Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease

The objective of the study is to assess the effects of emphysema on peak oxygen uptake ( $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ ) during a cardiopulmonary exercise test in patients with chronic obstructive pulmonary disease (COPD). We measured $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ and oxygen pulse in 80 patients with stable COPD exercising maximally. Oxygen saturation was measured by pulse oximetry (SpO₂), and the ventilatory response assessed by the ratio of tidal volume (V _T) at peak to slow vital capacity (SVC) at baseline, and by the percent increase of peak V _T over baseline. Computed tomography imaging (CT scan) served as the reference diagnostic standard for emphysema. Based on the panel-grading (PG) method, emphysema was rated absent or mild (PG ≤ 30, n = 54), or moderate to severe (PG > 30, n = 26). Multiple quantile regression was applied to estimate the effects of PG > 30 on $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ . At peak exercise, the patients with PG > 30 had significantly lower $ \dot{V}{\text{O}}_{ 2} $ , oxygen pulse and SpO₂, and featured a blunted ventilatory response with respect to those with PG ≤ 30 (p < 0.001). With multiple quantile regression, the effects of PG > 30 on $ \dot{V}{\text{O}}_{{ 2 {\text{Peak}}}} $ were only partially explained by the degree of lung hyperinflation, a substantial component being imputable to impairment of lung diffusing capacity. In conclusion, chronic obstructive pulmonary disease patients with moderate to severe emphysema feature significantly lower exercise tolerance than those with no or mild emphysema. Our findings underscore the need of tailoring therapeutic interventions for COPD to the predominant clinical phenotype to improve exercise capacity.     

Tryptophan availability selectively limits NO-synthase induction in macrophages

We studied the effects of tryptophan (TRP) availability on the synthesis and release of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) in interferon-gamma (IFN-gamma)-activated murine macrophages of the BAC1.2F5 cell line. IFN-gamma (100 U/ml) not only increased the synthesis and release of NO and TNF-alpha from these cells but also induced indoleamine-2,3-dioxygenase, the rate-limiting enzyme of TRP catabolism. This led to an increased metabolic flow through the kynurenine pathway and significantly decreased TRP levels in macrophage incubation media. Low TRP concentrations in the media, however, modified IFN-gamma effects. In TRP-"starved" cultures, in fact, the IFN-gamma-mediated NO synthase induction was significantly reduced, and the increased TNF-alpha synthesis and release were not affected. Our results suggest that a reduced local TRP availability may modify macrophage function and possibly the outcome of immune responses.     

Ecliptic method for the determination of backscatter into the beam monitor chambers in photon beams of medical accelerators

A new method to measure the effect of the backscatter into the beam monitor chambers in linear accelerators is introduced from first principles. The technique, applicable to high-energy photon beams, is similar to the well-known telescopic method although here the heavy blocks are replaced by a very small, centred block on the shadow tray, thus the name 'ecliptic method'. This effect, caused mainly by backscattering from the secondary collimators, is known to be an output factor constituent and must be accounted for when detailed calculations involving the machine's head are required. Since its magnitude is generally small, experimental errors might obscure the behaviour of the phenomenon. Consequently, the procedure introduced goes along with an uncertainty assessment. Our theory was confirmed via measurements in cobalt-60 beams, where the studied effect does not contribute to the output factor. Measurements were also performed on our Saturne 41 linear accelerator and the results were qualitatively similar to those described elsewhere. The collimation systems were studied separately by varying one jaw setting while keeping the other at its maximum value. In the light of these results, we deduced an algorithm that can correlate the former data with the effect of backscattering to the beam monitor chambers for any rectangular field within 0.5%, which is of the order of the experimental uncertainty (0.6%). As we show, the experimental procedure is safe, simple, not invasive for the linac and requires only basic dosimetry equipment.     

Elevated serum thiobarbituric acid reactive substances in clinically symptomatic schizophrenic males

Impaired antioxidant defenses are suggested to participate in the pathophysiology of schizophrenia. Altered superoxide dismutase (SOD) and increased lipid peroxidation, measured by the thiobarbituric acid reactive substances (TBARS), are increased in schizophrenia. The aim of this study was to determine the effects of clinical course and subtype on oxidative stress parameters. In this study, 68 male patients, classified according to DSM-IV schizophrenia subtypes and clinical course (partial remission, marked symptoms, and deteriorated), were studied, and TBARS and SOD measured. Mean serum SOD and mean serum TBARS concentrations were similarly not significantly different among different subtypes (paranoid, disorganized and undifferentiated). However, marked symptoms status was associated with higher TBARS levels compared to the deteriorated group. This suggests a possible relationship between symptom acuity and oxidative stress in males.     

Infections caused by Scedosporium spp

Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.     

Biphasic effect of linoleic acid on connexin 46 hemichannels

Connexins form hemichannels at undocked plasma membranes and gap-junction channels (GJCs) at intercellular contacting zones. Under physiological conditions, hemichannels have low open probabilities, but their activation under pathological conditions, such as ischemia, induces and/or accelerates cell death. Connexin 46 (Cx46) is a major connexin of the lens, and mutations of this connexin induce cataracts. Here, we report the effects of linoleic acid (LA) on the electrical properties of Cx46 GJCs and hemichannels expressed in Xenopus laevis oocytes. LA has a biphasic effect, increasing hemichannel current at 0.1 μM and decreasing it at concentrations of 100 μM or higher. The effects of extracellular and microinjected LA conjugated to coenzyme A (LA-CoA) suggest that the current activation site is accessible from the intracellular but not extracellular compartment, whereas the current inhibitory site is either located in a region of the hemichannel pore inaccessible to intracellular LA-CoA, or requires crossing of LA through an organelle membrane. Experiments with other fatty acids demonstrated that the block of hemichannels depends on the presence of a hydrogenated double bond at position 9 and is directly proportional to the number of double bonds. Experiments in paired oocytes expressing Cx46 showed that LA does not affect GJCs. The block by unsaturated fatty acids reported here opens the possibility that increases in the concentration of these lipids in the lens induce cataract formation by blocking Cx46 hemichannels.     

Transcranial magnetic stimulation of posterior parietal cortex affects decisions of hand choice

Deciding which hand to use for an action is one of the most frequent decisions people make in everyday behavior. Using a speeded reaching task, we provide evidence that hand choice entails a competitive decision process between simultaneously activated action plans for each hand. We then show that single-pulse transcranial magnetic stimulation to the left posterior parietal cortex biases this competitive process, leading to an increase in ipsilateral, left hand reaches. Stimulation of the right posterior parietal cortex did not alter hand choice, suggesting a hemispheric asymmetry in the representations of reach plans. These results are unique in providing causal evidence that the posterior parietal cortex is involved in decisions of hand choice.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.