Treatment of atopic dermatitis with KAM-3008, a barrier-based, non-steroidal topical cream.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyper-reactivity to environmental triggers, and is characterized by pruritic eczematous skin lesions. Recent insights into the pathophysiology of AD point to the important role that abnormal barrier permeability plays, which leads to compromised hydration, common micro-organismal colonization and immune dysregulation. Current treatment strategies for AD, such as topical corticosteroids and moisturizers, control the disease symptom's severity and duration. KAM-3008 is a novel, barrier-based, steroid-free, topical cream indicated for the relief of symptoms associated with AD. In addition to moisturizing and emollient ingredients, several herbal extracts have been incorporated into the formulation to enhance its anti-allergic and anti-inflammatory properties. METHODS: In this study, the safety and efficacy of KAM-3008 body cream in relieving the symptoms of AD in adult subjects after 7, 14 and 21 days of treatment were investigated using the transepidermal water loss (TEWL), skin hydration and scoring atopic dermatitis (SCORAD) measurements. RESULTS AND CONCLUSIONS: Based on both the quantitative TEWL and qualitative SCORAD assessments, we found that KAM-3008 body cream is a safe, well-tolerated and efficacious stand-alone treatment for the relief of AD symptoms.

Microsatellite instability in multiple nonfamilial malignancies.

Development of multiple tumors of different histopathologic types may suggest a profound generalized genetic defect, such as malfunction of DNA mismatch repair (MMR) mechanism. Defects in this mechanism are best reflected in microsatellite instability (MSI). We aimed to determine the role of MSI in a group of patients with dual malignancies and compared the data with that of patients with a single malignancy. Fifty patients were enrolled in the study, of whom 16 patients developed both solid and hematologic nonfamilial malignancies, 18 patients developed a single matched hematologic malignancy, and 16 a single matched solid malignancy. Five microsatellite markers were replicated by polymerase chain reaction (PCR) after DNA extraction from paraffin-embedded tissue blocks and analyzed by the GeneScan Analysis Software. The MSI-high phenotype was defined as instability in at least 40% of the examined loci. A higher prevalence of MSI-high phenotype was found in patients with dual malignancies (31.3%) compared with patients with single hematologic (5.6%) or solid malignancy (6.3%) (P = 0.0498 and 0.07, respectively). In conclusion, defects in DNA MMR mechanism may have an important role in the development of multiple sporadic nonfamilial malignancies.

Microsatellite instability in gastric MALT lymphoma.

The role of microsatellite instability and defects in DNA mismatch repair mechanism in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is still controversial, as both negative and positive findings have been reported. This may be explained mainly by arbitrary selection of the tested loci, the use of various techniques of microsatellite instability analysis and by different definitions of replication error positive phenotype. The aim of our study was to evaluate the instability at selected microsatellite markers using the GeneScan Analysis Software. DNA from paraffin-embedded tissue blocks of 13 previously untreated patients with localized gastric MALT lymphoma was extracted. Five microsatellite markers, which are located in hMSH2, hMLH1, P16, APC and MLL loci, were selected from the genetic database. We found genetic instability in tumors of 9/13 patients with gastric MALT lymphoma (69%). Seven of them had replication-error-positive phenotype (54%). Microsatellite instability was found in 39% of the samples in the MLL locus, 39% in the APC, 46% in the P16, 23% in the hMLH1 and none in the hMSH2. This study demonstrates that microsatellite instability has more prominent role in pathogenesis of gastric MALT lymphoma than reported to date. We suggest that microsatellite instability should be analyzed with markers adjacent to chromosomal loci that are involved in lymphomas. Our findings support the 'Real Common Target genes' theory of high rate of microsatellite instability in specific genes, which are associated with related tumors.

Features of skin-coincubated macrophages that promote recovery from spinal cord injury.

Uncontrolled inflammation is considered to exacerbate the neuronal loss that follows spinal cord trauma. However, controlled inflammation response appears to be beneficial. Skin-coincubated macrophages injected into contused spinal cord of rats resulted in improved motor recovery and reduced spinal cyst formation. The macrophages express elevated levels of cell-surface molecules CD80, CD86, CD54 and MHC-II, markers characteristic of antigen presenting cells (APCs). Additionally, skin-coincubation elevates secretion of interleukin-1 beta (IL-1 beta) and Brain-Derived Neurotrophic Factor (BDNF), and reduces secretion of tumor necrosis factor alpha (TNF-alpha). We propose that macrophages activated by skin-coincubation bolster neuroprotective immune activity in the spinal cord, making the environment less cytotoxic and less hostile to axonal regeneration.

The antiapoptotic effects of blood constituents in patients with chronic lymphocytic leukemia.

OBJECTIVE: Clonal B-lymphocytes of chronic lymphocytic leukemia (B-CLL) are characterized by decreased sensitivity to programmed cell death and, therefore, they accumulate in vivo. However, these malignant cells die rapidly in vitro. In the current study we concentrated on the contribution of autologous serum (AS) and lymphocyte subsets to the survival of the malignant cells in vitro. METHODS: Mononuclear cells from the peripheral blood of 26 CLL patients and 24 controls were incubated overnight in the presence or absence of AS and heat-inactivated AS (HI-AS) or fetal calf serum (FCS). Also, isolated B cells were incubated at different concentrations in the presence of AS and/or isolated T cells. The level of apoptosis of CD19+ cells was measured by flow cytometry. RESULTS: Spontaneous apoptosis of unfractionated B-CLL cells incubated with AS, FCS or without serum was significantly lower than the rate of B-cell death in the control group, in similar culture conditions. AS had an antiapoptotic effect on unfractionated B-CLL cells when compared with FCS. The rate of apoptosis of B-CLL cells was directly associated with stage. HI of AS had a variable effect, which was related to the stage of the disease. High concentrations of B cells and the addition of autologous T cells reduced the rate of apoptosis when incubated without serum. The antiapoptotic effect of T cells was most prominent in progressive stages. CONCLUSIONS: B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression.