79 research outputs found
Recent Strategies for Ocular Drug Delivery: Promises and Challenges
Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers. The emerging nanoscience is playing an important role in the development of novel strategies for ocular disease management. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and interact with certain ocular tissues. In this chapter, highlights will be made on barrier to intraocular delivery, general pathways for ocular absorption, and factors affecting intraocular bioavailability. The recent attempts of nanotechnology for treating anterior and posterior ocular diseases will be explored. This will include nanomicelles, nanoparticles, nanosuspensions, vesicular systems, in situ gel, dendrimers, contact lenses, implants, microneedles, and cell-based delivery systems. In addition, gene-based ocular delivery systems will be discussed. In this chapter, we will also provide a comprehensive overview of drug-device combinations used for ocular diseases such as glaucoma, dry eye disease, infections, and inflammations. Furthermore, drug delivery devices for ocular surgeries are discussed. Finally, challenges and future prospective of ocular delivery systems will be explored
Evaluation of The Economic Efficacy of Some Antimycotoxicosis Compounds on Production and Humoral Immunity in Broiler Chickens.
Mycotoxicosis is an important problem in poultry industry causing global economic losses constituting a great threat. The present study was designed to investigate the ameliorative effects of four different antimycotoxicosis compounds (AMCs) against production, economic performance and humoral immunity induced by intoxication of dietary aflatoxin (AF) and/or ochratoxin (OT) in broiler chicks. Experiment (I), AF (23 ppb) and OT (17 ppb) were fed alone or mixed and in association with antimycotoxin feed additives, product A or B (1 and 0.5 g/kg feed), respectively. In experiment (II), the intoxicated chicks treated with antimycotoxin drugs, product C or D in drinking water (1ml/liter/3 successive days and 0.5 ml/liter/one day), respectively. Results revealed that chicks intoxicated with AF and/or OT showed significant (P<0.05) increase in feed conversion ratio (FCR) and mortality percentages (%) while the antibody titers against Newcastle disease (ND) virus were significantly (P<0.05) reduced. It is interesting to note that the adverse effects on FCR and mortality % were significantly (P<0.05) reduced in the single AF or OT contaminated diets with dietary supplementation of product A but in the mixed AF and OT contaminated diet, FCR were significantly (P<0.05) decreased with addition of product B. Also, product B showed significant (P<0.05) increase in the antibody titers against ND in all AF and/or OT contaminated groups. Moreover, the treatment of AF and/or OT intoxicated chicks with product C or D in the drinking water was reported significant (P<0.05) decrease in the mortality% and non-significant (P>0.05) change in FCR and ND antibody titers
Enhanced oral permeability of Trans-Resveratrol using nanocochleates for boosting anticancer efficacy; in-vitro and ex-vivo appraisal
Hepatocellular carcinoma (HCC) is a prevalent liver cancer representing the fourth most lethal cancer worldwide. Trans-Resveratrol (T-R) possesses a promising anticancer activity against HCC. However, it suffers from poor bioavailability because of the low solubility, chemical instability, and hepatic metabolism. Herein, we developed T-R-loaded nanocochleates using a simple trapping method. Nanocarriers were optimized using a comprehensive in-vitro characterization toolset and evaluated for the anticancer activity against HepG2 cell line. T-R-loaded nanocochleates demonstrated monodispersed cylinders (163.27 ± 2.68 nm and 0.25 ± 0.011 PDI) and −46.6 mV ζ-potential. They exhibited a controlled biphasic pattern with minimal burst followed by sustained release for 72 h. Significant enhancements of Caco-2 transport and ex-vivo intestinal permeation over liposomes, with 1.8 and 2.1-folds respectively, were observed. Nanocochleates showed significant reduction of 24 h IC50 values compared to liposomes and free T-R. Moreover, an efficient knockdown of anti-apoptotic (Bcl-2) and cancer stemness (NANOG) genes was demonstrated. To the best of our knowledge, we are the first to develop T-R loaded nanocochleates and scrutinize its potential in suppressing NANOG expression, 2-folds lower, compared to free T-R. According to these auspicious outcomes, nanocochleates represent a promising nanoplatform to enhance T-R oral permeability and augment its anticancer efficacy in the treatment of HCC
Bioactive Metabolites from Propolis Inhibit Superoxide Anion Radical, Acetylcholinesterase and Phosphodiesterase (PDE4)
Cycloartane-triterpenes (cycloartenol, 3α-cycloartenol-26-oic acid and 3β-cycloartenol-26-oic acid) together with α-amyrin acetate
and flavonoids (pinostrobin, tectochrysin and chrysin) were isolated from Egyptian propolis for the first time. Their antioxidant
activity was evaluated with DPPH and superoxide anion radical (O2.-). All compounds possessed both (O2.-) scavenging as well as XOD
inhibitory activity in the range of 50 – 75 %. With DPPH, only the flavonoids showed scavenging activity (48 – 83 %).
Acetylcholinesterase (AChE) and phosphodiesterase type 4 (PDE4) inhibitors are currently considered as intracellular targets for treatment of Alzheimer’s disease and Chronic obstructive pulmonary disease (COPD). 3β-cycloartenol-26-oic acid moderately
inhibited AChE and PDE4 activities in vitro with IC50 values of 0.8±0.2 and 1.9±0.4 μM, respectively, while 3-cycloartenol-26-oic acid
inhibited AChE activity with an IC50 value of 2.1±0.1 μM. The flavonoids pinostrobin and chrysin reduced PDE4 activity by 43 and 40
%, respectively (10 μM) as well as moderately inhibited the growth of the HepG2 cell line, whereas chrysin reduced proliferation of
NIH-3T3 cells at 50 μM. Therefore, our results with 3β- and 3-cycloartenol-26-oic acids can contribute to further research on alternative drugs for the treatment of neurological and neurodegenerative diseases, as well as asthma and COPD
ASSESSMENT OF CYTOTOXIC AND ANTICANCER ACTIVITY OF Zygophyllum album AND Suaeda palastina EXTRACTS ON HUMAN LIVER CANCER CELL LINES
In this study, anticancer activity of Zygophyllum album and Suaeda palastina extracts was evaluated. Dichloromethane, methanol and hot water were used as solvents for extraction. Results indicated that the highest half-maximal inhibitory concentration (IC50) on human lung carcinoma (A549) cell lines was achieved by dichloromethane extracts of Z. album and S. palastina (70.48 μg/ml and 34.82 μg/ml respectively) compared to methanolic and hot water extracts. Furthermore, dichloromethane extracts of both plants had antiproliferative effect and highly cytotoxicity on human cancer cells. IC50 of Z. album was 27.74 μg/ml in the human hepatocellular carcinoma (HepG2), while IC50 of S. palaestina was 30.76 μg/ml with no cytotoxic activity on normal cell lines. In conclusion, these results suggest that Z. album and S. palaestina could be a good candidate species as a natural source of anticancer agents
Assessment of seminal plasma laminin in fertile and infertile men
Abstract Aim: To assess laminin levels in the seminal plasma of infertile and fertile men, and to analyze the correlation of laminin levels with sperm count, age, sperm motility and semen volume. Methods: One hundred and twenty-five recruited men were equally divided into five groups according to their sperm concentration and clinical examination: fertile normozoospermia, oligoasthenozoospermia, non-obstructive azoospermia (NOA), obstructive azoospermia (OA) and congenital bilateral absent vas deferens (CBAVD). The patients' medical history was investigated and patients underwent clinical examination, conventional semen analysis and estimation of seminal plasma laminin by radioimmunoassay. Results: Seminal plasma laminin levels of successive groups were: 2.82 ± 0.62, 2.49 ± 0.44, 1.77 ± 0.56, 1.72 ± 0.76, 1.35 ± 0.63 U/mL, respectively. The fertile normozoospermic group showed the highest concentration compared to all infertile groups with significant differences compared to azoospermic groups (P < 0.05). Testicular contribution was estimated to be approximately one-third of the seminal laminin. Seminal plasma laminin demonstrated significant correlation with sperm concentration (r = 0.460, P < 0.001) and nonsignificant correlation with age (r = 0.021, P = 0.940), sperm motility percentage (r = 0.142, P = 0.615) and semen volume (r = 0.035, P = 0.087). Conclusion: Seminal plasma laminin is derived mostly from prostatic and testicular portions and minimally from the seminal vesicle and vas deferens. Estimating seminal laminin alone is not conclusive in diagnosing different cases of male infertility. (Asian J Androl 2007 Jan; 9: 63-67
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 < 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
Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey
Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
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