Day 2 :
- Keynote Forum
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:
Hamed Benghuzzi is currently the Professor and Chairman at university of Mississippi medical center, USA. His area of research is the development and applications of novel ceramic drug delivery systems (over 26 years/over 250 publications and 600 abstracts at various meeting). He was fortunate to be recognized as a fellow by the American Institute of Medical and Biological Engineering, as well as, International Fellow by the World Congress of Biomaterials Societies (Japanese, American, Asian, and European). His passion is teaching and training students. He had been the mentor of several faculty at the school of health related professions and other clinical departments including two orthopedic surgery faculty through grants supported by OTA and OREF. He served and serving as a major advisor for over 30 PhD students as well as a mentor for students at various levels (High school, undergraduate, MS, residents and postdoctoral). He is also a course director for several graduate and undergraduate courses. These include Pathophysiology (I and II), Histopathology, Pathophysiological phenomena, Human Physiology and Pathology. Administratively; he served as a chair for departments of Health Sciences, Cytotechnology and currently he serve as a chair of the Department of Diagnostic and Clinical health sciences and Director of CHS program.
Abstract:
Evaluation of devices, drugs, and drug delivery systems (CDS) have been investigated by both in vitro and in vivo procedures. Ceramic drug delivery systems have shown to be biocompatible, non-toxic and highly acceptable by the host. The CDS can also reduce handling of animals and facilitate long-term evaluations before conducting clinical trials. To date, CDS have been used to deliver various biologicals such aldosterone, androstanedione, beta-lactoglobulin, bovine serum albumin, chymotrypsin, danazol, difluoromeythylornithine, dihydrotestosterone, estradiol, gamma globulin, gonadotrophic releasing hormone, gossypol, growth hormone, insulin, pepsin, progesterone, neuropeptide Y antagonist, thymoquinone, vitamins and testosterone to name a few . The results of ourfindings provided significant scientific evidence to effectively use CDS as an alternative route of drug administration to treat diseases requiring long-term chronic drug therapy as well as disorders caused by deficiency of certain medications (hormone replacement therapy).
Biography:
Alessandro Morelli (b. 1943) has studied enzyme Glucose-6-P-dehydrogenase and its molecular mechanism of senescence. He has been working in the field of phototransducion and molecular events in photoreceptor cells of vertebrate retina. He has discovered the protein FX, a NADP dependent enzyme catalizing synthesis of GDP-L-fucose. He has been working on the effects of electromagnetic fields of extremely low frequency on the activity of enzymes involved in bioenergeticprocess. Recently he has studied the myelin energetic function in brain put in in evidence the ATP extramitochondrial synthesis, with application in the study of Multiple Sclerosis and other neurodegenerative deseases.
Abstract:
A new paradigm other than insulator may arise for myelin, consistent to the fact that myelination is not continuous, as previously thought, and that myelin can aerobically synthesize ATP and deliver it to the axoplasm trough gap-junctions. Myelination is triggered by neuronal activity, which in turn regulates myelin remodeling. It may be hypothesized that after birth, intense firing depletes axonal ATP causing a rise in Adenosine, that triggers myelination (through purinergic receptor signalling): only those neurons which are fed with ATP can survive. Anoxia causes memory loss: i.e. memory requires energy. It may represent a neural network energized by myelination.
- Clinical Neurology and Neuro Therapeutics
Session Introduction
Harish C. Pant
NINDS, NIH, USA
Title: A novel approach to prevent Alzheimer’s and ALS phenotypes using a small peptide derived from a physiological activator, p35, of cyclin- dependent kinase (Cdk5) in transgenic mice models
Biography:
Dr. Pant received his M.A. and Ph.D. degrees in Physics from Agra University, Agra, India. His postdoctoral studies were conducted on the mechanisms of electron and ion transport in model membrane systems at the Department of Biophysics at Michigan State University. He joined the Laboratory of Neurobiology in the NIMH as a senior staff fellow in 1974 with Dr. Ichiji Tasaki where he studied the function of the axonal cytoskeleton in the squid giant axon. In 1979 he moved to the NIAAA extending his studies on the neuronal cytoskeleton and the effects of alcohol on its regulation. Dr. Pant moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently chief of the section on Cytoskeleton Regulation. His laboratory is studying the mechanisms of topographic regulation of neuronal cytoskeleton proteins by post-translational modification, including the role of kinase cascades in normal brain and during neurodegeneration
Abstract:
Besides the hallmark pathology of amyloid plaques and neurofibrillary tangles (NFTs), it has been well documented that cyclin-dependent kinase 5 (Cdk5), a critical neuronal kinase in nervous system development, function and survival, when deregulated and hyperactivated induces AD and ALS like phenotypes in mice. Under physiological conditions, Cdk5 activity is tightly regulated. The deregulation and hyperactivation of Cdk5/p25 induces neuropathology. Thus Cdk5/p25 becomes prime therapeutic target for AD and neurodegenerative diseases associated with the hyperactivation of Cdk5. In order to prevent hyperactivation of Cdk5/p25, we have designed several small peptides of p25 on the basis of Cdk5/p25 crystal structure and checked for competition with p25 and thus inhibiting selectively the hyperactivity of Cdk5. We discovered a small peptide (p5) comprising of 24 amino acids, inhibited Cdk5 hyperactivation. The modification of p5 to TFP5 crosses BBB, was tested in a transgenic AD and ALS model mice. The p25 transgenic AD model (p25Tg) and 5XFAD mice were chosen since these mice show similar phenotypes to AD patients. Post TFP5 injections in p25Tg mice, 5XFAD and ALS model mice displayed significant reduction in Cdk5/p25 hyperactivity, A- beta plaque formation along with AD behavioral rescue. TFP5 does not inhibit normal Cdk5/p35 activity, and therefore has no toxic side effects. In addition, treated mice rescued synaptic dysfunction, neuroinflammation and a reduction in phospho-neurofilaments / tau and cell death. These results indicate that TFP5 has a potential to be a therapeutic target for AD.
Biography:
Gülsel YurtdaÅŸ KırımlıoÄŸlu got her Msc on “Inclusion complexes with antifungal agents” in 2010. She had completed her PhD study “Nanosized drug delivery system interfering epileptic mechanism” in 2014. Since 2008 she has been working as a Research Assistant at the Department of Pharmaceutical Technology at Anadolu University. Her researches focuses on novel technologies to enhance drug delivery.
Abstract:
Gamma aminobutyric acid (GABA), serves as the major inhibitory neurotransmitter, has a central role in neural control. Inhibition of GABA synthesis, blockage of release or postsynaptic reaction were determined to provoke convulsions. Significant reductions in brain GABA concentration were seen in patients with different epileptic syndromes. Several new approaches are being developed in an attempt to increase the entry and persistence of antiepileptic agents in the brain. One of the main strategy is nanosized drug delivery systems for the treatment of epilepsy. Halloysite nanotubes (HNT) is natural aluminosilicate clay with hollow tubular structure which allows loading drugs inside nanotubes lumens. In this study, GABA was successfully incorporated into HNT depending on the most recent epilepsy theory related to GABA. Characterization, drug loading, in vitro release studies and cytotoxicity test were performed on HNTs. Anticonvulsant effect of drug loaded HNT system were evaluated using pentylenetetrazole induced epileptic rats for in vivo studies. The latency to myoclonic jerks and incidence of generalized tonic clonic seizures with loss of righting reflex were noted as seizure parameters.
Dana Byrd
Texas A&M - Kingsville, USA
Title: Behavioral and electroencephalographic progress toward a biomarker for Autism in early infancy
Biography:
Dr. Dana Byrd completed his PhD at the age of 29 years from University of Florida and postdoctoral studies from Columbia University School of Medicine.She has published more than 15 papers in reputed journals.
Abstract:
A biomarker in newborns at risk of developing Autism would be obviously highly valuable, allowing for very early intervention. Cerebellar structural and functional abnormalities have been found in individuals with Autism, as have been found abnormalities in the cerebellar-cortical-mediated learning, conditioning of eye blink. In the first two studies presented, we show behavioral and electroencephalographic evidence that sleeping newborn infants can present eye blink conditioning to a tone. In a third study, we produce evidence that 1-month-old infants’ eye blink conditioning is more rapid when the conditioned stimulus is a human voice as compared to a tone. These research studies have only been conducted on healthy infants, who are at no additional risk for Autism. However, research with populations at risk for Autism may show that these paradigms and their behavioral and electroencephalographic measures of conditioning may be able to detect atypical cerebellar functioning in at-risk populations. It should be pointed out that while these behavioral and electroencephalographic measures of conditioning to tones show some promise for determining risk for Autism, they are not as a diagnostic tool, but instead are a biomarker for risk for general cerebellar-cortical dysfunction, which is not only present in Autism but in other disorders as well such as Attention Deficit/Hyperactivity Disorder and Dyslexia. There is stronger hope for a specific biomarker for Autism in the form of atypical conditioning to the human voice since individuals with Autism have been found to process spoken stimuli differently than individuals without Autism.
Alessandro Morelli
Genova Universit, Italy
Title: Finding of myelin energetic function supporting theaxonal nervous conduction: Perspectives in neurology.
Biography:
Alessandro Morelli (b. 1943) has studied enzyme Glucose-6-P-dehydrogenase and it’s molecular mechanism of senescence. Has been working in the field of phototransducion and molecular events in photoreceptor cells of vertebrate retina. He has discovered the protein FX, a NADP dependent enzyme catalizing synthesis of GDP-L-fucose. He has been working on the effects of electromagnetic fields of extremely low frequency on the activity of enzymes involved in bioenergeticprocess. Recently he has studied the myelin energetic function in brain put in in evidence the ATP extramitochondrial synthesis, with application in the study of Multiple Sclerosis and other neurodegenerative deseases.
Abstract:
In the last years, we have focused our attention on the role of myelin sheath as an energy supporter for the nervous conduction [1]. We have observed that myelin is able to conduct and extramitochondrial oxidative phosphorylation, consuming oxygen to produce ATP [2]. Moreover, we have also demonstrated a direct connection among myelin sheath and neuron, which may allow the transfer of ATP from the sheath to the axon [3]. Interestingly, the energetic role of myelin sheath was recently confirmed by Gat-Viks et al, studying the alteration of the energetic metabolism in the vanish white matter disease [4]. This finding introduces two new paradigms, one in bioenergetic and the other in neurobiology. Firstly, our data demonstrated that mitochondria is not the only “power-house”, but the OXPHOS proteins could be exported to other membranous structure, to provide a more efficient energy production [5]. Moreover, our hypothesis on the energetic function of myelin sheath sheds a new light on the role of this structure, giving a possible explanation of the neuron degeneration observed in the demyelinating diseases, as Multiple Sclerosis
Laurence Lacoste
Ethical research committee of Saint Louis Hospital, France
Title: Interests and limits in evaluation of cognitif disorders for the elderly
Biography:
Dr Laurence Lacoste has completed his PhD at the age of 32 years from Nanterre University in France and postdoctoral studies from INSERM. She has worked in reputed Hospital in Paris as psychologist and as teacher in reputed French University. Now, she works asliberal psychologist and for the ethical research committee of Saint Louis Hospital in Paris. She has published more than 10 papers in reputed journals of medicine and psychology.
Abstract:
Lots of consultations exist at the moment to evaluate cognitive capacities of the Elderly. When elderly people begin to have memory problems, they often want to know if something is possible to help them and to have the opinion of specialists. Sometimes, it’s a member of the family, a general practitioneror a doctor of a hospital who do this request when they think that an elderly people begin to have troubles of memory or behavior. Also, when an elderly people is in an institution, neuropsychological evaluations are often asked. In geriatrics institutions, where there are people with Alzheimer disease or related disorders, neuropsychological evaluations are most often also present. In some epidemiological studies, neuropsychological evaluations are done from several years to try to find factors of risks and protection from pathological ageing. In this talk, we describe the interests of a neuropsychological evaluation, how we can do it with anamnesis and neuropsychological tests in the way to take care of the patientsand to answer to initial request. We also try to give the limits of this evaluation according to the question which is to treat and according to the way of the return which is done. It depends of each case, and it is not the same for the patient, the family the general practitioner, the other doctors in hospital, the members of an institution where is the patient for the end of his life or the public health.Finally, we try to give a general view of criticism and interest of early cognitive evaluation for the Elderly.
Zienab Alrefaie,
King Abdulaziz University, Saudi Arabia
Title: Vitamin D3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats
Biography:
His Current Position: Lecturer assistant at Department of Chemistry, Faculty of science, University of Cairo, Egypt. He is a Postdoctoral researcher at Institute of Physics, Rostock University, Germany . Education: Bachelor of Science in Chemistry (May 2005), Faculty of Science, University of Cairo “Excellent with Honor”. He did his Pre-Master in Physical Chemistry (October 2006), University of Cairo. Master of Science in Physical Chemistry (August 2009), University of Cairo, thesis entitled “Theoretical investigation of H-bond structure and dynamics in molecules of biological interest”. He did Ph.D. in Physical Chemistry (November 2013), University of Rostock, thesis entitled ’’Binding of chlorinated environmentally active chemicals to soil surfaces: chromatographic measurements and Molecular dynamic simulations’’.
Abstract:
Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Methods: 30 male Wistar rats (150-200 gm) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin (stz) 45mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Results: Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. Conclusion: The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect was mediated through enhancing the prefrontal cortex cholinergic transmission.
wael hayel khreisat
Royal Medical Services, Jordan
Title: Clinical profile of infants with Hypsarrhythmia
Biography:
M.B.B.S ,1991. School Of Medicine, University Of Salah AL-deen, Erbil - Iraq Jordanian Board of Pediatrics, Jordanian Medical Council, Sep 1999 , Clinical Fellow (SpR Level) in Pediatric neurology at King Hussein Medical Center Amman-Jordan / Royal Medical Services(RMS) from January 2003. Post doctorial clinical trainee in Pittsburgh children hospital- Neurological Department 2005-2006, Head of Pediatric Neurology and neurophysiology atQueen Rania Hospital for Children Royal Medical Services
Abstract:
Objective: The present study was done in order to obtain a baseline profile of infantile spasms and associated neurological disorders. Patient and methods:. The study included 50 patients with infantile spasm in Queen Rania Hospital for children in Jordan. The following data were obtained: sex, age at onset of spasms, details of seizure, family history of epilepsy, significant pre-/peri/post-natal insults, Electroencephalography and detailed neuroimaging evaluation , detailed neurological, neuro developmental ,assessment were done by. Broad categories of possible etiologies were used the results were recorded for further study. Results: Age of onset of infantile spasms ranged from 1month to 1 year and 6 months , (mean 4.8 months). The mean time of presentation was 9.4 months . A male preponderance was noted (74 %). flexor spasms (52%) was the commonest . Other types of seizures also accompanied infantile spasm in 44% children . (84%) were born of normal delivery, History of birth asphyxia was obtained in 48%, 3 (6%) had positive family history Developmental delay was recognized prior to onset of spasms in 52%, microcephaly was the commonest associated problem, Imaging studies of the brain revealed abnormality in 18 patients. 78% patients were classified as symptomatic and 22 % as cryptogenic. Conclusion and recommendation: the pattern of infantile spasm in our country do not differ from that of developed countries, further researches is required to prevent both chronic epilepsy and psychomotor retardation and .preventive measurement to prevent birth asphyxia is recommended
Jirapast Sichaem
Chulalongkorn University, Thailand
Title: New furoquinoline alkaloids from the leaves of evodia lepta as potential cholinesterase inhibitors and their molecular docking studies
Biography:
Jirapast Sichaem has completed his PhD at the age of 26 years from Chulalongkorn University. He is doing postdoctoral studies in the field of anticholinesterase compounds from Thai medicinal plants at Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University. He has published more than 22 papers in scientific journals.
Abstract:
Alzheimer's disease (AD) is the most common cause of neurodegenerative disorder and dementia in elderly people. The cholinergic hypothesis proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine (ACh) in the brain. In addition, a substrate non-specific butyrylcholinesterase (BChE) is also found to play a significant role in the hydrolysis of ACh. Moreover, there are several reports that have revealed that the reduction of AChE activity can be compensated for BChE activity. Thus, all of the above reasons have stimulated a great interest in screening natural cholinesterase (ChE) inhibitors as lead compounds for the intended treatment of AD as they should have significant inhibition activities towards both AChE and BChE. Previous reports have shown that some furoquinoline alkaloids and other constituents of the plants from Rutaceae family have ChEs activities revealed to the treatment of AD. Therefore, the successive extraction and isolation of bioactive ChE inhibiting compounds from the plants of this family were interesting, as they can themselves be active and used directly as a drug. Evodia lepta (Spreng.) Merr. (Rutaceae) is a traditional medicinal plant used for the treatment of arthritis, fever, chickenpox, epidemic influenza, meningitis, infectious hepatitis, antipruritic, depurative and febrifuge diseases. Several furoquinoline alkaloids, flavonoids and chromones have been also reported from this plant in previous studies. Three new furoquinoline alkaloids (1-3) along with six known furoquinoline compounds (4-9) were isolated from the leaves of Evodia lepta based on bioassay-guided fractionation and chromatographic techniques. All isolates were evaluated for their in vitro cholinesterase (ChEs) inhibitory activities, in which compounds 7 and 5 exhibited the highest activity toward AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were mixed mode inhibitors of both ChE enzymes. Finally, the molecular docking studies on the binding sites of AChE and BChE were performed in order to afford a molecular insight into the mode of action of these active compounds in a good agreement with their anti-ChE results. Therefore, this information can help in designing a new inhibitor in the class of furoquinoline alkaloids in against Alzheimer’s disease.
Alessandro Morelli
Genova University , Italy
Title: Finding of myelin energetic function supporting theaxonal nervous conduction: perspectives in neurology
Biography:
Alessandro Morelli (b. 1943) has studied enzyme Glucose-6-P-dehydrogenase and it’s molecular mechanism of senescence. Has been working in the field of phototransducion and molecular events in photoreceptor cells of vertebrate retina. He has discovered the protein FX, a NADP dependent enzyme catalizing synthesis of GDP-L-fucose. He has been working on the effects of electromagnetic fields of extremely low frequency on the activity of enzymes involved in bioenergeticprocess. Recently he has studied the myelin energetic function in brain put in in evidence the ATP extramitochondrial synthesis, with application in the study of Multiple Sclerosis and other neurodegenerative deseases.
Abstract:
In the last years, we have focused our attention on the role of myelin sheath as an energy supporter for the nervous conduction [1]. We have observed that myelin is able to conduct and extramitochondrial oxidative phosphorylation, consuming oxygen to produce ATP [2]. Moreover, we have also demonstrated a direct connection among myelin sheath and neuron, which may allow the transfer of ATP from the sheath to the axon [3]. Interestingly, the energetic role of myelin sheath was recently confirmed by Gat-Viks et al, studying the alteration of the energetic metabolism in the vanish white matter disease [4]. In the last years, we have focused our attention on the role of myelin sheath as an energy supporter for the nervous conduction. We have observed that myelin is able to conduct and extramitochondrial oxidative phosphorylation, consuming oxygen to produce ATP. Moreover, we have also demonstrated a direct connection among myelin sheath and neuron, which may allow the transfer of ATP from the sheath to the axon. Interestingly, the energetic role of myelin sheath was recently confirmed by Gat-Viks et al, studying the alteration of the energetic metabolism in the vanish white matter disease. This finding introduces two new paradigms, one in bioenergetic and the other in neurobiology. Firstly, our data demonstrated that mitochondria is not the only “power-house”, but the OXPHOS proteins could be exported to other membranous structure, to provide a more efficient energy production. Moreover, our hypothesis on the energetic function of myelin sheath sheds a new light on the role of this structure, giving a possible explanation of the neuron degeneration observed in the demyelinating diseases, as Multiple Sclerosis.