Enhanced Antibacterial Activity of Clindamycin Using Molecularly Imprinted Polymer Nanoparticles Loaded with Polyurethane Nanofibrous Scaffolds for the Treatment of Acne Vulgaris.

Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and azoisobutyronitrile (AIBN) as functional monomers, crosslinkers, and free-radical initiators, respectively. MIP characterization utilized Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) before being incorporated into polyurethane nanofibers through electrospinning. Further analysis involved FTIR, scanning electron microscopy (SEM), in vitro release studies, and an ex vivo study. Clin-MIP showed strong antibacterial activity against S. aureus, with inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 6.25 µg/mL, respectively. It significantly dropped the bacterial count from 1 × 108 to 39 × 101 CFU/mL in vivo and has bactericidal activity within 180 min of incubation in vitro. The pharmacodynamic and histopathology studies revealed a significant decrease in infected animal skin inflammation, epidermal hypertrophy, and congestion upon treatment with Clin-MIP polyurethane nanofiber and reduced pro-inflammatory cytokines (NLRP3, TNF-α, IL-1ß, and IL-6) conducive to acne healing. Consequently, the recently created Clin-MIP polyurethane nanofibrous scaffold. This innovative approach offers insight into creating materials with several uses for treating infectious wounds caused by acne.

Deciphering temporal perspectives: A key to happiness and optimism for healthy aging in nursing practices".

BACKGROUND: With the global population of older individuals increasing rapidly, it is important to understand the factors contributing to their well-being. The study aimed to investigate the relationship between older adults' time perspective and their experiences of happiness and optimism. METHODS: A cross-sectional survey was conducted on a substantial sample size of 300 older adults from January to March 2023. The study utilized reliable and validated measures, including the Short Version of the Zimbardo Time Perspective Inventory and the Arabic Scales of Happiness, Optimism, and Pessimism. RESULTS: The study found that older adults with a negative view of the past (PN perspective) had lower levels of happiness (r=-0.374, p<0.01), while those with a hedonistic view of the present (PH perspective) had higher levels of happiness (r=0.266, p<0.01). Additionally, a fatalistic view of the present (PF perspective) was associated with lower levels of happiness (r=-0.178, p<0.05) and optimism (r=-0.168, p<0.05). Negative views of the future (FN perspective) were correlated with lower happiness levels (r=-0.546, p<0.01), while positive views of the future (FP perspective) were associated with higher levels of optimism (r=0.432, p<0.01). CONCLUSION: Older adults with a balanced time perspective, marked by positive and negative views of the past and an optimistic outlook on the future, reported moderate happiness and optimism. Older adults with a negative view of the past and a fatalistic view of the present tend to have lower levels of happiness and optimism. On the other hand, those who have a hedonistic view of the present and a positive view of the future tend to have higher levels of happiness and optimism. Older adults with a pessimistic outlook toward past experiences or the future may require additional emotional support and targeted interventions to foster a more positive mindset.

Pinocembrin's protective effect against acute pancreatitis in a rat model: The correlation between TLR4/NF-κB/NLRP3 and miR-34a-5p/SIRT1/Nrf2/HO-1 pathways.

BACKGROUND: Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury. METHODS: Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model. RESULTS: Pinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio. CONCLUSIONS: Pinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.

Wound Healing Efficacy of Cucurbitaceae Seed Oils in Rats: Comprehensive Phytochemical, Pharmacological, and Histological Studies Tackling AGE/RAGE and Nrf2/Ho-1 Cue.

The Cucurbitaceae family includes several edible species that are consumed globally as fruits and vegetables. These species produce high volumes of seeds that are often discarded as waste. In this study, we investigate the chemical composition and biological activity of three seed oils from Cucurbitaceae plants, namely, cantaloupe, honeydew, and zucchini, in comparison to the widely used pumpkin seed oil for their ability to enhance and accelerate wound healing in rats. Our results showed that honeydew seed oil (HSO) was effective in accelerating wound closure and enhancing tissue repair, as indicated by macroscopic, histological, and biochemical analyses, as compared with pumpkin seed oil (PSO). This effect was mediated by down-regulation of the advanced glycation end products (AGE) and its receptor (RAGE) cue, activating the cytoprotective enzymes nuclear factor erythroid 2 (Nrf2) and heme oxygenase-1 (HO-1), suppressing the inflammatory mediators tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), and nod-like receptor protein 3 (NLRP3), and reducing the levels of the skin integral signaling protein connexin (CX)-43. Furthermore, immunohistochemical staining for epidermal growth factor (EGF) showed the lowest expression in the skin after treatment with HSO, indicating a well-organized and complete healing process. Other seed oils from cantaloupe and zucchini exhibited favorable activity when compared with untreated rats; however, their efficacy was comparatively lower than that of PSO and HSO. Gas chromatographic analysis of the derivatized oils warranted the superior activity of HSO to its high nutraceutical content of linoleic acid, which represented 65.9% of the fatty acid content. This study's findings validate the use of honeydew seeds as a wound-healing fixed oil and encourage further investigation into the potential of Cucurbitaceae seeds as sources of medicinally valuable plant oils.

Perlite incorporation for sedimentation reduction and improved properties of high-density geopolymer cement for oil well cementing.

Portland cement (PC) is known for its environmental and technical concerns and massive energy consumption during manufacturing. Geopolymer cement is a promising technology to totally replace the use of PC in the oil and gas industry. Although geopolymers are widely used in the construction industry, it is yet to see a full-scale application in the petroleum industry. High-density geopolymer cement development is essential to substitute heavy-weight Portland cement slurries for high pressure well cementing applications. Sedimentation issue is associated with high-density cement slurries which use high specific gravity solids such as weighting materials. This problem causes heterogeneity and density variation along the cemented sections. The main target of this work is to evaluate the use of perlite powder to address the sedimentation issue in the heavy weight geopolymer systems. Hematite-based Class F fly ash (FFA) geopolymer cement slurries with perlite concentrations of 0, 1.5, and 3% by weight of binder (BWOB) were prepared. The sedimentation problem was investigated using three techniques: API method, nuclear magnetic resonance (NMR), and computed tomography (CT) scan. The perlite effects on different geopolymer properties such as unconfined compressive strength (UCS), porosity, elastic and rheological properties were assessed. The results proved that perlite incorporation in high-density hematite-based FFA geopolymer significantly reduced sedimentation issue by increasing yield point and gel strength. NMR and CT scan showed that perlite decreases porosity and density variation across the geopolymer samples. The UCS increased with increasing perlite percentage from 0 to 3%. The measured Young's moduli (YM) and Poisson's ratios (PR) showed that the developed perlite based geopolymer systems are considered more flexible than Class G cement systems. It was found that the optimum perlite concentration is 3% BWOB for tackling sedimentation and developing a slurry with acceptable mixability and rheological properties.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Using shock generator for the fuel mixing of the extruded single 4-lobe nozzle at supersonic combustion chamber.

The importance of the fuel injection configuration on the propulsion efficiency of high-speed vehicles is apparent. In this article, the use of an annular extruded 4-lobe nozzle for the injection of fuel jet in a supersonic combustor of a scramjet engine in the existence of a shock generator is examined. The main aim of this study is to obtain the efficient jet arrangement for efficient fuel mixing inside the engine of hypersonic vehicles. A numerical approach is used to model the supersonic air stream and cross-jet flow with the SST turbulence model. The role of nozzle altitude and internal air jet on the fuel mixing of the hydrogen within the high-speed domain are disclosed. The importance of the horseshoe vortex and counter-rotating vortex on the fuel distribution is also presented. Our results show that the usage of a coaxial jet instead of an annular jet would increase fuel mixing by more than 40% in the combustion chamber.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Development of Heavy-Weight Hematite-Based Geopolymers for Oil and Gas Well Cementing.

In the petroleum industry, ordinary Portland cement (OPC) is utilized for different cementing applications. Yet, there are some technical and environmental issues for the usage of OPC in well cementing. The technical problems include gas invasion while setting, instability at corrosive environments, cement failure while perforation and fracturing due to high stiffness and brittleness, and strength reduction and thermal instability at elevated temperatures. Moreover, OPC production consumes massive energy and generates high greenhouse gas emissions. This study introduced the first hematite-based class F fly ash geopolymer formulation that can be used in oil and gas well cementing. Different properties of the designed slurry and hardened samples such as rheology, thickening time, strength, and elastic and petrophysical properties were evaluated. Moreover, mixability and pumpability challenges of heavy-weight geopolymer slurries were investigated. Unlike most of the studies in the literature, this work used 4 M NaOH solution only as an activator that can reduce the overall cost. The results showed that increasing the hematite percentage significantly decreased the thickening time. The developed formulation fell within the recommended fluid loss ranges for some cementing applications without using a fluid loss control additive. A proposed mixture of retarder and superplasticizer was introduced to enhance the thickening time by almost 5 times. The compressive strength increased by 49% and the tensile strength was enhanced by 27.4% by increasing the curing time from 1 to 7 days. The improvement in both compressive and tensile strength with curing time indicated that the geopolymerization reaction continued for extended time but with a smaller rate. The developed slurry acted more like a power law fluid at low temperatures and more like a Bingham plastic fluid at high temperatures. The elastic properties of the developed geopolymer samples proved that they are more flexible than some cement systems.

Assessment of binding interaction to salmon sperm DNA of two antiviral agents and ecofriendly nanoparticles: comprehensive spectroscopic study.

The direct binding of antiviral agents; Daclatasvir and valacyclovir and green synthesized nanoparticles to salmon sperm DNA have been assessed in a comparative study. The nanoparticles were synthesized by the hydrothermal autoclave method and have been fully characterized. The interactive behavior and competitive binding of the analytes to DNA in addition to the thermodynamic properties were deeply investigated by the UV-visible spectroscopy. The binding constants were monitored in the physiological pH conditions to be 1.65 × 106, 4.92 × 105 and 3.12 × 105 for daclatasvir,valacyclovir and quantum dots, respectively. The significant changes in the spectral features of all analytes have proven intercalative binding. The competitive study has confirmed that, daclatasvir, valacyclovir, and the quantum dots have exhibited groove binding. All analytes have shown good entropy and enthalpy values indicating stable interactions. The electrostatic and non-electrostatic kinetic parameters have been determined through studying the binding interactions at different concentrations of KCl solutions. A molecular modelling study has been applied to demonstrate the binding interactions and their mechanisms. The obtained results were complementary and afforded new eras for the therapeutic applications.

Comparative study between ultra-mini-percutaneous nephrolithotomy versus stented extracorporeal shock wave lithotripsy for treatment of renal stones in Egypt.

Objectives: The purpose of this study is to compare results, safety and outcome of ultra-mini-percutaneous nephrolithotomy (PCNL) versus stented shock wave lithotripsy (SWL) for the management of renal calculi sized 10-20 mm. Methods: This study was conducted at Urology Department, Faculty of Medicine, Ain Shams University. After meeting inclusion and exclusion criteria, 90 patients were randomized to either ultra-mini-PCNL group or stented SWL group through the closed-envelope technique, with 45 patients in each group. Patient data were collected preoperatively, immediately postoperatively and 2 and 4 weeks postoperatively assessing operative time, hospital stay, complications including haematuria, fever, the need for blood transfusion, residual stones and the need for retreatment. Results: Stone-free rate (SFR) was higher in the ultra-mini-PCNL group compared to the stented SWL group, with no statistically significant difference with P-value = 0.316. As for the need for retreatment, it was slightly higher in the stented SWL group compared to the ultra-mini-PCNL group, yet this difference was statistically insignificant with P-value = 0.681.We found no statistically significant difference between both groups regarding post-operative complications including fever, haematuria and need for blood transfusion, respectively.Operative time and hospital stay were significantly higher in the ultra-mini-PCNL group compared to the stented SWL group with P-value < 0.001 for both. Conclusion: Both stented SWL and ultra-mini-PCNL are good treatment choices for renal stones sized less than 2 cm with low complication rates. Stone size indices were significant predictor for the need for retreatment. Further studies to compare SFR based on stone size in both interventions are needed.

Neuroprotective Effects of Some Nutraceuticals against Manganese-Induced Parkinson's Disease in Rats: Possible Modulatory Effects on TLR4/NLRP3/NF-κB, GSK-3ß, Nrf2/HO-1, and Apoptotic Pathways.

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting the substantia nigra where functions controlling body movement take place. Manganese (Mn) overexposure is linked to a neurologic syndrome resembling PD. Sesamol, thymol, wheat grass (WG), and coenzyme Q10 (CoQ10) are potent antioxidants, anti-inflammatory, and anti-apoptotic nutraceuticals. We investigated the potential protective effects of these nutraceuticals alone or in combinations against MnCl2-induced PD in rats. Seven groups of adult male Sprague Dawley rats were categorized as follows: group (I) was the control, while groups 2-7 received MnCl2 either alone (Group II) or in conjunction with oral doses of sesamol (Group III), thymol (Group IV), CoQ10 (Group V), WG (Group VI), or their combination (Group VII). All rats were subjected to four behavioral tests (open-field, swimming, Y-maze, and catalepsy tests). Biochemical changes in brain levels of monoamines, ACHE, BDNF, GSK-3ß, GABA/glutamate, as well as oxidative stress, and apoptotic and neuroinflammatory biomarkers were evaluated, together with histopathological examinations of different brain regions. Mn increased catalepsy scores, while decreasing neuromuscular co-ordination, and locomotor and exploratory activity. It also impaired vigilance, spatial memory, and decision making. Most behavioral impairments induced by Mn were improved by sesamol, thymol, WG, or CoQ10, with prominent effect by sesamol and thymol. Notably, the combination group showed more pronounced improvements, which were confirmed by biochemical, molecular, as well as histopathological findings. Sesamol or thymol showed better protection against neuronal degeneration and some behavioral impairments induced by Mn than WG or CoQ10, partly via interplay between Nrf2/HO-1, TLR4/NLRP3/NF-κB, GSK-3ß and Bax/Bcl2 pathways.

Ethnicity affects the risk factors of acute myocardial infarction and should be considered in educational programs.

Acute Myocardial infarction is a non-communicable disease representing the leading cause of death in Saudi Arabia. Studying the ethnicity in its risk factors has been poorly investigated. Objectives: To compare risk factors among Saudi nationals and expatriates. Methods: A retrospective cohort study for patients admitted to the Cardiac Care Unit of one of the largest tertiary care hospitals in Tabuk diagnosed with acute myocardial infarction from September 2018 to August 2019. Risk factors were compared among groups on the basis of their ethnicity. Results: In total 18,746 patients were included. Gender and age were the predominant risk factors; Male (p < 0.05) and age >50 years (p < 0.05). There were significant differences between Saudis and expatriates in all measurable parameters indicating that a genetic factor contributes to the risk factors, which was proved by the significant differences between the Middle East North Africa and South Asia subgroups. Interestingly, the mean values of laboratory results were higher than Saudi populations. Conclusions: The disparity in lipid profile among the studied groups addresses the patient ethnicity should be considered during education programs for the risk factors of cardiovascular disease.

Preclinical study for the ameliorating effect of l-ascorbic acid for the oxidative stress of chronic administration of organic nitrates on myocardial tissue in high sucrose/fat rat model.

Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. Aim: The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.

The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/ß-Catenin signaling pathways in rat model.

Both thymoquinone (TQ) and thymol (T) have been proved to possess a positive impact on human health. In this research, we aimed to investigate the effect of these compounds separately and together on the Attention-deficit/hyperactivity disorder (ADHD)-like behavior induced by monosodium glutamate (MSG) in rats. Forty male, Spargue Dawley rat pups (postnatal day 21), were randomly allocated into five groups: Normal saline (NS), MSG, MSG+TQ, MSG+T, and MSG+TQ+T. MSG (0.4 mg/kg/day), TQ (10 mg/kg/day) and T (30 mg/kg/day) were orally administered for 8 weeks. The behavioral tests proved that rats treated with TQ and/or T showed improved locomotor, attention and cognitive functions compared to the MSG group with more pronounced effect displayed with their combination. All treated groups showed improvement in MSG-induced aberrations in brain levels of GSH, IL-1ß, TNF-α, GFAP, glutamate, calcium, dopamine, norepinephrine, Wnt3a, ß-Catenin and BDNF. TQ and/or T treatment also enhanced the mRNA expression of Nrf2, HO-1 and Bcl2 while reducing the protein expression of TLR4, NFκB, NLRP3, caspase 1, Bax, AIF and GSK3ß as compared to the MSG group. However, the combined therapy showed more significant effects in all measured parameters. All of these findings were further confirmed by the histopathological examinations. Current results concluded that the combined therapy of TQ and T had higher protective effects than their individual supplementations against MSG-induced ADHD-like behavior in rats.

Impact of automated drug dispensing system on patient safety

Objectives: Automated drug dispensing system (ADDs) is an emerging technology positively impacts drug dispensing efficiency by minimizing medication errors. However, the pharmacist perception of the impact of ADDs on patient safety is not well-established. This cross-sectional observational study aimed to evaluate the dispensing practice and pharmacist perception of ADDs towards patient safety through a validated questionnaire. Methods: A selfdesigned questionnaire was validated and the pharmacist perception of dispensing practice was compared between two hospitals adopting ADDs and traditional drug dispensing system (TDDs). Results: The developed questionnaire had an excellent internal consistency (both Cronbach’s α and McDonald’s ω coefficients were >0.9). Factor analysis retained three significant factors (subscales) that explained pharmacist perception of dispensing system, dispensing practice, and patient counseling (p<0.001 for each factor). The average number of prescriptions dispensed per day, drugs contained in each prescription, average time for labeling each prescription and inventory management were significantly varied between ADDs and TDDs (p=0.027, 0.013 0.044 and 0.004, respectively). The perception of pharmacists using ADDs on three domains were higher than the TDDs. The pharmacists in ADDs agreed that they had enough time to review the medications before dispensing than TDDs and this difference was found to be statistically significant (p=0.028). Conclusions: ADDs was highly effective in improving dispensing practice and medication review; however, the pharmacists need to emphasize the importance of ADDs to translate the pharmacists’ freed-time towards patient care. (AU)

Expanding the phenotypic spectrum of Dejerine-Sottas syndrome caused by the trembler mutation.

Dejerine-Sottas syndrome (DSS) is the earlier onset, more severe form of Charcot-Marie-Tooth (CMT) disease with heterogenous neurologic manifestations in addition to the peripheral neuropathy depending not only on the underlying causative gene but also the specific mutation. The Trembler mutation is an uncommon missense mutation in the PMP22 gene, the most commonly mutated gene responsible for CMT. We report two cases of DSS in a mother and son with the Trembler mutation, with associated findings of hearing loss and cognitive impairment. The mother had developmental gait abnormalities and became wheelchair bound in adolescence. She displayed impairment on cognitive and audiologic testing. Her son had similar developmental gait abnormalities and became wheelchair bound at age 19. Cognitive function showed an earlier decline in the son as compared to his mother. This report extends the clinical spectrum of the Trembler mutation in humans to include associated hearing loss with cognitive impairment.