Age-related macular degeneration: cost-of-illness issues

Macular degeneration refers to the breakdown of cells in the centre of the retina. Some degeneration is an inevitable consequence of the aging process; however, when this is associated with loss of sight in the central part of the field of vision an underlying pathology is considered present. Among those aged 55 years, the prevalence of the disease in the US was estimated at 1% rising to approximately 15% among those aged 80 years. Other studies estimate the prevalence of the disease to be higher and to be increasing. The main effect of the disease is to reduce the ability of the individual to engage in everyday activities that require clear central vision. It may also be associated with elevated risks of depression and increased levels of dependency. Currently there is no effective treatment for the majority of patients. For a minority (< 10%) laser photocoagulation therapy may be effective in reducing the risk of severe vision loss. Another treatment, photodynamic therapy, is in development and many others are at an experimental stage. This review sought to establish current knowledge on the cost of illness associated with age-related macular degeneration (ARMD). A search of the literature, together with direct communication with researchers in related fields and patient support/advocacy groups, was undertaken to ascertain current knowledge on the cost of illness of ARMD. While literature on the disease is extensive and literature on treatments is emerging, no substantive information on direct or indirect costs was found although evidence that loss of earnings may occur is beginning to emerge. Some information does exist on cost of illness in diabetic retinopathy, a disease with similarities to ARMD, though even for this disease gaps in knowledge are apparent and wide variations exhibited. Given current knowledge, it is not possible to report on the cost of illness for ARMD with confidence. The lack of information on the cost of illness in ARMD presents difficulties for researchers and policy makers in assessing the cost effectiveness of the existing treatment, as well as new treatments as they become available. Given developments in treatments and the increasing prevalence of the disease, it is important that cost-of-illness information is gathered for ARMD.     

The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: A review of in vivo and in vitro studies

Osteoporosis is a progressive systemic disease characterized by low bone mineral density and deterioration of bone microarchitecture. The current therapies are effective to prevent further bone loss and fractures but they are accompanied by undesirable side effects and cost issues. The discovery of Chinese herbal medicines with osteoprotective effects provides alternative treatments to prevent bone loss without causing severe side effects. Artemisinin (ARS) and its related compounds have been clinically used as antimalarial agents. Interestingly, their bioactivity is not limited to antimalarial treatment. Experimental evidences indicate that ARS compounds are a potential type of therapeutic alternative medicine for bone loss induced by accelerated osteoclastic bone resorption. The present review intends to summarize the current understandings of ARS compounds and their molecular mechanisms of actions in preventing bone loss. ARS compounds selectively inhibit osteoclast differentiation by downregulation of pathways involved in receptor activator of nuclear factor kappa-B ligand (RANKL) -induced osteoclastogenesis, and have no effect on osteogenic differentiation of osteoblasts. The exact mechanism of activation and action of these anti-resorption effects are not fully elucidated. Considering the characteristic of high levels of intracellular iron in osteoclasts, ARS compounds may inhibit osteoclast differentiation via mechanisms associated with intracellular iron, including the cleavage of endoperoxide bridge, oxidative damage and ferroptosis. The anti-resorptive effects of ARS compounds need to be further investigated in bone loss models caused by different factors, and to be under clinical development.     

Natural compounds with xanthine oxidase inhibitory activity: A review

Hyperuricemia (HUA), a disease due to an elevation of body uric acid level and responsible for various diseases such as gout, cardiovascular disorders, and renal failure, is a major ground debate for the medical science these days. Considering the risk factors linked with allopathic drugs for the treatment of this disease, the debate has now become a special issue. Previously, we critically discussed the role of dietary polyphenols in the treatment of HUA. Besides dietary food plants, many researchers figure out the tremendous effects of medicinal plants‐derived phytochemicals against HUA. Keeping in mind all these aspects, we reviewed all possible managerial studies related to HUA through medicinal plants (isolated compounds). In the current review article, we comprehensively discussed various bioactive compounds, chemical structures, and structure–activity relationship with responsible key enzyme xanthine oxidase.     

Correlation of platelet activating factor and age-related macular degeneration

Objective: To investigate the role of Platelet Activating Factor (PAF) in the pathogenesis and development of Age-Related Macular Degeneration (ARMD).

Research design and methods: Fifty six patients with ARMD (24 patients with dry ARMD and 32 patients with wet ARMD) and 25 age-matched control participants underwent ophthalmological examination, including visual acuity measurement and evaluation of the retina. The participants were classified into three groups according to their retinal status, based on indirect fundoscopy, Optical Coherence Tomography and fluorescein angiography findings. In order to evaluate the concentrations of PAF in serum, blood samples were collected from all participants and were analyzed with ELISA technique.

Results: The concentrations of PAF differed significantly according to macular lesions and were found to be lower in patients with ARMD than control participants.

Conclusions: PAF levels are decreased along with the severity of ARMD. Understanding the role of PAF in pathogenesis of ARMD could be the impetus for the development of new therapies field of treatment of ARMD or even other retinal diseases.     

Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD:A promising drug Potentilla discolor BungeOA

Nonalcoholic fatty liver disease(NAFLD) is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver injury.There are currently no approved effective pharmacological treatments for NAFLD.Traditional Chinese medicine(TCM) has been used for centuries to treat patients with chronic liver diseases without clear disease types and mechanisms.More recently,TCM has been shown to have unique advantages in the treatment of NAFLD.We performed a systematic review of the me...     

Natural compounds in epigenetics: A current view

The successful treatment of many human diseases, including cancer, has come to be considered a major challenge, as patient response to therapy is difficult to predict. Recently, considerable efforts are being focused on the development of new tools to meet the growing demand for personalized medicine. With few exceptions, synthetic compounds have been unable to meet initial expectations for their clinical use. The last twenty years have been characterized by the failure of several drugs in advanced clinical development, possibly due to the insufficient understanding of molecular pathways underlying their mechanism of action. Although the biodiversity of compounds found in nature has been poorly explored until now, the field of naturally occurring drugs is rapidly expanding. Here, we review the current knowledge on the use of natural compounds with particular emphasis on those that display a chromatin remodeling effect coupled with anticancer action.     

Update on current and future novel therapies for dry age-related macular degeneration

Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. There are currently no cures, but there are promising potential therapies that target the underlying disease mechanisms of dry ARMD. Stem cells, ciliary neurotrophic factor, rheopheresis, ozonated autohemotherapy and prostaglandins show promise in stabilizing or improving visual acuity. Age-Related Eye Disease Study vitamins may reduce progression to severe ARMD. Adjuvant therapy like low vision rehabilitation and implantable miniature telescopes may help patients adjust to the sequelae of their disease, and herbal supplementation with saffron, zinc monocysteine and phototrop may be helpful. Therapies that are currently in clinical trials include brimonidine, doxycycline, anti-amyloid antibodies (GSK933776 and RN6G), RPE65 inhibitor (ACU-4429), complement inhibitors (ARC1905, FCFD4514S), hydroxychloroquine, intravitreal fluocinolone acetate and vasodilators like sildenafil, moxaverine and MC-1101. Therapies that have not been shown to be effective include POT-4, eculizumab, tandospirone, anecortave acetate, the antioxidant OT-551, sirolimus and vitamin E.     

Current approaches to discover marine antileishmanial natural products

Leishmaniasis is a neglected infectious disease caused by kinetoplastid protozoans. An urgent need for novel chemotherapeutics exists. The current approaches to discover new antileishmanial compounds present many drawbacks, including high-cost and time-consuming bioassays. Thus, advances in leishmaniasis treatment are limited, and the development of screening assays is hindered. The combination of multidisciplinary approaches using standardised methods and synchronous projects could be an alternative to develop novel drugs for leishmaniasis treatment. In this review, we discuss the current status of leishmaniasis occurrence and treatment. In addition, we address the advantages and limitations of in vitro leishmaniasis bioassays and discuss the findings of drug discovery research using natural products. Finally, we comprehensively review the marine natural products that are active against Leishmania spp., including their natural sources and bioactivity profile.     

Discovery of MAO-B Inhibitors - Present Status and Future Directions Part I: Oxygen Heterocycles and Analogs

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The role of monoamine oxidase (MAO) inhibitors has expanded in the PD treatment. The present review will summarize the current structureactivity relationship information available on MAOs inhibitors of unrelated families of compounds of oxygen heterocyclic type based on coumarin, chromone and chalcone scaffolds. As the current hitting-one-target therapeutic strategy has been proved to be quite inefficient in PD, this review will also discuss about the development of multi-target drugs, in which MAO inhibition plays a counter-part, as a novel and promising treatment approach for PD.     

New concepts in the drug therapy of Alzheimer’s disease

There are currently four compounds approved for use in the treatment of Alzheimer’s disease (AD). These drugs are all cholinesterase (ChE) inhibitors, which are thought to provide predominantly symptomatic benefits by increasing the level of acetylcholine (ACh) in the synapse. Although there are slight differences in the mechanisms of action of these compounds, it remains to be determined whether any one of them has a significant therapeutic advantage over the others. Several other drugs have also been investigated for their potential use as either symptomatic or disease-modifying agents in the treatment of AD, with mixed results. Current therapeutic research is focused on addressing the underlying pathology of AD, in the hope of arresting or reversing the course of the disease. This review will provide an overview of the ChE inhibitors and other drugs used for treating the symptoms of AD, summarise the results of recent therapeutic trials, discuss directions of future research and outline the current treatment recommendations for AD.     

New concepts in the drug therapy of Alzheimer's disease

There are currently four compounds approved for use in the treatment of Alzheimer's disease (AD). These drugs are all cholinesterase (ChE) inhibitors, which are thought to provide predominantly symptomatic benefits by increasing the level of acetylcholine (ACh) in the synapse. Although there are slight differences in the mechanisms of action of these compounds, it remains to be determined whether any one of them has a significant therapeutic advantage over the others. Several other drugs have also been investigated for their potential use as either symptomatic or disease-modifying agents in the treatment of AD, with mixed results. Current therapeutic research is focused on addressing the underlying pathology of AD, in the hope of arresting or reversing the course of the disease. This review will provide an overview of the ChE inhibitors and other drugs used for treating the symptoms of AD, summarise the results of recent therapeutic trials, discuss directions of future research and outline the current treatment recommendations for AD.     

Recent developments in cholinesterases inhibitors for Alzheimer's disease treatment

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) which is the most common cause of dementia in the elderly. It is characterized by the deficits in the cholinergic system and presence of characteristic hallmarks: neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes it became a target for the design of anti-alzheimer drugs. Cholinesterase inhibitors enhance cholinergic transmission indirectly, by inhibiting the enzyme which hydrolyses acetylcholine. It has been also demonstrated that acetylcholinesterase (AChE) is involved in the development of amyloid plaques. Therefore, substances which are AChE inhibitors (AChEI) are the only drugs approved for the symptomatic treatment of AD. This review presents the main classes of cholinesterase inhibitors developed recently for the treatment of AD. We have started with the analogues of the existing drugs: tacrine, donepezil, rivastigmine and galantamine which are still of interest for many research groups. Among them there is a very interesting group--dual binding site inhibitors characterized by increased inhibitory potency against AChE and amyloid plaques formation. There is also a group of compounds with additional properties such as: antioxidant activity, affinity to 5-HT(3) receptors, inhibition of N-methyltransferase that metabolize histamine, which can be beneficial for the treatment of AD. Furthermore there are some interesting compounds which belong to different chemical groups also of natural origin. In this review we sum up current research concerned with development of AChEIs which can be more effective in the future treatment of AD.     

Progress in acetylcholinesterase inhibitors for Alzheimer’s disease

Current pharmacotherapy of Alzheimer’s disease (AD) involves drugs that are known as acetylcholinesterase inhibitors (AChEIs), which increase the acetylcholine concentration in the brain. Although effective in improving cognitive, behavioural and functional impairments, these drugs are not able to alter disease progression. In this review, the recent patent literature on AChEIs from 2002 to early 2005 will be discussed, focusing attention on the novel analogues of the approved drugs, as well as on the most important AD therapeutic advances. The clinical efficacy of AChEIs will probably be enhanced by their combination with other drugs acting through different pharmacological mechanisms. As the neuronal loss comprises more than the forebrain cholinergic system, the weak effectiveness of AChEIs is not surprising. Besides the ‘cholinergic hypothesis’ approaches, new treatments are emerging based on multipotent compounds able to target the underlying pathogenic mechanisms of AD; these treatments are summarised herein.     

Recent development of therapeutics for chronic HCV infection

The global prevalence of hepatitis C virus (HCV) infection and serious health consequences associated with chronic state of the disease have become a significant health problem worldwide. Currently, there is no vaccine to prevent the disease and no specific antiviral drug directed against HCV infection. The current standard of care, interferon-based therapies, both alone or in combination with ribavirin, has demonstrated limited success and is associated with undesirable side effects. Thus, the treatment of the chronic HCV infection represents an unmet medical need. With advances in the understanding of HCV replication and the crystal structures of the virally encoded enzymes, the HCV NS3/4A serine protease and the NS5B RNA-dependent RNA polymerase have emerged as ideal targets toward the control of the disease and the development of new anti-HCV agents. In this review, we will summarize the current treatment options, and outline the approaches toward discovery of small molecule antivirals against the virally encoded enzymes. The current clinical studies of promising lead compounds are also reviewed.     

Inhaled muscarinic antagonists for respiratory diseases: a review of patents and current developments (2006 - 2010)

INTRODUCTION: Because tiotropium has demonstrated clinical benefits as a long-term maintenance treatment for chronic obstructive pulmonary disease (COPD), the number of patent applications of new chemical entities with antimuscarinic activity has significantly increased, along with the number of compounds that have reached clinical development. AREAS COVERED: This review summarizes the current status of long-acting muscarinic antagonists (LAMA) in clinical development for COPD, and the associated patent literature since 2006, with a focus on new chemical entities. EXPERT OPINION: In recent years, companies have taken different approaches to obtain compounds with high potency, long duration of action and minimal systemic exposure. Several strategies for minimizing adverse effects due to systemic exposure have been identified (quaternization, higher rate of plasma hydrolysis and degradation, increased plasma protein binding). The beneficial effects beyond bronchodilation that may be provided in the treatment of COPD patients with a LAMA, and the advantages of combination therapies, such as LAMA + LABA and LAMA + corticosteroids, have also been taken into account in recent studies.     

Cancer prevention and treatment using combination therapy with plant- and animal-derived compounds

Compounds naturally occurring in plants and animals play an essential role in the prevention and treatment of various cancers. There are more than 100 plant- and animal-based natural compounds currently in clinical use. Similar to synthetic compounds, these natural compounds are associated with dose-related toxicity that limits efficacy. Scientists have investigated combination therapy with compounds that have different toxicities in order to optimize efficacy. These combination therapies may work additively or synergistically, there may be no effect or they may promote tumor formation. Combination therapy with agents that have similar mechanisms of action may increase toxicity. In this article, combination therapies that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined (pharmacologic and natural; two or more natural) interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted.     

Colorectal cancer in 2003: old principles,new strategies

In the last two decades the prognosis of colorectal cancer has improved for two reasons: (i) the proportion of patients with localized disease has increased and treatment has been standardized, and (ii) new chemotherapeutic agents have led to a longer life expectancy for patients with advanced disease. In this review the current insights in disease etiology and treatment of localized and disseminated colorectal cancer are discussed.     

The Dual Roles of Protein-Bound Solutes as Toxins and Signaling Molecules in Uremia

In patients with severe kidney disease, renal clearance is compromised, resulting in the accumulation of a plethora of endogenous waste molecules that cannot be removed by current dialysis techniques, the most often applied treatment. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds of which many are too large to be filtered and/or are protein-bound. Their renal excretion depends largely on renal tubular secretion, by which the binding is shifted towards the free fraction that can be eliminated. To facilitate this process, kidney proximal tubule cells are equipped with a range of transport proteins that cooperate in cellular uptake and urinary excretion. In recent years, innovations in dialysis techniques to advance uremic toxin removal, as well as treatments with drugs and/or dietary supplements that limit uremic toxin production, have provided some clinical improvements or are still in progress. This review gives an overview of these developments. Furthermore, the role protein-bound uremic toxins play in inter-organ communication, in particular between the gut (the side where toxins are produced) and the kidney (the side of their removal), is discussed.     

Recent advances in antileishmanial drug development

Leishmania are protozoan parasites responsible for a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many regions of the world and emerges as a serious co-infection in HIV-positive individuals. Current treatment of the disease is based on a limited number of chemotherapeutic agents which are rapidly becoming ineffective, and are characterized by high toxicity and cost. This review focuses on recent advances in antileishmanial drug development and improvements to current treatment options. Novel approaches currently used to identify leishmanicidal compounds as diverse as antimicrobial peptides and natural plant extracts are described in this review.