Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.
Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.
This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.
We examined the antibacterial action of several tannins on plasma coagulation by Staphylococcus aureus and the effect of conventional chemotherapy combined with tannic acid below the MIC. Coagulation was inhibited in plasma containing tannic acid (100 mg/L), gallic acid (5000 mg/L), ellagic acid (5000 mg/L), (-)-epicatechin (1500 mg/L), (-)-epicatechin gallate (500 mg/L) or (-)-epigallocatechin gallate (200 mg/L) after incubation for 24 h. All tannins inhibited coagulation at a concentration below the MIC. The MICs of oxacillin and cefdinir for S. aureus were reduced to < or = 0.06 mg/L in Mueller-Hinton agar plates with tannic acid (100 mg/L) at a concentration below the MIC. The antistaphylococcal activity of tannic acid was reduced in plates with 10% rabbit blood, but not in those with 10% rabbit plasma. Membranous structures formed in a culture medium containing equal proportions of plasma and tryptic soy broth after incubation for 24 h. The colony counts of S. aureus in membranous structures in the medium containing oxacillin (40 mg/L) and tannic acid (100 mg/L) were c. 10-fold lower than those in medium containing oxacillin (40 mg/L) alone (P< 0.01). Tannic acid merits further investigation as a possible adjuvant agent against S. aureus skin infections treated with beta-lactam antibiotics.
Summary
Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by kerati-nocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.
The effects of milk products fermented by Bifidobacterium longum strain BL1, a probiotic strain, on blood lipids in rats and humans were studied. Rats were fed a cholesterol-enriched experimental diet, supplemented with lyophilized powders of 1) acid milk (control), 2) milk fermented with a mixed culture of ordinary yogurt starters composed of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (SL), and 3) bifidobacterium milk fermented with the probiotic B. longum strain BL1, respectively. The bifidobacterium milk feeding brought about significant lowering of the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, in comparison with the control, while no change in high-density lipoprotein cholesterol concentration was observed. On the other hand, supplementation with SL milk resulted in only slight, nonsignificant decreases in serum lipid concentrations in comparison with the control. In the human study, 32 subjects with serum total cholesterol ranging from 220 to 280 mg/dl were randomly assigned to two treatments: 1) intake of a low-fat drinking yogurt prepared with ordinary yogurt starters composed of S. thermophilus and L. delbrueckii subsp. bulgaricus (P-group) and 2) intake of a low-fat drinking yogurt prepared with the two ordinary yogurt starters plus B. longum strain BL1 (B-group). After intake for 4 wk at 3 x 100 ml/day, reduction of serum total cholesterol was observed in approximately half of the B-group subjects; a particularly significant decrease in serum total cholesterol was found among subjects with moderate hypercholesterolemia (serum total cholesterol > 240 mg/dl). However, the serum lipid concentrations in the P-group subjects were almost stable during the experimental periods. The present results indicate the potential of the probiotic B. longum strain BL1 in serum lipid improvement.
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