Biomedical subjects

Z Cai

Publications and source records attributed to Z Cai.

At least 19 recordsLinked to original sources

PubMed1999

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb.

Tumor suppressor p53 is a nuclear transcription factor that blocks cell cycle progression and induces apoptosis. We have previously shown that the MCF7 resistance to the cytotoxic action of TNF correlates with p53 mutations. In the present study, we used a recombinant adenovirus carrying a wild-type p53 gene (Adwtp53) in order to investigate the effect of wt p53 transfer on modulation of cell resistance to the cytotoxic action of TNF. Our data indicate that infection of TNF resistant MCF7 cells (1001 and MCF7/Adr) with Adwtp53 resulted in the restoration of wt p53 expression and function as respectively revealed by the yeast assay and the induction of p53 inducible genes MDM2 and p21. Furthermore, the restoration of p53 function significantly sensitized TNF resistant cells to TNF cytotoxic action. This correlated with a significant down-regulation of c-myc in both TNF-resistant cell lines and a decrease of Retinoblastoma protein (Rb) in 1001 clone. In contrast, the effect of p53 seems to be independent from Bcl-2 and Bax protein level regulation. The present study suggests that the combination of TNF and Adwtp53 may be a potential strategy to sensitize mutant p53 TNF-resistant tumors to the cytotoxic action of this cytokine.

Adenoviridae↗

PubMed1999

Prenatal hypoxia-ischemia alters expression and activity of nitric oxide synthase in the young rat brain and causes learning deficits.

Inhibition of nitric oxide synthase (NOS) is known to possibly impair learning and memory. Our previous studies have demonstrated that prenatal hypoxia-ischemia (HI) decreases NOS expression and NOS activity in the neonatal rat brain. To investigate whether effects of prenatal HI on NOS expression continue and whether prenatal HI affects learning and memory in young rats, NOS expression and NOS activity were determined in the hippocampus of rat brains at 28 days of age following a prenatal HI insult on G17. Performances in the passive avoidance test and the Morris water maze test were also studied in these young rats prior to sampling. Rat fetuses were subjected to either a 30-min prenatal HI insult or a sham operation (SH) on gestation day 17 and rat pups were delivered naturally. Increased locomotor activity was observed in the prenatal HI rats as compared to the SH rats on postnatal days 13 and 15, but not on postnatal days 20 and 30. Prenatal HI affected learning ability in these young rats at 28 days of age, as indicated by a delayed acquisition of passive avoidance and by longer escape latency in the Morris water maze test as compared to the SH group. Prenatal HI did not affect retention of passive avoidance and spatial memory. Concomitant with these learning deficits, expression of neuronal NOS and endothelial NOS mRNAs as well as Ca2(+)-dependent NOS activity in the hippocampus of the prenatal HI rat brain were significantly decreased as compared to the SH group. These results suggest that a 30-min prenatal HI insult on gestation day 17 in rats has long-lasting effects on NOS expression and NOS activity in the offspring brain and on learning ability of these young rats. The learning deficit in offspring is possibly associated with the reduction in expression of NOS mRNA and NOS activity in the hippocampus of these animals.

Animals↗

PubMed1999

Ab Initio Study of the Electronic Spectrum of the SiO(+) Cation.

The potential energy curves of the SiO(+) cation for the low-lying electronic states, correlating to the first two lowest dissociation channels (Si(+)((2)P(u)) + O((3)P(g)) and Si(+)((2)P(u)) + O((1)D(g))), have been calculated at the internally contracted multireference configuration interaction (CMRCI) level with Dunning's correlation-consistent polarized valence quadruple zeta (cc-pVQZ) basis set. The equilibrium bond lengths (r(e)), harmonic frequencies (omega(e)), first- and second-order anharmonicity constants (omega(e)x(e), omega(e)y(e)), rotational constants (B(e)), vibrational separations (DeltaG(1/2)), dipole moments (µ(e)), excitation (T(e)), and dissociation energies (D(e)) for eight bound doublet states (X(2)Sigma(+), A(2)Pi, B(2)Sigma(+), (2)(2)Delta, (3)(2)Sigma(+), (4)(2)Pi, (3)(2)Sigma(-), and (1)(2)Phi) and four bound quartet states (a(4)Sigma(+), (1)(4)Pi, (1)(4)Delta, and (1)(4)Sigma(-)) have been calculated. The spectroscopic constants for the X(2)Sigma(+), A(2)Pi, and B(2)Sigma(+) states are in good agreement with the available experimental data. The dipole-allowed transition moments between the studied doublet states of SiO(+) have also been calculated at the same theoretical level. Based on both the computed potential energy curves and the electronic transition moments, radiative lifetimes for the bound electronic excited states at the v' = 0, 1, and 2 vibrational levels have been calculated. The lifetimes of the B(2)Sigma(+) ( Kv' = 0, 1, and 2) states are in excellent agreement with recent experimental data. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

In vitro corrosion resistance of titanium made using different fabrication methods.

The corrosion of cast or milled ASTM Grade II CP titanium with different surface conditions was studied by potentiodynamic anodic polarization and immersion testing. Specimens were fabricated using three dental titanium casting systems and from machined titanium. Three surface conditions were tested: (1) sandblasted with surface reaction layers remaining; (2) polished surface without surface reaction layers; and (3) sandblasted surface without surface reaction layers. An acidic saline solution (0.1 M lactic acid/0.1 M NaC1 [pH = 2]) and an artificial saliva were used as the corrosion media. Anodic polarization was performed starting at 50 mV below the rest potential and terminating at +2250 mV vs Ag/AgCl. Two surface conditions (sandblasted with the surface reaction layers and polished without such layers) were examined in the immersion test. Specimens were immersed in the corrosion media at 37 degrees C for six months. The recovered solution was analyzed by an atomic absorption spectrophotometer for titanium dissolution. A distinctive passive region on the polarization diagram, ranging from approximately 0 to approximately +1300 mV, was observed for all specimens in both media. Great similarity was observed for all the sandblasted specimens which had larger primary passive current densities and passive regions compared to the polished ones. A current density peak at approximately +1600 mV seen for all the specimens with sandblasted surfaces was less well defined for the polished specimens. Immersion testing in the acidic saline solution revealed no significant differences among the polished specimens. A significant increase (P < 0.05) in titanium dissolution was found for the sandblasted specimens with surface reaction layers remaining on the surfaces made with phosphate-bonded SiO2/Al2O3 investment compared to the polished ones. Significant differences were also found between sandblasted specimens with the surface reaction layers resulting from different investment materials and different casting methods. Measurable amounts of titanium were not found for all specimens in the artificial saliva after six months. It is evident that the corrosion behavior of cast CP titanium is similar to that of machined titanium. The surface roughness appears to be a more prominent factor than do the surface reaction layers on the polarization behavior of the CP titanium under the present experimental conditions. Surface roughness and the presence of the surface reaction layers both affect the dissolution of titanium.

Biocompatible Materials↗

PubMed1999

Interaction of hydrated electron with dietary flavonoids and phenolic acids: rate constants and transient spectra studied by pulse radiolysis.

The reaction rate constants and transient spectra of 11 flavonoids and 4 phenolic acids reacting with e(aq)- at neutral pH were measured. Absorption bands of the transients of e(aq)- reacting with the above compounds all located at a wavelength shorter than 400 nm. The e(aq)- scavenging abilities were divided into three groups: (+)catechin ((1.2 +/-0.1) x 10(8) M(-1)s(-1)) < 4-chromanol ((4.4 +/- 0.4) x 10(8) M(-1)s(-1)) < genistein ((6.2+/-0.4) x 10(9) M (-1) s(-1) approximately genistin ((8 +/- 1) x 10(9) M(-1)s(-1)) approximately rutin ((7.6 +/- 0.4) x M(-1)s(-1) approximately caffeic acid ((8.3 +/- 0.5) x 10(9)M(-1)s(-1)) < transcinnamic acid((1.1 +/- 0.1) x 10(10) M(-1)s(-1)) approximately p-coumaric acid ((1.1 +/- 0.1) x 10(10) M(-1)s(-1) approximately 2,4,6-trihydroxylbenzoic acid((1.1 +/- 0.1) x 10(10) M(-1)s(-1)) approximately baicalein ((1.1 +/- 0.5) x 10(10) M(-1)s(-1)) approximately baicalin((1.3 + 0.1) X 10(10) M(-1)s(-1)) approximately naringenin ((1.2 +/- 0.1) x 10(10) M(-1)s(-1)) approximately naringin ((1.0 +/- 0.1) x 10(10) M(-1)s(-1)) approximately gossypin((1.2 +/- 0.1) x 10(10) M(-1)s(-1)) approximately quercetin((1.3 +/- 0.5) x 10(10) M(-1)s(-1)). These results suggested that C4 keto group is the active site for e(aq)- to attack on flavonoids and phenolic acids, whereas the o-dihydroxy structure in B ring, the C2,3 double bond, the C3-OH group, and glucosylation, which are key structures that influence the antioxidant activities of flavonoids and phenolic acids, have little effects on the e(aq)- scavenging activities.

Electrons↗

PubMed1999

Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl- channels by non-sulphonylurea hypoglycaemic agents.

1. Hypoglycaemia-inducing sulphonylureas, such as glibenclamide, inhibit cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels. In search of modulators of CFTR, we investigated the effects of the non-sulphonylurea hypoglycaemic agents meglitinide, repaglinide, and mitiglinide (KAD-1229) on CFTR Cl- channels in excised inside-out membrane patches from C127 cells expressing wild-type human CFTR. 2. When added to the intracellular solution, meglitinide and mitiglinide inhibited CFTR Cl- currents with half-maximal concentrations of 164+/-19 microM and 148+/-36 microM, respectively. However, repaglinide only weakly inhibited CFTR Cl- currents. 3. To understand better how non-sulphonylurea hypoglycaemic agents inhibit CFTR, we studied single channels. Channel blockade by both meglitinide and mitiglinide was characterized by flickery closures and a significant decrease in open probability (Po). In contrast, repaglinide was without effect on either channel gating or Po, but caused a small decrease in single-channel current amplitude. 4. Analysis of the dwell time distributions of single channels indicated that both meglitinide and mitiglinide greatly decreased the open time of CFTR. Mitiglinide-induced channel closures were about 3-fold longer than those of meglitinide. 5. Inhibition of CFTR by meglitinide and mitiglinide was voltage-dependent: at positive voltages channel blockade was relieved. 6. The data demonstrate that non-sulphonylurea hypoglycaemic agents inhibit CFTR. This indicates that these agents have a wider specificity of action than previously recognized. Like glibenclamide, non-sulphonylurea hypoglycaemic agents may inhibit CFTR by occluding the channel pore and preventing Cl- permeation.

Adenosine Triphosphate↗

PubMed1999

Volume-dependent taurine release from cultured astrocytes requires permissive [Ca(2+)](i) and calmodulin.

Cell swelling results in regulatory activation of multiple conductive anion pathways permeable toward a broad spectrum of intracellular organic osmolytes. Here, we explore the involvement of extracellular and intracellular Ca(2+) in volume-dependent [(3)H]taurine efflux from primary cultured astrocytes and compare the Ca(2+) sensitivity of this efflux in slow (high K(+) medium induced) and fast (hyposmotic medium induced) cell swelling. Neither Ca(2+)-free medium nor Ca(2+)-channel blockers prevented the volume-dependent [(3)H]taurine release. In contrast, loading cells with the membrane-permeable Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM suppressed [(3)H]taurine efflux by 65-70% and 25-30% under high-K(+) and hyposmotic conditions, respectively. Fura 2 measurements confirmed that BAPTA-AM, but not Ca(2+)-free media, significantly reduced resting intracellular Ca(2+) concentration ([Ca(2+)](i)). The calmodulin antagonists trifluoperazine and fluphenazine reversibly and irreversibly, respectively, inhibited the high-K(+)-induced [(3)H]taurine release, consistent with their known actions on calmodulin. In hyposmotic conditions, the effects were less pronounced. These data suggest that volume-dependent taurine release requires minimal basal [Ca(2+)](i) and involves calmodulin-dependent step(s). Quantitative differences in Ca(2+)/calmodulin sensitivity of high-K(+)-induced and hyposmotic medium-induced taurine efflux are due to both the effects of the inhibitors on high-K(+)-induced cell swelling and their effects on transport systems and/or signaling mechanisms determining taurine efflux.

Animals↗

PubMed1999

Methyltransferase inhibitor S-adenosyl-L-homocysteine sensitizes human breast carcinoma MCF7 cells and related TNF-resistant derivatives to TNF-mediated cytotoxicity via the ceramide-independent pathway.

In this study we investigated the signalling requirements for TNF-induced cytotoxicity modulated by the methyltransferase inhibitor S-adenosyl-L-homocysteine (AdoHcy) using the TNF-sensitive human breast carcinoma MCF7 cells and its established TNF-resistant clones (R-A1 and clone 1001). Our data indicate that inhibition of methylation reactions by adenosine plus homocysteine, which are known to condense within cells to AdoHcy, markedly potentiated TNF-induced cytotoxicity in MCF7 cells and rendered related TNF-resistant variants, TNF-sensitive by a mechanism independent from the ceramide pathway. We demonstrated that the dominant-negative derivative of FADD (FADD-DN) blocked methylation inhibition/TNF-induced cell death. Moreover, TNF-mediated cytotoxicity modulated by AdoHcy was blocked by the ICE-inhibiting peptide z-VAD-fmk, suggesting that an ICE-like protease is required for the methylation inhibition/TNF-inducible death pathway. In conclusion, these results suggest that the methyltransferase inhibitor AdoHcy potentiates TNF-induced cytotoxicity in MCF7 cells and renders TNF-resistant MCF7 clones, TNF-sensitive via the ceramide independent pathway and that FADD and the ICE-like protease are likely necessary components in transducing methylation inhibition/TNF signals for cell death.

Adenocarcinoma↗

PubMed1998

Requirements for stimulating naive CD8+ T cells via signal 1 alone.

In the absence of costimulation, TCR recognition of peptide/MHC complexes is generally considered to be nonimmunogenic. In agreement with this view, naive TCR transgenic CD8+ cells failed to respond to specific peptides presented by MHC class I (Ld) molecules bound to mouse RBC. However, peptide/Ld complexes presented by cell-sized beads or bound to plastic led to overt proliferative responses in the absence of added cytokines. Significantly, equivalent strong proliferative responses occurred when mouse RBC were fixed with glutaraldehyde before Ld coupling. The implication therefore is that the intensity of signaling via the TCR is a reflection of the mobility of the ligand being recognized; TCR signaling is weak when the ligand can move laterally on the cell membrane but strong when the ligand is immobilized.

Animals↗

PubMed1998

Analysis of human breast adenocarcinoma MCF7 resistance to tumor necrosis factor-induced cell death. Lack of correlation between JNK activation and ceramide pathway.

Considerable progress has been made in the understanding of tumor necrosis factor (TNF) signaling; however, the molecular and biochemical basis of tumor resistance to the cytotoxic action of TNF are still not definitively identified yet. Although a role of c-Jun N-terminal kinase (JNK) pathway has been suggested as an effector in TNF signaling, its exact relative contribution and its interaction with ceramide pathway and tumor resistance to TNF remain unknown. The relationship between JNK activation and human breast adenocarcinoma MCF7 resistance acquisition to the cytotoxic action of TNF was therefore investigated. We demonstrate that TNF triggers JNK activation in both TNF-sensitive MCF7 cells and its resistant derivative, RA1/1001. In addition, when MCF7 cells were stably transfected with mitogen-activated protein kinase kinase 4 (MKK4) dominant-negative cDNA or transiently transfected with a dominant-negative c-Jun mutant (TAM 67), their susceptibility to the cytotoxic action of TNF remains comparable with control cells. We also demonstrated that JNK activation does not require ceramide generation since in MCF7 cells transfected with a dominant-negative derivative of FADD (FADD-DN), which are resistant to the cytotoxic action of TNF, TNF induced JNK activation in the absence of ceramide generation. Furthermore, our data indicate that exogenous permeable synthetic ceramide C-6 induced the killing of MCF7 cells transfected with MKK4 dominant-negative cDNA. These results provide strong evidence indicating that tumor acquisition of resistance to the cytotoxic action of TNF may occur either independently or at a level downstream of JNK activation and suggest that JNK activation is not linked to ceramide pathway in TNF-mediated apoptosis.

Adenocarcinoma↗

PubMed1998

Intrauterine hypoxia-ischemia alters nitric oxide synthase expression and activity in fetal and neonatal rat brains.

The effects of intrauterine hypoxia-ischemia (HI) on nitric oxide synthase (NOS) activity and on expression of NOS isoforms were investigated in fetal and neonatal rat brains. Rat fetuses were subjected to either a 30-min intrauterine HI insult or a sham operation (SH) on gestational day 17 (G17). NOS activity in the homogenate of the rat brain was detectable on G17 and increased with age. NOS activity in the HI group was 20-30% higher than in the SH group from 6 to 48 h after the HI, but was 30% lower than in the SH group from postnatal day 8 to 14. Expression of the inducible NOS (iNOS) mRNA, as examined by RT-PCR, was increased as compared to the SH group from 6 to 24 h after the HI surgery. Expression of the constitutive neuronal NOS (nNOS) mRNA was reduced in the HI group from 24 h after the HI surgery up to postnatal day 14. Immunoblotting data have shown that alterations in NOS isoform protein expression caused by the intrauterine HI were consistent with the mRNA expression data. The overall results indicate that prenatal HI has long-lasting effects on function and expression of NOS in fetal and neonatal rat brains and that the altered NOS activity may be associated with prenatal HI-induced neurological abnormalities.

Animals↗

PubMed1998

Regulation of major histocompatibility complex class I expression by NF-kappaB-related proteins in breast cancer cells.

Downregulation of MHC Class I antigens has been observed in many cancers and usually results from a decreased gene transcription. A reporter CAT gene dependent on the MHC Class I kappaB site or on a longer promoter is transactivated by NF-kappaB complexes containing p65 or RelB. p100 as well as IkappaB-alpha are potent inhibitors of this transcription and p100 sequesters RelB and p65 complexes in the cytoplasm of breast cancer cells. However, although p100 is highly expressed in a number of breast cancer cell lines, MHC Class I antigen expression was observed on all the cell lines we analysed and could be further induced by stimulation with the cytokines IFN-gamma or TNF-alpha. Stable transfection of a unresponsive mutated IkappaB-alpha Ser 32-36 expression vector showed that TNF-alpha induced MHC Cl I expression in an NF-kappaB-dependent way while IFN-gamma did it independently of any NF-kappaB activation.

Antineoplastic Agents↗

PubMed1998

Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors.

The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism. To directly investigate the role of AML1-ETO in leukemogenesis, we used gene targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21). Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5 from a complete absence of normal fetal liver-derived definitive hematopoiesis and lethal hemorrhages. This phenotype was similar to that seen following homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained dysplastic multilineage hematopoietic progenitors that had an abnormally high self-renewal capacity in vitro. To further document the role of AML1-ETO in these growth abnormalities, we used retroviral transduction to express AML1-ETO in murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing cells were again found to have an increased self-renewal capacity and could be readily established into immortalized cell lines in vitro. Taken together, these studies suggest that AML1-ETO not only neutralizes the normal biologic activity of AML1 but also directly induces aberrant hematopoietic cell proliferation.

Animals↗

PubMed1998

Accumulation of the p53 protein allows recognition by human CTL of a wild-type p53 epitope presented by breast carcinomas and melanomas.

The p53 protein is accumulated in tumor cells of many human cancers and can elicit in vivo humoral and proliferative responses. Rare reports about p53-mediated tumor recognition by CTLs have remained questioned. We therefore studied a panel of breast tumor and melanoma cell lines that we assayed for the presence of accumulated p53 and surface HLA-A2 and for the presentation of p53 epitopes. From PBMC of a healthy donor, we have generated a CTL line, D5/L9V, directed against HLA-A2-restricted peptide 264-272 from wild-type p53. It efficiently lysed breast adenocarcinomas MCF-7, MCF7/RA1, and MDA-MB-231, and melanoma M8, which all accumulate the p53 protein. Using competition assays, we made sure that tumor lysis by D5/L9V was due to recognition of endogenously produced p53 peptide 264-272 associated with the HLA-A2.1 molecule on the surface of these tumor cells. Cells with undetectable levels of wild-type p53, such as lymphoblastoid cells and melanoma M74, were not recognized by D5/L9V. Neither were breast tumor cell line MCF7/ADR nor melanoma line M44 because of HLA loss. This study therefore shows that it is possible to obtain in vitro CTL lines that specifically recognize a p53 epitope spontaneously presented by a variety of HLA-A2+ transformed cell lines provided they display abnormal patterns of p53 expression. This work points out that breast tumors and melanomas share a p53 epitope, and raises hopes for future immunotherapeutic approaches.

Antigen-Presenting Cells↗

PubMed1998

Ab Initio Study of the Electronic Spectrum of the SiN Radical

The potential energy curves of the SiN radical for the low-lying electronic states correlating up to the fourth dissociation channel have been calculated at the internally contracted multireference configuration interaction (CMRCI) level with Dunning's correlation-consistent polarization valence triple zeta (cc-pVTZ) basis set. The equilibrium bond length (re), harmonic frequency (omegae), first- and second-order anharmonicity constants (omegaexe, omegaeye), rotational constant (Be), centrifugal distortion constant (De), and rotation-vibrational and centrifugal coupling constants (alphae and betae, respectively), as well as the dipole moment (&mgr;0), excitation (Te), and dissociation energies (D0) for the 11 bound doublet states X2Sigma+, A2Pi, B2Sigma+, C2Pi, D2Sigma-, E2Delta, F2Pi, G2Delta, H2Sigma+, I2Phi, and J2Pi and 10 bound quartet states a4Sigma+, b4Pi, c4Delta, d4Sigma-, e4Sigma+, f4Sigma-, h4Delta, i4Sigma+, j4Pi, and k4Delta have been calculated at the CMRCI level with Dunning's correlation-consistent polarization valence quadruple zeta (cc-pVQZ) basis set. Our calculations imply that the D2Pi and L2Pi states in the literature should be reassigned as C2Pi and F2Pi, respectively. Where available, our results are found to be in good agreement with the experimental data. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Half-embryo cocultivation technique for estimating the susceptibility of pea (Pisum sativum L.) and lentil (Lens culinaris Medik.) cultivars to Agrobacterium tumefaciens.

Longitudinally sliced embryonic axes from pea and lentil mature seeds cocultivated with A. tumefaciens carrying a gus reporter gene in its T-DNA provided a convenient means to evaluate the efficiency of gene transfer to tissues in different cultivars and cocultivation conditions. Use of this technique demonstrated wide variation in susceptibility to Agrobacterium among several pea and lentil commercial genotypes.

Agrobacterium tumefaciens↗

PubMed1998

Prenatal ethanol exposure enhances glutamate release stimulated by quisqualate in rat cerebellar granule cell cultures.

Effects of prenatal ethanol exposure on extracellular glutamate accumulation stimulated by glutamate receptor agonists were studied in rat cerebellar granule cell cultures. The prenatal exposure to ethanol was achieved via maternal consumption of a Sustacal liquid diet containing either 5% ethanol or isocaloric sucrose (pair-fed) substituted for ethanol from gestation d 11 until the day of parturition. Neither the basal level of extracellular glutamate nor the increased accumulation of glutamate stimulated by KCl (40 mM) or by ionotropic glutamate receptor agonists, N-methyl-D-aspartate (NMDA) or kainate (KA) (100 microM each), in cells prepared from the ethanol-fed group was significantly different from that in cells prepared from the pair-fed group. Glutamate accumulation stimulated by quisqualate (QA, 100 microM) or by trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD, 250 microM) in the ethanol-fed group was higher than that in the pair-fed group by 116 and 36%, respectively. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM), an ionotropic QA receptor antagonist, the QA-induced accumulation of glutamate in the ethanol-fed group was still higher than that in the pair-fed group. In the presence of MK-801 (5 microM), an antagonist of the NMDA receptor, the enhanced accumulation of glutamate stimulated by either QA or t-ACPD was still observable in the ethanol-fed group as compared to the pair-fed group. Addition of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM), a selective antagonist of the metabotropic glutamate receptor, abolished the enhanced accumulation of glutamate stimulated by either QA or t-ACPD in the ethanol-fed group. Although immunoblotting of mGluR1 and mGluR2/3 did not show apparent differences between the pair-fed and the ethanol-fed groups, the overall results suggest that the effect of prenatal ethanol exposure was selectively through a pathway mediated by the metabotropic glutamate receptor.

Alcoholism↗

PubMed1998

Experimental studies on traumatic facial nerve injury.

PURPOSE: The purpose of this study was to investigate the outcome of different injuries to the facial nerve. MATERIALS AND METHODS: Six patterns of injuries (exposure, compression, crushing, stretching, division and post-division anastomosis) were produced in the buccal branches of the facial nerve in 60 rabbits. Electroneuronography (ENoG) and histology at definite time were used to evaluate the results. RESULTS AND CONCLUSIONS: Exposure and compression injuries produced a neuropraxic injury and rapid recovery. Crushing and stretching injuries resulted in axonotmesis and whilst complete recovery can take place it may be very slow. Division and post-division anastomosis fall into neurotmesis injury and do not completely recover within six months; the former recovers slower and later than the latter.

Animals↗