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D Xue

Publications and source records attributed to D Xue.

50 records · Page 3Linked to original sources
PubMed1994

A selective N-type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia.

SNX-111 (NEUREX Corporation, Menlo Park, CA, U.S.A.) an omega-conopeptide, was tested for cytoprotection following normothermic ischemia using both a four-vessel occlusion model of severe forebrain ischemia and a model of transient middle cerebral artery occlusion focal ischemia. Adult male Wistar rats were subjected to 10 min of forebrain ischemia followed by 7 days of reperfusion. A single dose of SNX-111 (5 mg/kg) was injected intravenously following delays of either 6 or 24 h after reperfusion. For 11 rats treated with saline, there was 78 +/- 13% CA1 neuronal injury (mean +/- SD); for 11 given SNX-111 delayed by 6 h, injury was reduced to 35 +/- 30% (p < 0.01); and remarkably, treatment delayed by 24 h (n = 10), still resulted in protection, with only 50 +/- 29% injury (p < 0.05). Adult male spontaneously hypertensive rats had transient occlusion of the right middle cerebral artery of 1.5- or 2-h duration followed by 22.5 or 22 h of reperfusion, respectively. Rats were randomly assigned to receive either saline or SNX-111 (5 mg/kg i.v.), with treatment starting immediately after reperfusion (1.5-h ischemic group) or at 1 h following the onset of ischemia (2-h ischemic group). In the 1.5-h ischemic group, saline-treated animals sustained 138 +/- 32 mm3 of neocortical infarction (n = 9), and SNX-111 treatment resulted in an infarct reduction to 76 +/- 25 mm3 (n = 9; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Delayed treatment with AMPA, but not NMDA, antagonists reduces neocortical infarction.

We tested the abilities of two potent non-N-methyl-D-aspartate (non-NMDA) glutamate antagonists [2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX)] and [1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazep ine hydrochloride (GYKI 52466)] to reduce neocortical infarction following 2 h of transient middle cerebral artery occlusion in a hypertensive stroke model in the rat and compared these effects against, and in combination with, a potent NMDA antagonist [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-amine maleate (MK-801)]. In Expt. 1, an already established cytoprotective dose of Na(+)-NBQX (30 mg/kg i.p. x 3) was compared with saline (1 ml), the NMDA antagonist MK-801 (1 mg/kg i.p. x 3), and a combination of the same doses of both NBQX and MK-801. Initial doses were delayed to 90 min following occlusion with subsequent injections at the time of reperfusion and 30 min following reperfusion. Saline-treated rats sustained 181 +/- 32 mm3 (n = 15) of neocortical infarction (mean +/- SD). This was significantly reduced by NBQX to 137 +/- 25 mm3 (n = 15, p < 0.05) of damage. Neither MK-801 (170 +/- 33 mm3; n = 11) nor the combination of MK-801 and NBQX (169 +/- 20 mm3; n = 6) proved to be cytoprotective when given with a 90-min delay. In Expt. 2, NBQX (30 mg/kg) was dissolved (6 mg/ml) in 5% dextrose and compared with both saline and dextrose (1.2 ml) i.v. infusions given over a 4-h period starting 1 h after occlusion. Saline-treated rats had a mean infarct of 183 +/- 27 mm3 (n = 6), dextrose-treated had 200 +/- 30 mm3 (n = 9), while for NBQX-treated rats it was reduced to 129 +/- 60 mm3 (n = 10, p < 0.05). Intravenous NBQX precipitated into the renal tubules, causing nephrotoxicity. In Expt. 3, rats were given either saline (1 ml i.p.) or GYKI 52466 (10 mg/kg i.p.) at 30 and 90 min following occlusion and at 30, 90, and 150 min following reperfusion. Saline-treated rats sustained 187 +/- 27 mm3 of neocortical infarction (n = 7), while those treated with GYKI 52466 were protected, with 139 +/- 38 mm3 of infarction (n = 7, p < 0.05). A clinically useful role for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate antagonists in embolic stroke is envisaged if nontoxic drugs can be developed, since cerebroprotection was achieved with delayed treatment with both of these lead compounds.

Animals↗
PubMed1993

Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3.

The POU-type homeodomain protein UNC-86 and the LIM-type homeodomain protein MEC-3, which specify neuronal cell fate in the nematode Caenorhabditis elegans, bind cooperatively as a heterodimer to the mec-3 promoter. Heterodimer formation increases DNA binding stability and, therefore, increases DNA binding specificity. The in vivo significance of this heterodimer formation in neuronal differentiation is suggested by (i) a loss-of-function mec-3 mutation whose product in vitro binds DNA well but forms heterodimers with UNC-86 poorly and (ii) a mec-3 mutation with wild-type function whose product binds DNA poorly but forms heterodimers well.

Amino Acid Sequence↗
PubMed1993

AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists?

The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal cerebral ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30 minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7 days. This effect was not obtained with the intraperitoneal administration of either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at the same time intervals. This effect of intraperitoneal NBQX alone was reproduced in a two-vessel occlusion/hypotension model using this same drug administration. Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the combination of NBQX and MK-801 given after a delay, produced a significant reduction in the mean volume of neocortical infarction after transient focal ischemia. We conclude that the AMPA receptor may play a more important role than the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and in neocortical infarction. AMPA antagonists should be subjected to clinical stroke trials.

Animals↗
PubMed1992

Immediate or delayed mild hypothermia prevents focal cerebral infarction.

The protective effect of mild hypothermia was studied in rodent models of both permanent and transient focal cerebral ischemia. In Expt. 1, Wistar rats were exposed to 6 h permanent ischemia by bilateral occlusion of both common carotid arteries and right middle cerebral artery. In Expt. 2, animals were exposed to 3 h transient ischemia followed by 21 h reperfusion, and in Expt. 3, 3 h transient ischemia was followed by 69 h of reperfusion. Expt. 4 used 3 h transient ischemia followed by 3 h reperfusion. In Expt. 1, animals maintained at 37 degrees C rectal (normothermia) suffered a mean infarct volume (+/- S.D.) of 142 +/- 44 mm3 (n = 6), which was reduced for those exposed to permanent hypothermic (32 degrees C) ischemia to 56 +/- 64 mm3 (n = 10) (P less than 0.05). In Expt. 2, normothermic ischemia and reperfusion resulted in an infarction of 211 +/- 35 mm3 (n = 6). Intra-ischemic hypothermia (32 degrees C) followed by 21 h of normothermic reperfusion resulted in 17 +/- 12 mm3 of infarction (n = 9) (P less than 0.001). Hypothermia for either the first or second 1.5 h of the 3 h ischemic insult reduced the infarct volume to 116 +/- 76 mm3 (n = 6) (P less than 0.05) or 108 +/- 73 mm3 (n = 7) (P less than 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effect of the NMDA receptor antagonist MK-801 on cerebral blood flow and infarct volume in experimental focal stroke.

The non-competitive N-methyl-D-aspartate receptor/channel antagonist dizocilipine maleate (MK-801) has been reported to reduce infarct volume in a variety of focal stroke models. We examined the effect of MK-801 on infarct volume and cerebral blood flow in temporary and permanent focal ischemia in rats. In Wistar rats exposed to permanent right common carotid artery and 2 h of transient right middle cerebral and left common carotid artery occlusion followed by 22 h of reperfusion, MK-801 reduced infarct volume by 73% (P less than 0.05) and significantly increased cerebral blood flow to the ischemic core throughout the 2-h period of ischemia. In spontaneously hypertensive rats (SHRs) exposed to permanent right common carotid artery occlusion and 2 h of transient right middle cerebral artery occlusion followed by 22 h of reperfusion, MK-801 decreased infarct volume by 13% (P greater than 0.05) and increased cerebral blood flow to the penumbral region. In SHRs subjected to permanent right common carotid and middle cerebral artery occlusion MK-801 reduced infarct volume by 18% at 3 h (P greater than 0.05), by 25% at 6 h (P less than 0.01) and by 18% at 24 h (P less than 0.05). MK-801-treated SHRs had no difference in cerebral blood flow to the ischemic core, but increased cerebral blood flow to penumbral zones as compared with untreated SHRs. These results suggest that the protective effect of MK-801, at least in part, relates to improved cerebral blood flow.

Animals↗
PubMed1992

Regulation of the mec-3 gene by the C.elegans homeoproteins UNC-86 and MEC-3.

The mec-3 gene encodes a homeodomain protein with LIM repeats that is required for the specification of touch cell fate in Caenorhabditis elegans. Previous experiments suggested that mec-3 expression requires the product of the unc-86 gene, a POU-type homeoprotein, and mec-3 itself. We have analyzed the control of mec-3 expression by identifying potential cis regulatory elements in the mec-3 gene (by conservation in a related nematode and by DNase I footprinting using unc-86 and mec-3 proteins) and testing their importance by transforming C.elegans with mec-3lacZ fusions in which these sites have been mutagenized in vitro. Both unc-86 and mec-3 proteins bind specifically to the promoter of the mec-3 gene, suggesting that both proteins may be directly involved in the regulation of the mec-3 gene. In addition, the footprint pattern with mec-3 protein is altered in the presence of unc-86 protein. In vivo transformation experiments reveal that some of the binding regions of the two proteins are needed for general positive control and maintenance of mec-3 expression while others have no detectable, unique function. Interestingly, the unc-86 gene appears to be required not only to initiate mec-3 expression but also to maintain it.

Amino Acid Sequence↗
PubMed1992

A new model of temporary focal neocortical ischemia in the rat.

BACKGROUND AND PURPOSE: We describe a new rat model of temporary focal ischemia that produces neocortical ischemia without the need for prolonged anesthesia. METHODS: Temporary focal cerebral ischemia was initiated during halothane anesthesia, maintained for varying periods without anesthesia, and reversed by clip removal requiring brief anesthesia. Tandem carotid and middle cerebral artery occlusion for 1-4 hours and permanent occlusion were used to determine the duration and extent of ischemia necessary to produce predictable volumes of neocortical infarction in Wistar and spontaneously hypertensive rats. RESULTS: In Wistar rats, occlusion of the right middle cerebral and both common carotid arteries resulted in cerebral blood flow reductions to approximately 8% of baseline. One hour of transient ischemia with 23 hours of reperfusion did not result in infarction. Three hours of ischemia followed by 21 hours of reperfusion resulted in infarction comparable to that caused by 24 hours of permanent ischemia. In spontaneously hypertensive rats, unilateral right middle cerebral and common carotid artery occlusion reduced cerebral blood flow to approximately 11% of baseline. Minimal damage was seen with 1 hour of reversible ischemia, but intervals of 2 and subsequently 3 hours followed by 22-21 hours of reperfusion produced progressively larger infarcts. Damage indistinguishable from that seen with 24 hours of permanent ischemia was seen with 3 or 4 hours of transient ischemia followed by 21 or 20 hours of reperfusion. CONCLUSIONS: For unanesthetized normothermic rats, cerebral blood flow reductions to 10-20% of baseline resulted in maximal infarction once ischemic durations exceeded 2-3 hours. To be effective, experimental therapies aimed at lessening infarct size or restoring blood flow must be initiated within this critical time interval.

Animals↗
PubMed1992

Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: We examined the cytoprotective effect of the lipid peroxidation inhibitor tirilazad mesylate (U74006F) in rodent models of neocortical infarction induced by transient and permanent focal cerebral ischemia. METHODS: Wistar rats (experiment 1) and spontaneously hypertensive rats (experiment 2) were subjected to 2 hours of transient middle cerebral artery occlusion followed by 22 hours of reperfusion and pretreated with 10 mg/kg i.p. tirilazad, vehicle, or saline. Repeat doses were given at 4 and 10 hours after reperfusion. Spontaneously hypertensive rats were also subjected to permanent middle cerebral artery occlusion and either pretreated with tirilazad, vehicle, or saline intraperitoneally (experiment 3) or treated with either tirilazad or vehicle intravenously after ischemia (experiment 4). Cortical infarct volumes were measured 24 hours after the onset of either transient or permanent ischemia, and changes in core regional cerebral blood flow were monitored with laser Doppler flowmetry. RESULTS: Tirilazad reduced infarct volume after transient ischemia by 40% in Wistar rats (p = 0.08) (experiment 1) and 23% in spontaneously hypertensive rats (p less than 0.05) (experiment 2) but did not reduce infarction after permanent ischemia whether it was given intraperitoneally (experiment 3) or intravenously (experiment 4). Ischemic core blood flows were not affected during ischemia, nor were they affected during reperfusion after transient ischemia. CONCLUSIONS: Tirilazad reduces cortical infarction in transient but not permanent ischemia, an effect not related to improvement in regional cerebral blood flow. Tirilazad might prove to be useful as an adjuvant therapy after successful thrombolysis in acute stroke patients.

Animals↗
PubMed1992

[A case-control study on the transmission factor of hepatitis A outbreak of Wenzhou in 1988].

This investigation described a pair-matched case-control study on transmission factors of hepatitis A outbreak in Wenzhou City in earlier 1988. The results during early stage of the epidemic showed that, for the people having had meal in eating houses OR was 9.08, whereas for those having eaten clams OR was 3.63. The results during middle and later stages showed that, for the contactor of hepatitis A patients OR was 5.02, while for those having eaten clams OR was 4.29. The result of this investigation showed that this outbreak was related to eating in eating houses during the early stage of the epidemic, but related to both contact with HA patients and eating clams during middle and later stages of the epidemic.

Adult↗
PubMed1991

Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia.

The potent and selective AMPA receptor antagonist NBQX was tested for cytoprotective properties in an adult rat model of transient focal neocortical ischemia. Nineteen spontaneously hypertensive rats sustained 2 h of middle cerebral artery occlusion, followed by 22 h of recirculation. Ninety minutes following the onset of ischemia, at the time of, and 30 min following reperfusion, they received i.p. injections of either saline (n = 10) or 30 mg kg-1 of NBQX (n = 9). Saline-treated rats had a mean volume of neocortical infarction ( +/- s.d.) of 181 +/- 31 mm3, while NBQX-treated rats sustained significantly less damage, 125 +/- 19 mm3 (p less than 0.001). Regional cerebral blood flows during ischemia and reperfusion were not affected by the drug. We suggest that the AMPA receptor may play an important role in ischemic cerebral infarction.

Animals↗
PubMedDate not supplied

The influence of proglumide, a putative CCK antagonist, on cerebral ischemia in gerbil.

Studies were conducted to clarify the possible role of CCK in cerebral ischemia and to evaluate the effects of proglumide, a competitive and reversible CCK antagonist, as a potential therapeutic or prophylactic tool in the treatment of cerebral ischemia. Proglumide at the doses of 10, 50 and 150 mg/kg was administered to gerbils before unilateral carotid ligation, and its effect on stroke index score, incidence and mortality rate was observed. Our results show that proglumide injected prior to carotid ligation at the dose of 150 mg/kg significantly reduces both incidence and mortality rate and changes the distribution of the stroke index score in gerbils. There was a significant inverse relationship between the dose of proglumide and both incidence and mortality: the greater the injection dose of proglumide, the lower the incidence and mortality. These results suggest that CCK may be involved in the pathological processes of cerebral ischemia and proglumide or related compounds prove to be effective in the pharmacological prophylaxis of ischemic brain damage.

Animals↗
PubMedDate not supplied

Enhanced effects of combined bu-zhong-yi-qi-tang (TJ-41) and interleukin-18 on the production of tumour necrosis factor-alpha and interferon-gamma in human peripheral blood mononuclear cells.

Co-stimulatory molecules play important roles in immune responses. We investigated the effect of Bu-Zhong-Yi-Qi-Tang (TJ-41) on the expression of intercellular adhesion molecule-1 (ICAM-1), B7.1 and B7.2 by peripheral blood mononuclear cells stimulated by interleukin-18 (IL-18) using fluorescence-activated cell sorter analysis. TJ-41 increased IL-18-induced ICAM-1 and B7.2 expression, resulting in enhanced production of tumour necrosis factor-alpha and interferon-gamma. These results suggest that TJ-41 enhances IL-18-induced cell-mediated immunity and may enhance host defence mechanisms against pathogens.

Antigens, CD↗