The Relationship Between Renal Resistive Index,Arterial Stiffness,and Atherosclerotic Burden: The Link Between Macrocirculation and Microcirculation

The renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status that can be generalized to the whole of the arterial tree. Its association with large‐vessel dysfunction, such as arterial stiffness or the atherosclerotic burden, can help to establish physiopathological associations between macrocirculation and microcirculation. The authors conducted a cross‐sectional study of hypertensive patients (n=202) and a healthy control group (n=16). Stiffness parameters, atherosclerotic burden, and determination of the RRI in both kidneys were performed. The average RRI was 0.69±0.08 and was significantly greater in patients with diabetes and chronic kidney disease. Renal resistive index positively correlated with age, creatinine, and albuminuria. Positive correlations were found with arterial stiffness parameters (pulse wave velocity, ambulatory arterial stiffness index, and 24‐hour pulse pressure), as well as atherosclerotic burden and endothelial dysfunction measured as asymmetric dimethylarginine in serum. In the multivariate analysis, independent factors for increased RRI were age, renal function, 24‐hour diastolic blood pressure, and arterial stiffness. The authors concluded that there is an independent association between renal hemodynamics and arterial stiffness. This, together with the atherosclerotic burden and endothelial dysfunction, suggests that there is a physiopathologic relationship between macrovascular and microvascular impairment.     

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.     

Potential Role of Proinflammatory Cytokines in the Pathogenetic Mechanisms of Vascular Lesions in Goats Naturally Infected with Bluetongue Virus Serotype 1

In vitro studies have demonstrated that bluetongue virus (BTV)‐induced vasoactive mediators could contribute to the endothelial cells dysfunction and increased vascular permeability responsible of lesions characteristic of bluetongue (BT) like oedema, haemorrhages and ischaemic necrosis in different tissues. However, few in vivo studies have been carried out to clarify the causes of these lesions. The aim of this study was to elucidate in vivo the pathogenetic mechanisms involved in the appearance of vascular lesions in different organs during BT. For this purpose, tissue samples from goats naturally infected with bluetongue virus serotype 1 (BTV‐1) were taken for histopathological and immunohistochemical studies to determine the potential role of proinflammatory cytokines (tumour necrosis factor alpha, TNFα and interleukin one alpha, IL‐1α) in the increased vascular permeability and their relationship with the presence of virus. Gross and histopathological examination revealed the presence of vascular damage leading to generalized oedema and haemorrhages. Immunohistochemical studies displayed that endothelial injury may have been due to the direct pathogenic effect of BTV infection on endothelial cells or may be a response to inflammatory mediators released by virus‐infected endothelial cells and, possibly, other cell types such as monocytes/macrophages. These preliminary results of what appears to be the first in vivo study of tissue damage in small BT‐infected ruminants suggest a direct link between the appearance of vascular changes and the presence of BTV‐induced vasoactive cytokines.