Mini Reviews in Medicinal Chemistry - Volume 8, Issue 2, 2008

Polyphenols are a family of natural compounds with many biological properties. This review focuses on their potential interaction on the cytochrome P450 system. Effects of phenolic acids, anthocyanins, stilbenes, catechins and other flavonoids on the drug metabolising function are revised. Their daily intake and presence in herbal medicines justify the study of potential drug-interaction to prevent undesirable clinical consequences.

Beneficial rapid onset effects of omega-3 fatty acids from fish oil on host defense compensatory fit into the comprehensive pathophysiology of critical illness. Because of balanced pro- and anti-inflammatory effects on a variety of host defense subsystems even septic patients had earlier recovery and improved survival. This review focuses in a compressed view on the beneficial aspects of omega-3 fatty acid supplementation on diverse organ functions, host defense and on balanced pro - and anti-inflammatory effects. Clinical impact of fish oil based pharmaconutrition during critical inflammation processes and immune response in humans is thoroughly discussed.

Flavonoids are natural plant compounds increasingly used in therapeutic applications. Their large spectrum of activities depends on their structures and cellular targets. Most recent research shows they are promising drugs for controlling human and animal parasitic diseases. Their multiple effects make it difficult to understand their modes of action, but some of them have been elucidated. This review also deals with their toxicity in mammals.

In celiac disease (CD), abnormal immune-mediated responses follow ingestion of gluten. Although the triggering agent is a dietary protein, the disease has autoimmune components because of the presence of autoantibodies and its association with autoimmune conditions. We review the most recent studies on CD pathogenesis and the possibilities to modulate immune dysfunction in CD.

There is an increasing evidence that Helicobacter pylori may interfere with gastrointestinal metabolism of micronutrients and drugs such as iron, cobalamin, thyroxine and levodopa, with relevant clinical effects. In this review we examine the strength of the causal association and the plausible pathophysiologic mechanisms underlying these adverse effects.

Myristoyl-CoA:Protein N-myristoyltranferase (NMT) is a cytosolic monomeric enzyme which catalyses the transfer of a rare fatty acid , myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. N-myristoyltransferase is a novel target for Anticancer, Antiviral and antifungal agents. Recent Nmyristoyltransferase inhibitors like benzofurans and benzothiazole derivatives show in vivo antifungal activity and are promising selective fungal N-myristoyltransferase inhibitors.

Approximately 30% of patients with chronic HCV infection show persistently normal alanine aminotransferase levels (PNAL). The prevalence of HCV carriers with normal liver seems to be very low (less than 15-20%). Liver disease is usually minimal/mild and fibrosis is generally absent or minimal, although the association of normal alanine aminotransferase (ALT) with cirrhosis or with liver cancer has been reported. In all studies, liver histology was, on average, significantly less severe in subjects with PNAL than with abnormal ALT. Although the majority of data seem to show that HCV carriers with normal ALT have mild and stable disease, with a favourable prognosis, several studies reported a significant progression of fibrosis in approximately 20-30% of the patients with ALT normality, and the development of HCC in some cases has been described, despite persistent ALT normality. Sudden worsening of disease with ALT increase and histological deterioration has been described after up to 15 years of follow-up, in particular in patients harboring genotype 2. As to antiviral treatment, it has been clearly stated that it no longer seems reasonable to affirm that sustained response rates for patients with normal ALT levels are any different than those for patients with elevated ALT levels when the combination of pegylated interferon (IFN) and ribavirin is used. The issue at hand is whether or not patients with mild disease should be treated. There are numerous other factors which impact on this decision, including genotype, histology, patients motivation, symptoms, co-morbid illness, and the age of the patient.

For examination of glucocorticoid metabolism and identification of hyper and hypocortisolism, various measurements and diagnostic tools are available. After a brief overview of the physiology of glucocorticoid secretion and glucocorticoid actions, the currently used measurements for blood, saliva, and urine samples and the corresponding physiological and metabolic implications are critically reviewed. A special emphasis is placed on the potential of 24-h urine analyses to assess not only glucocorticoid secretion, but also functional glucocorticoid activity.

Iron homeostasis disturbances are associated with liver disease. Non-alcoholic steatohepatitis is part of the spectrum of non-alcoholic fatty liver disease, which can progress to hepatic cirrhosis and end-stage liver disease. Increasing information supports that multiple factors underlie the development and progression of nonalcoholic steatohepatitis. However, the relation between non-alcoholic steatohepatitis and iron metabolism/ overload is still controversial. We review the recent literature, both basic and clinical, regarding iron homeostasis as it pertains to the pathogenesis of nonalcoholic fatty liver disease.

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.

The potential usefulness of surface-linked liposomal antigens for application to vaccine development was investigated. During the course of this investigation, a significant difference was observed in the recognition of liposomal antigens by antigen-presenting cells (APCs) between liposomes with different lipid components, and this difference was closely correlated with the adjuvant activity of liposomes. In addition to this “quantitative” difference between liposomes with differential lipid components, a “qualitative” difference (i.e., a differential ability to induce cross-presentation) was also observed between liposomes with different lipid components. Although the precise mechanism underlying this difference is currently unclear, the significant difference in membrane mobility observed between these liposomes might affect their ability to induce cross-presentation. Thus, surface-linked liposomal antigens may be applicable for the development of vaccines with minimal allergic side effects and for a novel protocol of allergen immunotherapy. In addition, by utilizing their ability to induce cross-presentation, surface-linked liposomal antigens could be used to develop virus vaccines that induce a cytotoxic T-cell (CTL) response, as well as tumor vaccine preparations that present tumor antigens to APCs and induce effective antitumor responses. These data suggest that differential lipid components in liposomes lead to differential processing and presentation of liposomal antigens in APCs.