Functionalised peptide hydrogel for the delivery of cardiac progenitor cells.

Heart failure (HF) remains one of the leading causes of death worldwide; most commonly developing after myocardial infarction (MI). Since adult cardiomyocytes characteristically do not proliferate, cells lost during MI are not replaced. As a result, the heart has a limited regenerative capacity. There is, therefore, a need to develop novel cell-based therapies to promote the regeneration of the heart after MI. The delivery and retention of cells at the injury site remains a significant challenge. In this context, we explored the potential of using an injectable, RGDSP-functionalised self-assembling peptide - FEFEFKFK - hydrogel as scaffold for the delivery and retention of rat cardiac progenitor cells (CPCs) into the heart. Our results show that culturing CPCs in vitro within the hydrogel for one-week promoted their spontaneous differentiation towards adult cardiac phenotypes. Injection of the hydrogel on its own, or loaded with CPCs, into the rat after injury resulted in a significant reduction in myocardial damage and left ventricular dilation.

Resident cardiac stem cells.

The introduction of stem cells in cardiology provides new tools in understanding the regenerative processes of the normal and pathologic heart and opens new options for the treatment of cardiovascular diseases. The feasibility of adult bone marrow autologous and allogenic cell therapy of ischemic cardiomyopathies has been demonstrated in humans. However, many unresolved questions remain to link experimental with clinical observations. The demonstration that the heart is a self-renewing organ and that its cell turnover is regulated by myocardial progenitor cells offers novel pathogenetic mechanisms underlying cardiac diseases and raises the possibility to regenerate the damaged heart. Indeed, cardiac stem progenitor cells (CSPCs) have recently been isolated from the human heart by several laboratories although differences in methodology and phenotypic profile have been described. The present review points to the potential role of CSPCs in the onset and development of congestive heart failure and its reversal by regenerative approaches aimed at the preservation and expansion of the resident pool of progenitors.

Two familial cases of perianal streptococcal dermatitis.

Two cases of perianal streptococcal dermatitis (PSD) occurred in a brother and sister, aged 4 and 6 years, respectively. The diagnosis was confirmed by the detection of group A beta-hemolytic streptococci in the perineal area and pharynx of both patients. We emphasize the importance of a quick and accurate diagnosis of the infection because PSD is frequently confused with other perianal diseases of infancy.

Expression of functional mGlu5 metabotropic glutamate receptors in human melanocytes.

Cultured human melanocytes express mGlu5 metabotropic glutamate (mGlu) receptors, as shown by RT-PCR, immunocytochemistry, Western blot analysis, and measurement of agonist-stimulated polyphosphoinositide hydrolysis. The mGlu5 receptor agonists (S)-3, 5-dihydroxyphenylglycine and quisqualate increased [(3)H-methyl]thymidine incorporation and melanocyte proliferation in subconfluent cultures, but impaired cell viability in confluent cultures. Both effects were prevented by 2-methyl-6-(2-phenyl-1-ethynyl)-pyridine, a potent and highly selective mGlu5 receptor antagonist. Agonists of other mGlu receptor subtypes (such as the mGlu2/3 receptor agonist, 2S,2'R,3'R-2-2', 3'-dicarboxycyclopropylglycine, or the mGlu4/6/7/8 receptor agonist, L-2-amino-4-phosphonobutanoate) or selective agonists of ionotropic glutamate receptors (N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate) did not affect melanocyte proliferation or viability. The presence of a receptor for glutamate, the major excitatory neurotransmitter, in human melanocytes is intriguing. mGlu5 receptors may be involved in the control of melanocyte proliferation (and perhaps in other functions), but harbor a potential toxicity and may therefore contribute to cell damage under pathological conditions.

Vitiligo, autoimmune thyroiditis: a rare thyroid cancer arising with bone metastates on maxillofacial area.

An association between vitiligo and autoimmune thyroid disorders had previously been postulated. Thyroid disorders were found in 18.5% of 15,126 patients with vitiligo, on the basis of the anamnestic data. Then, we investigated 255 healthy relatives in whom we tested only T3, T4 and TSH. With the immunological investigation we detected a higher incidence of TMA in vitiligo patients and in the family members. Therefore, on the basis of the immunologic and thyroid pathology functional data, we observed a thyroid pathology in 25% of the 890 vitiligo patients and in 21.1% of their first degree relatives. Then, clinical observation enabled to discover that 3 of 15,126 patients had undergone exeresis for a thyroid carcinoma and in the 890 vitiligo patients, who had undergone particular investigations, we found a thyroid carcinoma in 3 subjects. In one case lymphnodal involvement and bone metastases in the maxillary district were found. The purpose of this work is to evaluate the incidence of thyrosis and of thyroid carcinoma in vitiligo patients observed for 20 years.

Association of etretinate and fish oil in psoriasis therapy. Inhibition of hypertriglyceridemia resulting from retinoid therapy after fish oil supplementation.

We studied the main papers concerning treatment with fish oil (EPA and DHA) of patients with psoriasis vulgaris, psoriatic arthritis and pustular psoriasis. In our investigation, 25 patients with psoriasis vulgaris evidenced a statistically significant increase in triglyceride serum levels, compared with controls. 10 of these patients underwent therapy with etretinate 0.75-1.0 mg/kg daily for 2 months followed by 2-3 months of etretinate 0.35-0.50 mg/kg daily associated with fish oil 1.5 g (EPA and DHA) daily. According with several authors, fish oil is able not only to produce good clinical results, but also to minimize the side effects of retinoid therapy, especially hypertriglyceridemia.

Peripheral T-cell subset imbalance in patients with vitiligo and in their apparently healthy first-degree relatives.

Twenty-two patients with vitiligo had lesions stable for at least 1 year and 23 apparently healthy first-degree relatives were studied for T-cell subpopulations using monoclonal antibody technique. High levels of CD4+ lymphocytes and high CD4/CD8 ratios were found in both patients and their relatives, as compared with normal age-matched and sex-matched controls. This immunologic abnormality, together with the presence of autoantibodies previously reported in the apparently normal relatives, seems to be the hallmark of the disease. Further support of this interpretation comes from the observation that two out of the 23 apparently healthy relatives went on to develop vitiligo in a 2-year follow-up.

Clinical and immunological improvement in a patient with chronic mucocutaneous candidiasis treated with transfer factor.

In a 19 year old patient suffering from CMC since the first months of life, clinical improvement accompanied by correction of the immunologic defect was achieved by Transfer Factor therapy. After 12 months from the last administration of Transfer Factor the improvement persisted. The positive outcome of the treatment in this disease is not constant. Possibly only patients with cellular immunologic defects are susceptible of a favourable response, moreover it is thinkable that the quality of Transfer Factor and the dosage administered must play a role.