Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases that consists of ulcerative colitis (UC), an inflammation of the large intestine, and Crohn�s disease (CD), which can affect any part of the gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in western countries. There is a marked tendency in the age of onset toward gradually younger people. IBD represents a genuine problem in public health because of the absence of etiologic treatment. The clinical image is characterized by recurrent segmental or total inflammatory involvement of the large and/or small intestine, often resulting in a chronic, unpredictable course. The symptoms of both are extremely unpleasant and impact all aspects of quality of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea, weight loss, lethargy, and loss of appetite. If left untreated, malnutrition, dehydration, and anemia follow, which, in extreme cases, can even lead to death. Although many patients are managed successfully with conventional medical therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory to treatment, most will have recurrent activity of disease, and two thirds will require surgery. Administered orally or by injection, only a fraction of the active components of most conventional drugs reaches the intended target site, the inflamed intestinal lining. This is not only an inefficient way to deliver drugs, but, more important, means that patients are often subject to a spectrum of unpleasant side effects that result from the high levels of the drugs in other, otherwise healthy tissues and organs of the body.

Lothar Steidler

Lactococcus lactis, A Tool for the Delivery of Therapeutic Proteins Treatment of IBD

Studies using specific agonists, antagonists, and lesions have shown that nicotinic cholinergic systems participate in attention, learning, and memory[1,2]. The nicotinic manipulations usually have the greatest influence on difficult tasks or on cognitively impaired subjects[2]. For example, Alzheimer's disease is characterized by a loss of cholinergic projections and nicotinic acetylcholine receptors (nAChRs) in the cortex and hippocampus[3]. Nicotine skin patches can improve learning rates and attention in Alzheimer's patients[4].

John A. Dani

Nicotinic Receptor Activity Alters Synaptic Plasticity

Martin Götte

Frank Echtermeyer

Syndecan-1 as a Regulator of Chemokine Function

Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process.

Pratima Bansal-Pakala

Michael Croft

Breaking Immunological Tolerance through OX40 (CD134)

As the medical community strives to improve on the efficacy of anticancer treatments, a critical issue not to be overlooked since the overall quantity of life has been substantially increased in many cancer survivors is the quality of that life post-therapy. Indeed, one of the most worrisome side effects of conventional cancer treatments is damage to the gonads. This problem is compounded in females since the ovaries, unlike the testes, are incapable of germ cell renewal in postnatal life. As a consequence, the inappropriate destruction of female germ cells (oocytes) following exposure to chemotherapeutic drugs and radiation is irreparable, often leading to premature menopause and infertility [1]. Considering recent estimates that 1 in 52 human females between birth and age 39 (i.e., the pre-reproductive and reproductive years) will be diagnosed with, and presumably treated for, cancer [2], new strategies to minimize or prevent gonadal damage during such treatments would have a profound positive impact on millions of lives.

Jonathan L. Tilly

Emerging Technologies to Control Oocyte Apoptosis Are Finally Treading on Fertile Ground

High mountain areas have recently been observed to be polluted by organochlorine compounds (OC) despite their isolation. These persistent pollutants arrive at these remote regions through atmospheric transport. However, the mechanisms involving the accumulation of these compounds from the atmospheric pool to the lacustrine systems still need to be elucidated. These mechanisms must be related to the processes involving the transfer of these pollutant from low to high latitudes[1] as described in the global distillation effect[2].

Joan O. Grimalt

Pilar Fernandez

Rosa M. Vilanova

Trapping of Organochlorine Compounds in High Mountain Lakes

The &#x201C;aging&#x201D; of populations in the developed world is rapidly altering demographics and presents a number of challenges for science and medicine. Foremost among these challenges is the need to enhance the quality of life for this &#x201C;aging&#x201D; majority. Paradoxically, improved prevention and treatment of diseases will only increase the number of individuals who will lose quality of life because of cognitive deficits in learning and memory. Such cognitive deficits are particularly vexing in societies where the ability to deal with information technology has become an increasing necessity. Understanding how the human brain encodes and stores information becomes critical in designing required therapeutic strategies.

J.F. MacDonald

William Ju

Yu Tian Wang

LTP in a Culture Dish

Faris Farassati

Patrick W.K. Lee

Ras Signalling Pathway: A Gateway for HSV-1 Infection

Schizophrenia is a complex and devastating brain disorder that affects 1% of the population and ranks as one of the most costly disorders to afflict humans. This disorder typically has its clinical onset in late adolescence or early adulthood, presenting as a constellation of delusions and hallucinations (positive symptoms); decreased motivation, emotional expression, and social interactions (negative symptoms); and impaired learning and memory (cognitive symptoms). The etiology of schizophrenia is unknown, but appears to be multifaceted, with genetic and epigenetic developmental factors all implicated. A convergence of observations from clinical, neuroimaging, and anatomical studies has implicated the dorsal prefrontal cortex as a major locus of alterations in schizophrenia.

Karoly Mirnics

Frank A. Middleton

David A. Lewis

Pat Levitt

Delineating Novel Signature Patterns of Altered Gene Expression in Schizophrenia Using Gene Microarrays

Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident [1]. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors [2,3]. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1. However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear.

Yuri E. Nikiforov

Spatial Positioning of RET and H4 Following Radiation Exposure Leads to Tumor Development

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