Osama Badary

Ameliorative Effects of Resveratrol on Liver Injury in Streptozotocin-Induced Diabetic Rats

The objective of this study was to investigate the ameliorative property and potential mechanism of resveratrol (RVT) in a dose of 10 mg/kg for 15 consecutive days against liver injury in streptozotocin‐induced diabetic rats. Diabetic rats significantly (P < 0.05) exhibited liver injury manifested by increased aspartylaminotransferase, alanine aminotransferase, and bilirubin; disturbed liver weight to body weight; and confirmed by hematoxylin and eosin staining. Liver from diabetic rats exhibited significant increase in malondialdehyde level and significant decrease in reduced glutathione, glutathione‐S‐transferase, quinone reductase, catalase, and superoxide dismutase. Diabetic rats showed significant disturbance in serum lipid profile. Treatment with RVT significantly (P < 0.05) abrogated diabetes‐induced perturbation in these parameters and liver histology. These data suggest that RVT treatment is associated with promising hepatoprotective effect against diabetes‐induced liver damage via reduction of serum glucose level and oxidative damage and improving serum lipid profile.

Reducing prescribing errors in the paediatric intensive care unit: an experience from Egypt

Aim:  To investigate the impact of different measures, implemented by clinical pharmacists, on prescribing error rates in a paediatric intensive care unit (PICU) in Cairo, Egypt.

Transcriptional and posttranscriptional regulation of CYP1A1 by vanadium in human hepatoma HepG2 cells

We recently demonstrated that V5+ downregulates 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels in Hepa 1c1c7 cells through transcriptional mechanism. Therefore, it is important to investigate whether similar changes occur in humans. For this purpose, we examined the effect of V5+ (as ammonium metavanadate, NH4VO3) on the expression of aryl hydrocarbon receptor (AhR)-regulated gene; cytochrome P450 1A1 (CYP1A1) at each step of the AhR signal transduction pathway in human hepatoma HepG2 cells. Our results show a significant reduction in TCDD-mediated induction of CYP1A1 mRNA, protein, and activity levels after V5+ treatment in a dose-dependent manner. Investigating the effect of co-exposure to V5+ and TCDD at transcriptional levels revealed that V5+ significantly inhibited TCDD-mediated induction of AhR-dependent luciferase reporter gene expression. Looking at the posttranscriptional level, V5+ did not affect CYP1A1 mRNA stability, thus eliminating the possible role of V5+ in modifying CYP1A1 gene expression through this mechanism. On the other hand, at the posttranslational level, V5+ was able to significantly decrease CYP1A1 protein half-life contributing to the inconsistency between catalytic activity and transcriptional level. Importantly, we showed that V5+ did not significantly alter the heme oxygenase-1 mRNA level, thus eliminating any possibility that V5+ might have decreased CYP1A1 activity through affecting its heme content. This study demonstrates for the first time that V5+ downregulates the expression of CYP1A1 at the transcriptional, posttranscriptional and posttranslational mechanisms in the human hepatoma HepG2 cells.

Identification of Suitable Endogenous Normalizers for qRT-PCR Analysis of Plasma microRNA Expression in Essential Hypertension

Circulating microRNAs (miRNAs) are promising biomarkers for many diseases. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a gold standard for miRNA expression profiling that requires proper data normalization. Since there is no universal normalizer, it is recommended to evaluate normalizers under every experimental condition. This study describes the identification of suitable endogenous normalizer(s) (ENs) for plasma miRNA expression in essential hypertension. Expression levels of 5 candidate ENs and 2 plasma quality markers were determined by qRT-PCR in plasma samples from 18 hypertensive patients and 10 healthy controls. NormFinder, GeNorm, and DataAssist software programs were used to select the best EN(s). Expression levels of the 5 candidate ENs were also analyzed in urine samples from hypertensive patients and compared to the plasma samples of the hypertensive patients. Among the analyzed candidates, hsa-miR-92a-3p was identified as the best EN, and hsa-miR-21-5p and hsa-miR-16-5p as the next best. Moreover, hsa-miR-92a-3p showed the most consistent expression between plasma and urine. In conclusion, this study showed that hsa-miR-92a-3p, hsa-miR-21-5p, and hsa-miR-16-5p may be used as normalizers for plasma miRNA expression data in essential hypertension studies.

Implementation of clinical pharmacy services in a pediatric dialysis unit

BackgroundEnd-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis.MethodsFifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care.ResultsAfter 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p = 0.0001), serum phosphorus level (p = 0.006) and parathyroid hormone level (p = 0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p = 0.001) after intervention versus baseline. Serum calcium level significantly increased in test group (p = 0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p = 0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores.ConclusionsPharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis.

The clinical outcome of adjuvant therapy with black seed oil on intractable paediatric seizures: a pilot study

AimTo evaluate the effect of black seed oil, as add-on treatment to antiepileptic drugs (AEDs), on seizure frequency and severity as well as oxidative stress in intractable epilepsy patients.MethodsA prospective, randomised, single-blinded, controlled, crossover pilot study. Five healthy children were included as controls. Thirty intractable epileptic children were randomly assigned to either Group I or II. Group I received placebo for four weeks, followed by a two-week washout period, and subsequently black seed oil for four weeks. Group II received the same intervention but in the reverse order. All patients received AEDs throughout the study period. Prior to allocation, all patients underwent a neurological assessment and evaluation of oxidative stress markers; total antioxidant capacity (TAC) and malondialehyde (MDA). Patients were assessed at Weeks 4 and 10 for oxidative stress markers and seizure frequency and severity.ResultsAt baseline, both groups (I, II) had significantly lower serum TAC levels relative to healthy controls (p=0.007), while MDA levels were unchanged. After the 4-week period of black seed oil administration, there was no significant difference between the two groups with regards to seizure frequency, severity, or oxidative stress markers (TAC and MDA; p>0.05). Eight patients had>50% reduction in seizure frequency/severity after black seed oil versus placebo.ConclusionChildren with intractable epilepsy show evidence of oxidative stress. Administration of 40–80 mg/kg/day of black seed oil as add-on therapy did not alter either oxidative stress markers or seizure frequency or severity in intractable epileptic patients.

A Prospective Pharmacokinetic Study of Docetaxel in Breast Cancer Patients in Relation to CYP3A4 Activity

Abstract Purpose: To study the correlation between pharmacokinetics & pharmacodynamic of docetaxel and CYP3A4 activity in Egyptian cancer patients. Patients and methods: Fourteen Egyptian female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, had received prior chemotherapy regimen, were treated with single-agent docetaxel (100 mg/m2), given every 21 days. Hydrocortisone 300 mg IV was administered 2 days before docetaxel treatment and Cytochrome 3A4 activity was determined by measuring the level of urinary metabolites of 6β-hydroxy cortisol (6β-OHF) and cortisol (FC). For the pharmacokinetic study, Blood samples were taken before and after IV infusion for 1 hr of 100 mg/m2 docetaxel. The level of the drug was determined using HPLC and the correlation between pharmacokinetics and CYP3A4 activity were determined. Results: After cortisol administration, the total amount of 24-hour urinary 6β-OHF and FC were19.97 ± 10.43 and 16.84 ± 10.36 mg/24 h (mean ± SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86 ± 1.933. The pharmacokinetic parameters of docetaxel were clearance 19.9 ± 4.5 L/hr, the volume of distribution 65.6 ± 28.6 L (mean ± SD) and AUC 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr) ± SD). A significant correlation was found between 6β-OHF/FC ratio and neutropenia (p=0.04) in addition correlation between 6β-OHF and Cmax (p=0.04). Conclusion: The interpatient variability of CYP3A4 activity in each patient could be predicted by measuring the total amount of 24 hour urinary 63-OHF after cortisol administration. Individualized dosing to optimize drug exposure for each patient could be performed based on this method. A farther study of fixed versus individualized dosing of docetaxel is needed to determine whether individualized chemotherapy with the application of this method can reduce PK and toxicity variability.

Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes

Abstract Objectives: Thymoquinone (TQ), the main active ingredient in Nigella sativa oil, exhibits various bioactivities. This study aimed to investigate the effect of TQ on neurobehavioral and neuropathological alterations induced by aluminum trichloride (AlCl3) and D-galactose (D-gal)-in male rats and to explore the related mechanisms. Methods: D-gal (60 mg/kg day) and AlCl3 (10 mg/kg day) were given intraperitoneally (i.p.) once daily for 42 days and after 4 weeks TQ was concomitantly administered intragastrically (i.g.) (20 mg/kg/day) once daily for 14 days. Then, memory function was evaluated by Morris water maze test (MWM). Superoxide dismutase (SOD), Total antioxidant capacity (TAC), Acetylcholinesterase (AChE) activities, and malondialdehyde (MDA), nitric oxide (NO), brain-derived neurotrophic factor (BDNF), and B-cell lymphoma-2 (Bcl-2) levels in whole brain were assessed with the biochemical technique. Tumor necrosis factor-alpha (TNF-α) and Acetylcholine (ACh) were also assessed using an immunohistochemical technique. Results: Administration of TQ significantly improved cognition. In addition, TQ significantly increased SOD and TAC and decreased AChE activities. It also decreased MDA and NO levels as well as TNF-α immunoreactivity and increased BDNF and Bcl-2 levels as well as ACh immunoreactivity. Discussion: Our results indicate that TQ prevents D-gal/AlCl3-induced cognitive decline by enhancing cholinergic function and synaptic plasticity as well as attenuation of oxidative damage, neuronal apoptosis, and neuroinflammation. These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders.

Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling

Alzheimer’s disease (AD) is characterized by a robust inflammatory response elicited by the accumulation and deposition of amyloid-β (Aβ) within the brain. Aβ induces detrimental inflammatory responses through toll-like receptors (TLRs) signaling pathway. Thymoquinone (TQ), the main active constituent of Nigella sativa oil, has been reported by several previous studies for its potent anti-inflammatory effect. The aim of this study is to elucidate the effect of TQ in improving learning and memory, using a rat model of AD induced by a combination of aluminum chloride (AlCl3) and d-galactose (d-Gal). TQ was administered orally at doses of 10, 20, and 40 mg/kg/day for 14 days after AD induction. Memory functions were assessed using the step through passive avoidance test. Amyloid plaques were shown to be present using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) levels in brain were assessed via ELISA and profiling TLR-2, TLR-4, myeloid differential factor 88, toll–interleukin-1 receptor domain-containing adapter-inducing interferon-β, interferon regulatory factor 3 (IRF-3), and nuclear factor-κB (NF-κB) expressions via real-time polymerase chain reaction. TQ improved AD rat cognitive decline, decreased Aβ formation and accumulation, significantly decreased TNF-α and IL-1β at all levels of doses and significantly downregulated the expression of TLRs pathway components as well as their downstream effectors NF-κB and IRF-3 mRNAs at all levels of doses (p < 0.05). We concluded that TQ reduced the inflammation induced by d-Gal/AlCl3 combination. It is therefore reasonable to assign the anti-inflammatory responses to the modulation of TLRs pathway.

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib

AIM This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.