Current Pharmaceutical Design - Volume 16, Issue 6, 2010

Due to the high number of age-dependent diseases and the complexity of the therapeutic interventions this hot topic has been splitted into two parts. In Part I the physiopathology of immunosenescence; the age-related diseases and therapeutic attempts; the mechanisms of neurodegeneration; the relationship between cancer and ageing will be discussed. Candore and associates [1] will review the main mec Read More

Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and d Read More

The immune system undergoes a process of profound remodelling during aging, referred to as immunosenescence, and characterized by complex modifications of several components. In this review, we discuss recent developments and observations regarding the generation of T cells in the thymus during aging and longevity, and the regulation and maintenance of peripheral blood lymphocytes. The generation of new T cells Read More

Immunosenescence is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly. On the other hand centenarians are considered the best example of successful ageing. To gain insight into mechanisms of immunosenescence and its clinical relevance, a possible model is represented by centenarians and/or their offspring. Nowadays centenarians are not more a curiosity, but Read More

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of proinflammatory cytokines and inflammatory markers (“inflamm-ageing”). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related Read More

Changing demographics, including an increase in life expectancy and the growing numbers of elderly has recently focused attention on the need for geriatric dental care. Ageing affects oral tissues in addition to other parts of the human body, and oral health (including oral mucosa, lips, teeth and associated structures, and their functional activity) is an integral component of general health; indeed, oral disease can cause pain, Read More

Osteoarthritis (OA) is very disabling condition in the elderly. The current therapeutic approaches (analgesics, NSAIDs, COX-2 inhibitors, steroids) do not delay the OA progression or reverse joint damage. Moreover, they may cause relevant systemic side effects. Hyaluronic acid (HA) is a physiologic component of the synovial fluid and is reduced in OA joints. Therefore, intra-articular injection of HA, due to its viscoelastic p Read More

The authors review the ultra-structural aspects and permeability features of normal human oral mucosa, after having recently tested and used it as a new site of systemic drug delivery. The pertinent scientific literature from 1975 through 2009 has been analysed and discussed. Buccal epithelium is a relatively permeable, robust non-keratinized tissue and blood vessels drain directly into the jugular vein; due to its particular feature Read More

The transbuccal delivery of drugs could assist several categories of chronic, especially elderly, patients in adhering to a correct dosage regimen. In particular, patients suffering from dementia have several difficulties in following the prescribed dosage, in addition to problems associated with swallowing tablets. Galantamine is currently used for treating patients with mild to moderate Alzheimer's-type dementia. The transbucc Read More

Ageing is characterized by alterations in brain anatomy and physiology, finally contributing to an impairment in cognitive functions, such as memory. The most relevant observations indicate that senescent-related cognitive decline is not only due to neuronal loss, instead, functional changes occurring over time play a key role. Overall, these modifications are indeed responsible for an altered interneuronal communic Read More

The amyloid cascade hypothesis sustains that beta-amyloid (Aβ) is the main pathogenetic factor of Alzheimer's Disease (AD). Although the direct and indirect neurotoxic role of Aβ are unchallenged, recent findings suggest that the peptide may have so far unforeseen physiological roles. In this regard, the observations showing the ability of Aβ to exert synaptic activities in absence of neurotoxicity are very intriguing. In particular Read More

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Aβ, product of cleavage of Read More

In this manuscript we report an integrated study to develop simple choline esters as cholinergic agents potentially useful against the Alzheimer disease. In previously reported experiments we demonstrated the capability of the pivaloylcholine to exert cholinergic effects into the Central Nervous System, so we decided to explore small variants of choline esters. The knowledge of crystallographic models of the enzymes in Read More

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's dis Read More

Host genetic factors are crucial risk determinants for many human cancers. In this framework, an interesting model is represented by prostate cancer (PC), which is featured by a complex pathophysiology with a strong genetic component. Multiple genes seem to influence PC risk and several single nucleotide polymorphisms (SNPs) of candidate genes modifying PC susceptibility have been identified. It is noteworthy the Read More

It is well established that an increase of n-6 polyunsaturated (i.e. arachidonic and arachidonic-converted linoleic acids) fat dietary intake enhances carcinogenesis and promotes tumorigenesis through oxidative metabolism. The Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes mediate the oxidative metabolism of n-6 polyunsaturated fatty acids and generate a cascade of biological active molecules. Nonsteroidal antinfla Read More

Polyploidy, a state of increased number of chromosomes, occurs often in plants and less frequently in animals. Polyploidization is recognized as a part of a developmental program and can be achieved via different mechanisms bypassing certain stages of the cell cycle. However, polyploidization also accompanies some pathological conditions as well as ageing. It is believed that tetraploid cells precede aneuploid o Read More

Hepatocellular carcinoma (HCC) is the most frequent primary neoplasm of the liver, and is the fourth most common malignancy worldwide. It is also the third leading cause of cancer-related deaths. Most cases of HCC develop on a pre-existing chronic liver disease, usually due to hepatitis C virus (HCV), hepatitis B virus (HBV), or alcohol. However, between 15% and 50% of HCC develops in the absence of a known etiology of l Read More