1
Clinical Therapeutics e6 Volume 36 Number 8S Therefore, it is unlikely that an increased extracellular adenosine for- mation contributes to the cardioprotective effect of MR antagonists. Disclosure of Interest: None declared. EACPT-0018—NANOTECHNOLOGY-BASED STEM CELL MYOCARDIAL REGENERATION J.S. Peñataro * ; M. Ezzeldin-Sharaf; and G. Calvo-Rojas Clinical Pharmacology, Hospital Clínic de Barcelona, Barcelona, Spain Introduction: Stem cell therapy has been widely applied in cardio- vascular diseases, with high attrition rates. This therapeutic failure has been partly explained by a scarce cellular retention, survival, and differentiation in the ischemic myocardium. Nanotechnology has emerged as a cutting-edge field that may contribute to optimiza- tion of stem cell–mediated myocardium regeneration. Our goal was to review the current state-of-the-art in nanotechnology-based stem cell myocardial therapy. Patients (or Materials) and Methods: An exhaustive review was performed, involving the most relevant literature on the topic from the last 5 years. Results: Milestones Technology Applied Type of Studies Efficacy Results Micro- and nanofabricated niche properties *Nanofibrous construct *Cellular pretreatment *In vitro *Animal models Combined effect: biochemical stimuli and niche remodeling via a nanofibrous scaffold, fostering the formation of intercellular connections and cellular differentiation. Selection of cardiomyogenically differentiated stem cells *Nucleofection of molecular beacons detecting myosin RNA *In vitro Cardiomyocyte selection: optimized selection of cardiomyocytes in a mixture of differentiated pluripotent cell cultures. Cell tracking *Harmonic nonlinear nanodoublers *In vitro Capturing of a high- speed movie, tracking cell differentiation. Genetic modification *Gene transfection: preconditioning and reprogramming genes, therapeutic genes encoding proteins with therapeutic benefit *In vitro *Animal models *Better survival and differentiation rates *Successful therapeutic gene delivery. Conclusion: The application of nanotechnology to stem cell–mediated tissue regeneration is still at an early stage of development. Early studies have yielded promising results in cellular and animal models. Although further basic and clinical research is required, this novel approach seems capable of optimizing the efficacy of cell therapy in the short term. Disclosure of Interest: None declared. EACPT-0014—EFFECT OF COMBINATION OF NAD AND INOSINE-CONTAINING DRUG ON HEMODYNAMIC INDICES, BAROREFLEX SENSITIVITY, SYMPATHETIC NERVE ACTIVITY, AND ENDOTHELIN-1 PRODUCTION IN NITRATE TOLERANCE RATS S. Jibuti 1* ; N.N.V. Gongadze 1 ; T.T.D. Kezeli 2 ; G.G.V. Sukoyan 3 ; Z.Z.V. Chapichadze 4 ; N.N.M. Dolidze 2 ; S.Sh.M. Jibuti 4 ; M.M.G. Mirziashvili 5 ; and M.M.K. Chipashvili 6 1 Deparment of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; 2 Deparment of Pharmacology, Iv. Javakhishvili Tbilisi State University, Tbilisi, Georgia; 3 Research Laboratory, Biotechpharm, Tbilisi, Georgia; 4 Deparment of Pharmacology, Legal Entity of Public Law State Regulation Agency for Medical Activities, Tbilisi, Georgia; 5 Deparment of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; and 6 Deparment of Pharmacology, Iv. Javakhishvili Tbilisi State University, Tbilisi, Georgia Introduction: The purpose of the study was to evaluate the influence of NAD and inosine-containing drug (NADICD) on cardiovascu- lar events, reflex control of splanchnic sympathetic nerve activity (SSNA), and endothelin-1 (E-1) production in a rat model of nitrate tolerance (NTR). Patients (or Materials) and Methods: In anesthetized male Wistar rats, tolerance was induced by preliminary treatment with NTG (10 mg/kg SC) TID for 8 days. Animals were divided into 5 groups: I, control (C) were given subcutaneous injections of 0.1 mL 0.9% NaCl TID for 8 days; II, 0.1 mL 0.9% NaCl by the same method and then intravenous NTG (150 µg/kg); III, NTR followed by intravenous NTG (150 µg/kg); IV, NTR + NADICD IP and NTG IV (150 µg/kg) once-daily injection; and V, NaCl as in group C and then methylene blue (2.5 mg/kg IV) 20 minutes before intravenous NTG (150 µg/kg). Blood pressure, heart period, and reflex inhibition of SSNA were studied during testing of baroreflex (BRS) by using intravenous phe- nylephrine (3–10 µg/kg). Blood was sampled for the determination of E-1 plasma concentration (picograms per milliliter). Results: In anesthetized rats, BRS was attenuated in groups III and IV of rats versus group C. NTG in these animals, in contrast to groups II and IV, was accompanied by a reduction in BRS with respect to control of SSNA; this correlated with an increase in E-1 plasma con- centrations (7.8 [0.2] pg/mL) and (5.2 [0.1] pg/mL) in groups II and IV versus group C (2.6 [0.05] pg/mL; P < 0.05). Conclusion: It is suggested that NTG tolerance and inhibition of cyclic guanosine monophosphate pathways impaired homeostatic mechanisms of blood circulation, which may be improved by con- comitant administration of NADICD. Disclosure of Interest: None declared. EACPT-0033—COST CONSCIOUSNESS AND KNOWLEDGE OF CARDIOVASCULAR DRUGS AMONG STUDENTS AND PHYSICIANS T. Schutte 1* ; J. Tichelaar 1 ; B. Bilgi 2 ; M.C. Richir 1 ; T.P.G.M. de Vries 1 ; and M.A. van Agtmael 1 1 Internal Medicine–Pharmacotherapy, VU University Medical Center, Amsterdam, the Netherlands; and 2 Health Science Student, VU University, Amsterdam, the Netherlands Introduction: Medication costs should be taken into account in therapeutic decision making, according to the World Health Organization’s guide to good prescribing. Studies on prescribing errors are generally focused on (preventable) adverse events, rather than on cost-ineffective prescribing. To evaluate prescribing skills, our primary aim was to gain insight regarding attitudes toward medi- cation costs of students and physicians. The secondary aim was to examine their ability to estimate medication costs. Patients (or Materials) and Methods: This was a cross-sectional sur- vey, in medical students (bachelor/master) and physicians (special- ists/registrars), comprising 2 parts. Part 1 measured attitude toward costs by using a validated cost consciousness scale composed of 6 statements on a 5-point Likert scale. Part 2 assessed knowledge of drug costs through a list comprising open question estimations of the

Effect Of Combination Of Nad And Inosine-Containing Drug On Hemodynamic Indices, Baroreflex Sensitivity, Sympathetic Nerve Activity, And Endothelin-1 Production In Nitrate Tolerance

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Page 1: Effect Of Combination Of Nad And Inosine-Containing Drug On Hemodynamic Indices, Baroreflex Sensitivity, Sympathetic Nerve Activity, And Endothelin-1 Production In Nitrate Tolerance

Clinical Therapeutics

e6 Volume 36 Number 8S

Therefore, it is unlikely that an increased extracellular adenosine for-mation contributes to the cardioprotective effect of MR antagonists.Disclosure of Interest: None declared.

EACPT-0018—NANoTEChNology-BASEd STEm CEll myoCArdiAl rEgENErATioNJ.S. Peñataro*; M. Ezzeldin-Sharaf; and G. Calvo-RojasClinical Pharmacology, Hospital Clínic de Barcelona, Barcelona, SpainIntroduction: Stem cell therapy has been widely applied in cardio-vascular diseases, with high attrition rates. This therapeutic failure has been partly explained by a scarce cellular retention, survival, and differentiation in the ischemic myocardium. Nanotechnology has emerged as a cutting-edge field that may contribute to optimiza-tion of stem cell–mediated myocardium regeneration. Our goal was to review the current state-of-the-art in nanotechnology-based stem cell myocardial therapy.Patients (or Materials) and Methods: An exhaustive review was performed, involving the most relevant literature on the topic from the last 5 years.Results:

Milestones Technology Applied Type of Studies Efficacy Results

Micro- and nanofabricated niche properties

*Nanofibrous construct *Cellular pretreatment

*In vitro *Animal models

Combined effect: biochemical stimuli and niche remodeling via a nanofibrous scaffold, fostering the formation of intercellular connections and cellular differentiation.

Selection of cardiomyogenically differentiated stem cells

*Nucleofection of molecular beacons detecting myosin RNA

*In vitro Cardiomyocyte selection: optimized selection of cardiomyocytes in a mixture of differentiated pluripotent cell cultures.

Cell tracking *Harmonic nonlinear nanodoublers

*In vitro Capturing of a high-speed movie, tracking cell differentiation.

Genetic modification

*Gene transfection: preconditioning and reprogramming genes, therapeutic genes encoding proteins with therapeutic benefit

*In vitro *Animal models

*Better survival and differentiation rates *Successful therapeutic gene delivery.

Conclusion: The application of nanotechnology to stem cell–mediated tissue regeneration is still at an early stage of development. Early studies have yielded promising results in cellular and animal models. Although further basic and clinical research is required, this novel approach seems capable of optimizing the efficacy of cell therapy in the short term.Disclosure of Interest: None declared.

EACPT-0014—EffECT of ComBiNATioN of NAd ANd iNoSiNE-CoNTAiNiNg drug oN hEmodyNAmiC iNdiCES, BArorEflEx SENSiTiViTy, SymPAThETiC NErVE ACTiViTy, ANd ENdoThEliN-1 ProduCTioN iN NiTrATE TolErANCE rATSS. Jibuti1*; N.N.V. Gongadze1; T.T.D. Kezeli2; G.G.V. Sukoyan3; Z.Z.V. Chapichadze4; N.N.M. Dolidze2; S.Sh.M. Jibuti4; M.M.G. Mirziashvili5; and M.M.K. Chipashvili6

1Deparment of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; 2Deparment of Pharmacology, Iv. Javakhishvili Tbilisi State University, Tbilisi, Georgia; 3Research Laboratory, Biotechpharm, Tbilisi, Georgia; 4Deparment of Pharmacology, Legal Entity of Public Law State Regulation Agency for Medical Activities, Tbilisi, Georgia; 5Deparment of Medical Pharmacology, Tbilisi State Medical University, Tbilisi, Georgia; and 6Deparment of Pharmacology, Iv. Javakhishvili Tbilisi State University, Tbilisi, GeorgiaIntroduction: The purpose of the study was to evaluate the influence of NAD and inosine-containing drug (NADICD) on cardiovascu-lar events, reflex control of splanchnic sympathetic nerve activity (SSNA), and endothelin-1 (E-1) production in a rat model of nitrate tolerance (NTR).Patients (or Materials) and Methods: In anesthetized male Wistar rats, tolerance was induced by preliminary treatment with NTG (10 mg/kg SC) TID for 8 days. Animals were divided into 5 groups: I, control (C) were given subcutaneous injections of 0.1 mL 0.9% NaCl TID for 8 days; II, 0.1 mL 0.9% NaCl by the same method and then intravenous NTG (150 µg/kg); III, NTR followed by intravenous NTG (150 µg/kg); IV, NTR + NADICD IP and NTG IV (150 µg/kg) once-daily injection; and V, NaCl as in group C and then methylene blue (2.5 mg/kg IV) 20 minutes before intravenous NTG (150 µg/kg). Blood pressure, heart period, and reflex inhibition of SSNA were studied during testing of baroreflex (BRS) by using intravenous phe-nylephrine (3–10 µg/kg). Blood was sampled for the determination of E-1 plasma concentration (picograms per milliliter).Results: In anesthetized rats, BRS was attenuated in groups III and IV of rats versus group C. NTG in these animals, in contrast to groups II and IV, was accompanied by a reduction in BRS with respect to control of SSNA; this correlated with an increase in E-1 plasma con-centrations (7.8 [0.2] pg/mL) and (5.2 [0.1] pg/mL) in groups II and IV versus group C (2.6 [0.05] pg/mL; P < 0.05).Conclusion: It is suggested that NTG tolerance and inhibition of cyclic guanosine monophosphate pathways impaired homeostatic mechanisms of blood circulation, which may be improved by con-comitant administration of NADICD.Disclosure of Interest: None declared.

EACPT-0033—CoST CoNSCiouSNESS ANd KNowlEdgE of CArdioVASCulAr drugS AmoNg STudENTS ANd PhySiCiANST. Schutte1*; J. Tichelaar1; B. Bilgi2; M.C. Richir1; T.P.G.M. de Vries1; and M.A. van Agtmael11Internal Medicine–Pharmacotherapy, VU University Medical Center, Amsterdam, the Netherlands; and 2Health Science Student, VU University, Amsterdam, the NetherlandsIntroduction: Medication costs should be taken into account in therapeutic decision making, according to the World Health Organization’s guide to good prescribing. Studies on prescribing errors are generally focused on (preventable) adverse events, rather than on cost-ineffective prescribing. To evaluate prescribing skills, our primary aim was to gain insight regarding attitudes toward medi-cation costs of students and physicians. The secondary aim was to examine their ability to estimate medication costs.Patients (or Materials) and Methods: This was a cross-sectional sur-vey, in medical students (bachelor/master) and physicians (special-ists/registrars), comprising 2 parts. Part 1 measured attitude toward costs by using a validated cost consciousness scale composed of 6 statements on a 5-point Likert scale. Part 2 assessed knowledge of drug costs through a list comprising open question estimations of the