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Biomedical subjects

G W Lu

Publications and source records attributed to G W Lu.

At least 37 records · Page 2Linked to original sources
PubMed1995

Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus and topical routes of administration in dogs.

PURPOSE: The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. METHODS: A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. RESULTS: Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximately 4 hr, lasting for approximately 20 hr. The bioavailability of MTX from the gel was 11.8 +/- 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. CONCLUSIONS: Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation.

Administration, Topical↗
PubMed1994

Effects of extract from Clerodendron trichotomum on blood pressure and renal function in rats and dogs.

Clerodendron trichotomum Thunb. is a herb which has been used for treatment of hypertension in Chinese medicine. To assess the action of the herb on blood pressure and renal function, the extract was administered to rats and dogs. Intravenous administration of the extract elicited renal vasodilation and increased urine flow and urinary sodium excretion. Acute oral administration of the extract reduced blood pressure of spontaneously hypertensive rats but not of normotensive control rats. Chronic daily administration for 6 weeks prevented the increase in blood pressure of spontaneously hypertensive rats. These results may give some support to the claim on the clinical efficacy of the extract of Clerodendron trichotomum Thunb.

Administration, Oral↗
PubMed1993

Spontaneous activity of cat spinal ganglion neurons in vivo.

Recordings were made from L4-S1 spinal ganglion neurons of anesthetized cats while their associated dorsal root and the sciatic nerve were left intact, locally anesthetized, or locally anesthetized and sectioned. In all three experimental conditions spontaneous discharges were recorded. These discharges occurred in the absence of any electrical stimulation of the dorsal root or sciatic nerve, and were not due to peripheral exploration of receptive fields or sustained firing in joint or muscle afferents. The spontaneous discharges were relatively rhythmic, and their firing frequency ranged from 5 to 100 impulses per s. Interactions between spontaneous and electrically evoked discharges were observed that depended on the impulse's frequency of firing. High frequency discharges always abolished low frequency impulses regardless of whether these latter were spontaneous or evoked. Extra spikes and postspike events that followed impulses evoked by stimulation of the dorsal root or sciatic nerve were also recorded from some spinal ganglion neurons. These results suggest that spontaneous discharges may originate within the spinal ganglion itself, and that they can occur under normal circumstances.

Action Potentials↗
PubMed1993

Characteristics of action potentials recorded from cat spinal ganglion neurons in vivo.

Action potentials were recorded intracellularly from L4-S1 dorsal root ganglion (DRG) neurons of anesthetized cats. Based on the shape of their waveforms the action potentials were classified as either typical (n = 49) or atypical (n = 8). The atypical potentials were characterized by a slowly rising, well-defined early depolarization of small amplitude and long duration. This kind of prepotential randomly triggered spike potentials with varying latencies. The average rise time, duration, and area of atypical potentials were significantly different than those of typical ones. In some DRG neurons, the afterhyperpolarization was preceded by a delayed repolarization, or was followed by postspikes and long-lasting afteroscillations. In others, small depolarizations could be recorded during subthreshold stimulation. These depolarizations arose slightly later than the spike potential, and were all or none, with relatively stable onset latency and size. These results are explained by postulating the presence of chemical synapses and/or electrotonic coupling in the DRG.

Action Potentials↗
PubMed1993

[Responses of toad spinal ganglion neurons to repetitive stimulation of their central and peripheral processes].

Intracellular recordings were made from 48 toad dorsal root ganglion neurons in vitro while electrical stimulation was delivered respectively to their dorsal root or sciatic nerve input. The average conduction velocities were respectively 12 m/s and 15 m/s. With progressively increasing frequency of stimulation, 30% of the recorded cells showed simultaneous decrease of amplitude, wave decomposition and dropping of propagated response to both inputs while 70% of the cells showed more or less different patterns of degradation of the various parameters. Complete failure of neurons to follow the inputs occurred respectively at 126 and 323 Hz. Evidently the dorsal root ganglion neurons reported in the present work pertain to type A neuron with central processes smaller in diameter than peripheral ones A possible mechanism underlying the different changes is discussed.

Animals↗
PubMed1991

[Responses of toad spinal ganglion neurons in vitro to peripheral repetitive stimulation].

Responses of toad ganglion neurons in vitro to repetitive stimulation of their peripheral processes (sciatic nerve) were intracellularly recorded. The conduction velocity, threshold and resting membrane potential of the 66 recorded neurons ranged 5.3-20.0 m/s, 0.02-0.10 mA, and -50-(-)80 mV, respectively. As the stimulation frequency increased, jitter or delay in onset latency, reduction in amplitude, prolongation in duration, and decrease in afterhyperpolarization occurred in evoked responses of the spinal ganglion neurons. The responses decomposed into three subwaves of S, NM, and M and then missed. The ability of these three components to follow stimulation frequency was in the order of S less than NM less than M; the frequency range during which the spike potential or wave S misses was from 16.7 Hz to 250 Hz. These results indicate that there are three distinct zones in excitability in type A toad spinal ganglion neurons, and some of them may exhibit synaptic or junctional activity.

Animals↗
PubMed1991

[Bilateral changes of nociceptive sensitivity in rats with one paw inflamed].

Following a significant decrease in pain threshold (PT) in the carrageenin injected paw of rat, the PT of the contralateral uninjected paw was usually increased but might also be significantly decreased or unchanged. These three directions of PT change in the contralateral non-inflamed paws were found to be correlated with the magnitude of decrease in PT in the inflamed sides.

Animals↗
PubMed1990

Responses of type A cat spinal ganglion neurons to repetitive stimulation of their central and peripheral processes.

Intracellular recordings were made from L7-S1 type A spinal ganglion neurons of anesthetized cats while electrical stimulation was delivered repetitively to their associated dorsal root and the sciatic nerve. The general response pattern of these neurons changed during stimulation at progressively higher rates. The changes were observable as jitter in onset latency of the evoked spikes, inability of evoked responses to follow electrical stimuli in a 1:1 manner (spike failure), reduction in action potential amplitude, and decomposition of the full spike into its non-myelinated and myelinated components. The frequency following ability of these spike components was in the order of full spike less than non-myelinated less than myelinated. In jitter in onset latency and inability to follow high frequency stimulation was determined only for the full spike, as is typical for antidromicity criteria, a wide frequency following spectrum was obtained for our sample of spinal ganglion neurons. Less than a third of the cells were able to follow stimulation rates in excess of 200 Hz, and about a fifth of the neurons failed to follow any rates greater than 20 Hz. Most of the neurons activated from both the dorsal root and sciatic nerve responded with the same pattern of stimulus-evoked responses. However, some of these cells exhibited strikingly different patterns to dorsal root and sciatic stimulation, including the presence of prepotentials following stimulation of one, but not the other, process. These prepotentials occurred in the depolarizing direction, at threshold stimulation were all-or-none in nature, generated spikes that varied in onset latency, and failed to occur at even low-to-moderate rates of stimulation. The results indicate that the frequency following spectrum of cat type A ganglion neurons is wide, and that it is their somata that are most vulnerable to high frequency stimulation. It is possible that some of the observed prepotentials are functional manifestations of synaptic contacts in spinal ganglia.

Action Potentials↗
PubMed1989

The morphology of cat spinal neurons projecting to both the lateral cervical nucleus and the dorsal column nuclei.

Morphological features of physiologically characterized doubly projecting spinocervical tract-dorsal column postsynaptic (SCT-DCPS) neurons were examined following intracellular injections of horseradish peroxidase. Their cell bodies and majority of dendrites were located in laminae III-IV. The SCT-DCPS neurons have rostrocaudally elongated dendritic trees with spiny fine caliber dendrites, and issue local axon collaterals that are studded with varicosities. The results show that the doubly projecting SCT-DCPS neurons do not represent a morphologically distinct subset of the spinocervical tract (SCT) or dorsal column postsynaptic (DCPS) cells.

Animals↗
PubMed1989

Spinocervical tract-dorsal column postsynaptic neurons: a double-projection neuronal system.

Evidence is presented for the existence of a newly discovered double-projection spinal neuronal system, the spinocervical tract-dorsal column postsynaptic neurons. The neurons are characterized by axonal bifurcation in the cervico-thoracic junction, by branched axons traveling in the dorsal column and the dorsolateral funiculus, and by double projection to the dorsal column nuclei and the lateral cervical nucleus. The neurons, with longitudinally distributed dendritic trees and local axon collaterals, primarily originate in laminae III-V of the dorsal horn and receive innocuous and noxious inputs transmitted along the A-beta primary afferents from the periphery. These neurons are thought to be an intersection of the spinocervical tract and the dorsal column postsynaptic neurons, and to function as a nonlemniscal system in mediation and modulation of ascending sensory information, including pain.

Action Potentials↗
PubMed1989

[Effects of noradrenaline,glycine, gamma-aminobutyric acid and L-glutamic acid on spinal field potentials in the rat].

Noradrenaline (NE), glucine (GLY), gamma-aminobutyric acid (GABA) and L-glutamic acid (L-GLU) were locally applied to the dorsal surface of lumbar spinal cord on anesthetized and immobilized rats and their effects on segmental (SP) and descending (DP) spinal field potentials were examined. Both waves N and P of SP and DP were reduced markedly in amplitudes following local application of NE. A significant decrease in amplitude of wave N and a remarkable increase in wave P in both SP and DP were shown during the application of GLY, GABA and L-GLU. The results suggest that these neurotransmitters may be involved in the generation of waves N and P, particularly affecting the activities of interneurons in the spinal dorsal horn.

Animals↗
PubMed1988

Morphological evidence for newly discovered double projection spinal neurons.

A novel population of spinal neurons is shown to terminate in two nuclei: the lateral cervical nucleus and the dorsal column nuclei. Nuclear yellow and Fast blue injected respectively into these nuclei are retrogradely transported to common neurons in the lumbosacral dorsal horn. The bifurcation of these neurons' axons appears to occur at the cervico-thoracic junction. These results indicate that some dorsal horn neurons transmit sensory information to two distinct nuclei. The two projections and their branching points may play a special role in neuronal communication.

Animals↗