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Twenty-two compounds belonging to several classes of polyamine analogs have been examined for their ability to inhibit the growth of the human malaria parasite Plasmodium falciparum in vitro and in vivo. Four lead compounds from the thiourea sub-series and one compound from the urea-based analogs were found to be potent inhibitors of both chloroquine-resistant (Dd2) and chloroquine-sensitive (3D7) strains of Plasmodium with IC50 values ranging from 150 to 460 nM. In addition, the compound RHW, N1,N7-bis (3-(cyclohexylmethylamino) propyl) heptane-1,7-diamine tetrabromide was found to inhibit Dd2 with an IC50 of 200 nM. When RHW was administered to P. yoelii-infected mice at 35 mg/kg for 4 days, it significantly reduced parasitemia. RHW was also assayed in combination with the ornithine decarboxylase inhibitor difluoromethylornithine, and the two drugs were found not to have synergistic antimalarial activity. Furthermore, these inhibitors led to decreased cellular spermidine and spermine levels in P. falciparum, suggesting that they exert their antimalarial activities by inhibition of spermidine synthase.

Diabetic foot ulcers are an important clinical problem, leading to infection and loss of limb [1]. Diabetic foot ulcers occur in 15% of patients with diabetes mellitus, with a yearly incidence of 1%–2% [2]. Diabetic patients have higher rates of hospitalization for skin and soft-tissue infections than patients without diabetes [3]. Most studies based on culture have shown that the infections are polymicrobial, with Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus species (especially Staphylococcus aureus) being the most prevalent isolates [4, 5]. Traditionally, the pathogenesis of these wounds has been attributed to factors such as neuropathy (a functional disturbance in peripheral nerves), repeated trauma, and peripheral vascular disease [6]. More recently, the roles of wound bioburden and functionally equivalent pathogroups in diabetic wound infections have been studied [7, 8]. Data on the composition of the cutaneous microbiota of diabetic patients is lacking. One of the few studies to address this question was performed in 1975, in the era prior to high-throughput 16S rRNA sequencing (HTS) technology [9]. No differences in culturable organisms between control and diabetic skin were found, but the study also did not examine the feet. Staphylococcus species account for 70% of the normal skin microbiome on the plantar aspect of the foot [10, 11]; most are coagulase-negative Staphylococcus species that are of low virulence and may compete with the more virulent S. aureus [12]. In contrast, on intact skin on the contralateral (opposite) limb of patients with unilateral diabetic ulcers, only 7% of the microbiota was represented by Staphylococcus species [13], suggesting a loss of these protective organisms or their replacement by other species. HTS identification based on deep sequencing is currently being used to better characterize the human microbiome [14, 15]. We sought to use HTS along with quantitative polymerase chain reaction (qPCR) to better characterize the microbiota of the diabetic foot. The aim of this study was to determine whether there are differences in surface microbiota of the arm and foot between nondiabetic men and diabetic men without a history of diabetic foot ulcer.

Chikungunya virus is an emerging infectious disease that has started circulating throughout the Americas and Caribbean. It can lead to persistent arthralgia lasting months to years. Treatment has been symptomatic with nonsteroidal anti-inflammatory medications. This case report describes a trial of colchicine for chikungunya arthralgia in 1 patient.

Macrophage infiltration into adipose tissue has been demonstrated to accompany obesity, with a potential preferential infiltration into intraabdominal vs. sc fat.Our objective was to determine whether this occurs across different populations with a range of body mass indexes and to assess the relationship with regional adiposity and comorbidity of obesity.In two independent cohorts, we used paired omental (OM) and sc fat biopsies from lean controls or predominantly sc or intraabdominally obese persons with minimal comorbidity (n = 60, cohort 1), or from severely obese women with a significant rate of comorbidity (n = 29, cohort 2).Elevated macrophage infiltration into OM vs. sc fat was observable in lean subjects and exaggerated by obesity, particularly if predominantly intraabdominal. This was paralleled by increased monocyte chemoattractant protein-1 (MCP1) and colony-stimulating factor-1 (CSF1) mRNA levels. Level of CSF1 and MCP1 mRNA correlated with the number of OM macrophages (r = 0.521, P0.0001 and r = 0.258, P0.051, respectively). In severely obese women (mean body mass index = 43.0 +/- 1.1 kg/m(2)), higher protein expression of both MCP1 and CSF1 was detected in OM vs. sc fat. Number of OM macrophages, but not of sc macrophages, correlated with waist circumference (r = 0.636, P = 0.001 vs. r = 0.170, P = 0.427) and with the number of metabolic syndrome parameters (r = 0.385, P = 0.065 vs. r = -0.158, P = 0.472, respectively). Preferential macrophage infiltration into OM fat was mainly observed in a subgroup in whom obesity was associated with impaired glucose homeostasis.Preferential macrophage infiltration into OM fat is a general phenomenon exaggerated by central obesity, potentially linking central adiposity with increased risk of diabetes and coronary heart disease.