Wael Abu Dayyih

Pioglitazone Hcl Levels and Its Pharmacokinetic Application in Presence of Sucralose in Animals Serum by HPLC Method

Purpose: to develop a simple, valid and rapid chromatographic method for quantifying pioglitazone HCl in rats serum in order to study the pharmacokinetic parameters of pioglitazone HCl in rats serum fed with sucralose simultaneously for examination of interaction possibility between pioglitazone HCl and sucralose in rats. Methods: In our developed method of analysis, mobile phase was consisted of [51.50%] acetonitrile and [48.50%] 0.025 mM ammonium acetate with pH of 8, column of separation was C8 at temperature of 40°C using injection volume of 90 μl, mobile phase flow rate was 1 ml/min and samples run time was 10 min, the signals were monitored and analyzed at λ=269 nm and sildenafil citrate was used as internal standard. Pioglitazone was given to rats orally of [10mg/kg] dose while sucralose was given with [11 mg/kg/day] dose. Results: A successful HPLC method was validated and developed to quantify pioglitazone HCl in rats serum, overall intra-day precision and accuracy were reasonable with CV % values range [0.16-3.54] and accuracy % range [ 98.4-107.9], while inter-day precision and accuracy showed accepted precision with CV% range [ 0.15- 4.13] and accuracy % range [99.35-103.99]. The coefficient of correlation was 0.9991 with reasonable sensitivity and selectivity. Combination effect of pioglitazone with sucralose on pioglitazone serum profile was demonstrated as strong statistical effect according to Cohen’s d and significant P values too. Conclusion: A successful HPLC method was validated and developed to quantify pioglitazone HCl in rats serum, combination effect of pioglitazone with sucralose over all time intervals of pioglitazone serum profile was demonstrated as strong statistical effect.

Nationality, Gender, Age, and Body Mass Index Influences on Vitamin D Concentration among Elderly Patients and Young Iraqi and Jordanian in Jordan

Vitamin D is necessary for maintaining and regulating calcium levels; thus, insufficiency of vitamin D increases the risk of many chronic diseases. This study aimed to examine vitamin D levels among Jordanian and Iraqi volunteers and find the relation between vitamin D level and lipid profile patients. Vitamin D levels were evaluated using enzyme-linked immunosorbent assay. For young healthy group subjects, vitamin D levels were 20.60 ± 5.94 ng/mL for Jordanian and 27.59 ± 7.74 ng/mL for Iraqi. Vitamin D concentrations for young males and females were 25.82 ± 8.33 ng/mL and 21.95 ± 6.39 ng/mL, respectively. Females wearing hijab were 20.87 ± 6.45 ng/mL, while uncovered females were 23.55 ± 6.04 ng/mL. For >40 years Iraqi subjects, vitamin D level for healthy was 29.78 ± 9.49 ng/mL and 23.88 ± 7.93 ng/mL for hyperlipidemic subjects. Vitamin D levels for overweight and obese healthy groups were significantly higher (P < 0.050) than those for the hyperlipidemic patients groups. Vitamin D levels for males were significantly higher than females and were significantly higher for healthy than those hyperlipidemic Iraqi patients. These findings showed that vitamin D levels are affected by age, nationality, gender, and health statues and highlight the importance of vitamin D supplementation for groups with low levels particularly old, hijab wearing females, and hyperlipidemic groups.

Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation

The combination of cytotoxic drugs with immunotherapy should be more effective than monotherapy alone since both therapeutic modalities may target different mechanisms. In addition, combination therapy may reduce adverse events associated with cytotoxic drugs. Eriobotrya japonica hydrophilic butanol-treated extract (EJWR) was found to modulate cytokines by enhancing IL-12, IFN-γ and TNF-α in vitro and in vivo and within tumor microenvironment. This was associated with enhancing survival time of mice bearing intra-peritoneal MCA fibrosarcoma (MCA FS). In the present work, we evaluated the combination of EJWR with doxorubicin (Dox) on MCA FS cytotoxicity using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay in the absence and presence of spleen cells or Natural Killer (NK) lymphocytes from tumor bearing mice. The results showed that Dox exhibited mild cytotoxicity to healthy spleen cells and EJWR reversed such cytotoxicity. In addition, increasing concentrations of Dox induced 40% (p<0.01) MCA FS cytotoxicity. This percent increased significantly to 60% at Dox 5 μM when co-cultured with NK cells from tumor bearing mice and increased further to 80% (p<0.01) when Dox was combined with EJWR. The latter increase in cytotoxicity was significantly (p<0.01) higher than each agent alone. This enhancement was associated with significant production of TNF-α and retaining IFN-γ levels from NK cells lysates. This concluded that the immunomodulator, EJWR, mediates NK activation and enhances Dox- induced MCA FS cytotoxicity.

2-Bromo-1,3-diisopropyl-4,5-dimethyl-1H-imidazol-3-ium dicyanidoargentate

The title structure, (C11H20BrN2)[Ag(CN)2)], is built up from an approximately C 2v-symmetric imidazolium cation and a nearly linear dicyanidoargentate anion [N—Ag—N = 176.6 (9)° and Ag—C—N = 178.8 (9) and 177.2 (11)°]. These two constituents are linked by a remarkably short interaction between the Br atom of the imidazolium cation [C—Br = 1.85 (3) Å] and one N atom of the cyanidoargentate anion [Br⋯N = 2.96 (2) Å], which is much less than the sum of the van der Waals radii (3.40 Å). The crystal studied was twinned by merohedry.

The status of global DNA methylation in the spermatozoa of smokers and non-smokers

RESEARCH QUESTION Does regular smoking affect semen quality and the levels of DNA methylation in mature human spermatozoa? DESIGN Spermatozoa from 109 men were evaluated (55 smokers and 54 non-smokers). DNA was extracted from purified spermatozoa, and DNA methylation was quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS Global DNA methylation of non-smokers is significantly lower (P < 0.001) than that of smokers (4.85 ± 2.72 and 7.08 ± 1.77 ng/μl, respectively). Moreover, the mean global DNA methylation levels were significantly correlated (r = 0.22;P = 0.02) with non-condensed chromatin in the spermatozoa. Levels of non-condensed chromatin were significantly higher (P < 0.001) in smokers (29.75 ± 9.38%) compared with non-smokers (20.96 ± 11.31%). Furthermore, global sperm DNA methylation was negatively correlated with high significance (P < 0.010) with sperm: count (r = -0.27), motility (r = -0.30) and vitality (r = -0.26). CONCLUSION Smoking interferes with DNA methylation. Also, DNA methylation is significantly correlated with sperm parameters and sperm non-condensed chromatin. These data emphasize another detrimental effect of smoking on male fertility. DNA methylation may, therefore, be considered as a fertility marker in men.

Investigation of Possible Pharmacokinetic Interaction Between Ivabradine and Carvedilol in Rats using High Performance Liquid Chromatography/Mass Spectroscopy

Ivabradine is a new hyperpolarization-activated cyclic nucleotide-gated channel (HCN) blocker. It has been approved by the FDA in 2015 as a part of management of stable angina and congestive heart failure. The aim of this study was to investigate the possibility of pharmacokinetic interaction of a proposed combination of ivabradine and the âblocker carvedilol in rats using spectroscopy technique. A simple, rapid and sensitive method for validation and determination of ivabradine and carvedilol in the rats’ plasma was developed using HPLC/MS. The method was successfully developed and validated in terms of linearity, precision and accuracy which were within the values accepted by European Medical Agency and International Conference of Harmonization guidlines. Ivabradine and Carvedilol were given both intravenously and orally each alone and as oral combination to fasted SpragueDawley rats. Blood samples were withdrawn on scheduled time intervals up to 36 hours and analyzed for each drug. Results showed significant increase in bioavailability of both drugs in combination specially on elimination level expressed in decrease clearance and increase in the half-life for both drugs. In conclusion, a significant kinetic interaction occurred when ivabradine was given orally with carvedilol which makes dose adjustment of both drugs of much importance.

Ring opening of cyclobutane in 1,3-dimethyl-5-methylenebarbituric acid dimer by various nucleophiles

Abstract The reactivity of cyclobutane moiety in 1,3-dimethyl-5-methylenebarbituric acid dimer (5) towards different nucleophiles was investigated. New derivatives of 5-(substituted methyl)-1,3-dimethylbarbiturate 6–13 were prepared in good yields using various aliphatic amines, cyanide anion, and Ph3P, Ph3As, Ph3Sb. Chemical structures of synthesized products were characterized using NMR, MS, and elemental analysis. The reaction of thiophenoxide and thiocyanate nucleophiles with 5 did not give any new products.

A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear over the calibration range 1.0–200.0 ng/ml. Stability was >85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

The Effect of Some Fruit Juices on Glimepiride Pharmacokinetic in Rat Plasma by Using High Performance Liquid Chromatography-Mass Spectrometry

Food-drug interactions may affect pharmacokinetics or pharmacodynamics of a drug. Failure to identify and properly manage drug-nutrient interactions may lead to serious consequences. In this study, we try to develop and validate a simple and sensitive analytical method for measuring of glimepiride in rat plasma and examine of any possible interactions of glimepiride with different fruit juices. A mixture of 80 % methanol and 20 % of 0.1% FA in water was used as a mobile phase and ACE 5 C18 (50 X 2.1 mm, 5ìm) column were employed; and clarithromycin was used as internal standard. This method was confirmed in terms of linearity, precision, accuracy, stability and system suitability. The validated method was used to examine the effects of grapefruit and licorice of glimepiride pharmacokinetic in rat plasma. The kinetic data shows that glimepiride plasma level was high when combined with licorice, and at the same level when combined with grapefruit. The administration of grapefruit juice concomitantly with glimepiride shows insignificant effect on its Cmax, elimination half-life and clearance (P>0.05). While for licorice juice, it has no significant effects on glimepiride pharmacokinetic parameters. A simple and sensitive analytical method for determination of glimepiride in rat plasma has been developed and validated by using HPLC-MS. Also, we found that fruit juices can alter glimepirides pharmacokinetic if they were taken simultaneously.

Investigation of possible pharmacokinetic interaction of metformin with sugar replacement sweeteners in rats.

Metformin is widely used for type II diabetes. Sugar replacement sweeteners such as Aspartame and Stevia, are usually consumed concomitantly with other antidiabetics by patients The aim of this work is to investigate possible effects of two types of sweeteners; stevia and aspartame on the pharmacokinetic parameters of metformin in rats. A simple, validated bio-analytical HPLC method was developed to measure metformin in rat plasma. Three groups of rats, each of eight were subjected to this study. The first group was given metformin solution 20mg/kg alone , the second group was given 20 mg/kg metformin with 4mg/kg stevia and the third group was given 20 mg/kg metformin with 10 mg/kg aspartame on fasting state. Blood samples were taken on scheduled time interval up to 6 hours and analyzed for metformin concentration. Pharmacokinetic parameters were calculated by Non-Compartmental Model and data were interpreted. The results showed that administration of these two sweeteners did not have high effect on pharmacokinetics of metformin.