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Rofida Albash,1 Abdulaziz Mohsen Al-mahallawi,2 Mariam Hassan,3 Ahmed Adel Alaa-Eldin4 1Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, Fayoum University, Elfayoum, EgyptCorrespondence: Abdulaziz Mohsen Al-mahallawiFaculty of Pharmacy, Cairo University, 11562, EgyptTel +201008226524Email Abdulaziz.mohsen@pharma.cu.edu.egObjective: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection.Methods: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles’ features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear’s fluid at different time intervals after ocular application in albino rabbits.Results: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02± 2.35%, particle size of 287.25± 9.55 nm, polydispersity index of 0.46± 0.01 and zeta potential of 36.15± 1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes.Conclusion: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.Keywords: fenticonazole nitrate, histopathological study, ocular drug delivery, microbiological study, terpesomes

Albash R, Al-mahallawi AM, Hassan M, Alaa-Eldin AA. Int J Nanomedicine. 2021;16:609–621. Page 612, In vivo Studies, Animals section, second to last line, the text “Approval no. MIC2672” should read “Approval no. MI 2671”. The authors apologize for this error.

Amira Mohsen Ghoneim,1 Mina Ibrahim Tadros,2 Ahmed Adel Alaa-Eldin3 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), New Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science & Technology (MUST), 6th of October City, EgyptCorrespondence: Mina Ibrahim TadrosDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo 11562, EgyptTel +002-01223620458Email mina.tadros@pharma.cu.edu.eg; mina_ebrahim@yahoo.comPurpose: The current work aimed to develop spray-dried silica xerogel nanoparticles (SXNs) as a gastroretentive carrier for the dual delivery of chlorambucil (CHL) and granisetron hydrochloride (GR). As a low-density system, it was proposed to float over gastric fluids; allowing for the retention of CHL in the acidic medium where it is more stable while ensuring the solubility of GR.Methods: Silica xerogels were developed by sol-gel process, using Tetraethyl orthosilicate (TEOS) water and acetic acid, followed by spray drying. SXNs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), CHL and GR release after 1 hr (P1h) and after 8 hrs (P8h). The best achieved system (SXN4) was evaluated for morphology, pore diameter, total porosity, bulk density, wetting time, floating characteristics. Furthermore, the pharmacokinetics of the loaded drugs were evaluated in rats; relative to an aqueous CHL suspension containing GR.Results: SXN4 system had the highest desirability (0.69); showing spherical nanoparticles (181.63 nm), negative zeta potential (−5.18 mV), promising EE% of 59.39% and 73.94% (for CHL and GR, respectively) and sustained CHL and GR release profiles characterized by low P1h (22.75% and 30.74%) and high P8h (60.36% and 99.33%), respectively. It had a mean pore diameter of 8.622 nm, a total porosity of 62.27%, a bulk density of 0.605 g/mL, a wetting time of 292 sec, zero lag time and a floating duration of at least 8 h.Conclusion: The prolongation in the mean residence time (MRT(0-∞)) and the promotion of the relative oral bioavailabilities of both drugs could unravel the potential of this system for the management of chemotherapy-induced nausea and vomiting.Keywords: chlorambucil, granisetron hydrochloride, silica xerogel nanoparticles, low density, gastroretentive

Wheat leaf rust, caused by Puccinia triticina , poses a growing threat to global wheat production, necessitating alternative strategies for effective disease management. This study investigated the potential of gamma-aminobutyric acid (GABA) to enhance resistance to leaf rust in two wheat cultivars: the susceptible Morocco and moderately resistant Sakha 94 cultivar. Our findings revealed that GABA significantly improved resistance in both cultivars to P. triticina , particularly in Morocco, by mitigating disease severity and reducing pustule density and size while extending both incubation and latent periods. This study assessed the effectiveness of two GABA application methods: plants received 1 mM GABA treatment, as a foliar spray, twenty-four hours prior to infection (pre-GABA), and plants received 1 mM GABA treatment both 24 h before and after infection (pre-/post-GABA), with the latter yielding significantly better results in reducing infection severity and improving plant resilience. Additionally, GABA application influenced stomatal behavior, promoting closure that may enhance resilience against leaf rust. GABA application on plants also modulated the production of reactive oxygen species (ROS). This led to a stronger oxidative burst in both susceptible and moderately resistant cultivars. GABA increased O 2 ●- levels in guard cells and surrounding stomata, enhancing stomatal closure and the hypersensitive response. GABA enhanced the accumulation of soluble phenols and increased the activity of key antioxidant enzymes, catalase (CAT) and peroxidase (POX), which are vital for managing oxidative stress. To the best of our knowledge, this investigation represents the first report into the impact of GABA on wheat leaf rust disease.

Background: Blackberries have garnered attention recently due to their high concentration of bioactive components like anthocyanin and their health advantages. Therefore, this study aims to determine the bioactive profile, antioxidant and antibacterial effects of blackberry extracts (BBEs). Then, evaluate the protective effect of BBEs (20%, 30% and 40%) in a rat model of 2 mL of 4-8 × 10 6 Escherichia coli ATTC 25922 strain colony-forming unit mL -1 oral infection on the seventh day of the experiment., Results: Rats were divided into six groups: G1: control (C-: normal or negative group), G2: (C+: infected or positive group), G3: infected-treated group by 20% BBE, G4: infected-treated group by 30% BBE, G5: infected-treated group by 40% of BBE and G6: infected-treated group by Gentamicin. The results showed that BBE had a high content of total phenolic compounds, flavonoid, anthocyanin contents, and different vitamins (vitamins A, E and C), reaching 450, 186, 58.83 mg 100 g -1 , 2.68, 2.14 and 107.46 mg 100g -1 fresh weight, respectively, which showed great antioxidant and antibacterial effects. Therefore, liver enzymes, kidney function and lipid profiles were significantly higher in the infected group than in the control or infected-treated groups. Furthermore, BBE ameliorated inflammation of the intestine and hepatocyte damage compared to the infected control group., Conclusion: These results suggest that consistent intake of BBE might alleviate hepatic inflammation and the gut microbiota in ways that could significantly impact human health. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Phytochemicals from waste materials generated by agricultural and industrial processes have become globally significant due to their accessibility and potential effectiveness with few side effects. These compounds have essential implications in both medicine and the economy. Therefore, a quantitative analysis of the phytochemical profile, sugar types, and water-soluble vitamins of dried Corchorus olitorius L."DJMS" extract (dried Jew's mallow stem) was carried out with HPLC. In addition, the chemical composition, TPC, chlorophyll a and b, beta-carotene, and antioxidant effect using DPPH were investigated. Furthermore, the anticancer activity of the DJMS was evaluated by SRB assay using Huh-7 and MDA-MB-231 cell lines. In the quantitative study, DJMS extract showed a high antioxidant potential (67%) due to its content of bioactive compounds such as TPC (276.37 mg 100 g -1 ) and chlorophyll a and b (20.31, 12.02 mg 100 g -1 , respectively), as well as some vitamins and minerals such as B-complex (B12; 146.8 mg 100 g -1 and vitamin C 6.49 mg 100 g -1 ) and selenium (<0.2 μg kg -1 ). Moreover, the main sugar types found were sucrose and stachyose, which recorded 9.23 and 6.25 mg 100 g -1 , respectively. Identifying phenolic and flavonoids showed that the major components were ellagic acid (4905.26 μg kg -1 ), ferulic acid (3628.29 μg kg -1 ), chlorogenic acid (3757.08 μg kg -1 ), luteolin-7- O -glucoside (4314.48 μg kg -1 ), naringin (4296.94 μg kg -1 ) and apigenin-6-rhamnose-8 glucoside (3078.87 μg kg -1 ). The dried stem extract showed significant MDA-MB-231 inhibition activity and reached 80% at a concentration of 1000 µg/mL of DJMS extract, related to the content of phytochemical components such as isoflavones like genistein (34.96 μg kg -1 ), which had a tremendous anticancer effect. Hence, the stem of Jew's mallow (which is edible and characterized by its viability and low production cost) possesses the capacity to serve as a pharmaceutical agent for combating cancer owing to its abundance of bioactive components.

The combination of herbal drugs with a topical antibacterial for managing a chronic disease like acne vulgaris has emerged lately to settle side effects and bacterial multidrug resistance. Mixed micelles (MMs) incorporated into nanogel were explored for hybrid delivery of curcumin (Cur) and fusidic acid (FA) combination presenting a multi-strategic treatment. Curcumin-fusidic acid-loaded mixed micelles (Cur-FA-MMs) were assessed for size, surface charge, compatibility, in vitro release, and encapsulation. The selected formula was further loaded into nanogel and investigated for viscosity, ex vivo permeation, and in vivo potential. Cur-FA-MMs exhibited uniform nanosized spherical morphology, and negative surface charge affording high encapsulation for both drugs with a biphasic in vitro release over a period of 48h and good colloidal stability. The attained Cur-FA-MM-loaded nanogel had optimum viscosity with remarkable permeation coefficient values nearly 2-fold that related to plain nanogel. The pharmacodynamic effect of Cur on FA was pronounced by the significant improvement of the skin's degree of inflammation, epidermal hypertrophy, and congestion in animals treated with Cur-FA-MM-loaded nanogel. In conclusion, micellar nanogel could enable the progressive effect of Cur (an antioxidant with reported antibiotic activity) on FA (antibiotic) and decrease the risk of emerging antibiotic resistance by enhancing the solubility and permeation of Cur., (© 2023. The Author(s).)

Recently, the use of nanofertilizers has received a great deal of attention in managing plants under biotic and abiotic stresses. However, studies that elucidate the role of silicon dioxide nanoparticles (SiO 2 NPs) in regulating maize tolerance to drought stress are still at early stages of development. In this study, plants that were treated with SiO 2 NPs (0.25 g/L as foliar spray) displayed considerable improvement in the growth indices, despite being subjected to drought stress. In addition, the action of SiO 2 NPs led to a considerable rise in the levels of chlorophylls, proline, cell membrane integrity, leaf water content, and antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (G-POX)). In contrast, an inverse trend was seen in the oxidative injury, the total amount of soluble sugars, and the activity of ascorbate peroxidase (APX). At the same time, carotenoids were unaffected in SiO 2 NPs-treated and non-treated plants under drought stress. The results of the molecular investigation that was conducted using qRT-PCR showed that the relative expression of the D2 protein of photosystem II ( PsbD ) was elevated in SiO 2 NPs-treated plants in response to drought stress, while the expression of the osmotic-like protein ( OSM-34 ) and aquaporin ( AQPs ) was downregulated in SiO 2 NPs-treated plants in response to drought stress. This research could pave the way for further investigations into how SiO 2 NPs boost plant resistance to drought stress.

An efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5-a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5-a]pyrimidines) were prepared in 80-90 % yields by reacting the respective bis(enaminones) and 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine at reflux temperature for 5-7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane- and butane-linked bis(pyrazolo[1,5-a]pyrimidines), which are attached to 3-(4-methyl- or 4-methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 μM, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC 50 values up to 7.2 μM., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi's diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm 2 ) than LNCs (12.7 ± 1.52 µg/cm 2 ). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.

We provide a systematic review of published cases of optic neuropathy following COVID-19 vaccination. We used Ovid MEDLINE, PubMed, and Google Scholar. Search terms included: “COVID-19 vaccination”, “optic neuropathy”, “optic neuritis”, and “ischemic optic neuropathy”. The titles and abstracts were screened, then the full texts were reviewed. Sixty eyes from forty-five patients (28 females) were included. Eighteen eyes from fourteen patients (31.1%) were diagnosed with anterior ischemic optic neuropathy (AION), while 34 eyes from 26 patients (57.8%) were diagnosed with optic neuritis (ON). Other conditions included autoimmune optic neuropathy and Leber hereditary optic neuropathy. Fifteen patients (33.3%) had bilateral involvement. The mean age of all patients was 47.4 ± 17.1 years. The mean age of AION patients was 62.9 ± 12.2 years and of ON patients was 39.7 ± 12.8 years (p < 0.001). The mean time from vaccination to ophthalmic symptoms was 9.6 ± 8.7 days. The mean presenting visual acuity (VA) was logMAR 0.990 ± 0.924. For 41 eyes with available follow-up, the mean presenting VA was logMAR 0.842 ± 0.885, which improved to logMAR 0.523 ± 0.860 at final follow-up (p < 0.001). COVID-19 vaccination may be associated with different forms of optic neuropathy. Patients diagnosed with ON were more likely to be younger and to experience visual improvement. More studies are needed to further characterize optic neuropathies associated with COVID-19 vaccination.

In this investigation, we focused on ceramide IIIB, a skin component whose depletion tends to augment multiple skin disorders and fungal infections. Ceramide IIIB was included into PEGylated surfactant-based vesicular phospholipid system to formulate 'PEGylated cerosomes' (PCs) loaded with fenticonazole nitrate (FTN). FTN is a potent antifungal agent adopted in the treatment of mixed mycotic and bacterial infections. The ceramide content of the vesicles may provide protective and regenerative skin activity whereas Brij ® ; the PEGylated surfactant, can enhance drug deposition and skin hydration. Both components are expected to augment the topical effect of FTN. PCs were prepared by thin-film hydration technique. A 2 3 full-factorial design was applied to study the effect of ceramide amount (X 1 ), Brij type (X 2 ) and Brij amount (X 3 ) on the physicochemical properties of the formulated PCs namely; entrapment efficiency (EE%;Y 1 ), particle size (PS;Y 2 ), polydispersity index (PDI;Y 3 ) and zeta potential (ZP;Y 4 ). The optimal formula was selected for further in-vivo dermatokinetic and histopathological study. The optimal FTN-loaded PC (PC6) showed nanosized cerosomes (551.60 nm) with high EE% (83.00%w/w), and an acceptable ZP value of 20.90 mV. Transmission electron micrographs of the optimal formula illustrated intertwined tubulation form deviated from the conventional spherical vesicles. Finally, the dermatokinetic study of PC6 showed higher drug concentration and localization of FTN in skin layers when compared with FTN suspension and the histopathological study confirmed its safety for topical application. The overall findings of our study verified the effectiveness of utilizing PEGylated cerosomes to augment the activity of FTN as a topical antifungal agent.

Background: Polytrauma patients are at a higher risk of delayed gastric emptying. To assess the gastric volume, a reliable diagnostic tool is needed to prevent the occurrence of aspiration pneumonia, which remains a serious complication associated with anesthesia. Gastric antral ultrasound can provide reliable information about the size of the gastric antrum in traumatized patients undergoing emergency surgery., Methods: A prospective observational study of 45 polytrauma patients undergoing emergency surgery under general anesthesia was carried out. Prior to induction of anesthesia in the emergency department, gastric ultrasound was performed for qualitative and quantitative assessment of the gastric antrum in a supine position and right lateral decubitus (RLD) position. This was followed by routine placement of the nasogastric tube to aspirate and calculate the volume of the stomach contents., Results: Of the 45 polytrauma patients, the risk assessment of aspiration and the anesthesia technique changed in 14 patients (31.1%) after the gastric ultrasound examination. A very good relationship existed between the expected stomach volume at the RLD position and the suction volume in the nasogastric tube. In all cases, no aspirations were documented., Conclusion: Ultrasound examination of the stomach in polytrauma patients allows assessing the size and type of stomach contents. The data obtained can influence the choice of anesthesia technique and reduce the risk of aspiration pneumonia., Trial Registration: This trial was registered at ClinicalTrials.gov . registry number: NCT04083677 on September 6, 2019.

Fenticonazole nitrate (FTN) is a potent antifungal drug adopted in the treatment of vaginal candidiasis. It has inadequate aqueous solubility hence, novel ultra-deformable liposomes 'Terpesomes' (TPs) were developed that might prevail over FTN poor solubility besides TPs might abstain the obstacles of mucus invasion. TPs were assembled by thin-film hydration then optimized by Box Behnken design utilizing terpenes ratio (X 1 ), sodium deoxycholate amount (X 2 ), and ethanol concentration (X 3 ) as independent variable, whereas their impact was inspected for entrapment efficiency (Y 1 ), particle size (Y 2 ), and polydispersity index (Y 3 ). Design Expert ® was bestowed to select the optimal TP for more studies. The optimal TP had entrapment efficiency of 62.18 ± 1.39%, particle size of 310.00 ± 8.16 nm, polydispersity index of 0.20 ± 0.10, and zeta potential of -10.19 ± 0.2.00 mV. Elasticity results were greater in the optimal TP related to classical bilosomes. Further, ex vivo permeation illustrated tremendous permeability from the optimal TP correlated to classical bilosomes, and FTN suspension. Besides, in vivo assessment displayed significant inhibition effect in rats from FTN-TPs gel compared to FTN gel. The antifungal potency with undermost histopathological variation was detected in rats treated with FTN-TPs gel. Overall, the acquired findings verified the potency of utilizing FTN-TPs gel for treatment of vaginal candidiasis.

Aim: To determine age norms in the first three years of life for grating visual acuity and contrast sensitivity obtained with Lea grating test and Hiding Heidi low contrast face test., Methods: Lea grating test was used to estimate binocular grating acuity and Hiding Heidi low contrast face test was used to estimate contrast sensitivity in 600 healthy infants and children. Age ranged from 3 to 36mo subdivided into 12 groups subjected for full ophthalmologic and pediatric examinations., Results: The grating acuity developed along the first three years of life. It ranged from 1.88±0.32 c/d at 3mo to 30.95±0.77 c/d at 36mo. The most rapid development was during the first 12mo and the slowest development was from 30 to 36mo. The contrast sensitivity showed rapid development in the first two years of life. Its mean value ranged from 4.23±1.17 at 3mo to 78.26±8.21 at 24mo. It was constant at the highest score (80) thereafter., Conclusion: Age norms for grating acuity along with contrast sensitivity offer a more comprehensive measure of spatial vision and should be incorporated in clinical practice for better visual assessment in preverbal and nonverbal children.

Plasmonic photothermal therapy (PPTT) was introduced as a promising treatment of cancer. This work was conducted to evaluate the cytotoxic effect of intratumoral (IT) injection of 75μg gold nanorods (GNRs)/kg of body weight followed by direct exposure to 2 w/cm 2 near infra-red laser light for 10min on ablation of mammary tumor in 10 dogs and 6 cats. Complete blood count (CBC), liver and kidney function were checked before the start of treatment and one month after injection of GNRs. Results showed that 62.5% (10/16), 25% (4/16) and 12.5% (2/16) of treated animals showed complete remission, partial remission and no response, respectively. Tumor was relapsed in 4 cases of initially responding animals (25%). Overall survival rate was extended to 315.5±20.5days. GNRs have no toxic effect on blood profile, liver or kidney functions. In conclusion, GNRs can be safely used for treatment of mammary tumors in dogs and cats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Etodolac is a non-steroidal anti-inflammatory drug having an elimination half-life of 7 h; oral doses are given every 6-8 h. The aim of current work was the development of controlled-release etodolac lipid matrix tablets. The variables influencing design of these tablets (L1-L28) by the hot fusion method were investigated including; (1) lipid type (stearic acid, cetyl alcohol, cetostearyl alcohol, Imwitor® 900K, Precirol® ATO 5 and Compritol® ATO 888), (2) drug/lipid ratio (1:0.25 and 1:0.50, respectively), (3) filler type (lactose, Avicel® PH101 and their physical mixtures; 2:1, 1:1, and 1:2, respectively), (4) surfactant's HLB (5 and 11), and (5) drug/surfactant ratio (20:1 and 10:1, respectively). Statistical analysis and kinetic modeling of drug release data were evaluated. The inner matrix of the tablet was visualized via scanning electron microscopy (SEM). An inverse correlation was observed between the drug/lipid ratio and the drug release rate. Precirol®- and Compritol®-containing formulae showed more retarded drug release rates. Lactose/Avicel® physical mixture (1:1) was considered as a filler of choice where it minimized the burst effect observed with Avicel®-free formulae. The higher surfactant's HLB, the higher drug release rate. The similarity factor (f(2)) between the drug release profiles revealed similarity within the investigated drug/surfactant ratios. Sucrose stearate D1805®-based matrix (L21) succeeded in delivering more than 90% of etodolac over 12 h, following anomalous (non-Fickian) controlled-release kinetics. SEM micrographs confirmed pore formation, within the latter matrix, upon contact with dissolution medium.

The aim of the current work was the design and evaluation of etodolac controlled porosity osmotic pump (CPOP) tablets exhibiting zero-order release kinetics. Variables influencing the design of (1) core tablets viz., (a) osmogent type (sodium chloride, potassium chloride, mannitol, and fructose) and (b) drug/osmogent ratio (1:0.25, 1:0.50, and 1:0.75), and (2) CPOP tablets viz., (a) coating solution composition, (b) weight gain percentage (1-5%, w/w), and (c) pore former concentration (5%, 10%, and 20%, v/v), were investigated. Statistical analysis and kinetic modeling of drug release data were estimated. Fructose-containing core tablets showed significantly (P < 0.05) more retarded drug release rates. An inverse correlation was observed between drug/fructose ratio and drug release rate. Coating of the optimum core tablets (F4) with a mixture of cellulose acetate solution (3%, w/v), diethyl phthalate, and polyethylene glycol 400 (85:10:5, v/v, respectively) till a 4% w/w weight gain enabled zero-order sustained drug delivery over 24 h. Scanning electron microscopy micrographs of coating membrane confirmed pore formation upon contact with dissolution medium. When compared to the commercial immediate-release Napilac® capsules, the optimum CPOP tablets (F4-34) provided enhanced bioavailability and extended duration of effective etodolac plasma concentration with minimum expected potential for side effects in healthy volunteers.

The potential protective effects of taurine and quercetin against gentamycin (GM)/diclofenac (DC) combined nephrotoxicity were investigated in rats. The results showed that administration of DC alone at an oral dose of 5 mg/kg b.wt/day for 28 days had no significant effect on the measured parameters, except for marked increase in urinary uronic acid excretion. Administration of GM alone at a dose of 100 mg/kg b.wt/day i.p. for 8 days resulted in obvious nephrotoxicity. Combined GM-DC treatment led to the most pronounced nephrotoxicity, as indicated by greater elevations in serum urea, creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG), together with severe depression of renal cortical Na , K+-ATPase, compared to GM-treated group. Moreover, only combined treatment resulted in significant decrease in urinary potassium and renal cortical glutathione peroxidase (GSHPx), together with an increase in renal cortical lipid peroxidation products (LPOs). Co-administration of taurine or quercetin normalized creatinine clearance and ameliorated the elevations in urinary proteins, uronic acids, NAG and renal cortical LPOs in GM/DC treated rats. The study justifies the use of taurine and quercetin as renoprotective agents against the nephrotoxicity caused by GM/DC therapy.

The major goal of this study was to examine the ability of several antioxidants namely, vitamin E, beta-carotene and N-acetylcysteine, to protect the brain from oxidative stress induced by lipopolysaccharide (LPS, endotoxin). LPS, a component of the bacterial wall of gram-negative bacteria, has been recognized as one of the most potent bacterial products in the induction of host inflammatory responses and tissue injury and was used in this study to mimic infections. LPS injection resulted in a significant increase in the stress indices, plasma corticosterone and glucose concentration, a significant alteration of the brain oxidative status observed as elevation of the level of malondialdehyde (MDA, index of lipid peroxidation) and reduction of reduced glutathione (GSH), and a disturbance in the brain energy metabolism presented as a reduction in the ATP/ADP ratio and an increase in the mitochondrial/cytosolic hexokinase ratio. However, the activities of brain superoxide dismutase and Na+, K+-ATPase and contents of cholesterol and phospholipids were not altered. Administration of the aforementioned antioxidants prior to LPS injection ameliorated the oxidative stress by reducing levels of MDA, restoring GSH content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose. In conclusion, this study showed the increased free radical generation during infections and LPS-induced stress. It also suggests that brain oxidative status and energy is disturbed.

The effect of vitamin E (VE) or diazepam (DZ) pretreatment on some carbohydrate metabolic aspects in the brains of stressed rats was studied. DZ and VE were given i.p. at doses of 5 mg/kg body wt for 6 days prior to subjecting the animals to single swimming stress (SSS). Pretreatment of the rats with DZ or VE diminished the stress-induced increases in plasma corticosterone and glucose levels and reversed the decrease due to stress on brain ATP, glucose, glycogen and pyruvate contents. The increase in brain ADP and lactate was brought back to levels which approached the pre-stressed values. Moreover, DZ and VE pretreatments helped in attenuating the stress-induced alteration in brain mitochondrial and cytosolic hexokinase as well as sodium, potassium adenosine triphosphatase (Na+,K(+)-ATPase) activities. The change in these metabolic parameters produced by VE pre-treatment was less than that exhibited by DZ. The effects of VE were explained in light of its antioxidant property in preventing the free radical production and lipid peroxide formation which are important factors in the pathogenesis of stress.

Two phases of arthritis, acute phase (four days after adjuvant inoculation) and chronic phase (21 or 29 days after adjuvant inoculation) were studied in male rats. The effect of administration of vitamin C in a daily oral dose of 50 mg/kg body wt for four and 21 days starting on the day of adjuvant inoculation and for 7 days starting 21 days after adjuvant inoculation against these phases of arthritis was demonstrated. Results showed that prolonged administration of vitamin C (21 days) increased the lowered serum sulphydryl (SH-groups) to prearthritic values while it decreased the elevated level of blood glutathione (GSH) of arthritic rats. However, neither (four-day) nor seven-day treatment with vitamin C exerted any significant changes in these parameters. The results showed also a slight significant increase in the level of erythrocyte superoxide dismutase activity (SOD) [1.15.1.1] upon seven-day treatment with vitamin C. Meanwhile, four-, 21- or seven-day treatment with vitamin C produced no significant change in the elevated levels of serum ceruloplasmin (Cp) and alpha 2-macroglobulin (alpha 2-M) of arthritic rats. However, 21-day and 7-day administration of vitamin C has improved the lowered A/G ratio in these animals. The improvement in these parameters after prolonged administration of vitamin C was explained in the light of the antioxidant property of this vitamin and suggests a beneficial role for it in the treatment of arthritis.

Two phases of adjuvant arthritis, acute phase (4 days after adjuvant inoculation) and chronic phase (21 and 29 days after adjuvant inoculation) were studied in male rats. The effect of administration of vitamin E in a daily oral dose of 147 mg/kg body wt. for one week against these phases of arthritis were demonstrated before and after adjuvant inoculation. Results showed that administration of the vitamin before and after adjuvant inoculation increased the lowered serum-SH group in arthritic rats so that their level was restored to pre-arthritic values especially in chronic treated group. Meanwhile, these treatments produced no change in the increased level of blood GSH or erythrocyte SOD activity of arthritic rats. The results showed also that administration of vitamin E before adjuvant inoculation increased significantly the level of alpha 2-M while it did not alter the increased serum Cp in acute phase. However, administration of the vitamin after adjuvant inoculation failed to exert any change in these parameters. In the meantime, these treatments tended to increase the lowered A/G of arthritic rats in different phases especially in acute one. These observations suggest that antioxidants such as vitamin E may be beneficial for arthritis.

Factors of the contact activation complex--FXII, FXI, high-molecular-weight kininogen (HMWK) and prekallikrein (PK) as well as D-dimer were measured in 68 schistosomal patients with and without co-existing chronic hepatitis B virus infection (HBV). Fifty-four cases had mixed hepatosplenic schistosomiasis and HBV infection whereas 14 were suffering from hepatosplenic (HS) schistosomiasis alone. A group of twelve age-matched, healthy individuals served as controls. All coagulation parameters were significantly reduced in both disease groups compared to the healthy controls. The decreased activity of the contact proteins could be attributed to decreased hepatic synthesis, consumption due to disseminated intravascular coagulation (DIC) and to the effect of endotoxins. In mixed schistosomiasis and HBV infections, however, the levels of the contact activation factors were not significantly different from those obtained in patients with HS alone. This apparently paradoxical finding does not, however, exclude a role for co-existing HBV infection in speeding up complications in hepatosplenic schistosomiasis.

Gallstones are usually silent. Less commonly, patients with cholelithiasis develop symptoms and/or complications; biliary fistula occurs in 3% to 5% of the cases. When a large stone is passed and occludes the duodenum, gastric outlet obstruction (the Bouveret syndrome) may result. In reported cases, the stones are usually larger than 2.5 cm. The usual presenting symptoms are those of bowel obstruction: abdominal pain, nausea, and vomiting. Less commonly, the patients experience melena and, rarely, hematemesis. We describe a patient who had the largest stone reported to cause hematemesis rather than bowel obstruction and to be diagnosed endoscopically. The 5 X 4 X 3 cm stone was extracted surgically. Endoscopic diagnosis and extraction of stones up to 3 cm in size has been reported, avoiding the need for surgery.

Plasma total lipid phosphorus, individual phospholipid fractions, free and esterified cholesterol, triglycerides and nonesterified fatty acids were fractionated by thin-layer chromatography and determined in bilharzial hepatic fibrosis patients (57 cases) and normal controls (25 cases). Significant diminutions were encountered in the total and the individual phospholipids, especially the lysolecithin fraction in the 3 groups of patients studied. Total and esterified cholesterol and triglycerides showed significant decreases, especially in moderate and late cases. NEFA, on the other hand, did not reveal any change from normal level in either moderate, late or mixed cases. Such findings may be attributed to malabsorption, lack of energy, insufficiency of required precursors as well as impaired synthesis by the liver.

Cystadenocarcinoma is a rare tumor of the intrahepatic and a very rare tumor of the extrahepatic biliary system. In the reported cases, abdominal swelling is the most common presenting symptom, followed by right upper quadrant mass. Melena was the initial presenting symptom in the present case. Bleeding into the second part of the duodenum was observed only during the third diagnostic esophagogastroduodenoscopy. Hemobilia was suspected because of abnormal liver enzymes and a mass in the left lobe of the liver on computerized tomography. At laparotomy, we suspected that the mass was a hemangioma. Cystadenocarcinoma diagnosis was made only by histopathological examination.