Recent Patents on Biomarkers (Discontinued) - Volume 3, Issue 3, 2013

The purpose of this systematic review is to investigate on the relationship between synovial level of cytokines and matrix metallo-proteinases and temporo-mandibular joint (TMJ) internal derangements (IDs) and/or osteoarthritis (OA). Twelve studies were included in the review and markers were evaluated in respect to IDs and OA. Findings from these investigations highlighted that higher levels of IL1β, IL-6, IL-11, TGFβ1 were associated to TMJ's OA; on the other hand, higher levels of MMP-2 and MMP-9 could correlate to ID without reduction (IDw/oR). Furthermore, higher levels of MMP-9 could associate also to severe condition of TMJ's OA. The findings of this systematic review could represent a useful tool for diagnosis and prognosis of TMJ's diseases, particularly about the effectiveness of arthroscopy and/or arthrocentesis in patients submitted to repeated surgical treatments. The paper also outlines some recent patents.

Congestive heart failure (CHF) is an increasingly common and severe condition that confers substantial morbidity and mortality. In advanced CHF, progressive functional impairment of renal function and structural renal disease may eventually develop. This condition has been recognized and is increasingly referred to as one manifestation of the cardiorenal syndromes (CRS), particularly its subtypes 1 and 2. These are defined by either acute or chronic deterioration in renal function depending on the rate of progression of CHF. This review first briefly highlights important features of the epidemiology, pathophysiology and treatment of CHF, then defines and briefly describes the various cardiorenal syndromes and their unique features. Recent patents for diagnosis and treatment of the cardiorenal syndromes 1 and 2 are then presented in the patent review coverage section and summarized in a table. Patents and patent applications on pharmacotherapeutics including novel diuretic agents, natriuretic peptides, endothelin antagonists, vasodilators and renal drug delivery systems, vasopressin receptor antagonists, among other compounds are presented. In addition, device-based patents for renal sympathoadrenergic denervation or modulation, isolated transluminal renal perfusion, bio-artificial cellbased therapies and implantable fluid removal devices, among others, are a special focus of this review. Potential future developments are also touched upon in conclusion.

Endothelial cells are key modulators of multiple physiological processes, and their impairment may result in the generation of endothelial dysfunction and ultimately cardiovascular diseases. Under physiologic conditions, reactive oxygen and nitrogen mediators of endothelial cells act to propagate signals driven by different stimuli, by forming molecules with a longer half-life like hydrogen peroxide. Reactive oxygen species (ROS) are constantly produced as a consequence of aerobic metabolism. Under physiologic conditions, their tendency to cause oxidative damage is counterbalanced by the action of antioxidants or oxidant-scavenging enzymes. An imbalance in favour of oxidants leads to oxidative stress, which can result in cardiomyocyte apoptosis and reduced bioavailability of vascular nitric oxide (NO). Together, these processes may lead to altered vasodilatation of the coronary, pulmonary and peripheral vascular beds. Myeloperoxidase is a key enzyme, capable of impairing intracellular NO reservoirs as well as producing oxidized amino acids such as 3-chlorotyrosine or 3-nitrotyrosine. Recent literature data have shown that apart neutrophils, this enzyme may be expressed by other cell types, and remarkably by endothelial cells both in vitro and in vivo, as a consequence of the exposure to oxidative stress. In this review we analyze recent literature and patents related to the detection, quantification and role of myeloperoxidase as a biomarker in patients affected by chronic heart failure or other cardiovascular diseases. A particular focus is given to analytical approaches aimed to detect early signals of variations in ROS or related enzymes or their by-products, via serological or other low-invasivity assays. The developments in this field may constitute a key improvement of the ability to manage and treat patients suffering from CHF as well as allowing to elucidate the molecular mechanisms behind the clinical phenomena.

The etiology of Alzheimer's disease (AD) is complex which includes oxidative stress, apoptosis, mutations in genes, imbalance in metal homeostasis and neuroinflammation. Biomarkers such as micro RNAs, peptides, protein complexes and genes in various body fluids of AD patients play a pivotal role not only in diagnosis of the disease but also in following the therapeutic effects of drugs employed to treat this neurodegenerative disorder. However, there has been a substantial dearth in diagnosing this disease at the earliest. This review focuses on recent advances and patents in the field of biomarkers of AD. It strongly emphasizes the growing need to translate the available and upcoming knowledge into substantial clinical trials to streamline a vital armamentarium for the disease.

Bone and soft-tissue sarcomas tend to present in young adults. A wide variety of serological markers have been associated with osteosarcoma. Tumor markers involved in angiogenesis, cell adhesion, apoptosis, and the cell cycle have been shown to play an important role in osteosarcoma growth, differentiation, and metastasis. However, there are no universal and specific serum tumor markers for early diagnosis of osteosarcoma and primary screening in risk groups. There is strong empirical evidence that the IGF signal transduction pathway may be important in osteosarcoma. Several patents of IGF and molecular biomarkers/panels in osteosarcoma have been reported. The tissue/serum biomarker panels using high-throughput technology molecular signatures will have a role in early detection of the disease and noninvasive testing.

Catheterization is a risk factor for the development of urinary tract infections. On the other side, urinary tract infections in catheterized patients associated with abnormalities increase the risks of therapy failure. Different kinds of microorganisms (bacteria, yeasts) can be associated with urinary infections in catheterized patients. Aim of this review is to summarize the main factors involved in the development of infections in catheterized patients, focusing on the mechanisms related to colonization and biofilm formation. Current prevention and treatment strategies are also reviewed, both referring to experimental studies and to currently approved materials. Our experience in the field of chemically treated materials for preventing infection in intracorporeal urinary catheters (stents) and relevant patents are also reported.

MicroRNAs (miRNAs) are a class of endogenously expressed, small noncoding RNAs, which play a crucial role in regulating different cellular processes. They are emerging as a new class of cancer biomarkers due to their deregulation and their stability in formalin-fixed tissue, blood and urine, making them easy and non-invasive biomarkers. In this review, we summarize some current knowledge about the potential use of miRNAs as biomarkers for ductal breast carcinomas, acute myeloid leukemia, prostate and cervical cancers highlighting some recent patents on discovery of miRNAs as novel biomarkers for those four cancers. miRNAs have been found out as circulating biomarkers for breast, acute myeloid leukemia and prostate cancers, as well as urine biomarkers for prostate, and only tissue biomarkers for cervical cancers. Some miRNAs are commonly deregulated in several cancer types (e.g., miR-34a, miR-182) but only few are type specific, offering an accurate biomarker for a particular cancer. In addition, miRNAs can help in recognizing certain cancers subtypes, for example, there are 12 down-regulated and 3 up-regulated miRNAs for the diagnosis of HER+ve breast cancer subtype, while there are 2 down-regulated miRNAs and 11 up-regulated miRNAs for HER-ve. For cancer staging, miRNAs were found to be a useful tool, in breast and prostate cancers, giving accurate indication for the stage and grade of cancer. Moreover, miRNAs serve in prognosis of acute myeloid leukemia and prostate cancers. Thus, miRNA expression in different body sites and fluids could serve as a useful diagnostic and prognostic biomarker for different cancers that should be expanded upon for future improvements in this sector.

The aim of this study was to investigate whether the thyroid Triiodothronine (T3) levels in the serum could be interfered by the exposure to the 900MHz cell phones in the laboratory. We also reviewed a selected number of recent patents relevant to the area of RF radiation and biomarkers. Human serum samples from 29 healthy donors were labeled with ruthenium to form a sandwich complex based on an immunoassay technique. All of them were placed into two batches, and the well heads in the first batch were exposed to 900MHz exposure emitted from a GSM mobile phone simulator for 18 min. Unexposed batch was served as the control sample under identical conditions and was compared with the exposed one in quantitative determination of T3 using the Wilcoxon test with criterion level of P = 0.050. Using the Wilcoxon test, there was no significant difference in serum T3 in the exposed group compared to the control group (P = 0.541). More accurate follow up studies are needed for the evaluation of the effects of the mobile phone use. The results here should be confirmed in the in vivo situation on mammalians and in larger series.