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Background. The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient’s quality of life. Objectives. To review currently available measures and investigational agents to prevent OM in hematological patients. Methods: we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. Results/Conclusions. Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

Inflammatory bowel disease, such as ulcerative colitis and Crohns disease, results from an interaction between susceptibility genes, the hosts bacterial environment, gut barrier defects, and immunological factors. New management approaches have been evolved from advances in our understanding of the pathobiology of this common gut disorder In particular, the therapeutic manipulation of the bacterial microenvironment in the gut seems to offer an innovative tool for the treatment of those patients. Since the gut is a highly sensitizing organ that contributes to the systemic imune response, potent treatments need to be developed to reduce gut inflammation in this disorder. Recent studies have demonstrated that probiotic lactobacilli, and also immunostimulatory DNA sequences from those same bacteria have an important antiinflammatory potential in this context. Future research should better define among patients with inflammatory bowel disease the various clinical phenotypes with the greatest potential of response to probiotic treatment. Identification of the genes leading to the disease and a rather better understanding of the underlying immunoregulatory abnormalities will be crucial steps to define the different profiles of interaction between endogenous digestive bacterial flora and the immune system in each individual patient. Such advances will probably lead to targeting of effective treatments, including bacteriotherapy with probiotic lactobacilli, to subsets of patients with inflammatory bowel disease.

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity of L-carnitine was recognized. The addition of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.

THE authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

Transporter proteins of the solute carriers (SLCs) family play a role in epithelial permeability and barrier function in the intestine, and polymorphisms in SLC genes are associated with inflammatory bowel disease. Many SLCs also mediate the bioavailability of pharmaceutical compounds, and the modulation of such transport systems to increase drug efficacy is, therefore, of great interest. We have undertaken a large-scale project to evaluate whether bacteria can modulate the expression of SLCs in the intestine. Here we report the effect of VSL3 (a high-potency probiotic preparation) on the expression of 3 large solute carrier families, SLC4, SLC21, and SLC22, which are involved in the transport of bicarbonates, organic anions and cations, and affect the bioavailability of several pharmaceutical compounds. Two groups of animals (VSL3 and phosphate-buffered saline controls) were studied for SLC expression in the intestine by Real-Time PCR at the beginning (day 1) and at the end (day 20) of the treatment, and 7 days after the interruption of the treatment. An effect of VSL3 administration was detected on the expression of 10 of the studied genes. This reached statistical significance (P0.01) for the poorly characterized sodium-borate cotransporter SLC4A11, which showed a 5-times lower expression in VSL3 than in control mice on day 1 of probiotic treatment. VSL3-driven changes in the expression levels of SLC transporters might contribute to its reported effects on intestinal permeability. The elucidation of SLC4A11 function in the intestine will be the key to fully evaluate the relevance of specific findings.

The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.