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Biomedical subjects

M Kim

Publications and source records attributed to M Kim.

At least 145 records · Page 8Linked to original sources
PubMed2000

Chloroplast targeting, distribution and transcriptional fluctuation of AtMinD1, a Eubacteria-type factor critical for chloroplast division.

In Arabidopsis thaliana, a mature mesophyll cell contains approximately 100 chloroplasts. Although 12 arc mutants (accumulation and replication of chloroplasts) and two chloroplast division genes homologous to eubacterial ftsZ have been isolated from A. thaliana, the molecular mechanism underlying the chloroplast division is still unclear. We characterized AtMinD1, a eubacterial minD homolog, for chloroplast division in A. thaliana. AtMinD1-green fluorescent protein targeted to the chloroplasts and possibly associated with the envelope membranes in vivo. During the seed germination, the AtMinD1 transcripts were accumulated twice, just after release from cold treatment and at the beginning of rapid greening, in similar fashion to AtFtsZs. Furthermore the transcript level in a severest chloroplast division mutant, arc6, was 3-5-fold higher than that in wild-type.

Amino Acid Sequence↗
PubMed2000

Determinants of patient satisfaction in postmastectomy breast reconstruction.

In today's increasingly competitive health care marketplace, consumer satisfaction has become an important measure of quality. Furthermore, measures of satisfaction with treatment inteerventions are influential factors in determining patients' and payers' choices of health care. This study sought to evaluate satisfaction with postmastectomy breast reconstruction and to assess the effects of procedure type and timing on patient satisfaction. As part of the Michigan Breast Reconstruction Outcome Study, patients undergoing first-time mastectomy reconstruction were prospectively evaluated, including cohorts of women choosing expander/implant, pedicle TRFAM flap, and free TRAM flap procedures. Preoperatively and 1 year postoperatively, participants completed a questionnaire that collected a variety of health status information. The postoperative questionnaire had an additional seven items assessing both general satisfaction with reconstruction (five items) and aesthetic satisfaction (two items) as separate subscales. Patients were asked to respond to each item using a five-point Likert scale. Item responses ranged from 1, indicating high satisfaction, to 5, reflecting low satisfaction. In the data analysis, only patients responding with a 1 or 2 for all of the items within a subscale were classified as "satisfied" for the subscale. To assess the effects of procedure type (implant, pedicle TRAM flap, and free TRAM flap) and timing (immediate versus delayed) on satisfaction and to control for possible confounding effects from other independent variables, multiple logistic regression was employed. In our analysis, odds ratios and associated 95 percent confidence intervals were calculated for each independent variable in the regression. Statistical significance was designated at the p < or = 0.05 level. A total of 212 patients were followed during the period of 1994 to 1997, including 141 immediate and 71 delayed reconstructions. The study population consisted of 49 expander/implant, 102 pedicle TRAM flap, and 61 free TRAM flap reconstruction patients. The analysis showed a significant association between procedure type and patient satisfaction. TRAM flap patients (both free and pedicle) appeared to have significantly greater general and aesthetic satisfaction compared with expander/implant patients (p = 0.03 and 0.001, respectively). Furthermore, pedicle TRAM flap patients were more aesthetically satisfied than those with free TRAM flaps (p = 0.072). The other independent variables of age and procedure timing did not appear to significantly affect either general or aesthetic satisfaction. However, preoperative physical activity was positively correlated with general satisfaction at the p = 0.034 level. The choice of procedure seems to have a significant effect on both aesthetic and general patient satisfaction with breast reconstruction. In this study, autogenous tissue reconstructions produced higher levels of patient aesthetic and general satisfaction compared with implant techniques. Pedicle and free TRAM flap patients do not seem to differ significantly in general satisfaction. However, women receiving pedicle TRAM flaps reported greater aesthetic satisfaction compared with patients undergoing free TRAM flaps. Furthermore, patient age and procedure timing may not have an effect on patient satisfaction with breast reconstruction.

Adult↗
PubMed2000

Comparison of endocardial activation times at effective and ineffective ablation sites within the pulmonary veins.

INTRODUCTION: Recent studies demonstrated that atrial arrhythmias may be generated within pulmonary veins. The purpose of this study was to compare the endocardial activation times at effective and ineffective ablation sites during radiofrequency catheter ablation of arrhythmias initiated or generated within pulmonary veins. METHODS AND RESULTS: Twenty-one of 28 patients without structural heart disease underwent successful ablation of 23 arrhythmogenic foci within a pulmonary vein. Electrograms were recorded at 75 pulmonary venous sites and categorized into three groups: 23 successful ablation sites; 28 unsuccessful target sites within an arrhythmogenic pulmonary vein; and 24 sites within nonarrhythmogenic pulmonary veins. The endocardial activation time of premature depolarizations arising at successful target sites was significantly earlier than at other sites. During premature depolarizations, an endocardial activation time of -75 msec or earlier had a sensitivity of 83% and a specificity of 79% for identification of a successful ablation site. Endocardial activation times earlier than -100 msec were recorded only at successful ablation sites, and endocardial activation times later than -30 msec were recorded only at sites within nonarrhythmogenic pulmonary veins. The presence of a split potential during sinus rhythm or premature depolarizations was not a specific indicator of a successful ablation site. CONCLUSION: The endocardial activation times of premature depolarizations that arise within pulmonary veins and initiate atrial tachycardia/fibrillation are useful in identifying successful ablation sites.

Adult↗
PubMed2000

Prevalence and significance of exit block during arrhythmias arising in pulmonary veins.

INTRODUCTION: Recent studies described the occurrence of conduction block within pulmonary veins. The purpose of this study was to evaluate the prevalence of exit block during arrhythmias that arise in pulmonary veins. METHODS AND RESULTS: Twenty-five patients with atrial tachycardia/fibrillation underwent successful ablation of 28 arrhythmogenic foci within a pulmonary vein. The prevalence of exit block in the pulmonary veins was determined in 28 arrhythmogenic pulmonary veins and 40 nonarrhythmogenic pulmonary veins. During isolated premature depolarizations, exit block in a pulmonary vein was observed at 50% of arrhythmogenic pulmonary vein sites and was never observed within pulmonary veins that did not generate a tachycardia (P < 0.01). During tachycardia, exit block from a pulmonary vein was observed in 61% of the arrhythmogenic pulmonary veins. The mean cycle length of the pulmonary vein tachycardias associated with exit block was significantly shorter than the cycle length of tachycardias that were not associated with exit block (163 +/- 32 vs 251 +/- 45 msec, P < 0.001). Exit block in two pulmonary veins during the same episode of tachycardia was observed in 3 of the 28 arrhythmogenic pulmonary veins (11%) in three different patients. Simultaneous recordings in the two pulmonary veins demonstrated bursts of tachycardia in both veins that were not synchronized. Radiofrequency catheter ablation of the arrhythmogenic site in one of the pulmonary veins eliminated spontaneous recurrences of tachycardia from the other pulmonary vein. CONCLUSION: Exit block from pulmonary veins is a common observation during tachycardias generated within pulmonary veins and indicates that an arrhythmogenic pulmonary vein has been identified. The occurrence of exit block in more than one pulmonary vein most likely is attributable to simultaneous tachycardias, one or both of which may be tachycardia induced and perpetuated by the other.

Adult↗
PubMed2000

Expression of functional markers in acute nonlymphoblastic leukemia.

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIalpha was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

Adolescent↗
PubMed2000

Selenium and immunocompetence in patients with head and neck cancer.

This randomized double-blind placebo-controlled study aimed to determine whether oral intake of 200 microg/d of sodium selenite, a dose within the safe and adequate daily intake (50-200 microg/d) recommended by the U.S. Food and Nutrition Board, will abrogate depressed or enhance normal-level immune functions of patients receiving therapy for squamous cell carcinoma of the head and neck. Subjects were given one selenium/placebo tablet/d for 8 wk, beginning on the day of their first treatment for the disease (e.g., surgery, radiation, or surgery and radiation) and their immune functions were monitored. Supplementation with selenium (Se) during therapy resulted in a significantly enhanced cell-mediated immunue responsiveness, as reflected in the ability of the patient's lymphocytes to respond to stimulation with mitogen, to generate cytotoxic lymphocytes, and to destroy tumor cells. The enhanced responsiveness was evident during therapy and following conclusion of therapy. In contrast, patients in the placebo arm of the study showed a decline in immune responsiveness during therapy, which was followed, in some patients, by an enhancement, but the responses of the group remained significantly lower than baseline values. The data also show that at baseline, patients entered in the study had significantly lower plasma Se levels than healthy individuals, and patients in stage I or II of disease had significantly higher plasma selenium levels than patients in stage III or IV of disease.

Adult↗
PubMed2000

Novel approaches to fracture healing.

The fractures that occur as a result of trauma frequently require multiple stage surgical procedures to achieve adequate union. Bone grafting with autogenous cancellous or cortico cancellous bone grafts is the traditional method used to repair bone defects. Most fractures will heal using this traditional procedure, however a number of fractures, up to 10% of the cases in United States alone, will result in delayed or impaired healing. Novel approaches are currently being investigated for the augmentation and acceleration of fracture healing. Some of these approaches include the use of biodegradable matrices; cell based approaches supplemented with osteogenic factors and genetic therapy. Cell based approaches for fracture healing have roused intense interest because of the great advance in the isolation and expansion of cells from the marrow that have the ability to differentiate into various types of cells including osteoblasts. In addition, the discovery and cloning of several proteins (bone morphogenetic proteins) that have the ability to induce bone formation, have contributed to the investigation of novel approaches to augment fracture healing. Use of genetic therapy for the augmentation of fracture healing has also recently gained strong interest. The attractive feature of gene therapy is that therapeutic proteins can be delivered locally to the fracture site in relatively high concentrations and in a sustained fashion. This review discusses these novel approaches and presents an assessment of their future clinical applicability.

Animals↗
PubMed2000

New advances in the pharmacological management of chronic heart failure.

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. beta-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents--all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).

Adrenergic beta-Antagonists↗
PubMed2000

Accumulation of sestamibi in lymphoma cell lines in vitro.

Although some authors have suggested that sestamibi imaging is useful in evaluation of patients with lymphoma, others have obtained equivocal results. This discrepancy has been further investigated in vitro using two patient-derived non-Hodgkin's lymphoma cell lines, OCI-Ly3 and OCI-Ly18. Sestamibi (0.2 MBq/ml) was added to a suspension of OCI-Ly3 or OCI-Ly18 cells and aliquots were removed over 1 h and centrifuged to determine cell-associated radioactivity. Further experiments studied the effect of addition of a P-glycoprotein (Pgp) modulator or alteration in plasma and/or mitochondrial membrane potentials. Accumulation of sestamibi reached plateau values within 30 min, but these values were 6-fold higher in OCI-Ly3 than in OCI-Ly18. Inhibition of Pgp function with GG918 or PSC833 did not affect OCI-Ly3 cells but increased accumulation in OCI-Ly18 cells 3-fold, indicating a moderate level of Pgp. However, both cell lines responded similarly to membrane potential alterations: hyperpolarization of the mitochondrial membrane with nigericin had little effect on accumulation: in contrast, depolarization of the plasma membrane with an isotonic high potassium buffer reduced accumulation of sestamibi to 52% of control and additional depolarization of the mitochondrial membrane with valinomycin further reduced accumulation to 12% of control levels. These studies suggest that there can be wide differences in accumulation between cell lines, in part due to Pgp-mediated efflux, but that both of these cell lines have highly polarized mitochondria with little further capacity for hyperpolarization.

Biological Transport↗
PubMed2000

Evaluation of 11th rib extrapleural-retroperitoneal approach to the thoracolumbar junction. Technical note.

OBJECT: The 11th rib extrapleural-retroperitoneal approach offers an alternative means for access to the thoracolumbar junction. It provides excellent operative exposure without the need to transgress the diaphragm, resulting in less morbidity and reduced risk of pulmonary complications. This approach, however, has been dismissed by many surgeons offering the unsubstantiated criticism that it affords limited access. Thus far, only technical descriptions of the operative procedure are available in the literature, without documentation of the clinical outcomes of these patients. In the current study the authors describe the 11th rib extrapleural-retroperitoneal approach to the thoracolumbar junction, and they evaluate the associated early and late morbidity in these patients. METHODS: From September 1996 to August 1999, the authors collected prospective data of consecutive patients who underwent surgery for a variety of pathological conditions of the thoracolumbar junction via this approach. In 26 consecutive patients requiring an anterior spinal procedure, lesions located between T-10 and T-11 were studied and followed for a mean period of 17 months (range 1-36 months). There were 13 men and 13 women whose mean age was 47 years (range 16-80 years), with the following pathological entities: trauma (13 cases), neoplasm (six cases), infection (two cases), and deformity (five cases). There were no cases of neurological deterioration. There were no significant pulmonary complications, and only one patient required insertion of a postoperative chest tube. CONCLUSIONS: The 11th rib extrapleural-retroperitoneal approach was successfully used to treat patients with a variety of lesions in the thoracolumbar junction and was associated with little morbidity. The authors believe that previous criticism suggesting that this approach provides only limited access is unsubstantiated.

Adolescent↗
PubMed2000

Apoptosis in dilated cardiomyopathy.

OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.

Adult↗
PubMed2000

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Adolescent↗
PubMed1999

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.

OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Ipsilesional intentional neglect and the effect of cueing.

BACKGROUND: Contralesional hemispatial neglect may be induced by an attentional deficit where patients are inattentive to or unaware of stimuli in contralesional hemispace, an intentional deficit where patients are unable to act in or towards contralesional hemispace, or both. The deficits associated with ipsilesional neglect have not been as well characterized. Because cueing may be used as a rehabilitative assistive device, we wanted to learn whether the efficacy of an attentional or intentional cue was related to the type of bias. METHODS: We studied a patient with a right frontotemporal stroke who had ipsilesional neglect by using a video apparatus that dissociates sensory-attentional and motor-intentional systems. We also performed a cueing experiment with primarily sensory-attentional cues (i.e., read the letter at the end of the line) and primarily motor-intentional cues (i.e., touch the end of the line). RESULTS AND CONCLUSIONS: Ipsilesional neglect was primarily a motor-intentional deficit with a motor-action bias to the left and a secondary sensory-attentional bias for stimuli to the right. With cueing we found a double dissociation: the rightwards motor-intentional cue improved the primary left-sided intentional bias and the leftwards sensory-attentional cue improved the secondary right-sided attentional bias. Effective rehabilitation strategies need to address both sensory-attentional and motor-intentional deficits in patients with neglect.

Attention↗
PubMed1999

Effect of additives on the physicochemical properties of liquid suppository bases.

To investigate the effects of additives on the physicochemical properties of in situ gelling and mucoadhesive liquid suppository base, gelation temperature, gel strength and bioadhesive force of liquid suppository base, poloxamer 407 (P 407) and poloxamer 188 (P 188) (15/15%) were evaluated in the presence of following additives: solvent (ethanol, propylene glycol, glycerin), ionic strength-controlling agent (sodium chloride) and pH-controlling agent (hydrochloric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate). Among the additives studied, sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate increased to a great extent the gel strength and the bioadhesive force of P 407/P 188 (15/15%) with a decrease in gelation temperature. Glycerin slightly decreased the gelation temperature and slightly increased the gel strength and bioadhesive force. However, the addition of 1% of sodium chloride, sodium monohydrogen phosphate or sodium dihydrogen phosphate caused a greater than 60-fold increase in gel strength and over a tenfold increase in bioadhesive force with 2-4 degrees C decrease of gelation temperature within optimal range, compared with P 407/P 188 (15/15%) alone. On the other hand, ethanol, propylene glycol and hydrochloric acid increased the gelation temperature and slightly decreased the gel strength and the bioadhesive force. Taken together, these findings indicate that the effect of additives on the physicochemical properties of liquid suppository bases depends on their bonding capacities, in that additives such as sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate having strong cross-linking bonds with the components of liquid suppository base increase the strength and bioadhesive force of a gel compared to liquid suppository base alone, while additives such as ethanol, propylene glycol and hydrochloric acid having weaker hydrogen bonding result in a weaker response. Thus, sodium chloride and sodium phosphates appear to be promising additives for in situ gelling and mucoadhesive liquid suppository base, if used in adequate amounts.

Adhesiveness↗
PubMed1999

Low convulsive activity of a new carbapenem antibiotic, DK-35C, as compared with existing congeners.

Since carbapenems and cephalosporins have been suggested to induce convulsive side effects through an inhibitory action on the central gamma-aminobutyric acid (GABA)-mediated inhibitory transmission, the present study evaluated the convulsive activity of a new carbapenem antibiotic (1R,5S,6S)-6[(R)-1-hydroxyethyl]-2-[(3S,5S)-5(S-methyl-4thiomorpholin ylcarbonyl)pyrrolidin-3-thio]-l-methylcarbapen-2-em-3- carboxylic acid (DK-35C) in in vitro and in vivo experiments, in comparison with cefazolin, imipenem and meropenem. In in vitro experiments, their abilities to inhibit [3H]muscimol (5 nM) binding to GABA(A) receptors were measured using crude synaptic membranes prepared from the rat cerebral cortex. The concentrations (mM) of the antibiotics which inhibit 50% of the specific binding, were 0.6 for imipenem, 1.8 for cefazolin, 15.4 for DK-35C and 27.6 for meropenem. In in vivo experiments, intracerebroventricular (i.c.v.) injections of cefazolin, imipenem and DK-35C induced convulsions in a dose-dependent manner in rats. The doses (nmol/rat) of the antibiotics which induce convulsions in 50% of rats, were 57 for imipenem, 96 for cefazolin, 377 for DK-35C and >3000 for meropenem. In the mouse pentylenetetrazole (PTZ) convulsive model, intravenous pretreatment with cefazolin (800 mg/kg) or imipenem (200 mg/kg) shifted the dose-response curve of PTZ (i.p.) to the left, indicating enhancement of the convulsive activity of PTZ. However, pretreatment with cefazolin, meropenem or DK-35C at a dose of 400 mg/kg did not produce any marked effects on the convulsive activity of PTZ compared with the saline vehicle-pretreated control. The results clearly demonstrate a good correlation between in vitro GABA(A) receptor binding assay and in vivo i.c.v. convulsive model using rats, and suggest that DK-35C may possess a relatively weak convulsive activity mediated through an interaction with GABA(A) receptors.

Animals↗