Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype

A pseudo-randomised clinical trial of in situ gels of fluconazole for the treatment of oropharngeal candidiasis

<p>Abstract</p> <p>Background</p> <p>Oropharyngeal candidasis is a common opportunistic infection seen in immunocompromised patients. Fluconazole has a broad spectrum antifungal activity including a wide variety of <it>candida </it>species. Aim of the present investigation was to formulate and find out the relative efficacy of <it>in situ </it>gels of fluconazole.</p> <p>Method</p> <p>The <it>in situ </it>gels were prepared using polymers which exhibited sol-to-gel phase transition due to change in specific physico-chemical parameters, such as ion triggered system using gellan gum (0.5% w/v) along with sodium carboxylmethylcellulose (0.35%w/v). The study design was bicenter, 'pseudo-randomised, single blind trial conducted in Mangalore., India, which includes 15 HIV positive patients, 15 patients with partial or completes dentures, and 15 patients who were treated with (active control) fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on day 3, 7, 14, 18, 21, 35, and 42. Semiquantitative microbiological cultures of oral swabs were also obtained on same days.</p> <p>Results</p> <p>All patients had mycological documented oropharyngeal candidiasis and were treated with fluconazole (0.5%w/v) <it>in situ </it>gels for 14 days Severity of disease was scored clinically before treatment and at different predetermined time intervals along with semi quantitative culture of oral swabs. The clinical response rate showed 97% cure after 14 days in the treated with <it>in situ </it>gel. In comparison, the control group treated with fluconazole tablets showed 85% improvement in symptoms of oral candidiasis. The patients suffering from HIV infection showed relapse in oral candidiasis at the end of 21 days. The patients having oral candidiasis due to partial or complete dentures showed complete recovery and were free from signs and symptoms of oral candidiasis.</p> <p>Conclusions</p> <p>The <it>in situ </it>gel formulation of fluconazole was well tolerated with no severe adverse reaction and offers a better alternative to tablet formulation in the treatment of oropharyngeal candidasis.</p> <p>Trial registration</p> <p>Current Controlled Trails <a href="http://www.controlled-trials.com/ISRCTN90634047">ISRCTN90634047</a></p

Fibrocytes and the tissue niche in lung repair

Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases

Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities

Background Epidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities. Methods A multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities. Results Prophylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible. Conclusion Prevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients’ health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies

Prevention and treatment of acute and chronic radiodermatitis

Sophie Seit&eacute;,1 Ren&eacute;-Jean Bensadoun,2 Jean-Michel Mazer3 1La Roche-Posay Laboratoire Dermatologique, Levallois-Perret, 2Centre de Haute Energie (CHE), Nice, 3Centre Laser International de la Peau, Paris, France Abstract: More than half the number of patients with cancer, who are treated with radiotherapy, will have radiodermatitis at some point during their treatment. Radiodermatitis either occurs early on in the treatment period or appears months or up to several years later. Acute radiodermatitis is a burn injury that varies in severity according to both treatment and inherent patient factors. Most acute radiodermatitis reactions resolve after several weeks but some reactions persist and can cause complications. Late-onset radiodermatitis is characterized by telangiectasia that forms on atrophic and fragile skin. These radiodermatitis reactions can have a significant negative impact on concomitant and subsequent therapeutic protocols and most particularly on the patient&rsquo;s quality of life. Today, treatment of radiodermatitis reactions is in its infancy. Although there is insufficient evidence available to form recommendations that would prevent or reduce radiodermatitis, some advances have been made using low level light therapy (LLLT) or vascular lasers to control the symptoms. Some recent preclinical and clinical research suggests that LLLT has biostimulating properties which allow the tissues to regenerate and heal faster, reduce inflammation, and prevent fibrosis. Also, in late-onset radiodermatitis pulsed dye laser treatment has been shown to be beneficial in clearing radiation-induced telangiectasia. In the absence of evidence-based recommendations, the objective of this paper is to review how to prevent or manage the symptoms of radiodermatitis reactions. Keywords: acute radiodermatitis, chronic radiodermatitis, low level light therapy, laser, pulsed dye, prevention, management, skin car