bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyaluronan Secretion into the Synovial Cavity of Rabbit Knees and Comparison with Albumin Turnover
Authors: Coleman P. J. , Scott D. , Ray J. , Mason R. M. , Levick J. R. 
Published: September 2004

Hyaluronan is not only a lubricant but also enhances the synovial lining's resistance to fluid outflow. This finding led to the proposal that hyaluronan (> 2 × 106Da, ∼210 nm radius) may escape across the synovial lining less freely than smaller solutes (e.g. albumin, 6.7 × 104 Da, 3.6 nm radius) or water. Here multiple washouts were used to measure intra‐articular hyaluronan mass and secretion rate in rabbit knees, leading to an estimate of hyaluronan turnover time. Plasma albumin permeation into the joint cavity was also measured to enable comparison of turnover times between molecules of very disparate size.
Endogenous hyaluronan mass in the joint cavity, analysed by high performance liquid chromatography of joint washes, was 182 ± 9.9 μg (mean ± S.E.M; n= 21). Since hyaluronan concentration in synovial fluid averages 3.62 ± 0.19 μg μl−1, the endogenous synovial fluid volume was calculated to be 50 μl (mass/concentration), about double the aspiratable volume.
The hyaluronan secretion rate over 4h was 4.80 ± 0.77μg h−1 (n= 5). The rate was significantly higher in contralateral joints expanded by 2 ml Ringer solution (5.80 ± 0.84 μg h −1, n= 5, P= 0.01, Student's paired t test), indicating a stretch/hydration sensitive secretory mechanism. The newly secreted chains ((2.05–2.48) × 108 Da) were not significantly different in length from the endogenous chains (2.95 × 108 Da).
Hyaluronan turnover time, calculated as mass/secretion rate, was 31.4–37.9 h. This is more than an order of magnitude longer than turnover time for intra‐articular albumin. The latter, determined from the intra‐articular albumin mass and plasma‐to‐cavity permeation rate was 1.8 h (95% confidence intervals 1.2–3.5 h, n= 9). The big difference in turnover times support the view that, relative to albumin and water, hyaluronan is partially sieved out and retained in the joint cavity by the synovial lining. The lining cell layer is discontinuous, so it appears that interstitial matrix itself acts as a leaky size‐selective molecular filter.
Evidence for the involvement of histaminergic neurones in the regulation of the rat oxytocinergic system during pregnancy and parturition
Authors: Luckman Simon M. , Larsen Philip J. 
Published: September 2004

Previous studies have shown that histaminergic neurones of the tuberomammillary nucleus project directly to hypothalamic magnocellular nuclei and that intracerebroventricular administration of histamine increases the synthetic activity of magnocellular oxytocin neurones.
Histaminergic neurones of the dorsomedial tuberomammillary nucleus that project to the magnocellular region of the paraventricular nucleus are activated during late pregnancy and lactation, as measured by an increase in mRNA for the synthetic enzyme histidine decarboxylase.
There is a concomitant increase in oxytocin mRNA in magnocellular neurones of the paraventricular nucleus. This increase in mRNA contributes to an accumulation of oxytocin before birth and to continued oxytocin synthesis during lactation.
Intracerebroventricular administration of mepyramine, a specific antagonist of the H1histamine receptor, causes a delay in the birth of subsequent pups if given to the mother during parturition. Vehicle or the H2 receptor antagonist cimetidine has no effect. Thus, histamine acts centrally, via H1 receptors, during parturition and may have an excitatory effect on oxytocin release.
These results suggest that afferent histaminergic neurones show increased activity during pregnancy and may be responsible for the increase of synthesis in magnocellular oxytocin neurones at this time. If, as previously reported, these histamine neurones can reduce the electrical activity of oxytocin neurones via H2 receptors, then they may have a dual effect, increasing the synthesis of oxytocin while inhibiting its premature release. At term, any inhibitory effects of histamine are overcome to allow oxytocin secretion.
Block of open channels of recombinant AMPA receptors and native AMPA/kainate receptors by Adamantane derivatives
Authors: Magazanik L. G. , Buldakova S. L. , Samoilova M. V. , Gmiro V. E. , Mellor I. R. , Usherwood P. N. R. 
Published: September 2004

The effects of two adamantane derivatives, 1‐trimethylammonio‐5‐(l‐adamantane‐methylammoniopentane dibromide) (IEM‐1460) and 1‐ammonio‐5‐(l‐adamantane‐methylammoniopentane dibromide) (IEM‐1754) on kainate‐induced currents were studied in Xenopus oocytes expressing recombinant ionotropic glutamate receptors and in freshly isolated neurones from rat hippocampal slices.
The adamantane derivatives caused use‐and voltage‐dependent block of open channels of recombinant AMPA receptors. This antagonism was dependent on receptor subunit composition; channels gated by recombinant, homomeric GluRl and GluR3 receptors exhibited a higher sensitivity to block than those gated by receptors containing edited GluR2 subunits. In the former cases, IEM‐1460 had an IC50 of 1.6 μm at a holding potential (Vh) of −80 mV and IEM‐1754 was 3.8 times less potent than IEM‐1460. In contrast, 100 μm IEM‐1460 inhibited responses to 100 μm kainate of receptors containing edited GluR2 subunits by only 7.8 ± 2.4% (n= 5 oocytes) at a Vh of −80 mV.
Native AMPA/kainate receptors in isolated hippocampal cells were inhibited by adamantane derivatives in a use‐ and voltage‐dependent manner. This antagonism was dependent on cell type: pyramidal neurones were less sensitive to IEM‐1460 (IC50= 1617 μm at Vh=−80mV) than interneurones (IC50= 1.6 μm at Vh=−80 mV). IEM‐1460 and IEM‐1754 were equipotent when applied to pyramidal neurones, but IEM‐1754 was less potent (∼3 times) than IEM‐1460 when applied to interneurones.
It is concluded that the presence of the edited GluR2 subunit in recombinant AMPA receptors and native AMPA/kainate receptors inhibits channel block by organic cations and that adamantane derivatives are potentially valuable tools for identifying classes of AMPA/kainate receptors and their roles in synaptic transmission.
Renal tubular lithium reabsorption in potassium‐depleted rats
Authors: Shirley D. G. , Walter S. J. 
Published: September 2004

In order to identify the tubular sites responsible for the reduced fractional excretion of lithium (FELi) during potassium depletion, free‐flow micropuncture was performed in anaesthetized rats that had been fed a low potassium (low‐K+) diet or a control diet for 5–6 days. FELi in low‐K+ rats was 0.09 ± 0.02, compared with 0.25 ± 0.01 in control animals.
Fractional water reabsorption in proximal convoluted tubules was enhanced in potassium‐depleted rats. However, fractional lithium reabsorption was not. Consequently, the tubular fluid‐to‐plasma lithium concentration ratio at the late proximal convoluted tubule was raised in the low‐K+ animals (1.50 ± 0.03 vs. 1.18 ± 0.02; P < 0.001).
Fractional lithium delivery to the early distal tubule in low‐K+ rats (0.31 + 0.01) was similar to that in control animals (0.30 + 0.02). However, whereas in control rats there was no significant difference between early and late distal tubular deliveries of lithium, late distal fractional lithium delivery in the low‐K+ group was reduced markedly (to 0.10 ± 0.01).
Treatment of potassium‐depleted rats with amiloride had no effect on lithium reabsorption in the proximal convoluted tubule or loop of Henle. However, fractional lithium delivery to the end of the distal tubule was increased slightly (to 0.15 + 0.02; P < 0.05) and FELi was increased substantially (to 0.22 ± 0.01; P < 0.001).
It is concluded that two factors contribute to the reduced FELi seen in potassium‐depleted rats: lithium reabsorption in the superficial distal tubules and amiloride‐sensitive lithium reabsorption in the collecting ducts. The data also suggest heterogeneity with respect to lithium handling between superficial and deep nephrons during potassium depletion.
Partial depletion of sarcoplasmic reticulum calcium does not prevent calcium sparks in Rat Ventricular myocytes
Authors: Song Long‐Sheng , Stern Michael D. , Lakatta Edward G. , Cheng Heping 
Published: September 2004

The exact nature of calcium sparks in the heart remains highly controversial. We sought to determine whether calcium sparks arise from a single or multiple calcium release channels/ryanodine receptors in the sarcoplasmic reticulum (SR). If their genesis involves a calcium‐coupled recruitment of multiple channels, calcium sparks might be abolished by a modest depletion of SR. calcium (because of the decrease in unitary calcium flux and hence a decrease in the gain of local calcium‐induced calcium release). If, on the other extreme, calcium sparks are produced despite severe SR depletion, the single‐channel origin will be preferred.
Spontaneous calcium sparks were studied in rat ventricular myocytes using confocal microscopy and the fluorescent calcium probe fluo‐3. A computer algorithm was developed to count and measure objectively calcium sparks in linescan images.
Thapsigargin (25–150 nm) depleted caffeine‐releasable SR calcium by up to 64%, in a dose‐and time‐dependent manner, without altering the resting cytosolic calcium level. During SR depletion, calcium sparks were robustly observed, albeit at reduced frequency (≥ 30% of control) and amplitude (≥ 60% of control).
Due to the reduced detectability of small sparks against noise background, the observed data would overestimate reduction in spark frequency but underestimate amplitude reduction. After correction for this detection bias, we found that the spark frequency was independent of SR load, whereas the amplitude was proportional to load.
We conclude that, although spark amplitude depends on SR filling status, the frequency of spark generation is independent of SR calcium load, and therefore independent of the local calcium release rate. This implies that sparks are single‐channel events, or collective events that are well above threshold for local regeneration. Additionally, our results suggest that intraluminal SR calcium, at normal or low loads, does not play a major role in the regulation of on‐gating of the ryanodine receptor.
Sympathetic nerve traffic correlates with the release of nitric oxide in humans: implications for blood pressure control
Authors: Skarphedinsson Jon O. , Elam Mikael , Jungersten Lennart , Wallin B. Gunnar 
Published: September 2004

Resting human sympathetic vasoconstrictor traffic displays large reproducible inter‐individual differences which are similar in nerves to muscle, heart and kidney. In spite of this there is no correlation between levels of blood pressure and sympathetic traffic. To test the hypothesis that the pressor effect of the vasoconstrictor activity is counteracted by a circulating dilating factor we measured muscle nerve sympathetic activity (MSA) and an indicator of nitric oxide release (plasma nitrate) in healthy young males.
Sympathetic activity was recorded with the microneurographic technique in the peroneal nerve and a forearm venous plasma sample was obtained in twenty‐one normotensive males aged 21–28 years. Plasma nitrate was analysed by gas chromatography and mass spectrometry.
There was a positive linear correlation between the plasma nitrate concentration and the strength of MSA both when the nerve activity was expressed as bursts per minute and bursts per 100 heart beats (r= 0.51, P= 0.02 and r= 0.46, P= 0.04, respectively).
The data suggest that the stronger the sympathetic activity the higher the release of the dilating substance, nitric oxide. This would be expected to counteract vasoconstrictor effects of the nerve traffic and thereby contribute to the lack of relationship between resting levels of MSA and blood pressure. We speculate that altered coupling between sympathetic traffic and nitric oxide release may cause abnormal peripheral resistance, e.g. in hypertension.
Evidence from Motoneurone Synchronization for Disynaptic Pathways in the Control of Inspiratory Motoneurones in the Cat
Authors: Vaughan C. W. , Kirkwood P. A. 
Published: September 2004

Motoneurone synchronization was measured by cross‐correlation between paired inspiratory discharges in external and internal intercostal nerves or their intramuscular branches (T3 to T8) or in the phrenic nerve (C5 root or both C5 and C6 roots independently) in anaesthetized, paralysed cats.
All cross‐correlation histograms showed central peaks, for which the durations at half‐amplitude (half‐widths) from internal nerve pairs in adjacent segments were all less than for external nerve pairs in adjacent segments or within a segment (means, 1.6 ms vs. 3.4 ms for adjacent segments). Values for external‐internal pairs covered the ranges for both these two. Lowest values came from two phrenic pairs (1.2 and 1.4 ms).
The peaks from ipsisegmental external–internal pairs were usually asymmetric and the maximum of the peak was often displaced to a lag of about –1 ms (external nerve providing the reference spikes), whereas peaks from external–external pairs were always symmetrical and centred on zero. Phrenic–internal peaks gave maxima with lags about 1 ms less than for phrenic–external peaks from the same segments.
Two explanations were considered possible for the differences in duration and timing: an extra synapse on the pathway to the external nerve motoneurones, or a correlation kernel for a monosynaptic connection to the external nerve motoneurones that had a slower time course than that for the internal or phrenic nerve motoneurones. Computer simulations, assuming the extra synapse, gave a good fit to the observed time courses of the correlation peaks for all categories of nerve pairs using single values of parameters (e.g. EPSP rise time) consistent with those in the literature. This could not be achieved with the different correlation kernel model. The timing of high‐frequency oscillation (HFO), which was sometimes present in the correlations, was also better predicted with the extra synapse model.
It is concluded that most of the synchronization between external nerve motoneurones is derived from disynaptic common inputs and that any motoneurone synchronization peak with a half‐width greater than about 2.2 ms should be assumed to be likely to contain di‐ or oligosynaptically derived components.
The interplay of central and peripheral factors in limiting maximal O2 consumption in man after prolonged bed rest
Authors: Ferretti Guido , Antonutto Guglielmo , Denis Christian , Hoppeler Hans , Minetti Alberto E. , Narici Marco V. , Desplanches Dominique 
Published: September 2004

The effects of bed rest on the cardiovascular and muscular parameters which affect maximal O2 consumption (VO2,max) were studied. The fractional limitation of VO2,max imposed by these parameters after bed rest was analysed.
The VO2,max, by standard procedure, and the maximal cardiac output (Q̇max), by the pulse contour method, were measured during graded cyclo‐ergometric exercise on seven subjects before and after a 42‐day head‐down tilt bed rest. Blood haemoglobin concentration ([Hb]) and arterialized blood gas analysis were determined at the highest work load.
Muscle fibre types, oxidative enzyme activities, and capillary and mitochondrial densities were measured on biopsy samples from the vastus lateralis muscle before and at the end of bed rest. The measure of muscle cross‐sectional area (CSA) by NMR imaging at the level of biopsy site allowed computation of muscle oxidative capacity and capillary length.
The VO2max was reduced after bed rest (−16.6%). The concomitant decreases in Q̇max (−30.8%), essentially due to a change in stroke volume, and in [Hb] led to a huge decrease in O2 delivery (−39.7%).
Fibre type distribution was unaffected by bed rest. The decrease in fibre area corresponded to the significant reduction in muscle CSA (−17%). The volume density of mitochondria was reduced after bed rest (−16.6%), as were the oxidative enzyme activities (−11%). The total mitochondrial volume was reduced by 28.5%. Capillary density was unchanged. Total capillary length was 22.2% lower after bed rest, due to muscle atrophy.
The interaction between these muscular and cardiovascular changes led to a smaller reduction in VO2max than in cardiovascular O2 transport. Yet the latter appears to play the greatest role in limiting VO2max after bed rest (>70% of overall limitation), the remaining fraction being shared between peripheral O2 diffusion and utilization.
Mass spectrometric determination of HCO3− permeability and carbonic anhydrase activity in intact guinea‐pig colon epithelium
Authors: Böllert Petra , Peters Thomas , von Engelhardt Wolfgang , Gros Gerolf 
Published: September 2004

A mass spectrometric method originally used in red blood cells was applied to suspensions of isolated colonocytes and intact colonic epithelium to measure the exchange of 18O between HCO3−, CO2 and H2O to determine intracellular carbonic anhydrase activity (Ai) and membrane bicarbonate permeability (P).
In suspensions of isolated guinea‐pig colon epithelial cells, colonocytes, we found significantly higher values of Ai and P for cells derived from the proximal colon than for cells from the distal colon. In the case of Ai, this confirms earlier reports.
When the 18O exchange process was observed across the mucosal (apical) side of intact colon mucosa, the estimated values of Ai were identical to those obtained for isolated colonocytes, for both the proximal and the distal part of the colon. This is considered to be strong evidence that this method can be applied to a layer of intact epithelium as well as to cell suspensions.
The values of P obtained from the apical side of intact colon mucosa were 6 times higher than those estimated from measurements with isolated colonocytes. This indicates that the basolateral membrane of colon epithelium, which participates in the 18O exchange process in isolated colonocytes but not in the 18O exchange process across the apical side of intact mucosa, has a markedly lower bicarbonate permeability than the apical membrane.
When the 18O exchange process was observed across the serosal (basolateral) side of intact colon mucosa, the P values, as expected, were low compared with the apical side of intact mucosa. However, rather unexpectedly, the Ai values derived from these measurements were 2–3 times lower than those obtained with isolated colonocytes. It appears possible that the latter finding is an artifact due to the submucosal tissue markedly slowing down CO2 diffusion from the bathing medium into the epithelial cells, thus causing an apparent fall in Ai.
A
i decreased and P increased with increasing temperature, as expected, when studied on the mucosal side of intact colon. This provides additional support for the validity of the method.
Medium‐Latency Stretch Reflexes of Foot and Leg Muscles Analysed by Cooling the Lower Limb in Standing Humans
Authors: Schieppati Marco , Nardone Antonio 
Published: September 2004

In standing subjects, an ankle‐dorsiflexing perturbation of the supporting surface evokes a short‐latency response (SLR) and a medium‐latency response (MLR) to stretch in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. The SLR is the counterpart of the monosynaptic reflex, whilst the MLR might be either mediated by Ia fibres, the delay being due to a long‐loop central circuit, or by fibres of slower conduction velocity. Since small afferents are slowed more than large ones by low temperature, a greater latency increment for the MLR than the SLR induced by cooling of the limb would point to a peripheral origin of the MLR.
In nine subjects, one limb was cooled by circulating water in a tube wrapped around it for about 120 min. Perturbations were delivered to the same limb prior to and during cooling, and after rewarming. EMG was recorded by surface electrodes from the Sol and FDB muscles.
The mean increase in latency of MLRs was significantly greater than that of SLRs in both muscles. On average, the Sol SLR increased from 42.4 to 47.0 ms and the Sol MLR from 72.0 to 82.3 ms. The FDB SLR increased from 58.1 to 66.5 ms and the FDB MLR from 94.9 to 110.5 ms. The mean difference (MLR minus SLR) increased from 29.6 to 35.2 ms for Sol, and from 36.8 to 43.9 ms for FDB at the end of cooling. After 30 min of rewarming, the responses of both muscles recovered towards control values.
The greater latency increment of the MLRs than of the SLRs favours the hypothesis of a slower conduction velocity of the responsible afferent fibres. The most likely candidate fibres are the spindle group II afferents.
Control of motor units in human flexor digitorum profundus under different proprioceptive conditions
Authors: Garland S. Jayne , Miles Timothy S. 
Published: September 2004

Changing the posture of the human fingers can functionally ‘disengage’ the deep finger flexor muscle from its normal action on the terminal phalanx of the fourth (or third) finger. This enables the activity of the muscle to be studied both with and without its normal proprioceptive inputs.
Spike trains of long duration from pairs of concurrently active motor units in this muscle were recorded in both the engaged and disengaged hand postures. Subjects voluntarily kept one of the motor units (the ‘controlled’ unit) discharging at the same target frequency in both postures. The strength of short‐term synchrony, the strength of common drive, and the variability of discharge of these pairs of motor units were determined in both postures.
All subjects reported that the effort required to activate the motor units in the disengaged hand posture was substantially greater than in the normal engaged posture.
Short‐term synchrony, which is a function of common corticospinal inputs to pairs of motor units, was similar in both hand postures. However, the strength of common drive was significantly decreased when the muscle was disengaged. Although the neural substrate for common drive is not known, this observation suggests that proprioceptive feedback is involved either directly or indirectly.
Although the discharge rate of the ‘uncontrolled’ motor units increased when the muscle was disengaged, the variability of discharge of these and the ‘controlled’ motor units increased significantly. This supports the idea that the precision with which fine motor tasks can be performed is improved when proprioceptive feedback is intact.