Press Release for EurekAlert! Zebrafish as an animal model to study the effects of endocrine disruptors

zebra-fish

Water is vital for our survival. However, water quality is always a concern for public health authorities as it may contain diverse environmental pollutants, including endocrine disrupting chemicals (EDCs). Endocrine disrupting chemicals are one group of potentially hazardous substances that comprise natural and synthetic chemicals, with the ability to mimic endogenous hormones or interfere with their biosynthesis, metabolism, and normal functions. Common examples are bisphenol A, triclosan, phthalates, lead, mercury, nickel and polychlorinated biphenyls, among others.

Fish are known to be quite sensitive to the effects of EDCs and therefore, are employed as research models to study the possible impacts of these chemicals in humans. In a review led by Purdue University (USA) and the University of Cartagena (Colombia), a team of researchers has proposed the zebrafish as a model to predict the effects of EDCs on humans using toxicogenomic tools, such as microarrays or whole-genome sequencing. This is possible due to the fact that zebrafish genes that have significantly altered expression after exposure to EDCs are very similar to those found in humans. In addition, many of the glandular system found in zebrafish have similarities with those in humans, making this fish model suitable to study alterations on the endocrine system.

According to the authors, vitellogenin and aromatase cytochrome P450 are key genes that can be monitored in zebrafish to detect the presence of EDCs in water samples, especially at environmentally relevant concentrations.

Toxicogenomic tools also offer the possibility to find new mechanisms by which EDCs alter the reproductive status of zebrafish, allowing its use to test the safety of new products entering the market. The possibilities are immense and the goal is to continue finding new markers of toxicity, and therefore alternative bridges to link EDC exposure to common diseases in humans.

Co-authors of the paper include Karina Caballero-Gallardo, Jesus Olivero-Verbel (University of Cartagena, Cartagena, Colombia) and Jennifer L. Freeman (Purdue University, USA).

Reference: Caballero-Gallardo, K.; et al (2016). Toxicogenomics to Evaluate Endocrine Disrupting Effects of Environmental Chemicals Using the Zebrafish Model., DOI: 10.2174/1389202917666160513105959

For more information about the article, please visithttp://benthamscience.com/journals/current-genomics/volume/17/issue/6/page/515/

Press Release for EurekAlert! An innovative active platform for wireless damage monitoring of concrete structures

Structural Health Monitoring (SHM) is playing an important role in evaluationprocess of structural integrity of concrete structures mainly because much of the expected construction demands will have to be accommodated on existing concrete structures with widespread signs of deterioration.

Electromechanical Impedance (EMI) sensing approach has been proven that could be an effective alternative experimental approach for the damage detection of concrete structures even at very early-age stages. The wireless monitoring system proposed in the present work, denoted as Wireless impedance or Admittance Monitoring System (WiAMS), retains the benefits of low-budgeted EMI-based monitoring system but is not limited by the data acquisition device sampling rate in conventional EMI monitoring systems. This is achieved by utilizing a credit card-sized Raspberry Pi single-board computer which is capable of transferring data without a base station, can perform processing-hungry operations like video streaming by just simply adding the WiAMS device to the home network and perform SHM.

Moreover, the use of the Raspberry Pi expands the available hardware interfaces making the sensing device to be ready not only as an SHM control unit, but also as a base station for many other useful sensing platforms like motion with video, audio or environmental sensors.

WiAMS, as a whole, additionally offers extensive features such as remote control, high processing power, wireless data upload to an SQL database, email notifications, scheduled and iterative impedance (or admittance) measurements and frequency spans from 5kHz to 300 kHz with resolution down to 1 Hz.

The proposed WiAMS is successfully applied on various concrete specimens detecting damage even in very early-age stages by establishing a damage identification index based on extreme value statistics.

Reference: Providakis, C.; et al (2016). An Innovative Active Sensing Platform for Wireless Damage Monitoring of Concrete Structures. Current Smart Materials., DOI: 10.2174/2405465801666160830155120

For More information about the article, please visit: http://benthamscience.com/journals/current-smart-materials/article/145156/

 

Press Release for EurekAlert! The effect of exercise on vascular function and stiffness in type 2 diabetes

A new study from the University of Sydney has found that regular aerobic exercise can improve artery health in people with type 2 diabetes (T2D). The findings from this study have been published in Current Diabetes Reviews, and shed new light on exercise as a therapy in this population.

Compromised arterial health is an underlying mechanism that promotes the progression of cardiovascular disease (CVD), which is the leading cause of death in individuals with T2D. Effectively managing CVD risk in this population is a major challenge for health professionals.

Exercise is one of the first lines of treatment recommended by health professionals to manage the array of complications associated with T2D, such as controlling blood sugar. While it has been consistently shown that exercise is exceptionally beneficial for managing CVD, blood pressure medication is the main treatment used to manage arterial health problems.

This new study combined the results of nine randomised controlled clinical trials investigating the effects of exercise in T2D. Kimberley Way, who leads the research, says: “We focussed on measures looking at arterial stiffness, vascular reactivity and smooth muscle function, because there is evidence that suggests they are closely associated with disease progression and CVD mortality.”

Ms Way statesadds: “What we found from our analysis, is that aerobic exercise, such as brisk walking or cycling appears to have a significantly beneficial effect on the stiffness and the function of the smooth muscles in the arteries. This makes our findings very valuable to health professionals, because aerobic exercise can be used as a primary treatment strategy for arterial health, while also assisting with other health complications associated with T2D. “

Citation: Way, K.L., Keating, S. E., Baker, M.K., Chuter, V.H., & Johnson, N.A. (2016). The Effect of Exercise on Vascular Function and Stiffness In Type 2 Diabetes: A Systematic Review and Meta-Analysis. Current Diabetes Reviews, 12(4), 369-383.

For more information about the article, please visit http://benthamscience.com/journals/current-diabetes-reviews/article/134035/

Press Release for EurekAlert! Non-ambient conditions in the investigation and manufacturing of drug forms

Before it reaches the store shelf, a drug molecule must be prepared in a very specific way. The nature of this prepared form is of the utmost importance, as it must be robust through manufacture, packaging, transport and storage. Ultimately, this prepared drug form must have the necessary physical properties to ensure that the correct amount of drug is available to the consumer. For the successful preparation of this drug form, one often needs to produce solid samples with a controlled crystal structure and specific particle size and shape. To complicate matters, these drug crystals are often required as a part of multi-component composites. The present review summarizes how extreme pressure and temperature conditions help to achieve this goal.

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To become a drug, a pharmacologically active compound must be prepared in a specific form. This form must be robust during manufacturing, packaging, storage and transport, and must administer the correct dose to the patient. To successfully prepare a drug form, one often needs to produce solid samples with controlled crystal structure and a specific particle size and shape. To further complicate matters, these compounds, these drug particles must often end up as a part of a multi-component composite. The present review summarizes how extreme pressure and temperature conditions help achieve this highly tuned material.

In modern culture, it is very rare to find an individual who has never taken any form of medication. It must follow that the pharmaceutical industry is required to produce an enormous quantity of drug products, which can take  a variety of different forms: solutions for injections, inhalation powders, sprays, tablets, ointments, patches, amongst others. In many cases, although adopting different administration routes, different trade names are used to market the very same active pharmaceutical ingredient (API). This begs the question: if these products are the same API, is there any difference in which form is taken?

Quite simply put, yes.

Drug molecules move around the body and, by necessity, act at the molecular level. However, many of these compounds are manufactured as solids, which must either be dissolved prior to injection, or are expected to dissolve on digestion in biological fluids. In either case, dissolution is required to release individual molecules into the body.

Solid pharmaceuticals containing the same API (either pure or with additives) can have different crystal structures (polymorphism) or be amorphous. Additionally, solid particles can differ in size, shape, meso-structure, and surface charge. Within the bulk material, the spatial distribution of an API and the additives can vary. Control of these, and many other, characteristics is within the scope of materials sciences and solid-state chemistry. The chemical and material properties of their physical form therefore needs to be identified and optimized for in vivo performance, reliable manufacture and the protection of intellectual property. 

Drugs are materials, not simply molecules [1-12], By viewing drugs in this way, one can apply the knowledge of solid-state chemistry, materials science and non-ambient conditions to obtain solid forms with optimized properties. These conditions include, among others, different types of mechanical and ultrasonic treatment, hydrostatic compression, high-temperature or cryogenic spray-drying, and crystallization from supercritical solvents. Solid-state reactions (e.g. dehydration or clathrate decomposition) can be efficient in accessing metastable polymorphs or in uniformly micronizing the sample. To achieve control over drug forms and the processes used for their robust manufacturing, one needs to account for both the thermodynamic and kinetic aspects of their transformations.

The review contains over 400 references and provides a comprehensive guide through the vast ocean of publications in this field. This work is based on the personal experience of the author over several decades of active research. ###

For more information visit: http://benthamscience.com/journals/current-pharmaceutical-design/volume/22/issue/32/page/4981/

Elena V Boldyreva

Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch of Russian Academy of Sciences, ul. Kutateladze, 18, Novosibirsk 630128 Russia

 

Press Release for EurekAlert! Nanomaterials for neurology: State-of-the-art

Despite the numerous challenges associated with the application of nanotechnology in neuroscience, it promises to have a significant impact on our understanding of how the nervous system works, how it fails in disease, and the development of earlier and less-invasive diagnostic procedures so we can intervene in the pre-clinical stage of neurological disease before extensive neurological damage has taken place.

Chronic neurodegenerative disorders are disease processes in which intrinsic functions of brain cells and systems are progressively altered. The enormous growth in our understanding of the brain that has taken place over the past several decades has not been accompanied by a comparable increase in the efficacy of treatment of neurological disorders.

Because nanotechnology uses bio-engineered systems that interact with biological systems at a molecular level, it can offer impressive improvement in the treatment of these disorders. Nanotechnological tools operate on a dimensional scale that facilitates physical interactions with neurons as well as with the smaller glial cells. These small-scale tools and devices have great potential for medicinal and pharmaceutical applications. Nanomedicine has already made the current drug regimen more effective with attributes like sustained release, increased half-life, higher drug concentrations at target sites, reduced toxicity and fewer side effects.

Nanotechnology shows great promise for the diagnosis and therapy of neurodegenerative disorders by supporting and promoting functional regeneration of damaged neurons, providing neuroprotection, and enabling the delivery of drugs, growth factors, genes and cells across the blood brain barrier.

In this review we provide a neurobiological overview of key neurological disorders and describe the different types of nanomaterials in use. We present many of the different applications that advances in nanotechnology are having in the field of neurological sciences and discuss the issue of toxicity of the nanomaterials.

In conclusion, we weigh in on what the promises and challenges lie ahead of researchers for future developments in this groundbreaking field.

 

For More information about the article, please visit: http://benthamscience.com/journals/cns-and-neurological-disorders-drug-targets/volume/15/issue/10/page/1306/

Reference: Veloz-Castillo, M.F.; et al (2016). Nanomaterials for Neurology: State-of-the-Art. CNS Neurol. Disord. Drug Targets., DOI: 10.2174/1871527315666160801144637

Press Release for EurekAlert! Antibody drug conjugates have shown clinical efficacy with acceptable toxicity

press-release

 

Antibody Drug Conjugates (ADCs) have shown a clearly documented efficacy and acceptable toxicity and can be easily implemented in oncology departments where chemotherapy administration is a routine practice. A similar efficacy with acceptable toxicity has been documented with Antibody Radionuclide Conjugates (ARCs) which need to be injected with the help of a nuclear medicine department which can be a limitation for referral from an oncologist.

In a review collecting the clinical results of 11 studies including 598 patients treated with 6 ADCs and 9 studies (including 377 patients treated with 5 ARCs), toxicity was generally less frequent with ADCs than with ARCs but often led to more uncomfortable side effects. Both conjugates have shown some clinical efficacy in terms of survival (progression free survival or overall survival) depending on the tumor type, radiosensitive or not.

The good results of both conjugates could be significantly improved in the future.Targeting Cancer Stem Cells (CSC) using both cytotoxic payloads (drugs or radionuclides) could delay tumor relapse. Preclinical studies have shown a promising therapeutic index with long-term tumor regression warranting a clinical application.

Efficacy of ARCs could be improved with the use of alpha-emitting radionuclides which deliver a high fraction of their energy inside the targeted tumor cell leading to highly efficient killing especially for isolated tumor cells or clusters of malignant cells in the body.

The efficacy of both ADCs and ARCs could be enhanced by parallel treatment with immune checkpoint inhibitors thus providing synergistic immunogenic cell death.

In conclusion therapeutic immunoconjugates using chemotherapeutic drug or radionuclides as cytotoxic payloads have clearly shown clinical efficacy, which could be significantly improved in the near future.

For more information about the article, please visit: http://benthamscience.com/journals/current-cancer-therapy-reviews/volume/12/issue/1/page/54/

Reference: Chatal J.F. et al Therapeutic immunoconjugates. Which cytotoxic payload: chemotherapeutic drug (ADC) or radionuclide (ARC)? Current Cancer Therapy reviews, 2016 DOI: 10.2174/1573394712666160805121312

 

Press Release for EurekAlert! Nanomaterials for neurology: State-of-the-art

Despite the numerous challenges associated with the application of nanotechnology in neuroscience, it promises to have a significant impact on our understanding of how the nervous system works, how it fails in disease, and the development of earlier and less-invasive diagnostic procedures so we can intervene in the pre-clinical stage of neurological disease before extensive neurological damage has taken place.

Chronic neurodegenerative disorders are disease processes in which intrinsic functions of brain cells and systems are progressively altered. The enormous growth in our understanding of the brain that has taken place over the past several decades has not been accompanied by a comparable increase in the efficacy of treatment of neurological disorders.

Because nanotechnology uses bio-engineered systems that interact with biological systems at a molecular level, it can offer impressive improvement in the treatment of these disorders. Nanotechnological tools operate on a dimensional scale that facilitates physical interactions with neurons as well as with the smaller glial cells. These small-scale tools and devices have great potential for medicinal and pharmaceutical applications. Nanomedicine has already made the current drug regimen more effective with attributes like sustained release, increased half-life, higher drug concentrations at target sites, reduced toxicity and fewer side effects.

Nanotechnology shows great promise for the diagnosis and therapy of neurodegenerative disorders by supporting and promoting functional regeneration of damaged neurons, providing neuroprotection, and enabling the delivery of drugs, growth factors, genes and cells across the blood brain barrier.

In this review we provide a neurobiological overview of key neurological disorders and describe the different types of nanomaterials in use. We present many of the different applications that advances in nanotechnology are having in the field of neurological sciences and discuss the issue of toxicity of the nanomaterials.

In conclusion, we weigh in on what the promises and challenges lie ahead of researchers for future developments in this groundbreaking field.

For More information about the article, please visit http://benthamscience. com/ journals/ cns-and-neurological-disorders-drug-targets/ volume/ 15/ issue/ 10/ page/ 1306/

Reference: Veloz-Castillo, M.F.; et al (2016). Nanomaterials for Neurology: State-of-the-Art. CNS Neurol. Disord. Drug Targets., DOI: 10.2174/1871527315666160801144637

Press Release for EurekAlert! Recent advances in site specific conjugations of antibody drug conjugates

Antibody-drug conjugates take the advantage of antigen specificity of monoclonal antibodies to deliver highly potent cytotoxic drugs selectively to antigen-expressing tumor cells.

The recent approval of Adcetris™ and Kadcyla™ as well as emerging data from numerous ongoing clinical trials underscore the role of antibody-drug conjugates (ADCs) as a new therapeutic option for cancer patients. The site-specific conjugation technologies to develop next-generation ADCs have grown rapidly since then and have proven to be robust platform for generating next-generation homogeneous ADCs. These homogeneous ADCs have exhibited superior properties in terms of stability, manufacturing, and therapeutic index over the conventional ADCs. Although most ADCs currently in clinical development rely on conventional conjugation chemistries, the first wave of site-specific ADCs has been promoted to clinical trials. The increased understanding from the clinical investigation of current ADCs and site-specific bio-conjugation technologies has enabled scientists to accelerate the discovery and development of the next generation ADCs with defined and homogeneous compositions. Ongoing efforts to improve conjugation technologies and understanding of structure-activity relationship will certainly broaden the role of ADCs and other conjugates for the treatment of cancer and potentially other immuno-mediated diseases.

Read the recently published research on “Recent Advances in Site Specific Conjugations of Antibody Drug Conjugates (ADCs)” from the journal Current Cancer Drug Targets”

Press Release for EurekAlert! Role of vitamin D in vascular complications and vascular access outcome in patients with chronic kidney Disease

In recent years, a growing interest has prompted research to find new links between vitamin D and the renin-angiotensin-aldosterone system (RAAS), cell proliferation, and anti-apoptotic cell paths in the vascular system. The activation of vitamin D receptors (VDRs) on endothelial cells induces changes in the metabolic activity of the endothelium and is responsible for cell survival, proliferation and neoangiogenesis.

Recent studies linked vitamin D deficiency with cardiovascular diseases. For example, studies have shown that normal levels of vitamin D have a pivotal role in reducing the physiological activity of RAAS, due to the suppression of the renin gene, renin reduced disposal and the decrease of its circulating levels, thereby down-regulating the RAAS.

In particular, vitamin D blunts the compensatory increase of renin synthesis occurring during chronic administration of anti-RAAS agents. Indeed, in experimental models, the administration of vitamin D analogs blocked the compensatory increase of renin expression ameliorating the efficacy of RAAS inhibitors.

Deficiency of vitamin D in patients with chronic kidney disease (CKD) or in patients with end stage renal disease (ESRD) receiving hemodialysis is not only a key factor in the development of secondary hyperparathyroidism, but it is also associated with other complications. The immunomodulatory and anti-inflammatory effects of vitamin D may have particular relevance in CKD patients and in ESRD patients, as the uremic state induces biochemical changes that turn in a marked condition of inflammation and oxidative stress as observed in calcitriol deficiency status.

Few and very recent studies have directly investigated the role of vitamin D in vascular access. Two retrospective studies and one randomized, double-blind prospective study analyzed the effects of vitamin D on arterious-venous fistula (AVF) patency with contrasting results. Therefore, to better define the relationship between vitamin D and AVF outcomes, more studies involving a large number of patients are required.

Read the recently published research on “Role of vitamin D in vascular complications and vascular access outcome in patients with chronic Kidney disease” from the journal “Current Medicinal Chemistry”

Press Release for EurekAlert!Cyclic opioid peptides

Peptide based drug candidates are being discovered at an increasingly rapid pace as therapeutics for many diseases and pain management. . For decades the opioid receptors have been an attractive therapeutic target for pain management and many endogenous opioid peptides have been known to produce opioid activity and analgesia. However, their therapeutic potential has been limited due to a major drawback regarding their use as CNS drugs, mainly due to a lack of biodistribution to the brain caused by poor metabolic stability and an inability to penetrate the blood brain barrier.

Cyclic opioid peptides with more constrained topographical structure possess high potential to overcome these drawbacks compared to their linear parent peptides. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic peptides by implementing additional cycles. The increased rigidity/topological geometry of polycyclic peptides further attenuates the dynamic nature of the compound, promoting greater affinities and selectivities at target receptors as well as increased in vivo stability. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored, but should be considered for future designs in opioid receptor ligands.

In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches have been successfully used that highlight the benefit of cyclization and have provided many promising leads for novel therapeutics. The future of providing relief from disease states at the opioid receptors is encouraging as recent developments in our understanding about cyclic opioid peptide ligands are augmenting our capabilities of using biologically derived molecules as strong therapeutic agents.

Read the recently published research on Cyclic opioid peptides from the journal “Current Medicinal Chemistry”

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