Current Drug Therapy (v.6, #1)

Editorial by Joachim F. Wernicke (1-1).
There are many medical journals; hundreds, maybe thousands. Many of them focus on specific areas of interest, and rightly so. A person wanting to keep up with the latest developments in cardiology would probably not want to see a collection of articles on ophthalmology. Although often publishing review articles, specialty journals are an important vehicle for publication of original research. These journals provide the scientific and medical community with detailed information on specific topics. They serve a vital function in the dissemination of knowledge. Current Drug Therapy has taken a more diverse approach. Rather than focusing on a specific therapeutic or medical area, the goal has been to provide the reader with reviews dealing with drug therapy in a variety of disease states. The focus is on reviews of the field, as opposed to presentation of original research, which is more appropriate for disease specific journals. The diversity of reviews published in Current Drug Therapy is exemplified in this issue, where articles can be grouped into several categories. Several papers deal with the problem of enhancing drug effectiveness. In the area of drug delivery is a paper on chitosan. Another article deals with drug activation with light and ultrasound. In yet another paper, mechanisms of resistance to fluoroquinolones are reviewed. Buccoadhesive drug delivery as a drug delivery vehicle is reviewed in the context of treatment of candidiasis. Another group of papers deals with approaches to particular disease states. For example, there is a paper on piribidil as a possible treatment of dopaminergic disorders. Another paper deals with the role of complement in autoimmune disorders, and how it might be manipulated to treat these conditions. Oral antiarrhythmic therapy as an approach to treatment of atrial fibrillation is reviewed in another article. Thus, although this journal publishes primarily review articles, and their topics are quite divergent, it can be seen that there is a pattern and focus when articles are grouped into broad categories.

Naturally Occurring Chitosan and Chitosan Derivatives: A Review by Hemant K.S. Yadav, Gunjan B. Joshi, Mangla N. Singh, Hoskote G. Shivakumar (2-11).
Chitosan, a polymer obtained by deacetylation of chitin is widely studied for its pharmaceutical and nonpharmaceutical applications. Recommendations about uses of this polymer although could not be always realized due to limited solubility. Chitosan has been extensively evaluated for its mucoadhesive and absorption enhancement properties. The positive charge on the chitosan molecule gained by acidic environment in which it is soluble seems to be important for absorption enhancement. However chitosan is not soluble in medium except below pH 5.6. This limits its use as permeation enhancer in body compartments where pH is high. In this regard there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values. This review introduces the physical background of the special properties of the various chitosan derivatives and their application. Chitosan derivatives with different physicochemical properties especially water solubility at neutral and basic values are of interest. Chemical modification of chitosan is useful for the association of bioactive molecules to polymerize and controll the drug release profile. From the studies reviewed it is concluded that chitosan derivatives are promising materials for controlled drug and nonviral gene delivery.

Outcome Measures Following Sonodynamic Photodynamic Therapy - A Case Series by Julian Norman Kenyon, Richard James Fuller (12-16).
Sonodynamic Photodynamic Therapy (SPDT) is a novel cancer treatment approach using a photosensitive agent (Sonnelux-1) with reported ultrasound-activated properties. The sensitiser is administered prior to a cycle of light and low-intensity ultrasound exposure. Ultrasound has the advantage of significantly greater tissue penetrance compared to light, which potentially allows non-invasive activation of the sensitiser within deep-sited tumours. Sonnelux-1 has previously demonstrated significant tumour cell inhibition following ultrasound administration in animal studies, and several case reviews have been published reporting clinical benefits in metastatic cancer patients. This current case series presents outcome measures of five patients with a variety of cancer diagnoses following SPDT, providing further evidence of beneficial treatment outcomes.

Piribedil is a relatively unknown non-ergot dopamine agonist that has been in clinical use for over 3 decades for the symptomatic management of Parkinson's disease (PD). Piribedil is currently not approved for therapeutic use in the United States. It has unique pharmacological and pharmacokinetic attributes with a profile that is unlike many direct dopamine agonists. In addition to proven motor effects in PD, nonclinical and clinical evidence over the last few years indicate that piribedil may also exert beneficial non-motor effects such as in mild cognitive impairment and frontal cognitive dysfunctions prevalent in PD patients. This review presents the pharmaceutics, pharmacological pleiotropy, and clinical properties of piribedil with a focus on its utility in the therapy of motor and non-motor symptoms in PD and related dopaminergic disorders. The varied pharmacological, behavioral, and clinical properties of piribedil are related to current knowledge on its multifunctional pharmacology. Properties of piribedil that may differentiate it from other dopamine direct agonists are noted. As a partial agonist of dopamine D2 and D3 receptors with functional and#945;2 adrenolytic activity, piribedil may be an alternative to the inherent anti-akinetic (beneficial) and dyskinetic (unwanted) effects of some dopamine replacement therapies. The activation of limbic dopamine receptors by piribedil and stimulation of acetylcholine release in the frontal cortex provide a basis for improving mood and cognitive disturbances. Additionally, and#945;2 antagonism and weak 5-HT1A agonism may provide beneficial effects on dyskinesias, neuropsychiatric symptoms in PD, neurotrophic effects, and reduced sedation. The adverse effects of piribedil generally mirror its monoaminergic activity and include nausea, vomiting, abnormal sleep events, and psychiatric effects such as psychosis and compulsive disorders. While the therapeutic potential of piribedil may yet to be fully realized, investigations of its safety and toxicology under current standards of drug development are warranted before exposure to new patient populations.

Complement activation plays important roles in innate immunity. However, excessive or unregulated activation of complement can injure host tissues, not only causing local injuries but also systemic reactions. Autoimmune diseases such as rheumatoid arthritis, lupus nephritis and Guillain-Barre syndrome are among the pathological situations caused by aberrant activation of the host immune system and complement activation plays important roles to develop and/or augment these diseases. Recent therapeutic approaches in autoimmune disease have involved biological response modifiers such as anti-TNF, anti- TNF receptor and anti-IL6 agents, in addition to traditional therapies such as corticosteroid, methotrexate, azathioprine, mizoribine and cyclophosphamide in collagen diseases. These new biological reagents have shown promise but sometimes cause severe side effects or complications, including interstitial pneumonia and predispose to other infections such as tuberculosis. New strategies may therefore be required. As an alternative therapeutic approach, anti-complement agents might become a treatment of choice to control autoimmune diseases. This mini-review focuses on recent knowledge of the role of complement activation in human collagen diseases and the other autoimmune diseases, including relevant animal models, and discusses the possibility of using anti-complement therapies. Regulation of the complement system might be a new approach to be considered as an alternative therapeutic strategy.

Mechanisms of Resistance to Fluoroquinolones in Salmonella spp by Rafaela Ferrari, Rosa Cremades, Antonio Galiana, Tereza Oiveira, Juan Carlos Rodriguez (51-54).
Salmonella spp. generally causes self-limiting gastroenteritis, which often requires no treatment, but may be severe in young people, the elderly and patients with weakened immunity, and in these cases, the infection may be much more severe, present at extraintestinal sites and require prolonged antibiotic treatment. One of the treatments of choice is the fluoroquinolones. The main mechanisms of resistance to quinolones are mutations in the genes encoding topoisomerase II and topoisomerase IV in the QRDR region (Quinolone Resistance-Determining Region), but additional mechanisms may be present, such as change in permeability of the membrane, efflux pumps, and PMQR (plasmidmediated quinolone resistance. These mechanisms may be present individually or in combination but mutations in the gen gyrA are the most frequent and important mechanism in Gram-negative bacteria.

Buccoadhesive Dosage Form Containing Antifungal Agent for Treating Oropharyngeal Candidiasis: A Review by Mohamed S. Pendekal, Muzzammil Shariff, Pramod K. Tegginamat (55-64).
Oral candidiasis is a common fungal infection in patients with an impaired immune system, such as those undergoing chemotherapy for cancer and patients with AIDS (Acquired immune deficiency syndrome). The majority of infections are due to Candida albicans although other species such as Candida glabrata, Candida tropicalis, Candida krusei and Candida parapsilosis are increasingly isolated. The objective of this article is to review candidiasis, types of candidiasis, discussing the structure and environment and permeability of the oral mucosa. Buccoadhesive drug delivery will also be reviewed with an emphasis on Bioadhesion, theories of Bioadhesion, investigated mucoadhesive polymer's and Buccoadhesive tablet/film containing antifungal agent for treating oropharyngeal candidiasis.

Atrial Fibrillation with a Focus on Oral Antiarrhythmic Therapy by Jacqueline M. von Vital, Deborah L. DeEugenio, Anna Wodlinger Jackson, Thomas Kiernan, Nicholas J. Ruggiero (65-78).
Atrial fibrillation (AF) is considered the most common sustained arrhythmia resulting in significant morbidity, mortality, and cost. Management of AF includes rate control, prevention of thrombosis, and, in some patients, conversion and maintenance of normal sinus rhythm. Pharmacologic therapy is often used for maintenance of normal sinus rhythm. Current recommended antiarrhythmic drugs include dofetilide, propafenone, sotalol, and amiodarone. In March 2009 a new antiarrhythmic, dronedarone, was approved for use in patients with atrial fibrillation. The aim of this article is to review primary literature of currently available oral antiarrhythmic agents for efficacy, safety and place in therapy in the treatment of atrial fibrillation.