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Effective antimicrobials are critical in controlling one of the most common conditions encountered in medicine, namely, skin and skin structure infections. Unfortunately, the identification of appropriate and novel antimicrobials is continually challenged by the emergence of antimicrobial resistance among bacteria, fungi, and parasites. This work will focus on describing novel antibacterials and antifungals approved by the United States Food and Drug Administration in the past 4 years.

Kaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen ( LANA ) and k-cyclin ( kCYC ). To assess the oncogenic potential of LANA and kCYC , primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen ( LTAg ). Interestingly, LANA -transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean ± standard deviation, 38.3 ± 11.0 passages) than untransduced cells and vector-transduced cells (kCYC -transduced HUVEC did not proliferate faster or live longer than control cells. LANA - and kCYC -transduced HUVEC, but not LTAg -transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA - and kCYC -transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg -transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA -transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA -expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA Antibodies against desmoglein proteins account for intraepidermal immunobullous disorders in the pemphigus family of diseases. Antibodies against desmoglein 3 are responsible for the blisters seen in patients with pemphigus vulgaris, whereas antibodies against desmoglein 1 lead to the more superficial separation seen in pemphigus foliaceus. Similar in both clinical and histologic features to pemphigus foliaceus (PF), an endemic form of the disease, fogo selvagem (FS) is found in high prevalence in certain regions of Brazil (Diaz et al., 1989). The endemic nature of the condition is thought to be precipitated by an immune response to an environmental antigen(s), currently not yet identified. This unique epidemiologic phenomenon provides researchers with an opportunity to study the differences between endemic and sporadic forms of this disease. In this issue of the Journal, Diaz et al. (2008) studied early immunologic responses among patients with FS to determine whether the IgM response differs from that seen in patients with the sporadic disease. In a comprehensive assessment of immune responses, they evaluated sera from patients with FS in rural endemic and urban areas of Brazil, patients with PF in the United States and Japan, and control subjects in these locations. Detection of desmoglein 1 IgM varied, with the highest levels (58%) in FS patients in endemic regions and control subjects (>50%) from the same areas. The desmoglein 1 IgM response was considerably lower (12–18%) in FS patients from urban areas of Brazil and still lower in patients from the United States (10%) and Japan (0%). Less variability was found in IgG responses in patients, with markedly lower responses in control subjects, apart from control subjects from rural areas of Brazil. The investigators hypothesize that an environmental agent responsible for the development of FS may cause an early IgM response that predates clinical disease. Through the following questions we will examine this paper in greater detail. For brief answers please refer to http:// network.nature.com/group/jidclub.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA UV light is a major risk factor for skin cancer development (Essen and Klar, 2006). The mechanisms by which UV leads to cancer formation are complex and appear not to be limited solely to UV-induced DNA damage. UV induces immune suppression, which is associated with increased skin cancer formation, as evidenced by the increased cancer risk in immunosuppressed transplant patients (Bergstresser, 1983; Ulrich and Stockfleth, 2007). Therefore, protection against UV-induced immune suppression may have clinical benefits. In this issue, Damian et al. (2008) explore the potential role of topical nicotinamide in preventing UV immunosuppression in humans, based on animal models to prevent UV-induced immune suppression. Using volunteers with a positive Mantoux test (purified protein derivative positive from Bacille Calmette-Guerin vaccination), the authors studied the ability of topical nicotinamide to prevent UVB immune suppression and the mechanisms by which this occurred. They found that when nicotinamide was applied either before or after UV exposure (simulating normal sunlight exposure), the typically encountered immune suppression was reduced. Additionally, men were more sensitive to UV-light-induced immune suppression, which the investigators concluded may account, in part, for the greater incidence of skin cancer and skin cancer mortality in men. Nicotinamide did not work as a sunscreen but rather, as suggested by microarray analysis, as a mechanism that may include alterations in complement, energy metabolism, and apoptosis. Through the following questions we will delve into this paper in greater detail. For brief answers, please refer to http://network.nature.com/group/jidclub.