Nitric oxide-dependent neovascularization role in the lower extremity disease

Peripheral arterial occlusive disease (PAD) describes vascular disorders associated with ischemia and PAD affects about 8 million people in the United States. Moreover, PAD's prevalence can increase dramatically if cardiovascular disease is present. In healthy individuals reducing blood flow through the lower extremity is followed by a physiological process to limit ischemia in the distal tissue. This process is called revascularization and impairing revascularization results in PAD. Studies suggest nitric oxide (NO) maybe involved in the ischemia-dependent hindlimb revascularization process. NO is increased in the ischemic hindlimb and eliminating NO impairs the revascularization process. Moreover, restoring NO improves hindlimb revascularization. NO may be acting through its effects on vascular tone, cell migration, or extracellular matrix degradation. The present review illustrates nitric oxide's critical role in the ischemia-induced hindlimb revascularization. Thus, restoring normal NO levels in diseased arteries may represent a viable therapeutic avenue by supplementing exogenous NO or employing therapeutic strategies to either increase NO synthesis and its messengers or decrease NO catabolism.     

De novo synthesis of benzosceptrin C and nagelamide H from 7-15N-oroidin: implications for pyrrole-aminoimidazole alkaloid biosynthesis

De novo synthesis of the natural products benzosceptrin C (7) and nagelamide H (8) was achieved using cell-free enzyme preparations from the marine sponges Agelas sceptrum and Stylissa caribica employing synthetic 7-(15)N-oroidin. These studies provide direct experimental evidence to support the long-standing, but untested, hypothesis that oroidin is a precursor to more complex pyrrole-aminoimidazole alkaloids, such as the sceptrins, benzosceptrins, and nagelamides. In addition, a new nagelamide, didebromonagelamide A (5b), was isolated from S. caribica, representing the first report of a nagelamide-like compound from the Caribbean.     

Role of the neurotrophin network in eating disorders’ subphenotypes: Body mass index and age at onset of the disease

Eating disorders (ED) are severe psychiatric diseases that most likely result from, and are sustained by socio-cultural, psychological and biological factors. We explored whether members of the neurotrophin family are disease-modifying factors of quantitative traits, potentially contributing to the outcome or prognosis of the disease. We studied lifetime minimum and maximum body mass index (minBMI and maxBMI) and age at onset of the disease in a sample of 991 ED patients from France, Germany, Italy and Spain and analysed 183 genetic variants located in 10 candidate genes encoding different neurotrophins and their receptors. We used a hierarchical model approach to include prior genetic knowledge of the specific and found that variants in CNTF, in its receptor CNTFR, and in NTRK2 were significantly associated with a lower age at onset of the ED. In addition, one variant in NTRK1 was associated with a higher minBMI. The results suggest that for these two subphenotypes, CNTF, CNTFR, NTRK1 and NTRK2 might act as disease-modifying factors and add preliminary evidence to the global hypothesis that EDs are the result of complex interactions and reciprocal controls between the immune, endocrine and central nervous systems.     

Pacemaker-related endocarditis: clinical features and treatment

BACKGROUND AND AIM OF THE STUDY: Removal of the entire infected system is the traditionally indicated management of pacemaker lead endocarditis (PLE), based on expert recommendations. Herein is described the present authors' experience with this condition. METHODS: Between 1987 and 2004, all consecutive patients with PLE treated at a tertiary referral university hospital and a community hospital were prospectively selected. Clinical features, management and outcome were analyzed. RESULTS: Thirteen cases of PLE were diagnosed. Surgery was performed in 10 cases, and medical treatment alone in three (due to advanced age in two cases and because of terminal colon cancer in one case). Four subjects died before discharge: three deaths occurred after surgery (one patient died due to refractory ventricular arrhythmia and two from persistent sepsis), and one unoperated patient died from sepsis and severe renal failure. No deaths or late surgeries were observed after a mean follow up period of 37 +/- 14 months. Both patients who survived hospitalization and underwent only medical treatment were free from late complications after 30 and 60 months follow up, respectively. CONCLUSION: Some patients with PLE present a good evolution without surgery, suggesting that surgical treatment is not mandatory in this situation. However, an indication for surgery may be similar to that for other cases of infective endocarditis.     

Natural killer receptors distribution in multiple sclerosis: Relation to clinical course and interferon-beta therapy

NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56^bright NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-β-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-β therapy, may support the analysis of NKR distribution as new biomarkers.     

First positive reactions to cannabis constitute a priority risk factor for cannabis dependence

Aim   To assess the association between first reactions to cannabis and the risk of cannabis dependence.
Design   A cross-sectional population-based assessment in 2007.
Setting   A campus in a French region (Champagne-Ardennes).
Participants   A total of 1472 participants aged 18–21 years who reported at least one life-time cannabis consumption, of 3056 students who were screened initially [the Susceptibility Addiction Gene Environment (SAGE) study].
Measurements   Positive and negative effects of first cannabis consumptions, present cannabis dependence and related risk factors were assessed through questionnaires.
Findings   The effects of first cannabis consumptions were associated dose-dependently with cannabis dependence at age 18–21 years, both according to the transversal approach of the SAGE study and to the prospective cohort of the Christchurch Health and Development Study (CHDS) assessed at the age of 25 years. Participants of the SAGE study who reported five positive effects of their first cannabis consumption had odds of life-time cannabis dependence that were 28.7 (95% confidence interval: 14.6–56.5) higher than those who reported no positive effects. This association remains significant after controlling for potentially confounding factors, including individual and familial variables.
Conclusions   This study suggests an association between positive reactions to first cannabis uses and risk of life-time cannabis dependence, this variable having a central role among, and through, other risk factors.     

Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography?

In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft‐tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5‐year all‐cause mortality and 5‐year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal–Wallis test, Kaplan–Meier curves, and the log‐rank test. Over a mean duration of follow‐up of 10.4 ± 2.9 years (range: 0.01–12 years) post‐CMR, the overall all‐cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR‐confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow‐up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy.