were determined to harbour mecA gene, of these, two (4.2%) also contained pvl gene. The strains carrying mecA gene were found to be S. aureus (3/13), S. xylosus (3/6), S. epidermidis (2/13), S. lentus (1/1) and S. hyicus (1/3). The presence of pvl gene was determined in a total of eight strains (17.0%), six (12.8%) of these were alone. Of pvl positive strains, three, three, one, and one were S. aureus, S. xylosus, S. simulans and S. hyicus, respectively. To our knowledge, this is the first study showing the presence of mecA and pvl genes in the Staphylococci isolated from Pirlak sheep with subclinical mastitis in Turkey.Bu çalışmada, subklinik mastitis yönünden taranan 235 Pırlak koyuna ait 464 meme lobu süt örneğinden daha önce izole edilen 47 Stafilokok türünde mecA ve pvl genlerinin varlığının araştırılması amaçlandı. Çalışmada, Pırlak koyunlardan izole edilen 13 S. aureus, 13 S. epidermidis, altı S. xylosus, beş S. chromogenes, üç S. simulans, üç S. hyicus, iki S. warneri, bir S. lentus ve bir S. saprophyticus suşu kullanıldı. Toplam 10 suşun (%21,3) mecA geni taşıdığı, bunlardan ikisinin (%4,2) ayrıca pvl genine de sahip olduğu belirlendi. mecA geni taşıyan suşlar S. aureus (3/13), S. xylosus (3/6), S. epidermidis (2/13), S. lentus (1/1) ve S. hyicus (1/3) olarak bulundu. Toplam sekiz suşta (%17,0) pvl geni belirlenirken, bunlardan altısının (%12,8) bu geni tek başına taşıdığı tespit edildi. pvl pozitif suşların üçü S. aureus, üçü S. xylosus, biri S. simulans ve biri S. hyicus olarak belirlendi. Bilgimize göre, bu çalışma Türkiye'de subklinik mastitisli Pırlak koyunlardan izole edilen Stafilokoklarda mecA ve pvl genlerinin varlığını gösteren ilk çalışmadır

Postoperative Positional and Dimensional Changes of Mandibular Canal after Bilateral Sagittal Split Set-Back Osteotomy

Objective:This preliminary study was planned to provide information about preoperative mandibular canal (MC) position and the postoperative positional changes of MC and length in three dimensions, with the purpose of providing some assistance in reducing inferior alveolar neurosensory disturbance (IAND).Methods:MC was examined on CBCT data using SimPlant Pro Standalone 13.0. MC locations were measured in all dimensions, with respect to mandibular bony borders.Results:The results showed that MC is frequently located in the midthird of the ramus anteroposteriorly and superoinferiorly and in the midthird of the corpus superoinferiorly. Postoperatively, ramus width was increased, ramus length was decreased significantly, and MC was repositioned laterally and inferiorly. MC length was decreased on both sides, non-correlated with the set-back amounts.Conclusion:Preoperative results may be beneficial for the prediction of MC position for surgeons, and postoperative results will be used for the following studies to correlate postoperative positional changes with IAND

The comparison of milking hygiene with bulk tank somatic cell count and total bacterial count in dairy herds in Tekirdag province

Sunulan çalışma ile Tekirdağ ilindeki aile tipi süt işletmelerinde meme sağlığı ve sağım hijyeni uygulamalarının incelenmesi, işletmelerden alınan tank sütü örneklerinde somatik hücre sayısı (SHS) ve toplam bakteri sayısı sonuçlarının değerlendirilmesi, elde edilen sonuçların karşılaştırılması ve eksikliklerin ortaya konulması amaçlandı. Tekirdağ ilinin farklı bölgelerinde bulunan 50 farklı işletme ve çiğ süt toplama merkezi seçilerek, 150 mL’lik steril kaplara süt örnekleri alındı. Süt örneklerinde SHS ve toplam canlı bakteri sayısı ölçüldü. Tank sütü örneklerinin alındığı gün aynı işletmelerin çalışanlarına ya da işletme sahiplerine anket uygulaması yapılarak işletmede uygulanan mastitis kontrol programlarına ait bilgiler değerlendirildi. Alınan tank sütü örneklerinde SHS ortalaması 560.204,08 (±12.399,769) hücre/mL, toplam canlı bakteri sayısı ortalama 1.796.718,36 (±156.573,31) kob/mL olarak tespit edildi. Yapılan anket ve laboratuvar analizleri sonrası işletmelerde sağım öncesi meme başlarının yıkanması, kurulanması, teat dipping, ön sağım ve ön sütün kontrolü, kuru dönem idaresi ve meme sağlığı kontrollerinin neredeyse hiç uygulanmadığı görüldü. Sonuç olarak, Tekirdağ ilinde bulunan aile tipi sütçü işletmelerde tank sütü SHS ve toplam canlı bakteri sayısının kabul edilebilir değerlerin üzerinde olduğu, bunun sebebinin işletmelerde uygulanmayan veya dikkat edilmeyen meme sağlığı kontrol programları olabileceği kanısına varıldı. Bu bölgedeki sütçü işletmelere meme sağlığını üst seviyelerde tutmak ve süt kalitesini en iyi düzeye getirebilmek amacıyla bu konuda yoğun eğitim seminerleri ve/veya bilgilendirme toplantılarının yapılmasının uygun olacağı kanaatine varıldı.The investigation of mammary health and milking hygiene procedures, bulk tank milk somatic cell count (SCC) and total bacterial counts, and detecting deficiencies and mistakes following the comparisons of results in Tekirdag province were aimed. The bulk tank milk samples were collected from 50 family farms. 150 mL of sterile milk samples were taken from milk tanks. Somatic cell counts and total viable bacterial counts were analyzed. On the milk sampling day, a questionnaire was filled out to farm personal or owner to evaluate mastitis control programs applied in the farms. In the bulk tank milk samples, mean SCC was found 560204.08 (±12399.769) cells/mL, and mean total viable bacterial count were found 1,796,718.36 (±156,573.31) CFU/mL. After survey and laboratory analyzes, it was detected that premilking cleaning and drying, teat-dipping, strip before milking, dry-cow management and mastitis control program procedures were using hardly ever. In conclusion, SCC and total bacterial count were higher than acceptable values due to the insufficient practice of mastitis control programs in the small and middle family farms in Tekirdag province. It was considered that some education seminars and/or contact meetings about this issue should be planned to increase mammary health status and milk quality

The Effect of Out-of-School Learning Activities on Gifted Students’ Affective and Behavioral Tendencies Towards The Environment

This study investigates the effect of out-of-school activities on gifted students' affective and behavioral tendencies. Mixed method research with a single group pre and post-test experimental design was used in this study. Twenty-five gifted students from Turkey-İstanbul participated in this study. “Environmental Affect Scale” and “Environmental Behavior Scale” were used, and semi-structured interviews were conducted. Results showed that out-of-school activities positively affected the students’ affective and behavioral tendencies toward the environment. It was also found that the awareness of students on environmental problems increased, and they began to produce their solutions to these problems

Beyazlatma sonrasında antioksidan uygulamasının minenin bağlanma kuvvetine etkisi

Amaç: Bu çalışmanın amacı, % 10 sodyum askorbat (SA), %6.5 üzüm çekirdeği özü (ÜÇÖ) ve % 10 alfa-tokoferol (α-TP)’ ün farklı uygulama sürelerinde, beyazlatılmış mineye, adeziv rezin simanın makaslama bağlanma kuvvetini değerlendirmektir.Gereç ve Yöntemler: 108 adet insan üst santral dişi 9 gruba ayrılmıştır (n:12). Kontrol grubu dışındaki bütün gruplara % 40’lık hidrojen peroksit (HP) kullanarak beyazlatma işlemi uygulanmıştır. Gruplar; GK: Beyazlatma uygulanmadan restorasyon yapılan (kontrol grubu), GB: Beyazlatma yapıldıktan sonra restorasyon yapılan, GT7g: Yapay tükürükte 7 gün bekledikten sonra restorasyon yapılan, GSA15: 15 dakika süreyle % 10 SA uygulandıktan sonra restorasyon yapılan, GSA60: 60 dakika süreyle % 10 SA uygulandıktan sonra restorasyon yapılan, Gα-TP15: 15 dakika süreyle % 10 α-TP uygulandıktan sonra restorasyon yapılan, Gα-TP60: 60 dakika süreyle % 10 α-TP uygulandıktan sonra restorasyon yapılan, GÜÇÖ15: 15 dakika süreyle % 6.5 ÜÇÖ uygulandıktan sonra restorasyon yapılan, GÜÇÖ60: 60 dakika süreyle %6.5 ÜÇÖ uygulandıktan sonra restorasyon yapılan. Antioksidan uygulamasından hemen sonra, indirekt restorasyonlar adeziv rezin simanla diş yüzeyine bağlanmıştır. Örnekler distile suda 24 saat 37°C’de bekletildikten sonra, makaslama bağlanma kuvveti testi yapılmıştır. Kırılma tipleri stereomikroskop altında değerlendirilmiştir. Veriler tek yönlü varyans analizi, Levene ve Tukey HSD testleri kullanılarak yapılmıştır (