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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.

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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.

RESUMEN

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.

Asunto(s)

Modelos Animales de Enfermedad , Flavanonas , Hemo Oxigenasa (Desciclizante) , MicroARNs , Factor 2 Relacionado con NF-E2 , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Pancreatitis , Ratas Sprague-Dawley , Transducción de Señal , Sirtuina 1 , Receptor Toll-Like 4 , Animales , Pancreatitis/inducido químicamente , Pancreatitis/prevención & control , Pancreatitis/metabolismo , Pancreatitis/patología , Pancreatitis/tratamiento farmacológico , Sirtuina 1/metabolismo , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Flavanonas/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Hemo Oxigenasa (Desciclizante)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Arginina/farmacología , Enfermedad Aguda , Páncreas/efectos de los fármacos , Páncreas/patología , Páncreas/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos

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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.

Asunto(s)

Althaea , Quitosano , Diabetes Mellitus , Nanopartículas del Metal , Óxido de Zinc , Humanos , Animales , Ratas , Óxido de Zinc/química , Quitosano/química , Althaea/metabolismo , Interleucina-6 , Factor de Necrosis Tumoral alfa , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de Heridas , Antiinflamatorios/farmacología , Inflamación , Flores , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X

RESUMEN

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.

Asunto(s)

Antralina , Psoriasis , Humanos , Animales , Ratones , Antralina/farmacología , Antralina/uso terapéutico , Ciclosporina/farmacología , Fosfolípidos , Ceramidas/farmacología , Administración Cutánea , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel , Modelos Animales de Enfermedad

RESUMEN

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.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nanopartículas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Conejos , Canagliflozina , Comprimidos/química , Solubilidad , Povidona/química , Permeabilidad , Nanopartículas/química

RESUMEN

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.

RESUMEN

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.

RESUMEN

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.

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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)

Asunto(s)

Humanos , Sistemas de Registros Médicos Computarizados , Seguridad del Paciente , Comercialización de Productos , Estudios Transversales , Encuestas y Cuestionarios , Análisis Factorial

RESUMEN

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.

Asunto(s)

Trastorno por Déficit de Atención con Hiperactividad , Glutamato de Sodio , Animales , Masculino , Ratas , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/prevención & control , Proteína X Asociada a bcl-2 , beta Catenina/metabolismo , Factor Neurotrófico Derivado del Encéfalo , Calcio , Caspasa 1/metabolismo , Dopamina , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Norepinefrina , ARN Mensajero , Solución Salina , Timol/farmacología , Timol/uso terapéutico , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vía de Señalización Wnt

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/ß-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. OBJECTIVES: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl3)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. METHODS: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl3, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl3-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. RESULTS: AlCl3 caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-ß generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/ß-catenin/GSK3ß signaling pathway. CONCLUSIONS: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/ß-catenin/GSK-3ß signaling pathways.

RESUMEN

The current study investigated the neuroprotective activity of some drugs and nutriceuticals with antioxidant and anti-inflammatory potential on the pathogenesis of Parkinson's disease (PD). Rats were categorized into seven groups: Rats received tween80 daily for 5 weeks as a control group, MnCl2 (10 mg/kg, i.p) either alone (group II) or in combination with vinpocetine (VIN) (20 mg/kg) (group III), punicalagin (PUN) (30 mg/kg) (group IV), niacin (85 mg/kg) (group V), vitamin E (Vit E) (100 mg/kg) (group VI) or their combination (group VII). Motor activities was examined using open-field and catalepsy. Striatal monamines, acetylcholinesterase, excitatory/inhibitory neurotransmitters, redox status, pro-oxidant content, brain inflammatory, apoptotic and antioxidant biomarkers levels were assessed. Besides, histopathological investigations of different brain regions were determined. Groups (IV -GVII) showed improved motor functions of PD rats. Applied drugs significantly increased the brain levels of monoamines with the strongest effect to PUN. Meanwhile, they significantly decreased levels of acetylcholinesterase with a strongest effect to PUN. Moreover, they exhibited significant neuronal protection and anti-inflammatory abilities through significant reduction of the brain levels of COX2, TNF-α and Il-1ß with a strongest effect to the PUN. Interestingly; groups (IV - GVII) showed restored glutamate/GABA balance and exhibited a pronounced decrease in caspase-3 content and GSK-3ß protein expression levels. In addition, they significantly increased Bcl2 mRNA expression levels with a strongest effect for PUN. All these findings were further confirmed by the histopathological examinations. As a conclusion, we propose VIN and PUN to mitigate the progression of PD via their antioxidant, anti-inflammatory, anti-apoptotic, neurotrophic and neurogenic activities.

Asunto(s)

Fármacos Neuroprotectores , Niacina , Enfermedad de Parkinson , Acetilcolinesterasa , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta , Taninos Hidrolizables , Manganeso/farmacología , Neuroprotección , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Niacina/farmacología , Estrés Oxidativo , Enfermedad de Parkinson/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Alcaloides de la Vinca , Vitamina E/farmacología

RESUMEN

Nanotherapeutics can enhance the characteristics of drugs, such as rapid systemic clearance and systemic toxicities. Polymeric nanoparticles (PRNPs) depend on dispersion of a drug in an amorphous state in a polymer matrix. PRNPs are capable of delivering drugs and improving their safety. The primary goal of this study is to formulate doxycycline-loaded PRNPs by applying the nanoprecipitation method. Eudragit S100 (ES100) (for DOX-PRNP1) and hydroxypropyl methyl cellulose phthalate HP55 (for DOX-PRNP2) were tested as the drug carrying polymers and the DOX-PRNP2 showed better characteristics and drug release % and was hence selected to be tested in the biological study. Six different experimental groups were formed from sixty male albino mice. 1,2,-Dimethylhydrazine was used for 16 weeks to induce experimental colon cancer. We compared the oral administration of DOX-PRNP2 in doses of 5 and 10 mg/kg with the free drug. Results indicated that DOX-PRNP2 had greater antitumor activity, as evidenced by an improved histopathological picture for colon specimens as well as a decrease in the tumor scores. In addition, when compared to free DOX, the DOX-PRNP2 reduced the angiogenic indicators VEGD and CD31 to a greater extent. Collectively, the findings demonstrated that formulating DOX in PRNPs was useful in enhancing antitumor activity and can be used in other models of cancers to verify their efficacy and compatibility with our study.

RESUMEN

BACKGROUND: Cardiovascular disease (CVD) is a global burden particularly in developing countries necessitates the periodical monitoring for these vulnerable population. This study aimed to compare four tools to measure the CVD risk between the East Mediterranean and South Asian population. METHODS: This retrospective analysis included 139 patients from East Mediterranean (n=90) and South Asians (n=49) ethnicity who were admitted during the one-year period in a multi-specialty tertiary care hospital located in Tabuk, Saudi Arabia. Four different tools currently in use across the world were used to analyses the CVD risk. RESULTS: Atherosclerotic Cardiovascular Disease (ASCVD) from American College of Cardiology/American Heart Association (ACC/AHA) was found to be significant (P=0.0000) than World Health Organization/International Society of Hypertension (WHO/ISH) and Framingham Risk Score (FRS) European SCORE (Systematic Coronary Risk Evaluation) memo card from European Society of Cardiology risk prediction charts. Meanwhile, FRS looks equally good as it detects 44.89% of South Asian study population with >10% CVD risk while ACC/AHA detects 46.93%. CONCLUSION: The present study recommends ACC/AHA cardiac risk estimator to identify the CVD risk in East Mediterranean population. However, the South Asian population needed a population-based tool to assess the accurate CVD risk.

Asunto(s)

American Heart Association , Enfermedades Cardiovasculares , Pueblo Asiatico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Humanos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Estados Unidos

RESUMEN

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 self-designed 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.

RESUMEN

The chronic hyperglycemia in diabetes is associated with long-term damage, dysfunction, and failure of different organs. Lack of patient education and knowledge about these complications can worsen the quality of a patient's life. Hence, more efforts are needed to improve patient's education especially in rural areas. Aim. Our objective is to explore the association between demographic variables and the knowledge of self-care practices in type 2 diabetes mellitus. Methods. We used observational cross-sectional descriptive study using a validated self-administered questionnaire in both Arabic and English languages as well. A descriptive correlation design analyzed the questionnaire completed by a convenience sample meeting the inclusion criteria. Results. A total of 100 patients met the inclusion criteria for the analysis out of 3251 patients who completed the questionnaire. The study population has low moderate knowledge in diabetes, moderate knowledge in self-care practices, and good knowledge about complications of nephropathy and cardiovascular disease. No significant association between demographic variables. However, better knowledge observed in male (p = 0.028) and self-care practices with female (p = 0.020). Further, educational status is significantly influencing the knowledge of diabetic patients. Conclusion. The study emphasizing irrespective of demographic variable and the importance of patient education to achieve well glycemic control.

Asunto(s)

Diabetes Mellitus Tipo 2 , Conocimientos, Actitudes y Práctica en Salud , Autocuidado , Factores de Edad , Anciano , Estudios Transversales , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arabia Saudita , Factores Sexuales

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.