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Biomedical subjects

J M Zhang

Publications and source records attributed to J M Zhang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia.

Chronic compression of the dorsal root ganglion (CCD) was produced in adult rats by implanting a stainless steel rod unilaterally into the intervertebral foramen, one rod at L(4) and another at L(5). Two additional groups of rats received either a sham surgery or an acute injury consisting of a transient compression of the ganglion. Withdrawal of the hindpaw was used as evidence of a nocifensive response to mechanical and thermal stimulation of the plantar surface. In addition, extracellular electrophysiological recordings of spontaneous discharges were obtained from dorsal root fibers of formerly compressed ganglia using an in vitro nerve-DRG-dorsal root preparation. The mean threshold force of punctate indentation and the mean threshold temperature of heating required to elicit a 50% incidence of foot withdrawal ipsilateral to the CCD were significantly lower than preoperative values throughout the 35 days of postoperative testing. The number of foot withdrawals ipsilateral to the CCD during a 20-min contact with a temperature-controlled floor was significantly increased over preoperative values throughout postoperative testing when the floor was 4 degrees C (hyperalgesia) and, to a lesser extent, when it was 30 degrees C (spontaneous pain). Stroking the foot with a cotton wisp never elicited a reflex withdrawal before surgery but did so in most rats tested ipsilateral to the CCD during the first 2 postoperative weeks. In contrast, the CCD produced no changes in responses to mechanical or thermal stimuli on the contralateral foot. The sham operation and acute injury produced no change in behavior other than slight, mechanical hyperalgesia for approximately 1 day, ipsilateral to the acute injury. Ectopic spontaneous discharges generated within the chronically compressed ganglion and, occurring in the absence of blood-borne chemicals and without an intact sympathetic nervous system, were recorded from neurons with intact, conducting, myelinated or unmyelinated peripheral nerve fibers. The incidence of spontaneously active myelinated fibers was 8.61% for CCD rats versus 0.96% for previously nonsurgical rats. We hypothesize that a chronic compression of the dorsal root ganglion after certain injuries or diseases of the spine may produce, in neurons with intact axons, abnormal ectopic discharges that originate from the ganglion and potentially contribute to low back pain, sciatica, hyperalgesia, and tactile allodynia.

Animals↗
PubMed1999

Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion.

Pain and hyperalgesia can occur when the dorsal root ganglion (DRG) and its roots are deformed mechanically in association with injuries or diseases of the spine. To evaluate the electrophysiological changes that contribute to this sensory pathology, intracellular recordings were obtained in vitro from DRGs that had received a chronic mechanical compression [chronic compression of DRG (CCD)]. The compression was produced by inserting L-shaped rods ipsilaterally into the intervertebral foramina, one at L(4) and the other at L(5) in rats 1-14 days before the recording. Control rats received a sham operation. Postoperatively, the threshold force applied by punctate stimulation of the plantar surface of the hind paw decreased significantly on the foot ipsilateral to the CCD (mechanical hyperalgesia) but changed little on the contralateral foot or on either foot for control rats. DRG somata were viewed through a microscope during recording and classified as small, medium, and large according to their diameters. CCD cells in each size category were more excitable than those of comparable size from control rats as judged by the significantly lowered threshold currents and action potential voltage thresholds. Spontaneous activity was recorded in 11% of all the CCD cells tested. The spontaneous activity and/or changes in both the threshold currents and action potential thresholds were observed as early as one day after injury. The association of cutaneous hyperalgesia with changes in the electrophysiological properties of DRG cells suggests a possible role for intrinsic alterations in the membrane properties of compressed DRG cells in the production and persistence of chronic pain after certain spinal injuries or pathologies of the spine.

Animals↗
PubMed1999

Protective effects of pretreatment with ginsenosides on cardiac and coronary vascular function after hypothermic rat heart preservation.

Prevention of cardiac and vascular dysfunction with pretreatment has been accepted as an important factor in heart transplantation. Ginsenosides (GS) have been reported to have some beneficial effects on the cardiac and vascular system. We hypothesized that pretreatment with GS would result in an improvement of functional recovery after a 12 hour (hr) rat heart preservation. A Langendorff apparatus was applied to estimate the cardiac and vascular function in an isolated rat heart preparation. The hearts were preserved in University of Wisconsin solution at 0 degree C for 12 hr, after pretreatment with 0.9% sodium chloride or GS 100 mg/kg, respectively, in control (n = 9) and GS (n = 14) groups. After storage, the cardiac function, myocardial water content, and coronary vasodilatory response were evaluated. The GS group showed a significantly higher recovery percentage of cardiac function compared with the control group: aortic flow 81.4 +/- 21.4% versus 57.2 +/- 11.0% (p = 0.0052); coronary flow 81.4 +/- 14.5% versus 57.2 +/- 6.0% (p = 0.0001); +/- dp/dt max 72.5 +/- 16.1% and 66.0 +/- 16.1% versus 53.7 +/- 4.1% and 51.4 +/- 7.1% (p = 0.0027 and p = 0.0189) respectively. The GS group showed a lower increase in myocardial water content. With Langendorff perfusion, the endothelial and vascular smooth-muscle cell function were evaluated by an increasing percentage of coronary flow in response to acetylcholine chloride (0.3 x 10(-7) mol/liter) and nitroglycerin (0.5 x 10(-5) mol/liter). It was significantly higher in the GS group than that in the control group (19.2 +/- 8.8% and 28.0 +/- 14.1% versus 9.9 +/- 4.7% and 14.7 +/- 8.1%, p = 0.008 and p = 0.0187, respectively) at the first minute. These results suggest a protective effect on ventricular and coronary vascular function in the rats pretreated with Ginsenosides, indicating potential benefits for long-term heart preservation.

Animals↗
PubMed1999

Modulation of NMDA receptor by huperzine A in rat cerebral cortex.

AIM: To investigate the effects of huperzine A (Hup A) on NMDA receptors in rat cerebral cortex. METHODS: 1) The effect of hup A on NMDA-induced current was studied in acutely dissociated rat hippocampal pyramidal neurons using whole-cell recording. 2) The effect of Hup A on NMDA receptor binding was assessed using [3H] dizocilpine (Diz) binding assay in synaptic membrane preparation of rat cerebral cortex. RESULTS: 1) Hup A reversibly inhibited NMDA-induced current in a concentration-dependent manner with IC50 of 45.4 mumol.L-1. 2) Hup A inhibited the specific binding of [3H]MK-801 to extensively washed synaptic membrane of rat cerebral cortex in a concentration-dependent manner with IC50 of 0.5 (0.1-1.9) mumol.L-1 (n = 4). 3) L-Glutamate 10 mumol.L-1 markedly increased [3H] MK-801 binding. In the presence of L-glutamate, Hup A 0.001-0.1 mumol.L-1 caused a further increase of the binding, whereas Hup A 1-300 mumol.L-1 inhibited the binding in a concentration-dependent manner with IC50 of 12.3 (5.8-26.3) mumol.L-1 (n = 5). CONCLUSION: Hup A acted as an antagonist of NMDA receptor in cerebral cortex in addition to its inhibitory effect on acetylcholinesterase.

Alkaloids↗
PubMed1998

Patch clamp recording from the intact dorsal root ganglion.

A method for patch-clamp recording from intact dorsal root ganglion (DRG) cells in rat is described. The L4 and L5 DRGs with sciatic nerve attached were excised from rats (10-15 days old) and placed in a recording chamber after removing the ganglion sheath and dissolving the connective tissue with dilute collagenase. The somata of individual cells were exposed by gentle surface cleaning through a perfusion micropipette. Somata were classified as Abeta, Adelta or C based on the cell size and the shape of the action potential (AP). Under current clamp, axonal conduction velocity (CV) was calculated from the distance between a stimulating electrode and the center of the ganglion divided by the latency of the AP elicited by stimulation of the sciatic nerve. CVs ranged from 0.2-0.8 m/s for C cells, 0.8-2.4 for Adelta and 3.2-5.0 for A/beta cells. AP threshold occurred at a significantly more positive potential in C cells than in Adelta and Abeta cells. Under voltage clamp, sodium currents were recorded from C cells. Both TTX-resistant (TTX-R) and TTX-sensitive (TTX-S currents) were demonstrated in the present study. The results demonstrate the feasibility of patch-clamp recording from intact, identified DRG cells in vitro.

Animals↗
PubMed1997

Mitogenic and anti-proliferative signals for neural crest cells and the neurogenic action of TGF-beta1.

The influence of pertinent growth factors on proliferation and differentiation of quail neural crest cell was assessed by in vitro colony assay in a serum-free (0.5% chick embryo-extract supplemented) culture medium. The factors tested included basic fibroblast growth factor (bFGF; FGF-2), neurotrophins, and transforming growth factor-beta-1 (TGF-beta). Both bFGF and neurotrophins are implicated in the development of the peripheral nervous system, whereas TGF-beta can affect cell differentiation and modulate the action of other growth factors. Bromodeoxyuridine (BrdU) incorporation indicated that bFGF is mitogenic to pluripotent neural crest cells (and/or their immediate progeny) and to committed melanogenic cells. However, this was not reflected in an increase in colony size. In contrast, colony size did increase when nerve growth factor (NGF) was present in addition to bFGF. This indicated either that both factors are required to initiate cell proliferation or that at least some bFGF-exposed cells become dependent on neurotrophins for survival. Sequential addition of the factors showed that exposure to bFGF was required prior to the presence of a neurotrophin, thus favoring the latter possibility. All three neurotrophins tested, NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), were capable of supporting survival of pluripotent neural crest cells (or their closely related progeny) in the presence of bFGF. In the absence of bFGF, neurotrophins did not affect colony size. Although the BrdU data indicated that bFGF is also a mitogen for committed melanogenic cells, the size of pigmented colonies did not change in the presence of bFGF alone or of bFGF plus a neurotrophin. This suggested that another, yet to be determined, factor is required for the survival of proliferating melanogenic cells. Colony assays were also performed in the presence and absence of TGF-beta, both alone and in combination with bFGF plus NGF. TGF-beta inhibited proliferation of both pluripotent neural crest cells (and/or their immediate derivatives) and of committed melanogenic cells, causing a decrease in colony size. When TGF-beta was added to the culture medium together with the bFGF/NGF combination, this also caused a significant decrease in colony size, similar to the one observed with TGF-beta alone. TGF-beta blocked proliferation even when the cells were exposed 24 to 48 hr to the bFGF/NGF combination prior to addition of TGF-beta. Neurogenesis increased significantly in the presence of TGF-beta. The number per colony of both adrenergic cells and sensory neuron precursors increased in TGF-beta-treated neuroblast-positive colonies. The following new insights were derived from this study: 1) basic FGF is a mitogen for pluripotent neural crest cells (and/or their immediate derivatives); 2) pluripotent and committed melanogenic neural crest cells that have been exposed to bFGF become dependent on trophic support; 3) all neurotrophins tested (NGF, BDNF or NT-3) can fulfill the trophic requirement of bFGF-exposed pluripotent cells, but not for melanogenic cells; 4) TGF-beta is an anti-proliferative signal for pluripotent neural crest cells and for committed melanogenic cells; 5) the TGF-beta-mediated anti-proliferative signal dominates over the bFGF/neurotrophin-mediated mitogenic signal; and 6) TGF-beta enhances sensory and adrenergic neurogenesis, possibly by acting upon a common neurogenic precursor cell. Furthermore, our work confirms previous reports by other investigators, who showed that bFGF promotes and TGF-beta inhibits proliferation of pigment cells.

Animals↗
PubMed1997

The contribution of inflammatory mediators and nitric oxide to lipopolysaccharide-induced intussusception in mice.

Intussusception is a major cause for intestinal obstruction in children. Its etiology is unclear, but it is often associated with some kind of infection. We have developed a model for intussusception in mice using intraperitoneal (IP) injection of lipopolysaccharide (LPS). The objective of this study was to identify the putative mediators that participate in this LPS-induced intussusception. LPS (12 mg/kg) was injected into adult mice (N = 52) and 6 hr later, 25% of the animals demonstrated intussusception in the small or large intestine. We next tested whether nitric oxide (NO) or various inflammatory mediators contributed to this effect: Indomethacin (10 mg/kg) injected with LPS (12 mg/kg) completely prevented the effect of LPS (N = 20). The tumor necrosis factor (TNF) blocker pentoxifylline (200 mg/kg) significantly reduced the incidence of intussusception to 6.6% (N = 30). The platelet-activating factor (PAF) antagonist BN52021 (10 and 20 mg/kg) reduced the incidence of intussusception to 13.3% in both doses (N = 15 for each dose). Addition of 2% arginine (NO precursor) to the drinking water 36 hr before the injection of LPS increased the incidence of intussusception to 30.7% (N = 32). In mice injected with the NO synthase inhibitor L-NAME (20 mg/kg) only 3.8% developed intussusception (N = 26). Our results indicate that the induction of intussusception by LPS proceeds via parallel pathways involving cytokines, prostaglandins, and NO. Our previous pathological study showed that LPS did not cause any changes that may act as a lead point for the intussusception, suggesting that LPS induced intussusception by altering gut motility. We therefore propose that these mediators combine to induce disturbed gut motility that results in the formation of intussusception.

Animals↗
PubMed1997

An in vitro study of ectopic discharge generation and adrenergic sensitivity in the intact, nerve-injured rat dorsal root ganglion.

A chronic, loose constriction of the sciatic nerve in rat produces behavioral signs of spontaneous pain and cutaneous hyperalgesia (Bennett and Xie, Pain, 33 (1988) 87-107) as well as an abnormal spontaneous activity and adrenergic sensitivity of certain dorsal root ganglion (DRG) cells with axons in the injured nerve (Kajander et al., Neurosci. Lett., 138 (1992) 225-228; Xie et al., J. Neurophysiol., 73 (1995)1811-1820). The present study investigated whether the spontaneous activity and adrenergic sensitivity were intrinsic properties of injured DRG cells and manifested in vitro, i.e., not dependent on intact blood circulation and an intact, functioning sympathetic nervous system. Two weeks after a loose constriction of the sciatic nerve, the L4 or L5 DRG with its ligated nerve and dorsal root attached was removed from the rat and placed in a chamber. Extracellular recordings were made from teased dorsal root fibers. Spontaneous activity (>0.05 imp/s in 3 min) originating within or close to the DRG was often found in C-, Adelta- and Abeta-fibers from nerve-injured rats, but was rare in fibers with peripheral axons from uninjured nerve. The incidence of various patterns of spontaneous discharge was similar to that previously recorded in vivo. Nineteen of 30 C-fibers, four of five Adelta- and three of seven Abeta-fibers from injured nerve responded to different doses of norepinephrine (NE) applied topically to the DRG. Five of seven C- and one of two Abeta -fibers from injured nerve responded to clonidine, a more selective alpha2 adrenergic agonist. The thresholds ranged from 500 to 10 microM, the lowest dose delivered. None of the fibers from uninjured nerve responded to NE or clonidine (500 microM). Since the experiments were carried out in vitro in the intact DRG, the existence of spontaneous activity in DRG cells in nerve-injured rats was independent of any blood borne chemicals, such as norepinephrine. We hypothesize that abnormal activity and adrenergic sensitivity in injured DRG neurons are due to an intrinsic alteration of the cell body membrane.

Action Potentials↗
PubMed1997

Growth factor action in neural crest cell diversification.

At the onset of their migration into the embryo, many neural crest cells are pluripotent in the sense that they have the capacity to generate progeny that consist of more than one cell type. More recently, we have found that there are pluripotent neural crest cell-derived cells even at sites of terminal differentiation. These findings support the notion that cues originating from the microenvironment, at least in part, direct neural crest cell type specification. Based on the rationale that growth factors that are known to support survival of neural crest cell derivatives may have additional functions in progenitor cell development, we have examined the action of pertinent growth factors. Trophic, mitogenic, antiproliferative and differentiation promoting activities were found. Stem cell factor (SCF) is trophic for pluripotent neural crest cells. Contrary to expectation, SCF plus a neurotrophin, rather than SCF alone is trophic for committed melanogenic cells. Basic fibroblast growth factor (bFGF) is mitogenic both for pluripotent cells and committed melanogenic cells. However, the cells become dependent on another factor for survival. Whereas any neurotrophin tested can rescue bFGF-activated pluripotent neural crest cells, the factor that rescues melanogenic cells remains to be determined. Transforming growth factor beta 1 (TGF-beta 1) is a powerful antimitotic signal for all neural crest cells that overrides the bFGF/neurotrophin proliferative signal. Furthermore, SCF promotes differentiation of neural crest cells into cells of the sensory neuron lineage. Neurotrophin-3 (NT-3) specifically promotes high affinity uptake of norepinephrine by neural crest cells and is thus thought to play a critical role in the differentiation of sympathetic neuroblasts. In summary, our data indicate that neurotrophins and other pertinent growth factors affect survival, proliferation and differentiation of neural crest cells at multiple levels and in different lineages. Moreover, our findings emphasise the importance of the concerted action of combinations of growth factors, rather than of individual factors.

Animals↗
PubMed1997

Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons.

Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons. J. Neurophysiol. 78: 2790-2794, 1997. To better understand the neuronal mechanism of neuropathic pain, the effect of axotomy on the excitability of dorsal root ganglion (DRG) cells with unmyelinated axons (C cells) was investigated. Whole cell patch-clamp recordings were performed on intact DRG cells with intact axons or with axons transected 7-12 days earlier. C cells were identified by 1) soma size, 2) action potential morphology, 3) conduction velocity, and 4) in some cases, injection of Fast Blue into the injured nerve fibers. Axotomy reduced (more negative) action potential threshold but did not significantly change resting membrane potential, action potential duration, or maximal depolarization rate. Axotomy significantly increased the peak sodium current measured under voltage-clamp conditions. In Fast Blue-labeled (injured) cells, the tetrodotoxin (TTX)-sensitive current was enhanced while the TTX-resistant current was reduced. These results suggest that axotomy increased the excitability of C cells, possibly because of a preferential increase in expression of TTX-sensitive sodium currents.

Animals↗
PubMed1997

A C. elegans E/Daughterless bHLH protein marks neuronal but not striated muscle development.

The E proteins of mammals, and the related Daughterless (DA) protein of Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription factors that play a role in many developmental processes. We report here the characterization of a related C. elegans protein, CeE/DA, which has a dynamic and restricted distribution during development. CeE/DA is present embryonically in neuronal precursors, some of which are marked by promoter activity of a newly described Achaete-scute-like gene hlh-3. In contrast, we have been unable to detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility shift analysis detects dimerization of CeE/DA with HLH-3 while efficient interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple roles for CeE/DA in C. elegans development and provide evidence that both common and alternative strategies have evolved for the use of related HLH proteins in controlling cell fates in different species.

Amino Acid Sequence↗
PubMed1997

Neurotrophin-3- and norepinephrine-mediated adrenergic differentiation and the inhibitory action of desipramine and cocaine.

In the presence of neurotrophin-3 (NT-3), high-affinity norepinephrine (NE) uptake by quail neural crest cells was significantly increased as judged by in vitro colony assay of adrenergic differentiation. In the presence of the related neurotrophins nerve growth factor (NGF) or brain-derived neurotrophic (BDNF) factor, or of basic fibroblast growth factor (bFGF), there were no significant changes. When NE was added to the culture medium in addition to NT-3, more colonies contained dopamine-beta-hydroxylase (DBH)-immunoreactive cells, an enzyme that is characteristic for adrenergic cells. The NE-mediated increase in the portion of colonies that contained DBH-immunoreactive cells was prevented by the tricyclic antidepressant desipramine (DMI) and by cocaine, two types of drug that block cellular transport of NE. To further examine whether NE acts via uptake, colony assays were performed in the presence and absence of adrenergic antagonists and agonists. These would be expected to mimic the DMI and NE effects, respectively, if the mechanism of action involved activation of adrenergic autoreceptors. Neither class of drug showed a detectable effect within a wide range of concentrations. Immunocytochemistry using antibodies against beta 1 and beta 2 adrenergic receptors further supported the notion that DMI action and beta-receptor expression are not causally related. Ratio imaging was subsequently used in an attempt to elucidate the mechanism of NE action. Within a few minutes of addition of NE to the culture medium, there was an increase in intracellular free calcium in a subset of neural crest cells. Taken together, our data indicate that NT-3 is involved in the appearance of the NE transporter (NET) during embryonic development; internalized NE directly or indirectly increases adrenergic differentiation as measured by immunoreactivity of the adrenergic biosynthetic enzyme DBH; and norepinephrine uptake inhibitors have treatogenic potential.

Adrenergic Uptake Inhibitors↗
PubMed1996

The actions of ketotifen on intestinal smooth muscles.

Ketotifen is a tricyclic drug with a wide spectrum of pharmacological effects. We studied the actions of ketotifen on the mechanical activity of isolated segments of guinea-pig ileum, guinea-pig colon and mouse colon. In the guinea-pig ileum ketotifen induced small contractions and inhibited the contractions induced by carbachol and by electric field stimulation. Responses to bradykinin (in the absence or in the presence of atropine 1 microM) were similarly inhibited by ketotifen, with an IC50 of 23 microM. In the guinea-pig colon ketotifen evoked non-cholinergic contractions with a pD2 of 4.5, but still it inhibited responses to bradykinin (IC50 = 75 microM). Ketotifen relaxed the unstimulated mouse colon with a pD2 of 4.2. This effect persisted in the presence of propranolol and phentolamine (each 10 microM). Incubation of the mouse colon with the nitric oxide synthase inhibitors NG-nitro-L-Arginine methyl ester hydrochloride (L-NAME), or L-NG-nitro-arginine (L-NNA) (100-500 microM) did not alter the inhibitory action of ketotifen. The histamine H1 receptor antagonist chlorpheniramine (5 microM) or the nerve blocker tetrodotoxin (1 microM) did not alter the inhibitory effects of ketotifen. It is concluded that the actions of ketotifen are mediated by a non-cholinergic, non-histaminergic mechanisms.

Animals↗
PubMed1996

Cytoskeleton immunohistochemical study of early ischemic myocardium.

Previous studies on cytoskeletal changes of in vitro and in vivo animal models of ischemic myocardium have suggested the possibility of using alterations in cytoskeleton proteins as an early marker for the post-mortem diagnosis of myocardial ischemia in cases of sudden death due to coronary artery disease (CAD). In the present study, using the technique of ABC-immunohistochemistry, we examine the changes of three cytoskeletal proteins: vinculin, desmin and alpha-actinin in human myocardial samples taken from 14 cases of CAD sudden death and 13 cases of non-CAD death. Results of these examinations are compared with immunohistochemical changes of myoglobin and histochemical staining of hematoxylin and eosin and phosphotungstic acid, and Masson trichrome. Patchy and extensive loss of the three cytoskeletal proteins was demonstrated in the myocardium of victims who died 1 h or later following the onset of symptoms of ischemic myocardium. The pattern of cytoskeleton change is equivocal in the cases of CAD who died less than 1 h after the onset of symptoms and of the cases of non-CAD. In these cases, no significant histological change was observed. With less non-specific background changes and stronger positive staining, immunohistochemical staining of the three cytoskeletal proteins is more reliable than myoglobin, which has attracted the attention of many pathologists searching for anatomic evidence of ischemic myocardium in coronary artery disease.

Adolescent↗
PubMed1996

Abnormal spontaneous activity and responses to norepinephrine in dissociated dorsal root ganglion cells after chronic nerve constriction.

As a part of ongoing studies of the cellular mechanisms of sympathetically maintained pain, we investigated the effects of a peripheral nerve injury on the responses of dissociated dorsal root ganglion (DRG) cells to norepinephrine (NE). Whole-cell patch-clamp recordings under current clamp were obtained from L4 and L5 DRG cells from adult rats in acute culture 11-25 days after a loose or tight ligation of the sciatic nerve. Only small to medium-sized cells from normal (uninjured) nerves and from loosely ligated nerves were tested with NE. One of 15 cells obtained-from uninjured nerves responded to NE (500 microM, the highest dose, elicited a small depolarization without action potentials). In contrast, many cells from injured nerves responded to NE with a membrane depolarization, accompanied in some cases by the generation of action potentials. Fifty-two percent responded to 500 microM, while a significantly lower percentage responded to the lower doses of 100 microM (26%) and 10 microM (14%). Cells responsive to NE also responded to capsaicin. Spontaneous activity was observed in 14% and 21% of cells from loosely and tightly ligated nerves, respectively, but none of the cells from uninjured nerves. We conclude that the abnormal electrogenesis and responsiveness to NE in certain nerve-injured primary sensory neurons are due at least in part to changes in the membrane properties of the soma.

Adrenergic alpha-Agonists↗
PubMed1996

Ultrasound-guided internal radiotherapy using yttrium-90-glass microspheres for liver malignancies.

UNLABELLED: Treatment of liver malignancies, in particular hepatocellular carcinoma, remains a serious problem because of the difficulty of delivering adequate therapeutic agents to the lesions while sparing the surrounding normal tissue. In an attempt to overcome this obstacle, intratumoral injection of 90Y, a beta-emitter, was performed. METHODS: Twenty-seven hepatocellular carcinomas and six liver metastases were studied, most of which had failed other therapeutic modalities. Guided by ultrasound, 90Y-glass microspheres (GMS) were carefully injected into predetermined tumor sites. The procedure was repeated at 3--4-wk intervals where indicated. Echographic, clinical and laboratory follow-up was conducted at regular intervals. RESULTS: Twelve to 32 mo after treatment, 27 patients were still alive, with dramatic improvement of their clinical condition: 90.6% of the tumor foci became smaller, with echogenic or blood flow changes on liver sonograms. Serum titers of alpha-FP in 10 of 13 patients returned to normal levels. Repeat biopsy in nine patients showed complete tumor destruction in eight. Six patients died of either end-stage disease or wide dispersion of the tumor. CONCLUSION: The intratumoral administration of 90Y-GMS under ultrasound guidance yielded a higher cure rate for liver malignancy with no severe side effects. The higher radiation dosage delivered by injected 90Y to the periphery of the lesions (up to 28,215-75,720 cGy) was thought to account for the successful outcome. These results show that intratumoral radionuclide injection is feasible for treatment of malignant lesions inside the body.

Adult↗
PubMed1996

[Effect of membrane modification by PEG on prolongation of circulation time of liposomes in blood in vivo].

PEG-PE (polyethylene glycol-phosphatidyl ethanolamine) of different molecular weight (2000 and 5000) were used to modify the membrane of liposomes. Large unilamellar liposomes containing PEG-PE were prepared by reversed phase evaporation. Fluorescent label-calcein was encapsulated at the internal water phase. To compare the differance between the modified and unmodified membrane, the stability in vitro and distribution in vivo were investigated. The results indicated that the circulation half-life for liposomes unmodified, modified by PEG (2000)-PE and modified by PEG (5000)-PE were 13, 21 and 75 (min) respectively. At 6 h after injection, the ratio b/R (b: distribution in blood, R: distribution in liver and spleen) were 0, 0.8 and 1.4, respectively. The results mean that the stability increased and circulation time was prolonged by the PEG-PE modified membrane. The effect of PEG-PE on membrane was found to be directly proportional to the chain length of the polymer.

Animals↗