The glycemic and peak incremental indices of honey,sucrose and glucose in patients with type 1 diabetes mellitus: effects on C-peptide level—a pilot study

Our study was a case–control cross-sectional study that was conducted on 20 children and adolescents suffering from type 1 diabetes mellitus and ten healthy non-diabetic children and adolescents serving as controls. The mean age of patients was 10.95 years. Oral sugar tolerance tests using glucose, sucrose and honey and measurement of fasting and postprandial serum C-peptide levels were done for all subjects in three separate sittings. The glycemic index (GI) and the peak incremental index (PII) were then calculated for each subject. Honey, compared to sucrose, had lower GI and PII in both patients (P < 0.001) and control (P < 0.05) groups. In the patients group, the increase in the level of C-peptide after using honey was not significant when compared with using either glucose or sucrose. However, in the control group, honey produced a significant higher C-peptide level, when compared with either glucose or sucrose. In conclusion, honey, because of its lower GI and PII when compared with sucrose, may be used as a sugar substitute in patients with type 1 diabetes mellitus.     

Delay in invasive risk stratification of women with acute coronary syndrome is associated with worse outcomes

Background Invasive risk stratification in patients with acute coronary syndromes (ACS) has been shown to improve outcomes. There is paucity of data on women undergoing invasive risk stratification. We investigated whether the time to coronary angiography affects survival of female patients admitted with ACS. Method Female patients admitted to the coronary intensive care unit with ACS between 1/1/97 and 12/31/00 and undergoing coronary angiography during same hospitalization were divided into three groups based on the time to angiography: same day, 1–2 days and >2 days. The baseline clinical features, angiography results and outcomes were compared between the angiography groups. Results Of the total 350 female patients who fulfilled the inclusion criteria, 63% underwent angiography within two days of presentation. Three year mortality rates in women undergoing angiography on the same day, 1–2 days and >2-days were 7%, 7% and 22% respectively (p = 0.001). Using multivariate analysis, angiography beyond 2 days was a significant predictor of mortality among women (OR 2.6, 95% CI 1.3–5.0, p = 0.006) after adjusting for confounding variables. Conclusion Later invasive risk stratification after 2 days of presentation in women with ACS is associated with worse survivial. Gender should not be a reason to defer early coronary angiography in these patients.     

Protective immunity to genital herpes simplex virus type 1 and type 2 provided by self-adjuvanting lipopeptides that drive dendritic cell maturation and elicit a polarized Th1 immune response

Genital herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections are a significant health problem worldwide. While it is believed that CD4+ Th1 cells are among the effectors to herpes immunity, developing an epitope-based clinical vaccine capable of inducing an effective anti-herpes CD4+ Th1-mediated protection is still under investigation. Few molecules achieve this target without the aid of external immuno-adjuvant. The present study was undertaken to examine the immunogenicity in mice of five CD4+ T cell epitope peptides (gD1-29, gD49-82, gD146-179, gD228-257, and gD332-358), recently identified from the HSV-1 glycoprotein D (gD), covalently linked to a palmitic acid moiety (lipopeptides) using the high-yielding chemoselective ligation method and delivered subcutaneously in free-adjuvant saline. Their protective efficacy was evaluated in a progestin-induced susceptibility mouse model of genital herpes following intravaginal challenge with either HSV-1 or HSV-2. Four out of five gD lipopeptides effectively induced virus-specific CD4+ Th1 responses associated with a reduction of virus replication in the genital tract and protection from overt signs of genital disease. A cocktail of three highly immunogenic lipopeptides provoked maturation of dendritic cells, induced interferon gamma (IFN-gamma)-producing CD4+ T cells, and protected against both HSV- 1 and HSV-2 infections. Depletion of specific T cell subsets from lipopeptideimmunized mice before intravaginal HSV challenges demonstrated that CD4+ T cells were primarily responsible for this protection. The strength of induced T cell immunity, together with the ease of construction and safety of these totally synthetic self-adjuvanting lipopeptides, provide a molecularly defined formulation that could combat genital herpes and other human viral infections for which induction of Th1 immunity is crucial.     

Oxidant stress in primary nephrotic syndrome: does it modulate the response to corticosteroids?

In order to assess the oxidative stress in newly diagnosed children with primary nephrotic syndrome (PNS), we serially measured serum total antioxidant capacity (TAC) and malondialdehyde (MDA) in 33 children with PNS and ten healthy matched controls. Patients were classified into two groups: those who had steroid-sensitive nephrotic syndrome (SSNS; n = 26) and those who had steroid-resistant nephrotic syndrome (SRNS; n = 7). Of the patients with SSNS, 15 were non-relapsers and 11 were relapsers. At the proteinuric phase, all patients had significantly higher MDA levels and lower TAC than the controls. These changes were more marked in patients with SRNS than in those with SSNS. During remission and still on corticosteroids, patients had higher TAC and similar MDA levels as in the proteinuric phase, but the TAC and MDA levels still significantly differed from those of the controls. More improvement in TAC and MDA levels occurred in patients following the weaning of corticosteroids, but TAC was still lower in the patients than in the controls. Moreover, TAC was higher in non-relapsers than in relapsers. Using a receiver operating characteristic curve, the initial response to corticosteroids could be predicted at serum TAC level ≥0.73 mM/L (sensitivity 89%, specificity 86%), while serum TAC levels ≤ 1.14 mM/L after the weaning of corticosteroids could predict that the patient would not relapse (sensitivity 91%, specificity 80%). In conclusion, based on our results, PNS can be considered to be associated with oxidative stress even during remission. This stress may modulate the response to corticosteroids. Further prospective studies using larger numbers of patients are needed to validate these results.     

Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells

Previously, we demonstrated that CK30PEG10k-compacted DNA nanoparticles (NPs) efficiently target photoreceptor cells and improve visual function in a retinitis pigmentosa model. Here, we test the ability of these NPs in driving transgene expression in the retinal pigment epithelium (RPE), using an RPE-specific reporter vector (VMD2-eGFP). NPs, uncompacted plasmid, or saline were subretinally delivered to adult BALB/c mice. NP-based expression was specific to RPE cells and caused no deleterious effects on retinal structure and function. eGFP expression levels in NP-injected eyes peaked at post-injection day 2 (PI-2), stabilized at levels ~3-fold higher than in naked DNA-injected eyes, and remained elevated at the latest time-point examined (PI-30). Unlike naked DNA, which only transfected cells at the site of injection, NPs were able to transfect cells throughout the RPE. Subretinal injections of rhodamine labeled NPs and naked DNA showed comparable initial uptake into RPE cells. However, at PI-7 and -30 days significantly more fluorescence was detected inside the RPE of NP-injected eyes compared to naked DNA, suggesting NPs are stable inside the cell which could possibly lead to higher and sustained expression. Overall, our results demonstrate that NPs can efficiently deliver genes to the RPE and hold great potential for the treatment of RPE-associated diseases.     

Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer

Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels.     

Inherited thrombophilia in pediatric ischemic stroke: an Egyptian study

Pediatric stroke is relatively uncommon, with often subtle clinical presentations. Numerous predisposing risk factors can be both inherited and acquired, including cardiac disease, vascular abnormalities, infectious diseases, collagen tissue diseases, inborn errors of metabolism, anticardiolipin antibody, lupus anticoagulant, deficiencies of protein C, protein S, antithrombin, or plasminogen, and prothrombotic mutations. We explored risk factors, clinical features, and neuroimaging among Egyptian children with ischemic stroke, and estimated the prevalence of inherited thrombophilia. We included 20 children with ischemic stroke, recruited from the Pediatric Neurology Outpatient Clinic (Ain Shams University). Basic clinical evaluations for stroke and genotyping for factor V 1691 G-A (factor V Leiden), prothrombin 20210 G-A mutations, and methylenetetrahydrofolate reductase 677 C-T polymorphisms were performed using real-time polymerase chain reaction, with fluorescent melting curve detection analysis. Ten patients (50%) manifested methylenetetrahydrofolate reductase polymorphisms (six homozygotes and four heterozygotes). Heterozygous factor V Leiden was present in five (25%), whereas prothrombin mutation was present in only one (5%). Five patients (25%) manifested combined prothrombotic abnormalities. Thirteen demonstrated evidence of inherited thrombophilic disorder; 25% manifested more than one mutation. For appropriate risk assessment, even in the presence of overt acquired thrombotic risk factors, physicians should request complete thrombophilia screening for patients with stroke.