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Biomedical subjects

S J Hu

Publications and source records attributed to S J Hu.

At least 19 recordsLinked to original sources

Effects of homocysteine on number and activity of endothelial progenitor cells from peripheral blood.

The aim of this study is to investigate whether homocysteine (Hcy) has influences on endothelial progenitor cells (EPCs) number and activity. Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 d cultured, attached cells were stimulated with Hcy (to make a series of final concentrations: 10, 50, 100 and 200 micromol/l) or vehicle control for the respective time points (6, 12, 24 and 48 h). EPCs were characterized as adherent cells double positive for DiLDL uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. EPCs proliferation, migration and in vitro vasculogenesis activity were assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was performed by replating those on fibronectin-coated dishes, and then adherent cells were counted. Incubation of isolated human MNCs with Hcy dose and time dependently decreased the number of EPCs, maximum at 200 micromol/l, 24 h (approximately 50% reduction, P < 0.01). In addition, Hcy dose and time dependently impaired EPC proliferative, migratory, adhesive and in vitro vasculogenesis capacity. In conclusion, hyperHcy may induce the reduction of EPCs with decreased functional activity.

Cell Division↗

Subthreshold membrane potential oscillations of type A neurons in injured DRG.

An abundance of subthreshold membrane potential oscillations (SMPOs) at resting potential was observed in the neurons of chronically compressed dorsal root ganglia (DRG) using intracellular recording in vivo. Out of 386 neurons, 63 type A neurons displayed SMPOs. Three types of SMPOs were distinguished based on their characterizations of oscillation: (1) A regular pattern of SMPO emerged consistently with a mean frequency of 86 Hz and mean amplitudes of 3.3 mV. (2) A spindle-like pattern of SMPO was denominated by a spindle alteration of its amplitude. (3) An irregular pattern of SMPO had no rule on its change of amplitude and frequency. Compared with normal DRG neurons and injured DRG neurons but without SMPO, the injured DRG neurons with SMPO had the lowest spike rheobase, in accordance with the detection of spike accommodation. No significant differences among the three groups can be found in either membrane potential or input resistance. Further observation showed that the spontaneous discharge of hyperexcitable neurons usually occurred on the depolarizing phase of oscillations. In addition, the regular pattern of SMPO was based on the period and integer multiple patterns of spontaneous discharges. The spindle-like pattern of SMPO contributed to spontaneous bursting discharge. The irregular pattern of SMPO had a striking relation with irregular spontaneous discharge. The results show that neurons with SMPO in injured DRG have a higher excitability than those without SMPO, and that the SMPO underlie the patterns of spontaneous discharges, suggesting that SMPO is the basic electrophysiological change of hyperexcitable neurons.

Animals↗

Subthreshold membrane oscillations underlying integer multiples firing from injured sensory neurons.

Integer multiples firing (IMF), a special temporal pattern of firing, was recently observed in spontaneous discharge from injured dorsal root ganglion (DRG) neurons. To investigate the mechanism underlying IMF, the injured DRG neurons of rat were recorded intracellulary. Of 64 recorded A-neurons discharging spontaneously, eight fired spikes in the IMF pattern. Interspike interval (ISI) time series of IMF showed a structure of distinct bands on scatter map. Regular subthreshold membrane oscillations (SMOs) with relatively stable amplitude and frequency were observed on all eight IMF neurons. IMF could be induced from the neurons in periodic firing by local application of tetrodotoxin (TTX), a Na+ channel antagonist. During this process, the amplitude of SMOs varied markedly. Some SMOs were below action potential threshold so that they did not trigger spikes. Nor did some SMOs, though their amplitude were obviously beyond the threshold measured from nearby spikes. The results indicate that regular SMOs existent in injured DRG A-neurons underlie IMF, and the TTX-induced transformation of firing pattern from periodic to integer multiples may occur in two ways: decreasing the amplitude of SMOs and/or elevating action potential threshold.

Action Potentials↗

[Sympathetic-sensory coupling in neuropathic pains].

Peripheral tissue and nerve injury lead to chronic pain symptoms, including spontaneous pain, allodynia and hyperalgesia. Sympathetic nervous system involves in pathological changes above, either through development of abnormal sympathetic function or through its effects on abnormally functioning afferent nerves, thereby to cause many neuropathic pains. This review focuses on the progress at present of sympathetic-sensory coupling and its receptors, intracellular and neural mechanisms.

Animals↗

Detection of determinism within time series of irregular burst firing from the injured sensory neuron.

Irregular burst firing is spontaneously generated by rat dorsal root ganglion neuron after chronic compression. To investigate the time series of burst firing, we recorded interspike intervals (ISIs) of single-unit firing in vitro and processed the ISIs to obtain interevent intervals (IEIs). Then, two non-linear methods were applied to detect deterministic dynamic behaviors in IEI series. No evidence for the existence of determinism was found with non-linear prediction method. Using unstable periodic orbit identification method, significant period-1 orbits were identified in all 10 data, period-2 orbits in eight, and period-3 orbits in six. The results indicate that there exist significant deterministic behaviors in the time series of irregular burst firing from the injured sensory neuron.

Action Potentials↗

Adrenergic sensitivity of neurons with non-periodic firing activity in rat injured dorsal root ganglion.

In this study, we compared the sensitivity of non-periodically and periodically active neurons in chronically compressed dorsal root ganglion in rats to norepinephrine and sympathetic stimulation. Forty-nine of 58 (84.5%) neurons with non-periodic activity showed responses to norepinephrine, whereas only five of 48 (10.4%) neurons with periodic activity displayed any response. The dose-response relationship of norepinephrine to the irregular burst pattern neurons shifted towards the left significantly compared to that of the periodic activity neurons. Responses to norepinephrine became apparent in eight neurons after their periodic firing activity was transformed into the non-periodic firing activity through the increase in Ca(2+). Changes in the time-response curves indicate a higher sensitivity of irregular burst pattern neurons to sympathetic stimulation than the periodic activity neurons. Finally, deterministic dynamics contained within the interburst interval series for non-periodic activity were identified. From these results, we suggest that the non-periodic activity neurons have a higher adrenergic sensitivity than those displaying periodic activity, and that this sensitivity may depend on the deterministic chaos within its firing dynamic system.

Action Potentials↗

Studies of detrusor-sphincter synergia and dyssynergia during micturition in rats via fractional Brownian motion.

In normal humans, the bladder is supposed to empty by a synergistic contraction of the detrusor and relaxation of the sphincter during micturition. By contrast, suprasacral spinal cord injury (SCI) patients usually will have both of them contract simultaneously and result in the so-called detrusor-sphincter dyssynergia. In this study, the cystometrograms of the detrusor and the electromyograms of external urethral sphincter of intact and SCI female Wistar rats are used to investigate the detrusor-sphincter synergia and dyssynergia during micturition. Due to the statistical self-similarity of the waveforms, the cystometrogram is modeled as discrete-time fractional Brownian motion and the electromyogram as discrete-time fractional Gaussian noise. Fractal dimensions of both of them are calculated and used as indices in the investigation of synergia. Results indicate that, for intact rats, the sphincter muscle is not only active but also recruited in a synchronous fashion with the detrusor. Furthermore, clear-cut measure using the fractal dimensions can be used to diagnose detrusor-sphincter synergia and dyssynergia.

Algorithms↗

[Relationship between the sensitivity to tetraethylammonium and firing patterns of injured dorsal root ganglion neurons].

In order to study the relationship between the firing patterns of injured dorsal root ganglion (DRG) neurons of rat and their sensitivity to tetraethylammonium (TEA), spontaneous activities from single fibers of chronically compressed DRG neurons were recorded. Two patterns of spontaneous activity were found: periodic pattern and non-periodic pattern. These two types of neurons showed different sensitivity to TEA with 27.3% in periodic and 93.2% in non-periodic firing neurons responding to TEA (2 mmol/L) (P<0.01). The responses to TEA of different concentrations were greater in the non-periodic firing neurons than in the periodic firing ones (P<0.01). The responses to TEA became apparent in 5 neurons after their periodic firing pattern was transformed into non-periodic firing pattern through an increase in Ca(2+). The non-periodic interburst interval of the bursting discharge decreased significantly while the periodic burst interspike interval had no response to TEA. The unstable period orbits were found in bursting discharge, indicating deterministic chaos during bursting discharge. It is concluded that non-periodic firing neurons with chaos are more sensitive to TEA than periodic firing neurons.

Animals↗

[Alteration of sensitivity of supraoptic nucleus neurons to cytokine in the hypothalamic slices from the rat after lipopolysaccharide injection].

Using the whole cell patch clamp technique, the effects of interleukin 1beta (IL-1beta) and IL-2 on the membrane potential and spontaneous discharges in the supraoptic nucleus (SON) neurons from the rat hypothalamic slices in vitro were examined to determine the changes in sensitivity of supraoptic nucleus neurons to cytokine. The results obtained are as follows. IL-1beta (100 U/ml) hyperpolarized the SON neurons from the control rats (n=15) and the rats 9 d after i.p. lipopolysaccharide (LPS) (n=20), and decreased the rate of their spontaneous discharges. When 100 U/ml IL-2 was perfused, most SON neurons (n=14) from the control rats were hyperpolarized and the spontaneous firing decreased, but the rest (n=3) remained unchanged. When IL-2 (100 U/ml) was applied, 19 neurons out of the 45 SON neurons from the rats 9 days after i.p. LPS were depolarized accompanied with an increase of the discharges, 16 did not show significant changes in both membrane potential and spontaneous discharges, the rest 10 were hyperpolarized and their discharges were suppressed. These results show that the sensitivity of part of SON neurons from the immuned rat to cytokine IL-2 was altered, suggesting that IL-2 may be involved in modulation of the activity of SON neurons and thus play a role in modulation of the immune response.

Animals↗

Relationship between calcium-dependent potassium channel and ectopic spontaneous discharges of injured dorsal root ganglion neurons in the rat.

The ectopic spontaneous discharges (ESD) of single myelinated dorsal root fiber originated from the injured dorsal root ganglion (DRG) neurons were recorded in vivo. When [Ca(2+)](o) perfusing the injured DRG had been enhanced or caffeine been used, the ESD was inhibited in dose-dependent manner, while using Ni(2+) or EGTA, the ESD facilitated. The increment of [K(+)](o) and the use of TEA could both facilitate the ESD in dose-dependent manner. Apamin, a special antagonist of calcium-dependent potassium channel (K(Ca)), had markedly increased the number of ESD. These results suggest that the generation of ESD has close relation to the activity of K(Ca) channel.

Animals↗

Fractal geometry in urodynamics of lower urinary tract.

The physiological signals are usually extremely complicated and difficult to analyze. Recently, investigators have tried the fractal dimension that can characterize roughness and self-similarity of them. It turns out that it is also suitable for obtaining the modalities of lower urinary tract during normal micturition. In this investigation, the external urethral sphincter electromyogram (EUS EMG) and the cystometrogram (CMG) of the Wistar rats under both room temperature and cold water stimulation of the bladder are studied. The modified relative differential box-counting (RDBC) method is used to calculate the fractal dimensions of EMG and CMG time series. According to the experimental results, the modalities of micturition for the Wistar rats can be characterized as normal if both the fractal dimensions of EMG and CMG are of low values during voiding. Furthermore, the technique is validated in identifying the dyssynergia of the bladder and EUS under cold water stimulation.

Animals↗

Terrestrial gamma ray dose rates of Brunei Darussalam.

GPS-indexed in-situ and car-borne survey of terrestrial gamma-ray dose rates were carried out in Brunei and adjacent areas using two portable NaI(Tl) counters. The mean and population weighted average dose rates for Brunei are 34 and 33 nGy/h, respectively. The car-borne data and the in-situ data when spectral analysed separately, were found to show fractal behaviour with D of 1.7 and 1.8, respectively. A contour map of the dose rates was also produced.

Air Pollutants, Radioactive↗

Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia.

Chronic compression of the dorsal root ganglion (CCD) was produced in adult rats by implanting a stainless steel rod unilaterally into the intervertebral foramen, one rod at L(4) and another at L(5). Two additional groups of rats received either a sham surgery or an acute injury consisting of a transient compression of the ganglion. Withdrawal of the hindpaw was used as evidence of a nocifensive response to mechanical and thermal stimulation of the plantar surface. In addition, extracellular electrophysiological recordings of spontaneous discharges were obtained from dorsal root fibers of formerly compressed ganglia using an in vitro nerve-DRG-dorsal root preparation. The mean threshold force of punctate indentation and the mean threshold temperature of heating required to elicit a 50% incidence of foot withdrawal ipsilateral to the CCD were significantly lower than preoperative values throughout the 35 days of postoperative testing. The number of foot withdrawals ipsilateral to the CCD during a 20-min contact with a temperature-controlled floor was significantly increased over preoperative values throughout postoperative testing when the floor was 4 degrees C (hyperalgesia) and, to a lesser extent, when it was 30 degrees C (spontaneous pain). Stroking the foot with a cotton wisp never elicited a reflex withdrawal before surgery but did so in most rats tested ipsilateral to the CCD during the first 2 postoperative weeks. In contrast, the CCD produced no changes in responses to mechanical or thermal stimuli on the contralateral foot. The sham operation and acute injury produced no change in behavior other than slight, mechanical hyperalgesia for approximately 1 day, ipsilateral to the acute injury. Ectopic spontaneous discharges generated within the chronically compressed ganglion and, occurring in the absence of blood-borne chemicals and without an intact sympathetic nervous system, were recorded from neurons with intact, conducting, myelinated or unmyelinated peripheral nerve fibers. The incidence of spontaneously active myelinated fibers was 8.61% for CCD rats versus 0.96% for previously nonsurgical rats. We hypothesize that a chronic compression of the dorsal root ganglion after certain injuries or diseases of the spine may produce, in neurons with intact axons, abnormal ectopic discharges that originate from the ganglion and potentially contribute to low back pain, sciatica, hyperalgesia, and tactile allodynia.

Animals↗

[Protein kinase a mediated excitatory adrenergic effect on chronically compressed dorsal root ganglion neurons in rats].

With a model of chronically compressed dorsal root ganglion (CCD), the present study was undertaken to test how the plasticity of sympathetic-sensory coupling is and whether the coupling is mediated by intracellular messenger PKA by analysing extracellularly recorded spontaneous activity of single A-fibers originating from the CCD neurons in vitro. Eighty-five out of 95 neurons from injured DRGs during application of norepinephrine (NE) were adrenosensitive. Among the 85 neurons, 44 exhibited excitation, 21 showing excitation followed by suppression, 6 displaying alternated excitation and suppression, and 14 suppression. In addition, adrenosensitivity was observed in 15 silent injured DRGs. The excitatory effect of NE was blocked by alpha 1 and alpha 2 adrenoceptor antagonists yohimbine (10 mumol/L) or prazosin (5 mumol/L). Rp-cAMPS (50-250 mumol/L, n = 6), a specific inhibitor of PKA, and H-89 (10 mumol/L, n = 6), an inhibitor of PKA catalytic subunit, obviously suppressed the NE-evoked excitation. Furthermore, the excitatory effect of NE was attenuated by SQ 22, 536 (1 mmol/L), an adenylate cyclase inhibitor (n = 6). The above results demonstrate that injury to DRG neuron body triggered the adrenosensitivity, which was mediated by alpha 1, alpha 2 adrenoceptors and PKA.

Adrenergic Fibers↗

[Pattern and dynamic changes of integer multiples in spontaneous discharge of injured dorsal root ganglion neurons].

For the purpose of the present investigation, spontaneous discharges of dorsal root ganglion (DRG) neurons of the rats, which had undergone 3-10 days' chronic compression, were studied. It was found that the interspike interval (ISI) of 17 out of 156 fibers had integer multiples temporal rhythm pattern, in which all the ISI were integer multiples of a basic ISI and a return map of their ISI could be constructed as a crystal grid structure. This temporal pattern could be modified by Na+ channel and K+ channel on their membranes. These data indicated the presence of some irregular discharge trains with their intrinsic regularity.

Action Potentials↗

[Apamin sensitive component of Ca(2+)-activated K+ current of afterhyperpolarization, IAHP, in dorsal root ganglion neurons in rat].

Whole-cell voltage clamp technique was used to record the tail current in freshly isolated dorsal root ganglion (DRG) neurons of rat with an aim to investigate whether these neurons possess an apamin sensitive component of Ca(2+)-activated K+ current, IAHP. The results are as follows: (1) the amplitudes of the tail currents increased from 9.3 +/- 2.8 pA to 64.1 +/- 3.4 pA (P < 0.001) when the depolarizing duration was increased from 1 ms to 180 ms; (2) the amplitudes of the tail current were reduced when repolarizing pulses were applied, with a reversal potential of about -63 mV; (3) the amplitude of the tail current was significantly depressed or even almost completely blocked by extracellularly applied 500 mumol/L Cd2+ or intracellularly applied 11 mmol/L EGTA; (4) the amplitudes of the tail currents were decreased by about (26.32 +/- 3.9)% (P < 0.01) after 200 nmmol/L apamin was extracellularly applied; and (5) the fast component of the tail current was sensitive to 10 mmol/L TEA while the slow component was insensitive. These results suggest that an apamin sensitive component of Ca(2+)-activated K+ current may be present in afterhyperpolarization of DRG neurons.

Animals↗

[Alteration of inositol phosphate metabolism in aortic smooth muscle cells from spontaneously hypertensive rat].

The changes of inositol phosphates in quiescent and GTP gamma S activated vascular smooth muscle cells (VSMC) derived from aorta of spontaneously hypertensive rat (SHR) were examined. The inositol phosphate assay revealed that there was no difference in the inositol-1, 4, 5-triphosphate (InsP3) level between the quiescent VSMCs of SHR and that of normotensive Wistar-Kyoto rats (WKY). G-protein activator GTP gamma S caused a dose- and time-dependent increase in the InsP3 level in VSMCs. Activated G proteins increased significantly the InsP3 level in VSMCs of SHR. In conclusion, the highly sensitive reactivity to GTP gamma S in the generation of InsP3 in VSMCs from SHR may be related to the possible abnomality of the number, substructure or function of some components in G proteins, phosphoinositide turnover.

Animals↗

[G proteins-phosphoinositide pathways in hypertension].

The second messenger inositol-1,4,5-trisphosphate (InsP3) comes from two major pathways, one is initiated by a family of G protein-linked receptors and the other by receptors linked by tyrosine kinases. These separate receptors activate phospholipase C to hydrolyse phosphatidylinositol-4,5-bisphosphate to give both diacylglycerol and InsP3. The latter then mobilizes stored calcium and promotes an influx of external calcium. The alpha subunit of a newly discovered G protein (Gq) has recently been shown to stimulate the activity of PLC-beta 1. The alpha subunits of the Gq class of G proteins includes G alpha q, G alpha 11, G alpha 14, G alpha 15 and G alpha 16. The important pathologic changes in hypertension are arteriolar spasm and wall thickening. Many vasoactive substances can induce contractile response and proliferation of vascular smooth muscle cells and increase InsP3 level. However, the hypertension does not cause any persistent change in Gq.

Animals↗