Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy

Background Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. Methods Patients ( n  = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4 + T-cell counts had to be at or above the lower limit of normal. Results Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a ≥ 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses ( n  = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a ≥ 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. Conclusions Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65825/1/j.1365-4362.2003.01793.x.pd

Genomic variation landscape of the human gut microbiome

While large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the latter is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 fecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short indels, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This implies that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake

Differential Gene Expression by RamA in Ciprofloxacin-Resistant Salmonella Typhimurium

Overexpression of ramA has been implicated in resistance to multiple drugs in several enterobacterial pathogens. In the present study, Salmonella Typhimurium strain LTL with constitutive expression of ramA was compared to its ramA-deletion mutant by employing both DNA microarrays and phenotype microarrays (PM). The mutant strain with the disruption of ramA showed differential expression of at least 33 genes involved in 11 functional groups. The study confirmed at the transcriptional level that the constitutive expression of ramA was directly associated with increased expression of multidrug efflux pump AcrAB-TolC and decreased expression of porin protein OmpF, thereby conferring multiple drug resistance phenotype. Compared to the parent strain constitutively expressing ramA, the ramA mutant had increased susceptibility to over 70 antimicrobials and toxic compounds. The PM analysis also uncovered that the ramA mutant was better in utilization of 10 carbon sources and 5 phosphorus sources. This study suggested that the constitutive expression of ramA locus regulate not only multidrug efflux pump and accessory genes but also genes involved in carbon metabolic pathways

Editorial

Jerry BagelPsoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USATwenty-five years ago, inpatient Goekerman therapy was considered to be the "gold standard" treatment for psoriasis. We thought PUVA (psoralen + ultraviolet A light) worked because it intercalated keratinocytes inhibiting cell division, methotrexate affected keratinocytic proliferation, and broadband ultraviolet B creating thymine dimers which also prevented keratinocytic proliferation. The idea that psoriasis was an immunologic disease was in its embryonic development

Supplement for Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Patient-reported outcomes from the PSOARING 3 trial

Supplemental materials for the article entitled, "Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Patient-reported outcomes from the PSOARING 3 trial". Includes Supplemental Tables 1-4 and Supplemental Figures 1-3