World Congress on
Toxicology and Applied Pharmacology

Biography:

Giuseppe Assogna born in the Metropolitan city Rome, Italy. He studied a degree in medicine and Surgery cum Laude at University La Sapienza, Rome (Italy). He obtained qualification for medical profession at University of Rome. He obtained Specialization in Liver Diseases at University of Rome. He was worked as Contract Professor from 1990-1992at the University of Naples (Italy), School of Specialisation in Pharmacology and Clinical Pharmacology. He was worked as Contract Professor from 1990-1992at the University of Naples (Italy), School of Specialisation in Pharmacology and Clinical Pharmacology. He was also worked as Contract Professor from 2003- 2004 at the University of Pavia, School of Specialisation in Regulatory Disciplines. He currently works as a Senior Consultant at SIC (Italian Society of Cardiology), President at SIFEIT (Italian Society for Studies in Economics and Ethics on Drug and Therapeutic Interventions), Senior Pharma and Management consultant (Clinical Research, Medical Affairs, Regulatory, Market Access, Start-up foreign companies, Compliance and Governance, Crisis Management). He is a member of the SSFA (Italian Society of Applied Pharmacological Science), SIFEIT (Italian Society for the study of drug Economics and Ethics and Therapeutic Intervention), AILAS (Italian Society for avoiding Stigma), SITAC (Italian Society for Treating Alcohol Consumption) and Former active member of SIDR (Italian Society of Reproduction), ESHRE (European Society of Human Reproduction.

Abstract:

Clinical trials are research studies involving patients in order to evaluate how different treatments are safe and work. Similarly clinical trials are carried out to try to answer specific questions on health and illness and   are the best way to compare different approaches to preventing and treating illness and health problems.

Clinical trial methodology as well as rules governing this important area of research, are actually regulated, in EU countries, by the Directive 2001/20/EC, to be replaced by the clinical trials  - Regulation EU No 536/214, which will come into force, most likely, in October 2019.

The new regulation has many positive aspects, such as authorization timing, monitoring for all studies (profit and no profit), transparency of results, etc., while some aspects may raise criticalities,  like low intervention clinical trials and insurance indeminities.   

As for budget impact of clinical trials, according to a 2014 study by the Tufts Center for the Study of Drug Development (TCSDD), the cost of developing a new drug, from research and development (R&D) to marketing approval, is approximately $2.9 billion and althoug clinical trials evaluate pharmacotherapeutic intervention under highly controlled conditions, remainds a need to evaluate medication use in real clinical practice.

In this high cost scenario is there a concrete possibility to try to reduce (part of) the cost of drug development? Probably yes, according to the Avicenna - A Strategy for in Silico Clinical Trial – document, published in 2015.

The document focuses on “how biomedical products are developed today, where in silico clinical trials technologies are already used, and where else they could be used. From the identification of the barriers that prevent wider adoption, we derived a detailed list of research and technological challenges that require pre-competitive funding to be overcome”.

Biography:

Professor Nehal Afifi has worked at Pharmacology Department, Faculty of Veterinary Medicine, Cairo University from 1997 till now and Head of Pharmacology Department from 2009 to till now Associate Professor of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 1992. Lecturer, of Pharmacology, Faculty of Veterinary Medicine, 1987. Assistant Lecturer of Pharmacology, Faculty of Veterinary Medicine, 1985. Demonstrator at Pharmacology Department, Faculty of Veterinary Medicine, 1981. She is a member of American Society for Pharmacology and Experimental Therapeutics (ASPET) and member of the scientific committee for Veterinary Drugs Registration, Ministry of Health, Central Administration for Pharmaceutical Affairs.

Abstract:

Macrolide antibiotics, including azithromycin, have been involved in the modulation of host immune response,independently of their antimicrobial properties. Macrolides inhibit the production of various cytokines and the migration of inflammatory cells. These antiinflammatory actions may be beneficial in attenuating inflammatory process involved in bacterial sepsis. Therefore, we investigated the ability of azithromycin to attenuate the deleterious effects of lipopolysaccharide (LPS). This study was designed to determine the effect of azithromycin on proinflammatory cytokines ((TNFα , IL-6 and IL1β ) in healthy and lipopolysaccharide – treated mice. Moreover, to investigate the effect of that azithromycin on protective humoral immune responses induced by a 7-valent, polysaccharide, pneumococcal conjugate vaccine (PCV7) by determination of (IgG) and (IgM). Our results show that Oral administration of azithromycin (10 and 100 mg/kg) 30 minutes prior to lipopolysaccharide injection causing significantly decrease in total leucocytic count , lymphocytes %, neutrophils %,as well as significantly attenuated the LPS-induced increase in plasma( TNF-α) conc. By use of a pneumococcal conjugate vaccine(PCV7) , it was found that Oral administration of azithromycin(10 & 100mg/kg b.wt) one hour perior to vaccine causing significant decrease in immunoglobulins; (IgM) and(IgG) led to significantly lower primary antibody responses. The results demonstrate that azithromycin can be inhibitory with regard to protective immune responsiveness . In conclusion, azithromycin exhibits significant anti-inflammatory properties.

Biography:

Abstract:

The leaves of Chinopodium album Linn. Family Chinopodiaceae have been used in Ayurvedic medicine since ancient times for the treatment of male sexual disorders. The present study is aimed to investigate the effect of ethanolic extract of bathua on general mating behaviour, libido, potency along with its likely gastric ulceration and adverse effects on sexually normal male albino mice. The suspension of the extract was administered orally at the dose of 100, 250, and 500 mg / kg, to different groups of male mice (n = 6) once a day for seven days. The female albino mice involved in mating were made receptive by hormonal treatment. The general mating behaviour, libido and potency were determined and compared with the standard reference drug sildenafil citrate. The probable gastric ulceration and adverse effects of the extract were also evaluated. Oral administration of the extract significantly increased the Mounting Frequency, Intromission Frequency; Intromission Latency, Erections as well as aggregate of penile reflexes and caused significant reduction in the Mounting Latency and Post Ejaculatory Interval. The most appreciable effect of the extract was observed at the dose of 500 mg/kg. The test drug was also found to be devoid of any conspicuous gastric ulceration and adverse effects. The results indicated that the ethanolic extract of Chinopodium album Linn. Family Chinopodiaceae produced a significant and sustained increase in the sexual activity of normal male mice, without any conspicuous gastric ulceration and adverse effects. Thus, the resultant aphrodisiac affectivity of the extract lends support to the claims for its traditional usage in sexual disorders.

Biography:

Professor Nehal Afifi has worked at Pharmacology Department, Faculty of Veterinary Medicine, Cairo University from 1997 till now and Head of Pharmacology Department from 2009 to till now Associate Professor of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 1992. Lecturer, of Pharmacology, Faculty of Veterinary Medicine, 1987. Assistant Lecturer of Pharmacology, Faculty of Veterinary Medicine, 1985. Demonstrator at Pharmacology Department, Faculty of Veterinary Medicine, 1981. She is a member of American Society for Pharmacology and Experimental Therapeutics (ASPET) and member of the scientific committee for Veterinary Drugs Registration, Ministry of Health, Central Administration for Pharmaceutical Affairs.

Abstract:

Despite all the studies performed to date, therapy choices for liver injuries are very few. Therefore, the search for a novel drug that could safely and effectively treat liver injuries remains a challenge. The current study aimed at evaluating the potential hepatoprotective influence of Ellagic acid (EA) and silymarin as a reference drug against thioacetamide (TAA)-induced liver toxicity for rats. Methodology : Mature Albino Wister rats were orally daily treated with EA (50 and 100 mg/kg, PO), silymarin ((50 mg/kg, PO) for 21consecutive days, then were injected ip with TAA (300 mg/Kg, i.p.) twice with 24hours interval in the last two days of the experiment to induce hepatotoxicity. Blood samples wear withdrawn from all rats, liver tissue isolated and sera separated for serum liver function tests. Liver homogenates were used for assessment of oxidative stress biomarkers, inflammatory cytokines, hepatocellular apoptosis and histopathological examinations. Hepatic DNA fragmentation levels were examined calorimetrically by diphenylamine and electrophoreticaly by electrophoresis. Results of the present study revealed that oral administration of EA (50 and 100 mg/kg) for 21 days significantly improved the elevated liver enzymes (AST and ALT), alkaline phosphatase and total bilirubin with significant decreased oxidative stress biomarkers measured as malondialdehyde (MDA) , nitric oxide (NO) and reduced glutathione (GSH) levels in liver homogenate. In addition, EA decrease the elevated inflammatory cytokine; α-tumor necrosis factor (TNF-α), ẞ- nuclear factor kappa (NF-κ B) and DNA fragmentation. in a dose dependant manner. Conclusion & Significance: In this study EA is proved to has a hepatoprotective effect via mechanisms involving the attenuation of oxidative stress, antioxidant potential, and alleviation of inflammation and inhibition of hepatocellular apoptosis

Biography:

Pureun-Haneul Lee works for Genome Research Center for Allergy and Respiratory Diseases Soonchunhyang University Bucheon Hospital, Republic of Korea. He has contributed his work on Claudin 5 Transcripts Following Acrolein Exposure Affected by Epigenetic Enzyme in the Journal of Clinical Toxicology.

Abstract:

Purpose: Annexin A5 (ANXA5) has a potential role in cellular signal transduction, inflammation, and fibrosis. However, the exact role of ANXA5 in asthma remains to be clarified. The aims of the present study were to investigate ANXA5 protein expression in a mouse model of asthma and pollutant exposure and to elucidate the relationships between clinical variables and plasma ANXA5 levels in patients with asthma.

Methods: A murine model of asthma induced by ovalbumin (OVA) and titanium dioxide (TiO2) nanoparticles has been established using BALB/c mice, and we examined ANXA5 expression and lung fibrosis using this model. Moreover, we also compared ANXA5 plasma levels in patients with controlled vs. exacerbated asthma.

Results: ANXA5 protein levels were lower in lung tissue from OVA + OVA mice than in control mice. Lung ANXA5, connective tissue growth factor (CTGF), and transforming growth factor β1 (TGF-β1) protein levels were higher in OVA + TiO2-exposed mice than in control or OVA + OVA mice. Although Dermatophagoides pteronyssinus (Derp1) treatment increased lung ANXA5 protein levels in MRC-5 cells and A549 epithelial cells, it decreased lung ANXA5 levels in NHBE cells. Treatment with TiO2 nanoparticles increased lung ANXA5, CTGF, and TGF-β1 protein levels in MRC-5 cells, A549 epithelial cells, and NHBE cells. Plasma ANXA5 levels were lower in asthmatic patients than in healthy controls, and they were significantly enriched in patients with exacerbated asthma compared with those with controlled asthma (P < 0.05). ANXA5 levels were correlated with pulmonary function as assessed by spirometry.

Biography:

Professor Elsayed I. Salim has his expertise in molecular carcinogenesis, toxicogenomics, anticancer drug discovery and cancer risk assessment. He received his B.Sc. and M.Sc. degrees from Tanta university, Faculty of Science. Egypt, and his Doctorate of Medical Sciences from Osaka City University Medical School, Japan at 2000. His work focuses on the effect of different natural products during multistage carcinogenesis in animas and in vitro. He also concentrates on molecular mechanisms for cancer stem cells and nanoparticle toxicity during  carcinogenesis in vitro and in vivo.

Abstract:

It has been recently documented that mucin depletion in colonic epithelium is a hallmark for malignant transformation in human and rodents. To study the contribution of targeted therapy for mucous secreting cells during colon carcinogenesis, we used male rats divided into 5 groups. Group 1: Normal control; group 2: 1,2-dimethylhydrazine (DMH)-injected rats; group 3: Rats injected with DMH then received 10 mg/kg/b.wt. Cetuximab, a monoclonal antibody that targets epidermal growth factor receptor (EGFR); group 4: Rats injected with DMH then i.p. treated with Na-butyrate (200mg/kg body weight), known to cause colonocytes and mucous cells differentiation. Group 5: Rats received DMH then treated with both Cetuximab and Na-butyrate at the same doses. Rats from groups 3-5 had significant lower numbers of aberrant crypt foci (ACF) and mucin depleted foci (MDF), end point biomarkers for colon cancer, as compared with the DMH-administered group (G2). Combination therapy in G5 exerted most potent effect against ACF and MDF. All treatments retained the goblet cell numbers in colonic epithelium close to control levels with better effects obtained in G5. Moreover, all treatments have significantly inhibited the cellular proliferation levels of the colonic epithelia. Further, the drugs used have modulated the mRNA expression levels of MUC-2 and c-jun genes which are correlated with mucin secretion and early colon carcinogenesis respectively with most clear effects in G5. The data show that targeting epithelial and mucous cell growth and differentiation during carcinogenesis could recuperate the rats’ colonic epithelium integrity and counter carcinogenesis and turnover towards malignancy. This could be of importance to colorectal cancer therapy.

Biography:

Abstract:

Matrix metalloproteinases (MMPs) play a significant role in degrading the extra- cellular matrix in cancer development and metastasis. Overexpression of matrix metalloproteinases in tumour tissues relative to normal tissues has been exploited as a target for peptide-based therapeutics, to improve therapeutic index of currently used agents. The stability of MMP-activated prodrugs in normal tissue or organs is a significant challenge for their success in the clinic. In an in vitro study, the stability of twenty six prodrugs was studied in mouse liver, kidney, lung and tumour homogenates using HPLC and LC/MS. Selected agents were studied in vivo. Each prodrug has a characteristic amino acid sequence with dominant FITC N-terminal end cap. All prodrugs were conjugated to a colchicine derivative (ICT 2552) which is a vascular disrupting agent causing tumour vasculature shutdown and consequently, tumour necrosis. ICT 3146, ICT 3019, ICT 3120 and ICT 3115 prodrugs showed  significant stability in normal tissues and considerable activation in certain tumour tissues compared to the lead compound ICT 2588. Also, the selectivity of promising prodrugs to the MMP family was confirmed by using leupeptin (serine, cysteine and threonine protease inhibitor), pepstatin A (aspartate protease inhibitor), phosphoramidon (nepralysin inhibitor), ilomastat (metalloproteinase inhibitor) and BML-P115 (matrix metalloproteinase inhibitor). Moreover, members of the MMP family responsible for cleaving the selected prodrugs were identified using recombinant MMP enzymes. Furthermore, a LC/MS-MS method was developed to specifically detect and quantify MMP-16 protein expression in H460 tumour. MMP-16 was responsible for the cleavage of ICT 3146 and ICT 3115. Therefore, MMP-activated prodrugs could be a useful therapeutic approach to avoid off-site toxicities of currently used anti-tumour agents

Biography:

Abstract:

This study was conducted to investigate the impact of heavy metals (Cd, Pb, As, Hg, Cr, and Ni) on plants and soil samples in Camp2, quarry site, Akamkpa Local government area, Cross River State. Plant (T. Occidentalis Vegetables) samples were collected from farmlands within the study location, and soil samples were also taken at a depth of 0.15-0.30cm from the same location where the vegetable plants were sampled. Both samples were processed using standard procedures and heavy metals estimated using Atomic absorption spectrophotometry. The results obtained showed the presence of some heavy metals (Ni, Cd, and Pb) in high concentration in both soil and plant samples, while other heavy metals (As, Hg, and Cr) were present at low concentrations. When these results were compared with the permissible limit standards by World Health Organization (W.H.O). It could be suggested that pollution of the soil and plants around Camp2 community could be detrimental to the health condition of the people living around the quarry environment