Fahmy T. Ali

Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis.

Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions.

Abl Kinase Domain Mutations in Imatinib-treated Egyptian Patients with Chronic Myeloid Leukemia

Background: Point mutations within ABL kinase domain (AKD) of the BCR-ABL gene are the most common cause of resistance to Imatinib Mesylate (IM) treated Chronic Myeloid Leukemia (CML) patients. Objectives: To assess the frequency, type and impact of AKD mutations on prognosis in a cohort of Egyptian CML patients. Patients and methods: Serial measurements of BCR-ABL transcripts level in 175 IM treated CML patients were performed using real time quantitative polymerase chain reaction (RQ-PCR). Mutation screening was performed by allele specific oligonucleotide polymerase chain reaction (ASO-PCR) in 72 patients including all 42 non-optimal responders; 28 resistant patients, 18 suboptimal responders in addition to 30 patients randomly selected with stable/ decreasing transcript level representing an optimal responder category. Results: AKD mutations were detected in 16/28 resistant patients (57%) at time of >2-fold rise in BCR-ABL transcript and in none of the 44 optimal or suboptimal responders (0%) with decreasing or stable transcript levels. From 16 positive patients, P-loop mutations were detected in 9 patients; Q252H in 3 patients (19%), Y253H in 2 patients (12%), Y253F in 2 patients (12%) and E255K in 2 patients (12%). T315I was detected in 1/16 (6%) patient. Regarding non P-loop mutation; V299L was detected in one patient (6%), M351T in 4 patients (25%), F359V in 2 patients (12%). One patient had both Y253H and E255K mutations. Ten/16 (62%) patients carrying mutations experienced disease progression versus 1/56 (2%) in non mutation group (p=0.001). Median progression free survival (PFS) and overall survival (OS) of the mutation group was 13.5 months and 37.5 months, respectively versus 42.6 months in non mutation group (p=0.001). The estimated PFS and OS at 49 months in patients with mutations were 37.5% and 56.3% respectively versus 98.2% in non mutation carriers (p 2-folds in IM resistant patients may signal progression that implies testing for AKD mutations and early planning for second generation tyrosine kinase inhibitors (TKIs). P-loop mutations are significantly associated with advanced CML phases and poorer OS than non-P loop mutations. ASOPCR is a valuable tool for detection of mutations in countries where sequencing facilities are not available.

Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon α Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background/Aims The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon α (PEG-IFN-α)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. Methods Two SNPs in the promoter region of SPP1 at the −443 C>T and −1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. Results Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the −443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs 50.98%, p<0.001). At the −1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs 52.63%, p=0.001). Conclusions SPP1 SNPs at −443 C>T and −1748 G>A loci may be useful markers for predicting the response to PEG-IFN-α-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection.

Nilemycin, an intercalating agent for deoxyribonucleic acid.

1. Nilemycin (NM) is found to exert an inhibitory effect on the mouse tumor Sarcoma 180 near toxic doses but not with Leukemia 1210. 2. In Yoshida rat sarcoma cells NM inhibits cellular de novo nucleic acid synthesis and protein to a much lesser extent. 3. More than 50% inhibition by NM to de novo synthesis of RNA, in a system using calf thymus DNA as a template, could be observed. 4. Suitable levels of NM reduce the S values of DNA. 5. The antibiotic induced metachromatic changes in the u.v. spectrum of DNA solutions. 6. NM markedly inhibited the polynucleotide ligase repairing action on DNase-1-nicked DNA. 7. It is presumed that NM intercalates nicked DNA into such a configuration that the reactive sites of the polynucleotides are inaccessible to the ligase activities.