bluuebunny/crossref_metadata_2025 huggingface dataset:
Ineffectual Medical Treatment of Cesarean Scar Ectopic Pregnancy With Systemic Methotrexate
Authors: Kelekçi Sefa , Aydoğmuş Serpil , Aydoğmuş Hüseyin , Eriş Serenat , Demirel Emine , Şen Selim Halime
Published: March 2014

The implantation of a pregnancy within the scar of a previous cesarean section is known as a “cesarean scar pregnancy.” Its incidence was reported to be 6.1%. However, with the increasing rates of cesarean sections, the incidence is expected to rise. A variety of conservative and surgical treatment modalities have been proposed for the management of cesarean scar pregnancy; however, there are no optimal universal treatment guidelines because of its rarity. Treatment should be tailored to the individual patient. It is obvious that more scar pregnancies will be seen in the future and therefore a set of criteria for the choice of various modes of management should be developed. Here, we present 2 cases of cesarean scar pregnancies treated with a local injection of potassium chloride after the failure of methotrexate administration.
The empirical codon mutation matrix as a communication channel
Authors: Nigatu Dawit , Mahmood Attiya , Henkel Werner
Published: March 2014

Background

A number of evolutionary models have been widely used for sequence alignment, phylogenetic tree reconstruction, and database searches. These models focus on how sets of independent substitutions between amino acids or codons derive one protein sequence from its ancestral sequence during evolution. In this paper, we regard the Empirical Codon Mutation (ECM) Matrix as a communication channel and compute the corresponding channel capacity.

Results

The channel capacity of 4.1875 bit, which is needed to preserve the information determined by the amino acid distribution, is obtained with an exponential factor of 0.26 applied to the ECM matrix. Additionally, we have obtained the optimum capacity achieving codon distribution. Compared to the biological distribution, there is an obvious difference, however, the distribution among synonymous codons is preserved. More importantly, the results show that the biological codon distribution allows for a “transmission” at a rate very close to the capacity.

Conclusion

We computed an exponential factor for the ECM matrix that would still allow for preserving the genetic information given the redundancy that is present in the codon-to-amino acid mapping. This gives an insight how such a mutation matrix relates to the preservation of a species in an information-theoretic sense.
H ip joint pain in children with cerebral palsy and developmental dysplasia of the hip: why are the differences so huge?
Authors: Grzegorzewski Andrzej , Jóźwiak Marek , Pawlak Maciej , Modrzewski Tadeusz , Buchcic Piotr , Masłoń Adrian
Published: March 2014

Backgrounds

Non-traumatic hip dislocation in children is most often observed in the course of developmental dysplasia of the hip (DDH) and infantile cerebral palsy. The risk of pain sensations from dislocated hip joint differentiates the discussed groups of patients. Will every painless hip joint in children with cerebral palsy painful in the future?

Methods

Material included 34 samples of joint capsule and 34 femoral head ligaments, collected during open hip joint reduction from 19 children with CP, GMFCS level V and from 15 children with DDH and unilateral hip dislocation. All the children were surgically treated.

The density of nociceptive fibres was compared between the children with CP and DDH, using S-100 and substance P monoclonal antibodies.

Results

More frequent positive immunohistochemical reaction to S-100 protein concerned structures of the femoral head ligaments in children with CP and cartilage losses on the femoral head, when compared to the same structures in children with DDH (p = 0.010). More frequent were found positive immunohistochemical reactions for S-100 protein in the joint capsules of children with cartilage losses (p = 0.031) and pain ailments vs. the children with DDH (p = 0.027). More frequent positive reaction to substance P concerned in femoral head ligaments in CP children and cartilage lesions (p = 0.002) or with pain ailments (p = 0.001) vs. the DDH children.

Conclusions

Surgical treatment of hip joint dislocation should be regarded as a prophylactics of pain sensations, induced by tissue sensitisation, inflammatory process development or articular cartilage defects.
Choroidal atrophy and loss of choriocapillaris in convalescent stage of Vogt-Koyanagi-Harada disease: in vivo documentation
Authors: Nazari Hossein , Hariri Amirhossein , Hu Zhihong , Ouyang Yanwei , Sadda SiriniVas , Rao Narsing A
Published: March 2014

Background

The aim of this study was to determine the clinical significance of posterior choroidal thickness and vascular changes in the convalescent stage of Vogt-Koyanagi-Harada disease (VKH). Macular spectral domain optical coherence tomography (SD-OCT) images of 22 eyes of 13 consecutive patients with VKH at the convalescent stage were compared to 17 eyes of 9 age/sex/refraction-matched normal subjects. The choriocapillaris layer, medium choroidal vessels (Sattler's layer), and large choroidal vessels (Haller's layer) were assessed in foveal SD-OCT scans. The presence and the extent of disruption of outer retinal structures were also noted. Inner and outer choroid boundaries were manually drawn on horizontal raster SD-OCT scans, and choroidal thickness and volume maps were generated. Correlation analysis was run to assess the association of the above parameters in the VKH patients compared to the normal subjects.

Results

In the eyes with convalescent stage of VKH, mean choroidal thickness in the foveal central subfield (200 ± 60 μm) was lower than in matched controls (288 ± 40 μm) (P < 0.0001). A thinner sub-macular choroid correlated with a lower visual acuity in uveitis eyes (Pearson correlation, r = -0.5089, P = 0.005). While the choriocapillaris layer was continuous and intact in all control eyes, various degrees of choriocapillaris loss were observed in 11 eyes (50%) with VKH (P < 0.0001). In these patients, the presence of outer retinal disruption was associated with a lower visual acuity (Spearman correlation, P < 0.001).

Conclusions

The choroid is significantly thinner and the choriocapillaris layer is disrupted in the eyes with convalescent stage of VKH. Evaluation of the choriocapillaris in SD-OCT scans may be a useful surrogate marker for visual function in the convalescent stage of VKH.
At the Bench: Adoptive cell therapy for melanoma
Authors: Urba Walter J
Published: March 2014

The cellular and molecular principles that furnish the foundation for ACT of melanoma and their implications for further clinical research are reviewed. The parallel advances in basic immunology, preclinical animal studies, and clinical trials over the last two decades have been integrated successfully with improvements in technology to produce an effective ACT strategy for patients with melanoma. From the initial observation that tumors could be treated effectively by the transfer of immune cells to current strategies using preconditioning with myeloablative therapy before adoptive transfer of native or genetically altered T cells, the role of preclinical animal models is discussed. The importance of the pmel transgenic mouse model in the determination of the mechanisms of lymphodepletion, the ongoing work to identify the optimal T cells for adoptive immunotherapy, and the early impact of the emerging discipline of synthetic biology are highlighted. The clinical consequences of the research described herein are reviewed in the companion manuscript.
Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses
Authors: Collins Aideen S , Ahmed Suaad , Napoletano Silvia , Schroeder Martina , Johnston James A , Hegarty John E , O'Farrelly Cliona , Stevenson Nigel J
Published: March 2014

TNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α and negatively regulate its NF-κB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-α-mediated IκB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-α-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-κB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-α-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-α signal transduction and reveal a novel immune-modulatory mechanism by which HCV suppresses inflammatory responses in primary immune cells and hepatocytes, perhaps explaining mild pathology often associated with acute HCV infection.
Coilin association with Box C/D scaRNA suggests a direct role for the Cajal body marker protein in scaRNP biogenesis
Authors: Enwerem Isioma I. , Velma Venkatramreddy , Broome Hanna J. , Kuna Marija , Begum Rowshan A. , Hebert Michael D.
Published: March 2014

Spliceosomal small nuclear ribonucleoproteins (snRNPs) are enriched in the Cajal body (CB). Guide RNAs, known as small Cajal body-specific RNAs (scaRNAs), direct modification of the small nuclear RNA (snRNA) component of the snRNP. The protein WRAP53 binds a sequence motif (the CAB box) found in many scaRNAs and the RNA component of telomerase (hTR) and targets these RNAs to the CB. We have previously reported that coilin, the CB marker protein, associates with certain non-coding RNAs. For a more comprehensive examination of the RNAs associated with coilin, we have sequenced the RNA isolated from coilin immunocomplexes. A striking preferential association of coilin with the box C/D scaRNAs 2 and 9, which lack a CAB box, was observed. This association varied by treatment condition and WRAP53 knockdown. In contrast, reduction of WRAP53 did not alter the level of coilin association with hTR. Additional studies showed that coilin degrades/processes scaRNA 2 and 9, associates with active telomerase and can influence telomerase activity. These findings suggest that coilin plays a novel role in the biogenesis of box C/D scaRNPs and telomerase.
Various applications of TALEN- and CRISPR/Cas9-mediated homologous recombination to modify the Drosophila genome
Authors: Yu Zhongsheng , Chen Hanqing , Liu Jiyong , Zhang Hongtao , Yan Yan , Zhu Nannan , Guo Yawen , Yang Bo , Chang Yan , Dai Fei , Liang Xuehong , Chen Yixu , Shen Yan , Deng Wu-Min , Chen Jianming , Zhang Bo , Li Changqing , Jiao Renjie
Published: March 2014

Modifying the genomes of many organisms is becoming as easy as manipulating DNA in test tubes, which is made possible by two recently developed techniques based on either the customizable DNA binding protein, TALEN, or the CRISPR/Cas9 system. Here, we describe a series of efficient applications derived from these two technologies, in combination with various homologous donor DNA plasmids, to manipulate the Drosophila genome: (1) to precisely generate genomic deletions; (2) to make genomic replacement of a DNA fragment at single nucleotide resolution; and (3) to generate precise insertions to tag target proteins for tracing their endogenous expressions. For more convenient genomic manipulations, we established an easy-to-screen platform by knocking in a white marker through homologous recombination. Further, we provided a strategy to remove the unwanted duplications generated during the “ends-in” recombination process. Our results also indicate that TALEN and CRISPR/Cas9 had comparable efficiency in mediating genomic modifications through HDR (homology-directed repair); either TALEN or the CRISPR/Cas9 system could efficiently mediate in vivo replacement of DNA fragments of up to 5 kb in Drosophila, providing an ideal genetic tool for functional annotations of the Drosophila genome.
IPS-1 plays an essential role in stress granule formation induced by dsRNA through interacting with PKR and mediating its activation
Authors: Zhang Peifen , Li Yuye , Xia Jun , He Junfang , Pu Jieying , Xie Jiong , Wu Siyu , Feng Lianqiang , Huang Xi , Zhang Ping
Published: March 2014

Formation of cytoplasmic stress granules (SGs) and innate immune response are two distinct cellular responses to stresses. Our study investigated involvement of four innate immune proteins, retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), IFN-β promoter stimulator (IPS-1) and protein kinase regulated by dsRNA (PKR) in the formation of SGs. Knockdown of IPS-1 or PKR significantly decreased the SG formation induced by dsRNA. IPS-1 depletion markedly attenuated the phosphorylation of PKR and eIF2α triggered by dsRNA, and IPS-1 facilitated the in vitro autophosphorylation of PKR. In IPS-1 depleted cells, the dsRNA-mediated association of PKR with its dsRNA binding domains or full length PKR was significantly abrogated, suggesting IPS-1 might be involved in PKR dimerization. By co-immunoprecipitation and pulldown assays, our data demonstrated that IPS-1 directly binds to PKR via its CARD domain, suggesting that effect of IPS-1 on SG formation might exert through interacting with PKR and mediating its activation. PKR was recruited into SGs upon activation while majority of IPS-1 protein formed clusters on mitochondrial membrane. Our work provides first evidence that innate signaling molecule IPS-1 plays an essential role in SG formation.
P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils
Authors: Damoulakis George , Gambardella Laure , Rossman Kent L. , Lawson Campbell D. , Anderson Karen E. , Fukui Yoshinori , Welch Heidi C. , Der Channing J. , Stephens Len R. , Hawkins Phillip T.
Published: March 2014

G protein-coupled receptors (GPCRs) regulate organisation of the actin cytoskeleton by activating the Rac subfamily of small GTPases. The guanine nucleotide exchange factor (GEF) P-Rex1 is engaged downstream of GPCRs and PI3K in many cell types, and promotes tumorigenic signalling and metastasis in breast cancer and melanoma, respectively. Although P-Rex1-dependent functions have been attributed to its GEF activity towards Rac1, we show that P-Rex1 also acts as a GEF for the Rac-related GTPase RhoG, both in vitro and in GPCR-stimulated primary mouse neutrophils. Further, loss of either P-Rex1 or RhoG caused equivalent reductions in GPCR-driven Rac activation and Rac-dependent NADPH oxidase activity, suggesting they both function upstream of Rac in this system. Loss of RhoG also impaired GPCR-driven recruitment of the RacGEF DOCK2, and F-actin, to the leading edge of migrating neutrophils. Together, our results reveal a novel signalling hierarchy in which P-Rex1, acting as a GEF for RhoG, regulates Rac-dependent functions indirectly via RhoG-dependent recruitment of DOCK2. These findings thus have broad implications for our understanding of GPCR signalling to RhoGTPases and the actin cytoskeleton.
Novel apprehensions and hybrid utterances: Practice, research, language
Authors: Kill Rebekka
Published: March 2014

This article explores current debates on the role of writing in artistic research. This discussion has been in train for several decades, and yet we are still not clear, as an academic community, in regards to a number of issues related to the status of, role and purpose writing in research by practice. In order to explore this I initially look at some of the discussion, and confusion, surrounding the regulations on, and support for, Ph.D.s in practice in universities in the United Kingdom. I will also explore disciplinary notions of research and then the final part of the article digs a little deeper into the effect of language and logobias in the university.
Practice what you teach? Examining the significance and complexities of textile designer educator creative practice
Authors: Britt Helena
Published: March 2014

Learning to practice is central to undergraduate and the majority of taught postgraduate art and design programmes in the United Kingdom. Therefore, the creative practice of educators employed to teach, including part-time and visiting lecturers, has long been recognized as contributing to student learning. An emphasis on undertaking research has prompted educators, initially employed due to their expertise as creative practitioners, to formulate and adopt practice-led and practice-based approaches to research. The benefits of educator research to learning and teaching are also recognized. The higher education (HE) system is in a continual state of change, higher education institutions (HEIs) and educators respond to government policy and initiatives. Operating in the United Kingdom HE system together with pressures encountered can be counterproductive to educator creative practice. While research can involve creative practice activity there are issues, for example, with adoption of appropriate methodologies and difficulties with explicating tacit knowledge through writing. As a discipline, textile design exists on the periphery of design and design research discourse. The research project featured in this article responds to the context described and the deficit of literature surrounding contemporary textile design HE and educator creative practice and teaching linkages. The focus is on the textile designer educator role in the United Kingdom and examination of creative practice activity, to establish the means by which educator creative practice informs teaching and therefore influences student learning. The investigation used a combination of self-case study, survey, interview and case study methods. Findings indicate that textile designer educator creative practice is important to HE due to the positive impact that engagement has on teaching. However, issues are encountered and these are discussed in order to propose suggestions to improve the existent situation and to highlight areas for further investigation.
Medium of ‘Curiosità’: An innovative studio environment for design education
Authors: Yurtkuran Selay , Taneli Yavuz
Published: March 2014

Basic Design is a studio course in architectural education that requires creative problem-solving and critical thinking skills, a non-ending appetite for knowledge, and non-diminishing curiosity. This article describes an innovative studio environment that allows for this particular mentality to flourish and appropriate professional skills to be strengthened. The manuscript further outlines a studio project that utilizes an olfactory stimulus to rekindle curiosity. The project is an introductory exercise, using line as a conceptual design element, and a tool for communication. Through subsequent content analysis, the qualitative case study methodologically records this two-week exercise, and uses verbal and visual data, as well as written student responses to assess the benefits of this altered learning experience. The authors argue that, only through curiosity will the studio environment become the catalyst to foster innovative design ideas.
Inferring a collective concept of research from the actions of the art and design research community
Authors: Biggs Michael , Büchler Daniela
Published: March 2014

This article examines output types as manifestations of different concepts of research. We compare the UK academic scene to that of Brazil, identifying the former as responding ‘bottom-up’ to researcher needs and the latter determining ‘top-down’ what researchers can do. Taking the UK model as indicative of what researchers think they need, we undertook a detailed analysis of the output types used in RAE2008 across all subjects in order to see which types were used and by whom. We also undertook a further analysis of the use of traditional, text-based formats in art and design, and the use of non-traditional, non-textual output types in other subjects. We conclude that both the journal format and the exhibition format are expressive of the understanding each community has of the meaning of research as an activity. This is further reinforced by the national structures within which research is undertaken and evaluated.
Study of new capacities in the evaluation of glycemic control in patients with type 2 diabetes
Authors: Dreval' A V , Kovachev B P , Misnikova I V , Kovaleva Yu A , Dreval' O A
Published: March 2014

The purpose of the study was to comprehensively analyze glycemic control in type 2 diabetes (T2D) patients who were first given glucose-reducing therapy. Glidiab MB and Diabeton MB caused a comparable reduction in glycemic control parameters: the level of HbA1c, fasting glycemia, and mean glycemic levels as shown by the results of its continuous glucose monitoring system (CGMS) study. The lower glycemic level was not accompanied by weight gain and it improved lipid spectrum parameters. The readings of monthly self-control of glycemia were transformed to its deviation from the goal range (ADRR) that and the hyper- and hypoglycemia indices calculated from the continuous glycemic control were used to evaluate glycemic lability not reflected by HbA1c. In this connection ADRR may be used to evaluate the efficiency of sugar-reducing therapy and in the examined groups it proved to be low, which generally reflects the stable course of the disease in new cases of T2D. The mean glycemic value calculated from CGMS data virtually coincides with the mean glycemia estimated from glycemic self-control readings both on the day of continuous glucose monitoring and in the month to come before and after CGMS study. In this connection the latter is justified only when the continuous glycemic curve undergoes a complex analysis. The complex analysis of the continuous glycemic curve includes symmetrization of the continuous glycemia scale; calculation of hyper- and hypoglycemic indices, hourly diurnal hyperglycemic index and hourly glycemic variations (Poincare method). The use of this procedure could compare the glucose-reducing effect of the two drugs within the framework of a short-term study.
The antioxidant Dibicor in the treatment of vascular complications of type 2 diabetes
Authors: Bondar' I A , Shabel'nikova O Yu , Alina A R
Published: March 2014

The effects of Dibicor (taurine) were studied in 20 patients with type 2 diabetes (T2D) with a disease duration of 1 to 9 years and a mean body weight of 93.8±16 kg who received concomitant therapy (monotherapy with sulfonylurea (n = 7), novonorm (n = 1), sulfonylurea with metformin (n = 7); one patient was on diet therapy). Addition of Dibicor to the therapy following 3 months caused a statistically significant reduction in fasting and postprandial glycemia (from 7.9 to 6.3 mmol/l and from 7.9 to 6.9 mmol/l, respectively). Glycated hemoglobin decreased from 7.8 to 7.05% (p = 0.062). Lipid metabolic parameters improved after 3-month course of therapy. There was also a statistically significant fall in microalbuminuria from 0.082 to 0.054 g/day (p = 0.042). The administration of Dibicor can significantly improve T2D compensation.
Non-immune thyrotoxicosis caused by thyroid-stimulating hormone receptor activating gene mutation (the first description in Russia)
Authors: Peterkova V A , Vasyukova O V , Tyul'pakov A N
Published: March 2014

Thyrotoxicosis of newborns, observed in less than 1% of pregnant women with Graves disease, is due to transplacental transfer of stimulating antibodies to the thyroid stimulating hormone receptor (rTSH). The clinical picture manifests itself in the first days of a child’s life, is transient in nature and, as a rule, ends with a full recovery as the maternal antibodies to rTSH disappear from the bloodstream of the newborn. However, in addition to the "classic" autoimmune thyrotoxicosis, cases of congenital and familial non-autoimmune thyrotoxicosis, which are caused by inherited activating mutations of the gene encoding rTSH - TSHR, have been described. This article presents its own observation.
Clinical and molecular genetic verification of Frasers syndrome, false male hermaphroditism and chronic glomerulonephritis (the first description in Russia)
Authors: Novikova E O , Rubtsov P M , Sverdlova P S , Tyul'pakov A N
Published: March 2014

The Wilms tumor gene (WT1) encodes a transcription factor that plays a key role in the laying and differentiation of the kidneys and gonads. Mutations of the WT1 gene were detected in patients with the WAGR complex (Wilms tumor, aniridia, urogenital pathology, mental retardation), Denis-Drach syndrome (early renal failure, diffuse mesangial sclerosis, varying degrees of gonadal dysgenesis, high risk of Wilms tumor) and Fraser syndrome. The latter is characterized by a fully female phenotype with karyotype 46XY, focal segmental glomerulosclerosis with the development of renal failure in the 2nd decade of life, gonads in the form of cords and a high risk of gonadoblastoma. The presence of a heterozygous point mutation, which alters the donor site of splicing of the intron 9 of the WT1 gene, is also typical of Fraser syndrome. We present a case of characteristic clinical manifestations of Fraser syndrome in a patient in whom the diagnosis was confirmed by the detection of a mutation in the WT1 gene.
Role of adipokines and nonesterified fatty acids in the development of insulin resistance
Authors: Tanyanskiy D. A. , Firova E M. , Shatilina L. V. , Denisenko A. D.
Published: March 2014

The purpose of the study was to reveal a possible role of adipokines, biologically active adipose tissue proteins (leptin and adiponectin) and nonesterified fatty acids in generating insulin resistance (IR). One hundred and fifty-seven patients (90 females and 67 males) aged 57.5±9.2 years were enrolled in the study. According to the HOMA index for IR, the patients were divided into 3 equal groups. The examinees with a high HOMA index were found to have elevated levels of fatty acids, leptin and decreased concentrations of adiponectin. At the same time according to the linear regression analysis, all these indices are its independent determinants. However, analysis of the data in the groups of patients with different body weight revealed that the increased concentrations of fatty acids and leptin may play a role in the development of IR in subjects with obesity while the higher level of fatty acids and lower adiponectin may be involved in patients without noticeable obesity. Thus, it may be assumed that leptin, adiponectin and nonesterified fatty acids may affect the development of IR; however, their contribution depends on the degree of adiposity.
The level of antibodies to pneumococcal vaccine in children and adolescents with type 1 diabetes
Authors: Kostinov M P , Skochilova T V , Tarasova A A , Vorob'eva V A , Korovkina T I , Lukachev Igor' Viktorovich , Yushkova I Yu , Yastrebova N E
Published: March 2014

The trend in the formation of postvaccinal antibodies (Ab) to a mixture of S. pneumoniae polysaccharides (PS) was studied in 100 Pneumo 23-vaccinated children and adolescents with type 1 diabetic (T1D) (Group 1, n = 72) and its combination with the subunit vaccine Grippol (Group 2, n = 28). Following 1-1.5 months, the protective level of Ab l 40 conventional units (CU/ml) was revealed in 95.1 and 85.2% of Groups 1 and 2, respectively; and after 1 year, this was in 55.1 and 37%, respectively (p > 0.05). The level of formation of IgG Ab to a PS mixture did not depend on the age of patients, the duration of T1D, the presence of late diabetic complications. A relationship was found between the formation of postvaccinal Ab and their baseline level: in patients with very low (< 10 CU/ml) and low (10-20 CU/ml) levels of Ab after administration of pneumococcal vaccine, the level of IgG Ab to a S. pneumoniae PS mixture increased by 8.8-4.1 times in the early periods and exceeded the baseline levels by 4.8-2.8 times, respectively. The putative protective level of IgG AB to a S. pneumoniae PS mixture is proposed to be l 20 CU/ml.
Cardiac functional reserve and left ventricular parameters in patients with diffuse toxic goiter after drug correction of euthyroidism with thiamazol
Authors: Sviridenko N. Y. , Tugeeva E F , Aripov M A , Buziashvili Yu I
Published: March 2014

The aim of the investigation was to assess the time course of structural-and-functional and spatiogeometric changes following drug correction of euthyroidism in patients with diffuse toxic goiter and to determine prospects for restoring the cardiac functional reserve after elimination of thyrotoxicosis. The geometric parameters of the left ventricle (LV) and the readings of tissue Doppler echocardiography and exercise tests were compared in 27 female patients (mean age 53.3±9.2 years) who had thyrotoxicosis and 6 months after thyrosole-induced normalization of thyroid-stimulating and thyroid hormone. There were significant increases in myocardial mass and peak systolic and diastolic mitral ring motion rates and an increasing trend for LV linear sizes after correction of euthyroidism. Despite the fact that there were no significant differences in the majority of LV geometric parameters, with euthyroidism achievement, the cardiac functional reserve doubled as compared with the baseline values (105.7±11.4 and 57.8±14.7 W, respectively; p < 0.001), but remained below the control level (148.7±11.7 W; p < 0.05), which may contribute to the development of heart failure in future under certain conditions.
MODY2: Clinical and molecular genetic characteristics of 13 cases of the disease. The first description of MODY in Russia
Authors: Dedov I I , Zubkova Natal'ya Anatol'evna , Arbatskaya N Yu , Akopova A G , Tyul'pakov A N
Published: March 2014

Maturity-onset diabetes of the young (MODY) is a clinically heterogenic group of diseases, with an autosomal dominant mode of inheritance and gene mutations resulting in dysfunction of pancreatic β cells. The type of diabetes and further treatment policy can be reliably determined on the basis of the data of a molecular genetic study that confirms gene mutations. Today there are known mutations of 8 genes, of which glucokinase (GCK) gene mutation that leads to the development of MODY2 and occurs most frequently. The spread of this mutation among DM patients in our country has not been studied. The diagnosis of MODY2 was established in 13 members of 5 families with the clinical picture typical of this type. The molecular genetic study revealed 4 new and 1 earlier described mutations. The findings extend ideas on the molecular bases of MODY, which creates conditions for improving the diagnosis of this disease, genetic counseling and the development of pathogenetically founded approaches to treatment.
Pseudohypoparathyroidism: genetic aspects
Authors: Gerasimenko O. A. , Dzeranova L K , Rozhinskaya L Ya
Published: March 2014

The review of literature details the issues of genetics, the specific features of inheritance, the clinical picture and treatment of pseudohypoparathyroidisms (PHPT). In practice, clinicians more frequently deal with type 1 PHPT and the diagnosis of this type creates no significant problems. However, despite the low prevalence of the other types of PHPT - 1b, 1c, and 2, the diseases may run with noticeably clinical symptoms and present a significant problem in the context of diagnosis and treatment. This review may be of concern to both clinicians and geneticists who are interested in this problem.
Diagnostic capacities of determination of biologically active free testosterone in blood, by using current ultrafiltration techniques
Authors: Malysheva N M , Katsiya G V , Goncharov Nikolay Petrovich
Published: March 2014

In most cases, current methods for immunoassay of blood total testosterone fail to provide a sufficient diagnostic accuracy. The authors measured the concentration of free testosterone in the blood and saliva samples from 189 males aged 19 to 83 years who had come to the clinic to confirm or exclude the diagnosis of various endocrine dysfunctions. Ultrafiltration had been previously carried on Amicon® Ultra membrane 30K filters (MILLIPORE) to determine the serum level of free testosterone. The ultrasensitive enhanced luminescence technique (IBL-Hamburg, Germany) was used to measure its concentration in the ultrafiltrate and saliva. The detection rate of androgen deficiency from the levels of free testosterone in the ultrafiltrate was higher than that from those of total testosterone and calculated free testosterone in blood. The preultrafiltration salivary and serum free testosterone values measured by the ultrasensitive enhanced luminescence technique may complement a sensitive marker of clinical symptoms to detect different forms of androgenic disorders.
Effect of a complex of corticosteroids with apolipoprotein A-I on protein biosynthesis in cultured hepatocytes
Authors: Panin L E , Polyakov Lev Mikhaylovich , Usynin I F , Sumenkova D V , Knyazev R A
Published: March 2014

A complex of apolipoprotein A-I with steroid hormones containing reduced Δ4, 3-ketogroup in the A ring was shown to increase the rate of protein synthesis in the cultured rat hepatocytes. The biological activity of the hormones depends on the position of the oxygroup of the third carbonic atom and hydrogen at the fifth position of a carbonic atom. The cis-position is more preferable for the biological effect. The oxygroup at the third position of the A-ring may be replaced by the sulfo-group. The complex of dehydroepiandrosterone sulphate with apolipoprotein A-I increases the rate of protein biosynthesis in the cultured rat hepatocytes, which confirms the involvement of this hormone in the regulation of gene expression.
Endocrine aspects of the pathogenesis of cancer of the cervix uteri. New possibilities of primary prophylaxis
Authors: Uzhegova Z. A. , Grigoryan O. R. , Andreeva E. N.
Published: March 2014

The review gives updates on the pathogenesis of background, precancer, and cancer of the cervix uteri. Epidemiological and molecular biological studies have established that human papillomavirus infection is the most important factor of carcinogenesis of the cervix uteri. The impact of reproductive dysfunction on the development of cervical pathology has been assessed and a possible mechanism of involvement of sex steroids in carcinogenesis assumed.
Left ventricular remodeling in patients in patients with thyrotoxicosis
Authors: Aripov M. A. , Sviridenko N Y , Tugeeva E F , Buziashvili Y I
Published: March 2014

The aim of this paper was to investigate cardiac remodelling in thyrotoxicosis. The geometric parameters of the left ventricle (LV) and the readings of tissue Doppler echocardiography were compared in 27 patients (mean age 53.3±9.2 years) who had first-diagnosed moderate thyrotoxicosis without concomitant cardiac pathology and in 16 healthy individuals (mean age 45.1±4.7 years). The baseline data and the results of incremental treadmill exercise tests were analyzed. It was shown that in the relatively early periods of thyrotoxicosis development, there were decreases in the left ventricle (LV) longitudinally and transversely and in the thickness of LV, without altering its sphericity and conicity. Along with weight loss, there were reductions in cardiac sizes with decreases in the local rates of cardiac wall movement, peak systolic and early diastolic rates of mitral movement velocities. During a treadmill test, there was a drastic reduction in the exercise tolerance threshold as compared to healthy individuals: 57.81±14.7 and 148.3±11.7 W, respectively.
The antidepressant effects of α-lipoic acid and reamberin in murine alloxan diabetes
Authors: Volchegorskiy I A , Rassokhina L M , Miroshnichenko I Y
Published: March 2014

The development of alloxan diabetes in mice is followed by a longer duration of despair behavior, homologous depression in man and a concomitant decrease in the activity of animals in the open field. The 2-week course of α-lipoic acid (α-LA) and reamberin in the doses equivalent to the human therapeutic range exerts an antidepressant activity, as appeared by a reduction in despair behavior and activation of sick mice in the open field. The antidepressant effect of 2-week use of α-LA and reamberin is associated with diminished hyperglycemia. Unlike α-LA, reamberin lowers the blood content of glucose in mice with alloxan diabetes, reduces their mortality, and corrects behavioral disorders in the open field even when relatively low doses are singly administered.
Immunotherapy for type 1 diabetes: state-of-the-art and prospects. Part 1
Authors: Laptev D N
Published: March 2014

The review summarizes experimental data from immunological studies in diabetes. It presents the basic immunotherapeutic areas in diabetes and describes the proposed mechanism for developing immunological tolerance. On-going clinical studies are briefly overviewed.
Estrogen receptors in the diagnosis and treatment of hormone-dependent tumors
Authors: Babichev V N , Marova E I , Fedotcheva T A , Shimanovskiy N L
Published: March 2014

The paper presents the current data available on the etiology of tumor diseases, among other things, shows the role of hormones, namely: estrogens and their receptors, in the mechanism responsible for the occurrence of these diseases. Each tumor was shown to have its receptor status and to be unresponsive to this or that therapy differently. The efficiency of treatment and its prognosis may be determined if the receptor composition of an involved organ is estimated correctly. The authors summarize the data available in the literature, as well as the results of their own investigations explaining the selective effect of estradiol receptor agonists and antagonists in various tissues. The mRNA varieties that potentially encoding for the synthesis of different subtypes of estrogen receptors (ER) - ER-α and ERβ, which are also coded by various genes located in different chromosomes. Pituitary adenomas as hormone-dependent masses are described in detail. The authors data on the concentration of nuclear estrogen receptors in different types of adenomas are given.
Classification, diagnosis, and treatment of idiopathic short stature
Authors: Shandin A N , Peterkova V A
Published: March 2014

Idiopathic short stature is the low stature in which all possible causes are excluded. The diagnosis and treatment of idiopathic short stature are the subject of constant controversy and discussion. With the expansion of indications for growth hormone therapy for conditions unaccompanied by growth hormone deficiency, there has been recently a challenge as to its use in idiopathic short stature. To date, there has been much worldwide evidence for the efficiency and safety of growth hormone therapy in children with idiopathic short stature. In 2008, the International consensus on the diagnosis and management of idiopathic short stature, prepared through the joint collaboration of three research societies: the Growth Hormone Society, the Lowson Wilkins Society of Pediatric Endocrinology (USA), and the European Society of Pediatric Endocrinology. The main points of this document have formed the basis for this paper.
Adipose tissue inflammation. Part 1. Morphological and functional manifestations
Authors: Shvarts Viktor
Published: March 2014

The review describes a new pathomorphological phenomenon: adipose tissue inflammation (ATI) that develops in obesity and is characterized by cell infiltration, fibrosis, microcirculatory changes, a shift in adipokine secretion and adipose tissue metabolism, as well as blood accumulation of nonspecific inflammatory markers, such as C-reactive protein, fibrinogen, leukocytes, the level of which reflects the degree of the process. The changes in adipokine secretion and shifts in fat and carbohydrate metabolism, which are typical of ATI, favor the development of atherosclerosis, essential hypertension, type 2 diabetes, and the metabolic syndrome. ATI shows up as a connecting link between these diseases and obesity. The definition of obesity as a chronic inflammatory disease is justified.
Capacities of complex ultrasonography in the differential diagnosis and management of thyroid nodular masses
Authors: Ul'yanova A E , Yarchenkova L L
Published: March 2014

The review presents the capacities of Doppler ultrasound study in the differential diagnosis and management of thyroid nodular masses. The problem of goiter does not presently lose its urgency. Palpable thyroid nodular masses are detectable in 4-7% of the worlds population [3, 4, 25] and the detection rate of thyroid abnormalities via radiation studies is 20 to 50% [4, 5]. Complex ultrasonography (USG) increases the obtained volume of information and its clinical value in nodular goiter. Examination of blood circulation in the thyroid and nodular masses involves two-dimensional gray-scale echography, color Doppler coding and Doppler spectrum analysis. The present Doppler study with color Doppler coding makes it possible to unify an assessment of the distribution of color flow maps in the vessels of nodular masses. Doppler spectrum analysis in nodular masses can confirm the enhanced blood flow in nodular tissue as compared with that in the intact parenchyma (increased linear blood flow velocities in the intranodular and/or perinodular arteries as compared with those in the adjacent tissue arteries). Doppler USG introduced early after thyroid surgery provides objective information on the area operated on and evaluates the course of its wound process, diagnoses early postoperative complications, and defines the adequacy of performed surgical intervention [1, 3, 7].
Idiopathic short stature: nosological entity, terminology, capabilities of therapy
Authors: Kasatkina E P
Published: March 2014

The paper deals with idiopathic short stature, one of the problems of pediatric endocrinology, and discusses the pattern and causes of this condition. Recommendation are given on the examination and treatment of children with the most common forms of short stature, such as late puberty, family short stature.
Vaccination against pneumococcal and influenza infections in children and adolescents with type 1 diabetes
Authors: Skochilova T V , Vorob'eva V. A. , Kostinov M. P. , Tarasova A. A. , Korovkina T. I. , Yushkova I. Y. , Lukachev I. V.
Published: March 2014

The effect of a Pneumo 23 vaccine against pneumococcal infection (n = 72; Subgroup 1) in combination with a Grippol vaccine against influenza infection (n = 28; Subgroup 2) was studied in children and adolescents with type 1 diabetes on insulin therapy. A control group consisted of 30 unvaccinated children. Unlike monovaccination, combined vaccination was ascertained to cause a significant reduction in the glycated hemoglobin following a year. The daily dose of insulin and the levels of high-density lipoprotein cholesterol, triglycerides, and b-lipoproteins were unchanged in all the groups. The level of albumins increased, by approximating to the normal values. The blood content of urea and creatinine remained to be in the normal range at all stages of the study. In Subgroup 2 children microalbuminuria was significantly decreased. Within a year after vaccination, all the children and adolescents with T1D also showed a reduction in the number of disease decompensation episodes, which being significant in Subgroup 2, resulting from the reductions in the incidence and severity of acute respiratory infections. In the vaccinated children, the number of late vascular diabetic complications remained unchanged. Vaccination against pneumococcal infection in 13 children before hospital discharge in the subcompensation phase was followed by the same changes in the biochemical parameters and the clinical course of T1D parameters as in the patients vaccinated in the phase of compensation of the disease. The dynamic abdominal ultrasonographic pattern was found to become worse in the unvaccinated patients than that in Subgroup 1 patients. Analysis of clinical, laboratory, and instrumental results indicated the stability of the course of T1D in the children and adolescents vaccinated against pneumococcal and influenza infections.
Malignant insulinoma
Authors: Troshina Ekaterina Anatol'evna , Yukina M Y , Egorov A V , Vasilyev I A , Krivko A A , Vasil'eva A G
Published: March 2014

According to official statistics, malignant insulinomas account for a small fraction of gastroenteropathic endocrine neoplasms, the majority of insulinomas being essentially benign tumours. This paper reports a clinical case of malignant insulin-producing neuroendocrine tumour of the pancreas tail in a 28 year-old woman. She had multiple liver metastases and organic hyperinsulinism. Results of comprehensive examination of the patient at the Endocrinological Research Centre including laboratory diagnostic data and their evaluation are presented. Her surgical treatment was accomplished in N.N. Burdenko Facultative Surgery Clinic, I.M. Sechenov Moscow Medical Academy. Treatment strategy in the post-operative period and follow-up observations are described.
Inflammation of adipose tissue. Part 2. Pathogenetic role in type 2 diabetes mellitus
Authors: Shvarts V
Published: March 2014

This review deals with the role of adipose tissue inflammation (ATI) in the development of type 2 diabetes mellitus (DM2). ATI is regarded as a link between obesity and DM2. The review illustrates the involvement of main adipokines in pathogenesis of DM2 and provides a detailed description of such factors as impaired adiponectin and stimulation of cytokine production responsible for metabolic disorders, activation of lipolysis, in adipocytes, increased fatty acid and triglyceride levels, suppression of insulin activity at the receptor and intracellular levels. Adipokines, in the first place cytokines, act on the insulin signal pathway and affect the intracellular inflammatory kinase cascade. At the intercellular level, ATI stimulates JNK and IKK-beta/kB responsible for the development of insulin resistance via such mechanisms as activation of cytokine secretion in the adipose tissue, oxidative stress, and induction of endoplasmic reticulum enzymes. The key role of JNK and IKK-beta/kB in the inhibition of the insulin signal pathway is mediated through inactivation of insulin receptor substrate 1. Also, it is shown that ATI modulates B-cell function and promotes progressive reduction of insulin secretion.
Statistical methods for the analyses in clinical practice. Part 1. Univariate statistical analysis
Authors: Rumyantsev P O , Saenko U V , Rumyantseva U V
Published: March 2014

Statistical analysis is an integral component of any clinical study. The objective of the present work was to assist clinicians in understanding various methods of statistical treatment of medical findings without going into details of mathematical computation. The most strongly sought for and popular analytical procedures are considered in application to clinical and experimental medical research. Part 1 of this communication is focused on descriptive statistics and methods of univariate statistical analysis. Part II will be concerned with the analysis of survivorship and multivariate statistics.
The first experience with selective blood collection from the inferior petrosal sinuses in Russia (case reports)
Authors: Dedov I I , Sitkin I I , Belaya Z E , Marova E I , Przhiyalkovskaya E G , Remizov O V , Rozhinskaya L Y
Published: March 2014

This paper reports two clinical cases of ACTH-dependent hypercorticism. Difficulties encountered in differential diagnosis of this condition were due to poor informative value of routine diagnostic methods. The use of selective blood collection from the inferior petrosal sinuses (for the first time in Russia) greatly facilitated the choice of the adequate treatment strategy. A detailed description of clinical features of ACTH-dependent hypercorticism in two young women is presented along with the results of laboratory and instrumental studies. Technical aspects of selective blood collection from the inferior petrosal sinuses in conjunction with the desmopressin stimulation protocol are considered. Indications for the use of this diagnostic method under real clinical conditions are proposed. Results of the study are discussed with reference to the treatment strategy chosen for the management of ACTH-dependent hypercorticism and the outcome of surgical intervention.