Publications by authors named "Gomaa Mostafa-Hedeab"

12 Publications

  • Page 1 of 1

Haematological Indicators of Response to Erythropoietin Therapy in Chronic Renal Failure Patients on Haemodialysis: Impact of Angiotensin-Converting Enzyme rs4343 Gene Polymorphism.

Pharmgenomics Pers Med 2021 27;14:1055-1068. Epub 2021 Aug 27.

Pharmacology Department, Health Sciences Research Unit, Medical College, Jouf University, Sakaka, Kingdom of Saudi Arabia.

Purpose: This is the first cross-sectional study studying the changes in haematological indicators of the response to recombinant human erythropoietin (rHuEPO) therapy in chronic renal failure (CRF) patients on haemodialysis (HD) stratified according to ACE G2350A (rs4343) gene polymorphism.

Design: An observational cross-sectional study.

Setting: Nephrology department and Biochemistry and molecular biology department, faculty of medicine, Cairo University.

Patients: A total of 256 CRF patients on HD for at least six months (162 male and 103 female) and 160 healthy subjects (122 male and 38 female) were recruited in the current study after signing a consent form. ACE G2350A (rs4343) Insertion/Deletion (I/D) was tested, the association between ACE G2350A (RS4343) gene polymorphisms and patients response to rHuEpo was evaluated.

Results: ACE G2350A (rs4343) I/D was the most prevalent genotype, while I/I genotype was the lowest prevalent among patient or control subjects included in the study. D allele is the most prevalent allele, either among patients or the control group. Hemoglobin (Hb) level in patients with I/I and Deletion/Deletion (D/D) genotype was significantly higher compared to those with I/D genotype (P = 0.012 and P = 0.005, respectively). Serum iron in the I/D genotype was significantly higher than those with either I/I or D/D genotype (P = 0.045 and P = 0.018, respectively). Angiotensin-converting enzyme (ACE) content, total leukocytic count (TLC), and soluble erythropoietin receptor (sEpoR) were independent predictors of Hb level. The ACE gene, TLC, and serum iron were the independent factors that may affect the Haematocrit (Hct) level. ACE G2350A (rs4343) gene polymorphisms may affect the HD patient's responses to rHuEPOs.

Conclusion: In HD patients, screening for ACE G2350A (rs4343) gene polymorphisms before rHuEpo administration may help predict patient response.
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http://dx.doi.org/10.2147/PGPM.S311181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408344PMC
August 2021

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Drug Des Devel Ther 2021 31;15:2325-2337. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Methods: Three semi-synthetic series of compounds (, , and ) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of L. (-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds and showed superior inhibitory activity against EGFR (IC: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds and exhibited the highest cytotoxic activity with average IC values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
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http://dx.doi.org/10.2147/DDDT.S310820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178614PMC
May 2021

Therapeutic Value of miRNAs in Coronary Artery Disease.

Oxid Med Cell Longev 2021 12;2021:8853748. Epub 2021 Apr 12.

Cardiac Center, King Abdul Aziz Specialized Hospital, Sakaka, Saudi Arabia.

Atherosclerotic ischemic coronary artery disease (CAD) is a significant community health challenge and the principal cause of morbidity and mortality in both developed and developing countries for all ethnic groups. The progressive chronic coronary atherosclerosis is the main underlying cause of CAD. Although enormous progress occurred in the last three decades in the management of cardiovascular diseases, the prevalence of CAD continues to increase worldwide, indicating the need for discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Recently, several research groups established that microRNAs essentially regulate various cardiovascular development and functions, and a deregulated cardiac enriched microRNA profile plays a vital role in the pathogenesis of CAD and its biological aging. Numerous studies established that over- or downregulation of a single miRNA gene by ago-miRNA or anti-miRNA is enough to modify the CAD disease process, significantly prevent age-dependent cardiac cell death, and markedly improve cardiac function. In the light of more recent experimental and clinical evidences, we briefly reviewed and discussed the involvement of miRNAs in CAD and their possible diagnostic/therapeutic values. Moreover, we also focused on the role of miRNAs in the initiation and progression of the atherosclerosis plaque as the strongest risk factor for CAD.
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http://dx.doi.org/10.1155/2021/8853748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057887PMC
May 2021

Effects of Methylene Tetrahydro Folate Reductase Gene Polymorphisms on Methotrexate Toxicity in Egyptian Pediatric Acute Lymphocytic Leukaemia Patients.

Iran J Pharm Res 2020 ;19(4):387-393

Department of Clinical Pathology, National Cancer Institute, Cairo University, Egypt.

This study was designed to evaluate the effect of Methylenetetrahydrofolate reductase ( gene polymorphisms on MTX toxicity in pediatric Egyptian ALL patients. Ninety-Four of Pediatric ALL patients aged 3-13 years (7.6 ± 3.6) on oral maintenance dose of 50 mg/m weekly of MTX. MTHFR c.677C>T (rs1801133) and c.1298A>C (rs1801131) genotyping were performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The allele frequencies of were 42.6%, 46.8%, and 10.6% for , and respectively while c.1298A>C alleles frequencies were 62.7%, 24.5%, and 12.8% for , and respectively. None of the investigated polymorphism ( or alleles) was associated with either overall or site specific MTX toxicity regarding anemia ( 0.99) ( 0.4), platelets ( 0.4) ( 0.4), hepatotoxicity ( 0.4) ( 0.7), respectively. The results indicated that between genotypes, and were associated with hematopoietic toxicities 60.7% and 60% ( 0.2); platelet toxicities 76.2% and 80% ( 1) and, hepatotoxicities 40.5% and 60% ( 0.3), respectiv. In the genotypes, and AA presented hematopoietic toxicities 68.6% and 55.9% ( 0.2), platelet toxicities 82.9% 72.9% ( 0.3) and, hepatotoxicity 37.1% and 45.8% ( 0.5), respectively. No significant associations were detected between or polymorphisms and either overall or site specific MTX toxicity.
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http://dx.doi.org/10.22037/ijpr.2020.1101296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019867PMC
January 2020

Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats.

Rep Biochem Mol Biol 2020 Oct;9(3):278-290

Department of Medical Physiology, Faculty of Medicine, Cairo University, Egypt.

Background: Medications to prevent the development of NSAID-induced gastric ulcers have a large range of unpleasant side effects. Recent efforts have been focused on determining safer alternative nontoxic and natural forms of anti-ulcer treatments.

Methods: Twenty-four male rats were divided into 4 groups: 1: control group that received no treatment; 2: the ndomethacin-treated group that received 20 mg/kg of indomethacin for 2 days to induce the development of gastric ulcers; 3: quercetin-treated group that in addition to the indomethacin treatment, received 50 mg/kg of quercetin 6 hours after and then daily for 14 days and; 4: the melatonin-treated group which received 20 mg/kg of melatonin 6 hours after each indomethacin treatment and then daily for 14 days. All drugs were administered orally. The following parameters were assessed in each group: mean ulcer index of gastric tissue, gastric acid volume and pH, oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH), inflammatory markers: PGE-2, TNF-α, and IL-10, nitric oxide (NO) levels and the relative gene expression of BAX, BCL-2 and COX-2 by real time PCR.

Results: Our findings revealed that the indomethacin-treated group had a significantly increased (p< 0.05) ulcer index, gastric acid volume, and elevated levels of stress, inflammatory, and apoptotic markers compared to controls. In the groups that received quercetin or melatonin, these factors were all significantly decreased (p< 0.05). Between quercetin and melatonin, there was no significant difference in their gastroprotective effect.

Conclusion: Both quercetin and melatonin had protective antioxidant, anti-inflammatory and antiapoptotic activity against indomethacin-induced gastric ulcers.
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http://dx.doi.org/10.29252/rbmb.9.3.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816780PMC
October 2020

Chitosan-stabilized selenium nanoparticles alleviate cardio-hepatic damage in type 2 diabetes mellitus model via regulation of caspase, Bax/Bcl-2, and Fas/FasL-pathway.

Gene 2021 Feb 10;768:145288. Epub 2020 Nov 10.

Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt.

The present study was carried out to explore a novel strategy with the hypothesis that the combined treatment with standard antidiabetic drug metformin (MET) and chitosan stabilized nanoparticles (CTS-Se-NPs) may have a potential role on insulin level, hepatic damage and apoptosis, and cardiac injury markers of type 2 diabetes mellitus (T2DM) in rat model. T2DM was induced by a high fat diet (HFD) for 8 weeks and a single injection of a low dose streptozotocin (STZ) (35 mg/kg) in Sprague Dawley rats. A total number of one hundred rats were divided into five groups; the first served as a control (non-diabetic) group and the other four groups served as diabetic rats. The treatments were even mono or combined therapy by CTS-Se-NPs and/or MET for 8 weeks. A group was given only MET (500 mg/kg bw/day), another was administered only CTS-Se-NPs at a dose of 2 mg se/kg/day, while the last group was given both of them (co-treated group). Biochemical, molecular and histopathological analyses were conducted to figure out the efficiency of the treatment by the monotherapeutic mode or combination therapy on the insulin level, oxidants/antioxidants status, inflammatory mediators, hepatic and cardiac injury biomarkers and apoptotic/anti-apoptotic gene expressions. Our results indicated that HFD/STZ-induced toxic effects on the serum, hepatic and cardiac tissues including a remarkable elevation of the oxidative and inflammatory mediators, and up-regulation of the apoptotic genes (Bax, Caspase-3, Fas, Fas-L) expression. Histologically, the heart tissue revealed various degenerative, vascular and inflammatory alterations characteristic to murine cardiomyopathy. Besides, livers from HFD-STZ-treated rats showed numerous cytotoxic, circulatory and inflammatory alterations. Combined therapy with MET and CTS-Se-NPs resulted in a better remarkable anti-diabetic effect demonstrated by substantial decreases in fasting blood glucose and insulin levels, and elevated with up-regulation of anti-apoptotic gene (BCL-2) and down-regulation of apoptotic genes after 8 weeks of treatment than that revealed in the monotherapeutic strategy. In addition, it ameliorated the damage of cardiac and hepatic tissues and reduced lipid accumulation, and pro-inflammatory cytokines levels and restored the antioxidant capacity. It could be concluded that, the combined strategy applied in the current study have a potential role to limit the diabetic complications and restore insulin resistance to a higher extent than monotherapeutic strategy and could be considered a promising therapeutic alternative in T2DM rat model.
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http://dx.doi.org/10.1016/j.gene.2020.145288DOI Listing
February 2021

ACE2 as Drug Target of COVID-19 Virus Treatment, Simplified Updated Review.

Rep Biochem Mol Biol 2020 Apr;9(1):97-105

Pharmacology department, Medical College, Jouf University, KSA.

Background: Since its first appearance in December of 2019, regular updates around the world demonstrates that the number of new Corona Virus 2019 (COVID-19) cases are increasing rapidly, indicating that not only does COVID-19 exhibit a rapid spread pattern, but human intervention is necessary for its resolution. Up until today (27-5-2020) and according to the World Health Organization (WHO), the number of confirmed COVID-19 cases has surpassed 4.5 million with more than 307, 500 deaths. Almost all countries have been affected by COVID-19, and resultingly, various drug trials have been conducted, however, a targeted treatment remains to be made accessible to the public. Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19.

Methods: We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19.

Results: Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19.

Conclusion: ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.
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http://dx.doi.org/10.29252/rbmb.9.1.97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424417PMC
April 2020

Influence of Vitamin D Receptor Gene Polymorphisms on Response to Pegylated Interferon in Chronic Hepatitis B Egyptian Patients.

Rep Biochem Mol Biol 2018 Apr;6(2):186-196

Tropical medicine Department, Faculty of Medicine, Beni Seuf University, Beni Suef, Egypt.

Background: We explored the effect of vitamin D receptor gene () polymorphisms in response to PEG-IFN treatment in Egyptian chronic hepatitis B (CHB) patients.

Methods: Two hundred hepatitis B virus (HBV) patients (42.3±10.7 years) on PEG-IFN α-2a (180 µg /kg for 48 weeks) and one hundred control subjects (37.3 ±12 years) were enrolled in the study. Vitamin D levels and hepatitis B surface antigen (HBsAg) expression were assessed by ELISA. VDR polymorphisms FokI T>C (rs 10735810), BsmI A>G (rs 1544410), ApaI (rs7975253), and TaqI C>T (rs 731236), were genotyped using real-time PCR.

Results: Hepatitis B virus patients expressed significantly greater AST (p=< 0.00001) and ALT (P=< 0.00001), and significantly less vitamin D (P=0.01), than control subjects. Patients with Ff or ff alleles of the FokI single-nucleotide polymorphism (SNP), bb alleles of BsmI SNP, or TT alleles of the Taq1 single nucleotide polymorphisms (SNP) showed greater response to PEG-IFN therapy than those with the FF (P=0.02 and P=0.0002), Bb (P=0.023), or Tt/tt alleles (P=0.01 and P=0.004 respectively). Logistic stepwise regression showed that HBV DNA (r: 0.910, P< .00001), FokI SNP polymorphism (r: 0.919, (P=0.037) and bAt haplotype (r: .926, (P=0.043) are independent factors that determine PEG-IFN treatment response in the HBV-infected patients.

Conclusion: gene polymorphisms may be used as treatment response predictors in HBV patients receiving PEG-IFN. FokI SNP and bAt haplotype are independent factors that that can be used to determine PEG-IFN treatment responses in HBV-infected patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941126PMC
April 2018

Commiphora molmol resin attenuates diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis and Nrf2/ARE/HO-1 signaling.

Chem Biol Interact 2017 May 14;270:41-50. Epub 2017 Apr 14.

Department of Pharmacology, Faculty of Medicine, Beni-Suef University, Egypt.

The objective of the current study was to investigate the possible chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using DEN for initiation and PB as a promoting agent. The rats received 125 or 250 mg/kg C. molmol resin extract throughout the experiment. Both doses of myrrh improved liver function marker enzymes and prevented oval cells proliferation and the distortion of hepatic architecture. The pro-inflammatory cytokine interleukin-6, tumor markers, angiogenesis markers, lipid peroxidation and nitric oxide (NO) were significantly increased in DEN/PB-induced rats. In addition, the antioxidant defenses showed marked reduction in the liver of DEN/PB-induced rats. Oral administration of C. molmol extract to DEN/PB-induced rats significantly decreased circulating markers of inflammation, tumor proliferation and angiogenesis, and liver lipid peroxidation and NO. In addition, C. molmol markedly ameliorated the antioxidant defenses and up-regulated Nrf2 and hemeoxygenase (HO)-1 in the liver of DEN/PB-induced rats. In conclusion, these results provide evidence that C. molmol resin has a potent chemopreventive activity, possibly by up-regulating the Nrf2/HO-1 signaling and attenuation of inflammation, angiogenesis and oxidative stress.
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http://dx.doi.org/10.1016/j.cbi.2017.04.012DOI Listing
May 2017

Effects of telmisartan and pioglitazone on high fructose induced metabolic syndrome in rats.

Can J Physiol Pharmacol 2016 Aug 31;94(8):907-17. Epub 2016 Mar 31.

c Pharmacology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Metabolic syndrome (MS) is a cluster of hypertension, insulin resistance, dyslipidaemia, and hyperuricemia. This study was designed to assess the effect of telmisartan and pioglitazone on high fructose induced MS. Thirty-five male albino rats were classified into 5 groups: A, normal diet; B, high-fructose diet (HFD) subdivided into B1 (HFD only), B2 (telmisartan, 5 mg/kg), B3 (pioglitazone, 10 mg/kg), and B4 (telmisartan + pioglitazone). Administration of the drugs was started after the rats had been on HFD for 4 weeks and continued for 4 weeks. Body mass (BM), blood pressure (BP), uric acid (UA), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) were measured and the levels of fasting glucose and fasting insulin were estimated. Compared with group B1, telmisartan treatment significantly decreased BP, BM, serum glucose, insulin, UA, urea, cholesterol, TGA, and LDL and significantly increased HDL, whereas pioglitazone treatment significantly decreased BP, serum glucose, insulin, UA, urea, creatinine, cholesterol, TGA, and LDL and significantly increased HDL. Co-administration of pioglitazone + telmisartan significantly decreased insulin, urea, and creatinine compared with telmisartan alone. Combined telmisartan + pioglitazone allowed better control of BP, hyperglycaemia, insulin resistance, and the amelioration of BM increase that may be associated with pioglitazone treatment.
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http://dx.doi.org/10.1139/cjpp-2016-0090DOI Listing
August 2016

Ameliorating Effect of Olive Leaf Extract on Cyclosporine-induced Nephrotoxicity in Rats.

Iran J Kidney Dis 2015 Sep;9(5):361-8

Department of Pharmacology, College of Medicine, Beni Suef University, Beni Suef, Egypt; Department of Pharmacology, College of Pharmacy, Misurata University, Misurata, Libya.

Introduction: Olive leaves are traditionally used in the Mediterranean basin in many medical conditions for its potent antioxidant activity. Cyclosporine A, a well-known immunosuppressant, can induce nephrotoxicity through oxidative stress. This study investigated the effect of olive leaf extract (OLE) on cyclosporine-induced nephrotoxicity in rats.

Materials And Methods: Thirty Wistar rats (180 g to 200 g) were classified into 5 groups, each containing 6 rats. The first group received normal saline and served as control. The second group was treated with cyclosporine, 25 mg/kg for 21 days for nephrotoxicity induction. Groups 3 to 5 were treated with cyclosporine, 25 mg/kg in addition to different doses of OLE (40 mg/kg, 80 mg/kg, and 120 mg/kg), respectively, for 21 days. After 21 days, the rats' body weights were recorded and the rats were sacrificed. Blood samples were collected and the animals were necropsied. Both kidneys were removed, one for histopathological and one for antioxidant activity evaluations.

Results: Cyclosporine significantly reduced body weight and kidney weight; serum total protein, albumin, and sodium levels; and renal glutathione peroxidase, catalase, and superoxide dismutase. It also increased serum urea, creatinine, and calcium levels as compared to the control group. Groups 4 and 5 showed a significantly greater body weight and kidney weight; higher serum sodium, total protein, and albumin levels; greater glutathione peroxidase, catalase, and superoxide dismutase; and lower serum urea, creatinine, and calcium levels as compared to group 2.

Conclusions: Treatment with OLE can alleviate cyclosporine-induced nephrotoxicity when used in a proper dose.
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September 2015

Functional G1199A ABCB1 polymorphism may have an effect on cyclosporine blood concentration in renal transplanted patients.

J Clin Pharmacol 2013 Aug 30;53(8):827-33. Epub 2013 May 30.

College of Medicine, Beni-Suif University, Beni-Suif, Egypt.

Cyclosporine A (CsA) shows significant inter-individual variability in its pharmacokinetics, which may be due to polymorphisms in ABCB-1 genes coding for P-glycoprotein. The aim of this study was to explore the role of genetic polymorphisms of ABCB-1 in affecting the CsA blood concentrations in renal transplanted patients over the first 3 months after transplantation. Renal transplanted patients receiving CsA (n = 40) were genotyped for ABCB -1 C3435T (I1145I) and G1199A (S400N) polymorphisms. CsA blood concentrations were measured on Day 7, 30, and 90 after transplantation. G1199A variant showed higher CsA blood concentrations in stable patients, that was significant for trough levels (198 vs. 136 ng/mL on Day 7, P = .004, 196 vs. 125 ng/mL on Day 30, P = .007, 194 vs. 121 ng/mL on Day 90, P = .005 for stable vs. unstable groups). Polymorphisms of ABCB-1 have only a minor effect on CsA blood concentrations. The functional G1199A polymorphism can affect the drug levels more than non-functional C3435T. This polymorphism might be of a potential prognostic value in renal transplanted patients.
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http://dx.doi.org/10.1002/jcph.105DOI Listing
August 2013
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