Biography:

Sheila Leone had completed Medicine & Surgery degree and Post-graduated in Clinical Pharmacology from University of Modena and Reggio Emilia (Modena, Italy) She worked as assistant professor of Pharmacology (BIO/14), Department of Pharmacy from University of Chieti “G. D’Annunzio” (Chieti, Italy). The research activity is mainly focus on neuropharmacology, cardiopharmacology, endocrinology and behavior of synthetic and vegetal drugs. Department of Pharmacy, University “G.d’Annunzio” Chieti Pescara (Chieti, Italy). Author of papers (for the most part in international journals) and communications at National and International Congresses.

Abstract:

The endocannabinoid (eCB) system plays an important role in mood disorders, as such anxiety and depression. In addition, the eCB system is involved in the regulation of food intake, metabolism and calorie storage. However, it is well known that the first generation of CB1 blockers designed to reduce food intake and body weight, such as Rimonabant, was discontinued due to psychiatric disorders, such as anxiety and depression. The  discovery  of  RVD-hemopressin(α)  [RVD-hp(α)],  an hemoglobin α chain-derived peptide, revealed a promising research field for the pharmacotherapy of obesity. RVD-hp(α) was found to bind CB1 receptors, as negative allosteric modulator and as a positive allosteric modulator of CB2 receptor. In addition, pharmacological evidences reported a possible link between brain hypocretin/orexin, monoamine and eCB systems, as regards appetite and emotional behavior control. Considering this, the aim of our work was to investigated the effects of RVD-hp(α) on anxiety like behavior and food intake after central administration and related it to monoamine levels, proopiomelanocortin (POMC) and orexin-A gene expression, in the hypothalamus. We have studied the effects of central RVD-hp(α) (10 nmol) injection on anxiety-like behavior and feeding using different behavioral tests. Hypothalamic levels of norepinephrine (NE), dopamine (DA) and serotonin (5--HT) and gene expression of orexin-A and POMC were measured by high performance liquid chromatography (HPLC) and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis, respectively. Central RVD-hp(α) administration decreased locomotion activity and stereotypies. Moreover, RVD-hp(α) treatment inhibited anxiogenic-like behavior and food intake, NE levels and orexin-A gene expression, in the hypothalamus. Concluding, in the present study we demonstrated that central RVD-hp(α) induced anxiolytic and anorexigenic effects possibly related to reduced NE and orexin-A and POMC signaling, in the hypothalamus. These findings further support the central role of the peptide in rat brain thus representing an innovative pharmacological approach for designing new anorexigenic drugs targeting eCB system.

Biography:

Maria Laura Zuccoli obtained my medical degree from the University of Genoa, Italy, and I completed the residency in Clinical Toxicology at the University of Florence, in Italy. I am currently a PhD candidate in Experimental Medicine at the University of Genoa and a Visiting Fellow at the National Institute on Drug Abuse, in Baltimore, USA. My main research topics focus on the understanding of neurobiological mechanisms involved in the effects of widely abused substances such as cannabinoids, opioids and alcohol, using in vivo two-photon endomicroscopy, optogenetic and chemogenetic behavioral assays and molecular biology techniques.

 

Abstract:

Cannabis is a psychoactive substance widely used for both medicinal and recreational purposes. Cannabis-induced acute cognitive and motoric side effects are common and remain without effective treatment. A better understanding of the neurobiological mechanisms underlying cannabis-related effects is urgently needed to facilitate the discovery of novel therapeutics. We recently observed elevation in ammonia plasma concentrations during and after oral, smoke or vapor cannabis controlled administration (54mg) to 15 healthy cannabis users. Cannabis produced significant time (p<0.05) and treatment (p<0.001) effects, with differences in plasma ammonia between placebo and edible cannabis administration at 30 (p<0.05) and 90min (p<0.05), between placebo and vaporized (p<0.05) and smoking routes (p<0.05) at 90min. Plasma ammonia concentration positively correlated with blood -9-tetrahydrocannabinol (THC) concentrations (p<0.05). Using a translational approach, we then examined the acute effect of THC on plasma, liver and brain ammonia concentrations and enzyme activity in different brain regions of mice at 1, 3, 5 and 30min after a single THC injection. We found significant reduction in striatal glutamine synthetase (GS) activity (p<0.05) and increase in striatal ammonia concentration (p<0.05) 5min post-injection. THC plasma concentration correlated positively with striatal ammonia (p<0.001) and negatively with striatal GS activity (p<0.05). At 30min, we found marked increase in striatal ammonia (p<0.001), associated with significant increase in plasma ammonia (p<0.05). For the first time, we demonstrate that plasma ammonia concentration increases after controlled cannabis administration and we provide evidence that this increase could be generated in the brain through suppression of striatal GS activity.

Biography:

Edith Bianchi is a senior Global Business Development expert, specializing in the Medical device industry – specifically in Digital Health and Wearable applications. She has an impressive and quite extraordinary multi-disciplinary background and qualifications. Those are combining both clinical record as a CRA and Registered Nurse with CICU experience, as well as strong business management orientation with an MBA degree from University of Derby. Ms. Bianchi has a long track record in Medical Device sales organizations and was a key person in few meaningful strategic cooperations between major players in the industry.

 

Abstract:

New approaches to drug delivery are a fast growing field in the medical device industry. Strong market forces and healthcare trends are dramatically enhancing this evolution. Pharmacological advancements in drugs developments and their manufacturing have a tremendous contribution to the drug delivery field. One meaningful drive is the significant rise of injectable biologic therapies for more and more chronic conditions. The challenges presented by these drugs, are creating the need and opportunity for drug delivery systems.

The personalized medicine trend is obviously influencing drug related topics. The changes in approach to the patient are shifting hospital care to homecare setting, and simultaneously, shifting administrating injection of drugs subcutaneously instead of intravenous. Obviously intravenous injection demands costly skilled staff and mostly cannot be done in home setting. These are all taking part too in the evolution of drug delivery devices.

Another meaningful factor is patient's non-compliance to treatment, which is not only effecting the patient's health and poor outcomes, but is also baring substantial losses to pharmaceutical companies and resulting in a serious burden to the healthcare system. We are therefore, witnessing a great interest in adequate solutions for wearable drug delivery advanced devices which adhere to the patient's skin.

When designing such a system, some significant challenges arise. The development of a drug delivery patch device involves critical issues such as safety, the drug/reservoir interaction and many other elements which are necessary to be considered. However, engineering teams are becoming more and more familiar with yet another critical aspect- Human Factor and Ergonomics. These factors are most crucial with any S2T ("Skin to Thing") solution, and have an even more crucial weight when dealing with a drug delivery patch.

The "Skin to Thing" medical patch which is required to adhere the device to the body is indeed the body/machine crucial interface and should be given just as much a careful and thorough attention as the device itself, in order to achieve the device goals, assure the patient's compliance and successful treatment.

Biography:

Ali Shahraki has his expertise in Teaching and Research at the University of Sistan and Baluchestan, Zahedan, Iran. He supervised more than 25 theses of Biochemistry for Master’s Degree of Science students. He works in the fields of neuroscience, herbal medicine and signal pathways for inducing anti-proliferative and apoptosis in cancer cell lines through medicinal plants. He has built this model after years of experience in research, evaluation, teaching and administration in universities and education institutions.

 

Abstract:

Increased expression of cyclic guanosine 3′, 5′ monophosphate phosphodiesterase-5 (cGMP-PDEs) mRNAs has been demonstrated in several human carcinomas, including breast carcinoma, pancreatic cancer, bladder cancer, squamous cell carcinoma and prostate cancer, in comparison to adjacent normal tissues. Studies have elucidated that an increase in intracellular cGMP induces apoptosis and decreases cell population growth. Therefore, selective inhibitors of these PDEs might be potential anticancer agents. Previous investigations have demonstrated that Levisticum officinale contains flavonoids and alkaloids compound that are known as antitumoral components. The purpose of this study was to investigate the effect of Levisticum officinale hydroalcoholic extract on phosphodiesterase 5 gene expression, cGMP signaling pathway and its role in inducing apoptosis in the MCF-7(ER+) and in MDA-Mb-468 (triple-negative) cell lines. The mean inhibitory concentration (IC₅₀) of extract was determined in both cell lines using of MTT assay, and the type of cell death was detected by flow cytometry. The expression of PDE5 and cGMP levels was measured by real-time polymerase chain reaction and colorimetric assay, respectively. Treatment with hydroalchoholic extract of Levisticum officinale showed that 200 µg/ml to be the IC₅₀ for both cell lines. 12 hour treatment with IC₅₀ dosage showed a maximum decrease in the PDE5 expression and maximum increase in intracellular cGMP level, although, these effects were more significant in MDA-MB-468. In conclusion, our results showed that hydroalchoholic extract of Levisticum officinale had an anti-proliferative and apoptotic effect in MCF-7 and MDA-Mb-468 targeting PDE5 and cGMP signaling pathway.

Biography:

Piotr Wojciechowski is an Assistant in the Department of Respiration Physiology, Mossakowski Medical Research Centre, Warsaw, Poland. His interests scope within the crosstalk and interaction between neuropeptide and opioid systems and their effects on cardio-respiratory pattern.

Abstract:

Neuropeptide FF (NPFF) behaves as an endogenous opioid-modulation peptide that seems to be involved in opiate-induced tolerance and dependence and is thought to present strong inhibitory interaction with opioids. Although pharmacological properties of NPFF on pain perception and opioid-induced tolerance seem to be well documented, its effect on breathing pattern and respiratory depression induced by opioids remains unclear. The aim of the present study was to examine an impact of intravenous NPFF injection on respiration and its potency in elimination post-opioid apnoea. Experiments were performed on urethane-chloralose anaesthetized male Wistar rats breathing spontaneously room air. Respiratory parameters, arterial blood pressure and heart rate were measured. Rats were treated with an intravenous injection of NPFF in four doses: 0.1; 0.3; 0.6 and 1.2 mg/kg. Two minutes later, a dose of endomorphine-1 (EM-1) (50 μg/kg) was administered. Systemic injection of NPFF in doses: 0.1–0.6 mg/kg evoked only dose dependent hypertensive effect. The highest dose caused also a short-lived reduction in tidal volume, which affected minute ventilation immediately after the challenge and evoked a single episode of apnoea in one rat lasting 3.7 s. Bolus injection of 50 μg/kg of endomorphin-1 was administered into the femoral vein of control animals without NPFF pre-treatment evoked apnoea in 5 of 6 rats of mean duration of 11.2±1.2 s, short-lived hypotension and a slow down in the heart rate. Pre-treatment with NPFF diminished the number of post-endomorphin-1 apnoeas, to 2 in 5 rats at a dose of 0.1–0.3 mg/kg and to 1 in 5 animals at a dose of 0.6 mg/kg. EM-1 induced hypotensive effects and decrease in the heart rate were also reduced at all tested doses of NPFF. Our experiments showed that stimulation of neuropeptide FF receptors in the periphery diminishes the number of EM-1-induced arrests of breathing, as well as its hypotensive effect.

Biography:

Nermeen Salah El Deen is focused on improving public health and wellbeing. She started her career as a Demonstrator in the Pharmacology and Toxicology Department, Faculty of Pharmacy at Cairo University. Her work is based on decreasing acute renal failure rates caused by diclofenac which is one of the most commonly used NSAIDS through pre-treatment with different phosphodiesterase inhibitors.

Abstract:

Diclofenac is one of the most commonly used NSAID that leads to severe adverse effects on the kidneys. The aim of the present study is to investigate the potential pretreatment effect of phosphodiesterase 1, 3 and 5 inhibitors on diclofenac-induced acute renal failure in rats. Rats were classified into five groups (n=8); control group (received 1 ml saline), model group (received diclofenac; 15 mg/kg, i.p), vinpocetine group (received vinpocetine; 20 mg/kg, P.O), cilostazol group (received cilostazol; 50 mg/kg, P.O) and sildenafil group (received sildenafil; 5 mg/kg, P.O). Rats were treated with vinpocetine, cilostazol or sildenafil daily for six days. Diclofenac was injected on days four, five and six in all groups, except control group. On the seventh day, animals were sacrificed. Vinpocetine, cilostazol and sildenafil significantly reduced diclofenac-induced elevation in the serum levels of urea, creatinine and cystatin C as well as renal tissue contents of TNF-α, NF-κB, TLR4 and HMGB1. This was reflected on the marked improvement in histopathological changes induced by diclofenac. This study revealed the good protective effect of these phosphodiesterase inhibitors against diclofenac-induced acute renal failure. Sildenafil showed the best protection regarding TNF-α and NF-κB, while cilostazol showed the best results regarding TLR4, HMGB1 and histopathological examination.

Biography:

Clarissa Berardo, Doctorate in Biomedical Sciences, curriculum Pharmacology. Master Degree in Molecular Biology and Genetics. She has her expertise in mouse and rat liver isolation to study preservation techniques for organ transplantation (Cold Storage and Machine Perfusion), hepatocytes isolation from mouse and rat, primary and tumoral (HepG2 and Huh7.5) cell culture, use of genetic (Zucker) and nutritional (Methionine and Choline Deficient Diet) animal models to study hepatic diseases, such as NAFLD, NASH and ischemia/reperfusion injury. Knowledge of principal techniques performed in biomedical laboratory: western blot analysis, RT-PCR, histological techniques, biochemical and enzymatic assays.

 

Abstract:

The Negative Allosteric Modulator (NAM) 2-methyl-6-(phenylethynyl) pyridine (MPEP) of metabotropic Glutamate Receptor subtype 5 (mGluR5) improves viability of isolated anoxic hepatocytes1. It is known that during ischemia/reperfusion (I/R) injury, Kupffer cells activation occurs, causing an increase in TNF-α production. Moreover, TNF-α positively correlates with iNOS expression through NF-κB^2,3 and because of the presence of TNF Response Element on iNOS gene^4,5.

The aims of this study were: to investigate the protection mediated by other NAMs (MTEP and Fenoabam) against anoxic damage in isolated hepatocytes and to investigate the liver functionality in two ex vivo models of I/R.

Male Wistar rat hepatocytes were exposed to 90 minutes anoxia at 37°C with: MPEP and 3-((2-methyl-4-thiazolyl ethynyl pyridine (MTEP) at 3-30μM, Fenobam at 1-10-50-100μM. Hepatocytes viability was evaluated by trypan blue exclusion and LDH release. Wildtype and mGluR5 knockout livers from Balb-c mice were isolated, subjected to cold or normothermic I/R and treated with MPEP 0.3μM; transaminases release, BAX and Bcl-2, iNOS, eNOS and TNF-α protein expression were evaluated in cold I/R samples, while LDH, AST, TNF-α release were evaluated in normothermic samples.

MPEP 30μM, MTEP 3μM and Fenobam 50μM improved significantly anoxic isolated hepatocytes viability respect to anoxic controls. MPEP addition during I/R significantly reduced LDH, transaminases and TNF-alpha respect to ischemic controls in both cold and normothermic I/R, with a trend similar to mGluR5 knockout samples. Furthermore, MPEP reduced TNF-α levels, causing selectively iNOS expression decrease without affecting eNOS expression.

Our results demonstrated that MPEP, MTEP and Fenobam protect rat hepatocytes against ischemic injury. Furthermore, MPEP is able to reduce susceptibility of liver grafts to the preservation injury in two ex vivo models, in which the pharmacological blockade of mGluR5, interrupting the excitotoxic cascade, reduces the inflammation mediator TNF-α.