24^th World Congress on Pharmacology August 19-20, 2019 Vienna, Austria

Biography:

Gal Bitan, PhD, received his PhD in organic chemistry from the Hebrew University of Jerusalem, Israel. Following postdoctoral training at Harvard Medical School and affiliated hospitals, he joined the faculty at UCLA where he is currently a Professor of Neurology. Dr. Bitan’s research program focuses on neurodegenerative diseases caused by abnormal protein self-assembly, such as Alzheimer’s and Parkinson’s diseases. He has made seminal contributions to the study of amyloid-protein oligomers and has been developing novel drug candidates and biomarker measurements for these diseases.

Abstract:

Statement of the Problem: Biomarkers for neurodegenerative diseases are urgently needed. Definite diagnosis for most diseases is possible only postmortem and the rates of misdiagnosis are high. Monitoring progression and treatment effects using clinical criteria is inefficient due to high variability. Current biomarker strategies, such as brain imaging and cerebrospinal fluid analysis have major drawbacks. An attractive alternative is analysis of biomarkers in brain-derived exosomes isolated from the blood. Methodology & Theoretical Orientation: We examined α-synuclein in neuronal and oligodendroglial exosomes as a diagnostic biomarker for distinguishing between Parkinson’s disease (PD) and multiple system atrophy (MSA). α-Synuclein deposition is found as Lewy bodies in PD and glial cytoplasmic inclusions, primarily in oligodendrocytes, in MSA. We compared cohorts of healthy control individuals, patients with PD, and patients with MSA. Findings: α- Synuclein concentration in both exosome populations were significantly higher in the two diseases than in the controls and in MSA relative to PD. The total α-synuclein levels separated MSA from control with high sensitivity and specificity, whereas the PD group separated only moderately from the other groups. However, the ratio between the α- synuclein levels in the oligodendroglial relative to the neuronal exosomes separated the two disease groups with high sensitivity and specificity. The ratio also correlated significantly with progression of motor symptoms in the PD group. Conclusion & Significance: Measurement of α-synuclein in brain-derived exosomes offers a minimally invasive means for analyzing biomarkers for PD and MSA, suggesting that in the relatively near future these two diseases could for the first time be diagnosed with high sensitivity and specificity, and their progression could be monitored, using a simple blood test.

Biography:

Maria I. Yablonskaya has passion in clinical genetics and especially in diagnostics and management of inherited metabolic diseases.

Abstract:

Lesch-Nyhan syndrome is an X-linked inborn error of purine metabolism which is caused by mutations in the HPRT1 gene encoding the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HPTR), the prevalence is approximately 1:380000. The disease manifests during the first year of life and is characterized by uric acid overproduction and urate nephropathy combined with severe neurologic dysfunction including cognitive impairment, dystonia, choreoathetosis, spasticity and self-injurious behavior. Overproduction of uric acid is controlled well with allopurinol. But until now, there is no sufficiently effective pharmacologic therapy for neurologic dysfunction in Lesch-Nyhan syndrome. We hypothesized that HPRT deficiency leads to hyperactivation of guanine deaminase (GDA), which has the same localization and expression levels in the brain as HPRT. GDA irreversibly converts guanine to xanthine with the release of ammonia. Local excess of ammonia in brain structures triggers a cascade of pathological processes resulting in impaired transport and release of dopamine in the nigrostriatal pathway, hyperactivation of the NMDA receptors and combined hyperactivation of adenosine and dopamine receptors, neuronal insensitivity to exogenous dopamine. We offer to test the effect of ammonia binding remedy Sodium Phenylbutyrate for reducing dopamine depletion in the brain. To test this hypothesis, we created a new personalized genetic HPRT1-deficient mouse model. We used the CRISPR-Cas9 genomic editing system to introduce the deletion of 8Val in the first exon of the HPRT1 gene in the mouse model. This hemizygous mutation is the cause of Lesch-Nyhan syndrome in one of the patients observed in our clinic. Despite the fact that Hprt-deficient mice do not demonstrate a clinical complex characteristic of patients with Lesch-Nyhan syndrome, they have depletion of dopamine in the same brain structures. These models should be used in studies of brain metabolism and preclinical studies of the effectiveness of new treatments for this disease.

Biography:

Mal Galina Sergeevna throughout the 30 years dealing with the actual problems of cardiology, pharmacology and clinical pharmacology. In 1993 she defended her thesis and was awarded the degree of candidate of medical sciences.  In 2005, defended her doctoral thesis and awarded the degree of doctor.  Since 2005 she has been working as a professor of pharmacology.  She is the author of 500 scientific papers.  Develops issues of pharmacological correction of atherosclerosis of coronary heart disease, arterial hypertension.  Studies pharmacogenetic approaches to the modification of the drug response in cardiac patients. Her approach to optimizing treatment is based on the pharmacokinetic, pharmacodynamic and pharmacogenetic aspects of the treatment of cardiac patients.  That allows to implement personalized medicine in real life. She and her students present their work internationally.

Abstract:

Statement of the Problem: Development of CHD associated with atherosclerosis. One of the main pathogenetic causes of atherosclerosis development is inflammation, being an important atherogenesis component. Any acute infection may be the etiological factor which activates chronic inflammation in the atherosclerotic plaque, involving the cytokine system. A number of studies demonstrate the relation between an increase of cytokine level and the signs of atherosclerosis destabilization and CHD. The purpose of this study is to describe the drug response variability in CHD patients with an acute viral infection. Methodology & Theoretical Orientation: The study involved 170 CHD patients, 120 of whom also had infections (ARVI). The LDL-C and cholesterol levels were determined in the blood serum using an enzymatic method. Genotyping of polymorphisms IL-1β –511C>T, IL-6 –174G>C, IL-4 –589C>T, IL-10 –1082G>А was performed using a PCR method on the CFX96 Bio-Rad Laboratories amplifier (USA). Findings: Carriership of –511TT genotype were diagnosed with the lowest LDL-C level and a high HDL-C level (p<0.05), which confirmed the hypolipidemic statin effect. Carriers of –511СС genotype had the increased LDL-C levels. Carriership homozygous –1082GG genotype demonstrated the association with the level of Cholesterol (P=0.003). When the anti-inflammatory cytokine (IL-4, IL-10) level increased, C level decreased (P<0.05). The analysis of correlation between pro- /anti-inflammatory cytokine gene genotypes revealed the activity of genotypes –511TT (IL-1β gene), –174CC (IL-6 gene), –589TT (IL-4 gene), and –1082GG (IL-10 gene) in maintaining chronic inflammation stability (P=0.012).

Conclusion & Significance: The obtained correlations contributed to the preparation of personalized HLP pharmacotherapy algorithm in CHD patients in presence of ARVI. The presence of heterozygous –511CT genotype for –511C>T polymorphism of the IL-1β gene, homozygous –174GG genotype for –174G>C polymorphism of the IL-6 gene, and homozygous –1082AA genotype for polymorphism –1082G>A of the IL-10 gene did not lead to reaching the target LDL-C level.

Biography:

Abstract:

Myocardial infarction (MI) is myocardial cell death due to severe and prolonged ischemia produced from atherosclerosis-related coronary artery disease. MI triggers a cascade of events and reparative phases end with myocardial cell necrosis. MicroRNA (miR) is non-coding single stranded RNA that regulates protein expression. miR-103 is used to regulate expression of Fas-associated death domain (FADD) which decreases necroptosis of ischemic myocardium. The study aims to investigate the modulatory effect of up-regulating mRNAs translation processes of myocardial infarction induced with Isoprenaline HCL 100 mg/kg (ISO) by injecting miR-103 inhibitor. Eighteen mice (15-25 gm) were allocated into three groups; Group A (control) received normal saline, Group B received ISO and Group C received ISO and miR-103 inhibitor. Mice were sacrificed by cervical dislocation under urethane anesthesia. Blood and hearts samples were collected for biochemical analysis of miR103, FADD, receptor interacting protein kinase (RIPK), nuclear factor-kB (NF-kB), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6),Troponin-I and creatine kinase-MB (CK-MB). In addition, hearts were used for histopathological examination. Results showed that administration of miR-103 antagomir leads to increase in FADD protein levels in group C compared to A and B. While miR-103, RIPK, NF-kB, TNF-α and IL-6 showed high levels of expression in group B that is attenuated in group C. Troponin-I and CK-MB also supported the previous results. Histopathological test showed normal histological structure in groups A and C while focal degeneration in myocardium in B. Accordingly, these results indicate a promising suppression of MI manifestations upon inhibition of miR-103.

Biography:

Biography

Bland Bayar has is expertise in management and prevention of diabetes mellitus. He is a head of non communicable disease in Duhok city north of Iraq (Kurdistan) he is a clinician and part time lecturer at shexan polytechnic college and has many activities in prevention of non communicable and specially diabetes mellitus. This research was done to evaluate the role betatrophin and it is relation to type 2 diabetes mellitus patients. 

Abstract:

Abstract

Aims: Recently, it was suggested that betatrophin has a role in controlling pancreatic b cell proliferation and lipid metabolism, however, its role in human subjects has not been established yet. The predicting role of betatrophin and MDA along with other biochemical indicators in type 2 diabetes mellitus (T2DM) in a sample of the Iraqi population was examined in the present investigation.

Methods: A total of 31 patients diagnosed with T2DM and 30 adult subjects without diabetes were matched in age and gender in a case-control study. Logistic and linear regression models were performed

to examine the role of MDA and betatrophin in T2DM and triglyceride, respectively.

Results: The study confirmed a higher concentration of LDL (124.45 vs. 102.70 mg/dL; P ¼.001) and TG (191.13 vs. 103.83 mg/dL; P < .0001), insulin (18.40 vs. 10.97 mU/mL; P < .0001), and Hs. CRP (5.39 vs. 2.80 mg/L; P ¼.033) in diabetic patients compared to the controls. No significant difference in betatrophin and MDA was found between diabetic patients and non-diabetic healthy subjects. The study

Showed triglyceride as the only predictor of T2DM (P ¼.028). Similarly, total cholesterol (P < .0001), HDL (P ¼.001), LDL (P < .0003), and MDA (P ¼.010) were shown as predictors of triglyceride in diabetic patients.

Conclusion: The present study that triglyceride is a direct and MDA is an indirect predictor for T2DM.

Biography:

A practitioning veterinarian Samuel Drawbridge is very passionate about medicine, but also has a deep interest in chemistry. Pharmacology allows a combining of these two disciplines. His current research involves exploring medical solutions to calcium oxalate based urolithiasis. He hopes to develop a solution that could be used to dissolve calcium oxalate uroliths by direct irrigation of the urinary tract, as well as discovering those agents best suited for prevention of this disease. This research allowing him to improve the health and welfare of humans and animals, beyond that of working as a general practitioner.

Abstract:

Calcium urolithiasis is a disease of major concern given its high prevalence, welfare and economic implications, and complications associated with current treatment and prevention strategies. A large number of publications were evaluated in this review to determine chemicals most evidential of calcium oxalate dissolution potential, the most prevalent stone component. The relevant literature was sourced through a keyword search of several online databases, and studies included if they showed evidence of an agent exhibiting dissolution activity upon calcium oxalate powder, crystals or stones. A critical analysis of these chemicals was undertaken, to determine those most efficacious, whilst also considering safety of medical use. This evaluation revealed citrates to be the most promising candidates for future research, given in vivo and in vitro data. Other factors influencing dissolution were also considered, including the  ability of the immune system to dissolve calcium oxalate crystals.

Biography:

J Amin laboratory has a primary interest in GABA_A and NMDA receptor-channels. We have studied the structure/function relationship of subtypes of GABA_A receptors to enhance our understanding of the molecular mechanism of action of sedative/hypnotic drugs.  By co-expression of wild-type with anesthetic-sensitive subunits of GABA_A receptors, we have determined the minimal number of subunits required for orthosteric- versus allosteric-dependent activation of GABA_A receptor channels. The laboratory is also focused on drug discovery with particular interest in ketamine. In the last several years, we have synthesized a number of ketamine analogues and characterized their molecular actions on the NMDA and GABA_A receptors. One oxime analogues of ketamine has shown great promise in terms of molecular signature on NMDA and GABA_A receptors and in an animal model test for antidepressants.

Abstract:

Anesthetic molecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels, such as hetero-oligomeric α₁β₂γ₂ GABA_A receptors. To elucidate the overall activation paradigm via allosteric versus orthosteric sites, we used highly homologous, but homooligomeric, ρ₁ receptors that are contrastingly insensitive to anesthetics and respond partially to several full GABA α₁β₂γ₂ receptor agonists. Here, we co-expressed varying ratios of RNAs encoding the wild-type and the mutated ρ₁ subunits, which are anesthetic-sensitive and respond with full efficacy to partial GABA agonists, to generate distinct ensembles of receptors containing five, four, three, two, one, or zero mutated subunits. Using these experiments, we then demonstrate that, in the pentamer, three anesthetic-sensitive ρ₁ subunits are needed to impart full efficacy to the partial GABA agonists. By contrast, five anesthetic-sensitive subunits are required for direct activation by anesthetics alone, and only one anesthetic-sensitive subunit is sufficient to confer the anesthetic-dependent potentiation to the GABA current. In conclusion, our data indicate that GABA and anesthetics holistically activate the GABA_A ρ₁ receptor through distinct subunit level rearrangements and suggest that in contrast to the global impact of GABA via orthosteric sites, the force of anesthetics through allosteric sites may not propagate to the neighboring subunits and, thus, may have only a local and limited effect on the ρ₁ GABA_A receptor model system.             

Biography:

Tarsin has his expertise in evaluation of drug delivery reproducibility from different inhalation products using Pharmacokinetic methods and In-vitro characterisation of inhaled products focussing on DPI and MDI. He had several Clinical trials using the inhalation profile recorder to determine the total emitted dose and the fine particle mass of different inhalers in vitro by means of inhalation simulator (The Electronic Lung). He focused on clinical trials to identify which inhaled product to prescribe to an asthmatic patient and those with Chronic Obstructive Pulmonary Disease (COPD) using the In-Check Dial.

He has built this model after years of experience in research, evaluation, teaching and administration in hospital and education institutions in the UK and Libya.

Abstract:

Bronchial asthma is a serious chronic inflammatory disease of the respiratory system. Aerosol inhalation as a route of drug delivery has become well-known in therapy of asthma. This study was aimed to evaluate if the use of 2Tone helps patients maintain the correct inhalation technique after training and can improve the clinical benefit. 125 Libyan adult asthmatic patients were engaged from Tripoli Medical Centre, 2017. At the first clinical visit; 38, 44 and 43 patients were included as C, VT and 2T groups, respectively. Their IFR through an MDI was measured using an In-Check Dial. Patients in 2T group were trained on how to use the 2Tone Trainer according to its PIL and practiced inhaling through this training aid to familiarize themselves with the different sounds according to the IFR. At the second clinic visit for all the patients was held six weeks later, each patient was assessed in the same manner as on the first visit. Results indicate a significant positive correlation between percent predicted FEV₁ and PEFR with all AQLQ domains. Patients in the 2T group showed reduced IFR of about double that in VT group whereas in the C group, there was no significant difference in IFR. However, comparison of IFR between VT vs. 2T groups at visit one showed no statistical significant difference. On the other hand, at visit two, comparison between all the groups showed a highly significant difference. Thus, this study shows that 100% and 29% of the patients in the C and VT groups were inhaling at a high IFR while the 2T group shows only one patient (3%) was inhaling at the high flow rate while the rest of the patients managed to obtain the optimum IFR needed for the MDIs. Thus, the findings strongly recommend the importance of the use of the 2T device to train the patients to slow their IFR.