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Pharmaceuticals, Volume 3, Issue 3 (March 2010), Pages 441-781

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Research

Jump to: Review

Open AccessArticle Degradation of Methyldopa by Banana
Pharmaceuticals 2010, 3(3), 441-447; doi:10.3390/ph3030441
Received: 18 December 2009 / Revised: 12 February 2010 / Accepted: 2 March 2010 / Published: 2 March 2010
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Abstract
Methyldopa, an antihypertensive, is a very close analogue of DOPA. Drug interaction accompanied by degradation in a banana juice mixture was reported for DOPA. However, the effect of banana on methyldopa has not been reported. Therefore, we have investigated the impact of [...] Read more.
Methyldopa, an antihypertensive, is a very close analogue of DOPA. Drug interaction accompanied by degradation in a banana juice mixture was reported for DOPA. However, the effect of banana on methyldopa has not been reported. Therefore, we have investigated the impact of banana juice on methyldopa. The drug and supernatant of banana pulp were mixed, and the mixture was observed for changes in color, drug concentration, and ultraviolet-visible absorption spectra at 30 °C. The originally clear and colorless mixture started to acquire a yellow coloration after about 30 seconds after the mixing. The color tone increasingly deepened, then blistered solid particles that do not dissolve were observed after 3 hours. Concentration of methyldopa in the mixture decreased by 60% after 5 min, to 0.5% after 30 min of the mixing. From these findings, it was suggested that the drastic alterations were caused by banana polyphenol oxidase that plays a role in the biosynthesis of melanin pigment from levodopa in banana pulp. Because the degradation of methyldopa occurs extremely fast, it was suggested concomitant use of this anti-hypertensive and banana juice consumption should be avoided in clinical practice. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle Distribution of CPP-Protein Complexes in Freshly Resected Human Tissue Material
Pharmaceuticals 2010, 3(3), 621-635; doi:10.3390/ph3030621
Received: 28 December 2009 / Revised: 5 March 2010 / Accepted: 9 March 2010 / Published: 12 March 2010
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Abstract
Interest in cell-penetrating peptides (CPPs) as delivery agents has fuelled a large number of studies conducted on cultured cells and in mice. However, only a few studies have been devoted to the behaviour of CPPs in human tissues. Therefore, we performed ex [...] Read more.
Interest in cell-penetrating peptides (CPPs) as delivery agents has fuelled a large number of studies conducted on cultured cells and in mice. However, only a few studies have been devoted to the behaviour of CPPs in human tissues. Therefore, we performed ex vivo tissue-dipping experiments where we studied the distribution of CPP-protein complexes in samples of freshly harvested human tissue material. We used the carcinoma or hyperplasia-containing specimens of the uterus and the cervix, obtained as surgical waste from nine hysterectomies. Our aim was to evaluate the tissue of preference (epithelial versus muscular/connective tissue, carcinoma versus adjacent histologically normal tissue) for two well-studied CPPs, the transportan and the TAT-peptide. We complexed biotinylated CPPs with avidin--galactosidase (ABG), which enabled us to apply whole-mount X-gal staining as a robust detection method. Our results demonstrate that both peptides enhanced the tissue distribution of ABG. The enhancing effect of the tested CPPs was more obvious in the normal tissue and in some specimens we detected a striking selectivity of CPP-ABG complexes for the normal tissue. This unexpected finding encourages the evaluation of CPPs as local delivery agents in non-malignant situations, for example in the intrauterine gene therapy of benign gynaecological diseases. Full article
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
Open AccessArticle 2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin
Pharmaceuticals 2010, 3(3), 679-701; doi:10.3390/ph3030679
Received: 18 December 2009 / Revised: 8 March 2010 / Accepted: 10 March 2010 / Published: 15 March 2010
Cited by 2 | PDF Full-text (484 KB) | HTML Full-text | XML Full-text
Abstract
A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of [...] Read more.
A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli. Full article
(This article belongs to the Special Issue Antibiotics)
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Review

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Open AccessReview Cell-Penetrating Peptides for Antiviral Drug Development
Pharmaceuticals 2010, 3(3), 448-470; doi:10.3390/ph3030448
Received: 24 December 2009 / Revised: 6 February 2010 / Accepted: 1 March 2010 / Published: 2 March 2010
Cited by 10 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating [...] Read more.
Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. CPPs have been successfully utilized to enhance the cellular uptake and intracellular trafficking of antiviral molecules, and thereby increase the inhibitory activity of potential antiviral proteins and oligonucleotide analogues, both in cultured cells and in animal models. This review will address the notable findings of these studies, highlighting some promising results and discussing the challenges CPP technology has to overcome for further clinical applications. Full article
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
Open AccessReview Generic Medicine Pricing Policies in Europe: Current Status and Impact
Pharmaceuticals 2010, 3(3), 471-481; doi:10.3390/ph3030471
Received: 8 December 2009 / Revised: 11 February 2010 / Accepted: 3 March 2010 / Published: 5 March 2010
Cited by 17 | PDF Full-text (203 KB) | HTML Full-text | XML Full-text
Abstract
Generic medicine pricing is an area of national responsibility of European Union countries. This article aims to present the current status and impact of generic medicine pricing policies in ambulatory care in Europe. The study conducts a literature review of policies relating [...] Read more.
Generic medicine pricing is an area of national responsibility of European Union countries. This article aims to present the current status and impact of generic medicine pricing policies in ambulatory care in Europe. The study conducts a literature review of policies relating to free-pricing systems, price-regulated systems, price differentiation, price competition and discounts, and tendering procedures; and a survey of European generic medicine pricing policies. Competition from Indian generic medicine manufacturers, European variation in generic medicine prices and competition between generic medicine manufacturers by discount suggest that the potential savings to health care payers and patients from generic medicines are not fully realized in Europe. One way of attaining these savings may be to move away from competition by discount to competition by price. Free-pricing systems may drive medicine prices downwards under specific conditions. In price-regulated systems, regulation may lower prices of originator and generic medicines, but may also remove incentives for additional price reductions beyond those imposed by regulation. To date, little is known about the current status and impact of tendering procedures for medicines in ambulatory care. In conclusion, the European experience suggests that there is not a single approach towards developing generic medicine pricing policies in Europe. Full article
(This article belongs to the Special Issue Generic Drugs)
Open AccessReview The Chick Embryo Chorioallantoic Membrane as an In Vivo Assay to Study Antiangiogenesis
Pharmaceuticals 2010, 3(3), 482-513; doi:10.3390/ph3030482
Received: 12 January 2010 / Revised: 29 January 2010 / Accepted: 2 March 2010 / Published: 8 March 2010
Cited by 8 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
Antiangiogenesis, e.g., inhibition of blood vessel growth, is being investigated as a way to prevent the growth of tumors and other angiogenesis-dependent diseases. Pharmacological inhibition interferes with the angiogenic cascade or the immature neovasculature with synthetic or semi-synthetic substances, endogenous inhibitors or [...] Read more.
Antiangiogenesis, e.g., inhibition of blood vessel growth, is being investigated as a way to prevent the growth of tumors and other angiogenesis-dependent diseases. Pharmacological inhibition interferes with the angiogenic cascade or the immature neovasculature with synthetic or semi-synthetic substances, endogenous inhibitors or biological antagonists.The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane, which serves as a gas exchange surface and its function is supported by a dense capillary network. Because its extensive vascularization and easy accessibility, CAM has been used to study morphofunctional aspects of the angiogenesis process in vivo and to study the efficacy and mechanism of action of pro- and anti-angiogenic molecules. The fields of application of CAM in the study of antiangiogenesis, including our personal experience, are illustrated in this review article. Full article
(This article belongs to the Special Issue Angiogenesis Inhibitors)
Open AccessReview Inhaled Corticosteroids
Pharmaceuticals 2010, 3(3), 514-540; doi:10.3390/ph3030514
Received: 29 January 2010 / Accepted: 2 March 2010 / Published: 8 March 2010
Cited by 11 | PDF Full-text (1438 KB) | HTML Full-text | XML Full-text
Abstract
Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness [...] Read more.
Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and control asthma symptoms. ICS are now first-line therapy for all patients with persistent asthma, controlling asthma symptoms and preventing exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers, which improve compliance and control asthma at lower doses of corticosteroids. By contrast, ICS provide much less clinical benefit in COPD and the inflammation is resistant to the action of corticosteroids. This appears to be due to a reduction in HDAC2 activity and expression as a result of oxidative stress. ICS are added to bronchodilators in patients with severe COPD to reduce exacerbations. ICS, which are absorbed from the lungs into the systemic circulation, have negligible systemic side effects at the doses most patients require, although the high doses used in COPD has some systemic side effects and increases the risk of developing pneumonia. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
Open AccessReview Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure
Pharmaceuticals 2010, 3(3), 541-557; doi:10.3390/ph3030541
Received: 9 January 2010 / Revised: 7 February 2010 / Accepted: 5 March 2010 / Published: 8 March 2010
Cited by 3 | PDF Full-text (2256 KB) | HTML Full-text | XML Full-text
Abstract
Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme [...] Read more.
Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview NSAIDs and Acute Pancreatitis: A Systematic Review
Pharmaceuticals 2010, 3(3), 558-571; doi:10.3390/ph3030558
Received: 2 January 2010 / Revised: 11 February 2010 / Accepted: 9 March 2010 / Published: 10 March 2010
Cited by 8 | PDF Full-text (200 KB) | HTML Full-text | XML Full-text
Abstract
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In [...] Read more.
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas. Full article
(This article belongs to the collection Non-Steroidal Anti-Inflammatory Drugs)
Open AccessReview Platelet-Derived Growth Factor (PDGF)/PDGF Receptors (PDGFR) Axis as Target for Antitumor and Antiangiogenic Therapy
Pharmaceuticals 2010, 3(3), 572-599; doi:10.3390/ph3030572
Received: 28 January 2010 / Revised: 16 February 2010 / Accepted: 9 March 2010 / Published: 11 March 2010
Cited by 28 | PDF Full-text (2001 KB) | HTML Full-text | XML Full-text
Abstract
Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF), fibroblast growth factor (FGF)-2 or platelet-derived growth factors (PDGF). [...] Read more.
Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF), fibroblast growth factor (FGF)-2 or platelet-derived growth factors (PDGF). From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and significance of PDGF/PDGFR expression in normal conditions and tumors, focusing on this axis as a potential target for antitumor and antiangiogenic therapy. Full article
(This article belongs to the Special Issue Angiogenesis Inhibitors)
Open AccessReview Targeting the Tumour: Cell Penetrating Peptides for Molecular Imaging and Radiotherapy
Pharmaceuticals 2010, 3(3), 600-620; doi:10.3390/ph3030600
Received: 26 December 2009 / Revised: 2 February 2010 / Accepted: 10 March 2010 / Published: 11 March 2010
Cited by 14 | PDF Full-text (444 KB) | HTML Full-text | XML Full-text
Abstract
Over the last couple of years, the number of original papers and reviews discussing various applications of cell penetrating peptides (CPPs) has grown exponentially. This is not remarkable since CPPs are capable of transporting the most varying cargo across cell membranes which [...] Read more.
Over the last couple of years, the number of original papers and reviews discussing various applications of cell penetrating peptides (CPPs) has grown exponentially. This is not remarkable since CPPs are capable of transporting the most varying cargo across cell membranes which is one of the biggest problems in drug delivery and targeted therapy. In this review, we focus on the use of CPPs and related peptides for delivery of imaging contrast agents and radionuclides to cells and tissues with the ultimate goal of in vivo molecular imaging and molecular radiotherapy of intracellular and even intranuclear targets. Full article
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
Open AccessReview Dendritic Guanidines as Efficient Analogues of Cell Penetrating Peptides
Pharmaceuticals 2010, 3(3), 636-666; doi:10.3390/ph3030636
Received: 18 December 2010 / Revised: 10 February 2010 / Accepted: 9 March 2010 / Published: 12 March 2010
Cited by 16 | PDF Full-text (398 KB) | HTML Full-text | XML Full-text
Abstract
The widespread application of cell penetrating agents to clinical therapeutics and imaging agents relies on the ability to prepare them on a large scale and to readily conjugate them to their cargos. Dendritic analogues of cell penetrating peptides, with multiple guanidine groups [...] Read more.
The widespread application of cell penetrating agents to clinical therapeutics and imaging agents relies on the ability to prepare them on a large scale and to readily conjugate them to their cargos. Dendritic analogues of cell penetrating peptides, with multiple guanidine groups on their peripheries offer advantages as their high symmetry allows them to be efficiently synthesized, while orthogonal functionalities at their focal points allow them to be conjugated to cargo using simple synthetic methods. Their chemical structures and properties are also highly tunable as their flexibility and the number of guanidine groups can be tuned by altering the dendritic backbone or the linkages to the guanidine groups. This review describes the development of cell-penetrating dendrimers based on several different backbones, their structure-property relationships, and comparisons of their efficacies with those of known cell penetrating peptides. The toxicities of these dendritic guanidines are also reported as well as their application towards the intracellular delivery of biologically significant cargos including proteins and nanoparticles. Full article
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
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Open AccessReview Hybridoma-Derived Idiotype Vaccine for Lymphoma: Approval Must Wait
Pharmaceuticals 2010, 3(3), 667-678; doi:10.3390/ph3030667
Received: 5 February 2010 / Revised: 3 March 2010 / Accepted: 8 March 2010 / Published: 15 March 2010
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Abstract
Hybridoma-derived idiotype vaccines have been used for the experimental treatment of human lymphoma over the last twenty years, providing evidence of biological efficacy, clinical efficacy and clinical benefit. However, the product that has come closer to regulatory approval is unlikely to clear [...] Read more.
Hybridoma-derived idiotype vaccines have been used for the experimental treatment of human lymphoma over the last twenty years, providing evidence of biological efficacy, clinical efficacy and clinical benefit. However, the product that has come closer to regulatory approval is unlikely to clear that hurdle due to the insufficiently robust data obtained in a recently closed clinical trial. This review aims at discussing the reasons for hybridoma-derived idiotype vaccines, more difficult to produce but also more successful than recombinant idiotype vaccines so far, are unlikely to gain regulatory approval. In particular, it is necessary to examine the many peculiar features of this therapeutic approach in a broader context, with special attention to concepts like customized active immunotherapy and randomization. Most published trials based on hybridoma-derived idiotype vaccines are being analyzed, together with the yet non-peer reviewed data from the only randomized study conducted so far with this product, and with the main trials on recombinant idiotype vaccines for thorough comparison. All in all, the sole randomized trial ever conducted on hybridoma-derived idiotype vaccines failed to achieve its primary clinical end point because of an insufficient accrual and because the statistical significance achieved was not as stringent as required for regulatory approval. Full article
(This article belongs to the Special Issue Targeted Therapy)
Open AccessReview Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment
Pharmaceuticals 2010, 3(3), 702-724; doi:10.3390/ph3030702
Received: 24 January 2010 / Revised: 24 February 2010 / Accepted: 5 March 2010 / Published: 16 March 2010
Cited by 30 | PDF Full-text (161 KB) | HTML Full-text | XML Full-text
Abstract
Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of [...] Read more.
Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain neuropeptides, characterized by discrete synthesis sites and multiple receptors, represent likely research candidates for novel therapeutic targets. The present review summarises the available preclinical and human evidence regarding the neuropeptide, oxytocin, and its implications in the aetiology and treatment of MDD. While the evidence is not conclusive at present additional studies are warranted to determine whether OXT may be of therapeutic benefit in subsets of MDD patients such as those with comorbid anxiety symptoms and low levels of social attachment. Full article
(This article belongs to the Special Issue Antidepressants)
Open AccessReview Theophylline
Pharmaceuticals 2010, 3(3), 725-747; doi:10.3390/ph3030725
Received: 14 January 2010 / Accepted: 18 March 2010 / Published: 18 March 2010
Cited by 8 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became [...] Read more.
Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is markedly reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) and blood concentrations are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids and in COPD patients with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
Open AccessReview Phytochemicals in the Control of Human Appetite and Body Weight
Pharmaceuticals 2010, 3(3), 748-763; doi:10.3390/ph3030748
Received: 9 December 2009 / Revised: 10 March 2010 / Accepted: 19 March 2010 / Published: 22 March 2010
Cited by 8 | PDF Full-text (191 KB) | HTML Full-text | XML Full-text
Abstract
Since obesity has grown to epidemic proportions, its effective management is a very important clinical issue. Despite the great amount of scientific effort that has been put into understanding the mechanisms that lead to overconsumption and overweight, at the moment very few [...] Read more.
Since obesity has grown to epidemic proportions, its effective management is a very important clinical issue. Despite the great amount of scientific effort that has been put into understanding the mechanisms that lead to overconsumption and overweight, at the moment very few approaches to weight management are effective in the long term. On the other hand, modern society is also affected by the growing incidence of eating disorders on the other side of the spectrum such as anorexia and bulimia nervosa which are equally difficult to treat. This review will try to summarise the main findings available in the literature regarding the effect of plants or plant extracts (phytochemicals) on human appetite and body weight. The majority of plant extracts are not single compounds but rather a mixture of different molecules, therefore their mechanism of action usually targets several systems. In addition, since some cellular receptors tend to be widely distributed, sometimes a single molecule can have a widespread effect. This review will attempt to describe the main phytochemicals that have been suggested to affect the homeostatic mechanisms that influence intake and body weight. Clinical data will be summarised and scientific evidence will be reviewed. Full article
(This article belongs to the Special Issue Phytochemicals with actions on the Central Nervous System)
Open AccessReview Liraglutide Therapy for Type 2 Diabetes: Overcoming Unmet Needs
Pharmaceuticals 2010, 3(3), 764-781; doi:10.3390/ph3030764
Received: 15 January 2010 / Revised: 3 March 2010 / Accepted: 19 March 2010 / Published: 22 March 2010
Cited by 9 | PDF Full-text (1095 KB) | HTML Full-text | XML Full-text
Abstract
Although advances have been achieved in the management of type 2 diabetes, current treatment options for patients with this disease still fail to address disease progression, glycaemic control remains suboptimal and therapies are often associated with weight gain and hypoglycaemia. Thus, new [...] Read more.
Although advances have been achieved in the management of type 2 diabetes, current treatment options for patients with this disease still fail to address disease progression, glycaemic control remains suboptimal and therapies are often associated with weight gain and hypoglycaemia. Thus, new antidiabetes therapies are being sought. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that have been the recent focus of research. The physiological action of GLP-1, in particular, has demonstrated its potential in addressing the therapeutic needs of patients with type 2 diabetes. To exploit this action, liraglutide, a human GLP-1 analogue that shares 97% of its amino acid sequence identity with native GLP-1, has been developed. In a recent phase 3 trial programme (LEAD, Liraglutide Effect and Action in Diabetes), treatment with liraglutide was associated with substantial improvements in glycaemic control and low risk of hypoglycaemia. In addition, reductions in weight and systolic blood pressure were reported. There is also an indication that liraglutide is capable of improving β-cell function and increasing β-cell mass. Thus, liraglutide may overcome the limitations with current therapies and help to address the unmet clinical needs of patients with type 2 diabetes. Full article
(This article belongs to the Special Issue Antidiabetic Drugs)

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