Reference intervals of aortic pulse wave velocity assessed with an oscillometric device in healthy children and adolescents from Argentina

Age-related reference intervals (RIs) of aortic pulse wave velocity (Ao-PWV) obtained from a large healthy population are lacking in South America. The aims of this study were to determine Ao-PWV RIs in a cohort of healthy children and adolescents from Argentina and to generate year-to-year percentile curves.

Ao-PWV was measured in 1000 healthy subjects non-exposed to traditional cardiovascular risk factors (Age: 10–22 y. o., 56% males). First, we evaluated if RIs for males and females were necessaries (correlation and covariate analysis). Second, mean (M) and standard deviation (SD) age-related equations were obtained for cf-PWV, using parametric regression methods based on fractional polynomials. Third, age-specific (year to year) percentiles curves (for all, males and females children and adolescents) were generated using the standard normal distribution. They were, age-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th and 99th percentile curves and values.

After covariate analysis (i.e., adjusting by age, jugulum-symphysis distance, body weight and height), specific RIs for males and females of children and adolescents were evidenced as necessaries. The equations were

For all subjects:

Ao-PWV_Mean = 4.98 + 12.86x10^?5 Age³.

Ao-PWV_SD = 0.47 + 21.00x10^?6Age³.

For girls:

Ao-PWV_Mean = 5.07 + 10.23x10^?5Age³.

Ao-PWV_SD = 0.50 + 10.00x10^?6Age³.

For boys:

Ao-PWV_Mean = 4.87 + 15.81x10^?5Age³.

Ao-PWV_SD = 0.46 + 22.34x10^?6Age³.

Our study provides the largest database to-date concerning Ao-PWV in healthy children and adolescents in Argentina. Age-related equations (M and SD values) for Ao-PWV are reported by the first time. Specific RIs and percentiles of Ao-PWV are now available according to age and sex for an Argentinian population.     

Arterial wall structure and dynamics in type 2 diabetes mellitus methodological aspects and pathophysiological findings

Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.     

Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression

Aim To determine whether depression and family history of alcoholism are associated with heightened sweet preferences in children, before they have experienced alcohol or tobacco and at a time during the life‐span when sweets are particularly salient. Design Between‐ and within‐subject experimental study. Participants Children, 5–12 years old (n = 300), formed four groups based on family history of alcohol dependence up to second‐degree relatives [positive (FHP) versus negative (FHN)] and depressive symptoms as determined by the Pictorial Depression Scale [depressed (PDEP) versus non‐depressed (NDEP)]. Measurements Children were tested individually to measure sucrose preferences, sweet food liking and, for a subset of the children, the analgesic properties of sucrose versus water during the cold pressor test. Findings The co‐occurrence of having a family history of alcoholism and self‐reports of depressive symptomatology was associated significantly with a preference for a more concentrated sucrose solution, while depressive symptomatology alone was associated with greater liking for sweet‐tasting foods and candies and increased pain sensitivity. Depression antagonized the analgesic properties of sucrose. Conclusions While children as a group innately like sweets and feel better after eating them, the present study reveals significant contributions of family history of alcoholism and depression to this effect. Whether the heightened sweet preference and the use of sweets to alleviate depression are markers for developing alcohol‐related problems or responses that are protective are important areas for future research.     

Selective white matter pathology induces a specific impairment in spatial working memory

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice.     

Delirium in palliative care

Delirium is highly prevalent in cancer patients with advanced disease. Frequently a preterminal event, the condition is a sign of significant physiologic disturbance, typically involving multiple medical etiologies including infection, organ failure, adverse medication effects, and in rare situations, paraneoplastic syndromes. Unfortunately, delirium is frequently unrecognized or misdiagnosed and, therefore, inappropriately treated or untreated in terminally ill patients. The clinical features of delirium are numerous and encompass a variety of neuropsychiatric symptoms common to other psychiatric disorders. Three clinical subtypes of delirium, based on arousal disturbance and psychomotor behavior, have been described: hyperactive, hypoactive, and mixed. The differential diagnosis for delirium includes depression, mania, psychosis, and dementia. Numerous instruments have been developed to aid the clinician in rapidly screening for the disorder. Standard management requires an investigation of the etiologies, correction of the contributing factors, and management of symptoms. Symptomatic and supportive therapies, including numerous pharmacologic approaches, are important, but several aspects of the use of neuroleptics and other agents in the management of delirium in the dying patient remain controversial.     

The 'immunological-synapse' at its APC side in relapsing and secondary-progressive multiple sclerosis: modulation by interferon-beta

Reciprocal interactions between T cells and antigen-presenting cells (APCs) within the 'Immunological-Synapse' (IS) govern immune cell autoreactivity in multiple sclerosis (MS). The present study examined the expression of a range of co-stimulatory molecules: CD40, CD54, CD80, CD86 and HLA-DR, on the cell-surface of CD14(+) peripheral blood monocytes (PBM) from relapsing-remitting (RR) and secondary-progressive (SP)-MS patients, prior to and during 1 year of Interferon (IFN)-beta-1a (Rebif(R)) therapy. Prior to treatment, patients from both MS subtypes expressed elevated CD80 and reduced CD40 levels in comparison to controls. CD86 expression was significantly reduced in SP compared to RR patients and controls. IFN-beta therapy led to a significant reduction in the expression of CD54 and CD80 in both groups of patients as well as to elevation of CD40 and CD86 expression in SP patients. These results confirm IFN-mediated modulation of the APC surface within the immunological-synapse and implicate CD80 and CD86 as targets for interventional therapies in MS as well as other Th1-mediated autoimmune diseases.     

Nonpeptide antagonists of AT1 receptor for angiotensin II delay the onset of acute respiratory distress syndrome

We have previously reported that losartan, a selective antagonist of AT1 receptors for angiotensin II (AII), strongly suppresses the activation of neutrophils by N-formylmethionyl-leucyl-phenylalanine (fMLP) through a mechanism that does not involve inhibition of AT1 receptors. Herein, we analyze whether losartan would prevent the development of the acute respiratory distress syndrome (ARDS) triggered by lung bacterial infection. We found that losartan (0.2-200 microg/kg/min) delays the onset of ARDS in Wistar rats challenged by i.t. instillation of Bordetella bronchiseptica. Although this effect was associated with a significant inhibition of lung-neutrophil recruitment, lung bacterial clearance was not impaired but rather, it was significantly improved. We also found that another nonpeptide AT1 receptor blocker, irbesartan, exerted similar effects to losartan, i.e., it was also able to inhibit neutrophil activation by fMLP and to delay the onset of ARDS in B. bronchiseptica-challenged rats. Neither the inhibitor of angiotensin-converting enzyme captopril, nor the nonselective peptide inhibitor of AII receptors saralasin reproduced these effects. Our data are consistent with the possibility that nonpeptide AT1 receptor blockers delay the onset of ARDS triggered by bacterial infection through a mechanism dependent, at least in part, on their ability to prevent neutrophil activation by N-formyl-peptides.     

Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice 1 month after STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: (a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; (b) abnormal expression of early gene products associated with neuronal activation, including a high number of Jun + neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; (c) augmented activity of NADPH-diaphorase, linked to oxidative stress, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex.