The renal resistive index is associated with microvascular remodeling in patients with severe obesity

BACKGROUND Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. METHODS We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with N G -nitro arginine methyl ester (L-NAME), were measured. RESULTS Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT ( P = 0.042). Multivariable analysis showed a relationship between M/L and RRI ( P  = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation ( P   =  0.036, St. β = -0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. CONCLUSIONS The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption

Mapping a Sex Hormone–Sensitive Gene Determining Female Resistance to Liver Carcinogenesis in a Congenic F344.BN-Hcs4 Rat

Hepatocellular carcinoma (HCC) is prevalent in human and rodent males. Hepatocarcinogenesis is controlled by various genes in susceptible F344 and resistant Brown Norway (BN) rats. B alleles at Hcs4 locus, on RNO16, control neoplastic nodule volume. We constructed the F344.BN-Hcs4 recombinant congenic strain (RCS) by introgressing a 4.41-cM portion of Hcs4 from BN strain in an isogenic F344 background. Preneoplastic and neoplastic lesions were induced by the ''resistant hepatocyte'' protocol. Eight weeks after initiation, lesion volume and positivity for proliferating cell nuclear antigen (PCNA) were much higher in lesions of F344 than BN rats of both sexes. These variables were lower in females than in males. Lesion volume and PCNA values of male RCS were similar to those of F344 rats, but in females corresponded to those of BN females. Carcinomatous nodules and HCC developed at 32 and 60 weeks, respectively, in male F344 and congenics and, rarely, in F344 females. BN and congenic females developed only eosinophilic/clear cells nodules. Gonadectomy of congenic males, followed by B-estradiol administration, caused a decrease in Ar expression, an increase in Er-a expression, and development of preneoplastic lesions comparable to those from BN females. Administration of testosterone to gonadectomized females led to Ar increase and development of preneoplastic lesions as in F344 males. This indicates a role of homozygous B alleles at Hcs4 in the determination of phenotypic patterns of female RCS and presence at Hcs4 locus of a high penetrance gene(s), activated by estrogens and inhibited/unaffected by testosterone, conferring resistance to females in which the B alleles provide higher resistance. (Cancer Res 2006; 66(21): 10384-90

State of the low-carbon energy union : assessing the EU's progress towards its 2030 and 2050 climate objectives

Rather than examining aggregate emissions trends, this study delves deep into the dynamics affecting each sector of the EU energy system. It examines the structural changes taking place in power production, transport, buildings and industry, and benchmarks these with the changes required to reach the 2030 and 2050 targets. In so doing it aims to influence both the ambition and direction of future policy decisions, both at Member State and EU level. In order to assess the adequacy of the EU and its Member States policies with the 2030 and 2050 decarbonisation objectives, this study goes beyond the aggregate GHG emissions or energy use figures and analyse the underlying drivers of emission changes, following a sectoral approach (power generation, buildings, industry, and transport). Historical trends of emission drivers are compared with the required long-term deep decarbonisation pathways, which provide sectoral "benchmarks" or "corridors" against which to analyse the rate and direction of historical change for each Member State and the EU in aggregate. This approach allows the identification of the necessary structural changes in the energy system and policy interventions to reach deep decarbonisation, and therefore the comparison with the current policy programs at European and Member State level

Economic and environmental factors relevant to the Italian energy structure: Theoretical and applicative issues

The main objective of the project is to quantify, in the Italian context, some relationships among technology, energy and the economy, which can be used in an existing modeling framework to simulate the impact of atmospheric pollution control policies on the economic system. The framework consists of an Input-Output model with variable coefficients (the PFE model), and a Linear Programming model (MARKAL-Italy), linked by a two-way feedback. The specific object of this project is to expand the energy section of the I/O model to include inter-energy substitution elasticities. For this purpose, econometric models of translog input-demand equations are estimated for thirteen final energy consumption sectors and five energy commodity groups. As a necessary step, a data-base on energy consumption and prices for the various sectors covering the period 1966-1992 is created. A trend decomposition analysis, separating energy consumption in a growth component, an activity mix component and a technological change component, is performed on these data to obtain some insight on the evolution of final energy use. A better understanding of these processes is obtained through a review of energy and environmental policies in Italy over the period considered. Both the quantitative and the descriptive analyses stress the role of fiscal policy on energy products, carried out by the Italian governments, in shaping energy consumption patterns. The effect of including the estimated elasticities in the existing modeling framework is then tested in an experiment in which the technological and economic response of the energy system to changes in CO2 emissions standards is simulated via the LP model MARKAL, and the resulting changes in energy prices are used as inputs into the expanded I/O model. The latter, in turn, measures the impacts of each environmental tax policy scenario on total output, value added, final demand, imports, exports and prices. The results of this experiment, which assumes an explicit tax redistribution scheme, help define the feasibility margin for policy action on CO2 emission standards in the Italian context, indicating the structural changes that would take place as control policies tighten

U.S. smelter acid sales and revenues: The implications of adopting European acid trade and marketing practices

Sulphuric acid obtained as a byproduct of non-ferrous metal ore smelting is often the mandatory result of stringent environmental policies adopted in the industrialized countries to limit sulphur dioxide emissions. For the primary copper industry in the southwestern U.S., improvement of sulphuric acid marketing and distribution economies is a critical factor. In this thesis, through a comparison of the European and U.S. sulphuric acid market structure and organization, both the opportunity and the implications of adopting European acid marketing practices are discussed. A more centralized system of acid distribution, as in the European model, if applied to the U.S. smelter acid market, proves to be potentially beneficial for net revenue enhancement. A rationalization of the logistic aspects could substantially reduce acid transportation costs, allow repayment of at least average variable costs of production and improve southwestern smelter acid competitiveness in the domestic markets

Gender differences in the relationships between psychosocial factors and hypertension

Gender differences in the epidemiology, pathophysiology, clinical manifestations and outcomes of cardiovascular disease are well established but there is still a lack of awareness of this both in the general population and among healthcare providers. In addition to the traditionally recognized cardiovascular risk factors, more recently psychosocial risk factors such as stress, mood disorders, low socioeconomic status and sleep disorders have been linked to cardiovascular diseases and hypertension. Psychosocial factors may have different cardiovascular consequences in men and women; thus further efforts are required to explore pathophysiological mechanisms, to obtain gender-specific data from clinical trials and to translate this knowledge into everyday clinical practice

Essential Hypertension and Functional Microvascular Ageing

In healthy conditions, the endothelium plays a pivotal role in maintaining vascular homeostasis, mainly by the production of the relaxing factor nitric oxide (NO), which protects the vessel wall from those mechanisms favouring the development of vascular atherosclerosis. Aging is a powerful cardiovascular risk factors associated with endothelial dysfunction. In details, an alteration in the NO substrate L-arginine is the major factor responsible for endothelial dysfunction with advancing age, while reactive oxygen species (ROS) excess generation, which in turn reduce NO availability, plays a role in oldest individuals only. NO inhibition by ROS excess is the main cause of endothelial dysfunction which occurs in many other clinical conditions including arterial hypertension. Although hypertension induces early vascular aging in several arterial districts, however vascular features of physiological aging and hypertension are not necessarily similar. While an impaired NO availability represents the common final effect, aging and hypertension seem to adopt different mechanisms, at least at the level of microcirculation. Indeed, physiological aging shows a progressive reduced NO availability, while in advanced age some degree of oxidative stress emerges. In hypertensive patients, NO availability is early reduced, but the progression rate with age appears to be similar. Whether the hypertensive- and age-related vascular alterations represent only a mere additive effect of two independent risk factors resulting in endothelial dysfunction awaits further clarification

Age- and Sex-Specific Reference Values for Media/Lumen Ratio in Small Arteries and Relationship With Risk Factors

Small-artery remodeling is an early feature of target organ damage in hypertension and retains a negative prognostic value. The aim of the study is to establish age- and sex-specific reference values for media/lumen in small arteries obtained in humans by biopsy. Data from 91 healthy individuals and 200 individuals with cardiovascular risk factors in primary prevention from 4 Italian centers were pooled. Sex-specific equations for media/lumen in the healthy subpopulation, with age as dependent variable, were calculated. These equations were used to calculate predicted media/lumen values in individuals with risk factors and Z scores. The association between classical risk factors and Z scores was then explored by multiple regression analysis. A second-degree polynomial equation model was chosen to obtain sex-specific equations for media/lumen, with age as dependent variable. In the population with risk factors (111 men, age 50.5±14.0 years, hypertension 80.5%), media/lumen Z scores were independently associated with body mass index (standardized β=0.293, P=0.0001), total cholesterol (β=0.191, P=0.031), current smoking (β=0.238, P=0.0005), fasting blood glucose (β=0.204, P=0.003), systolic blood pressure (β=0.233, P=0.023), and female sex (β=0.799, P=0.038). A significant interaction between female sex and total cholesterol was found (β=-0.979, P=0.014). Results were substantially similar in the hypertensive subgroup. A method to calculate individual values of remodeling and growth index based on reference values was also presented. Age- and sex-specific percentiles of media/lumen in a healthy population were estimated. In a predominantly hypertensive population, media/lumen Z scores were associated with major cardiovascular risk factors, including body mass index, cholesterol, smoking, glucose, and systolic blood pressure. Significant sex differences were observed