Independent and additional prognostic value of aminoterminal propeptide of type III procollagen circulating levels in patients with chronic heart failure

BACKGROUND: In chronic heart failure (CHF), changes in the extracellular space contribute to cardiac dysfunction. We aimed to determine whether aminoterminal-propeptide of type III procollagen (PIIINP), a marker of extracellular matrix turnover, might provide prognostic information in CHF patients. METHODS AND RESULTS: A total of 101 consecutive CHF patients (mean age 61.7 +/- 8.7 years, 88% males) were followed up between 1999 and 2001. The combined endpoint of the study was death and hospitalization for heart failure. During follow-up there were 15 deaths and 11 hospitalizations for worsening heart failure. At the survival analysis, age (P = .02), New York Heart Association class (P = .014), s-creatinine (P = .014), plasma-PIIINP (p-PIIINP) levels (P = .005), left ventricular ejection fraction (LVEF) (P = .0002), and a restrictive mitral filling pattern (P = .0003) predicted event-free survival. At the multivariate analysis, p-PIIINP levels predicted outcome independently of other clinical variables, hormones, and echocardiographic and exercise testing variables (P < .05 in all models). In patients with LVEF <31%, the presence of p-PIIINP >4.7 microg/L levels was significantly associated with a higher risk of death and hospitalization as compared with the other patients (event-free survival rate at 12 months: 45% versus 95%; at 24 months: 27% versus 88%; at 36 months: 18% versus 85%, P < .0001). CONCLUSIONS: In patients with CHF, PIIINP levels predict outcome independently of clinical status, hemodynamics and hormonal activation. PIIINP levels provide additional prognostic information to that of left ventricular function alone, suggesting that it may reflect more than cardiac extracellular matrix turnover.     

Endothelial Dysfunction in Early Systemic Lupus Erythematosus Patients and Controls Without Previous Cardiovascular Events

Objective

To assess the prevalence and risk factors for endothelial dysfunction detected by peripheral artery tonometry in systemic lupus erythematosus patients with early disease without cardiovascular disease and risk factors.

Methods

All the consecutive adult lupus patients, with a disease duration <5 years, seen in our hospital from December 2014 to March 2016 were considered. We excluded patients with any history of cardiovascular disease or risk factors possibly affecting peripheral artery tonometry. Enrolled patients were matched for sex, age, body mass index, and blood pressure with healthy controls with the same exclusion criteria. Patients and controls received a transthoracic Doppler echocardiogram and an evaluation of endothelial function by peripheral artery tonometry.

Results

Twenty patients (100% female) with a median disease duration of 14 months (range 1–58 months), a mean ± SD age of 42 ± 15 years, and a mean ± SD age at diagnosis of 40 ± 16 years were enrolled and matched with 20 controls. Peripheral artery tonometry showed a significantly higher prevalence of endothelial dysfunction (P = 0.003) and vascular stiffness (P = 0.02), while echocardiography detected a significantly higher prevalence of left ventricular concentric remodeling (P = 0.003), grade I diastolic dysfunction (P = 0.047), and subclinical increase of filling pressures (P = 0.039) in lupus patients compared to controls. Among lupus patients, no features were associated with endothelial dysfunction.

Conclusion

A high rate of endothelial dysfunction and vascular stiffness occurs in early lupus patients without cardiovascular risk factors and disease. Larger studies are needed to confirm our results and to look for patients’ characteristics possibly associated with these abnormalities.

     

The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF‐α

The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL‐1β release. Since innate immune activation and IL‐1β release seem to be implicated in Behçet's disease (BD), a systemic immune‐inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca²⁺ permeability induced by the selective P2×7r agonist 2′‐3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL‐1β release from LPS‐primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF‐α‐incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP‐induced Ca²⁺ intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF‐α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti‐TNF‐α drugs in the treatment of the disease.     

Immunocytochemical characterisation of olfactory ensheathing cells of zebrafish

Continuous lifelong neurogenesis is typical of the vertebrate olfactory system. The regenerative ability of olfactory receptor neurons is dependent on the glial cell type specific to the olfactory pathway, designated ‘olfactory ensheathing cells’. Several studies to date have focused on mammalian olfactory ensheathing cells, owing to their potential roles in cell‐based therapy for spinal cord injury repair. However, limited information is available regarding this glial cell type in non‐mammalian vertebrates, particularly anamniotes. In the current immunocytochemical study, we analysed the features of olfactory ensheathing cells in the zebrafish, Danio rerio. Fish provide a good model for studying glial cells associated with the olfactory pathway of non‐mammalian vertebrates. In particular, zebrafish has numerous valuable features that enable its use as a prime model organism for genetic, neurobiological and developmental studies, as well as toxicology and genomics research. Paraffin sections from decalcified heads of zebrafish were processed immunocytochemically to detect proteins used in the research on mammalian olfactory ensheathing cells, including glial fibrillary acid protein (GFAP), S100, neural cell adhesion molecule (NCAM), polysialylated NCAM (PSA‐NCAM), vimentin (VIM), p75NTR and galactin (Gal)‐1. Notably, GFAP, S100, NCAM and Gal‐1 were clearly observed, whereas no vimentin staining was detected. Weak immunostaining for PSA‐NCAM and p75NTR was evident. Moreover the degree of marker expression was not uniform in various tracts of the zebrafish olfactory pathway. The immunostaining patterns of the zebrafish olfactory system are distinct from those of other fish to some extent, suggesting interspecific differences. We also showed that the olfactory pathway of zebrafish expresses markers of mammalian olfactory ensheathing cells. The olfactory systems of vertebrates have similarities but there are also marked variations between them. The issue of whether regional and interspecific differences in immunostaining patterns of olfactory pathway markers have functional significance requires further investigation.     

Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians

Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal and cardiovascular diseases, is caused by either increased production or decreased excretion of uric acid or a mix of both. The solute carrier protein 2 family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux across the renal proximal tubule. Genome-wide association studies have consistently shown the association of single-nucleotide polymorphisms in this gene with SUA in majority populations. American Indian participants of the Strong Heart Family Study, belonging to multigenerational families, have high prevalence of hyperuricemia. We conducted measured genotype analyses, based on variance components decomposition method and accounting for family relationships, to assess whether the association between SUA and SLC2A9 gene polymorphisms generalized to American Indians (n=3604) of this study. Seven polymorphisms were selected for genotyping based on their association with SUA levels in other populations. A strong association was found between SLC2A9 gene polymorphisms and SUA in all centers combined (P-values: 1.3 × 10⁻³¹–5.1 × 10⁻²³) and also when stratified by recruitment center; P-values: 1.2 × 10⁻¹⁴–1.0 × 10⁻⁵. These polymorphisms were also associated with the estimated glomerular filtration rate and serum creatinine but not albumin–creatinine ratio. In summary, the association of polymorphisms in the uric acid transporter gene with SUA levels extends to a new population of American Indians.     

Gastrointestinal complications after kidney transplantation

Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease(IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.     

Narcolepsy treatment: pharmacological and behavioral strategies in adults and children

Sleep and Breathing - Narcolepsy is a disabling, rare, and chronic sleep disorder, currently classified as distinct central nervous system hypersomnia in narcolepsy type 1 (NT1) and narcolepsy type...     

Dimensions of personality structure among patients with substance use disorders and co-occurring personality disorders: A comparison with psychiatric outpatients and healthy controls

Background

Although dual diagnosis has been a topic of great scientific interest for a long time, few studies have investigated the personality traits that characterize patients suffering from substance use disorders and co-occurring personality disorders through a dimensional approach. The present study aimed to evaluate structural personality profiles among dual-diagnosis inpatients to identify specific personality impairments associated with dual diagnosis.

Methods

The present study involved 97 participants divided into three groups: 37 dual-diagnosis inpatients, 30 psychiatric outpatients and 30 nonclinical controls. Dimensions of personality functioning were assessed and differences between groups were tested using Kernberg's dimensional model of personality.

Results

Results showed that dual diagnosis was associated with the presence of difficulties in three main dimensions of personality functioning. Dual-diagnosis inpatients reported a poorly integrated identity with difficulties in the capacity to invest, poorly integrated moral values, and high levels of self-direct and other-direct aggression.

Conclusions

The present study highlighted that a dimensional approach to the study of dual diagnosis may clarify the personality functioning of patients suffering from this pathological condition. The use of the dimensional approach could help to advance research on dual diagnosis, and it could have important implications on clinical treatment programs for dual-diagnosis inpatients.     

Endogenous Secretory RAGE in Obese Women: Association with Platelet Activation and Oxidative Stress

Context: The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis. Objective: We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk. Patients: Eighty otherwise healthy obese women and 20 nonobese women were studied. Results: esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2). Conclusion: In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.