Toward the biochemical assessment of myocardial fibrosis in hypertensive patients

The serum concentrations of amino-terminal procollagen type III and carboxy-terminal procollagen type I-derived peptides, which have been proposed as useful markers of the tissue synthesis of collagen types III and type I, respectively, were abnormally increased in patients with essential hypertension and became normal after angiotensin-converting enzyme (ACE) inhibition. An association was found between baseline serum concentrations of these peptides and left ventricular hypertrophy, diastolic dysfunction, and ventricular arrhythmias in hypertensive patients. On the other hand, increased serum concentration of the carboxy-terminal procollagen type I-derived peptide was found in spontaneously hypertensive rats compared with normotensive Wistar-Kyoto control rats. An association was found between the serum concentration of this peptide and the extent of myocardial fibrosis and the hydroxyproline concentration in the left ventricle of spontaneously hypertensive rats. It is proposed that procollagen-derived peptides in serum may be markers of exaggerated collagen tissue synthesis involved in hypertensive myocardial fibrosis

Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease

OBJECTIVE: To investigate whether cardiac expression of the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha) is altered in patients with hypertensive heart disease (HHD). METHODS: We studied endomyocardial septal biopsies from 24 patients with essential hypertension divided into three groups: 6 without left ventricular hypertrophy (LVH) (HT group), 10 with LVH (LVH group), and 8 with LVH and heart failure (HF) (HF group). The expression of two PPARalpha isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARalpha target genes were evaluated by RT-PCR. Histomorphological features were evaluated in a second myocardial sample from LVH and HF groups. RESULTS: Whereas the expression of native PPARalpha protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPARalpha protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARalpha was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPARalpha target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARalpha protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPARalpha protein was directly correlated with left ventricular volumes, and inversely with ejection fraction in all hypertensives. CONCLUSIONS: These findings suggest that post-transcriptional regulation of PPARalpha isoforms is altered in patients with HHD, namely in those developing HF. An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling

Transcription factor mediated control of anthocyanin biosynthesis in vegetative tissues

Plants accumulate secondary metabolites to adapt to environmental conditions. These compounds, here exemplified by the purple-colored anthocyanins, are accumulated upon high temperatures, UV-light, drought, and nutrient deficiencies, and may contribute to tolerance to these stresses. Producing compounds is often part of a more broad response of the plant to changes in the environment. Here we investigate how a transcription-factor-mediated program for controlling anthocyanin biosynthesis also has effects on formation of specialized cell structures and changes in the plant root architecture. A systems biology approach was developed in tomato (Solanum lycopersicum) for coordinated induction of biosynthesis of anthocyanins, in a tissue- and development-independent manner. A transcription factor couple from Antirrhinum that is known to control anthocyanin biosynthesis was introduced in tomato under control of a dexamethasone-inducible promoter. By application of dexamethasone, anthocyanin formation was induced within 24 h in vegetative tissues and in undifferentiated cells. Profiles of metabolites and gene expression were analyzed in several tomato tissues. Changes in concentration of anthocyanins and other phenolic compounds were observed in all tested tissues, accompanied by induction of the biosynthetic pathways leading from Glc to anthocyanins. A number of pathways that are not known to be involved in anthocyanin biosynthesis were observed to be regulated. Anthocyanin-producing plants displayed profound physiological and architectural changes, depending on the tissue, including root branching, root epithelial cell morphology, seed germination, and leaf conductance. The inducible anthocyanin-production system reveals a range of phenomena that accompanies anthocyanin biosynthesis in tomato, including adaptions of the plants architecture and physiology

Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease

Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia

A moving mesh finite element algorithm for the adaptive solution of time-dependent partial differential equations with moving boundaries

A moving mesh finite element algorithm is proposed for the adaptive solution of nonlinear diffusion equations with moving boundaries in one and two dimensions. The moving mesh equations are based upon conserving a local proportion, within each patch of finite elements, of the total “mass” that is present in the projected initial data. The accuracy of the algorithm is carefully assessed through quantitative comparison with known similarity solutions, and its robustness is tested on more general problems. Applications are shown to a variety of problems involving time-dependent partial differential equations with moving boundaries. Problems which conserve mass, such as the porous medium equation and a fourth order nonlinear diffusion problem, can be treated by a simplified form of the method, while problems which do not conserve mass require the full theory

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors

OBJECTIVES: Recent epidemiologic studies have shown that obesity is associated with elevated blood concentrations of prothrombotic-proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWF), and homocysteine. We have assessed whether these markers are associated with percentage of body fat (BF), insulin sensitivity as well as with leptin concentrations. DESIGN AND METHODS: Twenty-five men aged 49.6 +/- 12.7 yr (mean +/- SD) underwent whole-body air displacement plethysmography (Bod-Pod(R)) for estimating BF. Blood analyses for leptin and several other metabolic and cardiovascular markers were carried out. RESULTS: Obese subjects had higher levels as compared to controls of BF (37.5 +/- 5.1 vs. 26.0 +/- 6.6, p < 0.01), fibrinogen (3.30 +/- 0.43 vs. 2.67 +/- 0.11, p < 0.01), vWF (136.4 +/- 50.4% vs. 81.6 +/- 12.6%, p < 0.05), and leptin (17.6 +/- 8.7 vs. 6.2 +/- 3.3, p < 0.01), lower concentrations of HDL-cholesterol (1.09 +/- 0.20 vs. 1.51 +/- 0.10, p < 0.001) and lower QUICKI (1/[log(Ins(0)) + log(Glu(0))]) (0.31 +/- 0.03 vs. 0.34 +/- 0.02, p < 0.05). No significant changes were observed in CRP (5.7 +/- 3.4 vs. 3.8 +/- 1.6, p = 0.327) and homocysteine (9.4 +/- 4.2 vs. 8.3 +/- 0.9, p = 0.749). A positive correlation was observed between BF and fibrinogen (r = 0.67, p = 0.0003). Plasma leptin concentrations were correlated with fibrinogen (r = 0.71, p = 0.0001) and CRP (r = 0.43, p = 0.044). After adjustment for BF leptin emerged as a significant predictor of fibrinogen (beta = 0.47, p = 0.023; R(2) = 0.59, p < 0.001). QUICKI was positively correlated with HDL-cholesterol (r = 0.59, p = 0.010) and negatively with fibrinogen (r = -0.53, p = 0.025), CRP (r = -0.52, p = 0.028) and vWF (r = -0.56, p = 0.013). CONCLUSIONS: Increased BF and impaired insulin sensitivity are associated with increased concentrations of cardiovascular risk factors. Leptin seems to be involved in this elevation and emerges as a predictor of circulating fibrinogen concentrations

Papel de los polimorfismos de los genes CFH y ARMS2 en el desarrollo de la retinopatía y la cardiopatía isquémica en la diabetes tipo 1

Fundamento. La diabetes tipo 1 (DT1) es un enfermedad con elevada morbilidad vascular. El objetivo de este estudio es valorar la asociación de los polimorfismos rs1410996 del gen CFH y rs10490924 del gen ARMS2 en pacientes con DT1. Material y métodos. Se trata de un estudio retrospectivo, en el que se han analizado las características clínicas y los polimorfismos rs1410996 del gen CFH y rs10490924 del gen ARMS2 de 147 pacientes con DT1 valorados en la consulta de Endocrinología. Resultados. Todos los pacientes que desarrollaron retinopatía diabética proliferativa en los primeros 20 años de evolución eran portadores del polimorfismo rs1410996 del gen CFH. La frecuencia del alelo de riesgo fue significativamente mayor en los pacientes con cardiopatía isquémica que en los que no la presentaban (75 frente a 53%, p<0,001). Conclusiones. Parece existir una tendencia a aumentar el riesgo de desarrollar retinopatía diabética proliferativa en los pacientes con DT1 asociado con el polimorfismo rs1410996 del gen CFH. Este polimorfismo parece asociarse también con el desarrollo de cardiopatía isquémica en estos pacientes. Sin embargo, el polimorfismo rs10490924 del gen ARMS2 no parece asociarse con la retinopatía ni con la cardiopatía isquémica.Background. Type 1 diabetes is associated with vascular morbidity. The aim of this study was to evaluate the role of polymorphisms rs1410996 CFH and rs10490924 ARMS2 with proliferative diabetic retinopathy and coronary disease in type 1 diabetes patients. Material and methods. We present a retrospective study that analyses the clinical characteristics and the polymorphisms rs1410996 CFH and rs10490924 ARMS2 of 147 type 1 diabetes patients. Results. The patients who developed proliferative diabetic retinopathy in the first 20 years carried the rs1410996 CFH polymorphism. The overall risk-allele frequency was significantly higher among patients with coronary artery disease than in those without it (75 vs. 53%, p<0.001). Conclusions. rs1410996 CFH polymorphism could be associated with both proliferative diabetic retinopathy and coronary artery disease in type 1 diabetes patients. However, rs10490924 ARMS2 does not seem to be associated either with retinopathy or coronary artery disease

Conventional Chemotherapy Followed By Consolidation With Autologous Hematopoietic Transplantation vs Chemotherapy Alone In HIV+ Patients With Large B Cell Lymphoma (LBCL) In First Complete Remission (CR). A Retrospective Analysis On Behalf Of The EBMT Lymphoma Working Party And The GESIDA/PETHEMA Registry Of HIV+ Patients With Non-Hodgkin's Lymphoma (NHL)

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Prevalence of vertebral fractures and their prognostic significance in the survival in patients with chronic kidney disease stages 3-5 not on dialysis

The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. 612 NDD 3-5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. VF were detected in 110patients(18%). Serumphosphatelevels(OR0.719,95%CI0.532to0.972,p = 0.032),ankle-brachial index 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009-3.898, p = 0.047) were an independent predictor of all-cause mortality. In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3-5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis