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X Q Gu

Publications and source records attributed to X Q Gu.

At least 19 recordsLinked to original sources
PubMed2003

The role of HCO3(-)-dependent mechanisms in pHi regulation during O2 deprivation.

We have reported in our previous work that, in the absence of HCO(3)(-), Na(+)/H(+) exchanger is responsible for an anoxia-induced alkalinization in hippocampal CA1 neurons. HCO(3)(-)-dependent mechanisms have been reported to play a key role in pH(i) regulation in nerve cells, but how their function is affected by O(2) deprivation has not been well studied. In this work, pH(i) measurements (obtained from dissociated neurons loaded with carboxy-seminaphthorhodafluor-1 and using confocal microscopy) and whole-cell patch clamp recording techniques were used to investigate the role of HCO(3)(-)-dependent membrane exchangers on CA1 neurons during O(2) deprivation. Anoxia (5 min) induced a small acidification in neurons in the presence of HCO(3)(-) and this acidification was changed to a significant alkalinization when neurons were bathed with Hepes buffer or when 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid was applied in a HCO(3)(-) solution, indicating that HCO(3)(-)-dependent mechanisms were involved. A marked anoxia-induced acidification (0.33+/-0.11 pH unit) was seen when the Na(+)/H(+) exchange was blocked with 3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate in the presence of HCO(3)(-), but the same anoxia did not cause a significant pH(i) change in a Na(+) free, HCO(3)(-) solution, suggesting that the anoxia-induced acidification in the presence of 3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate is dependent on both Na(+) and HCO(3)(-). Furthermore, anoxia did not cause a significant pH(i) change when both 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate were present. Current clamp recordings showed a significant membrane depolarization following anoxia in HCO(3)(-) solution but not in Hepes buffer. Our data suggest that, in hippocampal neurons: a) pH(i) regulation during O(2) deprivation is affected not only by metabolism but also by membrane exchangers, and b) besides the activation of Na(+)/H(+) exchange, anoxia activates a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive, Na(+)-dependent acid loader (possibly electrogenic).

Animals↗
PubMed2001

Increased neuronal excitability and seizures in the Na(+)/H(+) exchanger null mutant mouse.

Mice lacking the Na(+)/H(+) exchanger isoform 1 (NHE1) manifest neurological diseases that include ataxia, motor deficits, and a seizure disorder. The molecular basis for the phenotype has not been clear, and it has not been determined how the lack of NHE1 leads, in particular, to the seizure disorder. We have shown in this work that hippocampal CA1 neurons in mutant mice have a much higher excitability than in wild-type mice. This higher excitability is partly based on an upregulation of the Na(+) current density (608.2 +/- 123.2 pA/pF in NHE1 mutant vs. 334.7 +/- 63.7 pA/pF in wild type in HCO/CO(2)). Alterations in Na(+) channel characteristics, including steady-state inactivation (shift of 18 mV in the depolarization direction in the mutant), recovery from inactivation (tau(h) = 5.22 +/- 0.49 ms in wild-type neurons and 2.20 +/- 0.20 ms in mutant neurons), and deactivation (at -100 mV, tau(d) = 1.75 +/- 0.53 ms in mutant and 0.21 +/- 0.05 ms in wild-type neurons) further enhance the differences in excitability between mutant and wild-type mice. Our investigation demonstrates the existence of an important functional interaction between the NHE1 protein and the voltage-sensitive Na(+) channel. We hypothesize that the increased neuronal excitability and possibly the seizure disorder in mice lacking the NHE1 is due, at least in part, to changes in Na(+) channel expression and/or regulation.

Action Potentials↗
PubMed2001

Role of Na(+)/H(+) exchanger during O(2) deprivation in mouse CA1 neurons.

To determine the role of membrane transporters in intracellular pH (pH(i)) regulation under conditions of low microenvironmental O(2), we monitored pH(i) in isolated single CA1 neurons using the fluorescent indicator carboxyseminaphthorhodafluor-1 and confocal microscopy. After total O(2) deprivation or anoxia (PO(2) approximately equal to 0 Torr), a large increase in pH(i) was seen in CA1 neurons in HEPES buffer, but a drop in pH(i), albeit small, was observed in the presence of HCO(3)(-). Ionic substitution and pharmacological experiments showed that the large anoxia-induced pH(i) increase in HEPES buffer was totally Na(+) dependent and was blocked by HOE-694, strongly suggesting the activation of the Na(+)/H(+) exchanger (NHE). Also, this pH(i) increase in HEPES buffer was significantly smaller in Na(+)/H(+) exchanger isoform 1 (NHE1) null mutant CA1 neurons than in wild-type neurons, demonstrating that NHE1 is responsible for part of the pH(i) increase following anoxia. Both chelerythrine and H-89 partly blocked, and H-7 totally eliminated, this anoxia-induced pH(i) increase in the absence of HCO. We conclude that 1) O(2) deprivation activates Na(+)/H(+) exchange by enhancing protein kinase activity and 2) membrane proteins, such as NHE, actively participate in regulating pH(i) during low-O(2) states in neurons.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic hypoxia.

To study the physiological effects of chronic intermittent hypoxia on neuronal excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h daily (12 cycles/h) for approximately 4 wk, starting at 2-3 days of age, and examined the properties of freshly dissociated hippocampal neurons in vitro. Compared with control (Con) hippocampal CA1 neurons, exposed (Cyc) neurons showed action potentials (AP) with a smaller amplitude and a longer duration and a more depolarized resting membrane potential. They also have a lower rate of spontaneous firing of AP and a higher rheobase. Furthermore, there was downregulation of the Na(+) current density in Cyc compared with Con neurons (356.09 +/- 54.03 pA/pF in Cyc neurons vs. 508.48 +/- 67.30 pA/pF in Con, P < 0.04). Na(+) channel characteristics, including activation, steady-state inactivation, and recovery from inactivation, were similar in both groups. The deactivation rate, however, was much larger in Cyc than in Con (at -100 mV, time constant for deactivation = 0.37 +/- 0.04 ms in Cyc neurons and 0.18 +/- 0.01 ms in Con neurons). We conclude that the decreased neuronal excitability in mice neurons treated with cyclic hypoxia is due, at least in part, to differences in passive properties (e.g., resting membrane potential) and in Na(+) channel expression and/or regulation. We hypothesize that this decreased excitability is an adaptive response that attempts to decrease the energy expenditure that is used for adjusting disturbances in ionic homeostasis in low-O(2) conditions.

Action Potentials↗
PubMed2001

Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster.

O2 deprivation can produce many devastating clinical conditions such as myocardial infarct and stroke. The molecular mechanisms underlying the inherent tissue susceptibility or tolerance to O2 lack are, however, not well defined. Since the fruit fly, Drosophila melanogaster, is extraordinarily tolerant to O2 deprivation, we have performed a genetic screen in the Drosophila to search for loss-of-function mutants that are sensitive to low O2. Here we report on the genetic and molecular characterization of one of the genes identified from this screen, named hypnos-2. This gene encodes a Drosophila pre-mRNA adenosine deaminase (dADAR) and is expressed almost exclusively in the adult central nervous system. Disruption of the dADAR gene results in totally unedited sodium (Para), calcium (Dmca1A), and chloride (DrosGluCl-alpha) channels, a very prolonged recovery from anoxic stupor, a vulnerability to heat shock and increased O2 demands, and neuronal degeneration in aged flies. These data clearly demonstrate that, through the editing of ion channels as targets, dADAR, for which there are mammalian homologues, is essential for adaptation to altered environmental stresses such as O2 deprivation and for the prevention of premature neuronal degeneration.

Adenosine Deaminase↗
PubMed2000

Effect of extracellular HCO(3)(-) on Na(+) channel characteristics in hippocampal CA1 neurons.

The effect of HCO(3)(-)/CO(2) on membrane properties of isolated hippocampal CA1 neurons was studied with the use of the whole cell configuration of the patch-clamp technique. Neurons were acutely dissociated from 21- to 30-day-old mice. In the current-clamp mode, HCO(3)(-)/CO(2) significantly hyperpolarized CA1 neurons by more than 10 mV and decreased their input resistance. In addition, the overall excitability of these neurons was lower in the presence of HCO(3)(-)/CO(2) than in HEPES. Spontaneous and evoked action potential firing frequency was lower in the presence of HCO(3)(-)/CO(2) than in its absence. In the voltage-clamp mode, both activation and steady-state inactivation of a fast Na(+) current were shifted in the hyperpolarized direction in such a way that the window currents were smaller in HCO(3)(-)/CO(2) than in HEPES. Recovery from inactivation and deactivation from the open state of the fast Na(+) current was slower in HCO(3)(-)/CO(2) than in HEPES. We conclude that HCO(3)(-)/CO(2) decreases the intrinsic excitability of CA1 neurons by altering not only the passive properties of the neuronal membranes but also by changing several characteristics of the fast Na(+) current, including activation and inactivation kinetics as well as the recovery from inactivation and deactivation.

Action Potentials↗
PubMed1999

Drosophila neurons respond differently to hypoxia and cyanide than rat neurons.

Compared with mammalian species, Drosophila melanogaster exhibits marked tolerance to hypoxia or anoxia. However, the underlying cellular mechanisms of tolerance are still largely unknown. In order to assess the electrophysiologic response to O(2) lack in Drosophila neurons and compare them to those in mammals, we used neurons from embryonic cultures of both Drosophila and rat. We studied the effects of hypoxia on membrane potential V(m), input resistance R(m), rheobase, and action potential characteristics before, during and after 3 to 5 min of hypoxia (measured PO(2)<20 Torr). In Drosophila neurons, on the one hand, V(m) reversibly hyperpolarized with hypoxia by an average of about 20 mV and input resistance decreased by 71% from control. In most cells studied, action potential (AP) amplitude decreased, its duration increased, and its threshold shifted in a hyperpolarized direction before AP generation was attenuated. On the other hand, V(m) in rat cortical neurons reversibly depolarized by an average of 10 mV with hypoxia. Input resistance was reversibly reduced by 58% and, in most cells studied, AP amplitude also decreased and its duration increased. In contrast to the effects of hypoxia on V(m), CN caused a depolarization by 22 mV and a slight increase in R(m) in Drosophila. In the rat, CN was similar to hypoxia in its effect on R(m). We conclude that (1) rat and Drosophila neurons decrease their excitability in hypoxia by activating different mechanisms; (2) the most likely explanation for the hyperpolarization and the decrease in R(m) in Drosophila neurons is the activation of a K(+) conductance; this activation, by itself, cannot explain the results in rat neurons and (3) hypoxia and cyanide have similar effects in rat neurons but are divergent in their effects in Drosophila neurons.

Animals↗
PubMed1999

Intracellular pH regulation of CA1 neurons in Na(+)/H(+) isoform 1 mutant mice.

To understand the role of Na(+)/H(+) exchanger 1 (NHE1) in intracellular pH (pH(i)) regulation and neuronal function, we took advantage of natural knockout mice lacking NHE1, the most ubiquitously and densely expressed NHE isoform in the central nervous system (CNS). CA1 neurons from both wild-type (WT) and NHE1 mutant mice were studied by continuous monitoring of pH(i), using the fluorescent indicator carboxy-seminaphthorhodafluor-1 (SNARF-1) and confocal microscopy. In the nominal absence of CO(2)/HCO(3)(-), steady-state pH(i) was higher in WT neurons than in mutant neurons. Using the NH(4)Cl prepulse technique, we also show that H(+) flux in WT neurons was much greater than in mutant neurons. The recovery from acid load was blocked in WT neurons, but not in mutant neurons, by removal of Na(+) from the extracellular solution or by using 100 microM 3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate (HOE 694) in HEPES buffer. Surprisingly, in the presence of CO(2)/HCO(3)(-), the difference in H(+) flux between WT and mutant mice was even more exaggerated, with a difference of more than 250 microM/s between them at pH 6.6. H(+) flux in CO(2)/HCO(3)(-) was responsive to diisothiocyanato-stilbene-2, 2'-disulfonate (DIDS) in the WT but not in the mutant. We conclude that (a) the absence of NHE1 in the mutant neurons tended to cause lower steady-state pH(i) and, perhaps more importantly, markedly reduced the rate of recovery from an acid load; and (b) this difference in the rate of recovery between mutant and WT neurons was surprisingly larger in the presence, rather than in the absence, of HCO(3)(-), indicating that the presence of NHE1 is essential for the regulation and/or functional expression of both HCO(3)(-)-dependent and -independent transporters in neurons.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

High-performance liquid chromatographic separation and nanogram quantitation of bupivacaine enantiomers in blood.

Chiral separation of rac-bupivacaine extracted from blood was achieved with similar limits of detection but using a much simpler sample preparation than reported previously. The simple one-step sample preparation devised was highly robust and efficient and allowed a very high throughput of samples. The high-performance liquid chromatography (HPLC) conditions used gave baseline separation of the enantiomers with high sensitivity. R-(+)-bupivacaine and S-(-)-bupivacaine blood concentrations were determined using a chiral stationary phase (AGP, ChromTech) with diode array detection at 220 nm; this wavelength produced a stable baseline allowing semi-automated analysis. Sample preparation involved addition of internal standard (diphenhydramine), basification of blood, extraction with n-hexane, concentration of the extract to dryness and reconstitution in 0.002 M phosphoric acid. At rac-bupivacaine concentrations of 0.5, 5 and 50 microg/ml in blood, assay accuracy as estimated by coefficients of variation (C.V.s), were 3.3, 1.4, and 1.6%, respectively, for R-(+)-bupivacaine and 3.7, 2.0 and 1.5%, respectively, for S-(-)-bupivacaine. Using 0.6-ml samples, the estimated limits of detection for R-(+)-bupivacaine and S-(-)-bupivacaine were both 15 ng/ml of blood. Calibration curves (n=188) were linear from 0.1 to 50 microg/ml with all correlation coefficients being greater than 0.99. This semi-automated method was applied to studies involving whole body pharmacokinetics with intravenous doses ranging from 12.5 to 350 mg and regional myocardial pharmacokinetics with coronary arterial doses ranging from 2.5 to 12.5 mg. These studies generated approximately 12000 blood samples.

Anesthetics, Local↗
PubMed1997

Schwann cells modulate sodium channel expression in spinal sensory neurons in vitro.

In order to study the factors that govern the expression of sodium channel alpha-, beta1- and beta2-subunits, the influence that Schwann cells (SC) exert in the expression of sodium channels in DRG neurons was examined with in situ hybridization, immunocytochemistry, and patch clamp recording. The expression of sodium channel alpha-, beta1-, and beta2-subunit mRNAs in DRG neurons isolated from E15 rats cultured in defined medium in the absence (control) or presence of SC, or in SC-conditioned medium, was examined with isoform-specific riboprobes for sodium channel alpha-subunits I, II, III, NaG, Na6, hNE/PN1, SNS, and beta1- and beta2-subunits. DRG neurons cultured in the presence of SC displayed a significant (P < 0.05) increase in the hybridization signal for NaG, Na6, SNS, and Na beta2 mRNAs in comparison to control DRG neurons. In contrast, in SC-conditioned medium, only the hybridization signal for SNS mRNA was significantly increased. The upregulation of sodium channel mRNAs in DRG neurons co-cultured with SC was paralleled by an increase in sodium channel immunoreactivity of these cells. An increase in the mean sodium current density in DRG neurons in the presence of SC was also observed. These results demonstrate that a SC-derived factor selectively upregulates sodium channel alpha- and beta-subunit mRNAs in DRG neurons isolated from E15 rats that is reflected in an increase in functional sodium channels in these cells. This culture system may allow elucidation of the SC factor(s) that modulate the expression of sodium channels in DRG neurons.

Animals↗
PubMed1997

TTX-sensitive and -resistant Na+ currents, and mRNA for the TTX-resistant rH1 channel, are expressed in B104 neuroblastoma cells.

To examine the molecular basis for membrane excitability in a neuroblastoma cell line, we used whole cell patch-clamp methods and reverse transcription-polymerase chain reaction (RT-PCR) to study Na+ currents and channels in B104 cells. We distinguished Tetrodotoxin (TTX)-sensitive and -resistant Na+ currents and detected the mRNA for the cardiac rH1 channel in B104 cells. Na+ currents could be recorded in 65% of cells. In the absence of TTX, mean peak Na+ current density was 126 +/- 19 pA/pF, corresponding to a channel density of 2.7 +/- 0.4/micron 2 (mean +/- SE). Time-to-peak (t-peak), activation (tau m), and inactivation time constants (tau h) for Na+ currents in B104 cells were 1.0 +/- 0.04, 0.4 +/- 0.06, and 0.9 +/- 0.04 ms at -10 mV. The peak conductance-voltage relationship had a V 1/2 of -39.8 +/- 1.5 mV. V 1/2 for steady-state inactivation was -81.6 +/- 1.5 mV. TTX-sensitive and -resistant components of the Na current had half-maximal inhibitions (IC50), respectively, of 1.2 nM and, minimally, 575.5 nM. The TTX-sensitive and -resistant Na+ currents were kinetically distinct; time-to-peak, tau m, and tau h for TTX-sensitive currents were shorter than for TTX-resistant currents. Steady-state voltage dependence of the two currents was indistinguishable. The presence of TTX-sensitive and -resistant Na+ currents, which are pharmacologically and kinetically distinct, led us to search for mRNAs known to be associated with TTX-resistant channels, in addition to the alpha subunit mRNAs, which have previously been shown to be expressed in these cells. Using RT-PCR and restriction enzyme mapping, we were unable to detect alpha SNS, but detected mRNA for rH1, which is known to encode a TTX-resistant channel, in B104 cells. B104 neuroblastoma cells thus express TTX-sensitive and -resistant Na+ currents. These appear to be encoded by neuronal-type and cardiac Na+ channel mRNAs including the RH1 transcript. This cell line may be useful for studies on the rH1 channel, which is known to be mutated in the long-QT syndrome.

Brain Neoplasms↗
PubMed1996

Action potential-like responses in B104 cells with low Na+ channel densities.

Action potential generation and Na+ currents were studied in B104 neuroblastoma cells in vitro using the whole-cell patch-clamp method in voltage-clamp and current-clamp mode. Action potential-like responses were elicited in 38 of 42 cells, with a threshold close to -55 mV for depolarizing stimuli, and -56 mV for anode-break stimuli. Response amplitudes were larger when cells were held at more negative prepulse potentials, and were well fit by a Boltzmann distribution with a midpoint of approx. -75 mV, close to the V1/2 for Na+ current steady-state inactivation in these cells. Cells displaying action potential-like responses exhibited a peak Na+ current density of 133 +/- 0.14 pA/pF (range, 10.2-296.2 pA/pF) and a low gK:gNa ratio (0.0067 +/- 0.0023). Exposure to 0.1 mM Cd2+ did not block the generation of action potential-like responses in B104 cells, while 1 microM TTX abolished the responses. We conclude that low densities of Na+ channels (< 3/microns2, and < 1/micron2 in some cells) can support the generation of action potential-like responses in B104 cells if they are held at hyperpolarized levels to remove inactivation. The low leak and K+ conductance of these cells may contribute to their ability to generate action potential-like responses under these circumstances.

Action Potentials↗
PubMed1995

The development of occupational exposure limits for chemical substances in China.

This paper presents a comprehensive review of the occupational exposure limits (OELs) of chemical substances in China. It provides historical background on the development of OELs in this country, with a complete list of traditionally adopted and newly developed OELs for chemicals in workplaces. The philosophical thoughts, the administrative system, the scientific protocols for setting and amending health standards, with emphasis on making health a basic criterion for setting health standards, strengthening epidemiological studies of the human population, integrating epidemiological and toxicological studies, considering technological and economical feasibilities, and making full use of literature information sources are discussed. Further perspectives with respect to practical issues of maximum allowable concentration and time-weighted average, selection of safety factors, and establishment of biological exposure limits are also considered, with the authors' contributions to a discussion on these topics.

Air Pollutants, Occupational↗
PubMed1995

Ascertainment corrected prevalence rate (ACPR) of leukopenia in workers exposed to benzene in small-scale industries calculated with capture-recapture methods.

ACPRs of leukopenia in peripheral blood of workers exposed to benzene in small-scale industries are calculated using capture-recapture methods. The results from two figures with 6-month apart demonstrate that the ACPR in workers exposed to benzene is 36.81(29.14-44)%, significantly higher than that of control 12.71(7.20-18.22)% (P < 0.05), with a relative risk of 2.9. The prevalences of 4 cross-sectional investigations in exposure group calculated with routine method are 18.73%, 26.37%, 27.93%, and 36.76% respectively; in controls, 8.38%, 6.85%, 7.94%, and 15.00% respectively and all fall in the range of 95% CI of ACPR. It is suggested that the methods of calculating ACPR by capture-recapture methods is simple, feasible and efficient, with the results more precise than with traditional methods.

Adult↗
PubMed1992

Effects of lectins on quantal release at the frog neuromuscular junction.

This work was initiated because pretreatment with concanavalin A was reported to abolish the increase in spontaneous quantal release produced by hypertonic solutions [Gorio A. and Mauro A. (1979) J. gen. Physiol. 73, 245-263]. This suggested that lectins might be valuable tools for investigating the role of glycoproteins in the response to tonicity. We compared muscles soaked for 2 h in hypertonic solution containing concanavalin A with paired muscles soaked in hypertonic solution without lectin. The lectin treatment decreased miniature end-plate potential frequencies in Ringer and in hypertonic solutions compared with the controls. Even after lectin treatment hypertonic solutions and elevated K+ solutions increased miniature end-plate potential frequencies, and the proportional increases were the same as in controls. The lectin treatment lowered baseline frequency, but the preparation still responded to hypertonic solutions. Concanavalin A effects appeared after treatment for more than 1 h and required concentrations of 10 micrograms/ml or higher. Higher concentrations did not produce more effect. Similar results were obtained with four other lectins with different sugar specificities. Treatment in hypertonic solution without lectin produces a similar, but smaller, decrease in baseline frequency. Concanavalin A pretreatment had no detectable effects on evoked release or facilitation. We conclude that the effects of lectins on quantal release are not mediated by binding to a single sugar group. The lectins do not produce a unique effect; they exaggerate the changes produced by hypertonic pretreatment. All of the effects could be accounted for by a reduction in baseline [Ca2+] in the nerve terminal. Such reductions are produced by lectins in many cell types.

Animals↗
PubMed1991

The current status of hygiene standard setting for chemical substances in workplaces in China.

The hygiene standard setting for occupational hazards was started in the mid 1950s in China. Three documents on exposure limits for chemical substances in the work environment and some other documents related to exposure limits for physical agents have been published since then. The latest documentation on "Hygiene Standards for the Design of Industrial Premises" (Standard TJ 36-79) was promulgated in 1979. It contains a MAC list of 134 toxin agents and dusts which are most frequently used and encountered in China. However, a more sophisticated system of scientific research on hygiene standard setting has been created since the establishment of the National Scientific Commission of Hygiene Standard Setting in 1980. This system emphasizes health as a basic criterion, it strengthens epidemiological study of the human population, it integrates domestic and international information sources and it periodically reappraises the recommended standards. Based on these principles, more than forty new standards have been set for both chemicals and dusts since the founding of the committee. These new MACs are now in the process of being promulgated and are expected to take effect as the additional part of the MAC list published in 1979. In addition, further considerations of hygiene standard setting related to the conceptual renewal, selection of safety factor, legislation and enforcement of the hygiene standard, recommendations of exposure limits for occupational carcinogens, and speeding up the pace of hygiene standard setting are proposed in this paper.

Carcinogens↗
PubMed1991

[Temperature sensitive liposome encapsulated adriamycin combined with hepatic artery embolization].

A temperature sensitive liposome composed of a vesicle membrane of dipalmitoyl phosphatidylcholine and encapsulated adriamycin was made by the modified reverse-phase evaporation method. The encapsulation efficiency measured with a centrifugal filtration method was about 38%. The phase-transition temperature of the liposome determined by DSC was 41 degrees C. The liposome size was 851 +/- 50 nm, and the size distribution was from 772 to 952 nm as measured by laser particle analyzer with dynamic light scatter method. Eighty-four percent of the encapsulated drug could be released at precisely the phase-transition temperature of liposome in vitro. The results show that the liposomal drug is sensitive to temperature-controlled release.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

[Investigation of temperature sensitive liposome encapsulated adriamycin injected into hepatic artery for targeted behavior and cancer therapy].

Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 degrees C and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The 14C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery-injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W256 carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and iv injected liposome group.

Animals↗