Radical modulation activity of pine cone extracts of Pinus elliottii var. Elliottii.

The radical modulation activity of lignins prepared from the cone of Pinus elliottii var. Elliottii was investigated, using ESR spectroscopy. These lignins produced radical(s) under alkaline conditions, and the radical intensity was increased with increasing pH. Lower concentrations of lignins slightly reduced the radical intensity of sodium ascorbate, whereas higher concentrations of lignins enhanced both the radical intensity and cytotoxic activity of sodium ascorbate. Lignins effectively scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction. Elliottii lignins significantly inhibited the human immunodeficiency virus (HIV)-induced cytopathic effect, in similar fashions to other natural, commercial and synthetic lignins. Pretreatment of mice with lignins significantly protected them from the lethal infection with E. coli. Crude alkaline extracts of Elliottii pine cone displayed similar magnitude of activity with lignins. These data further supports the medicinal efficacy of plant extracts.

Distribution of nociceptive neurons in the ventrobasal complex of macaque thalamus.

In urethane-chloralose anesthetized Japanese macaques, the distribution of nociceptive neurons within the thalamic ventrobasal (VB) complex was studied. Nociceptive specific (NS) and wide dynamic range (WDR) neurons were found in the periphery of the contralateral integument compartment of the VB complex. Thus, they formed a shell at the perimeter of this compartment with a somatotopic organization. The compartment consisted of large parts of nucleus ventralis posteromedialis (VPM) and nucleus ventralis posterolateralis, pars caudalis (VPLc). NS neurons were located more caudally than WDR neurons. In the NS zone of VPM, the forehead was represented caudally, and oral structures rostrally. In the ventral NS zone of VPM, there was a sequential representation of the tongue, gum and mandibular skin from the medial to the lateral edge. The hand was represented medially in the NS zone of VPLc, and its representation dominated in the rostral NS zone. There was a sequential representation of the cervical, thoracic, lumbar, sacral and caudal segments mediolaterally along the dorsal VPLc. In the medial half of ventral NS zone of VPLc, the upper body half was represented, and in the lateral half, the lower body half. The foot was represented at or near the medial edge of lateral half. In the rostral WDR zone, the trunk and peripheral face were represented.

Mechanism of angiogenic effects of saponin from ginseng Radix rubra in human umbilical vein endothelial cells.

1. The effects of saponin from Ginseng Radix rubra on angiogenesis (tube formation) and its key steps (protease secretion, proliferation and migration) in human umbilical vein endothelial cells (HUVEC) were examined to elucidate the mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a wound healing model was also studied. 2. Tube formation was measured by an in vitro system. The activity and immunoreactivity of tissue-type plasminogen activator (tPA) as a protease for angiogenesis and the immunoreactivity of its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were measured in conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation was measured by counting the cell numbers at 2-7 days after seeding. Migration was measured by Boyden's chamber method. The effect on wound healing was studied in the skin of diabetic rats. 3. Saponin at 10-100 micrograms ml-1 significantly stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a similar concentration-range increased the secretion of tPA from HUVEC as estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1 immunoreactivity was slightly increased at 10 micrograms ml-1 of saponin, but then was significantly decreased at 50 and 100 micrograms ml-1. Cell proliferation was only slightly enhanced by 1-100 micrograms ml-1 of saponin, but migration was significantly enhanced by 10-100 micrograms ml-1 in a dose-dependent manner. Moreover, saponin stimulated wound healing with enhanced angiogenesis in vivo. 4. These results indicate that saponin stimulates tube formation mainly by modifying the balance of protease/protease inhibitor secretion from HUVEC and enhancing the migration of HUVEC, and that it is effective in vivo.

Differential inhibitory mechanisms in VPL versus intralaminar nociceptive neurons of the cat: I. Effects of periaqueductal gray stimulation.

Nociceptive thalamic units receiving afferent input from the greater splanchnic nerve (SPL) were recorded from the nucleus ventralis posterolatealis (VPL) and intralaminar nuclei in urethane-chloralose anesthetized cats. The effects of stimulating the periaqueductal gray (PAG), or the nucleus raphe dorsalis (NRD) on responses of nociceptive thalamic units were investigated. Forty-eight nociceptive specific (NS) and 20 wide dynamic range (WDR) units with SPL input were found in the shell region of the caudal VPL. Following electrical stimulation of either the ventral PAG or the NRD, responses to SPL input were inhibited in all NS and WDR units tested. Responses of these units to electrical stimulation of spinothalamic tract fibers in the ventrolateral funiculus (VLF) were also inhibited following the PAG/NRD stimulation. These results suggest that PAG/NRD stimulation-produced inhibition of both NS and WDR units may be partially mediated by an ascending antinociceptive mechanism. Intralaminar nociceptive units with SPL input were found in the nuclei centralis lateralis (CL), paracentralis (Pc), and parafascicularis (Pf). The effects of conditioning electrical stimulation of either the ventral PAG or the NRD on responses of intralaminar nociceptive units were studied. Of 113 intralaminar nociceptive units studied, 68 units were unaffected, 23 units were excited and 22 units were inhibited following the conditioning stimulation. In the units in which responses to SPL stimulation were inhibited, responses elicited by electrical stimulation of the mesencephalic reticular formation (MRF) were also inhibited. These data suggest that although there is an ascending inhibitory pathway from PAG/NRD to intralaminar nuclei, this system is far less potent compared with the ascending inhibitory system acting upon the VPL.

Differential inhibitory mechanisms in VPL versus intralaminar nociceptive neurons of the cat: II. Effects of systemic morphine and CCK.

In urethane-chloralose anesthetized cats, the effects of intravenous morphine on responses of thalamic nociceptive units were studied. In both nociceptive specific (NS) and wide dynamic range (WDR) units recorded from the nucleus ventralis posterolateralis (VPL), intravenous morphine suppressed unit responses to the greater splanchnic nerve (SPL) stimulation, but had little effect on responses to stimulation of spinothalamic tract fibers in the ventrolateral funiculus. In nociceptive units recorded from nuclei centralis lateralis (CL) and parafascicularis (Pf) of the intralaminar nuclei, intravenous morphine suppressed responses to stimulation of the mesencephalic reticular formation as well as to SPL stimulation. Intravenous cholecystokinin (CCK) antagonized the suppressive action of morphine on responses of VPL units, but did not antagonize the suppressive action of morphine on responses of intralaminar units. The results suggest that intravenous morphine inhibits synaptic transmission of nociceptive impulses in the intralaminar nuclei as well as in the spinal cord, but not in the VPL, and that CCK antagonizes the antinociceptive action of morphine in the spinal cord, but not in the intralaminar nuclei.

Inhibitory effect of ginsenosides on migration of arterial smooth muscle cells.

Migration of arterial smooth muscle cells (SMC) in the arterial wall plays an important role in the formation of intimal thickening of atherosclerotic lesions. In this study, we examined the effect of ginsenosides on SMC migration induced by platelet-derived growth factor (PDGF) and SMC-derived migration factor (SDMF). Ginsenosides had inhibitory effects on SMC migration and the striking effects were observed with ginsenoside-Rb2 and -Rc in a dose-dependent manner. These results suggest that the administration of ginsenosides on the patients may prevent intimal thickening, in part, by inhibiting SMC migration in the arterial wall.

Trigeminal nociceptive neurons in the subnucleus reticularis ventralis. II. Ascending projection.

Ascending projection of trigeminal nociceptive neurons in the subnucleus reticularis ventralis (SRV) was studied in urethane/chloralose-anesthetized cats. Thalamic neurons having complex trigeminal receptive fields similar to those of SRV neurons were found in the intralaminar nuclei, i.e. nuclei centralis lateralis, centralis medialis and parafascicularis. About half of the SRV units tested were antidromically activated by electrical stimulation of the nucleus centralis lateralis. It was also found that a significant proportion of SRV units was antidromically activated by electrical stimulation of the mesencephalic reticular formation (MRF), and retrogradely labelled neurons were found in the SRV after HRP injection into the MRF. These findings suggest that SRV neurons relay trigeminal nociceptive inputs directly or indirectly via the MRF to the intralaminar nuclei.

Ipsilateral somatosensory tongue representation within the lateral subdivision of the nucleus ventralis posteromedialis parvocellularis of the cat thalamus.

Neurons in the lateral subdivision of nucleus ventralis posteromedialis parvocellularis (VPMpcl) were studied in urethanchloralose anesthetized cats. The great majority of units responded to innocuous mechanical stimulation of the ipsilateral tongue, and the rest were responsive to innocuous mechanical stimulation of intraoral structures outside the tongue. No units responded to gustatory stimulation. These findings support the idea that VPMpcl receives ipsilateral trigeminal somatosensory input rather than gustatory input.

Somatotopic distribution of trigeminal nociceptive neurons in ventrobasal complex of cat thalamus.

Recordings were made from single thalamic units in the urethan-chloralose anesthetized cat. Altogether 2,905 trigeminal single units having a receptive field in the contralateral trigeminal integument were isolated from the somatosensory part of nucleus ventralis posteromedialis, or VPM proper. Each isolated unit was tested for responses to a series of mechanical stimuli. The stimuli included brushing the skin, touch, pressure, noxious pinch, and pinpricks. The majority of VPM proper units responded with the greatest discharge frequency to gentle mechanical stimulation: either hair movement or light pressure to the trigeminal integument, but 341 units were identified as trigeminal nociceptive units. They were partitioned into two functionally defined subclasses, nociceptive specific (NS) and wide dynamic range (WDR) units, but not intermingled with low-threshold mechanoreceptive (LTM) units. Both NS and WDR units were found at or near the margin of the VPM proper but not outside this nucleus. This marginal area was referred to as the shell region of the VPM proper. A total of 248 NS units was found within the shell region of the caudal third of the VPM proper. This part was called the NS zone. These units were somatotopically organized. In the rostral part of the NS zone, ophthalmic NS units having a receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary NS units occurred dorsomedially, and mandibular NS units were found ventromedially. In the caudal part of the NS zone, maxillary NS units were encountered in the dorsal shell region, whereas mandibular NS units were found in the ventromedial shell region. Ophthalmic NS units were not found in this part of the NS zone. Altogether 93 WDR units were encountered in the shell region of the VPM proper. They were confined to a narrow band approximately 300 micron wide just rostral to the NS zone. These units were somatotopically organized. Ophthalmic WDR units having a low-threshold center of the receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary WDR units were located dorsomedially, and mandibular WDR units were located ventromedially. The majority of maxillary as well as mandibular WDR units were activated by electrical stimulation of the contralateral maxillary and/or mandibular canine tooth pulp afferents. Both NS and WDR zones of the VPM proper extended into the shell region of the nucleus ventralis posterolateralis (VPL).(ABSTRACT TRUNCATED AT 400 WORDS)