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Y F Zhang

Publications and source records attributed to Y F Zhang.

At least 19 recordsLinked to original sources
PubMed2000

Regionally selective blockade of GABAergic inhibition by zinc in the thalamocortical system: functional significance.

The thalamocortical (TC) system is a tightly coupled synaptic circuit in which GABAergic inhibition originating from the nucleus reticularis thalami (NRT) serves to synchronize oscillatory TC rhythmic behavior. Zinc is colocalized within nerve terminals throughout the TC system with dense staining for zinc observed in NRT, neocortex, and thalamus. Whole cell voltage-clamp recordings of GABA-evoked responses were conducted in neurons isolated from ventrobasal thalamus, NRT, and somatosensory cortex to investigate modulation of the GABA-mediated chloride conductance by zinc. Zinc blocked GABA responses in a regionally specific, noncompetitive manner within the TC system. The regional levels of GABA blockade efficacy by zinc were: thalamus > NRT > cortex. The relationship between clonazepam and zinc sensitivity of GABA(A)-mediated responses was examined to investigate possible presence or absence of specific GABA(A) receptor (GABAR) subunits. These properties of GABARs have been hypothesized previously to be dependent on presence or absence of the gamma2 subunit and seem to display an inverse relationship. In cross-correlation plots, thalamic and NRT neurons did not show a statistically significant relationship between clonazepam and zinc sensitivity; however, a statistically significant correlation was observed in cortical neurons. Spontaneous epileptic TC oscillations can be induced in vitro by perfusion of TC slices with an extracellular medium containing no added Mg(2+). Multiple varieties of oscillations are generated, including simple TC burst complexes (sTBCs), which resemble spike-wave discharge activity. A second variant was termed a complex TC burst complex (cTBC), which resembled generalized tonic clonic seizure activity. sTBCs were exacerbated by zinc, whereas cTBCs were blocked completely by zinc. This supported the concept that zinc release may modulate TC rhythms in vivo. Zinc interacts with a variety of ionic conductances, including GABAR currents, N-methyl-D-aspartate (NMDA) receptor currents, and transient potassium (A) currents. D-2-amino-5-phosphonovaleric acid and 4-aminopyridine blocked both s- and cTBCs in TC slices. Therefore NMDA and A current-blocking effects of zinc are insufficient to explain differential zinc sensitivity of these rhythms. This supports a significant role of zinc-induced GABAR modulation in differential TC rhythm effects. Zinc is localized in high levels within the TC system and appears to be released during TC activity. Furthermore application of exogenous zinc modulates TC rhythms and differentially blocks GABARs within the TC system. These data are consistent with the hypothesis that endogenously released zinc may have important neuromodulatory actions impacting generation of TC rhythms, mediated at least in part by effects on GABARs.

2-Amino-5-phosphonovalerate↗
PubMed2000

[Nutrition condition of hyaluronic acid fermentation with Streptococcus zooepidemicus].

Based on the analysis of metabolic pathway Streptococcous zooepidemicus for hyaluronic acid (HA) synthesis, nucleotide, especially uracil, was considered to be important to cell growth and metabolism. When 0.005 g.L-1 uracil added in the media in which yeast extract as complex nitrogen source, cell growth and HA production were increased by 32% and 34% respectively. From analysis of amino acid in fermentation process, it was show that arginine(Arg) was needed for cell metabolism, and concentration of free Arg maintained at 0 g.L-1 in fermentation process, which was proposed to limit cell growth and HA production. By shake-flask experiment HA concentration reached 0.510 g.L-1 when 0.06 g.L-1 Arg added, in the fermentation with 2.5 L fermentor, when uracil 0.005 g.L-1 and Arg 0.06 g.L-1 were added, the rate of cell growth increased, maximum of specific growth rate, concentration of HA and HA molecular weight reached 0.67 h-1, 5.2 g.L-1 and 2.15 x 10(6) Da from 0.54 h-1, 4.2 g.L-1, 2.0 x 10(6) Da, respectively.

Arginine↗
PubMed2000

[Study on preparation and biodistribution of PEG-immunoliposomes with active carboxylic terminals].

AIM: In order to accumulate into its target specifically, the immunoliposomes must possess two characteristics: specific target efficiency to its target cells and prolonged circulation in blood. A new type of polyethylene glycol (PEG)-immunoliposomes carrying monoclonal antibodies at the distal end of PEG chains should be developed. METHODS: A dipalmitoylphosphatidylethanolamine (DPPE) derivative of PEG with carboxyl group (DPPE-PEG3000-COOH) was newly synthesized. Small unilamellar liposomes were prepared from egg phosphatidyl choline and cholesterol (5:4, mol/mol) containing 6 mol% DPPE-PEG3000-COOH using reverse-phase evaporation method followed with bath sonication. Monoclonal antibody of human bladder cancer cell (BDI-1), which is highly specific to human bladder cancer cell, was conjugated to PEG-liposomes as well as mouse IgG at the distal end of polyethylene glycol chain. Doxorubicin was entrapped into these immunoliposomes by remote (NH4)2SO4 gradient loading method. The specific targeting efficiency of these immnoliposomes was tested by cytotoxicity test in vitro, enzyme-linked immune sorbent assay (ELISA) and indirect fluorescent immunoassay. Its biodistribution was carried out in mice. RESULTS: The specific targeting efficiency of BDI-1 immunoliposomes (BDI-1-IML) to EJ cells has been demonstrated, in contrast to the nonspecific human colon carcinoma cells (LOVO). PEG-liposomes linked with mouse IgG (mouse-IgG-immunoliposomes, IgG-IML) displayed lower reticulo-endothelial systems (RES) uptake and longer circulation time than liposomes without PEG after intravenous injection. CONCLUSION: The long circulation of these PEG-immunoliposomes in vivo, combined with its specific targeting efficiency demonstrated in vitro, guarantees the positive targeting efficiency of these immunoliposomes to its target carcinoma in vivo.

Animals↗
PubMed1999

The evolutionary history of carbamoyltransferases: A complex set of paralogous genes was already present in the last universal common ancestor.

Forty-four sequences of ornithine carbamoyltransferases (OTCases) and 33 sequences of aspartate carbamoyltransferases (ATCases) representing the three domains of life were multiply aligned and a phylogenetic tree was inferred from this multiple alignment. The global topology of the composite rooted tree (each enzyme family being used as an outgroup to root the other one) suggests that present-day genes are derived from paralogous ancestral genes which were already of the same size and argues against a mechanism of fusion of independent modules. A closer observation of the detailed topology shows that this tree could not be used to assess the actual order of organismal descent. Indeed, this tree displays a complex topology for many prokaryotic sequences, with polyphyly for Bacteria in both enzyme trees and for the Archaea in the OTCase tree. Moreover, representatives of the two prokaryotic Domains are found to be interspersed in various combinations in both enzyme trees. This complexity may be explained by assuming the occurrence of two subfamilies in the OTCase tree (OTC alpha and OTC beta) and two other ones in the ATCase tree (ATC I and ATC II). These subfamilies could have arisen from duplication and selective losses of some differentiated copies during the successive speciations. We suggest that Archaea and Eukaryotes share a common ancestor in which the ancestral copies giving the present-day ATC II/OTC beta combinations were present, whereas Bacteria comprise two classes: one containing the ATC II/OTC alpha combination and the other harboring the ATC I/OTC beta combination. Moreover, multiple horizontal gene transfers could have occurred rather recently amongst prokaryotes. Whichever the actual history of carbamoyltransferases, our data suggest that the last common ancestor to all extant life possessed differentiated copies of genes coding for both carbamoyltransferases, indicating it as a rather sophisticated organism.

Amino Acid Sequence↗
PubMed1999

[Cloning and sequence analysis of ATCase genes from Psychrophilic vibrio].

The gene encoding for aspartate transcarbamoylase (ATCase) from Psychrophilic vibrio, strain 2693 was cloned and sequenced. The sequence revealed the existence of two gene encoding respectively for a catalytic chain (pyrB) and a regulatory chain (pyr I). The catalytic and regulatory polypeptide chains of Vibrio 2693 ATCase are encoded by a single pyrBI bicistronic operon, and appear to be transcribed under the control of the same promoter. The 3'-terminus of the catalytic cistron (pyrB) is adjacent to the 5'-terminus of the regulatory cistron, these is only a 4 bp space between the two coding regions.

Amino Acid Sequence↗
PubMed1998

Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma.

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs.

Alternative Splicing↗
PubMed1998

Streptomyces thermogriseus, a new species of the genus Streptomyces from soil, lake and hot-spring.

Many thermophilic actinomycetes were isolated from samples collected from a hot-spring, lake and soil in Yunnan, China. Chemical and molecular classification of four selected strains of thermophilic Streptomyces with an upper limited growth temperature of 65-68 degrees C and autolytic characteristics was carried out. A new species, Streptomyces thermogriseus sp. nov. is described. The type strain is Y-14046T (= CCTCC AA97014T).

China↗
PubMed1997

Changes in N-acetylglucosaminyltransferase III, IV and V in renal cell carcinoma.

The activities of N-acetylglucosaminyltransferase (GnT) III, IV and V were determined in 10 cases of renal cell carcinoma (RCC) and compared with the normal kidney cortex (NKC) regions of the same kidney resected from RCC patients. It was found that the GnT III and GnT IV activities decreased consistently in all samples of RCC, while GnT V activity increased, decreased or did not change in different samples. The mean levels of GnT III and GnT IV activities in RCC were found to be very significantly lower than those of NKC on statistical analysis, but the mean value of GnT V activity was almost identical in RCC and NKC. The decrease in GnT activities in RCC were compatible with the decrease in bisecting N-acetylglucosamine (GlcNAc) and antennary number of complex-type N-glycans in gamma-glutamyltranspeptidase (gamma-GT) partially purified from RCCs as studied with concanavalin A (ConA) affinity column chromatography, which showed a decrease of unbound fraction and increase of bound fractions.

Adult↗
PubMed1997

Androgen modulation of the messenger ribonucleic acid of retinoic acid receptors in the prostate, seminal vesicles, and kidney in the rat.

Previously, we reported that the steady state level of messenger RNA (mRNA) transcripts of retinoic acid receptors (RAR) alpha and gamma in the testes of 20-day-old rats can be modulated by exogenous testosterone. These results suggest that androgen regulation of Sertoli cell functions may involve biochemical events mediated by RAR genes. In this study, we examined the effects of castration and testosterone replacement on the steady state level of mRNA transcripts for RAR alpha and gamma in the prostate, seminal vesicles, and kidney of the rat. Northern blot analysis revealed that in intact adult rats, the relative steady state levels of the 3.4- and 2.7-kilobase (kb) mRNA transcripts for RAR alpha and the 3.4-kb transcript for RAR gamma in the prostate were at least 20-fold higher than those in the seminal vesicles and kidney. The relatively high abundance of RAR mRNA transcripts in the prostate suggests the physiological importance of RAR-mediated processes in this organ. Castration resulted in an increase in the level of RAR mRNA transcripts in the prostate and seminal vesicles, reaching a maximum of 2- to 4-fold in the prostate and 15- to 23-fold in the seminal vesicles within 6 days. On the other hand, the levels of mRNA transcripts of RAR alpha and -gamma in the kidney were reduced by 40-50% 1 day after castration. The effects of castration on RAR mRNA levels in all three organs were prevented by implantation of 3-cm testosterone capsules at the time of castration, a regimen that provides physiological levels of serum testosterone. In a subsequent experiment, adult male rats were given a single sc injection of 2 mg testosterone 3 days after castration. This treatment resulted in an acute suppression of the level of RAR mRNA transcripts in all three organs within 30 min. Thereafter, the levels of RAR alpha and -gamma mRNA transcripts in the prostate continued to decrease, whereas those in the seminal vesicles returned to the castrated levels within 6 h. On the other hand, RAR mRNA levels in the kidney rebounded by 1 h and remained at the level found in the untreated castrated rats. These results demonstrate that the steady state level of mRNA transcripts for RAR alpha and -gamma in the prostate, seminal vesicles, and kidney can be modulated by testosterone in organ-specific manners, thus suggesting that the RAR-mediated processes may be involved in the effects of androgen in these organs. Furthermore, the relatively low increment in prostatic RAR mRNA levels after castration compared to that in the seminal vesicles demonstrates a difference in androgen responses between these two organs. This difference could dictate the efficacy of the effects of androgen on cellular function and may contribute to the disparate vulnerabilities to androgen-related uncontrolled cell proliferation and/or malignancy in the prostate and seminal vesicles.

Animals↗
PubMed1997

Modulation of phosphatidylinositol turnover on central nicotinic receptors.

AIM: To study the modulatory effects of phosphatidylinositol (PI) turnover on nicotinic receptors in CNS, and to study the relationship between brain nicotinic receptors and PI turnover. METHODS: Effects of inositol phosphatase inhibitor lithium chloride (LiCl) and muscarinic receptor agonist oxotremorine (Oxo) on nicotine-induced convulsions were investigated in mice. RESULTS: The effects of nicotine for producing convulsions were modified by LiCl 2.5-10 mmol.kg-1, revealing the convulsive effects of nicotine > 0.8 mg.kg-1 were increased by acute pretreatment with LiCl rather than oxotremorine. Mice were given LiCl 5.0 mmol.kg-1 once a day for 7 d, the ED50 value of nicotine for producing convulsions was increased from 0.58 to 0.97 mg.kg-1, suggesting that the sensitivity of central nicotinic receptors for mediating convulsions was decreased by chronic treatment with LiCl. CONCLUSION: The functions of central nicotinic receptors were modulated by PI turnover.

Animals↗
PubMed1996

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: ethosuximide, trimethadione, and dimethadione.

Spontaneous generalized epileptiform discharges were elicited in rodent thalamocortical slices by perfusion with a medium containing no added Mg2+. In multiple-channel extracellular field potential recordings in thalamus and cortex, several distinct types of discharges were recorded, with two principal variants bearing marked similarity to spike-wave and generalized tonic-clonic seizure discharges recorded in patients with generalized seizure disorders. These discharges were termed sTBCs and cTBCs, respectively, for simple and complex thalamocortical burst complexes. The sensitivity of these discharges to the generalized absence anticonvulsants ethosuximide, trimethadione and dimethadione (the active metabolite of trimethadione) was studied. sTBCs were reduced or blocked by ethosuximide and dimethadione, when these drugs were applied in clinically relevant concentrations. The order of effectiveness of these agents was dimethadione > or = ethosuximide >> trimethadione. This paralleled the relative efficacy of these drugs in blocking T current in thalamic neurons. cTBCs were unaffected or exacerbated by these drugs. Structural control drugs including succinimide, the behaviorally inactive ring base of ethosuximide, and alpha, alpha-dimethyl-beta-methylsuccinimide, a convulsant succinimide, were inactive or exacerbated either sTBCs or cTBCs, respectively. These spontaneous generalized thalamocortical discharges in rodent thalamocortical slices may represent a potentially valuable in vitro model of generalized seizure discharges, with marked pharmacological and physiological similarities to various forms of clinical epileptic seizure activity.

Animals↗
PubMed1996

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: valproic acid, clonazepam, and alpha-methyl-alpha-phenylsuccinimide.

Spontaneous thalamocortical epileptiform activity was elicited in rodent thalamocortical slices by a medium containing no added Mg2+. Multiple varieties of activity were generated in these slices, including simple thalamocortical burst complex (sTBC) activity that resembled the spike-wave discharges of generalized absence epilepsy, and complex thalamocortical burst complex (cTBC) activity that resembled generalized tonic-clonic seizure discharges. In a further pharmacological characterization of this activity, the effects of the broad-spectrum anticonvulsants valproic acid, alpha-methyl-alpha-phenylsuccinimide (the active metabolite of methsuximide) and clonazepam were studied. All three drugs were found to be effective in controlling both sTBC and cTBC activity when applied in clinically relevant concentration ranges. The effectiveness of valproic acid against spontaneous rhythms in vitro was not due to augmentation of GABAergic inhibition. No effect of valproic acid on GABA-activated chloride currents was evident in patch-clamp recordings of acutely isolated thalamic or cortical neurons. The equivalent general clinical and experimental spectrum of action of broadly effective anticonvulsants provided an additional correlation between the clinical efficacy of anticonvulsant drugs and their effects against epileptiform discharges in rodent thalamocortical slices. This further validates spontaneous generalized low-Mg2+ thalamocortical activity as a potentially valuable in vitro model of the primary generalized epilepsies, in which the cellular mechanisms underlying generation and control of these seizure discharges can be studied.

Action Potentials↗
PubMed1996

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: phenytoin, carbamazepine, and phenobarbital.

When perfused with a medium containing no added Mg2+, rodent thalamocortical brain slices generate spontaneous generalized thalamocortical discharges of several types. Two of these discharges, termed simple and complex thalamocortical burst complexes (sTBCs and cTBCs), are physiologically and pharmacologically similar to the spike-wave discharges of generalized absence epilepsy and to the discharges underlying generalized tonic-clonic seizures, respectively. In a further characterization of the pharmacology of generalized thalamocortical discharges recorded in rodent thalamocortical slices, the actions of anticonvulsants effective in control of partial and generalized tonic-clonic seizures, but not generalized absence seizures, were studied on these rhythms. The effects of phenytoin, carbamazepine, and phenobarbital were tested against sTBCs and cTBCs recorded in vitro in rodent thalamocortical slices. When applied in clinically relevant concentrations, phenytoin and carbamazepine were very effective in reducing or blocking cTBCs. These drugs were much less effective in controlling sTBCs. Phenobarbital was effective in controlling both sTBCs and cTBCs, but the level of block was greater for cTBCs. Therefore, it appears that sTBCs and cTBCs are quite distinct in their relative sensitivity to anticonvulsant drugs, and this differential sensitivity parallels the relative effectiveness of these drugs in controlling generalized absence and generalized tonic-clonic seizures.

Animals↗
PubMed1996

Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats.

PURPOSE: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (Tmax), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. METHODS: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature > 42 degrees C). RESULTS: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0.05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. CONCLUSIONS: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.

Adult↗
PubMed1996

Characterization of GABAA receptor function in human temporal cortical neurons.

1. Surgically resected tissue from the tip of the human temporal lobe of seven patients undergoing temporal lobectomy was employed to study functional properties of GABAergic inhibition mediated through activation of GABAA receptors, using patch-clamp recording techniques in acutely isolated neurons and in slices of human temporal cortex. 2. Human temporal cortical pyramidal neurons from surgically resected tissue could be acutely isolated with the use of conventional methods. These neurons appeared normal in morphology, in their intrinsic membrane properties, and in their response to application of exogenous gamma-aminobutyric acid (GABA). 3. Application of GABA to acutely isolated human temporal cortical neurons elicited a large current with an average reversal potential of -65 mV, presumably mediated through a GABAA-activated chloride conductance. Application of varying concentrations of GABA generated a concentration/response relationship that could be well-fitted by a conventional sigmoidal curve, with an EC50 of 25.5 microM and a Hill coefficient of 1.0 4. Coapplication of the benzodiazepine clonazepam and 10 microM GABA augmented the amplitude of the GABA response. The concentration dependence of this benzodiazepine augmentation could be best-fitted by an equation assuming that the benzodiazepine interacted with two distinct binding sites, with differing potencies. The high-potency site had an EC50 of 0.06 nM and maximally contributed 38.5% augmentation to the total effect of clonazepam. The lower potency site had an EC50 of 16.4 nM, and contributed 66.1% maximal augmentation to the overall effect of clonazepam. These data derived from adult human temporal cortical neurons were very similar to our findings in adult rat sensory cortical neurons. 5. The effects of equimolar concentrations (100 nM) of clonazepam, a BZ1 and BZ2 agonist, and zolpidem, a selective BZ1 agonist, on acutely isolated human temporal cortical neurons were also investigated. Zolpidem and clonazepam were equally effective (71.5 vs. 65.0%, respectively) in potentiating GABA responses elicited by application of 10 microM GABA. This suggests that many of the functional benzodiazepine receptors in these neurons were of the BZ1 variety. 6. GABAergic synaptic inhibition was also studied with the use of patch-clamp recordings in slices of human temporal cortex. Extracellular stimulation at the white matter/gray matter border elicited compound synaptic events in layer II-V cortical neurons. These events usually consisted of an early excitatory postsynaptic potential (EPSP) and a late multiphasic inhibitory postsynaptic potential (IPSP). Application of either clonazepam or zolpidem (both at 100 nM) to the slice during extracellular stimulation reversibly augmented the late compound IPSP. 7. Spontaneous IPSPs were also recorded in approximately 50% of human temporal cortical neurons. These events did not have a preceding EPSP and were usually monopolar, with a single exponential rise and decay. This supported the idea that these events were triggered by spontaneous activity of GABAergic interneurons. Bath application of either clonazepam or zolpidem (both at 100nM) to the slice during ongoing spontaneous IPSP activity increased the amplitude and lengthened the time constant of decay of these events. 8. To our knowledge, this is one of the first detailed characterizations of the functional properties of GABAA-mediated inhibition in human cortical neurons using patch-clamp recordings in both isolated cells and slices of resected temporal cortex. Isolated pyramidal neurons exhibited GABAA-mediated currents that were comparable in many aspects with GABA currents recorded from adult rat cortical neurons, including similar GABA concentration/response curves, and similar two differing potency site effects for clonazepam augmentation of GABA currents. In addition, evoked and spontaneous IPSPs recorded in human cortical neurons appeared similar to IPSPs in rat cortical

Animals↗
PubMed1995

Long-duration self-sustained epileptiform activity in the hippocampal-parahippocampal slice: a model of status epilepticus.

1. Combined hippocampal-parahippocampal slices were employed to study the development of complex epileptiform discharges after Schaeffer collateral stimulation in vitro. With repeated stimulation, slices generated several different types of epileptiform discharges, which were temporally linked to the preceding stimulus, and predictable in their progression. The first epileptiform discharge to be elicited by stimulation was a primary afterdischarge, which began immediately after the stimulation train and progressed with repeated stimulation until it had peaked in amplitude and duration by the third to fifth stimulus train. After development of the primary afterdischarge, a secondary afterdischarge began to appear, with a 2- to 5-min latency after the third to sixth stimulation train, and progressed in amplitude and duration with repeated stimulation, sometimes to durations > 30 min. 2. After development of the secondary afterdischarge, 65-70% of rostral slices triggered long-duration, spontaneous self-sustained activity. This activity consisted of repeated spontaneous 3- to 5-min duration ictallike discharges with a short interval (< 15 min between events), lasting for hours in many cases. These discharges were similar to activity seen in depth recordings of patients with complex partial status epilepticus. This cyclic spontaneous epileptiform activity was blocked by diazepam (100 nM to 1 microM), and potentiated by the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid (APV, 50 microM). Analysis of the temporal progression of epileptiform activity through multiple channel extracellular recordings demonstrated that both the interictal and ictal discharges evident during spontaneous recurrent ictal-like status epilepticus (SE) originated at a site distant from the stimulation locus, and then propagated to area CA1. 3. Intracellular recordings from CA3 neurons during spontaneous recurrent ictallike SE activity revealed the cellular correlates of this activity. Recurrent ictallike discharges were initiated at a cellular level by a large depolarization, accompanied by tonic action-potential firing. As the ictal event progressed, the neuron continued to depolarize, and a period of depolarization block ensued, which was terminated by the gradual repolarization of the neuron, with accompanying phasic burst firing. 4. A second variety of long-duration self-sustained activity was also seen in 5-10% of slices. This type of continuous sustained activity was initiated by an increase in duration of the secondary afterdischarge to 30-120 min duration with repeated stimulation. These sustained discharges were also increased in amplitude and frequency by APV (50 microM) and reduced or blocked by the benzodiazepines diazepam or clonazepam (1 microM). Sustained epileptiform discharges seen in vitro were similar to one form of seizure discharges seen in patients with SE in their frequency, duration, in their progression through a similar electrographic series of stages, and their sensitivity to benzodiazepines. 5. Intracellular recordings from CA3 neurons during continuous SE-like discharges revealed large bursts within this area during generation of generalized epileptiform activity. These bursts were coincident with extracellularly recorded population burst activity in CA1, and so were a circuit phenomenon. 6. This physiological and pharmacological correspondence between the multiple types of SE-like activity seen in vitro and in patients with SE suggests that these long-duration limbic discharges seen in slices may constitute a valuable model for study of the seizure discharges of SE. Future studies exploiting the advantages of in vitro preparations may aid in understanding physiological and pharmacological factors important in generation and control of this grave neurological condition.

Animals↗
PubMed1994

Effect of lanthanide ions on the phase behavior of dipalmitoylphosphatidylcholine multilamellar liposomes.

The effect of lanthanide ions (Ln3+) and their coordination compounds of diethylenetriamine pentaacetic acid (DTPA) on the phase behavior of dipalmitoylphosphatidylcholine (DPPC) multi-lamellar liposomes has been studied by differential scanning calorimetry (DSC), Raman spectroscopy, and freeze-fracture electron microscopic techniques. The displacement of Ca2+ binding on DPPC liposomes by lanthanide ions was also studied. The results show that the binding degree of four kinds of chloride salts with DPPC liposomes is: YbCl3 > GdCl3 > LaCl3 > CaCl2. Lanthanide ions increase the phase transition temperature of DPPC liposomes and decrease the membrane fluidity. Freeze-fracture electron microscopic results show that La3+ enhances the order of DPPC membrane. The effect of coordination compounds of lanthanides with DTPA on the phase behavior of DPPC liposomes is smaller than that of their chlorides. La3+, Gd3+, and Yb3+, can displace Ca2+ binding on DPPC liposomes, but there coordination compounds of DTPA can hardly displace Ca2+. Raman spectroscopic results show that a very slight effect in lateral packing order of DPPC liposomes was observed at various concentrations of lanthanides.

1,2-Dipalmitoylphosphatidylcholine↗