Flavonoids from the leaves ofRhododendron brachycarpum

The flavonoids isolated from the leaves ofRhododendron brachycarpum, were identified as quercetin, avicularin, quercitrin and hyperin.     

A novel cycloartane glycoside fromThalictrum uchiyamai

A new cycloartane glycoside (1) was isolated from the aerial part ofThalictrum uchiyamai Nakai (Ranunculaceae). On the basis of chemical and physicochemical evidence, the aglycone structure of this compound was characterized as 16,25-dihydroxy-3,24-diacetoxy-9, 19-cycloartane-29-oic acid, a new derivative of cycloartane triterpene. Also, the oligosaccharide moiety of this glycoside were determined as 29-O-α-L-rhanmnopyranosyl-(1→2)-[β-D-xylofuranosyl-(1→6)]-β-D-glucopyranosy by application of HMBC technique. Consequently, the structure of compound 1 was elucidated as 29-O-α-L-rhanmnopyranosyl-(1→2)-[β-D-xylofuranosyl-(1→6)]-β-D-glucopyranosyl-16, 25-dihydroxy-3,24-diacetoxy-9,19-cycloartane-29-oic acid ester.     

Extensive Aberrant Mongolian Spot

A 9-month-old male infant had generalized diffuse blue-gray pigmentation over most of his body, sparing the scalp, face, neck, palms, soles, periumbilical area, genital area, and nipples. Within the lesion, there were several conspicuous macules of considerably darker hue. Histologic examination revealed numerous dermal melanocytes. By 16 months of age, the child's blue-gray pigmentation had decreased substantially.     

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D-aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate-induced neuronal cell loss markedly. Lower concentrations of APV or D-APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the "late" addition of 10-1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino-7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium.     

GABAergic neocortical neurons are resistant to NMDA receptor-mediated injury

N-methyl-D-aspartate (NMDA) receptors are thought to mediate much of the central neuronal loss produced by certain neurologic insults, including hypoxia-ischemia, hypoglycemia, and trauma. Therefore, the specific vulnerability of GABAergic inhibitory neurons to NMDA receptor-mediated toxicity might be an important determinant of the potential for epileptogenesis following these insults. We have examined the fate of GABAergic cortical neurons in mouse cell cultured neuronal population) were identified either by immunoreactivity with antisera to GABA or by autoradiography following high-affinity uptake of 3H-GABA. Cultures exposed for 5 min to 20 to 750 microM NMDA showed NMDA concentration-dependent, widespread neuronal loss. However, GABAergic neurons were relatively spared, and thus represented an enhanced fraction of neuronal survivors. These observations suggest that GABAergic cortical neurons may possess some intrinsic resistance to NMDA receptor-mediated neurotoxicity, a property which might convey an anticonvulsant "inhibitory safety factor" to neocortex against certain forms of injury.     

Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI

The literature suggests that in children with severe head injury, cerebral hyperemia is common and related to high intracranial pressure (ICP). However, there are very few data on cerebral blood flow (CBF) after severe head injury in children. This paper presents 72 measurements of cerebral blood flow ("CBF15"), using the 133Xe inhalation method, with multiple detectors over both hemispheres in 32 children aged 3 to 18 years (mean 13.6 years) with severe closed head injury (average Glasgow Coma Scale (GCS) score 5.4). In 25 of the children, these were combined with measurements of arteriojugular venous oxygen difference (AVDO2) and of cerebral metabolic rate of oxygen (CMRO2). In 30 patients, the first measurement was taken approximately 12 hours postinjury. In 18 patients, an indication of brain stiffness was obtained by withdrawal and injection of ventricular cerebrospinal fluid and calculation of the pressure-volume index (PVI) of Marmarou. The CBF and CMRO2 data were correlated with the GCS score, outcome, ICP, and PVI. Early after injury, CBF tended to be lower with lower GCS scores, but this was not statistically significant. This trend was reversed 24 hours postinjury, as significantly more hyperemic values were recorded the lower the GCS score, with the exception of the most severely injured patients (GCS score 3). In contrast, mean CMRO2 correlated positively with the GCS score and outcome throughout the course, but large standard deviations preclude making predictions based on CMRO2 measurements in individual patients. Early after injury, there was mild uncoupling between CBF and CMRO2 (CBF above metabolic demands, low AVDO2) and, after 24 hours, flow and metabolism were completely uncoupled with an extremely low AVDO2. Consistently reduced flow as found in only four patients; 28 patients (88%) showed hyperemia at some point in their course. This very high percentage of patients with hyperemia, combined with the lowest values of AVDO2 found in the literature, indicates that hyperemia or luxury perfusion is more prevalent in this group of patients. The three patients with consistently the highest CBF had consistently the lowest PVI: thus, the patients with the most severe hyperemia also had the stiffest brains. Nevertheless, and in contrast to previous reports, no correlation could be established between the course of ICP or PVI and the occurrence of hyperemia, nor was there a correlation between the levels of CBF and ICP at the time of the measurements. The authors argue that this lack of correlation is due to: 1) a definition of hyperemia that is too generous, and 2) the lack of a systematic relationship between CBF and cerebral blood volume     

CD154-CD40-independent up-regulation of B7-2 on splenic antigen-presenting cells and efficient T cell priming by staphylococcal enterotoxin A

It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal enterotoxin A (SEA), could up-regulate B7-2 on most splenic APC independently of the CD154-CD40 interaction, followed by efficient expansion of SEA-reactive V(beta)3(+) T cells in CD154- or CD40-deficient mice. However, the CD154-CD40 interaction may be involved in SEA-mediated T cell activation, since a contribution of the CD154-CD40 interaction was observed when a lower dose of SEA was injected. CD154-independent T cell priming by SEA appeared also independent of the TRANCE-RANK pathway, which was shown to be capable of mediating CD154-independent activation of naive T cells during the infection of some viruses. These results indicate that SEA, which provokes rapid and efficient T cell responses without adjuvant, could utilize multiple CD154/TRANCE-independent pathways, to prime T cells.