Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

PARP INHIBITORS IN OVARIAN CANCER: TOXICITY PROFILE

Today, the role of the genetic factor in the etiology of ovarian cancer is unquestionable. Genetic disorders in low-differentiated serous adenocarcinoma of ovaries in about 50 per cent of cases occur in the form of a lack of homologous DNA reparation. About 2/3 of these cases are associated with mutations in BRCA genes. The use of PARP inhibitors is a promising direction in the treatment of BRCA-mutated ovarian cancer, and a number of studies have proven their advantage. But because they are used in supporting mode, one of the basic requirements for this group of drugs is the toxicity profile. The most common complications in taking PARP-inhibitors are nausea, fatigue, vomiting, anaemia, thrombocytopenia. Olaparib has the lowest toxicity range of all the PARP inhibitors known today in the treatment of ovarian cancer

Juvenile myoclonic epilepsy: neurophysiological aspects

The review presents an update on the electroencephalographic characteristics and neurophysiology of juvenile myoclonic epilepsy (JME) in Russia and foreign countries.Materials and methods. The authors have performed a literary search for the full-text publications on JME electroencephalography and neurophysiology worldwide and in the Russian Federation, which are available in Russian and foreign databases.Results and discussion. Analysis of the literature suggests that JME patients have some electroencephalographic pattern features that include the atypical morphology of spike-and-slow-wave  complexes, as well as amplitude asymmetry, focal discharges, focal  onset of paroxysms, focal paroxysmal shift, and generalized paroxysmal fast rhythm.The analysis of the literature also indicates that primary care neurologists, clinical neurophysiologists, and epileptologists should be informed about the electroencephalographic characteristics of JME to timely diagnose the disease and to rule out the use of inadequate therapy

Problems of differential diagnosis of myoclon us-epilepsy associated with the mutation of the POLG gene and juvenile myoclonic epilepsy: a clinical case

Mutations of POLG gene can cause a variety of clinical manifestations, including autosomal recessive or autosomal dominant mitochondrial diseases. The article presents a clinical case demonstrating the difficulty of differential diagnosis of POLG-associated disease and juvenile myoclonic epilepsy. The case demonstrates the importance of molecular genetic diagnosis in idiopathic generalized epilepsy with atypical features for timely administration of appropriate therapy and minimize the development of adverse side reactions

Association of carriers of single nucleotide polymorphisms rs206787 and rs516535 in gene BRD2 and rs3743123 in gene GJD2 with juvenile myoclonic epilepsy of Caucasian patients in the Siberia

This article outlines recent findings on genetics of juvenile myoclonic epilepsy (JME), where JME occurrence is associated with polymorphic allelic variants in BRD2 gene (locus EJM3) and GJD2 gene (locus EJM2).Objective: To establish risk factors for development of JME in the context of genetic predisposition; specifically, polymorphic allelic variants rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene.Materials and Methods: Using RT-PCR, we identified carriers of single nucleotide polymorphisms (SNPs) rs206787 and rs516535 in gene BRD2 and rs3743123 in gene GJD2, from samples of 79 JME patients and 150 healthy volunteers of European descent residing in the Siberian Federal District.Results: We found complete linkage disequilibrium between studied loci in patients with JME and healthy controls, however there was no association between SNPs rs206787 and rs516535 and JME development in our study population (р &gt; 0,05). Haplotype TT/TT for SNPs rs206787 and rs516535 in the BRD2 gene associated with photoparoxysmal response (OR = 3,6; 95% CI 1,37 – 9,48; p = 0,02) in JME patients. Homozygosity of allele T (rs3743123) in the GJD2 gene was associated with risk of JME development in our study population (OR = 2,66; 95% CI 1,24 – 5,74; р = 0,04).Conclusion: These results strongly suggest that genotyping JME patients of European descent living in Siberia to identify carriers of haplotype TT/TT in BRD2 SNPs (locus EJM3) and T allele (rs3743123) in the GJD2 gene will enable personalised approach to JME diagnosis and management, as well as identification of high-risk individuals in affected families

CLINICAL AND GENETIC HETEROGENITY OF JUVENILE MYOCLONIC EPILEPSY

The idiopathic generalized epilepsies constitute roughly one-third of all epilepsies. Juvenile myoclonic epilepsy (Janz syndrome) is characterized by myoclonic jerks on awakening, generalized tonic-clonic seizures, and typical absences, with the latter occurring in more than one-third of the patients. However, typical absences are not the predominant seizure type, and are usually very mild and simple (with no automatisms or localized limb jerks). Juvenile myoclonic epilepsy usually appears in adolescents between 12 and 18 years old. Half of patients with this condition have relatives with epilepsy. The genetic basis of this syndrome is complex and the mechanism of transmission is unclear. It is possible that several different genes are responsible. The authors presented the review of results modern clinical and genetic studies of juvenile myoclonic epilepsy. Information obtained from this review strongly suggests a heritable condition that merits further investigation

Association of the carriage of <i>BRD2</i> rs206787 and rs516535 and <i>GJD2</i> rs3743123 polymorphisms with juvenile myoclonic epilepsy in Caucasian patients of Siberia

In recent years, the genetics of juvenile myoclonic epilepsy (JME) has been actively studied; the association of JME with the carriage of polymorphic allelic variants of the BRD2 (EJM3 locus) and GJD2 (EJM2 locus) genes has been established. Objective: to establish risk factors for JME in terms of a genetic predisposition; specifically, polymorphic allelic variants rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene. Patients and methods: Examinations were made in 79 patients with JME and in 150 healthy volunteers, who were Caucasian and resided in the Siberian Federal District (SFD) and underwent determination of the carriage of single nucleotide polymorphisms (SNPs) rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene by real-time polymerase chain reaction. Results and discussion. In 2003, American scientists from New York showed that the alleles associated with the development of JME with an autosomal recessive inheritance pattern might be located in the BRD2 gene. Patients with JME are assumed to have an autosomal dominant inheritance pattern of mutations in the BRD2 gene. British scientists revealed that different populations were found to have an association of SNP rs3918149 and no relationship of BRD2 rs206787 to the development of JME in Caucasians, as well as ascertained local linkage disequilibrium in the BRD2 gene. Our investigation has established complete linkage disequilibrium between the loci in patients with JME and in healthy individuals and no association of the carriage of SNPs rs206787 and rs516535 in the BRD2 gene with the development of JME in the patients residing in the SFD (p &gt;0.05). German scientists studied the impact of SNP in the BRD2 gene on a predisposition to a photoparoxysmal response in patients with JME/genetic generalized epilepsy. Our investigation has indicated the association of the carriage of TT/TT haplotype for SNP rs206787 and rs516535 in the BRD2 gene with a photoparoxysmal response in patients with JME (odds ratio (OR), 3.6; 95% confidence interval (CI), 1.37–9.48; p=0.02). We have confirmed that in the studied sample, the carriage of the T allele in the GJD2 gene (rs3743123) in the homozygous form is associated with the development of JME in Caucasian patients residing in the SFD and is a risk factor for JME (OR, 2.66; 95% CI, 1.24–5.74; p=0.04). The clinically significant association of this SNP in the GJD2 gene with the development of JME had been also previously demonstrated in two independent studies conducted in the European populations in the UK and Germany. There is a rise in the proportion of homozygotes in JME patients versus the control group, suggesting that the 588T allele under consideration increases the risk for JME in the homozygous state in the autosomal recessive inheritance pattern. Conclusion. The findings suggest that it is necessary to genotype Caucasian patients with JME, who reside in Siberia, for determination of the carriage of the TT/TT haplotype in terms of the investigated SNPs in the BRD2 gene (EJM 3 locus) and the carriage the T allele (rs3743123) in the GJD2 gene via a personalized approach to predicting the course of JME, as well as for identification of persons at risk for JME in the families having a history of this disease