Cyclodextrin/Adamantane-Grafted Polyethylene Glycol-Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies.

Topical formulation of non-steroidal anti-inflammatory drugs (NSAIDs) exhibits many advantages over the oral administration route, such as avoiding the direct effect on GIT and avoiding the poor oral bioavailability of such drugs. Our study aims to develop a new self-assembling construct based on the hydrophobic interaction between adamantane terminated poly (ethylene glycol) polymers and polymerized ß-cyclodextrin. The viscous constructs were developed from direct mixing of host and guest polymer solutions, indicating spontaneous formation without cross-linkers. The modified system was evaluated by different analyses, including X-ray diffractometry, electron microscopy, isothermal titration calorimetry, and rheological analysis. Moreover, such a system's ability for drug loading and release was investigated via the in vitro release of ketorolac tromethamine (KT) as a model of NSAIDs. Finally, the prepared formulas were applied on a rat paw edema model to prove the enhanced anti-inflammatory activities. The obtained results indicated that the modified constructs have a rubbery porous structure with an amorphous nature. Also, from rheological results, the modified system exhibited a viscous behavior with higher loss modulus (G″) compared with storage (G'). The inclusion complexation between cyclodextrin and adamantane moieties was proved by the recorded high binding constants with a 1:1 stoichiometric ratio. Furthermore, the results showed the successful KT incorporation into the modified system and quantitatively released through a semi-permeable membrane in a sustained fashion (over 24 h). Finally, the in vivo results of the medicated constructs showed a significant inhibition of the induced inflammation and swelling, indicating that the modified construct has a great utility for safe non-irritating topical delivery applications.

Fluorouracil-Loaded Gold Nanoparticles for the Treatment of Skin Cancer: Development, in Vitro Characterization, and in Vivo Evaluation in a Mouse Skin Cancer Xenograft Model.

Fluorouracil (5-FU) is an antimetabolite drug used in the treatment of various malignancies, such as colon and skin cancers. However, its systemic administration results in severe side effects. Topical 5-FU delivery for the treatment of skin cancer could circumvent these shortcomings, but it is limited by the drug poor permeability through the skin. To enhance 5-FU efficacy against skin cancer and reduce its systemic side effects, it was loaded into a gold nanoparticle (GNP)-based topical delivery system. 5-FU was loaded onto GNPs capped with CTAB through ionic interactions between 5-FU and CTAB. GNPs were prepared at different 5-FU/CTAB molar ratios and evaluated using different techniques. GNP stability and drug release were studied as a function of salt concentration and solution pH. Optimum 5-FU/CTAB-GNPs were incorporated into gel and cream bases, and their ex vivo permeability was evaluated in mice dorsal skin. The in vivo anticancer efficacy of the same preparations was evaluated in A431 tumor-bearing mice. The GNPs had spherical shape and a size of ∼16-150 nm. Maximum 5-FU entrapment was achieved at 5-FU/CTAB molar ratio of 1:1 and pH 11.5. Drug release from GNPs was sustained and pH-dependent. 5-FU GNP gel and cream had around 2-fold higher permeability through mice skin compared with free 5-FU gel and cream formulations. Further, in vivo studies in a mouse model having A431 skin cancer cells implanted in the subcutaneous space showed that the GNP gel and cream achieved 6.8- and 18.4-fold lower tumor volume compared with the untreated control, respectively. These results confirm the potential of topical 5-FU/CTAB-GNPs to enhance drug efficacy against skin cancer.

Cross-sectional study on Asthma Insights and Management in the Gulf and Russia.

Background: Asthma is a chronic and complex lung disease that is not completely understood. It involves airway inflammation, reversible airflow obstruction, and bronchial hyperresponsiveness. The most common symptoms are recurrent wheezing, chest tightness, shortness of breath, and coughing. Objective: The Asthma Insights and Management study gathered information on the burden of asthma in the Gulf region (United Arab Emirates, Kuwait, Saudi Arabia) and Russia. Methods: This was a cross-sectional, multinational, noninterventional, two-phase study that collected data from patients ages ≥ 12 years, through interviews and a survey questionnaire. Phase 1 consisted of survey questions focused on estimating the asthma prevalence in the community. Phase 2 was designed to assess the level of asthma control, asthma-related perceptions and behaviors, and presentation patterns. Data were summarized by using descriptive analyses. Results: Analysis of data of 711 patients revealed that the prevalence of asthma among patients who lived in the community was 7.9% and that 66% subjectively perceived their asthma as being controlled. However, 97% of the patients' asthma were partially controlled or uncontrolled based on the Global initiative for Asthma control classification. Troubling symptoms were daytime coughing (33.3%) and shortness of breath (20.3%). With respect to medications for asthma, 76.2% of the patients reported the use of quick relief medication and 80.8% of maintenance medication during the past 4 weeks. Asthma exacerbation in the past year was reported by 40% of adults and adolescents in the study. Conclusion: The results showed that a significant proportion of the patients experienced bothersome symptoms and that many had a lack of knowledge about asthma control and treatment recommendations, which indicated that there is a need for improvements in patient education and asthma care in the Gulf and Russia regions.

Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil.

OBJECTIVE: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. METHODS: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. RESULTS: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4 °C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. CONCLUSION: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.

Relation of left atrial stiffness to insulin resistance in obese children: Doppler strain imaging study.

BACKGROUND: The main objective of the study was to assess the strain measures (peak systolic longitudinal strain [LAS] and stiffness index [LASt]) and their relation to insulin resistance in obese children. METHODS AND RESULTS: Eighty obese children (body mass index was 28.2 ± 3.1) and 60 age-matched healthy nonobese children were recruited. Conventional, tissue Doppler imaging LAS and LASt were measured for all children using 2D speckle tracking imaging (2DSI). Insulin resistance was assessed for obese children. Mean LAS was lower, and mean LASt was higher in obese children as compared to control group (11.3 + 2.2 vs. 38.2 + 11.6, P < 0.001, and 1.12 ± 0.23 vs. 0.21 ± 0.11, P < 0.001, respectively). LASt was significantly correlated with insulin resistance (P < 0.0001), and a value of >1.0 of LASt was the best cutoff value which can predict insulin resistance in obese children with a sensitivity of 92% and specificity of 86%. CONCLUSIONS: LAS and LASt differed significantly in obese and nonobese children, in spite of normal left ventricular systolic and diastolic functions. LAS and LASt were associated with insulin resistance in obese children.

Prevalence and Co-prevalence of Comorbidities Among Patients with Type 2 Diabetes Mellitus in the MENA Region: A Systematic Review.

AIM: The management of type 2 diabetes mellitus is affected by the presence of comorbidities. This meta-analysis aimed to determine how likely it is for individuals with type 2 diabetes in the Middle East and North Africa (MENA) to be living with additional chronic health conditions. METHODS: We searched for studies published from January 2010 to December 2020 in PubMed, Ovid MEDLINE®, Cochrane CENTRAL, Scopus, and Web of Science. Studies of adults with type 2 diabetes in the MENA region were included. We performed a random-effects meta-analysis of single proportions to calculate each comorbidity's overall prevalence/co-prevalence. RESULTS: Statistically significant co-prevalence was detected at p < 0.01 for angina (pooled proportion: 0.24, 95% CI: 0.06, 0.49), cerebrovascular accident (pooled proportion: 0.16, 95% CI: 0.08, 0.26), coronary artery disease (pooled proportion: 0.25, 95% CI: 0.16, 0.35), coronary heart disease (pooled proportion: 0.05, 95% CI: 0.01, 0.12), peripheral vascular disease (pooled proportion: 0.19, 95% CI: 0.13, 0.26), hypertension (pooled proportion: 0.56, 95% CI: 0.43, 0.69), renal impairment (pooled proportion: 0.19, 95% CI: 0.10, 0.29), in addition to hyperlipidemia and overweight/obesity. CONCLUSION: There is evidence of co-prevalence of several comorbidities in patients with type 2 diabetes. This highlights the importance of enhancing communication among healthcare professionals to develop the optimal management plan for each patient.

Bioaccumulation of natural radio-nuclides in aquatic, riparian and terrestrial animals along Suez-Azzafrana coastline, Egypt: insights from RESRAD-BIOTA.

PURPOSE: The protection of endogenous species is one of the important ecological issues in which all the World Environmental Agreements are searching for. The purpose of the study is to calculate the bioaccumulation impacts of some natural radio-nuclides as: Ra-226, K-40 and Th-232 in the selected Egyptian Endogenous Aquatic Red Sea Fusileer fish, Red sea Riparian Turtle and the Red sea Terrestrial Lizard by using RESAD BIOTA version 1.8. MATERIAL AND METHODS: Ten water and sediments samples were collected from different 10 sites, along the inshore of the Egyptian Suez bay beach till El-Zafarna coastal region, as these samples were taken from subsurface (20 cm-1 m). The radioactivity concentrations of some natural radioactivity radionuclides as; 226Ra, 232Th and 40K, which were measured, using gamma-ray spectrometer based on high-purity germanium (HPGe) detector of 40% relative efficiency. RESULTS: The results of the study showed that the radioactivity of some selected natural radionuclides in the selected 10 sites of Suez costal samples were arranged as: K-40 > Th-232 > Ra-226, as this was related to the characteristics of soil and rock precipitation in this zone besides the industrial activates along the selected coastal line zone of Suez bay till Al-Zafrana. On the other hand, it was observed that all the calculated Biota contamination Guide (BCG) values of the selected Egyptian endangerous species (Aquatic, Riparian and terrestrial) animals in the 10 selected sites samples were below the recommended (BCG), as the result, no radioactivity increment being detected at these selected sites. On the other hand, the BCG values of Ra-226 in both water and sediment samples for the selected Egyptian endangerous Aquatic Sea Fusileer Fish were higher than the recommended BCG values in water, while were comply with BGC values of the sediment, while in case of Egyptian endangerous Red Sea Turtle's BCG values were comply with the recommended BCGs in water while were higher than the recommended BCGs values of sediment. In case of the selected Egyptian endangerous terrestrial Lizard its BCG values of Ra-226 were higher than the recommended BCGs in both water and sediment media. While in case of Th-232 it was observed that the BCG values of selected endangerous Red Sea Fusileer Fish were higher than the recommended BCGs in both water and sediment and also the BCG values of selected endangerous Riparian Turtle were also higher than the recommended BCGs of both water and sediment, these results may increase the suitability of the selected Egyptian endangerous Marine, Riparian and Terrestrial species to the different radiological risks. The results showed also the decrement of the radioactivity values of the measured radionuclides in the internal tissue of the Egyptian selected endangerous Red Sea Lizard (Uromastyx aegyptia) than both the selected endangerous Red Sea Turtle and Red Sea Fish species, support the reptiles, which are cold blood animals, and is less affected by gamma radiation than other terrestrial animals.

Role of serum biomarkers in predicting management strategies for acute pulmonary embolism.

Background: Acute pulmonary embolism (APE) is a condition that can be fatal. The severity of the disease influences therapeutic decisions, and mortality varies significantly depending on the condition's severity. Identification of patients with a high mortality risk is crucial. Since inflammation, hemostatic, and coagulation abnormalities are linked to APE, serum biomarkers may be helpful for prognostication. Aim: To evaluate the significance of serum biomarkers in APE risk assessment and the suitability of these biomarkers for management and decision-making. Methods: This study involved 60 adult patients with APE who were divided according to risk categorization. It was conducted in Chest, Cardiology and Internal Medicine department, Zagazig University Hospitals from December 2022 to May 2023. Several hematological biomarkers and their significance in APE risk assessment were measured with a comparison with the latest risk stratification methods which include haemodynamic measures and right ventricular (RV) dysfunction echocardiographic markers. Results: Each risk group involved 20 patients (high, intermediate (10 were intermediate-high and 10 were intermediate-low) and low risk group). They were 34 females and 26 males with the mean ± SD of their age was 59.25 ± 13.06 years. Regarding hematological biomarkers, there were statistically significant differences as regards; lymphocytes, platelet to lymphocyte ratio (PLR), albumin, blood urea nitrogen (BUN), C-reactive protein (CRP) and D-dimer with highly statistically significant differences as regards; neutrophil to lymphocyte ratio (NLR), BUN to albumin (B/A) ratio, troponin I (TnI), and brain natriuretic peptide (BNP). TnI had the highest specificity and predictive value positive (PVP) and BNP had the highest sensitivity and predictive value negative (PVN) in predicting high risk groups. The Lymphocyte and NLR showed the lowest sensitivity and the albumin and B/A ratio had the lowest specificity. Regarding transthoracic echocardiography (TEE); there was a statistically significant increase regarding pulmonary artery systolic pressure (PASP) and a highly statistically significant increase regarding the right ventricle/left ventricle (RV/LV) ratio. There were statistically significant decreases regarding tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity of tricuspid annulus (S') among risk groups. Conclusion: APE prognosis can be judged accurately by simultaneously measuring a few biomarkers along with haemodynamic variables and echocardiographic parameters of RV dysfunction.

Brain Targeting of Citicoline Sodium via Hyaluronic Acid-Decorated Novel Nano-Transbilosomes for Mitigation of Alzheimer's Disease in a Rat Model: Formulation, Optimization, in vitro and in vivo Assessment.

Background: Alzheimer's disease (AD) is one of the furthermost advanced neurodegenerative disorders resulting in cognitive and behavioral impairment. Citicoline sodium (CIT) boosts the brain's secretion of acetylcholine, which aids in membrane regeneration and repair. However, it suffers from poor blood-brain barrier (BBB) permeation, which results in lower levels of CIT in the brain. Purpose: This study targeted to encapsulate CIT into novel nano-platform transbilosomes decorated with hyaluronic acid CIT-HA*TBLs to achieve enhanced drug delivery from the nose to the brain. Methods: A method of thin-film hydration was utilized to prepare different formulae of CIT-TBLs using the Box-Behnken design. The optimized formula was then hyuloranated via integration of HA to form the CIT-HA*TBLs formula. Furthermore, AD induction was performed by aluminum chloride (Alcl3), animals were allocated, and brain hippocampus tissue was isolated for ELISA and qRT-PCR analysis of malondialdehyde (MDA), nuclear factor kappa B (NF-kB), and microRNA-137 (miR-137) coupled with immunohistochemical amyloid-beta (Aß1-42) expression and histopathological finding. Results: The hyuloranated CIT-HA*TBLs formula, which contained the following ingredients: PL (300 mg), Sp 60 (43.97 mg), and SDC (20 mg). They produced spherical droplets at the nanoscale (178.94 ±12.4 nm), had a high entrapment efficiency with 74.92± 5.54%, had a sustained release profile of CIT with 81.27 ±3.8% release, and had ex vivo permeation of CIT with 512.43±19.58 µg/cm2. In vivo tests showed that CIT-HA*TBL thermogel dramatically reduces the hippocampus expression of miR-137 and (Aß1-42) expression, boosting cholinergic neurotransmission and decreasing MDA and NF-kB production. Furthermore, CIT-HA*TBLs thermogel mitigate histopathological damage in compared to the other groups. Conclusion: Succinctly, the innovative loading of CIT-HA*TBLs thermogel is a prospectively invaluable intranasal drug delivery system that can raise the efficacy of CIT in Alzheimer's management.

New Acaciin-Loaded Self-Assembled Nanofibers as MPro Inhibitors Against BCV as a Surrogate Model for SARS-CoV-2.

BACKGROUND: SARS-COVID-2 has recently been one of the most life-threatening problems which urgently needs new therapeutic antiviral agents, especially those of herbal origin. PURPOSE: The study aimed to load acaciin (ACA) into the new self-assembled nanofibers (NFs) followed by investigating their possible antiviral effect against bovine coronavirus (BCV) as a surrogate model for SARS-COV-2. METHODS: ACA was identified using 1H-NMR and DEPT-Q 13C-NMR spectroscopy, the molecular docking study was performed using Autodock 4 and a modification of the traditional solvent injection method was applied for the synthesis of the biodegradable NFs. Different characterization techniques were used to inspect the formation of the NFs, which is followed by antiviral investigation against BCV as well as MTT assay using MDBK cells. RESULTS: Core/shell NFs, ranging between 80-330 nm with tiny thorn-like branches, were formed which attained an enhanced encapsulation efficiency (97.5 ± 0.53%, P<0.05) and a dual controlled release (a burst release of 65% at 1 h and a sustained release up to >24 h). The antiviral investigation of the formed NFs revealed a significant inhibition of 98.88 ± 0.16% (P<0.05) with IC50 of 12.6 µM against BCV cells. CONCLUSION: The results introduced a new, time/cost-saving strategy for the synthesis of biodegradable NFs without the need for electric current or hazardous cross-linking agents. Moreover, it provided an innovative avenue for the discovery of drugs of herbal origin for the fight against SARS-CoV-2 infection.

A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Midkine: Utility as a Predictor of Early Diabetic Nephropathy in Children with Type 1 Diabetes Mellitus

Objective: This study aimed to assess the role of serum midkine (MK) as a biomarker for early detection of diabetic nephropathy in children with type 1 diabetes mellitus (T1DM) before microalbuminuria emerges. Methods: A total of 120 children with T1DM, comprising 60 microalbuminuric patients (Group 1), 60 normoalbuminuric patients (Group 2), and 60 healthy participants as a control group (Group 3) were included. Detailed medical history, clinical examination, and laboratory assessment of high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c percentage (HbA1c%), lipid profile, urinary albumin to creatinine ratio (ACR), serum MK and estimated glomerular filtration rate based on serum creatinine were performed in all participants. Results: Both Group 1 and Group 2 had significantly higher serum MK compared to controls (p<0.001). Additionally, significantly higher MK concentrations were present in Group 1 compared with Group 2 (p<0.001). Receiver operating characteristic curve analysis revealed that the MK concentration cutoff value of 1512 pg/mL was able to predict microalbuminuria with a sensitivity of 96% and specificity of 92%. Stepwise regression analysis revealed that HbA1c%, hs-CRP, and ACR were independently related to MK levels (p<0.001 for each). Conclusion: The results of this study suggest that serum MK is a useful, novel, practical marker for the evaluation of renal involvement in children with T1DM, especially in normoalbuminuric children.

Blood Pressure Variability and Atrial Fibrillation in Patients with Acute ST Segment Elevation Myocardial Infarction: The Relation with Left Atrial Electromechanical Delay - A 1-Year Follow-Up Study.

PURPOSE: To investigate the association between 24-h blood pressure variability (BPV) and atrial electromechanical delay (EMD) in patients with ST segment elevation myocardial infarction (STEMI) who developed new-onset atrial fibrillation (NOAF). MATERIALS AND METHODS: A total of 175 STEMI patients (age 56.6 ± 10.5 years) who underwent primary percutaneous coronary intervention were subjected to in-hospital 24-h ambulatory BP monitoring, comprehensive echocardiography, and assessment of atrial EMD. The parameters of BPV analyzed were: (a) 24-h standard deviation (SD), (b) the coefficient of variation, and (c) the average of the daytime and nighttime SDs weighted for the duration of the daytime and nighttime interval (SDdn ). RESULTS: Based on the median of BPV index (SDdn) = 9.5 mm Hg of all participants, patients were stratified into low and high variability groups (SDdn: 7.1 ± 1.5 vs.13.5 ± 2.9; p < 0.001). Of the 175 patients with STEMI, 29 (16.7%) patients developed NOAF; 26 (28.9%) were in the high variability group and 3.5% were in the low variability group (p < 0.001). Echocardiographic data showed that the left atrial volume index (p < 0.01) and E/e' ratio (p < 0.001) were significantly higher in patients with high BPV. Inter and intra-atrial EMD were significantly increased in the high variability group compared to the low variability group (p < 0.001). With multiple linear analysis, there was significant correlation between SDdn and intra-left atrial and inter-atrial EMD (p < 0.001 and <0.01, respectively). Cox regression analysis revealed that SDdn and intra-atrial EMD were independent predictors for NOAF in patients with STEMI (OR = 3.75 and 02.72, respectively; p < 0.001). ROC analysis revealed that SDdn ≥12.8 was the optimal cut-off value for predicting NOAF during follow-up. CONCLUSIONS: Short-term BPV was associated with NOAF during the 1-year follow-up in patients with STEMI. In addition, BPV was correlated significantly with atrial EMD. Herein, BPV was predicted to be an early predictor of NOAF in patients with STEMI.

Effect of chronic nicotine consumption on motor cortical excitability: A transcranial magnetic stimulation study.

OBJECTIVES: Transcranial magnetic stimulation (TMS) allows exploration of the mode of action of neuroactive substances in the human brain, and allows evaluation of neuronal networks, which might be involved in the action of nicotine. The aim of the present study was to explore motor cortex excitability in chronic smokers and non-smokers using TMS. METHODS: The study included 50 healthy subjects, of whom 25 were chronic smokers and 25 were age- and sex-matched non-smokers. Number of cigarettes per day and duration of smoking in years were documented. Serum level of cotinine was measured. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O) were performed to assess corticospinal excitability. The duration of the contralateral silent period (cSP) at different ranges of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. RESULTS: There were no significant differences either in RMT or AMT between groups. I/O curve showed a significant intensity×group interaction (P=0.008). This was attributable to significantly higher amplitudes of MEP among smokers than non-smokers especially at 130, 140 and 150% of RMT (P=0.0001 and P=0.03 and 0.02 respectively). The mean duration of the cSP at different intensities and iSP duration were similar in both groups. Nicotine level and smoking index were correlated respectively with rMT and iSP (P=0.03 and 0.01). CONCLUSION: The present results confirm previous findings by Grundey et al. (2013) that chronic nicotine consumption is characterized by hyperexcitability of corticospinal output. We speculate that it is a secondary adaptation to long-term nicotine use with high inter-individual variance.

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and in vivo evaluation in a rabbit ocular inflammatory model.

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6-12% and 15-25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice.

Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

Hepatitis B care pathway in Saudi Arabia: Current situation, gaps and actions.

Hepatitis B virus (HBV) infection remains a public health problem worldwide. In this review, we aim to assess the current situation of the HBV care pathway in the Kingdom of Saudi Arabia (KSA), identify gaps/barriers therein, and recommend initiatives to be taken to improve the management of such patients. Towards this end, a literature search was conducted in PubMed and free Internet searches. Interviews with individuals and focus group discussions were held with HBV experts in KSA. Although significant improvements have been made in the past 30 years in KSA in terms of the decline in prevalence (currently estimated to be around 1.3%), the morbidity and mortality related to the disease have not shown a parallel decline. This makes HBV an important public health concern. Furthermore, poor disease awareness, low diagnosis rates, and nonadherence to therapy amplify the disease burden. There are several mandated national screening structures present; however, established protocols for those who test positive and subsequent linkage-to-care are inadequate. In the absence of a virologic cure, a concerted effort should be made to provide safe and effective lifelong treatment. This review provides recommendations to reduce the HBV disease burden in the Saudi population.

Isolation and evaluation of cocktail phages for the control of multidrug-resistant Escherichia coli serotype O104: H4 and E. coli O157: H7 isolates causing diarrhea.

Escherichia coli serotype O157: H7 and E. coli O104: H4 are well known foodborne pathogens causing sever enteric illness. Using bacteriophages as biocontrol agents of some foodborne pathogens and multidrug-resistant (MDR) bacteria has a great attention nowadays. This study aims to test the effect of cocktail phages on the growth of some foodborne pathogens and MDR E. coli. Routine conventional PCR was used to confirm the identification of E. coli isolates. Double-layered culture technique was used to isolate phages from sewage water. Morphology of bacteriophage was described using transmission electron microscopy, and spot test was performed to determine host range of the phage cocktail. Phage cocktail of Siphoviridae and Podoviridae family infecting E. coli O157: H7, E. coli O104: H4 and untypeable E. coli (neither O157 nor O104) has been isolated from sewage water. Phage cocktail showed both lytic and lysogenic activity. Lytic activity was observed against E. coli O157: H7, E. coli O104: H4 isolates, Staphylococcus. aureus ATCC6538 and Pseudomonas aeruginosa ATCC 10145, while the lysogenic activity was observed against the untypeable strain. The tested phage cocktail showed a promising inhibitory action on E. coli O157: H7 and O104: H4, S. aureus ATCC6538 and P. aeruginosa ATCC 10145, suggesting the possibility of its use as a biocontrol tool or as natural food preservatives for many food products.

Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells.

5-Fluorouracil (5-FU), an antimetabolite drug, is extensively used in the treatment solid tumors. However, its severe side effects limit its clinical benefits. To enhance 5-FU anticancer efficacy and reduce its side effects it was loaded onto gold nanoparticles (GNPs) using two thiol containing ligands, thioglycolic acid (TGA) and glutathione (GSH). The GNPs were prepared at different 5-FU/ligand molar ratios and evaluated using different techniques. Anticancer efficacy of 5-FU/GSH-GNPs was studied using flow cytometry in cancerous tissue obtained from patients having colorectal cancer. The GNPs were spherical in shape and had a size of ∼9-17nm. Stability of the GNPs and drug release were studied as a function of salt concentration and solution pH. Maximum 5-FU loading was achieved at 5-FU/ligand molar ratio of 1:1 and 2:1 for TGA-GNPs and GSH-GNPs, respectively. GNPs coating with pluronic F127 improved their stability against salinity. 5-FU release from GNPs was slow and pH-dependent. 5-FU/GSH-GNPs induced apoptosis and stopped the cell cycle progression in colorectal cancer cells. They also had a 2-fold higher anticancer effect compared with free 5-FU. These results confirm the potential of GNPs to enhance 5-FU anticancer efficacy.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: Report on 17 cases from an endemic area.

BACKGROUND: After malaria, schistosomiasis is the second most prevalent tropical disease. The prevalence of oviposition in CNS of infected persons varies from 0.3 to 30%. The conus medullaris is a primary site of schistosomiasis, either granulomatous or acute necrotizing myelitis. OBJECTIVE: To report the clinical, radiological, and laboratory results of spinal cord schistosomiasis (SCS) and to design proper therapeutic regimens. MATERIALS AND METHODS: Seventeen patients (13 males and four females) with SCS were enrolled between 1994 and 2009 at Mansoura University Hospitals. Their median age at diagnosis was 19 years (13-30 years). Independent neurological, radiological, and laboratory assessments were performed for both groups, excluding pathological confirmation that was done earlier in eight patients (Group 1). In the group 2 (nine patients), indirect hemagglutination (IHA) test for bilharziasis in blood and cerebrospinal fluid (CSF) was performed. Higher positive titer in CSF than serum indicated SCS plus induction of antibilharzial and corticosteroid protocols for 12 months with a three-year follow-up. RESULTS: Rate of neurological symptoms of granulomatous intramedullary cord lesion was assessed independently in 16 cases and acute paraparesis in one case. All patients in group 2 had positive IHA against Schistosoma mansoni with median CSF and serum ranges 1/640 and 1/320, respectively. Seven patients (41.18%) had complete recovery, eight patients (47.06%) showed partial recovery, and no response was reported in two patients (11.76%) (P = 0.005). There was no recorded mortality in the current registry. CONCLUSIONS: Rapid diagnosis of SCS with early medical therapies for 12 months is a crucial tool to complete recovery.