153 research outputs found
Incontinence, bladder neck mobility, and sphincter ruptures in primiparous women
<p>Abstract</p> <p>Objective</p> <p>To compare the function of the pelvic floor in primiparae before and during pregnancy with the status post partum concerning symptoms of incontinence, sphincter ruptures, bladder-neck mobility and the influence of the different modes of deliveries.</p> <p>Methods</p> <p>Questionnaire evaluating symptoms of urinary and anal incontinence in nulliparous women before and after delivery and correlating these symptoms with functional changes of the pelvic floor based on a careful gynaecologic examination as well as perineal and endoanal ultrasound.</p> <p>Results</p> <p>112 women were included in our study and came for the first visit, 99 women returned for follow-up 6 months after childbirth. Stress and flatus incontinence significantly increased from before pregnancy (3 and 12%) to after childbirth (21 and 28%) in women with spontaneous delivery or vacuum extraction. No new symptoms occurred after c-section. There was no significant difference between the bladder neck position before and after delivery. The mobility of the bladder neck was significantly higher after vaginal delivery using a vacuum extraction compared to spontaneous delivery or c-section.</p> <p>The bladder neck in women with post partum urinary stress incontinence was significantly more mobile than in continent controls. The endoanal ultrasound detected seven occult sphincter defects without any correlation to symptoms of anal incontinence.</p> <p>Conclusion</p> <p>Several statistically significant changes of the pelvic floor after delivery were demonstrated. Spontaneous vaginal delivery or vacuum extraction increases the risk for stress or anal incontinence, delivery with vacuum extraction leads to higher bladder neck mobility and stress incontinent women have more mobile bladder necks than continent women.</p
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)
A Clathrin light chain A reporter mouse for in vivo imaging of endocytosis
Clathrin-mediated endocytosis (CME) is one of the best studied cellular uptake pathways and its contributions to nutrient uptake, receptor signaling, and maintenance of the lipid membrane homeostasis have been already elucidated. Today, we still have a lack of understanding how the different components of this pathway cooperate dynamically in vivo. Therefore, we generated a reporter mouse model for CME by fusing eGFP endogenously in frame to clathrin light chain a (Clta) to track endocytosis in living mice. The fusion protein is expressed in all tissues, but in a cell specific manner, and can be visualized using fluorescence microscopy. Recruitment to nanobeads recorded by TIRF microscopy validated the functionality of the Clta-eGFP reporter. With this reporter model we were able to track the dynamics of Alexa594-BSA uptake in kidneys of anesthetized mice using intravital 2-photon microscopy. This reporter mouse model is not only a suitable and powerful tool to track CME in vivo in genetic or disease mouse models it can also help to shed light into the differential roles of the two clathrin light chain isoforms in health and disease
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Selective liposomal transport through blood brain barrier disruption in ischaemic stroke reveals two distinct therapeutic opportunities
The development of effective therapies for stroke continues to face repeated translational failures. Brain endothelial cells form paracellular and transcellular barriers to many blood-borne therapies and the development of efficient delivery strategies is highly warranted. Here, in a mouse model of stroke, we show selective recruitment of clinically used liposomes into the ischaemic brain that correlates with biphasic blood brain barrier (BBB) breakdown. Intravenous administration of liposomes into mice exposed to transient middle cerebral artery occlusion took place at early (0.5h and 4h) and delayed (24h and 48h) timepoints, covering different phases of BBB disruption after stroke. Using a combination of in vivo real-time imaging and histological analysis we show that selective liposomal brain accumulation coincides with biphasic enhancement in transcellular transport followed by a delayed impairment to the paracellular barrier. This process precedes neurological damage in the acute phase and maintains long-term liposomal co-localisation within the neurovascular unit, which could have great potential for neuroprotection. Levels of liposomal uptake by glial cells are similarly selectively enhanced in the ischaemic region late after experimental stroke (2-3 days), highlighting their potential for blocking delayed inflammatory responses or shifting the polarization of microglia/macrophages towards brain repair. These findings demonstrate the capability of liposomes to maximise selective translocation into the brain after stroke and identify two windows for therapeutic manipulation. This emphasizes the benefits of selective drug delivery for efficient tailoring of stroke treatments
Transition to Long Range Magnetic Order in the Highly Frustrated Insulating Pyrochlore Antiferromagnet Gd_2Ti_2O_7
Experimental evidence from measurements of the a.c. and d.c. susceptibility,
and heat capacity data show that the pyrochlore structure oxide, Gd_2Ti_2O_7,
exhibits short range order that starts developing at 30K, as well as long range
magnetic order at K. The Curie-Weiss temperature, =
-9.6K, is largely due to exchange interactions. Deviations from the Curie-Weiss
law occur below 10K while magnetic heat capacity contributions are found
at temperatures above 20K. A sharp maximum in the heat capacity at K
signals a transition to a long range ordered state, with the magnetic specific
accounting for only 50% of the magnetic entropy. The heat capacity above
the phase transition can be modeled by assuming that a distribution of random
fields acts on the ground state for Gd. There is no
frequency dependence to the a.c. susceptibility in either the short range or
long range ordered regimes, hence suggesting the absence of any spin-glassy
behavior. Mean field theoretical calculations show that no long range ordered
ground state exists for the conditions of nearest-neighbor antiferromagnetic
exchange and long range dipolar couplings. At the mean-field level, long range
order at various commensurate or incommensurate wave vectors is found only upon
inclusion of exchange interactions beyond nearest-neighbor exchange and dipolar
coupling. The properties of Gd$_2Ti_2O_7 are compared with other geometrically
frustrated antiferromagnets such as the Gd_3Ga_5O_{12} gadolinium gallium
garnet, RE_2Ti_2O_7 pyrochlores where RE = Tb, Ho and Tm, and Heisenberg-type
pyrochlore such as Y_2Mo_2O_7, Tb_2Mo_2O_7, and spinels such as ZnFe_2O_4Comment: Letter, 6 POSTSCRIPT figures included. (NOTE: Figure 5 is not
included --) To appear in Physical Review B. Contact:
[email protected]
Gestational Weight Gain and Body Mass Index in Children: Results from Three German Cohort Studies
Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring's body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.
We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring's mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5-6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.
In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m(2) of 'real' BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.
Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers
Vasodilator factors in the systemic and local adaptations to pregnancy
We postulate that an orchestrated network composed of various vasodilatory systems participates in the systemic and local hemodynamic adaptations in pregnancy. The temporal patterns of increase in the circulating and urinary levels of five vasodilator factors/systems, prostacyclin, nitric oxide, kallikrein, angiotensin-(1–7) and VEGF, in normal pregnant women and animals, as well as the changes observed in preeclamptic pregnancies support their functional role in maintaining normotension by opposing the vasoconstrictor systems. In addition, the expression of these vasodilators in the different trophoblastic subtypes in various species supports their role in the transformation of the uterine arteries. Moreover, their expression in the fetal endothelium and in the syncytiotrophoblast in humans, rats and guinea-pigs, favour their participation in maintaining the uteroplacental circulation. The findings that sustain the functional associations of the various vasodilators, and their participation by endocrine, paracrine and autocrine regulation of the systemic and local vasoactive changes of pregnancy are abundant and compelling. However, further elucidation of the role of the various players is hampered by methodological problems. Among these difficulties is the complexity of the interactions between the different factors, the likelihood that experimental alterations induced in one system may be compensated by the other players of the network, and the possibility that data obtained by manipulating single factors in vitro or in animal studies may be difficult to translate to the human. In addition, the impossibility of sampling the uteroplacental interface along normal pregnancy precludes obtaining longitudinal profiles of the various players. Nevertheless, the possibility of improving maternal blood pressure regulation, trophoblast invasion and uteroplacental flow by enhancing vasodilation (e.g. L-arginine, NO donors, VEGF transfection) deserves unravelling the intricate association of vasoactive factors and the systemic and local adaptations to pregnancy
Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors
Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation due to a lack of mechanistic understanding. Specifically, CXCL4 (Platelet Factor 4, PF4) has no established receptor that explains its function. Here, we use biophysical, in vitro, and in vivo techniques to determine the mechanism underlying CXCL4-mediated leukocyte recruitment. We demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars on proteoglycans within the endothelial extracellular matrix, resulting in increased adhesion of leukocytes to the vasculature, increased vascular permeability, and non-specific recruitment of a range of leukocytes. Furthermore, GAG sulfation confers selectivity onto chemokine localization. These findings present mechanistic insights into chemokine biology and provide future therapeutic targets
Contrast Adaptation Contributes to Contrast-Invariance of Orientation Tuning of Primate V1 Cells
BACKGROUND: Studies in rodents and carnivores have shown that orientation tuning width of single neurons does not change when stimulus contrast is modified. However, in these studies, stimuli were presented for a relatively long duration (e. g., 4 seconds), making it possible that contrast adaptation contributed to contrast-invariance of orientation tuning. Our first purpose was to determine, in marmoset area V1, whether orientation tuning is still contrast-invariant with the stimulation duration is comparable to that of a visual fixation. METHODOLOGY/PRINCIPAL FINDINGS: We performed extracellular recordings and examined orientation tuning of single-units using static sine-wave gratings that were flashed for 200 msec. Sixteen orientations and three contrast levels, representing low, medium and high values in the range of effective contrasts for each neuron, were randomly intermixed. Contrast adaptation being a slow phenomenon, cells did not have enough time to adapt to each contrast individually. With this stimulation protocol, we found that the tuning width obtained at intermediate contrast was reduced to 89% (median), and that at low contrast to 76%, of that obtained at high contrast. Therefore, when probed with briefly flashed stimuli, orientation tuning is not contrast-invariant in marmoset V1. Our second purpose was to determine whether contrast adaptation contributes to contrast-invariance of orientation tuning. Stationary gratings were presented, as previously, for 200 msec with randomly varying orientations, but the contrast was kept constant within stimulation blocks lasting >20 sec, allowing for adaptation to the single contrast in use. In these conditions, tuning widths obtained at low contrast were still significantly less than at high contrast (median 85%). However, tuning widths obtained with medium and high contrast stimuli no longer differed significantly. CONCLUSIONS/SIGNIFICANCE: Orientation tuning does not appear to be contrast-invariant when briefly flashed stimuli vary in both contrast and orientation, but contrast adaptation partially restores contrast-invariance of orientation tuning
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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