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Current Pharmaceutical Design

Yun Chen, Guorong Wu, Ruichun Wang, Junping Chen
OBJECTIVE: Postoperative pulmonary complications (PPCs) can contribute to increased mortality and prolonged hospital stay in surgical patients with gastric cancer (GC). This study aimed to investigate potential risk factors for PPCs in elderly GC patients following elective laparoscopic gastrectomy. METHODS: Eligible consecutive elderly GC patients (aged over 65 years) who were scheduled to undergo elective laparoscopic gastrectomy were enrolled in this study. The demographic, clinicopathological characteristics and laboratory variables were compared in patients with or without PPCs within postoperative 30 days...
July 12, 2018: Current Pharmaceutical Design
Sven Seiwerth, Rudolf Rucman, Branko Turkovic, Marko Sever, Robert Klicek, Bozo Radic, Domagoj Drmic, Mirjana Stupnisek, Marija Misic, Lovorka Batelja Vuletic, Katarina Horvat Pavlov, Ivan Barisic, Antonio Kokot, Mladen Japjec, Alenka Boban Blagaic, Ante Tvrdeic, Dinko Stancic Rokotov, Hrvoje Vrcic, Mario Staresinic, Bozidar Sebecic, Predrag Sikiric
Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the stable gastric pentadecapeptide BPC 157, a peptide given always alone vs. standard peptidergic angiogenic growth factors (EGF, FGF, VEGF), and numerous carriers. Further, we reviewed how the gastrointestinal tract healing could be generally perceived (i) in terms of angiogenic growth factors, and/or (ii) through the healing of extra-gastrointestinal tissues healing, such as tendon, ligament, muscle and bone, and vice versa...
July 11, 2018: Current Pharmaceutical Design
Jaleh Varshosaz, Erfaneh Ghassami, Fatemeh Ahmadipour
BACKGROUND: Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. METHODS: This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS)...
July 11, 2018: Current Pharmaceutical Design
Zorana Vasiljevic, Gordana Krljanac, Marija Zdravkovic, Ratko Lasica, Danijela Trifunovic, Milika Asanin
BACKGROUND: The heart failure with preserved ejection fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be an important factors in the pathophysiology of HFpEF...
July 11, 2018: Current Pharmaceutical Design
Rohit Gundamaraju, Ravichandra Vemuri, Wai Chin Chong, Dominic P Geraghty, Rajaraman Eri
Initiating anti-apoptotic signaling or triggering cell death depends to a great extent on the nature or source of cellular stress and cell type. Interplay between each stress response eventually determines the fate of stressed cell. Numerous factors induce cell death by a number of pathways including apoptosis, autophagy and necrosis. Not surprisingly, some of the pathways are interrelated to each other through a mediator that could articulate the entire mechanism. The present review attempts to consolidate all the pathways included in intrinsic cellular stress such as oxidative stress and autophagy, endoplasmic reticular stress (ERS) and mitophagy and apoptosis as fate in cell stress...
July 11, 2018: Current Pharmaceutical Design
Teresa Padro, Gemma Vilahur, Lina Badimon
Dyslipidemia is widely accepted as one of the major risk factors in cardiovascular disease mainly due to its contribution in the pathogenesis of atherosclerosis in medium-sized and large arteries. However, it has become increasingly accepted that high-cholesterol levels can also adversely affect the microvasculature prior the development of overt atherosclerosis. Moreover, hypercholesterolemia has shown, in preclinical animal models, to exert detrimental effects beyond the vascular tree leading to larger infarcts and adverse cardiac remodeling post-myocardial infarction...
July 2, 2018: Current Pharmaceutical Design
D Trifunovic, J Dudic, O Petrovic, Z Vasiljevic-Pokrajcic
Myocardial contrast echocardiography has been used in clinical arena and for scientific research extensively in the last fifteen years. This non-invasive, bed-side and radiation free imaging technique offers several important possibilities: better delineation of the endocardial border, more reliable assessment of the left ventricular wall motion abnormalities, both in rest and during stress, and myocardial perfusion evaluation. Here we provide an overview on the different application of the myocardial contrast echocardiography in the ischemic heart disease with the special focus on perfusion studies and evaluation of coronary microcirculation...
July 1, 2018: Current Pharmaceutical Design
Lucian Calmac, Vlad Bataila, Bogdan Dragoescu, Cosmin Mihai, Alexandru Scafa-Udriste, Maria Dorobantu
Myocardial ischemia is the consequence of an unbalance between coronary flow that can be achieved and myocardial metabolic needs. Pathological state of both epicardial and intramyocardial vessels may be responsible for inducing ischemia. However revascularization decision should be based on the severity of each epicardial lesion that is evaluated. There are different diagnostic tools that may help for evaluation of each compartment which are based on measurement of coronary hemodynamics. Pressure derived indices are recommended by current guidelines for evaluation of epicardial stenosis significance...
July 1, 2018: Current Pharmaceutical Design
Marialuisa Scarpone, Edina Cenko, Olivia Manfrini
Timely delivered coronary revascularization with no residual anatomical stenosis does not always lead to prompt restoration of anterograde coronary flow and complete myocardial reperfusion. This condition is known as coronary no-reflow and is associated with major clinical adverse events and poor prognosis. The pathophysiology of no-reflow phenomenon is still poorly understood. Proposed mechanisms include distal microembolization of thrombus and plaque debris, ischemic injury, endothelial dysfunction and individual susceptibility to microvascular dysfunction/obstruction...
July 1, 2018: Current Pharmaceutical Design
Sasko Kedev, Ivan Vasilev
Functional tests used in the catheterization laboratory have emerged as a very important adjunctive tool to coronary angiography that can identify patients with myocardial blood flow impairment. Fractional flow reserve (FFR) measurement is highly recommended for detection of ischemia-related coronary lesion(s) when objective evidence of vessel-related ischemia is not available. Recently, much simpler instantaneous wave free ratio (iFR) was proposed as an alternative to FFR without requirement for administration of vasodilators...
July 1, 2018: Current Pharmaceutical Design
Seniz Demiryurek, Elif Baysalman, Azad Mammadov, Abdullah T Demiryürek
BACKGROUND: The small GTPase Rho family and its effectors, Rho-kinases (ROCK) play essential roles in the actin cytoskeleton organization and coordinate a broad range of cellular functions, such as inflammatory responses, cell contractility, migration, adhesion, proliferation, and apoptosis. METHODS: The goal of this work is to review of existing literature about systemic sclerosis and Behçet's disease in relation to ROCK. RESULTS: There are some evidences that ROCK expression is elevated in patients with systemic sclerosis and Behçet's disease...
July 1, 2018: Current Pharmaceutical Design
Hong Seo Jin, Cho Kye Soo, Ahn Min Hye, Pal Sukdeb, Choung Pill-Hoon, Jaiprakash Sangshetti, Rohidas B Arote
BACKGROUND: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles to achieving the permanent "magic bullet" cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention...
July 1, 2018: Current Pharmaceutical Design
Lina Badimon, Maria Borrell
Advances on early reperfusion therapies focused on the revascularization of the ischemic tissues have lead, in the last decades, to reduced mortality in acute myocardial infarction (MI) patients. However, a large proportion of patients show inadequate myocardial perfusion because of dysfunction of the microcirculation. The high prevalence of microvascular dysfunction after reperfusion therapies and the negative prognostic of this procedure justify the search for therapeutic strategies that aim to restore the microvascular network...
June 29, 2018: Current Pharmaceutical Design
Rita Rosado-Ramos, Joana Godinho-Pereira, Ines Figueira, Carolina Jardim, Goncalo Garcia, Regina Menezes
Our society is currently experiencing increased lifespan; one of the top causes for the high incidence of neurodegenerative disorders. The lack of effective treatments delaying or blocking disease progression has encouraged the active search for novel therapies. Many evidences support the protective role of phytochemicals in the prevention of neurodegenerative diseases, particularly (poly)phenols. In this review, we described the use of cellular-based models of neurodegenerative diseases and the benefits of their use as potent tools in the search for bioactive molecules, particularly (poly)phenols...
June 28, 2018: Current Pharmaceutical Design
Chandrakant R Malwade, Haiyan Qu
BACKGROUND: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities. Crystallization with its ability to engineer the final product to the desired qualities such as purity, polymorphic form, particle size and shape is one of the most important steps involved in the manufacturing of APIs...
June 28, 2018: Current Pharmaceutical Design
Koji Takeuchi, Kikuko Amagase
Endogenous prostaglandins (PGs), produced from arachidonic acid by the two isoforms of cyclooxygenase (COX), play a pivotal role in maintaining mucosal integrity by modulating various functions of the gastrointestinal (GI) tract, and PGE2 is most effective in these actions. The PGE2 receptor is classified into 4 specific G-protein coupled subtypes, EP1-EP4, and their distribution accounts for the multiple effects of this prostanoid. PGE2 prevents acid-reflux esophagitis and indomethacin-induced gastric lesions through EP1 receptors, while endogenous PGs protect the stomach against cold restraint stress mediated by mainly PGI2/IP receptors and partly EP4 receptors...
June 28, 2018: Current Pharmaceutical Design
Edina Cenko, Maria Bergami, Elisa Varotti, Raffaele Bugiardini
Vasospastic angina is an import cause of chest pain due to coronary artery vasospasm that is related with poor quality of life and can lead to myocardial infarction, arrhythmias and death. Since its first description as "Prinzmetal or variant angina" which was believed to be a focal spam that occurred in non-obstructed epicardial coronary arteries, physician and researchers were gradually, confronted with the clinical reality, and came to the conclusion that the coronary artery vasospasm was considerably more polymorphic than initially described...
June 25, 2018: Current Pharmaceutical Design
Davor Milicic, Nina Jakus, Dora Fabijanovic
The idea of coronary microcirculation playing a role in the pathophysiology of heart failure dates from decades ago, with authors hypothesizing that structural and functional alterations in the coronary microcirculation could potentially contribute to heart failure. It is known that in a wide range of primary cardiomyopathies, from dilated to hypertrophic, there are pathological alterations in myocardial vasculature structure and function, playing a role in the clinical course of the disease. Needless to say, many patients with normal epicardial coronary arteries can suffer from coronary microvascular dysfunction, that could lead to a wide variety of clinical problems - from impaired functional capacity to stable and unstable angina, Takotsubo syndrome, myocardial infarction with normal coronary arteries and can also end up with either acute or chronic heart failure...
June 25, 2018: Current Pharmaceutical Design
Axel R Pries, Wolfgang M Kuebler, Helmut Habazettl
BACKGROUND: Ischemic heart disease has long been considered to be exlusively caused by stenosis or occlusion. However, the coronary microcirculation too may play an important role in ischemic conditions. Also, the crucial role of microvessels in not only regulating blood flow on a local level but also mediating vascular permeability or inflammatory responses has been recognized. OBJECTIVE: To review important physiological and pathophysiological mechanisms of coronary microcirculatory control with focus on heterogeneity of local perfusion, microvascular permeability and inflammation...
June 25, 2018: Current Pharmaceutical Design
Akos Koller, Annamaria Szenasi, Gabriella Dornyei, Nora Kovacs, Adam Lelbach, Imre Kovacs
In various metabolic diseases both the coronary circulation and cardiac metabolism are altered. Here we summarize the effects of a condition called hyperhomocysteinemia (HHcy) - which can develop due to genetic or environmental causes - on the function of coronary microvessels and heart. This metabolic disease is underappreciated, yet even mild or moderate elevation of plasma concentrations of homocystein (Hcy, plasma Hcy >16 M), a sulfur-containing amino acid produced via methionine metabolism) leads to coronary and peripheral artery and even venous vessel diseases, leading to vasomotor dysfunction and increased thrombosis, consequently increased morbidity and mortality...
June 25, 2018: Current Pharmaceutical Design
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