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Biomedical subjects

A Nguyen

Publications and source records attributed to A Nguyen.

At least 55 records · Page 3Linked to original sources

Integrating innate and adaptive immunity in the whole animal.

The mammalian defense system can respond to a variety of threats, but this capability is not just a simple alarm system for triggering antigen-presenting cells and initiating cellular immunity. Instead, the body is an integrated system in which nearly every cell type can relay the alarm through the production of chemokines, which recruit specific inflammatory cells to the target tissues. This chemokine production is carefully regulated at several levels so that the kinetics and character of local tissue inflammation is tailored to the specific threat. First, the production of nuclear factor-kappa B-regulated chemokines can be modulated in non-bone marrow-derived cells through transcriptional repression mediated by RelB. RelB is also implicated in the differentiation of lymphoid dendritic cells, suggesting that this gene regulates the transition from acute inflammation to adaptive immunity. Second, tissue parenchymal cells, in their capacity as sentinel cells, are able to produce different patterns of chemokines in response to different alarm stimuli. Third, cells from different tissues also show distinct potentials for chemokine responses so that the non-specific damage from inflammation might be avoided in some cases. Finally, the differentiation of T-cell effectors allows for further regulation of local inflammation as their cytokines can also affect chemokine production. This integration of innate and adaptive immunity allows for both rapid responses and dynamic regulation of inflammation in vivo.

Adaptation, Physiological↗

A comparison of HIV/AIDS knowledge among high school freshmen and senior students.

Statistical data show that heterosexual transmission of AIDS among teenagers is a significant problem. The purpose of this study was to assess and compare the level of knowledge concerning HIV/AIDS among high school freshmen- and senior-level students and to determine the association between certain demographic variables and the students' knowledge level. A convenience sample of 169 freshmen and 274 senior high school students were surveyed at a local area high school (N = 443). A 49-item knowledge questionnaire, used by the high school district HIV/Abstinence program, and a demographic questionnaire developed by the investigators were used to collect the data. The findings revealed that both the freshmen and senior students had several misconceptions about HIV/AIDS, including the modes of transmission, the sure way of preventing the sexual transmission, donating blood, and the usual causes of death for people with AIDS. A comparison of the mean knowledge scores among freshmen and senior students indicated there was no significant difference among the two groups. The mean knowledge score of the seniors was significantly affected by whether they had received HIV/AIDS education. However, this was not the case for the freshmen. African American students, especially the female students, had significantly lower knowledge scores than other ethnic groups.

Adolescent↗

In the radiotherapy of prostate cancer, technique determines the doses to the penile structures.

For 11 consecutive prostate cancer patients undergoing three-dimensional conformal radiotherapy (3DCRT) in our institution, penile structures (PNS) were outlined in CT images obtained for treatment planning purposes. Dose-volume histograms (DVHs) were compared in order to study dose-volume relations for three techniques: 4FLD, an axial coplanar, four-field box technique; 6FLD, a six-field coplanar technique; and 4NAX, a coplanar but non-axial, four-field technique. All three techniques delivered equal doses to the planning target volumes (PTV). Our statistical analyses strongly indicate that the three techniques can be ranked as 6FLD better than 4FLD (and 4FLD better than 4NAX) as far as irradiating PNS volume during treatment of prostate cancer (PC) is concerned. For each technique, there is a "spread" owing to differences in patient anatomy and/or target size, position, and extent, but each technique has a similar "profile" or "shape" distinct from other techniques. Whether irradiating smaller volumes of PNS will influence the sexual potency outcome remains to be demonstrated. However, PNS should be considered as another critical structure in addition to rectum, bladder and femoral heads in the radiotherapy (RT) of PC, especially in 3DCRT dose escalation studies. Sexual potency outcomes can be correlated to dose-volume relations in the future and this will help refine radiotherapy techniques further.

Humans↗

A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Very little research has focused on the efficacy of Adderall (Shire-Richwood Inc, Florence, KY) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD), and no studies have compared it with standardized doses of Ritalin (Novartis Pharmaceuticals, East Hanover, NJ). It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion. We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications' time courses. DESIGN: Within-subject, double-blind, placebo-controlled, crossover design lasting 6 weeks. As in our previous work, medication changes occurred on a daily basis in random order over days. SETTING: Eight-week, weekday (9 hours daily) summer treatment program at the State University of New York at Buffalo, using an intensive behavioral treatment program including a point system and parent training. STUDY PARTICIPANTS: Twenty-five children (21 boys and 4 girls) diagnosed as ADHD using standardized structured interview and rating scales, mean age 9.6 years, 88% Caucasian, of average intelligence, with no medical conditions that would preclude a trial of stimulant medication. Thirteen were comorbid for oppositional-defiant disorder and another 8 for conduct disorder. INTERVENTIONS: Children received 10 mg of Ritalin, 17.5 mg of Ritalin, 7.5 mg of Adderall, 12.5 mg of Adderall, or placebo, twice a day (7:45 AM and 12:15 PM), in random order with conditions changing daily for 24 days. OUTCOME MEASURES: Daily rates of behaviors in recreational and classroom settings, and standardized ratings from counselors, teachers, and parents, were averaged across days within condition within child and compared. Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo standard deviation for each child, and were compared hourly between first daily ingestion (7:45 AM) and 5:00 PM to assess the time course of the two drugs. Measures were taken at 12:00 PM (recess rule violations) and at 5:00 PM (parent behavior ratings) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off. Parent ratings were also made for evening behavior to assess possible rebound, and side effects ratings were obtained from parents, counselors, and teachers. Parents, counselors, and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day. Finally, a clinical team made recommendations for treatment taking into account each child's individual response. RESULTS: Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior, academic productivity, and staff/parent ratings of behavior. The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin, particularly the lower dose of Ritalin, on numerous but not all measures. This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin. Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening. The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin. Both drugs produced low and comparable levels of clinically significant side effects. Staff clinical recommendations for continued medication favored Adderall three to one. Almost 25% of the study participants were judged to be nonresponders by the clinical team, presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication. CONCLUSIONS: This is the first investigation to assess comparable doses of Adderall and Ritalin directly. (ABSTRACT TRU

Amphetamines↗

A simple objective method of adjusting sling tension.

PURPOSE: Pubovaginal sling is gaining widespread acceptance as a primary form of treatment for types II and III stress urinary incontinence. However, a major drawback is postoperative obstructed voiding due to excessive force placed on the suspension suture. We describe a simple objective method for intraoperative adjustment of sling tension that can be performed by a single surgeon during pubovaginal sling surgery. MATERIALS AND METHODS: A cotton swab is inserted into the urethra and placed at the urethrovesical junction after the sling is fixed suburethrally and the vaginal mucosa is closed. The suspension sutures are tied down directly onto the rectus fascia with enough tension to keep the cotton swab angle between 0 and 10 degrees to the horizontal plane. A total of 29 patients with an average age of 62 years underwent pubovaginal sling surgery with rectus and cadaveric fascia using this technique for tension adjustment. Of the patients 21 were diagnosed with types II and III, 5 had type II only and 3 had type III only incontinence. Preoperative evaluation revealed detrusor instability in 5 patients. Mean postoperative indwelling catheterization period was 6.2 days. Average followup was 15.6 months. RESULTS: To date no permanent urinary retention has occurred. Of the patients 15 voided without difficulty after catheter removal, 13 had urinary difficulty requiring intermittent catheterization for 1 week or less and 1 had retention requiring intermittent catheterization for 10 weeks. Preoperative symptoms of detrusor instability resolved in all cases. De novo detrusor instability in 3 cases was controlled with anticholinergics. CONCLUSIONS: Overzealous sling tension adjustment has been recognized as a cause of treatment failure leading to urethral obstruction. Our technique is effective in preventing over adjustment of tension, is reproducible and can be performed by 1 surgeon.

Adult↗

ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide.

The voltage-gated potassium channel in T lymphocytes, Kv1.3, is an important molecular target for immunosuppressive agents. A structurally defined polypeptide, ShK, from the sea anemone Stichodactyla helianthus inhibited Kv1.3 potently and also blocked Kv1.1, Kv1.4, and Kv1.6 at subnanomolar concentrations. Using mutant cycle analysis in conjunction with complementary mutagenesis of ShK and Kv1.3, and utilizing the structure of ShK, we determined a likely docking configuration for this peptide in the channel. Based upon this topological information, we replaced the critical Lys22 in ShK with the positively charged, non-natural amino acid diaminopropionic acid (ShK-Dap22) and generated a highly selective and potent blocker of the T-lymphocyte channel. ShK-Dap22, at subnanomolar concentrations, suppressed anti-CD3 induced human T-lymphocyte [3H]thymidine incorporation in vitro. Toxicity with this mutant peptide was low in a rodent model, with a median paralytic dose of approximately 200 mg/kg body weight following intravenous administration. The overall structure of ShK-Dap22 in solution, as determined from NMR data, is similar to that of native ShK toxin, but there are some differences in the residues involved in potassium channel binding. Based on these results, we propose that ShK-Dap22 or a structural analogue may have use as an immunosuppressant for the prevention of graft rejection and for the treatment of autoimmune diseases.

Amino Acid Sequence↗

Th2-induced eotaxin expression and eosinophilia coexist with Th1 responses at the effector stage of lung inflammation.

The T cell-mediated lung inflammation that is associated with allergic asthma is characterized mainly by massive eosinophil infiltration, which induces airway injury and the subsequent late-phase reactivity. Because Th2 cells are often isolated from asthmatic subjects, these cells are postulated to play a role in asthma pathogenesis. We report that adoptively transferred, influenza hemagglutinin-specific Th1 and Th2 cells induced different patterns of chemokines leading to different types of cellular infiltration. Th2 cells were sufficient to induce dramatic Ag-dependent lung eosinophilia and eotaxin expression; by contrast, Th1 transfer primarily induced neutrophil recruitment with little eotaxin production. To determine whether Th1 cells show inhibitory effects on Th2 cell-mediated responses, Th1 and Th2 cells were cotransferred. Hemagglutinin-specific Th1 cells did not inhibit Ag-induced lung eosinophilia, nor did they inhibit eotaxin expression. Furthermore, influenza virus infection of the lung in mice receiving hemagglutinin-specific Th2 cells also induced eotaxin expression and eosinophilia that could not be inhibited by the cotransfer of Th1 cells. Our results show that Th2-mediated allergic lung inflammation coexists with the Th1-mediated responses that are stimulated by diverse forms of Ags.

Adoptive Transfer↗

Regulation of p21(WAF1) expression during normal myeloid differentiation.

The G1-phase cell-cycle inhibitor p21 has been proposed to mediate growth arrest during differentiation. Upregulation of p21 has been shown in multiple cell lines induced to differentiate; however, the mechanism of p21 induction during normal differentiation is largely unknown. In this report, we use normal hematopoietic precursor cells obtained from umbilical cord to model p21 regulation during differentiation. Myeloid maturation of CD34+ precursor cells is associated with a marked increase in p21 expression at the RNA and protein level. The upregulation of p21 transcripts during differentiation is associated with decreased binding to a highly conserved 44-bp fragment within the p21 promoter. This 44-bp regulatory element binds a novel modulator of p21 expression. It is of considerable interest that, although the binding activity is expressed in p53-negative as well as in p53-positive cells, the DNA sequence recognized by this protein overlaps a PuPuPuC(A/T)(T/A)GPyPyPy consensus sequence for p53.

Cyclin-Dependent Kinase Inhibitor p21↗

Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7.

We report the isolation of a novel mouse voltage-gated Shaker-related K+ channel gene, Kv1.7 (Kcna7/KCNA7). Unlike other known Kv1 family genes that have intronless coding regions, the protein-coding region of Kv1.7 is interrupted by a 1.9-kilobase pair intron. The Kv1.7 gene and the related Kv3.3 (Kcnc3/KCNC3) gene map to mouse chromosome 7 and human chromosome 19q13.3, a region that has been suggested to contain a diabetic susceptibility locus. The mouse Kv1.7 channel is voltage-dependent and rapidly inactivating, exhibits cumulative inactivation, and has a single channel conductance of 21 pS. It is potently blocked by noxiustoxin and stichodactylatoxin, and is insensitive to tetraethylammonium, kaliotoxin, and charybdotoxin. Northern blot analysis reveals approximately 3-kilobase pair Kv1.7 transcripts in mouse heart and skeletal muscle. In situ hybridization demonstrates the presence of Kv1.7 in mouse pancreatic islet cells. Kv1.7 was also isolated from mouse brain and hamster insulinoma cells by polymerase chain reaction.

Amino Acid Sequence↗

Production of early expressed parasitism-specific proteins in alternate sphingid hosts of the braconid wasp Cotesia congregata.

Parasitism of Manduca sexta larvae by the braconid wasp Cotesia congregata or injection of C. congregata polydnavirus (CcPDV) causes numerous alterations in host physiology, including developmental arrest, abrogation of host immunity, and the production of three abundant early expressed proteins (EP1, EP2, and EP3) that are secreted in large amounts into the host's hemolymph. Here we compare the levels of these proteins present in the hemolymph of three other sphingid species that vary in their compatibility for C. congregata. Hyles lineata was found to be permissive for C. congregata and EP1, EP2, and EP3 were present in larval hemolymph at levels comparable to those found in hemolymph from parasitized M. sexta larvae. By contrast, the lowest levels of EP proteins were found in hemolymph from parasitized Pachysphinx occidentalis larvae and this species was found to be completely refractory, since C. congregata eggs were invariably encapsulated. Parasitism of Sphinx vashti by C. congregata resulted in moderate levels of EP production. While the observed immune response was incomplete and some encapsulation of C. congregata eggs and/or larvae was observed, low numbers of S. vashti nevertheless were able to complete their development and emerge as adults. Thus, a correlation was established between host compatibility and induction of synthesis of the three parasitism-specific proteins, although the linkage between quantitative levels of EP production and the extent of encapsulation was variable.

Animals↗

Nicotine and cotinine replacement when nicotine nasal spray is used to quit smoking.

Nicotine nasal spray (NNS) is generally considered to be an effective smoking cessation aid, but all studies to date of NNS effectiveness have also utilized group therapy sessions or frequent laboratory visits to support their subjects' stop smoking efforts. We studied 50 volunteers before they attempted to quit smoking and again at 1, 2 and 3 months after they received NNS to assist them in quitting smoking. No other stop smoking intervention was used, which more closely mimics the common practice of many individuals trying to stop smoking with the aid of a nicotine replacement product but without other supportive interventions. We found that 50% of the subjects quit smoking for the first month, 34% were still abstinent after 2 months and 32% quit smoking for 3 months. Those who quit smoking for the entire 3 months and who continued regular NNS use throughout had 67% cotinine replacement at the end of the first month, while another group which quit smoking for only the first month with the aid of NNS had 42% cotinine replacement at the end of that month. Our data confirm that NNS is an effective smoking cessation aid, but our abstinent rate at 3 months is slightly lower than in other studies in which group therapy was provided. Our data also indicate that higher NNS-induced cotinine replacement during the first month of quitting smoking (suggesting more frequent use of NNS) is associated with longer term quit-smoking success rate.

Administration, Intranasal↗

Rods affect S-cone discrimination on the Farnsworth-Munsell 100-hue test.

Rod influence on hue discrimination was assessed by the Farnsworth-Munsell 100-hue test. Rod influence was taken as the difference in error scores obtained after complete dark adaptation and during the cone plateau at three mesopic (23, 9, 3 td) and one standard (158 td) light level. On the FM 100, rods produced a differential discrimination loss along a tritan axis as compared with a red-green axis without any bias toward a rod confusion axis. Rods appear to impair discrimination mediated by S-cone pathways, which at moderate levels of illumination can differentially elevate tritan errors on the FM 100.

Adult↗

Ethanol inhibits thrombin-induced secretion of the contents of human platelet dense and alpha-granules and lysosomes.

Moderate consumption of alcoholic beverages is associated with a reduction in thromboembolic complications of coronary artery disease, possibly partially attributable to inhibition by ethanol of platelet responses to some aggregating agents. Although ethanol is known to inhibit thrombin-induced secretion of platelet dense granule contents, the effect of ethanol on secretion of alpha-granule and lysosomal contents has not been studied. Using suspensions of washed platelets, and a range of thrombin concentrations (up to 0.1 U/ml), we examined the effect of 87 mM ethanol on secretion of [14C]serotonin from prelabelled platelets as a measure of secretion of dense granule contents. Secretion of alpha-granule and lysosomal contents was examined by flow cytometric measurement of the surface expression of CD62P (P-selectin) and CD63, respectively. Secretion of the lysosomal enzyme, beta-N-acetylglucosaminidase was also quantified. Results were expressed as % of maximum response induced by 1 U/ml thrombin. Ethanol inhibited the thrombin-induced secretion of both dense and alpha-granule contents (P <0.001, 2-way ANOVA), and of lysosomal contents (P <0.005 for CD63 expression and P <0.001 for beta-N-acetylglucosaminidase secretion). When platelets were pretreated with aspirin, thrombin-induced secretion of storage granule and lysosomal contents was slightly inhibited, but secretion was inhibited by ethanol to the same extent as the untreated platelets, indicating that this inhibition was independent of thromboxane A2. Surface expression of CD63 occurred at lower thrombin concentrations than those required for secretion of beta-N-acetylglucosaminidase, possibly due to the presence of some CD63 on granule membranes. Although the role of lysosomal contents in thrombus formation is not established, some constituents of storage granules are known to augment thrombus formation; ethanol's inhibition of their secretion by stimulated platelets may contribute to its beneficial effect on thromboembolism.

Blood Platelets↗

Purification, visualization, and biophysical characterization of Kv1.3 tetramers.

The voltage-gated K+ channel of T-lymphocytes, Kv1.3, was heterologously expressed in African Green Monkey kidney cells (CV-1) using a vaccinia virus/T7 hybrid expression system; each infected cell exhibited 10(4) to 5 x 10(5) functional channels on the cell surface. The protein, solubilized with detergent (3-[cholamidopropyl)dimethylammonio]-1-propanesulfonic acid or cholate), was purified to near-homogeneity by a single nickel-chelate chromatography step. The Kv1.3 protein expressed in vaccinia virus-infected cells and its purified counterpart are both modified by a approximately 2-kDa core-sugar moiety, most likely at a conserved N-glycosylation site in the external S1-S2 loop; absence of the sugar does not alter the biophysical properties of the channel nor does it affect expression levels. Purified Kv1.3 has an estimated size of approximately 64 kDa in denaturing SDS-polyacrylamide electrophoresis gels, consistent with its predicted size based on the amino acid sequence. By sucrose gradient sedimentation, purified Kv1.3 is seen primarily as a single peak with an approximate mass of 270 kDa, compatible with its being a homotetrameric complex of the approximately 64-kDa subunits. When reconstituted in the presence of lipid and visualized by negative-staining electron microscopy, the purified Kv1.3 protein forms small crystalline domains consisting of tetramers with dimensions of approximately 65 x 65 A. The center of each tetramer contains a stained depression which may represent the ion conduction pathway. Functional reconstitution of the Kv1.3 protein into lipid bilayers produces voltage-dependent K+-selective currents that can be blocked by two high affinity peptide antagonists of Kv1.3, margatoxin and stichodactylatoxin.

Animals↗

Morphological effects of ArF excimer laser irradiation on enamel and dentin.

BACKGROUND AND OBJECTIVE: The aim of this investigation to determine the range of morphological and ablative effects that can be achieved on dental enamel and dentin using ArF excimer laser irradiation at a wavelength of 193nm. STUDY DESIGN/MATERIALS AND METHODS: Caries-free coronal enamel and dentin surfaces of 20 extracted human teeth were subjected to irradiation at 193nm using a Lamda-Physik model EMG 103 MSC and ArF fill. Morphology of cavity floors and walls were assessed by light microscopy and SEM. RESULTS: Morphological surface effects and ablation could be controlled effectively and reliably by choice of parameter combination, allowing the operator to achieve either a smooth, flat, or increasingly rough surface with differing degrees of selective ablation. No signs of thermal damage were apparent. CONCLUSION: Excimer laser irradiation at 193nm provided clinically useful cavity preparations and surface morphological effects.

Dental Enamel↗

Use of DHEA in a patient with advanced prostate cancer: a case report and review.

Dehydroepiandrosterone (DHEA) is being evaluated in the basic science laboratories as a potential treatment for adenocarcinomas, with some initial promise for success. However DHEA can be metabolically converted to androgenic compounds, possessing unwanted side effects. A patient with advanced prostate cancer with progressive symptomatology was treated with DHEA after other treatment regimens failed. Many of his symptoms improved on DHEA therapy, but his cancer also flared dramatically during treatment. His previous hormonally unresponsive cancer subsequently responded transiently to third-line hormonal therapy with diethylstilbestrol (DES). Adrenal precursor molecules such as DHEA may have significant therapeutic benefits in a number of diseases of the elderly, however their utility may be limited by potential androgenic side effects including endocrine epithelial cell growth. The development of analogue compounds with less conversion to androgenic metabolites should be considered, as molecules such as DHEA are more widely tested and utilized clinically.

Aged↗

In vitro neuromuscular effects of valproic acid.

The contribution of the anticonvulsant agent, valproic acid, to the interaction between neuromuscular blockers and anticonvulsants remains unclear. Therefore, this study was undertaken to examine the acute neuromuscular effects of valproic acid and its potential for interaction with neuromuscular blocking drugs. Phrenic nerve-hemidiaphragm preparations from rats were mounted in modified Krebs buffer, maintained at 37 degrees C and aerated with a 5% carbon dioxide-95% oxygen gas mixture. Phrenic nerves were stimulated with 0.1 Hz supramaximal pulses of 0.2-ms duration and the elicited tension of the hemidiaphragm was recorded in seven preparations in the presence of valproic acid 100, 500 and 1000 mumol litre-1. In another six preparations, neuromuscular transmission was blocked completely with the non-depolarizing blocker tubocurarine 3 mumol litre-1 and the hemidiaphragm muscle was stimulated directly (2 Hz and 2 ms duration). The effect of the anticholinesterase drug, neostigmine, on an established block induced by valproic acid 1000 mumol litre-1 was also evaluated in five phrenic nerve stimulated preparations. The effect of valproic acid 100, 500 or 1000 mumol litre-1 on suxamethonium- or atracurium-induced neuromuscular block was also evaluated. Valproic acid produced a mean of 29.7 (SEM 1.7)% and 24.7 (1.7) % block of indirectly or directly elicited muscle twitches. The concentration of valproic acid that caused half maximal paralysis did not differ between indirect (460 (59) mumol litre-1) and direct (329 (35) mumol litre-1) stimulation. Neostigmine 1-3 mumol litre-1 failed to significantly alter the block of 19.8% induced by valproic acid 1000 mumol litre-1. Valproic acid 100, 500 or 1000 mumol litre-1 did not alter the concentrations of suxamethonium or atracurium needed to produce paralysis. These findings suggest that valproic acid does not produce significant block at the rat neuromuscular junction. The partial block that is produced is caused predominantly by a direct inhibitory effect on the muscle itself.

Animals↗

Acute in vitro neuromuscular effects of carbamazepine and carbamazepine-10,11-epoxide.

We examined the acute neuromuscular effects of the anticonvulsant, carbamazepine, and its major metabolite, carbamazepine-10,11-epoxide, using the in vitro rat phrenic nerve-hemidiaphragm muscle preparation. Carbamazepine produced 8.8% +/- 2.2% (n = 12) neuromuscular paralysis as its concentration was increased from 1 to 50 microg/mL (4.2-210 microM). In contrast, carbamazepine-10,11-epoxide produced maximum paralysis of 65% +/- 8% (n = 10) in the concentration range 1-100 microg/mL (4-400 microM) and the concentration required to produce half this paralysis was 36 +/- 7 microg/mL (144 +/- 28 microM). Carbamazepine 10 microg/mL (42 microM) shifted the response-concentration curve for both a depolarizing (succinylcholine) and a nondepolarizing (atracurium) neuromuscular blocker, reducing their concentrations required for 50% paralysis by approximately 30%. In contrast, the metabolite, which was a more potent neuromuscular blocker by itself, failed to alter either succinylcholine or atracurium effect. These results concur with previous clinical reports where anticonvulsants have acutely reduced neuromuscular blocker dose requirements.

Animals↗