Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loratadine for Topical Application: Physicochemical Stability and Drug Penetration through Rat Skin

Purpose: To prepare solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) of loratadine (LRT) for the treatment of allergic skin reactions.Methods: SLN and NLC were prepared by high pressure homogenization method. Their entrapment efficiency (EE) and loading capacity (LC) were determined. The physical stability of nanoparticles was investigated during 6 months of storage at room temperature (RT), 4 and 40oC. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and laser diffraction (LD) were used for the investigation of drug:excipient compatibility, thermal behaviour and particle size of the nanoparticles. In vitro release and ex vivo skin penetration of LRT were studied. Nanoemulsions (NE) were also prepared and characterized for comparison.Results: Nanoparticles sizes ranged from 0.222 ± 0.011 μm to 0.252 ± 0.014 μm (D50 as a value based on the volume distribution, the maximum particle diameter below which 50 % of the sample volume exists) They were obtained with high drug payloads (> 90.67 %). LRT was compatible with the other excipients after 6 months. Particle size did not significantly alter particularly at RT. The highest release rate was obtained with NE (1.339 ± 0.026 mcg/ml/h) followed by NLC (1.007 ± 0.011 mcg/ml/h) and SLN (0.821 ± 0.012 mcg/ml/h), indicating anomalous transport (p < 0.05). Penetration profiles of LRT through skin were statistically similar for SLN and NLC (p > 0.05). NE showed the highest penetration rate (0.829 ± 0.06 mcg/cm2/h) (p < 0.05).Conclusion: SLN and NLC of LRT are alternative formulations for immediate treatment of allergic skin reactions with prolonged drug delivery via reservoir action.Keywords: Loratadine, Transdermal delivery, Controlled drug delivery, Solid Lipid nanoparticles, Nanostructured lipid carriers, Allerg

IMPROVING THE ACCURACY OF SATELLITE-BASED NEAR SURFACE AIR TEMPERATURE AND PRECIPITATION PRODUCTS

In this study, we evaluate the performance of several reanalyses and satellite-based products of near-surface air temperature and precipitation to determine the best product in estimating daily and monthly variables across the complex terrain of Turkey. Each product’s performance was evaluated using 1120 ground-based gauge stations from 2015 to 2019, covering a range of complex topography with different climate classes according to the Köppen-Geiger classification scheme and land surface types according to the Moderate Resolution Imaging Spectroradiometer (MODIS). Furthermore, various traditional and more advanced machine learning downscaling algorithms were applied to improve the spatial resolution of the products. We used distance-based interpolation, classical Random Forest, and more innovative Random Forest Spatial Interpolation (RFSI) algorithms. We also investigated several satellite-based covariates as a proxy to downscale the precipitation and near-surface air temperature, including MODIS Land Surface Temperature, Vegetation Index (NDVI and EVI), Cloud Properties (Cloud Optical Properties, Cloud Effective Radius, Cloud Water Path), and topography-related features. The agreement between the ground observations and the different products, as well as the downscaled temperature products, was examined using a range of commonly employed measures. The results showed that AgERA5 was the best-performing product for air temperature estimation, while MSWEP V2.2 was superior for precipitation estimation. Spatial downscaling using bicubic interpolation improved air temperature product performance, and the Random Forest (RF) machine learning algorithm outperformed all other methods in certain seasons. The study suggests that combining ground-based measurements, precipitation products, and features related to topography can substantially improve the representation of spatiotemporal precipitation distribution in data-scarce regions

Suitability of foramen magnum measurements in sex determination and their clinical significance

Background: The foramen magnum provides a transition between fossa cranii posterior and canalis vertebralis. Medulla oblongata, arteria vertebralis and nervus accessorius spinal part pass through the foramen magnum. In this study, we aimed to make the morphometric measurements of the foramen magnum on computed tomography (CT) and to determine the feasibility of sex determination based on these measurements. Besides sex determination, from a clinical aspect, it is important to know the measurements of the foramen magnum in the normal population in terms of diseases characterised by displacement of the posterior fossa structures through foramen magnum to upper cervical spinal canal such as Chiari malformations and syringomyelia. Materials and methods: All the data for our study was obtained retrospectively from 100 patients (50 males, 50 females) who had a CT scan of the head and neck region in Adnan Menderes University Hospital, Department of Radiology. To examine the foramen magnum in each and every occipital bone, we measured the foramen magnum’s anteroposterior diameter, transverse diameter, the area of the foramen magnum and its circumference. Results: We found that men have a higher average value than women in our study. According to Student’s t-test results; in all measured parameters, there is significant difference between the genders (p < 0.05). When multivariate discriminant function test is performed for all four measurements, the discrimination rate is 64% for all women, 70% for all men and 67% for both genders. Conclusions: As a result of our study, the metric data we obtained will be useful in cases where the skeletons’ sex could not be determined by any other methods. We believe that, our study may be useful for other studies in determining of sex from foramen magnum. Our measurements could give some information of the normal ranges of the foramen magnum in normal population, so that this can contribute to the diagnosis process of some diseases by imaging. (Folia Morphol 2018; 77, 1: 99–104)  

Porphyry Cu-Mo-(Au) Mineralization at Paraga Area, Nakhchivan District, Azerbaijan: Evidence from Mineral Paragenesis, Hyrothermal Alteration and Geochemical Studies

The Paraga area is located at the extreme eastern part of Nakhchivan district at the boundary with Armenia. The field study is situated at Ordubad region placed in 9 km from Paraga village and stays at 2300-2800 m height over sea level. It lies within a region of low-grade metamorphic porphyritic volcanic and plutonic rocks. The detailed field studies revealed that this area composed mainly of metagabbro-diorite intrusive rocks with porphyritic character emplaced into meta-andesitic rocks. This complex is later intruded by unmapped olivine gabbroic rocks. The Cu-Mo-(Au) mineralization at Paraga deposit is vein-type mineralization that is essentially related to quartz veins stockwork which cut the dioritic rocks and concentrated at the eastern and northeastern parts of the area with different directions N80W, N25W, N70E and N45E. Also, this mineralization is associated with two shearing zones directed N75W and N15E. The host porphyritic rocks were affected by intense sulfidation, carbonatization, sericitization and silicification with pervasive hematitic alterations accompanied with mineralized quartz veins and quartz-carbonate veins. Sulfide minerals which are chalcopyrite, pyrite, arsenopyrite and sphalerite occurred in two cases either inside these mineralized quartz veins or disseminated in the highly altered rocks as well as molybdenite and also at the peripheries between the altered host rock and veins. Gold found as inclusion disseminated in arsenopyrite and pyrite as well as in their cracks

Porphyry Cu-Mo-(Au) Mineralization at Paraga Area, Nakhchivan District, Azerbaijan: Evidence from Mineral Paragenesis, Hyrothermal Alteration and Geochemical Studies

The Paraga area is located at the extreme eastern part of Nakhchivan district at the boundary with Armenia. The field study is situated at Ordubad region placed in 9 km from Paraga village and stays at 2300-2800 m height over sea level. It lies within a region of low-grade metamorphic porphyritic volcanic and plutonic rocks. The detailed field studies revealed that this area composed mainly of metagabbro-diorite intrusive rocks with porphyritic character emplaced into meta-andesitic rocks. This complex is later intruded by unmapped olivine gabbroic rocks. The Cu-Mo-(Au) mineralization at Paraga deposit is vein-type mineralization that is essentially related to quartz veins stockwork which cut the dioritic rocks and concentrated at the eastern and northeastern parts of the area with different directions N80W, N25W, N70E and N45E. Also, this mineralization is associated with two shearing zones directed N75W and N15E. The host porphyritic rocks were affected by intense sulfidation, carbonatization, sericitization and silicification with pervasive hematitic alterations accompanied with mineralized quartz veins and quartz-carbonate veins. Sulfide minerals which are chalcopyrite, pyrite, arsenopyrite and sphalerite occurred in two cases either inside these mineralized quartz veins or disseminated in the highly altered rocks as well as molybdenite and also at the peripheries between the altered host rock and veins. Gold found as inclusion disseminated in arsenopyrite and pyrite as well as in their cracks

İntraoperative sonography ın evaluation and surgical treatment of liver metastases

Amaç: intraoperatif sonografinin, karaciğer tümörlü hastalarda teknik uygulama koşullarini, tani ve tedaviye olan katkisini ortaya koymak. Gereç ve Yöntem: Preoperatif inceleme yöntemlerine göre opere edilebilir olarak değerlendirilen 93 karaciğer metastazi olgusu sonografi ile incelenmiştir. Hastalar operasyondan önce ultrasonografi, bilgisayarli tomografi, anjiografi ve bazi olgularda sintigrafi ile değerlendirilmiş olup; intraoperatif sonografi bulgulari, preoperatif inceleme sonuçlari ve cerrahi bulgular ile karşilaştirilmiştir. Bulgular: Operasyonun gidişi 37 olguda (%40) değişmiştir.Yeni bulgular nedeniyle 14 olguya (%15) ek cerrahi girişim gerekirken, 7 olguda (%8) operasyon küçültülmüş, 16 olgu (%17) inoperabl bulunarak operasyon sonlandirilmiştir. Cerrahi gidişin değişme nedenini 10 (%11) olguda sadece intraoperatif sonografi, 10 (%11) olguda sadece cerrahi bulgular, 17 (%18) olguda ise her ikisi oluşturmuştur. Sonuç: Karaciğer metastazlarinin doğru evrelendirilerek gereksiz cerrahinin önlenmesinde intraoperatif sonografinin, duyarliği yüksek ve etkin bir inceleme yöntemi olduğu sonucuna varilmiştir. Genel olarak, hastalarin üçte birinde intraoperatif sonografi, operasyon gidişini değiştirdiğinden; özellikle karaciğer rezeksiyonu uygulanan merkezlerde intraoperatif karaciğer sonografisi, rutin uygulama olarak önerilmiştir.Purpose: The aim of this study was to evaluate the impact of intraoperative ultrasonography, on surgical decision making in patients with liver metastases. The technique of intraoperative ultrasonography also was discussed. Materials and Methods: intraoperative ultrasonography of the liver was performed in 93 patients operated for liver metastases. The patients were evaluated preoperatively by ultrasonography, computed tomography and in some cases by scintigraphy. intraoperative ultrasonography findings were compared with the results of preoperative imaging, surgical findings and the findings at surgery. Results: The surgical procedures were altered in 37 patients (40%). The procedure was extended in 14 patients (15%) and reduced in 7 patients (8%). Sixteen patients (17%) were found inoperable. The reason for the surgical modification was intraoperative ultrasonography alone in 10 patients (11%), surgical findings alone in 10 patients (11%), and a combination of both in 17 patients (18%). Conclusion: intraoperative ultrasonography is a precise diagnostic tool for staging the operability of liver metastases. Thus, unnecessary surgical procedures can be avoided. Totally, intraoperative ultrasonography altered the preoperative plan in one third of the patients and therefore is recommended as a routine procedure in connection with major liver surgery

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Bilkent University at TRECVID 2005

We describe our second-time participation, that includes one high-level feature extraction run, and three manual and one interactive search runs, to the TRECVID video retrieval evaluation. All of these runs have used a system trained on the common development collection. Only visual and textual information were used where visual information consisted of color, texture and edgebased low-level features and textual information consisted of the speech transcript provided in the collection. With the experience gained with our second-time participation, we are in the process of building a system for automatic classification and indexing of video archives