Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies

Aims: The aim of the presented study was to clarify the relationship between the pulsatility index of the uterine arteries and the maternal cubital artery and peripheral concentrations of the metabolites of nitric oxide (NO) and its second messenger cyclic guanosinmonophophate (cGMP) during the normal course of pregnancy and postpartum. Methods: 49 uncomplicated pregnancies were investigated every 46 weeks until delivery, 29 of them were additionally investigated postpartum. Paralleling each Doppler sonografic investigation maternal blood and urine samples were taken. The measurements of nitrite/ nitrate and cGMP were performed with a colorimetric and radio immuno assay. We demonstrate a significant decrease of the PI of the uterine arteries and of the cubital artery with inverse correlation to advancing gestational age. Results: The concentrations of nitrite/nitrate and cGMP remain stable during gestation and do not correlate to the PI of the uterine and cubital artery. Postpartum a reincrease in the uterine and peripheral resistance can be shown. The concentrations of urinary cGMP and nitrite/ nitrate as well as plasma cGMP remain unchanged, whereas plasma nitrite/nitrate decreases postpartum. Conclusions: The status of NO biosyntheses in normal pregnancy remains controversial. We hypothesize further systemically acting mediators which contribute to the decreasing vascular resistance

The effect of acute and chronic elevation of temperature on aspects of the physiology of Antarctic nototheniid fishes

The notothenioid fishes, which dominate the upper shelf habitats of the Antarctic Continental Shelf, have evolved in a relatively thermally stable environment for at least 10-15 million years. With the upper lethal limits of these fishes around 4-6°C and the lower limits set by the freezing point of seawater, they are described as extreme stenotherms. As a result, it has been hypothesized that these fishes should exhibit marked responses to acute changes in temperature, but that acclimatory effects may be reduced with prolonged exposure to elevated temperatures is not likely to increase their thermal tolerance. This study was designed to investigate aspects of the physiological response of Antarctic nototheniid fishes to both acute and prolonged increases in temperature. Changes in haematology, metabolic scope for activity, cardiovascular performance, aerobic swimming ability and the capacity to tolerate additional stressors were investigated in the Antarctic nototheniid Pagothenia borchgrevinki, with some comparative work carried out on the closely related Trematomus bernacchii and the temperate-water notothenioids Notothenia angustata and Bovichtus variegatus. The responses to an acute change in temperature were found to vary between the closely related Antarctic nototheniids, most likely as a consequence of their differing ecotypes. Plasma glucose levels were measured in these fish for the first time and exhibited a delayed rise in response to an acute increase in temperature. Cardiac performance was found to be closely linked to prolonged swimming ability through thermal changes in P. borchgrevinki, indicating a cardiac limitation of aerobic performance. One factor which became apparent was that the acclimation of Antarctic nototheniids to temperatures only ~2°C above their habitat temperature results in a decrease in thermal sensitivity of a variety of physiological parameters. The most notable finding was that P. borchgrevinki possesses sufficient phenotypic plasticity to warm-acclimate prolonged swimming ability, cardiac performance and osmo-regulatory capacity after 4-6 weeks of exposure to 4°C, suggesting that the Antarctic nototheniids may not be as extremely stenothermal as previously assumed and that the consequences of climate change may not be as dire as has been predicted

Decreased Haemodynamic Response and Decoupling of Cortical Gamma Band Activity and Tissue Oxygen Perfusion after Striatal Interleukin-1 Injection.

Background: Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow; known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study we set out to investigate if increased cerebral levels of IL-1 have a negative effect on neurovascular coupling in the cortex in response to sensory stimulation. Methods: We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intrastriatal injection of interleukin-1β or vehicle. First, we used two dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of IL-1β. Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a ‘Clark-style’ electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs) respectively. Results: 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-bandactivity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post IL-1β injection, whereas IL-1β had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1β-injected group. Conclusions: We conclude that intrastriatal IL-1β decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1β plays a part, especially those involving reductions in cerebral blood flow (such as stroke)

Four projection streams from primate V1 to the cytochrome oxidase stripes of V2

In the primate visual system, areas V1 and V2 distribute information they receive from the retina to all higher cortical areas, sorting this information into dorsal and ventral streams. Therefore, knowledge of the organization of projections between V1 and V2 is crucial to understand how the cortex processes visual information. In primates, parallel output pathways from V1 project to distinct V2 stripes. The traditional tripartite division of V1-to-V2 projections was recently replaced by a bipartite scheme, in which thin stripes receive V1 inputs from blob columns, and thick and pale stripes receive common input from interblob columns. Here, we demonstrate that thick and pale stripes, instead, receive spatially segregated V1 inputs and that the interblob is partitioned into two compartments: the middle of the interblob projecting to pale stripes and the blob/interblob border region projecting to thick stripes. Double-labeling experiments further demonstrate that V1 cells project to either thick or pale stripes, but rarely to both. We also find laminar specialization of V1 outputs, with layer 4B contributing projections mainly to thick stripes, and no projections to one set of pale stripes. These laminar differences suggest different contribution of magno, parvo, and konio inputs to each V1 output pathway. These results provide a new foundation for parallel processing models of the visual system by demonstrating four V1-to-V2 pathways: blob columns-to-thin stripes, blob/interblob border columns-to-thick stripes, interblob columns-to-pale(lateral) stripes, layer 2/3– 4A interblobs-to-pale(medial) stripes

Magnitude and Mechanism of Siderophore-Mediated Competition at Low Iron Solubility in the Pseudomonas aeruginosa Pyochelin System

A central question in microbial ecology is whether microbial interactions are predominantly cooperative or competitive. The secretion of siderophores, microbial iron chelators, is a model system for cooperative interactions. However, siderophores have also been shown to mediate competition by sequestering available iron and making it unavailable to competitors. The details of how siderophores mediate competition are not well understood, especially considering the complex distribution of iron phases in the environment. One pertinent question is whether sequestering iron through siderophores can indeed be effective in natural conditions; many natural environments are characterized by large pools of precipitated iron, and it is conceivable that any soluble iron that is sequestered by siderophores is replenished by the dissolution of these precipitated iron sources. Our goal here was to address this issue, and investigate the magnitude and mechanism of siderophore-mediated competition in the presence of precipitated iron. We combined experimental work with thermodynamic modeling, using Pseudomonas aeruginosa as a model system and ferrihydrite precipitates as the iron source with low solubility. Our experiments show that competitive growth inhibition by the siderophore pyochelin is indeed efficient, and that inhibition of a competitor can even have a stronger growth-promoting effect than solubilization of precipitated iron. Based on the results of our thermodynamic models we conclude that the observed inhibition of a competitor is effective because sequestered iron is only very slowly replenished by the dissolution of precipitated iron. Our research highlights the importance of competitive benefits mediated by siderophores, and underlines that the dynamics of siderophore production and uptake in environmental communities could be a signature of competitive, not just cooperative, dynamics

Recommendations for raloxifene use in daily clinical practice in the Swiss setting

Background/aim: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. Methods: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. Results: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2×2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. Conclusion: Postmenopausal women between 50 and 70years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precaution

Increased Serum Concentrations of Circulating Glycocalyx Components in HELLP Syndrome Compared to Healthy Pregnancy: An Observational Study

Severe inflammation has been shown to induce a shedding of the endothelial glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), impede the thickness of the EGX. While a controlled inflammatory reaction occurs already in normal pregnancy, women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory response. This study investigates the shedding of the glycocalyx during normal pregnancy and in women with HELLP syndrome. Glycocalyx components (syndecan 1, heparan sulfate, and hyaluronic acid) were measured in serum of healthy women throughout pregnancy (4 time points, n = 26), in women with HELLP syndrome (n = 17) before delivery and in nonpregnant volunteers (n = 10). Serum concentrations of TNF-alpha and soluble TNF-alpha receptors (sTNF-Rs) were assessed once in all 3 groups. Syndecan 1 serum concentrations constantly rose throughout normal pregnancy. Immediately before delivery, a 159-fold increase was measured compared to nonpregnant controls (P < .01). Even higher amounts were observed in patients with HELLP prior to delivery (median 12 252 ng/mL) compared to healthy women matched by gestational age (median 5943 ng/mL; P < .01). Relevantly, increased serum levels of heparan sulfate, hyaluronic acid, and sTNF-Rs were only detected in patients with HELLP (P < .01). These findings suggest that considerable amounts of syndecan 1 are released into maternal blood during uncomplicated pregnancy. The HELLP syndrome is associated with an even more pronounced shedding of glycocalyx components. The maternal vasculature as well as the placenta has to be discussed as a possible origin of circulating glycocalyx components

Is infant neural sensitivity to vocal emotion associated with mother-infant relational experience?

An early understanding of others’ vocal emotions provides infants with a distinct advantage for eliciting appropriate care from caregivers and for navigating their social world. Consistent with this notion, an emerging literature suggests that a temporal cortical response to the prosody of emotional speech is observable in the first year of life. Furthermore, neural specialisation to vocal emotion in infancy may vary according to early experience. Neural sensitivity to emotional non-speech vocalisations was investigated in 29 six-month-old infants using near-infrared spectroscopy (fNIRS). Both angry and happy vocalisations evoked increased activation in the temporal cortices (relative to neutral and angry vocalisations respectively), and the strength of the angry minus neutral effect was positively associated with the degree of directiveness in the mothers’ play interactions with their infant. This first fNIRS study of infant vocal emotion processing implicates bilateral temporal mechanisms similar to those found in adults and suggests that infants who experience more directive caregiving or social play may more strongly or preferentially process vocal anger by six months of age