Biomedical subjects

J Feng

Publications and source records attributed to J Feng.

At least 235 records · Page 13Linked to original sources

PubMed1996

Regional and functional factors determining induction and maintenance of atrial fibrillation in dogs.

The present study was designed to determine the factors governing the ability of premature beats at various atrial sites to initiate atrial fibrillation (AF) and the determinants of the duration of AF in dogs at 1-10 Hz. The site of atrial extrasystoles determined their ability to induce AF. Regional differences in AF inducibility were due to differences in local refractoriness. Premature beats initiated AF by blocking in regions of greater refractoriness, causing macroreentrant activation with subsequent disorganization producing fibrillation. The atrial refractory period and wavelength during rapid 1:1 atrial pacing were weak predictors of AF duration (r = 0.24 and 0.23, respectively), which depended strongly on variability in regional refractoriness measured by the standard deviation in local refractory periods (r = 0.80, P < 0.001) and on the heterogeneity of activation during AF (r = 0.74, P < 0.001). Thus, premature beats cause AF by initiating a single macroreentrant cycle that degenerates into multiple wavefronts, regional refractoriness is the primary determinant of AF induction by premature beats, and variability in refractoriness may be an important determinant of the ability of AF to sustain itself.

Animals↗

PubMed1996

Evidence for two components of delayed rectifier K+ current in human ventricular myocytes.

Previous voltage-clamp studies have suggested that the delayed rectifier current (IK) is small or absent in the human ventricle and, when present, consists only of the rapid component (IKr); however, molecular studies suggest the presence of functionally important IK in the human heart, specific IKr blockers are known to delay ventricular repolarization and cause the long QT syndrome in humans, and we have shown that the expression of IK is strongly influenced by cell isolation techniques. The present experiments were designed to assess the expression of IK in myocytes obtained by arterial perfusion of right ventricular tissue from explanted human hearts. Of 35 cells from three hearts, 33 (94%) showed time-dependent currents typical of IK. The envelope-of-tails test was not satisfied under control conditions but became satisfied in the presence of the benzenesulfonamide E-4031 (5 micromol/L). E-4031 suppressed a portion of IK in 32 of 33 cells, with properties of the drug-sensitive and -resistant components consistent with previous descriptions of IKr and the slow component (IKs), respectively. Action potential duration to 95% repolarization at 1 Hz was prolonged by E-4031 from 336+/-16 (mean +/- SEM) to 421 +/- 19ms (n = 5, P < .01), indicating a functional role for IK. Indapamide, a diuretic agent previously shown to inhibit IKs selectively, suppressed E-4031-resistant current. The presence of a third type of delayed rectifier, the ultrarapid delayed rectifier current (IKur), was evaluated with the use of depolarizing prepulses and low concentrations (50 micromol/L) of 4-aminopyridine. Although these techniques revealed clear IKur in five of five human atrial cells, no corresponding component was observed in any of five human ventricular myocytes. We conclude that a functionally significant IK, with components corresponding to IKr and IKs, is present in human ventricular cells, whereas IKur appears to be absent. These findings are important for understanding the molecular, physiological, and pharmacological determinants of human ventricular repolarization and arrhythmias.

4-Aminopyridine↗

PubMed1996

Adrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial myocytes.

The ultrarapid delayed rectifier K+ current (IKur) in human atrial cells appears to correspond to Kv1.5 cloned channels and to play an important role in human atrial repolarization. Kv1.5 channels have consensus sites for phosphorylation by protein kinase A and C, suggesting possible modulation by adrenergic stimulation. The present study was designed to assess the adrenergic regulation of IKur in human atrial myocytes. Isoproterenol increased IKur in a concentration-dependent manner, with significant effects at concentrations as low as 10 nmol/L. The effects of isoproterenol were reversible by washout or by the addition of propranolol (1 mumol/L). Isoproterenol's effects were mimicked by the direct adenylate cyclase stimulator, forskolin, and by the membrane-permeable form of cAMP, 8-bromo cAMP. Isoproterenol had no effect on IKur when the protein kinase A inhibitor peptide, PKI(6-22)amide, was included in the pipette solution; in a separate set of experiments in which isoproterenol alone increased IKur by 45 +/- 9% relative to control, subsequent superfusion with isoproterenol in the presence of the protein kinase inhibitor H-7 failed to alter IKur. In contrast to isoproterenol, phenylephrine (in the presence of propranolol to block beta-adrenegic effects) induced a concentration-dependent inhibition of IKur, with significant effects observed at concentrations as low as 10 mumol/L. The inhibitory actions of phenylephrine were reversed by the addition of prazosin and prevented by coadministration with a highly selective inhibitor of protein kinase C, bisindolylmaleimide. These results indicate that beta-adrenergic stimulation enhances, whereas alpha-adrenergic stimulation inhibits, IKur and suggest that these actions are mediated by protein kinase A and protein kinase C, respectively. The modulation of IKur by adrenergic influences is a potentially novel control mechanism for human atrial repolarization and arrhythmias.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

Lineage involvement by BCR/ABL in Ph+ lymphoblastic leukemias: chronic myelogenous leukemia presenting in lymphoid blast vs Ph+ acute lymphoblastic leukemia.

Chronic myelogenous leukemia (CML) can sometimes present in lymphoid blast phase (L-BP), and can be difficult to distinguish from Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Some have suggested that the determination of cell lineages involved by the Ph chromosome may be used for distinguishing CML presenting in L-BP (presumably multilineage disease) from Ph+ ALL (presumably lymphoid-restricted), although others have suggested the term 'stem cell ALL' for the multilineage process. Because it has been difficult to perform lineage studies of the Ph chromosome, we investigated the use of fluorescence in situ hybridization (FISH) with probes for BCR (on chromosome 22) and ABL (on chromosome 9) to study lineage involvement in Ph+ lymphoblastic malignancies. We analyzed routine blood and marrow specimens from eight patients who presented with Ph+ lymphoblastic leukemia and found that FISH recognized the 9;22 translocation, distinguished between the two common molecular variants, and readily identified multilineage vs lymphoblast-restricted disease. In our series, four patients had multilineage and four had lymphoblast-restricted disease. Multilineage disease was associated with morphologic features of CML at diagnosis and/or reversion to chronic phase CML after treatment leading us to consider it as CML presenting in L-BP. Patients with lymphoid-restricted disease lacked such findings. The survival of three of our four patients with multilineage disease was prolonged, at 25, 28+, and 126+ months, and when data from our entire series are added to those of 18 previously reported cases that were studied for lineage involvement (reviewed in Leukemia 1993; 7: 147), the difference in overall survival between patients with multilineage and lymphoblast-restricted disease is significant (median overall survival of 47 months vs 8 months, respectively; P=0.013, log rank). Our findings illustrate that FISH analysis can be used to recognize lineage involvement in patients presenting with Ph+ lymphoblastic malignancies, and they provide further support to the notion that multilineage and lymphoblast-restricted disease are distinct clinically as well as biologically.

Adolescent↗

PubMed1996

Brief repetitive ischemia: effect on norepinephrine release, arrhythmias, and functional recovery in isolated perfused rat heart.

The objective of the present study was to determine norepinephrine release, functional recovery, and incidence of arrhythmias following multiple episodes of brief (5 min) ischemia and to compare these variables with those obtained after continuous ischemia (30 min) in isolated rat hearts perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and cardiac rhythm were continuously recorded. The amount of norepinephrine in perfusate was measured by high-performance liquid chromatography. The data showed no increases in LVEDP during the six successive 5-min periods of ischemia interrupted by 5-min reperfusion. The six repetitive periods of reperfusion after repetitive 5-min periods of ischemia were associated with a restoration of left ventricular diastolic function and preservation of reactive hyperemia (23.3 +/- 1.5 mL/min vs. baseline 16.5 +/- 1.3 mL/min; p < 0.05). The incidences of ventricular fibrillation (VF) (10/10) and ventricular tachycardia (VT) (10/10) upon reperfusion in the continuous ischemia group were higher than those in the repetitive ischemia group (VF, 2/10; VT, 3/10; p < 0.05). Norepinephrine washout upon reperfusion after 30-min continuous ischemia was 58.2 +/- 17.4 ng/g of heart, but no increase in norepinephrine washout was observed after brief repetitive ischemic episodes (11.2 +/- 2.4 ng/g of heart) (p < 0.05). Our results show a substantial release of norepinephrine only after 30 min of continuous ischemia, in the isolated rat heart.

Animals↗

PubMed1996

[The study of immunotherapy of ovarian carcinoma with anti-idiotypic antibody].

OBJECTIVES: To study the role of anti-idiotypic antibody in immunotherapy of ovarian carcinoma, and to investigate the effect of anti-idiotypic antibody (Ab2) on ovarian carcinoma in vivo. METHODS: Six to eight week-old female BCF1 mice were immunized three times at 28 days intervals with 50-100 micrograms of anti-idiotypic antibody Ab2 of ovarian carcinoma. The initial immunization was given with complete Freund's adjuvant (CFA), followed by incomplete Freund's adjuvant (IFA). The control mice were immunized with normal mouse IgG. The ovarian carcinoma cells (SKOV3) passaged from nude mice were transplanted to the subrenal capsules of immunized BCF1 mice after the last injection. Then the mice were bred separately on the 2nd, 4th, 6th, 8th and 10th days after the transplantation operations. Specific anti-Ab2(Ab3) in sera was detected by using inhibition assay of enzyme-linked immunospecific assay. Tumor infilitration lymphocytes (TIL) and tumor cells from the tumor tissue of BCF1 were observed microscopically. RESULTS: The sera levels of Ab3 in Ab2 immunized mice were higher than those of the controls. TIL in the former were found to reach their highest peak on the 6th day, where as the highest peak for the controls was on the 8-10th days, tumor cell viability rate in the former decreased rapidly after 6 days, but in the controls decreased only gradually. CONCLUSIONS: Ab2 could induce specific immuno rejection to ovarian carcinoma in vivo. It is predicted that anti-idiotypic antibody Ab2 might be used in immunotherapy of ovarian cancer patients and also as a preventive for post treatment clinical recurrence of ovarian carcinoma.

Animals↗

PubMed1996

[The study of radioimmunoimaging on the nude mice bearing human ovarian carcinoma by labelling monoclonal antibody with 99mTc].

OBJECTIVE: To investigate the feasibility of radioimmunoimaging (RII) on the nude mice model by labelling anti-ovarian carcinoma monoclonal antibody (McAb, COC166-9) with 99mTc, and the possibility for clinical application. METHODS: McAb reduced by beta-mercaptoethanol was labelled directly with 99mTc. Imaging positive rate, negative rate and tumor/non-tumor (T/N) ratio were calculated. RESULTS: (1)McAb COC166-9 labelled with 99mTc reacted with ovarian carcinoma. (2) 8 nude mice models were injected with the labelled antibodies and were then imaged. In the experimental group the positive imaging rate of tumor was 100%, in the control group the negative rate was 100%. The results were the same as those of T/N ratios. (3)In two groups (10 nude mice), intraperitoneal (i.p.) or intravenous (i.v.) injection of McAb labelled with 99mTc, positive imaging rates of tumor 100%. The IV group was better than IP group in the radio-background. CONCLUSIONS: Immunoactivity of 99mTc-COC166-9 used for RII on the nude mice models was good, and the imaging effect was specific. Clinical application is promising.

Animals↗

PubMed1996

[Urine level of trans, trans-muconic acid used as an index of internal dose of exposure to benzene].

Urine trans, trans-muconic acid (TTMA) in population exposed to benzene was determined with a high performance liquid chromatography-ultra violet detection system. Result showed urine TTMA increased significantly with increasing of air benzene levels, showing a good correlationship between them (r = 0.940, P < 0.05). Even in relatively low air benzene levels (with an average of 2.46 mg/m3), urine TTMA in exposed group was higher, as compared with that in controls, and their difference reached statistically significant level. It suggests that urine TTMA level can be used as a sensitive and specific indicator for biological monitoring, especially for low exposure to benzene. There was no significant difference in urine TTMA between males and females exposed. Urine TTMA formation can be inhibited by toluene, and confounding of toluene can be roughly adjusted by analysis of covariance.

Adult↗

PubMed1996

[Influence of qingdai compound capsule (QDCC) on the expression of c-myc in psoriatic keratinocytes].

In this immunohistochemical study the authors detected the expression of c-myc in keratinocytes (ECK) from 30 psoriatic patients before and after QDCC treatment and 12 normal subjects for control. The results showed that the ECK of patients before treatment was significantly higher than that in normal control, and its level was correlated with histopathological changes. After treatment the ECK was normalized. It is believed that QDCC could decrease the EKC in psoriatic patient and this effect probably was mediated by inhibiting c-myc expression. This study provided an experimental evidence for the application of QDCC in treating psoriasis.

Adolescent↗

PubMed1996

[Serological analysis of antibodies by anti-idiotypic monoclonal antibody 6B11 against ovarian carcinoma].

OBJECTIVE: To establish a method for detection of serologic antibody by anti-idiotypic monoclonal antibody 6B11 against ovarian carcinoma. METHOD: Sera-antibody exminations from 172 cases, malignant and benign ovarian and uterine tumors as well as normal individuals as control were done respectively. 15 cases of ovarian epithelial carcinoma with 133 blood samples were examined serially by enzyme linked immunoabsorbent assay during the first 12 month after treatment. RESULTS: The cutoff value was determined and calculated from sera of normal controls. The positivity of epithelial ovarian carcinoma was 67.3%, much higher than that in the benign ovarian tumor and malignant or benign uterine tumors with statistical significant difference. The serial examinations of the sera in 15 cases of ovarian epithelial carcinoma showed that the negative result turned from the positive one was corresponding with disease status. CONCLUSIONS: The examination of sera-antibody tested by anti-idiotypic monoclonal antibody 6B11 may give a help for the diagnosis of ovarian carcinoma and may be used as one of the tumor markers for follow up.

Antibodies, Anti-Idiotypic↗

PubMed1995

The RNA component of human telomerase.

Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.

Animals↗

PubMed1995

Cataloging altered gene expression in young and senescent cells using enhanced differential display.

Recently, a novel PCR-based technique, differential display (DD), has facilitated the study of differentially expressed genes at the mRNA level. We report here an improved version of DD, which we call Enhanced Differential Display (EDD). We have modified the technique to enhance reproducibility and to facilitate sequencing and cloning. Using EDD, we have generated and verified a catalog of genes that are differentially expressed between young and senescent human diploid fibroblasts (HDF). From 168 genetags that were identified initially, 84 could be sequenced directly from PCR amplified bands. These sequences represent 27 known genes and 37 novel genes. By Northern blot analysis we have confirmed the differential expression of a total of 23 genes (12 known, 11 novel), while 19 (seven known, 12 novel) did not show differential expression. Several of the known genes were previously observed by others to be differentially expressed between young and senescent fibroblasts, thereby validating the technique.

Base Sequence↗

PubMed1995

Contribution of ATP-sensitive potassium channels to the electrophysiological effects of adenosine in guinea-pig atrial cells.

1. Adenosine caused dose-dependent action potential abbreviation in multicellular guinea-pig atrial preparations, an action antagonized by glyburide (IC50, 31 microM) in both physiological and low-chloride superfusate. 2. When 5 mM ATP was included in pipettes for whole-cell voltage clamp of isolated guinea-pig atrial myocytes, adenosine (10 microM) increased the holding current at -40 mV from 41 +/- 8 to 246 +/- 31 pA (mean +/- S.E.M., P < 0.01), and glyburide (20 microM) returned the holding current to 69 +/- 11 pA (P < 0.01 vs. adenosine alone). Acetylcholine (10 microM) also increased the holding current, but its effects were not altered by glyburide. 3. Both adenosine and acetylcholine induced an additional current component in response to 500 ms voltage steps. Glyburide partially inhibited the adenosine-induced current, but did not alter the effect of acetylcholine. In the presence of maximally effective acetylcholine concentrations, adenosine increased membrane conductance (P < 0.01), although to a lesser extent than in the absence of acetylcholine. 4. Single K+ channel activity was seen in only one of eight cell-attached patches in the absence of adenosine or acetylcholine (0.5 mM Ba2+ in bath and pipette solutions). With acetylcholine (10 microM) in the pipette, inwardly rectifying channels (conductance, 41 +/- 5 pS) were seen in five of six patches. With adenosine (10 microM) in the pipette, single-channel activity was seen in twelve of fourteen patches with two populations of channels, one similar to that induced by acetylcholine and another higher-conductance channel (72 +/- 5 pS) that showed less inward rectification. Glyburide (20 microM) suppressed the high-conductance channel (68 +/- 2 pS) leaving a single channel type with a conductance of 36 +/- 5 pS and strong inward rectification. 5. We conclude that K+ATP channels contribute to the electrophysiological actions of adenosine on guinea-pig atrium in the presence of physiological intracellular ATP levels, and may therefore play a role in the cardiac electrophysiological effects of adenosine in the absence of myocardial ischaemia.

Acetylcholine↗

PubMed1995

N-methyl-D-aspartate receptors are implicated in hyperresponsiveness following naloxone reversal of alfentanil in isolated rat spinal cord.

In isolated neonatal rat spinal cord, naloxone administered after an opioid increases a nociceptive-related slow ventral root potential (sVRP) to levels above pre-drug controls. We studied the role of N-methyl-D-aspartate (NMDA) receptors in this phenomenon, which may be related to acute tolerance and to hyperalgesia on antagonist-precipitated withdrawal. Naloxone (200 nM) alone produced no significant effect on sVRP area, while naloxone (560 nM) increased area to 121 +/- 17.7% of control (mean +/- SD). Following 200 nM alfentanil, naloxone (200 nM) was associated with a significant rebound in sVRP area to 138 +/- 18.0% of pre-drug control. Hyperresponsiveness developed within 7 min of initial alfentanil exposure. The non-competitive NMDA antagonist MK-801 (20 nM) had no effect on sVRP area when applied alone; higher concentrations produced irreversible depression. MK-801 (20 nM) co-applied with 200 nM alfentanil blocked the rebound increase in sVRP area following naloxone 200 nM and also the increase following naloxone alone (560 nM). The results suggest that alfentanil induces a rapid NMDA receptor-dependent change in spinal cord neuronal excitability.

Alfentanil↗

PubMed1995

Decreased levels of salivary prostaglandin E2 and epidermal growth factor in recurrent aphthous stomatitis.

Prostaglandin E2 and epidermal growth factor are two important cytoprotective compounds in saliva. This study investigated their salivary levels in controls and individuals with minor recurrent aphthous stomatitis. The development of recurrent aphthous stomatitis was divided into three stages: (1) early active stage (mucosal redness); (2) active stage (mucosal ulceration); (3) convalescent stage. Unstimulated mixed saliva was collected from each volunteer. Salivary prostaglandin E2 and epidermal growth factor concentrations were determined by radioimmunoassay. Their levels (mean +/- SEM) were significantly lower during the active stage of ulceration as compared to the control: (a) for prostaglandin E2, 200 +/- 55 versus 73 +/- 11 pg/mg salivary protein (p < 0.01), 447 +/- 123 versus 112 +/- 19 pg/ml saliva (p < 0.01), 215 +/- 30 versus 63 +/- 12 pg/min salivary flow (p < 0.01), control (n = 12) versus active stage (n = 15); (b) for epidermal growth factor, 1.09 +/- 0.17 versus 0.67 +/- 0.17 ng/mg salivary protein (p < 0.05); 2.51 +/- 0.53 versus 0.84 +/- 0.19 pg/ml saliva (p < 0.05), 1.24 +/- 0.26 versus 0.41 +/- 0.09 pg/min salivary flow (p < 0.05), control (n = 12) versus active stage (n = 12). Salivary prostaglandin E2 and epidermal growth factor showed stage-dependent alterations during the development of the stomatitis. The prostaglandin E2 concentration decreased significantly during the active stage of ulceration, and then increased significantly during the convalescent stage. However, the recovery of salivary epidermal growth factor after the ulceration was slower than that of the prostaglandin E2. It is suggested that the diminution of prostaglandin E2 and epidermal growth factor in the saliva may be associated with the ulcer development.

Adult↗

PubMed1995

Reactivity of monoclonal antibodies established against a recombinant human endogenous retrovirus-K (HERV-K) envelope protein.

Human endogenous retroviruses (HERVs) are widely believed to represent possible pathogenic agents in autoimmune disorders and carcinogenesis. We generated 2 monoclonal antibodies (mAbs) against a recombinant HERV-K outer-membrane envelope protein. These mAbs were capable of immunoprecipitating protein bands of 55, 51 and 45 kDa, respectively, from [35S]methionine-labeled lysates of T47D (human breast carcinoma), Raji, Bjab (both human beta-lymphoblastoid) and H9 (human T-cell lymphoma) cells. Furthermore, the 55 kDa band could be precipitated from cell-free supernatant of biosynthetically labeled T47D cells, indicating that this molecule may be secreted. Indirect immunofluorescence and subsequent FACS analysis demonstrated the presence of these molecules on T47D, HeLa, Raji, Bjab and H9 cells as well as on lymphocytes isolated from tonsils and stimulated with poke weed mitogen (PWM). Due to the broad distribution and lack of detection of HERV-K-env mRNA in these cells, we believe that these antigens are of cellular origin detected by crossreactivity of mAbs against HERV-K-env protein with cellular molecules.

Antibodies, Monoclonal↗

PubMed1995

Idiopathic atrial fibrillation in dogs: electrophysiologic determinants and mechanisms of antiarrhythmic action of flecainide.

OBJECTIVES: This study sought to determine the mechanisms of idiopathic atrial fibrillation and the atrial antifibrillatory action of flecainide in dogs. BACKGROUND: In a small subset of dogs, sustained atrial fibrillation can be readily induced in the absence of vagal tone. The electrophysiologic mechanisms underlying this ability to sustain atrial fibrillation, and of flecainide action on the arrhythmia, are unknown. METHODS: Six dogs with inducible sustained atrial fibrillation were studied before and after flecainide administration and compared with a control group of 10 dogs. RESULTS: Dogs with atrial fibrillation differed in displaying more shortening of the atrial refractory period with increased rate, resulting in a significantly shorter refractory period and wavelength for reentry at rapid rates, and in increased regional dispersion in refractoriness. Activation maps during sustained fibrillation showed a mean (+/- SE) of 6.3 +/- 0.4 coexistent zones of reentry, compatible with short wavelengths, whereas in control dogs activation during self-limited atrial fibrillation was better organized, and the number of reentrant circuits was smaller. Quantitative analysis demonstrated significantly greater inhomogeneity of activation during atrial fibrillation in dogs with atrial fibrillation than in control animals. Flecainide terminated atrial fibrillation by increasing the duration and homogeneity of atrial refractoriness at rapid rates, thereby reducing the number of reentry circuits and the heterogeneity of activation. CONCLUSIONS: The ability of atrial fibrillation to sustain itself resulted from enhanced rate-dependent shortening of atrial refractoriness and increased regional heterogeneity. Flecainide reversed these changes and restored sinus rhythm. These results suggest potential mechanisms of idiopathic atrial fibrillation and are pertinent to understanding the clinical actions of flecainide.

Action Potentials↗

PubMed1995

Selective effects of alfentanil on nociceptive-related neurotransmission in neonatal rat spinal cord.

We have examined the effects of alfentanil on nociceptive-related neurotransmission in isolated neonatal rat spinal cord, with particular attention to acute tolerance. Electrical stimulation of a lumbar dorsal root was used to evoke the monosynaptic reflex (MSR), a slow ventral root potential (sVRP), and the dorsal root potential (DRP). Alfentanil (0.5 nmol litre-1 to 1 mumol litre-1) depressed sVRP area by a maximum of 85%; EC50 was approximately 2 nmol litre-1. The effects of alfentanil were selective for very slow, metabotropically mediated sVRP components compared with faster NMDA receptor-mediated components. The MSR was unaffected. Alfentanil depressed DRP area by a maximum of 50% at 1 mumol litre-1. Naloxone antagonized all alfentanil effects. Morphine depressed sVRP area with an approximate EC50 of 90 nmol litre-1, giving an alfentanil:morphine potency ratio of 45:1. The effects of alfentanil on sVRP showed no biphasic time dependence up to 60 min. Naloxone administered after alfentanil produced a significant rebound in sVRP area to a level of 143 (SD 21.3)% above control. Thus, in this study there was no evidence for acute tolerance, as measured by a decrease in effectiveness over time, but there was evidence as measured by rebound following naloxone.

Alfentanil↗