Session Introduction

Hamed Benghuzzi

University of Mississippi Medical Center USA

Title: The impact of sustained delivery of reproductive hormones on the hypothalamic-pituitary-gonadal axis in males and females using different animal models

Biography:

Dr. Hamed A. Benghuzzi, professor of health sciences at UMC, has been elected as the president of the Mississippi Academy of Sciences.Benghuzzi earned his PhD at the University of Dayton.He completed a pathology fellowship at the University of Michigan.He joined the UMC faculty in 1993 as assistant professor of health sciences.

Abstract:

Manipulation of gonadotropin hormones (luteinizing (LH) and follicle stimulating hormones (FSH)) in ewes in non-breading season is a major challenge to the scientific community. We hypothesized that sustained delivery of progesterone and estrogens by means of Tricalcium-Phosphate-Lysine delivery systems (TCPL) can suppress the rise in LH and FSH levels and ultimately induce cycling activities. The specific objective of this study was to design an implantable TCPL system capable of delivering progesterone (P) for about two weeks and Estradiol (E) in a short burst that mimics the ovulatory surge in adult ewes. TCPL implants were fabricated in four different sizes (1.5, 2.3, 3.5, or 5.6 cm) using four different ceramic compositions and impregnated with P (20-45%) and E (4-16%). Surgical aseptic techniques were employed following standard approved lab protocols. Blood samples were collected daily and anlyzied for P, E, LH and FSH levels. X-ray procedure was performed twice a week to assure the intactness of the devices. The results of this student revealed: (1) TCPL were cable of delivering P and E at levels that mimic the estrus cycle, (2) remarkable reduction of LH and FSH levels in all experimental animals compared to sham operated group. Overall conclusion, results of this study demonstrated that the anterior pituitary gonadotropin hormones can be regulated through sustained delivery of reproductive hormones.

Tarit Kanti Ghosh

The University of Melbourne Australia

Title: Surgery and chronic stress ultimately leading to major health risks

Biography:

Tarit Kanti Ghosh MSc, MBBS, born in 1968 is a renowned Neurologist in Bangladesh. Since the very childhood he was extraordinary talented i.e. he always stood as topper in the class. In secondary school certificate & higher secondary certificate public exam he was one of seven among about 400,000 students all over the country. Being a son of a doctor his ambition was to become a benevolent physician. Thereby, he completed his graduation from the then British recognized medical college in Dhaka, Bangladesh in 1993. Then he did post-graduation(MSc) in internal medicine & Neurology from United Kingdom. He accomplished “Leading edge neurology for the practising clinicians, 2014” course in University college of London, UK. Due to thirst of knowledge he is still studying in the university of Melbourne, Australia in the Specialist Certificate Course in Clinical Research Neuroscience.

Abstract:

In this article I shall be trying to show how surgery irrespective to age and/ or organ becomes a prospective major health problem. In general about 50-60% patients undergone anyhow surgery suffer mild/moderate/severe psychobiological illness in future for a long time due to feeling of fear that he/she (1:3)(1) has lost part of his body, inside unhealed or prolonged healing process . So anxiety, tension, emotion and depression gradually burden their daily life style eventually leading to chronic stress (about 10%) in 4 years after surgery along with some major health risk. Background: This is an observational, prospective and multi centred study under intention to treat principle. This study is a over-view about the patients from January’08 to July’14. Data was collected from the leading practitioners of a district named Khulna in Bangladesh. The practitioners are Medicinist, Gynaecologist, Orthopaedician, Eye Surgeon, General Surgeon, Psychiatrist and Neurologist. In this study the outcome shows that about 10% of post surgical (mainly those who were undergone major surgery) had been suffering from chronic stress and among them some patients experienced major health risks i.e. Hypertension, Diabetes, Stroke, Heart attack, Panic disorder, Generalised Anxiety Disorder etc.

Fakhir Al-Ani

Mutah University, Jordan

Title: Tears examination as a substitute for CSF examination in MS patients

Biography:

Fakhir Al-Ani has completed his M.Sc. study and PhD study from Baghdad University ,College of Medicine. School of Medicine. He spend about 30 yars as a teaching staff in medical college. He is now working in Mutah University, Medicl College as the head of Physiology & Pathology Dept. He has supervised more than 13 Ph.D thesis, and more than 23 M.Sc. thesis. He has published more than 35 papers in reputed journals.

Abstract:

The bizarre confusing symptoms of multiple sclerosis (MS) with its remission and relapse property, and the unavailability of a single neurological or laboratory test, which can definitively confirms or rules out MS, make it difficult to be diagnosed. Cerebrospinal fluid (CSF) analysis is often performed in cases of suspected MS to identify the elevation of immunoglobulin (mainly IgG) in the form of oligoclonal band. Although CSF as a test is a highly useful test in the diagnosis of MS, but it is not free of risk and complication moreover it can not be performed frequently. It had been noticed that the tears of MS patients compose immunological abnormalities, namely, increased immunoglobulin levels (mostly IgG), and the appearance of oligoclonal bands in electrophoresis like that of the CSF analysis. Accordingly in this study we tried to explore the significant of tear analysis in the diagnosis of MS. Materials and methods: Fifty six tear samples were tested; those include normal subjects, MS patients, and patients with other neurological diseases Collection of tears after simple induction of lacrymation., the microns of this tears were used. Tear electrophoresis using conventional SDS polyacrylamide gel electrophoresis according to the recommendations of LKB was used. Results Tear electrophoresis had showed two specific bands appearing in tear samples of multiple sclerosis patients, which were absent in samples of normal subjects. One band appeared in the immunoglobulin region. While the second band had a lower molecular weight, which was about 25 kD. It had been noticed that the tears of MS patients compose immunological abnormalities, namely, increased immunoglobulin levels (mostly IgG), and the appearance of oligoclonal bands in electrophoresis like that of the CSF analysis. Accordingly in this study we tried to explore the significant of tear analysis in the diagnosis of MS.

Hiroshi Nakanishi

Kyushu University, Japan.

Title: Lessons from cathepsin deficient mice on human brain diseases

Biography:

Dr. Hiroshi Nakanishi is currently a Professor of Department of Aging Science and Pharmacology, Kyushu University. He completed his PhD in Kyushu University and his post-doctoral trainingin the University of Tennessee at Memphis. He became a Professor of Laboratory of Oral Aging Science, Kyushu University in 2000. He was the Dean of Faculty of Dental Science, Kyushu University from 2011 to 2013. He is now the vice Dean Faculty of Dental Science, Kyushu University from 2014. His research is focusing on the physiological and pathological functions of microglia in the central nervous system.

Abstract:

A group of proteases in the endosomal/lysosomalproteolytic system have been designated as cathepsins, which is derived from the Greek term meaning “to digest”. Considering that cathepsins can irreversibly cleave peptide bonds, the primary function of cathepsins has been believed to be their “disintegration actions”. However, there is increasing evidence that cathepsins can also exert “modulator actions” by which substrates are activated after limited cleavage. For examples, we have recently found that cathepsin B (CatB) is involved in the maturation of pro-IL-1through proteolytic activation of pro-caspase-1 in the autophagosomes of spinal microglia following peripheral inflammation, leading to the induction and maintenance of inflammatory pain.On the other hand, cathepsin S (CatS) is involved in proteolytic processing of the MHC class II-associated invariant chain in splenicdendritic cells following peripheral nerve injury, leading to activation of CD4+ T cells. Infiltration of activated CD4+ T cells may contribute to transition of nerve injury-induced acute pain to a chronic pain state.Beyond a bulk proteolysis in the endosomal/lysosomal system, the growing understanding of modulator actions of cathepsins in microglia and other mononuclear phagocytes could contribute to the development of protease inhibitors as therapeutic interventions against brain diseases associated with chronic inflammation and immune response.

Benjamin Chitambira

East Kent Hospitals University NHS Foundation Trust,U.K

Title: Evolution of optokinetic chart stimulation as a novel neurorehabilitation intervention

Biography:

Benjamin Chitambira completed his BSc Physiotherapy Honours degree from the University of Zimbabwe in 1995. He also completed a Postgraduate Certificate in Healthcare Leadership from the Open University in the UK in 2014. With over 19 years’ experience as a neuro-physiotherapist, he has been carrying out research on optokinetic chart stimulation as a clinical specialist physiotherapist in the Richard Stevens Stroke Unit for over 8 tears.With over 9 papers published in peer reviewed journals, he has been a peer reviewer for reputable journals and now serves as an editorial board member of peer reviewed journals.

Abstract:

Background: This presentation aims to describe optokinetic chart stimulation and its evolution as a recovery focused neurorehabilitation intervention. Stroke, traumatic brain injuries and critical care polyneuropathy and or myopathy can cause severe disability.
Methods: The optokinetic chart is made of laminated A4 paper. It consists of repeated bundles of the colours of the rainbow. The chart is placed 20 centimetres in front of a patient’s face. It is moved from side to side atapproximately one cycle per second for 3 minutes. This is followed bymoving the chart up and down for 3 minutes and then forwards and backwards for another 3 minutes.
Results: The first task was to identify which strokes benefited most from the intervention. A case seriespublished in 2011 identified that strokes not involving simultaneous infarcts or haemorrhages of parietal and temporal lobes recovered movements. A case control series published in 2014 demonstrated statistically significant upper limb recovery (P<0.05). The author has been pilot-testing to see if these differences are reproducible under randomized controlled trial conditions. First set of comparable results point to the potential of a future full trial achieving an all and none principle of the ideal scientific experiment. Preliminary efficacy has also been demonstrated in difficult to rehabilitate traumatic brain injuries and critical care polyneuropathies and or myopathies.
Conclusion: Optokinetic chart stimulation shows promise as a novel recovery focused neurorehabilitation intervention. Further research with fully powered studies is required to provide evidence for its inclusion in future guidelines.

Fakhir Salman

Mutah University, Jordan

Title: Fibrin sealant-Bi mechanical properties and bio-compatibility

Biography:

Fakhir Al-Ani has completed his M.Sc. study and PhD study from Baghdad University ,College of Medicine. School of Medicine. He spend about 30 yars as a teaching staff in medical college. He is now working in Mutah University, Medicl College as the head of Physiology & Pathology Dept. He has supervised more than 13 Ph.D thesis, and more than 23 M.Sc. thesis. He has published more than 35 papers in reputed journals.

Abstract:

Fibrin sealant “fibrin glue" is a unique surgical hemostatic/adhesive material. It is a natural, biocompatible and biodegradable material, resembling the final step of the coagulation cascade. It is composed of cryoprecipitate, thrombin and anti-fibrinolytic agent. Fibrin sealant is being utilized with increasing frequency in a variety of surgical situations with a wide range of clinical applications for suture support, tissue adhesion, and hemostasis. In clinical use, many factors may influence the outcome like; the time of clotting onset, the duration before lysis, biocompatibility, as well as some of its biomechanical properties such as tensile strength and elasticity. The aim of this study was to assess the optimization of the biomechanical criteria which are important for the surgeons for each specific surgical task. The method that we use is to synthesis fibrin glue with different concentrations and additions (tranexamic acid, platelets). Then we monitor the clotting times, durations need for clot to lysis, as well as explore the biomechanical behavior (tensile strength and elasticity). Synthesis of the glue revealed significant increase clotting times and durations for clot lysis when cryoprecipitate concentration was increased and when tranexamic acid or platelets are added to the glue. The elasticity tests clarified that the increase of cryoprecipitate concentration or tranexamic acid addition to fibrin glue formula caused significant higher elasticity. On the other hand, platelets or both tranexamic acid and platelets additions caused significant decrease elasticity results, which increase with time. The tension tests revealed that the increase of cryoprecipitate concentration or additions of platelets or both tranexamic acid and platelets caused significant higher resistance to tension, and this resistance decreases with time, while the addition of tranexamic acid alone causes a significant decrease in tension results, which increase with time. The biocompatibility was studied for all the components by a rat models with severed sciatic nerve was employed to evaluate the clinical efficacy of the glue. The results present gradual clinical improvement of the paralyzed leg with symmetrical bilateral movements at 6 weeks to 2 months duration. In conclusion, changing the concentration of the cryoprecipitate in relation to the thrombin and the addition of tranexamic acid and or platelet can change the duration, elasticity and tensile strength to make it compatible for specific operation.

Session Introduction

Nicholas Cunniffe

University of Cambridge, United Kingdom

Title: Saccadometry: a novel diagnostic tool in Covert Hepatic Encephalopathy

Biography:

Dr Nick Cunniffe graduated from Cambridge University with degrees in neuroscience and medicine. After completing junior years in Cambridge, he is now undertaking specialist training in London, while lecturing neuroscience at the University of Cambridge and continuing to conduct research with Prof. Carpenter who was originally invited to this meeting, but prevented from travelling by a medical condition: Dr Cunniffe is representing him. Roger Carpenter is Emeritus Professor of Oculomotor Physiology at Cambridge, and directed medical studies for many years at Gonville and Caius College. Well known as the author of the classic Movements of the Eyes, he has published many papers using eye movements to study decision mechanisms of the brain (the LATER model) and their clinical applications. He is also the author of the highly successful Neurophysiology, now in its fifth edition.

Abstract:

The study of saccadic latency, the variable time between presentation of a peripheral stimulus and foveation of the target, has provided important insights into the neural mechanisms underlying reaction times and decision. It has emerged as a powerful tool to quantify neurological impairment in a wide range of conditions. Patients with Huntington’s disease and Frontotemporaldementia, for example, generate saccades with significantly increased latency. In Parkinson’s disease meanwhile, saccadometrydemonstrates how neural function is affected by the disease and its treatment, for example deep brain stimulation. Our latest work has shown measurement of saccadic latency distributions in patients with liver cirrhosis can accurately detect Covert Hepatic Encephalopathy (CHE). This cognitive defect, found in 30-70% of cirrhosis patients, has been linked to poor quality of lifeand increased mortality, while early detection and appropriate treatment may reverse the deficit. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for clinical use. Our study diagnosed CHE in a subset among 36 cirrhosis patients by subjecting them to the World Congress of Gastroenterology standard of psychometric tests. We then used a portable saccadometer to measure their saccadic eye movements. We found those with CHE (16) had significantly prolonged saccadic latencies when compared with those without (20). There was in fact a spectrum of cognitive impairment among cirrhosis patients, with those defined as having CHE by psychometric testing having slower reaction times. Saccadometry therefore represents an opportunity for accurate and early diagnosis of CHE, better informing treatment in these patients.

Preshita Desai

Institute of Chemical Technology, India.

Title: t-Micelles of curcumin: strategy for enhanced brain uptake

Biography:

Preshita Desai is an INSPIRE-Fellow currently pursuing Ph.D. (Tech.) in Pharmaceutics at Institute of Chemical Technology, India under Prof. Vandana Patravale. She has two patents, two reviews, two scientific publications in peer-reviewed international journals and a book chapter to her credit. She has presented 13 scientific abstracts in national and international proceedings and has received awards for 11. She was recently bestowed with Ranbaxy Science Scholar Award 2014. Her research interests include synthesis and application of novel lipid bioconjugates for targeted delivery to central nervous system, exploring hot melt extrusion, high pressure homogenization techniques toward bioenhancement of poorly bioavailable drugs.

Abstract:

Curcumin -a polyphenol, exhibits strong anti-oxidant, neuroprotective and anti-amyloid potential that makes it a potent candidate for alleviation of oxidative stress induced neurodegenerative ailments viz. Alzheimer’s disease. Though potent, its clinical translation is restricted due to poor aqueous solubility (~11ng/ml in pH5 aqueous buffer), chemical instability and meager permeability across brain barrier. This demands a smart nanodelivery platform that will not only ensure the drug stability but will also facilitate drug transport across brain barrier. With this rationale, we propose curcumin loaded targeted micellar nanocarriers (t-micelles) comprising a novel lipid bioconjugate (t-bioconjugate) with an ability to cross brain barrier via receptor mediated active transport. The synthesized t-bioconjugate was characterized for its physicochemical properties, safety and brain permeation efficacy both in vitro and in vivo. The curcumin loaded t-micelles exhibited a spherical geometry (size:21.3±2.68 nm, PDI:0.148) and demonstrated safety and acceptable properties for nasal spray application. In vitro anti-oxidant assay revealed 1.6 fold better anti-oxidant activity (DPPH assay) of curcumin loaded t-micelles in contrast to curcumin loaded plain micelles and could be attributed to mild antioxidant potential of t-bioconjugate. In vivo pharmacokinetic and biodistribution studies demonstrated enhanced brain transport of t-micelles via active transport and curcumin was quantified in brain tissue upto 12 hours predominantly in the olfactory region, hippocampus and cerebellum of the brain. The developed formulation was stable as per ICH stability guidelines. The studies corroborated the potential of t-micelles as a platform and potential strategy in treatment of neural ailments to enhance brain bioavailability of therapeutic actives.