The endocannabinoid system: critical for the neurotrophic action of psychotropic drugs

There is growing evidence that neurotrophins besides their well-established actions in regulating the survival, differentiation, and maintenance of the functions of specific populations of neurons, act as the potential mediators of antidepressant responses. Previous studies on the regulation of nerve growth factor (NGF) levels by psychotropic medications are limited in scope and the underlying mechanism(s) remain elusive. In this review, the latest findings on the effects of pharmacologically heterogeneous groups of psychotropic drugs on NGF contents in the brain regions involved in the modulation of emotions are summarized. Moreover, the therapeutic potentials of the endocannabinoid system which is linked to depression and/or antidepressant effects and appears to interact with neurotrophin signalling, are reviewed. New findings demonstrate that endocannabinoid system is involved in the mechanisms of action of certain psychotropic medications including neurokinin receptor antagonists and that these are mediated via the upregulation of brain regional levels of NGF. This provides a better understanding of the pathophysiological mechanisms underlying neuropsychiatric disorders, leading to novel drug designs.Biomedical Reviews 2010; 21: 31-46

Tissue engineering and growth factors: updated evidence

In difficult-to-treat disorders, the traditional pharmacological agents or medical devices alleviate the symptoms but do not reverse the condition. In recent years, the increasing interest into the field of tissue engineering has generated different strategies for tissue growth in vitro or the enhanced repair of damaged tissues in vivo. The core approach of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells in a variety of ways. In this context, identification of the ideal cells and development of biomaterials including the scaffolds for potential applications in the repair, replacement, or regeneration of damaged tissues appear crucial. Meanwhile, successful tissue engineering is often dependent on the delivery of growth factors to the regenerating tissues. Growth factors are multifunctional peptides which play fundamental roles in a wide variety of physiological processes including cell proliferation, chemotaxis, intercellular signalling, angiogenesis and the formation of extracellular matrix, also the re-establishment of tissue integrity. In order to mimic the endogenous profile of growth factor production during the natural tissue morphogenesis or regeneration, the sophisticated mechanisms of growth factor delivery should be developed. This review highlights the general aspects of tissue engineering along with the approaches taken to incorporate growth factors within the biomaterials and their delivery to injured tissue.Biomedical Reviews 2012; 23: 19-35

Nanopharmaceuticals: Innovative theranostics for the neurological disorders

Over the past few decades, nanotechnology has emerged as a topic of great interest with a wide range of scientific investigations. This highly sophisticated technology covers a vast array of materials and devices including the high-resolution imaging for the early diagnosis of diseases and targeted delivery of genes or drugs leading to a more efficient therapeutic outcome. The limited efficacy of currently available therapeutic options against the neurological disorders have evoked tremendous efforts towards the development of novel treatment strategies. In this respect, multifunctional nanoparticles for targeted delivery of drugs across the blood-brain barrier have been designed to improve the bioavailability and reduce the side effects. Nanoengineered materials or nanodevices with ability to interact with biological systems including the nervous system have been designed for tracking the real-time dynamics of receptors in the central nervous system as well as neuronal recording or stimulation that may result in the neuroprotection or neural regeneration. Indeed, application of the cutting-edge nanotechnologies may revolutionize our knowledge about the neurophysiology and neurobiology including the cellular or molecular events in neurons leading to the more efficient treatments in central nervous system disorders. In the present article, an overview of the theranostic (therapeutic and diagnostic) potential of nanopharmaceuticals in the neurological disorders has been provided.Biomedical Reviews 2014; 25: 25-34

Computational modelling: moonlighting on the neuroscience and medicine

Computational modelling has emerged as a powerful tool to study the behaviour of complex systems. Computer simulation may lead to a better understanding of the function of biological systems and the pathophysiological mechanisms underlying various diseases. In neuroscience, modelling techniques have provided knowledge about the electrical properties of neurons, activity of ion channels, synaptic function, information processing, and signalling pathways. Using simulations and analysis in network models has resulted in greater understanding of the behaviour of neural networks and dynamics of synaptic connectivity. Moreover, the correlation between the neurobiological mechanisms and a cluster of physiological, cognitive, and behavioural phenomena may be explored by the computational modelling of the neuronal systems. In this context, a significant progress has been made in understanding of the neural network architectures including those with a high degree of connectivity between the units, information processing, performance of complex cognitive tasks, integration of brain signals, as well as the dynamic mechanisms and computations implemented in the brain for making goal-directed choices. Computational models are able to explore the interactions between the brain areas which are involved in predictive processes and high-level skills. In this review, the significance of computational modelling in the study of neural networks, decision-making procedure, nerve growth factor signalling, and endocannabinoid system along with its medical applications have been highlighted.Biomedical Reviews 2013; 24: 25-31

Nanoparticles reshape the biomedical industry

Over the last decades, increasing interest has been attracted towards the nanotechnology which provide a set of promising research tools and theranostic approaches. Tremendous research efforts in nanofabrication technology have led to the production of biocompatible nanostructures and advanced carriers with various configurations for protection of the loaded biomolecules or drugs against the metabolism or excretion. Furthermore, controlled delivery and targeted therapy may result in the improved therapeutic effects against a variety of diseases and reduced adverse effects of drugs. The efficiency of protein drugs may be negatively affected by their limited transportation within the body and short half-lives. Application of nanoparticles may significantly improve the pharmacological profiles of protein drugs. In neurology, high-resolution imaging techniques, nanoengineered materials capable of interaction with the nervous systems, and nanopharmaceuticals with minimal toxicity and improved bioavailability may be of great theranostic significance. This may provide remarkable breakthroughs in the pharmaceutical industry and health-care system. In the present review, the significance of nanotechnology and modeling approaches in health-care system has been highlighted

Resveratrol: More than a phytochemical

In recent years, alternative and complementary medicine including the plant-based drugs with antioxidant and neuroptotective effects has attracted a growing interest. Resveratrol, a polyphenolic compound which is found in various plant species, has emerged as a promising nutraceutical with therapeutic potentials in neuropsychiatric, cardiometabolic and cancer diseases, also aging. The abundance of research providing promising findings about the multi-spectrum therapeutic applications of resveratrol and its encouraging potential to treat or prevent chronic and age-related disorders has raised a considerable number of clinical trials. Recently, resveratrol is implicated the biology of nerve growth factor (NGF), a critical player in the maintenance of neuronal growth and function. Furthermore, resveratrol affects the endocannabinoid signalling (eCBs) which exerts modulatory effects in the survival signalling pathways, neural plasticity, and a variety of neuroinflammatory and neurodegenerative processes. The therapeutic effects of this ubiquitous signalling system in Alzheimer`s disease, epilepsy, multiple sclerosis, mood and movement disorders, spinal cord injury, and stroke have been well-documented. In the present review, the implication of NGF and eCBs in the mechanism of action of resveratrol, that may be of therapeutic significance in neurological and non-neurological disorders, is highlighted. Biomed Rev 2015; 26: 13-21

Creation of Nanorobots: Both State-of-the-Science and State-of-the-Art

Over the last decade, remarkable achievements in nanofabrication technology has led to the development of hybrid intelligent systems including the nanomechanical devices powered by the chemical energy sources or biomolecular motors. In this context, nanorobotics has emerged as a highly-advanced technology for designing the fully functional smart devices or robots at nano scale. Development of these highly-controlled and functional nanostructures for sensing, information processing, signaling, and actuation may provide remarkable breakthroughs in medicine such as the improved imaging or targeted therapeutic interventions. Besides the detection and destroying the toxic materials and ecosystem restoration, the stimuli-responsive nanorobots may be used for the diagnosis or treatment of cardiac disorders, traumatic injuries, diabetes, and bacterial or viral infections. These molecular tools with nanoscale resolution facilitates early diagnosis in cancer and precise localization of anticancer agents leading to the minimal side effects. Nanorobots may easily traverse the human body and repair the cells or assist an improper functioning organ. These tiny devices integrated with wireless locomotion, external or internal power supply, artificial intelligence, and smart sensors may also be used for targeted delivery of genes or drugs into the single cells or tissues, tele-operation, or patient monitoring. Indeed, development of the medical nanorobots with a wide range of capabilities is a proof of concept and art in modern science and a breakthrough in nanotechnology which has been highlighted in the present manuscript

Application of Carbon Nanotubes for Controlled Release of Growth Factors or Endocannabinoids: A Breakthrough in Biomedicine

Carbon nanotubes, the nanostructures with immense potential in various scientific fields such as the regenerative medicine, have emerged as innovative nanosreservoirs with multimodal functionality and application in theranostic sessions. The superior mechanical properties, high thermoelectrical conductivities, or improved solubility and biocompatibility have made CNTs as suitable candidates for biosensing, high-resolution imaging, tissue-engineering, and delivery of a variety of compounds with poor solubility or short half-life. These advanced nanovectors which promote neuronal growth and functional connectivity, have shown great theranostic potential in the central nervous system disorders. Several pioneering works have shown the ability of CNTs for controlled release of drugs or growth factors into the brain. Over the last decade the neurotropic and metabotrophic effects of nerve-growth factor, brain-derived neurothropic factor and endocannabinoid system and their involvement in the mechanism of action of a wide variety of drugs have been the focus of intense research. In order to overcome the rapid degradation and/or non-specific distribution of nerve-growth factor or endocanabinoids, conjugation with CNTs has led to the prolonged effects of these modulating factors. Based on their unique properties, the appropriate application of functionalized CNTs may indeed revolutionize the current biomedical interventions that has been highlighted in the present review

A Case Based-Shared Teaching Approach in Undergraduate Medical Curriculum: A Way for Integration in Basic and Clinical Sciences

To present a multiple-instructor, active-learning strategy in the undergraduate medical curriculum. This educational research is a descriptive one. Shared teaching sessions, were designed for undergraduate medical students in six organ-system based courses. Sessions that involved in-class discussions of integrated clinical cases were designed implemented and moderated by at least 3 faculties (clinicians and basic scientists). The participants in this study include the basic sciences medical students of The Tehran University of Medical Sciences. Students’ reactions were assessed using an immediate post-session evaluation form on a 5-point Likert scale. Six two-hour sessions for 2 cohorts of students, 2013 and 2014 medical students during their two first years of study were implemented from April 2014 to March 2015. 17 faculty members participated in the program, 21 cases were designed, and participation average was 60 % at 6 sessions. Students were highly appreciative of this strategy. The majority of students in each course strongly agreed that this learning practice positively contributed to their learning (78%) and provided better understanding and application of the material learned in an integrated classroom course (74%). They believed that the sessions affected their view about medicine (73%), and should be continued in future courses (80%). The percentage demonstrates the average of all courses. The program helped the students learn how to apply basic sciences concepts to clinical medicine. Evaluation of the program indicated that students found the sessions beneficial to their learning

Effect of Celecoxib on the Peripheral NO Production

Objective(s)Celecoxib acts through both COX-2-dependent and -independent pathways. According to the paradoxical effect of NO on the inflammatory and nociceptive signal processing, the present study designed to evaluate the probable contribution of NO in the analgesic and anti-inflammatory properties of celecoxib. Materials and MethodsDifferent intensities of inflammatory pain were induced by acute and chronic sc administration of 1%, 2.5%, or 5% formalin and spectrophotometrical analysis of the serum nitrite was performed. Then, in the pretreatment process, the effect of celecoxib (10, 20, or 40 mg/kg/ip) was evaluated on the inflammatory pain induced-nitrite. Also, the effect of celecoxib alone (under non-inflammatory condition) was evaluated on the peripheral NO production and the results compared with that of the vehicle. ResultsFormalin-induced inflammatory pain led to an enhancement of the serum nitrite in intensity- and time-dependent manners. Celecoxib (40 mg/kg/ip), except its ineffectiveness on the nitrite level, induced 1.5 hr after 5% formalin, reduced production of formalin-induced nitrite in other cases. Meanwhile, under non-inflammatory condition, 1.5 hr after the administration of celecoxib (40 mg/kg/ip), a considerable elevation of nitrite was observed. Celecoxib 10 or 20 mg/kg/ip did not show a significant effect on either inhibition or stimulation of the peripheral NO.ConclusionNO is involved both in the inflammatory and non-inflammatory conditions. It seems that celecoxib exerts a dual effect on the peripheral NO production; it prevents overproduction of NO due to the induction of inflammatory pain, while, it stimulates NO synthesis at the early stage of its action