Cyclodextrin enhances corneal tolerability and reduces ocular toxicity caused by diclofenac

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation

Adenosine A2A Receptor Blockade Prevents Rotenone-Induced Motor Impairment in a Rat Model of Parkinsonism

Pharmacological studies implicate the blockade of adenosine receptorsas an effective strategy for reducing Parkinson’s disease (PD) symptoms. The objective of this study is to elucidate the possible protective effects of ZM241385 and 8-cyclopentyl-1, 3-dipropylxanthine, two selective A2A and A1 receptor antagonists, on a rotenone rat model of PD. Rats were split into four groups: vehicle control (1 ml/kg/48 h), rotenone (1.5 mg/kg/48 h, s.c.), ZM241385 (3.3 mg/kg/day, i.p) and 8-cyclopentyl-1, 3-dipropylxanthine (5 mg/kg/day, i.p). After that, animals were subjected to behavioral (stride length and grid walking) and biochemical (measuring concentration of dopamine levels using high performance liquid chromatography, HPLC). In the rotenone group, rats displayed a reduced motor activity and disturbed movement coordination in the behavioral tests and a decreased dopamine concentration as foundby HPLC. The effect of rotenone was partially prevented in the ZM241385 group, but not with 8-cyclopentyl-1,3-dipropylxanthine administration. The administration of ZM241385 improved motor function and movement coordination (partial increase of stride length and partial decrease in the number of foot slips) and an increase in dopamine concentration in the rotenone-injected rats. However, the 8-cyclopentyl-1,3-dipropylxanthine and rotenone groups were not significantly different. These results indicate that selective A2A receptor blockade by ZM241385, but not A1 receptor blockadeby 8-cyclopentyl-1,3-dipropylxanthine, may treat PD motor symptoms. This reinforces the potential use of A2A receptor antagonists as a treatment strategy for PD patients

The Computer Science Ontology: A Large-Scale Taxonomy of Research Areas

Ontologies of research areas are important tools for characterising, exploring, and analysing the research landscape. Some fields of research are comprehensively described by large-scale taxonomies, e.g., MeSH in Biology and PhySH in Physics. Conversely, current Computer Science taxonomies are coarse-grained and tend to evolve slowly. For instance, the ACM classification scheme contains only about 2K research topics and the last version dates back to 2012. In this paper, we introduce the Computer Science Ontology (CSO), a large-scale, automatically generated ontology of research areas, which includes about 26K topics and 226K semantic relationships. It was created by applying the Klink-2 algorithm on a very large dataset of 16M scientific articles. CSO presents two main advantages over the alternatives: i) it includes a very large number of topics that do not appear in other classifications, and ii) it can be updated automatically by running Klink-2 on recent corpora of publications. CSO powers several tools adopted by the editorial team at Springer Nature and has been used to enable a variety of solutions, such as classifying research publications, detecting research communities, and predicting research trends. To facilitate the uptake of CSO we have developed the CSO Portal, a web application that enables users to download, explore, and provide granular feedback on CSO at different levels. Users can use the portal to rate topics and relationships, suggest missing relationships, and visualise sections of the ontology. The portal will support the publication of and access to regular new releases of CSO, with the aim of providing a comprehensive resource to the various communities engaged with scholarly data

Effects of administration of 10 nm or 50 nm gold nanoparticles (AuNPs) on blood profile, liver and kidney functions in male albino rats

This work aimed to investigate the effect of acute and chronic administration of gold nanoparticles (GNPs) on liver and kidney functions, blood glucose concentration, lipid profile, and haematological parameters in male albino rats. Two experiments were conducted. In acute study: Fifty-four adult mature male rats were randomly assigned into three equal groups (18 per group). Group 1 (control group): in which rats were received intramuscular (i.m) injection of 1 ml normal saline 0.9%. Group 2 (50 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 50 nm GNPs/kg body weight (bwt). In Group 3 (10 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 10 nm GNPs/kg bwt. In chronic study: Eighteen adult male rats were randomly divided into three equal groups (6 per group). Group І (control): rats were intramuscular (i.m) repeatedly injected with 1 ml normal saline 0.9% once/week 5 for weeks. Group 2 (50 nm GNPs): rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt) for 5 weeks. In Group 3 (10 nm GNPs): male rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt for 5 weeks, followed by 3 weeks washout period for all groups. Blood was collected at 3, 7, and 60 days in acute experiment, while, they were collected only before and after 2 months in chronic experiment. Acute and chronic administration of GNPs (10 or 50 nm size) in male albino rats induced no significant alterations for liver and kidney functions, lipid profile parameters and different haematological parameters at days 3 and 60 of the study. However, on day-7 post-treatment, GNPs-treated rats showed significantly (P <0.05) higher serum ALT, AST, ALP, urea, creatinine, glucose, and different lipid profile and decreased HDL level. Chronic administration of 10 nm or 50 nm GNPs significantly (P <0.05) decreased serum glucose levels. In conclusion acute or chronic administration of 10 nm or 50 nm GNPs could alter the liver, kidney functions and blood profile on day 7 post-treatment, however, these values returned to the normal levels on day 60 post- injection. Also, the chronic administration of GNPs induced a hypoglycemic effect in male albino rats

Effects of administration of 10 nm or 50 nm gold nanoparticles (AuNPs) on blood profile, liver and kidney functions in male albino rats

486-493This work aimed to investigate the effect of acute and chronic administration of gold nanoparticles (GNPs) on liver and kidney functions, blood glucose concentration, lipid profile, and haematological parameters in male albino rats. Two experiments were conducted. In acute study: Fifty-four adult mature male rats were randomly assigned into three equal groups  (18  per  group).   Group   1   (control   group):  in   which  rats   were  received   intramuscular   (i.m)   injection  of 1 ml normal saline 0.9%. Group 2 (50 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 50 nm GNPs/kg body weight (bwt). In Group 3 (10 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 10 nm GNPs/kg bwt. In chronic study: Eighteen adult male rats were randomly divided into three equal groups (6 per group). Group І (control): rats were intramuscular (i.m) repeatedly injected with 1 ml normal saline 0.9% once/week 5 for weeks. Group 2 (50 nm GNPs): rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt) for 5 weeks. In Group 3 (10 nm GNPs): male rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt for 5 weeks, followed by 3 weeks washout period for all groups. Blood was collected at 3, 7, and 60 days in acute experiment, while, they were collected only before and  after  2  months  in  chronic  experiment.  Acute  and  chronic  administration  of  GNPs  (10  or 50 nm size) in male albino rats induced no significant alterations for liver and kidney functions, lipid profile parameters and different haematological parameters at days 3 and 60 of the study. However, on day-7 post-treatment, GNPs-treated rats showed significantly (P P <0.05) decreased serum glucose levels. In conclusion acute or chronic administration of 10 nm or 50 nm GNPs could alter the liver, kidney functions and blood profile on day 7 post-treatment, however, these values returned to the normal levels on day 60 post- injection. Also, the chronic administration of GNPs induced a hypoglycemic effect in male albino rats

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P &lt; 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

Breast-feeding and risk of epithelial ovarian cancer.

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Reproductive factors for ovarian cancer in southern Chinese women

Objective: To investigate the association between reproductive factors and the risk of ovarian cancer among southern Chinese women. Methods: A hospital-based case-control study was undertaken in Guangzhou, Guangdong Province, between 2006 and 2008. A structured questionnaire was used to obtain information on parity, oral contraceptive use and other reproductive factors in a sample of 500 incident ovarian cancer patients and 500 controls (mean age, 59 years). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. Results: High parity was inversely associated with ovarian cancer, with an adjusted OR 0.43 (95% CI, 0.30 to 0.62) for women who had given birth to 3 or more children compared to women who had given no more than one birth. Ever use of oral contraceptives was also protective against ovarian cancer; adjusted OR 0.56 (95% CI, 0.40 to 0.78). No association was found for hormone replacement therapy, menopausal status, hysterectomy and family history of ovarian and/or breast cancer. Conclusion: High parity and oral contraceptive use are associated with a lower risk of ovarian cancer in southern Chinese women