Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Image formation in vibro-acoustography with depth-of-field effects.

We study the image formation of vibro-acoustography systems based on a concave sector array transducer taking into account depth-of-field effects. The system point-spread function (PSF) is defined in terms of the acoustic emission of a point-target in response to the dynamic radiation stress of ultrasound. The PSF on the focal plane and the axis of the transducer are presented. To extend the obtained PSF to the 3D-space, we assume it is a separable function in the axial direction and the focal plane of the transducer. In this model, an image is formed through the 3D convolution of the PSF with an object function. Experimental vibro-acoustography images of a breast phantom with lesion-like inclusions were compared with simulated images. Results show that the experimental images are in good agreement with the proposed model.     

Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

Protein nutrition and amino acid metabolism after 4 weeks of total parenteral nutrition with a mixture of 14 dipeptides: serendipitous observations on effects of sepsis in baboons

We investigated parameters of nutrition, metabolism, and organ function after 4 wk of total parenteral nutrition (TPN) in baboons receiving either dipeptides or amino acids as the nitrogen source. The two groups showed no significant difference with respect to gain in body weight, nitrogen balance, plasma and muscle concentrations of amino acids, plasma concentrations of proteins, and leucine incorporation into muscle protein. All dipeptides were efficiently utilized as evidenced by trace concentrations of dipeptides in plasma and urine; they produced no deleterious effect on the function of liver, kidney, or immune system. Development of infection in several baboons increased urinary excretion of urea nitrogen but had no effect on urinary excretion of dipeptides and amino acids with the single exception of taurine, which was greatly increased. In conclusion, the data show long-term efficacy and safety of the dipeptide mixture as the sole nitrogen source for TPN.     

Extent of ictal origin in mesial temporal sclerosis patients monitored with subdural intracranial electrodes predicts outcome.

In patients with mesiotemporal sclerosis, posterior hippocampal involvement at the ictal onset is not associated with an excellent outcome. A study confirmed that ictal onset in the posterior parahippocampal gyrus is associated with a less favorable outcome compared with ictal onset in the anterior parahippocampal gyrus in patients with mesiobasal temporal lobe epilepsy who are undergoing foramen ovale recording. The authors hypothesized that involvement of the two medial contact points of posterior basal temporal subdural (SD) strip at the ictal onset, representing ictal onset in the posterior parahippocampal gyrus, may also adversely influence the surgical outcome. With this objective, the authors assessed the incidence of posterior basal temporal SD strip (the two medial contact points) involvement at the ictal onset in patients with mesiotemporal sclerosis and determined whether presence of this finding influenced surgical outcome. Thirty-six patients with mesiotemporal sclerosis underwent a single SD grid (lateral frontotemporal) and strips (three basal temporal and one orbitosubfrontal) monitoring. Based on the earliest involvement of basal temporal strips (the two medial contact points) during the seizure, patients were classified into (1) anterior and/or middle basal temporal, or (2) posterior basal temporal (with or without involvement of anterior and/or middle basal temporal) ictal onset groups. A temporal lobectomy with adequate resection of the ictal onset zone was performed in all patients. Surgical outcome was based on Engel's classification. Six of 36 (17%) patients were classified into the posterior basal temporal ictal onset group. Only two patients from the posterior basal temporal ictal onset group experienced a good outcome compared with 26 of 30 patients from anterior and/or middle basal temporal ictal onset group (P = 0.01). In patients with mesiotemporal sclerosis who were monitored with SD electrodes, involvement of the two medial contact points of posterior basal temporal strip at the ictal onset (representing ictal onset in the posterior parahippocampal gyrus) occurred in 17% of the patients. These patients might not experience an excellent surgical outcome despite including the ictal onset zone in resection. These findings may be useful in presurgical counseling of patients with mesiotemporal sclerosis who undergo intracranial SD monitoring.