Preeclampsia is a major cause of maternal and fetal morbidity and mortality and its prediction, diagnosis and management still remain to be challenging. However, recent technological advances in the understanding of its pathophysiology have identified many biomarkers to aid prediction of women at risk of developing preeclampsia (PE). Many etiological factors for PE have been evaluated as biochemical markers in the maternal blood for the prediction and diagnosis of PE such as markers for renal dysfunction, hemolysis, metabolic status, inflammatory markers oxidative stress, placenta-derived factors, and endothelial dysfunction. Pregnancy can be regarded a state of oxidative stress as a result of increased placental metabolic activity and antioxidant defenses. Evaluation of markers of oxidative stress and their molecular pathways may be useful in finding the possible solutions for this disease entity. This article aims to review various oxidative stress biomarkers in preeclampsia and gives an account of cellular responses to oxidative stress at transcript, protein and metabolite level and summarizes the available patents with special emphasis on redox genomics, metabolomics and proteomics applications in maternal-fetal medicine. Keywords: Biomarkers, cord blood, maternal-fetal, oxidative stress, patents, preeclampsia, reactive oxygen species.
The kidneys control homeostasis by regulating plasma volume and hormone secretion and acid-base balance. These are delicate organs and, sometimes are weakened due to many kidney diseases and use of some toxins and excess drugs. Acute kidney injury (AKI) is an important cause of renal failure. The serum creatinine and blood urea are classical kidney biomarkers. New kidney acute injury biomarkers i.e. acute kidney injury (AKI) biomarkers are early indicators of kidney diseases, which may be used to save the lives of the patients. Therefore, analysis of AKI is essential and urgent issue in urology. The analysis of AKI biomarkers is reviewed. The article describes the-state-of-the art of the analyses of AKI biomarkers in urine, blood and breath samples. The attempts are made to discuss the sample handlings and analyses techniques. The analyses techniques discussed are chromatography, ELISA, NMR, nano technology and others. Some recent patents (2014-2015) have also been reviewed. Most of the patents available used immune assays detections of AKI biomarkers; except few where chromatography was used. Besides, the efforts have also been made to discuss correlation among AKIs biomarkers, serum creatinine and blood urea nitrogen. Additionally, the current and future developments are also highlighted in AKI biomarkers analyses. Keywords: Acute kidney injury, biomarkers, current and future developments, patents, sample handlings, techniques.
The aim of this study was to evaluate the diagnostic significance of the bone resorption marker β-Crosslaps for the detection of bone metastases in renal cell cancer patients. β-Crosslaps concentrations were measured in serum samples from 87 renal cell cancer patients. Of these, 35 men, 19 women, and 17 boys showed no bone involvement. 15 men and two women suffered from bone metastases. When comparing women with and without bone metastases by using an optimal cut off value (11.25ng/ml), the sensitivity of β-Crosslaps for detecting bone metastases was 100% and the specificity was 57.89%. Using an optimal cut off value (81.2ng/ml) in men, the sensitivity and specificity for detecting bone metastases was 93.33% and 91.42%, respectively. There was a significant increase (p < 0.01) in β-Crosslaps in patients with renal cell cancer as compared to healthy subjects. This difference existed even in the patients without bone metastases. Furthermore, the β-Crosslaps values increased with the tumor-node-metastases (TNM) system (T-value). β-Crosslaps were suitable as a diagnostic tool for the detection of bone metastases in men with renal cell cancer. In addition, the study showed a significant increase of the β-Crosslaps concentration in renal cell cancer patients without bone metastases, accompanied by an increase as the TNM stage (T-value) increased. β-Crosslaps could be useful as a tumor marker for renal cell cancer. Additionally a review of recent patents on tumor markers is provided. Keywords: Bone metastasis, bone turnover marker, β-Crosslaps, renal cell cancer, renal cell carcinoma, tumor marker
Diagnosis of glomerular diseases is based on renal biopsy, an invasive method that offers information about the type and severity of renal damage and predicts renal function outcome. Types of glomerulonephrities differ in etiology, pathogenesis, type of cell involvement, immune reactions, and subsequently in the disease outcome. During evolvement of the disease cytokines, chemokines, growth factors are produced by native of infiltrating kidney cells and excreted in the urine. These molecules may serve as biomarkers and may provide useful information in diagnosis, prognosis and response to treatment. An ideal biomarker should be easily collected and measured and have high sensitivity and specificity. Particular cytokines may have central roles in glomerular diseases. IL-6, MCP-1, IL-1β and EGF urinary excretion can predict renal function outcome in IgA nephropathy. Metaloproteinases, A1 antitrypsin, Tamm-Horsfall protein, MCP-1 and other molecules have been used in the discrimination between focal segmental sclerosis and minimal change disease, in predicting relapse of FSGS after transplantation and response to treatment. Recent patents have established measurement of urinary cytokines in follow up and treatment of renal diseases. Keywords: Biomarkers, cytokines, diagnosis, glomerulonephritis, histology, outcome, treatment.
El Editor Cientifico y Editor Tecnico de Maderas, Ciencia y Tecnologia agradecen a los revisores por su asistencia como arbitros en los procesos de revision por pares de la revista. La calidad de los contenidos cientificos de Maderas, Ciencia y Tecnologia depende del trabajo a conciencia de los colaboradores. Apreciamos su esfuerzo en la revision de los manuscritos y valoramos enormemente su disponibilidad para compartir su tiempo y experiencia con la Revista Maderas, Ciencia y Tecnologia. Apreciamos su evaluacion cuidadosa de los manuscritos recibidos durante 2014-2015.
Given the diabesity and Metabolic Syndrome epidemics, fatty liver disease is reaching epidemic proportions. Relatively indolent, this disease is often asymptomatic and the patient is often made aware of its presence only during a routine physical exam. Nevertheless, fatty livers are more susceptible to insult compared to their non-fatty counterparts and persons with fatty livers are at increased risk for morbidity and mortality following consumption of commonly used substances such as alcohol (EtOH) and acetaminophen (APAP). We have developed a rat model of natural diet-induced fatty liver disease and evaluated the effects of two commonly used substances viz. EtOH and APAP in this phenotype. High fat diet (HFD) fed animals exhibited steatosis, liver inflammation and liver fibrosis with an increase in serum aspartate aminotransferase. Bolus administration of EtOH, which was without effect on the livers from standard diet fed animals, had a profound and adverse impact on the HFD fatty liver. Similarly, APAP administration which was without effect on liver function tests in control animals, also provoked an increase in liver enzymes in HFD animals. Treatment with the poly(ADP-ribose) polymerase-1 inhibitor (PARP-1), veliparib, reduced the increase in liver function tests secondary to EtOH and APAP. This model forms the framework for identification of fatty liver disease biomarkers given that this disease is relatively asymptomatic but fraught with risk for acute injury. This model also forms the framework for evaluation of novel drugs for acute injury in fatty livers especially given that current strategies for management of acute liver failure in non-fatty livers are inadequate. Also, relevant patents related to the use of liver biomarkers as diagnostic are discussed.
Polycystic kidney disease (PKD) is characterized by the formation and expansion of fluidfilled cysts within the kidneys, painful renal enlargement and declining kidney function. Often, PKD manifests in other organs, including the liver and pancreas. In addition to cyst formation, interstitial collagen deposition is sometimes observed in both the kidney and the liver. While a diagnosis of PKD may be made using ultrasonography coupled with family history, monitoring disease progression is challenging as imaging techniques remain inadequate to track an increasing cystic index over time. Using the PCK rat model of PKD, we have identified a minimally invasive biomarker cluster with high correlative value for renal cystic index. This finding is important in that disease prognosis, patient compliance, interventional decisions and outcomes stand to be improved by regular disease monitoring. Identification of biomarkers of PKD also can better stratify transplant waitlists for kidneys or livers. Furthermore, rather than reliance upon a single biomarker, clinical outcomes may be better predicted from a cluster of disease-relevant biomarkers that correlates strongly with outcome. Clinical trials would also benefit from such biomarkers given the reluctance to invest in trials wherein clinical endpoints could be years away. Moreover, relevant patents are also discussed related to the use of renal biomarkers as diagnostics.
We examined the prognostic performance of measurements of cTnT concentrations at admission compared to discharge, in predicting major cardiovascular events during hospital admission and at six months follow-up. Methods and Results: The study population comprised 1351 patients with AMI and a mean age of 57.5 + 11.4 years, of whom 66% were males. Cardiac TnT was measured on admission, 24 hours, and at discharge using the Elecsys 2010 [Roche Diagnostics]. No significant difference was found in patients who were cTnT negative on admission [n = 345 (26%)] compared to the cTnT positive group [n = 1006 (74%)], with respect to baseline characteristics, infarct pattern, biochemical data, and major cardiac events. In 475 patients [35%], serum cTnT levels were found to be higher on discharge from the CCU compared to admission/24 hour levels. A significantly greater proportion of patients had hypertension [63% vs. 50%, p < 0.001], higher systolic blood pressures [133, IQR 115 -154 vs. 127, IQR 111 -147, p < 0.001], history of previous AMI [17% vs. 9%, p < 0.001], and previous angina [17% vs. 9%, p = 0.001] if the discharge cTnT levels exceeded the admission/24 hour levels. A total of 120 deaths occurred during the study period with a significantly greater number of deaths recorded in patients whose discharge cTnT levels were higher than the admission/24 hour values [54(11%) vs. 66 (8%); p = 0.02, respectively]. Multivariable analysis using logistic regression showed that cardiogenic shock [OR 5.92 {95% CI 2.86 - 12.28}; p < 0.001], cardiac failure [ OR 4.80 {95% CI 2.61 - 8.82}; p < 0.001], cerebrovascular accident [ OR 3.95 {95% CI 1.48 - 10.58}; p = 0.01], complete heart block [ OR 3.50 { 95% CI 1.22 - 10.09}; p = 0.02], increasing age [ OR 1.04 {95% CI 1.02 - 1.01}; p < 0.001], and a greater discharge cTnT value [ OR 1.61 (95%CI 1.01 - 2.56); p = 0.04] conferred a significantly higher odds of mortality. Conclusions: This study shows that, in addition to cardiogenic shock, cardiac failure, cerebrovascular accident, complete heart block, and increasing age, higher cTnT level at discharge is an important independent predictor of mortality in patients with AMI, and could further improve the prognostic accuracy of admission values of cTnT, based on relevant patents. Keywords: Acute myocardial infarction, adverse events, cardiac failure, cardiac mortality, coronary angiogram, troponin T.
Viruses lack the synthetic machinery, so they hijack the synthetic machinery of host cells to produce proteins; and in this process trigger cancer. Since current therapies are ineffective in dealing with virally induced cancers, a future goal could be to develop vaccines against these tumor viruses. Indeed, a recent patent has demonstrated the utility of host p16 peptide fragments to vaccinate against various HPV induced tumors like penile, anal, cervical, vulvar, vaginal and head and neck cancers. Another patent describes the use of host cell peptide fragments (Rb, Mupp, DLG1 and AP) expressed on surface of virally infected host for vaccinating against the various HPV induced cancers including head and neck cancers. A vaccine has been prepared from peptide antigens derived from HPV L2, to vaccinate against diverse strains of HPV. An HPV assay (RNAscope®) has been recently developed utilizing E6/E7 mRNA to detect high-risk HPV subtypes in head and neck cancer. Another patent deals with the use of two RNAases (ranpirnase and 805 variant of ranpirnase) against HPV infections. We have undertaken this review to summarize and delineate the role of viruses in carcinogenesis in the oral region. Keywords: Cells, dysplasia, host, lymphocytes, neoplasia, vaccine.
Preeclampsia is a multisystem disorder, pathophysiology of which is still not clear. It is one of the leading causes of maternal and fetal morbidity and mortality. Epigenetic programing is altered during fetal life and postnatal period and after birth, this sceniaro is changed to metabolic disorders of metabolic syndrome complex and this may contribute to future risk of hypertension, DM2, and cardiovascular disease. During (normal and abnormal) gestations, complex physiological changes occur in maternal blood. For studying next generation diagnostic biomarkers for maternal-fetal interface, it is essential to explore the protein changes in maternal serum during healthy gestation. Umbilical cord blood (UCB) is in contact with all the fetal tissues and can reflect both normal physiological as well as pathological states of the fetus. UCB can be compared with adult blood and the diagnostic potential of UCB still remains to be tapped. UCB will be a potential diagnostic medium in future in assessing infant health. Also, UCB can aid in detection and identification of candidate biomarkers for various disease pathways and it can be of help in assessing the existing or future adverse effects. Patents are available for biomarkers in preeclampsia and fewer patents are reported in UCB. Future studies will further uncover the diagnostic value of the umbilical cord blood in human physiology and pathology. Keywords: Cord blood, diagnostic, markers preeclampsia, maternal, patents.
Cancer Stem Cells (CSC) comprise a concept proposed in the 1990s in hematopoietic cancers. These cells were considered, by similitude to normal stem cells, to constitute a small pool of self-renewing cells able to maintain a tumor. Due to their quiescence, CSC would be able to avoid chemotherapeutics targeting fast proliferation rates, or radiotherapy, thus being responsible for tumour relapse. Since CSCs have also been implicated in invasion and metastasis and epithelial to mesenchymal transition (EMT) was proposed as a determinant of malignancy in epithelial cancers, the relationship between EMT and CSC is an important issue, which has been increasingly addressed in recent patents on CSC biology. A thorough search for a more accurate identification of these cells, as well as more effective drug search yielded a number of interesting research patents during the last 5 years, several of which are to be detailed in the present review. Keywords: Cancer stem cells, epithelial to mesenchymal transition, patents, stem cell markers, stemness targeting drugs, targeted therapy.
The genetic and epigenetic events appear to control the initiation and progression of cancer. The tenuous link between the environmental, lifestyle factors and genetic influences is being actively researched across the world. Epigenetic changes can control gene expression independent of mutations. The current advances in the cancer therapy are targeting on epigenetic mechanisms such as tumor- specificity of genes, DNA methylation, histone modifications, and the role of mi RNAs. The identification of cancer stem cells is a recent promising area in oncological research for a better understanding of tumor genesis. The lack of markers for the identification of cancer stem cells and their therapeutic targets currently has hindered the immediate applications in the clinical and management domain. The recent patents and their application are discussed. Keywords: Alcohol, epigenetic, genetic, oral cavity, squamous cell carcinoma, tobacco, viral oncogenesis.
Metastasis accounts for 90% of the mortality associated with breast cancer. Upregulated expression of members of the lysyl oxidase (LOX) family of secreted copper amine oxidases catalyzes the crosslinking of collagens and elastin in the extracellular matrix. LOXs are linked to the development and metastatic progression of breast cancers. Accordingly, aberrant expression of LOX-like 2 (LOXL2) is observed in poorly differentiated, high-grade tumors and is predictive of diseases recurrence, and for decreased overall patient survival. Therefore, LOXL2 expression may serve as a biomarker for breast cancer. Mechanistically, hydrogen peroxide is produced as a byproduct of LOXL2 when using an appropriate substrate, lysine. We exploited this chemistry to generate a revolutionary gold-based electrochemical biosensor capable of accurately detecting nanomolar quantities of LOXL2 in mouse blood, and in human blood samples. Two different sources of the blood samples obtained from breast cancer patients were used in this study indicating the applicability of detecting LOXL2 in breast cancers patients. Limited numbers of urine specimens from breast cancer patients were also tested. Collectively, all of these tests show the promise and potential of this biosensor for detecting LOXL2 as a surrogate biomarker of breast cancer. This work is described in WO 052962 A1 (2014).
The prevalence of cancer in our days remains at high level all over the world. Implementing and improving tools for better diagnostics and prognostics is a very active field of research aimed towards giving the patients the best possible management of their disease. Since the discovery of the presence of cell-free circulating DNA (ccfDNA) in the blood of cancer patients, it has been proposed as a tool for tumor diagnosis, follow-up of treatment and prognosis assessment. In fact, the strong link with molecular alterations found in the tumor has demonstrated effective as a prognostic tool specially regarding invasive types of cancers. Today, the circulating plasma tumor DNA (cptDNA), also known as liquid biopsy, promises an outstanding clinical test in routine cancer patient management, which is currently used in numerous clinical trials as a secondary parameter to follow outcome of the treatments being investigated. Besides describing patents covering specific markers, several patents have been recently filed for methods of cptDNA analysis. In this review, we aim to provide with a succinct summary of the current application of cptDNA as a tool for clinical management of the cancer patient. Keywords: Circulating plasma tumor DNA, copy number variation, liquid biopsy, loss of heterozygosity, methylation, mutation, prognosis.
Previously, preliminary results of our researches showed that, mobile phone radiofrequency radiation does not affect human serum in an in vitro immunoenzymometric assay. However, we stated that the results should be confirmed in a larger series and employing different exposure doses on a specific hormone. Considering this statement, the aim of this study was to investigate whether the exposure from a 900MHz cell phone can affect the thyroid Triiodothronine (T3) levels in human serum. In addition, a review of the recent patents in radiation and immunoenzymometric assays is also presented. Human serum samples from 63 healthy donors were placed into two groups, and the well heads in the first group were exposed to 900MHz exposure emitted from a GSM mobile phone (Nokia, Model 1202, India) with 1.09Watt per kilogram (W/kg) of the tissue locally in the head specific absorption rate for 30 minute. Unexposed group 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. There was no significant difference in serum T3 in the exposed group compared to the control group (P > 0.05). According to this study, mobile phone radiation at frequency of 900MHz does not affect human T3 hormone in an in vitro immunoassay under the conditions used. Keywords: Biomarkers, human thyroid hormone, immunoassay technique, mobile phone, radiofrequency radiation, triiodothronine.
Only in the last year, over 100 reports were published focusing on innovative dressing for hard to heal wounds. Complex technologies were developed to tackle the intricate mechanisms of wound healing and moreover to overcome the chronic status of the wound. The essential wound management recommendations include compression and moist wound environment maintanance. In clinical practice semi-occlusive/occlusive, antimicrobial, and advanced wound matrix dressings are already implemented. In the last 10 years, several patents disclosing materials, new approaches and technologies for biomarkers detection were published. Moreover patents that can indicate the stage of wound healing were also disclosed. The criteria for choosing the primary dressings should be patient-oriented meeting both patient’s characteristics and wound peculiarities, while not ignoring healthcare costs. Keywords: Biomarkers, inflammation, innovative dressings, nanotechnology, patents, proliferation, wound healing phases.
Objectives: Pronounced wound healing responses induced by phenytoin in inflamed gingivae have potential for matrix regeneration in this context. It enhances matrix formation in tissues and impairs their breakdown. The matrixregenerative responses of human periosteal fibroblasts to phenytoin and histamine were studied using the metabolite 5 alpha- dihydrotestosterone (DHT) as a marker of inflammatory wound repair; derived from 14C-testosterone and 14C-4- androstenedione as independent substrates in order to ascertain metabolic responses. Methods: Confluent monolayer cultures of human periosteal fibroblasts of the 5th-9th passage from eight subjects were incubated individually in 24-well multiwell plates in Eagle’s MEM. Independent incubations were performed with each of the substrates 14C-T and 14C-4- A, with optimal concentrations of histamine (H; 8μg/ml) and phenytoin at 1(Ph1) and 5μg/ml (Ph5) alone and in combination (H+Ph1; H+Ph5). Following 24h incubation the eluent was prepared for TLC in a benzene. Acetone solvent system (4:1) for the separation of metabolites. They were quantified using a radioisotope scanner. Results: The substrates a.14CT and b.14C-4A were metabolized to DHT, diol and 4-A or T respectively. With each substrate, yields of DHT were significantly increased over controls in response to H (a.74%; b.2.3-fold), Ph1, 5 (a.70%, 2-fold;b. 2.8-,1.9-fold) and the combinations (a.60%; b.2-fold and 73%), respectively (n = 8; p < 0.01/0.001). There were also significant increases in the yields of diol and T respectively in response to agents tested. Conclusion: Significant increases in yields of DHT in response to Ph and H with both substrates indicate their anabolic potential in periosteal fibroblasts. This has implications for diverse applications in tissue repair in an inflammatory environment. Patents relevant to matrix synthesis and its modulation by microRNAs during inflammatory healing responses have been discussed. Keywords: Biomarkers, histamine, inflammation, periosteal fibroblasts, phenytoin, wound repair.
Electromagnetic interference (EMI) is a phenomenon that may occur when an electronic device is exposed to an electromagnetic (EM) field. The aim of this study was to investigate whether the CC could be interfered by exposure to the 900MHz cell phones in the laboratory. In addition, a review of the recent patents in electromagnetic interference is also presented. Human whole blood samples were collected from 20 healthy donors and each sample was divided to four aliquots and was placed into four batches for in vitro quantitative determination of human whole blood components. During CC reading of the first, second and third batches, the CC (Technicon H3 RTCTM, Bayer Diagnostics GmbH, München, Germany) was exposed to 1.90, 0.69 and 0.38 W/kg exposure of 900MHz radiation, respectively. For the fourth batch (control group), no radiation was applied. The final scores in the exposed batches I, II and III were statistically significant relative to the control batch (P = 0.03). The EMI caused profound changes on the CC reading of whole blood valid and macro cells in the exposed batches compared to the control batch (P = 0.001). This study showed that CC can be interfered by mobile phone RF radiation at a closed contact (less than 5cm distance). More accurate follow-up studies are needed for the evaluation of the electromagnetic interference due to radiofrequency radiation from external sources such as mobile phones in medical environments. Keywords: Cell Counter, electromagnetic immunity, electromagnetic interference, electromagnetic shielding, mobile phone, radiofrequency radiation.
Identification of putative biomarkers is a need of modern society today. Biomarker measures a biological or pathogenic process that can predict disease prognosis. It is important for monitoring drug safety, identification of individuals who are most likely to respond to specific treatments, stratification of presymptomatic patients and quantification of treatment benefits. The peripheral blood based identification of biomarkers or disease signatures from psychiatric patients possesses an immense potential towards drug developmental process. Biomarkers have been used as an early diagnostic tool for neuropsychiatric disorders. Identification of potential biomarkers of psychiatric disorders has become most important when it comes to biological psychiatry related research area. Patent provides a legal protection given to a new invention which gives the holder exclusive right to use or sell the patented product. Hence, deep understanding towards patent system is important as it protects novel research outputs that may lead to invention of new drugs. The present review describes patents, its methods and validations focused on peripheral biomarkers including cerebrospinal fluid (CSF), plasma, serum and various neuropsychiatric disorders. Keywords: Biomarker, cerebrospinal fluid (CSF), epigenetics, miRNA, neuropsychiatric disorders, patent, plasma, serum.
Background: Metastatic Renal Cell Carcinoma (mRCC) is a malignancy with a poor prognosis due to inefficacy of chemotherapy and to the efficacy of immunotherapy only in few patients. The availability of agents directly targeting tumorigenic and angiogenic pathways, as Vascular Endothelial Growth Factors (VEGF) inhibitors, has significantly improved the outcome of these patients. Aim of this work is to evaluate the possible prognostic and predictive role of patent biomarkers on mRCC. Methods: We have done a critical review based on Level of Evidence (LOE) analysis of recent publications indexed on PubMed from January 2011 up to August 2014. These studies have evaluated whether biomarkers can have a correlation with clinical outcomes in metastatic RCC patients treated with VEGF-targeted therapy. Results: We identified a total of 25 articles. On the basis of results of randomized controlled trials and prospective and retrospective observational studies, we tried to assess the predictive role of biomarkers. Six of these biomarkers (VEGF, interleukin (IL)-6, hepatocyte growth factor (HGF), osteopontin, IL-8 and sVEGFR-3) showed a potential predictive role. Moreover, VEGF-A, IL-6 and IL-8 seem to have prognostic value. Conclusion: Despite intensive efforts, there are no validated predictive or prognostic biomarkers currently in use in patients with mRCC. This literature up date is trying to highlight the biomarkers potentially useful to predict response to VEGF-targeted therapy and those with a prognostic value. Keywords: Angiogenesis, HIF, kidney cancer, monoclonal antibodies, prognosis, therapy, VEGF.
