Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-based derivatives as multitarget anti-Alzheimer agents.

A series of novel 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their potential anti-Alzheimer disease activity. The results revealed that compounds 2b, 2c, 2d, 3a, 4a, 6, 9a, 9b, and 13b showed excellent inhibitory activity against acetylcholinesterase (AChE) with IC50 values in the range of 0.0158 to 0.121 µM. They were 1.01 to 7.78 times more potent than donepezil (IC50 = 0.123 µM). The newly synthesized compounds exhibited lower activity towards butyrylcholinesterase (BuChE) when compared to rivastigmine. Compounds 4b and 13b showed the most prominent inhibitory potential against BuChE with IC50 values of 11.50 and 15 µM, respectively. Moreover, 4b, and 9b were found to be more potent antioxidant agents (IC50 values of 59.25, and 56.69 µM, respectively) in comparison with ascorbic acid (IC50 = 74.55 µM). Compounds 2b and 2c exhibited monoamine oxidase-B (MAO-B) inhibitory activity with IC50 values of 74.68 and 225.48 µM, respectively. They were 3.55 and 1.17 times more potent than biperiden (IC50 = 265.85 µM). The prominent interactions of the compounds with the AChE active site can be used to computationally explain the high AChE inhibitory activity. The results unveiled 1,2,4-oxadiazole derivatives 2c and 3a as multitarget anti-AD agents. The predicted ADME properties for compounds 2b and 4a were satisfactory, and 4a had the highest likelihood of crossing the blood-brain barrier (BBB), making it the optimum compound for future optimization.

Nutritional rehabilitation of malnourished children: are nutritional supplements a must?

OBJECTIVE: Malnutrition threatens children worldwide. The objective of the current study was to highlight the role of nutritional screening, evaluate the effectiveness of nutritional intervention program, and whether nutritional supplements have surplus benefit. PATIENTS AND METHODS: Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) was used to screen 3640 clinically stable 2-5 years old children recruited from the outpatient clinics, Children's Hospital, Ain Shams University. A total of 100 patients at high risk of malnutrition were enrolled. Full nutritional assessment was done and according to the distribution of the calories in the daily meal plan, the patients were randomly divided into two groups each comprised 50 patients. Group A received tailored nutritional dietary rehabilitation plan including dietary supplements, while Group B received only dietary advice. Anthropometric measurements, laboratory tests, as well as STAMP scoring were reassessed after the nutritional rehabilitation programs. RESULTS: Nutritional screening revealed that 5.14% were at high risk of malnutrition. Both studied groups showed significant improvement in caloric intake and all anthropometric measurements upon nutritional rehabilitation, except for the height z scores. Patients who received nutritional supplements showed significantly better changes regarding weight, BMI, caloric intake, and hemoglobin. Regarding STAMP categories during follow up, Group A had only 6% of the patients still in the high-risk category and 76% were at low risk compared to 14% high risk and only 54% were at low risk in Group B. CONCLUSIONS: Nutritional screening in pediatric outpatient facilities can lead to implementing prompt nutritional rehabilitation, which can reflect on the patients' overall health. Tailored nutritional plan can accomplish good response in terms of improvement of caloric intake, anthropometric measurements and laboratory parameters. Adding a nutritional supplement to the dietary plan during nutritional rehabilitation isn't a must but it ensures superior goal achievement.

Removal of a Past Varnish Treatment from a 19th-Century Belgian Wall Painting by Means of a Solvent-Loaded Double Network Hydrogel.

Polymeric materials have been used by painting conservator-restorers as consolidants and/or varnishes for wall paintings. The application of these materials is carried out when confronting loose paint layers or as a protective coating. However, these materials deteriorate and cause physiochemical alterations to the treated surface. In the past, the monumental neo-gothic wall painting 'The Last Judgment' in the chapel of Sint-Jan Berchmanscollege in Antwerp, Belgium was treated with a synthetic polymeric material. This varnish deteriorated significantly and turned brown, obscuring the paint layers. Given also that the varnish was applied to some parts of the wall painting and did not cover the entire surface, it was necessary to remove it in order to restore the original appearance of the wall painting. Previous attempts carried out by conservator-restorers made use of traditional cleaning methods, which led to damage of the fragile paint layers. Therefore, gel cleaning was proposed as a less invasive and more controllable method for gently softening and removing the varnish. The work started by identifying the paint stratigraphy and the deteriorated varnish via optical microscopy (OM), scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy. A polyvinyl alcohol-borax/agarose (PVA-B/AG) hydrogel loaded with a number of solvents/solvent mixtures was employed in a series of tests to select the most suitable hydrogel composite. By means of the hydrogel composite loaded with 10% propylene carbonate, it was possible to safely remove the brown varnish layer. The results were verified by visual examinations (under visible light 'VIS' and ultraviolet light 'UV') as well as OM and FTIR spectroscopy.

Is There a Benefit of Vitamin D Supplementation in Deficient Children and Adolescents Suffering from Obesity? A Meta-Analysis.

This systematic review/meta-analysis aims to highlight the effect of vitamin D supplementation in deficient children suffering from obesity. Published clinical studies on vitamin D supplementation in obese children and adolescents with vitamin D deficiency were identified through a comprehensive MEDLINE/PubMed search (from July 1966 to November 2017). Outcomes intended after vitamin D supplementation were improvements in vitamin D status, BMI alterations and appetite changes. The inclusion criteria were children aged 2 to 18 years of both sexes in clinical trials that specified the oral and/or intramuscular dose of vitamin D supplementation. Ten studies were retrieved, but only 6 were relevant. First, supplemented obese children and adolescents were compared to non-obese controls; thereafter, supplemented obese children and adolescents were compared to matching obese peers given placebo. Pooled risks from the 2 studies that evaluated the number of obese and non-obese children and adolescents who improved upon vitamin D supplementation revealed that obesity poses a risk for not benefiting from the vitamin D supplementation regardless of the dose and the duration of supplementation. Pooled results from the 6 retrieved studies that compared supplemented obese children and adolescents to matching non-obese or obese peers given placebo revealed significantly lower vitamin D levels in obese participants than in non-obese peers. Vitamin D levels are significantly lower in obese children and adolescents with obesity, posing a risk for not benefiting from vitamin D supplementation regardless of the dose and duration of supplementation.

Stability-indicating HPLC-DAD methods for determination of two binary mixtures: Rabeprazole sodium-mosapride citrate and rabeprazole sodium-itopride hydrochloride.

Two selective stability-indicating HPLC methods are described for determination of rabeprazole sodium (RZ)-mosapride citrate (MR) and RZ-itopride hydrochloride (IO) mixtures in the presence of their ICH-stress formed degradation products. Separations were achieved on X-Bridge C18 column using two mobile phases: the first for RZ-MR mixture consisted of acetonitrile: 0.025 M KH2PO4 solution: TEA (30:69:1 v/v; pH 7.0); the second for RZ-IO mixture was at ratio of 25:74:1 (v/v; pH 9.25). The detection wavelength was 283 nm. The two methods were validated and validation acceptance criteria were met in all cases. Peak purity testing using contrast angle theory, relative absorbance and log A versus the wavelengths plots were presented. The % recoveries of the intact drugs were between 99.1% and 102.2% with RSD% values less than 1.6%. Application of the proposed HPLC methods indicated that the methods could be adopted to follow the stability of their formulations.

Development and application of a novel, dual-mode gradient, stability-indicating HPLC-DAD method for the simultaneous determination and purity assessment of mebeverine hydrochloride, diloxanide furoate and their corresponding major degradation products in combination with some gastrointestinal drugs in the form of oral doses.

A simple, precise, rapid, stability-indicating reversed phase high performance liquid chromatographic method with photodiode array detection was developed and validated for the determination of mebeverine hydrochloride in combination with sulpiride or with diloxanide furoate and metronidazole in the presence of their corresponding degradation products. Optimum separation was achieved in less than 10 min using an X-Bridge C18 column (150 mm × 4.6 mm i.d., 3.5 µm particle size); elution was accomplished via the application of a dual-mode solvent and flow rate gradient system. This elution system enables the separation of nine components within a cycle time of 15 min and with a resolution greater than 2.5. Detection was conducted at 230 nm, and purity assessment was performed using a photodiode array detector. The method has been validated with respect to specificity, linearity, accuracy, precision, limit of quantitation, limit of detection, robustness and ruggedness. The validation criteria were met in all cases. The developed HPLC method was successfully applied to commercial tablets. It was shown that this method is very sensitive to the determination of the degradation products, downward to 0.1 w/w% levels, which is far below the limits for testing these degradation products within their corresponding intact drugs.

Development and application of a validated stability-indicating high-performance liquid chromatographic method using photodiode array detection for simultaneous determination of granisetron, methylparaben, propylparaben, sodium benzoate, and their main degradation products in oral pharmaceutical preparations.

A simple, rapid, and sensitive RP-HPLC method using photodiode array detection was developed and validated for the simultaneous determination of granisetron hydrochloride, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of granisetron), sodium benzoate, methylparaben, propylparaben, and 4-hydroxybenzoic acid (the main degradation product of parabens) in granisetron oral drops and solutions. The separation of the compounds was achieved within 8 min on a SymmetryShield RP18 column (100 x 4.6 mm id, 3.5 microm particle size) using the mobile phase acetonitrile--0.05 M KH2PO4 buffered to pH 3 using H3PO4 (3+7, v/v). The photodiode array detector was used to test the purity of the peaks, and the chromatograms were extracted at 240 nm. The method was validated, and validation acceptance criteria were met in all cases. The robust method was successfully applied to the determination of granisetron and preservatives, as well as their degradation products in different batches of granisetron oral drops and solutions. The method proved to be sensitive for determination down to 0.04% (w/w) of granisetron degradation product relative to granisetron and 0.03% (w/w) 4-hydroxybenzoic acid relative to total parabens.

Development and application of a validated stability-indicating HPLC method for simultaneous determination of granisetron hydrochloride, benzyl alcohol and their main degradation products in parenteral dosage forms.

A simple, rapid and sensitive reversed phase high performance liquid chromatographic method using photodiode array detection was developed and validated for the simultaneous determination of granisetron hydrochloride, benzyl alcohol, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of granisetron) and benzaldehyde (the main degradation product of benzyl alcohol) in granisetron injections. The separation was achieved on Hypersil BDS C8 (250 mm x 4.6 mm i.d., 5 microm particle diameter) column using a mobile phase consisted of acetonitrile:0.05 M KH(2)PO(4):triethylamine (22:100:0.15) adjusted to pH 4.8. The column was maintained at 25 degrees C and 20 microL of solutions was injected. Photodiode array detector was used to test the peak purity and the chromatograms were extracted at 210 nm. Naphazoline hydrochloride was used as internal standard. The method was validated with respect to specificity, linearity, accuracy, precision, limit of quantitation and limit of detection. The validation acceptance criteria were met in all cases. Identification of the pure peaks was carried out using library match programmer and wavelengths of derivative optima of the spectrograms of the peaks. The method was successfully applied to the determination of the investigated drugs and their degradation products in different batches of granisetron injections. The method was proved to be sensitive for the determination down to 0.03 and 0.01% of granisetron degradation product and benzaldehyde, respectively, which are far below the compendia limits for testing these degradation products in their corresponding intact drugs.

Cognitive functions in protein-energy malnutrition: in relation to long chain-polyunsaturated fatty acids.

Aiming to find out a correlation between plasma LC-PUFA levels and neurodevelopmental status of malnourished infants, the present study was conducted on 42 infants suffering from PEM, with a mean age of 11.28 +/- 4.59 months. They were divided clinically into edematous and non-edematous groups. Fifteen age and sex matched well nourished apparently healthy infants were chosen to serve as controls. All patients were subjected to a 3-phase workup, while controls were subjected only to phase 1. Phase I: includes clinical assessment, laboratory investigations including plasma LC-PUFA levels and Neurodevelopmental assessment. In Phase II: An interventional program of 8 weeks duration; where all patients were receiving an initial supportive treatment followed by nutritional rehabilitation according to WHO guidelines, 1999 as well as developmental stimulation. According to the formula supplied to patients, they were randomly divided into either PUFA supplemented (+ve group) or nonBsupplemented (-ve group). In Phase III: All patients were re-assessed clinically and neurodevelopmentaly as well as re-evaluation for plasma LC-PUFA levels. The study revealed that, the mean plasma AA and DHA levels as well as the mean MDI and PDI scores of BSID-II were significantly lower in PEM patients compared to those levels after nutritional rehabilitation and to controls. Moreover, the mean MDI score was significantly lower in edematous subgroup compared to non-edematous one. Meanwhile, the mean rate of change in plasma DHA level was significantly higher in edematous subgroup compared to non-edematous one. However, there was no significant difference in the mean of rate of change in AA level or MDI and PDI scores between the 2 subgroups. Further, the mean rate of change in plasma AA and DHA levels as well as MDI score were significantly higher in PUFA +ve patients compared to PUFA Bve ones after nutritional rehabilitation. Finally, the study showed significant positive correlations between plasma AA and DHA levels and both MDI and PDI scores. From the course of this study we concluded that malnourished infants had impaired neurodevelopmental functions that could be related to the poor status of plasma LC-PUF. Thus, we recommend early intervention including nutritional rehabilitation and LC-PUFA supplementation as well as stimulation program, so as to have a better effect on future cognitive abilities of these infants.