ApoA-I mimetics favorably impact cyclooxygenase 2 and bioactive lipids that may contribute to cardiometabolic syndrome in chronic treated HIV.

OBJECTIVE: We investigated whether apolipoprotein A-I (apoA-I) mimetic peptides 4F and 6F can be a novel therapeutic strategy to reduce blood and gut bioactive lipids, proinflammatory effects of endotoxin (LPS) and aberrant activation of cyclooxygenase 2 (COX-2) as instigators of increased risk for cardiometabolic disease in chronic treated HIV. METHODS: We used two humanized murine models of chronic treated HIV infection (n = 109 mice) and gut explants from HIV infected (n = 10) persons to determine whether Tg6F and 4F attenuate in vivo and ex vivo increased blood and gut bioactive lipids (measured by mass spectrometry) and intestinal protein levels of COX-2 (measured by immunoassays) in chronic treated HIV. RESULTS: In these models of HIV, when compared to HIV-1 infected mice on antiretroviral therapy (ART) alone, oral Tg6F in combination with ART attenuated increases in plasma and gut bioactive lipids (and particularly COX lipids) and intestinal COX-2. 4F and Tg6F also reduced ex vivo production of COX-2 protein and associated secretion of bioactive lipids in gut explants from HIV-1 infected persons treated with LPS. CONCLUSION: ApoA-I mimetics favorably impact the proinflammatory effects of LPS, COX-2 and production of bioactive lipids that collectively drive gut and systemic inflammation in chronic treated HIV. Given prior experimental evidence that the proinflammatory effects of LPS, COX-2 and gut dysfunction contribute to cardiometabolic syndrome in chronic HIV, apoA-I mimetic peptides may be a novel therapy to treat cardiometabolic syndrome in chronic HIV.

Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function.

BACKGROUND/OBJECTIVE: Youth with obesity have an altered high-density lipoprotein (HDL) subspecies profile characterized by depletion of large apoE-rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile is reversible and that HDL function would improve with metabolic surgery. METHODS: Serum samples from adolescent males with severe obesity mean±s.d. age of 17.4±1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group. RESULTS: After VSG, body mass index decreased by 32% and insulin resistance as estimated by homeostatic model assessment of insulin resistance decreased by 75% (both P<0.01). Large apoE-rich HDL subspecies increased following VSG (P<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. In addition, HDL function improved compared with baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30% and HDL anti-oxidative capacity improved by 25%, all P<0.01). CONCLUSIONS: Metabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults.

The zoonotic potential of daptomycin non-susceptible enterococci.

Daptomycin non-susceptible Enterococcus (DNSE) is an emerging clinical problem. Little is known about how de novo DNSE infections develop or the risk factors associated with them. Determining risk factors associated with de novo DNSE infections will aid in understanding the mechanisms of daptomycin non-susceptibility. Humans in contact with animals worldwide are at risk of carriage of multidrug-resistant bacteria. Herein, I review the scientific evidence that supports the hypothesis that transport of daptomycin non-susceptibility genes between animals and humans may be a possible mechanism for development of de novo daptomycin non-susceptibility in enterococci.

Proximity to animal or crop operations may be associated with de novo daptomycin-non-susceptible Enterococcus infection.

Daptomycin-non-susceptible enterococci (DNSE) are emerging pathogens. We have previously reported de novo DNSE isolates in patients with agricultural activities and exposure to livestock. We studied the geographical distribution of the residencies of 34 patients with DNSE infections described in a tertiary centre over a 5-year period in an effort to explore the association between patients' residential locations and agricultural and farm lands. Nine patients had no prior exposure to daptomycin (de novo) and seven of these lived in areas with animal or crop operations. Of those living near an animal or crop operation, the mean number of operations in the proximity of the residence of patients with daptomycin-exposed DNSE was 13.8 (range 1-67) compared to 98.6 (3-529) for those patients with de novo DNSE (P = 0.0486). These data are consistent with previous reports that the transport of daptomycin resistance genes between animals and humans may be a possible mechanism for development of de novo daptomycin resistance in enterococci.

Smooth muscle tumour of the right groin: description of a unique case.

INTRODUCTION: A deep soft tissue smooth muscle tumour is a rare entity with few cases described in the literature. MATERIALS AND METHODS: Herein, we report a case of a smooth muscle tumour of the right inguinal area which presented as a painful mass. This case is unique because of the anatomic location of the tumour, which has not been reported before, and the clinical presentation of this tumour mimicked a hernia. CONCLUSION: Smooth muscle tumours in the inguinal area are an exceptionally rare occurrence, but clinicians should always consider less routine causes for a painful inguinal mass.

Community-acquired Acinetobacter infections.

Acinetobacter infections have been attracting increasing attention during recent years because they have become common in hospitalized patients, especially in the intensive care unit (ICU) setting. However, the available literature suggests that the pathogen has another fearful potential; it can cause community-acquired infections. We searched PubMed and the reference lists of the initially identified articles and identified six case series regarding a total of 80 patients with community-acquired Acinetobacter baumannii infections; from these, 51 had pneumonia and 29 had bacteremia. Of these 80 patients, 45 (56%) died of the infection. In addition, we identified 26 case reports regarding 43 patients with community-acquired Acinetobacter infections; from these, 38 had pneumonia, two had meningitis, one had soft-tissue infection, one had ocular infection, and one had native valve endocarditis. Comorbidity was commonly present in patients reported in the case series as well as the case reports, mainly, chronic obstructive pulmonary disease, renal disease, and diabetes mellitus; heavy smoking and excess alcohol consumption were also common. Most of the studies originated from China, Taiwan, and tropical Australia. We also identified 12 retrospective or prospective studies (seven from the Far East, two from Oceania, one from N. Guinea, one from Palestine, and one from USA/Canada) that reported the frequency of community-acquired Acinetobacter infections; the range of isolation of Acinetobacter from patients with community-acquired pneumonia in these studies was 1.3%-25.9%. In conclusion, most community-acquired Acinetobacter infections have been reported from countries with tropical or subtropical climate, and mainly affect patients with some form of comorbidity or are associated with heavy smoking and excess alcohol consumption.

Adiponectin and cancer: a systematic review.

Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies, but the mechanisms underlying this relationship remain to be fully elucidated. Adiponectin, an adipocyte secreted endogenous insulin sensitizer, appears to play an important role not only in glucose and lipid metabolism but also in the development and progression of several obesity-related malignancies. In this review, we present recent findings on the association of adiponectin with several malignancies as well as recent data on underlying molecular mechanisms that provide novel insights into the association between obesity and cancer risk. We also identify important research questions that remain unanswered.

Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin.

AIMS/HYPOTHESIS: Peptide YY (PYY) is a gut-derived hormone that has been shown to reduce short-term food intake in animals and humans. It has been proposed that deficiency of PYY contributes to obesity in humans. However, the physiology of PYY regulation by factors such as caloric restriction, or by other molecules important in energy homeostasis, e.g. leptin, remains to be fully elucidated. MATERIALS AND METHODS: We evaluated the effect on PYY levels of: (1) caloric ingestion (a mixed meal) in five healthy normal-weight subjects; (2) fasting for 2 or 3 days in eight lean men and seven lean women respectively; and (3) recombinant human leptin administration at physiological replacement and pharmacological doses. RESULTS: PYY levels increased 50% after a mixed meal (p=0.01), and short-term complete fasting for 2 or 3 days decreased leptin and PYY levels to 20-30% and 40-60% of baseline, respectively (both p<0.05). However, recombinant human leptin administration at physiological doses to restore the fasting-induced decrease of leptin levels and at pharmacological doses over the short term had no effect on PYY levels. CONCLUSIONS/INTERPRETATION: PYY increases after meal ingestion and decreases after fasting in a manner consistent with a meal-related signal of energy homeostasis. Importantly, circulating levels of this gut-secreted molecule are independent of regulation by leptin over the short term. These findings contribute towards our understanding of the homeostatic systems that regulate appetite in humans, including the possible redundancy of gastrointestinally secreted and adipocyte-secreted signals. This may be of importance for the future development of medications to treat obesity.

Central nervous system manifestations of Mycoplasma pneumoniae infections.

Mycoplasma pneumoniae infection is associated with several manifestations from the central nervous system (CNS) such as encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy. In the current paper epidemiologic, clinical, laboratory and treatment data on these manifestations are reviewed. The M. pneumoniae induced immune dysregulation and its contributing role in the pathogenesis of neurological insult is discussed. The recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between M. pneumoniae infection and CNS disease especially encephalitis. Clinicians should be aware of the potential association between M. pneumoniae infection and several CNS manifestations. The role of various anti-microbial or immunomodulating therapies in treating such manifestations should be further explored.