Effect of empagliflozin in peripheral diabetic neuropathy of patients with type 2 diabetes mellitus.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most dominant cause of neuropathy worldwide, and there has been no specific treatment until now. The aim of the current study was to assess the probable protective effect of empagliflozin in type 2 diabetics who are suffering from DPN. METHODS: Fifty eligible type 2 diabetes mellitus (T2DM) cases with diabetic peripheral neuropathy were recruited in this study and classified into 2 groups. Group I (n=25) (control group) received placebo tablets once daily. Group II (n=25) (empagliflozin group) received empagliflozin 25mg once daily for three months. Empagliflozin efficacy was evaluated using electrophysiological studies, and HbA1c levels, the brief pain inventory short-form item (BPI-SF) score, the diabetic neuropathy symptom (DNS) score, the atherosclerotic cardiovascular disease (ASCVD) risk score, and the serum levels of neuron-specific enolase (NSE), malondialdehyde (MDA) and calprotectin (Calpro), lipid profile, and random blood glucose level (RBG). RESULTS: After three months, comparing the results of the empagliflozin arm to the control arm showed a significant improvement in the electrophysiological studies and a significant decrease in the BPI-SF score and the mean serum levels of NSE and MDA. However, no significant difference was determined in HbA1c, Calpro, lipid profile, and RBG levels. In addition, the DNS and ASCVD risk scores were not significantly different. The NSE and MDA levels were significantly negatively correlated with the electrophysiological parameters. However, the BPI-SF score showed a non-significant difference. CONCLUSIONS: Empagliflozin may be a promising neuroprotective and therapeutic agent for diabetic peripheral neuropathy. Trial registration Identifier: NCT05977465.

Effectiveness of epigallocatechin gallate nanoparticles on the in-vivo treatment of Alzheimer's disease in a rat/mouse model: a systematic review.

BACKGROUND: Alzheimer's disease (AD) is a neurological disease that causes memory loss over time. Current therapies are limited and frequently inadequate. Epigallocatechin gallate (EGCG), has antioxidant, anti-inflammatory, antifibrosis, anti-remodeling and tissue-protective qualities that may be effective in treatment of different diseases, including AD. Because of nanoparticles' high surface area, they can enhance solubility, stability, pharmacokinetics and biodistribution, and diminish toxicities. Besides, lipid nanoparticles have a high binding affinity that can enhance the rate of drug transport across BBB. So, EGCG nanoparticles represent a promising treatment for AD. OBJECTIVES: This systematic review sought to assess the efficacy of EGCG nanoparticles against AD in rat/mouse models. METHODS: Study was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO. Electronic databases were searched to discover relevant studies published up to October 2022. RESULTS: Two studies met the inclusion criteria out of 1338 and were included in this systematic review. Collectively, the results indicate that EGCG has a significant potential for reducing AD pathology and improving cognitive deficits in rat/mouse models. The formulated particles were in the nanometer range, as indicated by TEM, with good particle size control and stability. EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG. Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats. CONCLUSION: This systematic analysis of the two studies included showed that EGCG nanoparticles are efficacious as a potential therapeutic intervention for AD in rat/mouse models. However, limited number of studies found indicates insufficient data in this research point that requires further investigation by experimental studies.

Electrospun PVA nanofiber mat for topical Deflazacort delivery: accentuated anti-inflammatory efficacy for wound healing.

PURPOSE: Asses the wound healing activity of Polyvinyl alcohol - Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. METHODS: PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. RESULTS: Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. CONCLUSION: PVA-DEF nanofiber mats can be used effectively for improving wound healing.

The Potential Roles of Ficus carica Extract in the Management of COVID-19 Viral Infections: A Computer-Aided Drug Design Study.

INTRODUCTION: The conventional processes of drug discovery are too expensive, time-consuming and the success rate is limited. Searching for alternatives that have evident safety and potential efficacy could save money, time and improve the current therapeutic regimen outcomes. METHOD: Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis, treatment, or management of human disorders. In this work, the potential role of common Fig (Ficus carica) in the management of COVID-19 infections has been explored. The antiviral effects of Cyanidin-3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm associated with coronavirus infections have also been highlighted. This work involves various computational studies to investigate the potential roles of common figs in the management of COVID-19 viral infections. RESULTS: Two molecular docking studies of all active ingredients in common Figs were conducted starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation of the results of the top five compounds with the best docking score. CONCLUSION: Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted using GROMACS to endorse and validate the entire work.

Development of eplerenone nano sono-crystals using factorial design: enhanced solubility and dissolution rate via anti solvent crystallization technique.

OBJECTIVE: The purpose of this work was to improve EP solubility by using a sono-crystalization approach to reduce particle size and hence, increase the dissolution rate. Significance Eplerenone (EP) is an antagonist of the aldosterone receptor and is used for the treatment of hypertension and chronic heart failure. EP was classed as biopharmaceutical classification (BCS) class II because of its poor solubility and high permeability, which retards dissolution rate and drug absorption, and decreases bioavailability. METHODS: Three-factors and two-level (23) multifactorial design have been employed to study the effect of independent variables which are drug concentration; (X1), stabilizer type (X2), and stabilizer concentration (X3) on responses; saturated solubility of EP in distilled water (Y1), saturated solubility in acidic media pH 1.2 (Y2), particle size (Y3), and polydispersity index, PDI (Y4). Also, they were characterized by Fourier transformed infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and yield percentage. The optimum formula was further subjected to an in-vitro release study. RESULTS: The optimized formulation showed a saturated solubility of EP as 1.29, and 1.86 (mg/ml) in distilled water and acidic media (pH 1.2) respectively. Also, the particle size of 133 nm, and PDI of 0.824 with a small percentage of the difference between the observed and predicted values. Ninety-one percent of EP was released within 10 min., and it was completely released within 45 min. with a significantly higher release rate compared to raw drug. CONCLUSION: This work resulted in a satisfactory enhancement of solubility and dissolution rate which, is suitable for further in-vivo analysis.

Investigating the Impact of Optimized Trans-Cinnamic Acid-Loaded PLGA Nanoparticles on Epithelial to Mesenchymal Transition in Breast Cancer.

PURPOSE: To design and optimize trans-cinnamic acid-loaded PLGA nanoparticles (CIN-PLGA-NPs) and assess its inhibitory effect on epithelial-mesenchymal transition (EMT) in triple-negative breast cancer. METHODS: The quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the free trans-cinnamic acid (CIN-Free) was investigated in vitro using MDA-MB-231, triple-negative breast cancer cells, followed by scratch wound assay for evaluating the impact on the migratory potential of MDA-MB-231 cells. In vivo antitumor activity was evaluated using Ehrlich ascites carcinoma solid tumor animal model where tumor volumes were measured at different time points and necrotic/apoptotic indices were estimated in tumor sections. EMT markers, E- and N-cadherin, were assessed in solid tumors as well. RESULTS: The optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of -28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8±1.89% of the total CIN-Free within 24 hours compared to 29±1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition. CONCLUSION: Our findings proved the capability of PLGA nanoparticles in loading trans-cinnamic acid in addition to enhancing its antitumor efficacy in triple-negative breast cancer possibly via inhibiting EMT.

Cardiac calcium score in systemic sclerosis.

Cardiac coronary Ca score (CCS), and extra coronary Ca score (ECCS) estimation in asymptomatic systemic sclerosis (SSc) patients and their relation to different disease and patients' variables. The CCS and ECCS were estimated in asymptomatic 20 SSc patients compared to 20 age and sex-matched healthy control using non-contrast cardiac computed tomography. All were applied for cardiac history taking, examination, echocardiography, body mass index (BMI), complete blood picture, erythrocyte sedimentation rate, and lipid profile estimation. The SSc patients were 11 females and 9 males with a mean age of (42.55 ± 9.145) and mean disease duration (12.9 ± 6.774). CCS was reported in 9 (45%) SSc cases and 2 (10%) of the control; (p = 0.013) and was significantly greater in SSc patients (58.4 ± 175.443) than in the control group (0.7 ± 2.25); (p = 0.01). The ECCS was significantly higher in SSc cases (194.45 ± 586.511) than control group (2.8 ± 7.8); (p = 0.001) and reported in 16 (80%) SSc cases and 3 (15%) of controls; (p = 0.000). Limited scleroderma cases had higher scores than diffuse type. Patients with total ca score (> 100) were older (p = 0.016), had longer disease duration (p = 0.001) and greater BMI (p = 0.002). Significant correlation was found between the log-transformed CCS and disease duration, age, BMI, left ventricular mass, and mass index. Systemic sclerosis patients are at increased risk of subclinical cardiovascular disease determined by cardiac Ca scoring as a noninvasive and reliable method. Extra coronary calcification may be an earlier indicator for this. Disease duration is a determinant risk factor for cardiac calcification in SSc. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • Systemic sclerosis patients are at high risk of accelerated atherosclerosis and cardiovascular diseases. Coronary atherosclerosis was previously estimated in SSc patients through coronary angiography. A novel method of assessing coronary artery disease is the coronary calcium score, as determined by multidetector computed tomography, it measures coronary artery calcification that occurs in atherosclerotic plaque. In this study, the cardiac coronary and extra coronary Ca score were evaluated in relation to disease characteristics in asymptomatic SSC patients for early detection of coronary artery disease.

Preventive infection control in cardiac device implantation.

BACKGROUND: Cardiac implantable electronic devices have been increasingly used in recent years; as a result, there has been a rise in device-related complications. Pacemaker-associated infection is challenging to manage, including system removal, antimicrobial therapy and reimplantation at another site. The aim of this study was to evaluate adherence to the steps in an infection control protocol in cardiac device implantation. RESULTS: A total of 100 patients referred for cardiac device implantation were enrolled in the study. They were evaluated with regard to the application of infection control measures during device implantation and followed-up for 6 months to detect clinical signs of device-related infection (DRI). A significant correlation was found between the development of postoperative DRI and the presence or absence of the following factors: increasing patient age (p = 0.010), diabetes mellitus (p = 0.024), number of operators ≥4 (p = 0.001), implantation of a biventricular system (p = 0.025), duration of sterilization (p = 0.001), wearing double gloves (p < 0.001) and postoperative hematoma (p = 0.021). CONCLUSIONS: The study identified the following risk factors for DRI: age, diabetes mellitus and cardiac resynchronization therapy system implantation (p = 0.025). Antiseptic measures such as double-glove technique and duration of skin disinfection prior to the procedure, as well as environmental factors, also influenced device infection, as did the number of operators/staff and pocket hematoma.

QRS Duration as a Predictor of Left Ventricular Outflow Tract Velocity Time Integral in Patient with Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has a morbidity and mortality benefits in moderate to severe heart failure. It reduces mortality and hospitalization and improves cardiac function. It can be used according to the European guidelines in severely depressed left ventricular ejection fraction (i.e., ≤35%) and complete left bundle branch block. However, 30% of patients may show no benefit from CRT therapy. Therefore, prediction of CRT response seems to be an important subject for study in the current researches. We aimed to study the correlation between Surface ECG QRS complex duration (QRS) duration and cardiac output measured by ventricular outflow tract velocity time integral (LVOT VTI) as a predictor of response in patients with CRT implantation. METHODS: We studied 100 consecutive patients prospectively with biventricular pacing system. The patients were studied at the pacemaker follow-up clinic. Each patient was subjected to: Full medical history, general and local examination, a 12 lead electrocardiogram and QRS duration in ms was measured. All patients were subjected to a focused transthoracic echocardiographic examination in which a parasternal long axis view was obtained to measure the diameter of the LVOT diameter in mid-systole. The LVOT VTI was measured by pulsed-wave Doppler in the LVOT using a 2-mm sample volume positioned just proximal to the aortic valve in the apical five chamber view. RESULTS: We found a statistically significant difference between CRT responders and nonresponders as regards age, body surface area (BSA), time since CRT implantation and smoking status (P = 0.018, 0.039, 0.002, <0.001). There was negative significant correlation between QRS duration and LVOT VTI and stroke volume index. The optimal cut off values for optimal response to CRT using receiver operating characteristics curves were 130 ms for postimplant QRS duration and 17.1 cm for LVOT VTI. We also found a significant difference between responders and nonresponders as regard CO. It was higher in responders (5.97 vs. 3.34, P < 0.001). CONCLUSION: CRT response is more in patients with lower BSA, and without previous history of ischemic heart disease or smoking. There is a significant negative correlation between QRS duration and LVOT VTI.

Current Topical Strategies for Skin-Aging and Inflammaging Treatment: Science versus Fiction.

Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Inflammaging has recently emerged as a pathway that correlates aging and age-related diseases with inflammation. This review discusses the role and pathways of inflammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with inflammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier-based formulations. In recent years, consumers' demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the efficacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations.

Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients.

The aim of this work is to develop self-nano emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of zaleplon (Zal) as a poorly water-soluble drug. Moreover, the bioavailability and the effect on the quality of sleep among a sample of psychiatric patients is to be assessed. D-optimal mixture design was used for optimization. Optimized SNEDDS formulation was evaluated for droplet size, transmission electron microscope (TEM) and in-vitro dissolution test. Zal bioavailability was evaluated by determining its serum concentration and pharmacokinetic parameters in 8 patients after oral administration. Effect on sleep quality was assessed among 40 psychiatric patients. Patients' sleep quality was assessed in 40 psychiatric patients before and after medication using the Arabic version of the Pittsburgh Sleep Quality Index (PSQI). Zal- SNEDDS appeared as nano-sized spherical vesicles. Moreover, Zal was completely dissolved from optimized formulation after 45 min indicating improved dissolution rate. Zal-SNEDDS showed significantly higher Cmax, Tmax and AUC0→∞ compared to commercial product after oral administration. Zal-SNEDDS significantly improved the total score of PSQIs (p < .001) with higher subjective sleep quality, reduced sleep latency, improved day time function and sleep disturbance (p < .001). Using sleep medication was reduced significantly (p = .027). However, it did not modify sleep duration or sleep efficiency. SNEDDS have improved Zal solubility and enhanced its bioavailability. Furthermore, Zal-SNEDDS have improved the total score of PSQIs and may be considered a good choice to enhance the quality of sleep among psychiatric patients.

Proniosomal gel-mediated topical delivery of fluconazole: Development, in vitro characterization, and microbiological evaluation.

The aim of this study was to explore the potential of proniosomal gel for topical delivery of fluconazole, an antifungal drug used in fungal infections caused by pathogenic fungi. Fluconazole-loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared fluconazole proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE%), and in vitro drug release. The experimental results showed that the EE% for the prepared formulae are acceptable (85.14%-97.66%) and they are nanosized (19.8-50.1 nm) and the diffusion from the gels gave the desired sustaining effect. F4, which was prepared from span 60, tween 80 (1:1), and cholesterol showed highest EE% and gave slow release (40.50% ± 1.50% after 6 h), was subjected to zeta potential (ZP) test, transmission electron microscopy as well as microbiological study. The results showed a well-defined spherical vesicle with sharp boundaries with good physical stability of fluconazole within the prepared gel. Moreover, F4 showed an excellent microbiological activity represented by a greater zone of inhibition (5.3 cm) compared to control gel (fluconazole in 2% hydroxy propyl methyl cellulose (HPMC) gel formula) (4.2 cm) and plain gel with no drug (0 cm) against Candida albicans. This study showed the suitability of the proniosomal gel in attaining the desired sustainment effect for topical delivery of fluconazole for the management of fungal infection. The physical stability study showed that there was no significant change in EE%, PS, and ZP of fluconazole proniosomal gel after storage for 6 months.

New thiobarbituric acid scaffold-based small molecules: Synthesis, cytotoxicity, 2D-QSAR, pharmacophore modelling and in-silico ADME screening.

A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4-7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Compound 12d exhibited potent sub-micromolar activity against HepG-2 and MCF-7 (IC50 = 0.07 and 0.08 µM, respectively). In-silico pharmacophore modelling of this chemotype compounds disclosed a five features' pharmacophore model representing essential steric and electronic fingerprints essential for activity. Finally, a 2D-QSAR model was devised to quantitatively correlate the 2D molecular feature descriptors of this series of thiobarbiturates with their cytotoxic activity against MCF-7. Finally, in silico evaluation of the physicochemical and ADME properties of these derivatives was performed.

Early changes in longitudinal deformation indices in young asymptomatic patients with type 1 diabetes mellitus: assessment by speckle-tracking echocardiography.

BACKGROUND: We explored early changes in regional left ventricular systolic and diastolic function assessed by speckle-tracking echocardiography (STE) in young asymptomatic patients with type 1 diabetes mellitus (DM), compared with healthy controls. METHODS: We enrolled 30 normotensive asymptomatic patients with type 1 DM, age ≤40 years, DM duration >5 years, and left ventricular ejection fraction ≥50%; and thirty matched controls. They underwent conventional echocardiography, and tissue Doppler imaging (TDI). Myocardial deformation indices were measured by STE. We measured global longitudinal systolic strain, global longitudinal systolic strain rate, and global longitudinal early diastolic strain rate, as an average of 18 myocardial segments. RESULTS: The mean age was 27.7±4.5 years, (41.7% males). The mean duration of diabetes was 14.3±5.8 years. The 2-D ejection fraction was lower in diabetic patients versus controls (P=0.03). The trans-mitral A peak was higher, and isovolumetric relaxation time longer in diabetics (P<0.05 for both). Both lateral and septal É values were lower, and E/É ratio higher in diabetics (P<0.05 for all). The global longitudinal systolic strain and strain rate were decreased in diabetics (-17.7±2.5% versus -21.2±1.7%, and -1.1±0.2 versus -1.3±0.2 s-1, P<0.001 and P=0.003, respectively). The global longitudinal early diastolic strain rate was comparable to controls (1.5±0.4 versus 1.6±0.3 s-1, respectively, P=0.33). CONCLUSIONS: In asymptomatic patients with type 1 DM, global longitudinal systolic function measured by STE was impaired versus controls; diastolic function was impaired by conventional echocardiography and TDI.

Synthesis of new pyrrolo[2,3-d]pyrimidine derivatives as antibacterial and antifungal agents.

A series of new pyrrole derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrrolotriazolopyrimidines and pyrrolotetrazolopyrimidines were synthesized. The evaluation of their antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans were carried out. Pyrrolo[2,3-d]pyrimidines 3a-d, 7a,e, 11d exhibited excellent activity against C. albicans with MIC 0.31-0.62 mg/mL. These compounds displayed better antifungal activity than that of standard drug (fluconazole with MIC 1.5 mg/mL). Furthermore, pyrrolo[2,3-d]pyrimidines 3b,c, 7e exhibited the best activity against S. aureus with MIC 0.31 mg/mL, compared with the standard drug (ampicillin with MIC 0.62 mg/mL). The rest of the compounds were found to be inactive against bacteria and fungi.

Synthesis and biological evaluation of novel imidazolone derivatives as potential COX-2 inhibitors.

Three novel series of 2-(substituted phenyl)-4-(substituted arylidene)-imidazolone-5-(4H)-ones were derived from the corresponding oxazolones by condensation with different arylamines. Eleven of the synthesized compounds were selected and evaluated for their effect on carrageenan-induced rat paw edema. Compound 4b had the same efficacy as the reference standard (indomethacin), and compounds 3b, 3c, 4a, 4d and 9a showed good to excellent activities, with other compounds only weakly active. The potent compounds were evaluated for their inhibitory activities against COX-2-catalyzed PGE(2) production, with 4a, 4b and 3c showing strong inhibitory activity.

Synthesis of new imidazolyl acetic acid derivatives with anti-inflammatory and analgesic activities.

We synthesized 2-(4-(4-fluorobenzylidene)-2-(4-fluorophenyl) 5-oxo-4,5-dihydroimidazol-1-yl) acetic acid 3. Chlorination afforded the chloro derivative 4, which reacted with different amines and hydrazine to afford compounds 5-8. Pyrazole, pyrazolone, and thiazolidinone derivatives were also synthesized from Imidazol-1-ylacetic acid hydrazide 8 to give compounds 9-12. Compounds were then evaluated for their anti-inflammatory activity against carrageenan-induced rat paw edema and their analgesic activity using the writhing test in albino mice. Compounds 5, 9, 10, 12 exhibited maximum anti-inflammatory activity, and all the compounds inhibited writhing, with 10 and 12 being two times more effective than the reference standard.

Impact of an educational program based on evidence related to Fever management.

Quality care is dependent on best evidence. Children's nurses are no exception to this and their philosophy of "the child first and always" will ensure that their evidence base for practice is commensurate with stance. For this reason, this study was conducted to assess the impact of an educational program based on evidence related to fever management on nurses' evidence-based knowledge and reported practices. An Educational program based on evidence was designed according to nurses' needs and new evidence findings in fever management. Results of the study showed that at the pre program phase, nurses had lower level of evidence-based knowledge than at the first follow-up. Their means of knowledge scores related to fever, measuring temperature, nursing management, administration of antipyretics and documentation were 3.69 vs 8.00, 5.06 vs 7.49, 3.99 vs 6.94, 4.07 vs 7.33 and 6.81 vs 9.76 respectively. Also, there was no statistical significant difference between level of evidence-based knowledge for nurses at the first and second follow-ups. It was concluded that an educational program based on evidence promotes the quality of nursing care in fever management.

Impact of supplemental feeding on pain in neonatal intensive care unit.

Neonates can't report pain for a variety of reasons. Therefore, behavioral changes and physiological changes such as heart and respiratory rates, facial expression, reduction in crying, position in bed, activity and consolability were used to assess pain for 60 newborns (30 experimental and 30 control). Neonates in the experimental group were provided supplemental feeding during painful procedures. Meanwhile, neonates in the control group were not provided any feeding while painful procedures were carried up by nurses. Results showed greater reductions in means heart rate (143.0 vs 158.2 b/m), respiratory rate (43.4 vs 61.2 c/m)and scores of observational checklist (2.3 vs 5.0) between newborns in the experimental group than in the control group. Therefore, it was concluded that supplemental feeding should be provided during painful procedures because it provides some form of pain reduction during painful procedures.