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BACKGROUND: Resistance to antiepileptic drugs (AEDs) remains one of the main challenges to neurologists. Polymorphisms of drug efflux transporters such as multidrug resistance (MDR1) gene and target sites such as the nucleus accumbens-associated 1 (NAC1) gene have been suggested to influence the responsiveness to treatment. AIM: Evaluation of the association of MDR1 and NAC1 polymorphisms with AEDs resistance among Jordanian epileptic patients. SUBJECTS AND METHODS: 86 Jordanian epileptics were included in the study. DNA was extracted and genotyping was conducted by polymerase chain reaction followed by sequencing. Nine single nucleotide polymorphisms (SNPs) on the MDR1 gene and six SNPs on the NAC1 gene were investigated. RESULTS: MDR1 and NAC1 polymorphisms don't seem to influence the resistance to AEDs at the genotype or allele level. However, a strong association was found between MDR1 rs2032588 (OR = 5; 95%CI = [1.3-18.8], p = 0.01) and AEDs resistance among males at the allele level. Also, data revealed an association between MDR1 rs1128503 and AEDs resistance among females at the allele level. CONCLUSION: The data suggest that MDR1 and NAC1 polymorphisms do not influence the AEDs resistance among Jordanian epileptics. However, there is a gender-dependent association between MDR1 polymorphisms and resistance to AEDs at two SNPs (rs2032588 and rs1128503).
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Anticonvulsivantes , Epilepsia , Masculino , Femenino , Humanos , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Estudios Transversales , Jordania , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/uso terapéutico , Frecuencia de los Genes , Resistencia a Múltiples Medicamentos/genética , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Polimorfismo de Nucleótido Simple , GenotipoRESUMEN
BACKGROUND: Pharmacogenetics (PGx) science has evolved significantly with a huge number of studies exploring the effect of genetic variants on interindividual variability of drug response. In this study, we assessed the knowledge, attitudes and preparedness of Pharm-D vs. medical students toward PGx. METHOD: A paper-based cross-sectional survey was performed. A pilot-tested questionnaire consisting of 21 questions (demographics 5, knowledge 6, attitude 6, and preparedness 4) was administered to 900 healthcare students at different years of study. Descriptive and inferential analyses were used. RESULTS: Out of the 900 students approached, 852 (94.7%) completed the questionnaire. The overall students' mean (SD) percentage knowledge score (PKS) was poor [46.7% (18.7)]. The mean (SD) attitude and preparedness scores for all students were 4.68 (1.32), and 1.9 (1.40), respectively, indicating overall positive attitudes, but low preparedness to apply PGx to clinical care. Pharm-D students' overall PKS was significantly higher than medical students (P < 0.0001). However, there was no significant difference in terms of attitude and preparedness scores. Interestingly, as the year of study increased, the knowledge scores increased as well, with 6th-year students had the highest knowledge scores, while preparedness in applying PGx was higher among the junior students (the 3rd and 4th year of study). CONCLUSION: Pharm-D and medical students have inadequate knowledge and low preparedness despite the overall positive attitude towards PGx. There is a need to raise knowledge and to enhance the level of preparedness of medical and Pharm-D students towards PGx and its applications in clinical practice.
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Estudiantes de Medicina , Actitud del Personal de Salud , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Jordania , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c). METHODS: A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined. RESULTS: Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P<.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P = .002) and HbA1c (ρ = 0.56, P<.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0 .37, P<.001). CONCLUSION: We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values. ABBREVIATIONS: ADA = American Diabetes Association BMI = body mass index CA 19-9 = carbohydrate antigen 19-9 CEA = carcinoembryonic antigen CRP = C-reactive protein DM = diabetes mellitus HbA1c = glycated hemoglobin JUH = Jordan University Hospital T2DM = type 2 diabetes mellitus ρ = Spearman's correlation coefficient.
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Antígeno Carcinoembrionario/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Jordania , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The prevalence of short stature (SS) and underweight in Jordan on a national level is unknown. This study aimed to investigate, on a national level, the prevalence of short stature (SS), underweight, overweight, and obesity among school aged children in Jordan. METHODS: This cross-sectional study was conducted from May 2015 to January 2016 and included 2702 subjects aged 6-17 years. Jordan was classified into 3 regions; North, Center (urban), and South (rural). Public and private schools were randomly selected from a random sample of cities from each region. The socioeconomic status of the sampling locations was assessed using several indicators including education, income, healthcare and housing conditions. For each participating subject, anthropometrics were obtained. SS, underweight, overweight and obesity were defined using Center of Disease Control's (CDC) growth charts. Median Z-scores for each region, age and gender were calculated. RESULTS: The Central and Northern regions enjoyed higher socioeconomic status compared to rural Southern regions. The overall prevalence of SS, underweight, overweight, and obesity were 4.9 %, 5.7 %, 17.3 %, and 15.7 %, respectively. SS and underweight were most prevalent in the rural South, while obesity was highest in the Central region. Females were more likely to be overweight, while males were more likely to be obese. Private schools had higher prevalence of obesity and overweight than public ones. CONCLUSIONS: Variations in height and weight among Jordanian school children might be affected by socioeconomic status.
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Estatura , Estado de Salud , Obesidad Infantil/epidemiología , Adolescente , Índice de Masa Corporal , Niño , Estudios Transversales , Femenino , Humanos , Jordania/epidemiología , Masculino , Sobrepeso/epidemiología , Prevalencia , Distribución por Sexo , Clase Social , Delgadez/epidemiologíaRESUMEN
OBJECTIVE: The prevalence of isolated growth hormone deficiency (IGHD) among short-statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short-statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity. DESIGN: We conducted a 24-month cross-sectional observational trial at an outpatient tertiary care center in Amman, Jordan. PATIENTS: We obtained detailed family histories, medical evaluations and laboratory tests for 94 short-statured children (50 boys and 44 girls aged 6-16 years). MEASUREMENTS: Complete and partial GHD were defined as peak GH responses of 5 and 7 µg/l (15 and 21 mIU/l) [IRMA/DiaSorin®], respectively, in both exercise and insulin tolerance tests. RESULTS: GHD was diagnosed in 69·1% of the short children, including 86% (43/50) of the children of consanguineous parents (83·3%, 93·8% and 81·8% of children of first cousins, first cousins once removed and second cousins, respectively) and 50% (20/44) of the children of nonconsanguineous parents (P = 0·039, 0·002 and 0·013, respectively). However, there was no statistically significant difference in the prevalence of small pituitary MRI between GH-deficient children of consanguineous parents and those of nonconsanguineous parents (28·6% vs 13·6%, P = 0·3). CONCLUSIONS: The prevalence of IGHD among referred short children in Jordan was exceptionally high and significantly higher in the children of CM. In countries where CM is common, preconception counselling and rigorous surveillance for GHD in short children may be indicated.
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Consanguinidad , Enanismo Hipofisario/epidemiología , Adolescente , Niño , Estudios Transversales , Enanismo Hipofisario/genética , Femenino , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/genética , Humanos , Jordania , Masculino , Prevalencia , Centros de Atención TerciariaRESUMEN
Thrombosis is a major cause of morbidity and mortality worldwide. Genetic factors are one component of thrombosis. We studied the prevalence of two mutations that are known risk factors in the pathogenesis of arterial and venous thrombosis in the genetically isolated Circassian population in Jordan. Factor II G20210A and Factor V Leiden single nucleotide polymorphisms were analysed by polymerase chain reaction and restriction fragment length polymorphism method in 104 random unrelated subjects from the Circassian population in Jordan. The prevalence rates among the Circassian population in Jordan for Factor II G20210A was 12.2% and for Factor V Leiden was 7.7%. We have shown that the population is in Hardy-Weinberg equilibrium and that the prevalences of both mutations are within the range of other ethnic groups. This is the first study to describe Circassian health related genetic characteristics in Jordan. Such population-based studies will contribute to understanding the interaction between genetic and environmental risk factors. It will remain to be seen whether carriers of Factor II G20210A and Factor V Leiden are more likely to develop thrombosis. This issue should be studied in the future to determine the need for screening of these mutations particularly in thrombophilia patients.
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Factor V/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Protrombina/genética , Trombofilia/genética , Trombosis/genética , Adolescente , Adulto , Anciano , Sustitución de Aminoácidos , Femenino , Humanos , Jordania/epidemiología , Jordania/etnología , Masculino , Persona de Mediana Edad , Mutación Missense , Trombofilia/etnología , Trombofilia/mortalidad , Trombosis/etnología , Trombosis/mortalidadRESUMEN
Background: The aim of this study was to evaluate whether the voltage-gated sodium channel alpha subunit 1 (SCN1A) gene polymorphisms influence the responsiveness of Jordanian epileptic patients to antiepileptic drugs (AEDs). Methods: A total of 72 AEDs-treated epileptics were polymerase chain reaction (PCR)-genotyped for six single nucleotide polymorphisms (SNPs), including SCN1A rs2298771, rs3812718, rs3812719, rs2217199, rs2195144 and rs1972445. Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. The six SNPs haplotypes were examined, and the linkage disequilibrium (LD) was assessed. Results: The genotypes of drug-resistant and drug-responsive groups were in Hardy-Weinberg equilibrium. Three genetic polymorphisms of the SCN1A gene seemed to influence the resistance to AEDs, on the level of alleles and genotypes. Data revealed that rs2298771 G allele, rs3812719 C allele, and rs2195144 T allele increased the risk of developing AEDs-resistance (OR=2.9; 95%CI= 1.4-5.9, p=0.003; OR=2.4; 95%CI=1.2-4.7, p=0.01; OR=2.3; 95%CI=1.2-4.7, p=0.01), respectively. Haplo type analysis of SCN1A polymorphisms revealed high-degree LD associated with resistance to AEDs. A synergetic effect appears with highly significant association in GCCATG haplotype of rs2298771, rs3812718, rs3812719, rs2217199, rs2195144, and rs1972445 respectively (OR=2.8; 95%CI=1.5-6.2, p=0.002). Conclusions: Data suggests that SCN1A polymorphisms could influence the resistance to AEDs in Jordanian epileptics at three SNPs (rs2298771; rs3812719; rs2195144). Additionally, haplotype analysis indicated a substantial degree of LD between the six SCN1A polymorphisms. Further investigation with larger sample size is needed to confirm the results of the current study.
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Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). One of the subfamilies is UGT1A. Allele frequencies in UGT1A4 differ among ethnic groups. The aim of this study was to determine the allelic frequency of two most common defective alleles: UGT1A4*2 and UGT1A4*3 in a Jordanian population. A total of 216 healthy Jordanian Volunteers (165 males and 51 females) were included in this study. Genotyping for UGT1A4*1, UGT1A4*2 and UGT1A4*3 was done using a well established polymerase chain reaction-restriction fragment length polymorphism test. Among 216 random individuals studied for UGT1A4*2 mutation there were 26 individuals who were heterozygous, giving a prevalence of 12% and an allele frequency of 6.5%. Only one individual was homozygous for UGT1A4*2. The UGT1A4*3 mutation was detected as heterozygous in 9 of 216 individuals indicating a prevalence of 4.2% and allele frequency of 3.5%. Three individuals were homozygous for the UGT1A4*3 indicating a prevalence of 1.4%. The prevalence of UGT1A4*2 is similar to the Caucasians but different from other populations whilst the UGT1A4*3 prevalence in the Jordanian population is distinct from other populations. Our results provide useful information for the Jordanian population and for future genotyping of Arab populations in general.
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Frecuencia de los Genes , Glucuronosiltransferasa/genética , Femenino , Variación Genética , Genotipo , Humanos , Jordania , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (2 and 3), CYP2C19 (2 and 3), CYP3A4 5, CYP3A5 (3 and 6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1 1, 0.165 for CYP1A1 2A and 0.071 for CYP1A1 2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9 1, 0.135 for CYP2C9 2 and 0.068 for CYP2C9 3. For CYP2C19, the frequencies of the wild type (CYP2C19 1) and the nonfunctional (2 and 3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for 2/2. Regarding CYP3A4 1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5 1, 3 and 6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.
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Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP3A/genética , Frecuencia de los Genes , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , Humanos , Jordania , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADNRESUMEN
Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients. Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 . Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.
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BACKGROUND: High-dose methotrexate (HD- MTX) is the cornerstone of chemotherapy for acute lymphoblastic leukemia (ALL), and one of its target enzymes is Thymidylate Synthase (TYMS). We hypothesized that genetic polymorphisms of TYMS gene would be associated with MTX toxicity in ALL children. METHODS: 64 children with ALL were included in this study. Genotyping analysis was conducted on three common polymorphisms: tandem repeats in the promoter-enhancer region (VNTR), 6 bp ins/del (1494del6) in the 5'UTR, and rs2790 A > G in the 3'-untranslated region (3'-UTR). The association between genetic polymorphisms and MTX toxicity was studied. RESULTS: Genetic polymorphism of TYMS was associated with hematological toxicities but not with non-hematological adverse events. A significant association between TYMS 1494del6 genotypes and incidence of neutropenia (ANC < 1700 mm3), infection and leukopenia was observed. Carriers of the dominant allele (Del) were 6 times more likely to develop neutropenia compared to minor genotype carriers (OR (95% CI) 6 (1.2-31.1); p = 0.04), and 4.2 times less likely to have infection, as compared to Ins/Ins carriers (OR 4.2, 95% CI (1.1-16); p = 0.04). Carriers of Del allele were 9.2 times more likely to develop grade 3 and 4 leukopenia, p = 0.02, 95% CI (1.1-75.6). Significant association was found between 28 bp VNTR and thrombocytopenia; (OR 3.3, 95% CI (1.1-10), p = 0.04). No significant association was found between TYMS rs2790 A > G genetic polymorphisms and MTX hematologic toxicities. CONCLUSION: Genetic polymorphism of TYMS1494del6 may modulate susceptibility to MTX toxicity.
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Antimetabolitos Antineoplásicos/administración & dosificación , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Timidilato Sintasa/genética , Adolescente , Alelos , Antimetabolitos Antineoplásicos/efectos adversos , Niño , Preescolar , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Genotipo , Humanos , Masculino , Metotrexato/efectos adversos , Polimorfismo Genético , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Genetic polymorphisms of drug efflux transporters as ATP-binding cassette subfamily B, member 1 (ABCB1) have been suggested to modulate antiepileptic drugs (AEDs) response. We aimed to explore the association of ABCB1 polymorphisms and AEDs resistance among epileptic patients. METHODS: A total of 86 Jordanian epileptic patients treated with AEDs was included in the study. DNA was extracted from blood samples and genotyping and haplotypes analyses were conducted for Nine single nucleotide polymorphisms (SNPs) on the ABCB1 gene. RESULTS: Data revealed that none of the examined SNPs were associated with resistance to AEDs neither on the level of alleles nor genotypes. However, strong association was found between rs2235048 (OR = 10.6; 95%CI = [1.89-59.8], p= 0.01), rs1045642 (OR = 14; 95%CI = [1.3-156.7], p= 0.02), rs2032582 (OR = 9.1; 95%CI = [1.4-57.3], p= 0.04) and rs1128503 (OR = 18.7; 95%CI = [1.6-222.9], p= 0.02), ABCB1 polymorphisms and resistance to AEDs among females but not males. Haplotype analysis revealed statistically significant associations. The strongest significant associations were for haplotypes containing 2677G_1236 T in two-SNPshaplotypes (OR = 4.2; 95%CI = [1.2-14.9], p = 0.024); three-SNPs-haplotypes (OR = 4.2; 95% CI = [1.2-14.9], p = 0.02); four-SNPs-haplotypes (OR = 4.1; 95%CI = [1.2-14.3], p = 0.026). CONCLUSION: Data suggests that there is a gender dependent association between ABCB1 genetic polymorphisms and response to AEDs. Additionally, ABCB1 haplotypes influence the response to AEDs. Further investigation is needed to confirm the results of this study.
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Anticonvulsivantes/administración & dosificación , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Resistencia a Medicamentos/genética , Femenino , Genotipo , Haplotipos , Humanos , Jordania , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Objective: To evaluate the impact of a 10-week lockdown on children with asthma aged 4-17 years in terms of presentations to the emergency department (ED), frequency of admissions, compliance with medications and changes in pulmonary function testing results. Design and setting: A questionnaire-based cross-sectional study using Google Forms to collect parents' and caregivers' responses after they consented to participation. Results: A total of 374 parents/caregivers were contacted and 297 (79%) responded. The majority of the children were male (188 or 63%) and 49.8% were aged 7-12 years. More than half of the participants (194 or 65%) reported improved compliance with medications and spacer use. There was a significant reduction in the number of presentations to the ED from 137 to 80 and admissions to hospital from 56 to 24 during the 10-week lockdown period compared with the same time period in the previous year (p≤0.0001). Around 25% of the participants used telemedicine by phone and social media applications for communication with their treating physician and 59 (80%) described it as easy and smooth. Conclusion: The national lockdown in Jordan due to the COVID-19 pandemic was associated with a fall in emergency presentations and hospital admissions for acute asthma exacerbations. Parental responses indicate that fears focused around COVID-19 were associated with enhanced compliance with use preventer medications during the lockdown.
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Asma , COVID-19 , Adolescente , Asma/tratamiento farmacológico , Niño , Preescolar , Control de Enfermedades Transmisibles , Estudios Transversales , Servicio de Urgencia en Hospital , Femenino , Humanos , Jordania/epidemiología , Masculino , Pandemias , Padres , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
The aim of this study was to investigate abuse/misuse of prescription and nonprescription drugs in community pharmacies in Jordan by random distribution of a structured questionnaire to 405 pharmacies (November 2005-January 2006). Data were analyzed using SPSS for windows (version 14.0). Most respondents (94.1%) suspected that some level of abuse/misuse occurred in their pharmacy, which was highest for decongestants, cough/cold preparations, benzodiazepines, and antibiotics. Abuse/misuse of prescription and nonprescription drugs is present in Jordan, but current methods for controlling the problem are ineffective, and better methods should be developed. The study's limitations are noted..
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Medicamentos sin Prescripción , Medicamentos bajo Prescripción , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Estudios Transversales , Femenino , Humanos , Jordania , Masculino , Persona de Mediana Edad , Farmacias/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. METHODS: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. RESULTS: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein - cholesterol (LDL-C) - but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). CONCLUSION: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.
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Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/orina , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/orina , Vitamina D/administración & dosificación , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Pharmacists have crucial role in providing drug information and medication counseling to patients. This survey aimed to benchmark the current knowledge of the pharmacists concerning food-drug interactions (FDIs) in Jordan. METHODS: A cross-sectional study was conducted in Amman, the capital and largest city of Jordan, using a validated questionnaire. It was distributed to pharmacists working in community and hospital pharmacies using a convenience sampling technique. Descriptive and inferential statistics were performed in this study. RESULTS: A total of 340 questionnaires distributed, 300 (88%) pharmacists responded. Over 50% of pharmacists claimed that they have sufficient knowledge regarding FDI. Virtually, the overall median (interquartile range) knowledge score was 18 (15-21), approximately 60%. The highest knowledge scores were for alcohol-drug interactions section (66.6%) followed by both common food-drug interactions and the timing of drug intake to food consumption sections with a score of (58.3%) for each, reflecting a suboptimal knowledge of FDIs among the pharmacists. CONCLUSION: Pharmacists had unsatisfactory knowledge about common FDIs, with no significant difference between hospital and community pharmacists. Therefore, more attention and efforts should be played to improve awareness about potential food-drug interactions.
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Interacciones Alimento-Droga , Conocimientos, Actitudes y Práctica en Salud , Farmacéuticos/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Jordania , Masculino , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the major malignancies affecting children in Jordan. Methotrexate (MTX) is the cornerstone of chemotherapy for ALL, and works by targeting enzymes involved in the folate pathway. We hypothesize that genetic polymorphisms of the folate pathway are associated with MTX toxicity in children with ALL. METHODS: A total of 64 children with ALL were included in this study; 31 (48.4%) boys and 33 (51.6%) girls aged 2-16 years. The folate pathway genes were genotyped using polymerase chain reaction followed by sequencing and studying the association between genetic polymorphisms and MTX toxicity. RESULTS: The immunophenotype was B-lineage in 55 patients (85.9%) and T-lineage in nine patients (14.1%). All genetic polymorphisms, except for dihydropyrimidine dehydrogenase polymorphisms, were associated with hematological toxicities and did not appear to precipitate any non-hematological adverse events. Patients with ALL carrying dominant alleles of methylene tetrahydrofolate (MTHFR) C677T and dihydrofolate reductase 19 bp deletion were at a higher risk of developing severe leucopenia [OR (95% CI) = 4.5 (1.2-17), p = 0.03; 5.4 (1.6-17.8); p = 0.006] while minor allele carriers of MTHFR A1298C were more likely to develop neutropenia [OR (95% CI) = 6.1 (1.3-29.5); 0.04]. Furthermore, dominant allele carriers of thymidylate synthase 1494 del6 were at a higher risk of developing neutropenia [OR (95% CI) = 6 (1.2-31.1); p = 0.04]. CONCLUSION: Genetic polymorphisms of the folate pathway may modulate MTX-induced toxicity in childhood ALL.
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Antimetabolitos Antineoplásicos/efectos adversos , Ácido Fólico/metabolismo , Metotrexato/efectos adversos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Antimetabolitos Antineoplásicos/administración & dosificación , Niño , Preescolar , Estudios Transversales , Femenino , Genotipo , Humanos , Masculino , Metotrexato/administración & dosificación , Polimorfismo Genético , Estudios Prospectivos , Estudios Retrospectivos , Tetrahidrofolato Deshidrogenasa/genética , Timidilato Sintasa/genéticaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes. METHODS: A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyping was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease-free survival (DFS). RESULTS: The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFSGG vs AA: 8.0 ± 4 vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04-18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild-type TT carriers (DFSCC vs TT: 5.0 ± 1.5 vs 42.0 ± 7.6 months; HR 12.7, 95% CI 2.2-71.4; p = 0.004). However, there were no significant associations with the other studied polymorphisms. CONCLUSION: Genetic polymorphism in DPYD seems to be associated with DFS in CRC patients receiving an adjuvant regimen of 5-FU/capecitabine-based chemotherapy. Further studies are needed to verify these findings.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Ácido Fólico/metabolismo , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Adulto , Anciano , Capecitabina/administración & dosificación , Quimioterapia Adyuvante , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/metabolismo , Dihidrouracilo Deshidrogenasa (NADP)/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS: 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. RESULTS: Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P<0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods. CONCLUSION: In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P<0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P<0.05) with total cholesterol.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Estilo de Vida , Metformina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Estado Prediabético/tratamiento farmacológico , Adulto , Anciano , Biomarcadores/análisis , Glucemia/análisis , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Estado Prediabético/metabolismo , Estado Prediabético/patología , Pronóstico , Adulto JovenRESUMEN
Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and to compare it with other ethnic groups. Methods: We included 52 ALL childhood cases from King Hussein Cancer Research Center in Jordan. Genotyping of the rs1800460, rs1800462, and rs1142345 SNPs was performed by polymerase chain reaction (PCR) followed by sequencing. Comparisons were made with historical data for controls and for both volunteers and cases from other middle-eastern countries. Results: Mutant TPMT alleles were present in 3.8% (2/52) of patients. Allelic frequencies were 1.0% for both TPMT*B and TPMT*C. None of the patients were heterozygous or homozygous for TPMT*3A or TPMT *2. We did not find statistically significant differences in the distribution of mutant alleles between Jordan and other middle-eastern countries for both healthy volunteers or ALL patients. Conclusions: The overall frequency of TPMT mutant alleles was low and did not exhibit differences compared to other middle-eastern countries, including Jordanian studies assessing TPMT mutant alleles in healthy volunteers. The current results question the value of TPMT genotyping in the Jordanian population.