YKL‐40: The Search for New Biomarkers in Rheumatoid Arthritis

There is a need for biomarkers to detect early joint inflammation and destruction of cartilage in different types of arthritis. YKL‐40, a 39 kDa heparin‐ and chitin‐binding secreted glycoprotein (also known as human cartilage gp39), has been recently discovered. Its exact biological function is still unclear. Specific receptors for YKL‐40 have not been identified yet. The clinical significance of YKL‐40 as a biomarker is discussed in different aspects. High level of YKL‐40 is found in various human i`nflammatory and neoplastic diseases. We present a review highlighting the information available on YKL‐40 and its significance in inflammatory joint diseases, like rheumatoid arthritis (RA). We also report original personal data on the topic concerning YKL‐40 levels in serum and synovial fluid of patients with RA in comparison with ultrasonographic parameters and cytokine levels. The findings suggest that YKL‐40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation

Regulation of Retinoid Receptors by Retinoic Acid and Axonal Contact in Schwann Cells

Background: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type. Methodology/Principal Findings: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-c depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-c mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-b mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability. Conclusions/Significance: All together, our results show that retinoid receptors are regulated in a complex manner i

Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment

Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>Community acquired (CA) methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear.</p> <p>Results</p> <p>We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from <it>S. epidermidis</it>. The USA300 sequence was aligned with other sequenced <it>S. aureus </it>genomes and regions unique to USA300 MRSA were identified.</p> <p>Conclusion</p> <p>USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.</p

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis?

Background: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction

Glioblastoma Multiforme Classified As Mesenchymal Subtype

ВВЕДЕНИЕ: В качестве неблагоприятных прогностических факторов при первичных глиобластомах в последнее время обсуждаются не только клинические показатели, но и различные клеточные, генетические и иммунологические маркеры. ЦЕЛЬ: Работа ставит себе целью анализировать случай с первичной мультиформенной глиобластомой и краткой выживаемостью после оперативной интер- венции, а также и определить неблагоприятные прогностические маркеры. ПРЕДСТАВЛЕНИЕ СЛУЧАЯ: Авторы представляют случай 71-оголетнего мужчины с доказанной мультиформенной глиобластомой и постоперативной выживаемостью в 48 дней. Из-за непродолжительной выживаемости пациент не подвергнут телегамматерапии и адювантной терапии Темозоломид- ом. С помощью молекулярно- биологических и иммунологических анализов определены транскрипционные и сывороточные уровни TNF-α, IL-6, YKL-40 и CD44. Устанавливаются экстремно высокие транскрипционные уровни генов CD44, IL-6 и YKL-40, увеличенная экспрессия TNF-α, сопровожденные повышенной сывороточной концентрацией IL-6, TNF-α и YKL-40 и пониженной сывороточной концентрацией CD44. ЗАКЛЮЧЕНИЕ: Молекулярно-биологически