Search PubMed⌕ Search

Biomedical subjects

C Fukaya

Publications and source records attributed to C Fukaya.

At least 37 records · Page 2Linked to original sources
PubMed2000

Double blinded evaluation of the effects of pallidal and subthalamic nucleus stimulation on daytime activity in advanced Parkinson's disease.

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6-8months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (-57 and -29%, respectively) and the on-period (-36 and -25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients' preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.

Journal Article↗
PubMed2000

Molecular modelling and conformational analysis of novel glycoprotein (Gp) IIb/IIIa antagonists. Molecular orbital calculation and the condensed heterocyclic derivatives.

A naphthalene compound was chosen as lead compound to develop a new series of fibrinogen receptor antagonists. Eight new compounds with different condensed heterocyclic parts were prepared and their in vitro activities were evaluated. 5-Amidinobenzofuran compound 2, 6-amidinobenzothiophene 7, and 5-amidinofuro[2,3-b]pyridine 8 were more active than lead compound 1. Molecular orbital calculation studies suggested the presence of a preferred spatial orientation between the amidine and the carboxylic acid.

Acetates↗
PubMed2000

Intraoperative electro-oculographic Monitoring for Skull Base Surgery.

During surgery on the skull base, preservation of the integrity of the ocular motor nerves is vitally important. Intraoperative electrophysiological monitoring methods for protecting such functions have been reported by several investigators. However, these methods so far have not been popularized sufficiently, due to the difficulty and complexity of the procedures involved. The authors have developed an extremely simple but far more reliable method using electro-oculography under total intravenous anesthesia with propofol to preserve the integrity of the ocular motor nerves. The ocular motor nerves were stimulated with a monopolar electrode intracranially, and the polarity of the waves was recorded using surface electrodes placed around the eyeball, yielding precise information concerning the locations of the oculomotor nerve and/or abducent nerve. In addition, by performing continuous monitoring, invasive procedures affecting the ocular motor nerves could be detected as spontaneous ocular movements. In practice at our department, this method has been applied in 12 cases with tumors close to the ocular motor nerves, and has produced excellent results.

Journal Article↗
PubMed2000

Thalamotomy caused by cardioversion in a patient treated with deep brain stimulation.

Deep brain stimulation (DBS) has been applied mainly for the treatment of intractable pain and involuntary movement disorders. Based on the rising numbers of patients undergoing DBS therapy, the possibility of emergent application of cardioversion for the treatment of occasional severe arrhythmia in DBS patients has also increased. However, there has been insufficient discussion about cardioversion in DBS patients. We employed a radiofrequency receiver that transmits to the brain impulses provided by an external generator through an antenna applied to the skin in front of the receiver. We experienced a patient who displayed almost complete cessation of his action tremor with thalamic stimulation. He also developed central dysesthetic pain and showed complete disappearance of his action tremor, even without stimulation, following successful application of cardioversion. It is considered that slight changes in the high-voltage electrical current or high-voltage electrical current spread induced central dysesthetic pain and almost identical effects to thalamotomy. We report for the first time a case of thalamotomy induced by cardioversion in a DBS patient. Clearly, we need to bear in mind that cardioversion has the capability to cause brain lesions in DBS patients with a radiofrequency receiver implanted subcutaneously at the anterior chest wall.

Atrial Fibrillation↗
PubMed2000

Effects of anterodorsal pallidal stimulation on gait freezing (Kinesia paradoxa) in Parkinson's disease.

The results of a double-blind evaluation of the effects of internal globus pallidus (GPi) stimulation in 7 patients with advanced Parkinson's disease are summarized. The evaluation was performed 6-8 months after surgery while the patients were on medication with an optimal dose and schedule. The stimulation was turned off for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during their daytime activity were recorded as the on-period and off-period scores, respectively. A significant reduction in the total score on part III of the Unified Parkinson's Disease Rating Scale was induced by GPi stimulation at the off-period (-57%) as well as the on-period (-36%). Clinically important improvement was also achieved in severe gait freezing (kinesia paradoxa) in 2 patients when stimulation was applied to the anterodorsal portion of the GPi. Such an effect was observed during unilateral stimulation of the right side alone.

Aged↗
PubMed1999

Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 1. The selection of naphthalene derivatives.

The synthesis and design using molecular modeling techniques for non-peptide, low molecular weight novel fibrinogen receptor (glycoprotein IIb/IIIa: Gp IIb/IIIa) antagonists, is reported. We used a highly potent serine protease inhibitor, Nafamostat, having an amidinonaphthyl unit as the starting compound. The compounds 4-(6-amidino-2-naphthylaminocarbonyl)phenoxyacetic acid (5a) and 4-(6-amidino-2-naphthalenecarboxamido)phenoxyacetic acid (5b) inhibited adenosin-5'-diphospate (ADP)-induced aggregation of human platelet-rich plasma (PRP) with IC50 values of 0.05 and 0.07 microM, respectively, and had lost their ability to inhibit a variety of serine proteases, including thrombin, factor Xa, plasmin and trypsin.

Adenosine Diphosphate↗
PubMed1999

Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives.

A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetic+ ++ acid 17e and trans-3-[4-(5-amidinobenzofuran-2- carboxamido)cyclohexyl]propionic acid 17f produced marked inhibitions with IC50 values of 0.018 and 0.006 microM, respectively in a human platelet adenosin-5'-diphospate (ADP)-induced aggregation assay; they also exhibited a wide spectrum of inhibition toward major aggregation agonists (ADP, collagen, thrombin, PMA (tumor promoter) and arachidonic acid). These compounds were > 2-3 orders of magnitude more effective in inhibiting platelet aggregation than human umbilical vein endothelial cell (HUVEC) binding. The oral administration of 10 mg/kg of either 17e and 17f to guinea pig, resulted in a 60% inhibition of ex vivo platelet aggregation after 5 h. Oral administration of ethyl trans-4-(5-amidinoben-zofuran-2- carboxamido)cyclohexyloxyacetate 18e (10 mg/kg) resulted in 80% inhibition of platelet aggregation in dogs for 6 h after oral administration with a return to baseline by 24 h. Ethyl trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionat e 18f (AR0598) produced 80% inhibition for 5 h after oral administration. Prodrug 18e showed a good profile in dogs with a long duration of action. 18e (AR0510) was selected as suitable clinical candidate for development as an orally active antithrombotic agent.

Adenosine Diphosphate↗
PubMed1999

Intraoperative electrooculographic monitoring of oculomotor nerve function during skull base surgery. Technical note.

Intraoperative monitoring techniques for protecting the integrity of the oculomotor nerves during skull base surgery have been reported by several investigators, all of which involved the use of electromyographic responses to extraocular muscles. However, these techniques have not yet become popular because of the complexity of the procedures. The authors report an extremely simple and far more reliable technique in which electrooculographic (EOG) monitoring is used. The oculomotor nerves were stimulated with a monopolar electrode during skull base exposure. The polarity of the EOG responses recorded with surface electrodes placed on the skin around the eyeball yielded precise information concerning the location and function of the oculomotor and abducent nerves. In addition, with the aid of continuous EOG monitoring that detected transient changes in the background waves, surgical procedures that might impinge on oculomotor nerve function could be avoided. The present technique has been used in eight patients with skull base tumors and with it, the authors have achieved excellent results.

Electrooculography↗
PubMed1998

Synthesis and pharmacological activity of triazolo[1,5-a]triazine derivatives inhibiting eosinophilia.

In continuation of our previous work on eosinophilia inhibitors, we synthesized an additional series of inhibitors, which consisted of 5-amino-1-[(methylamino)thiocarbonyl]-1H-1,2,4-triazole derivatives and a newly developed series of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives. We evaluated their inhibitory activity on the airway eosinophilia model, which was induced by the intravenous (iv) injection of Sephadex particles. In the 1,2,4-triazole series with various substituents at the 3 position of the triazole ring such as 2-furyl, pyridyl, and phenoxy, none of derivatives had comparable activity to the previously reported compound GCC-AP0341, 5-amino-3-(4-chlorophenyl)-1-[(methylamino)thiocarbonyl]-1H-1,2, 4-triazole. In the triazolo[1,5-a]triazine series, 2-(4-chlorophenyl)-6-methyl-1,2,4-triazolo[1,5-a]-1,3, 5-triazine-7(6H)-thione (3h) was highly potent, and when given orally it had an ID50 value of 0.3 mg/kg, which is comparable to that of GCC-AP0341. The fact that the structure-activity relationship of these two series was quite similar suggests that a common substructure, such as the 1,2,4-triazole ring with a substituted phenyl ring at the 3 position and a thiocarbonyl moiety at the 1 position, could contribute to the activity. Our selected compound 3h was less active than GCC-AP0341 in the antigen-induced hyper-responsiveness model in guinea pigs; however, we plan to carry out further studies on eosinophil functions, especially on their activation, using our two compounds, 3h and GCC-AP0341.

Animals↗
PubMed1998

Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site.

Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = > 100 microM). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions.

Animals↗
PubMed1998

Poststroke pain control by chronic motor cortex stimulation: neurological characteristics predicting a favorable response.

OBJECT: The goal of this study was to identify the neurological characteristics of patients with poststroke pain who show a favorable response to motor cortex (MC) stimulation used to control their pain. METHODS: The neurological characteristics of 31 patients treated by MC stimulation were analyzed. In 15 patients (48%), excellent or good pain control (pain reduction > 60%) was achieved for follow-up periods of more than 2 years by using MC stimulation at intensities below the threshold for muscle contraction. Satisfactory pain control was achieved in 13 (73%) of 18 patients in whom motor weakness in the painful area was virtually absent or mild, but in only two (15%) of the 13 patients who demonstrated moderate or severe weakness in the painful area (p < 0.01). Muscle contraction was inducible in the painful area in 20 patients when stimulated at a higher intensity. No such muscle response was inducible in the remaining 11 patients, no matter how extensively the authors attempted to determine appropriate stimulation sites. Satisfactory pain control was achieved in 14 (70%) of the 20 patients in whom muscle contraction was inducible, but in only one (9%) of the 11 patients in whom muscle contraction was not inducible (p < 0.01). No significant relationship was observed between pain control and various sensory symptoms, including the presence of hypesthesia, spontaneous dysesthesia, hyperpathia, and allodynia, or the disappearance of the N20 component of the median nerve-evoked somatosensory scalp potential. No significant relationship existed between the effect of MC stimulation on the pain and stimulation-induced phenomena, including paresthesia, improvement in motor performance, and attenuation of involuntary movements. CONCLUSION: These findings suggest that the pain control afforded by MC stimulation requires neuronal circuits that are maintained by the presence of intact corticospinal tract neurons originating from the MC. Preoperative evaluation of motor weakness of the painful area appears to be useful for predicting a favorable response to MC stimulation in the control of poststroke pain.

Cerebrovascular Disorders↗
PubMed1997

Control of poststroke involuntary and voluntary movement disorders with deep brain or epidural cortical stimulation.

The effects of deep brain or epidural cortical stimulation on poststroke involuntary and voluntary movement disorders were analyzed in a total of 64 patients. Among them, 22 patients underwent either deep brain or epidural cortical stimulation in order to control their poststroke involuntary movements. The remaining 42 underwent epidural cortical stimulation for the purpose of controlling their poststroke pain. In the latter group of patients, we analyzed the changes in coexistent involuntary or voluntary movement disorders during stimulation for pain control. Stimulation of either the thalamic nucleus ventralis intermedius or the motor cortex proved to be useful in 13 (59%) of the patients who underwent deep brain or epidural cortical stimulation for control of poststroke involuntary movements. Satisfactory control was often achieved in patients with hemiballismus, hemichorea or resting tremor. In 8 (19%) of the patients who underwent epidural cortical stimulation for pain control, stimulation of the motor cortex improved motor performance which had been impaired in association with hemiparesis. Such an effect was independent of pain control and apparently resulted from an inhibition of their rigidity. We believe that these findings justify further clinical studies on deep brain or epidural cortical stimulation for the control of poststroke movement disorders.

Brain↗
PubMed1997

Novel histamine H3 receptor antagonists: synthesis and evaluation of formamidine and S-methylisothiourea derivatives.

In order to obtain a new, potent and selective histamine H3 receptor antagonists, chemical modifications of thioperamide, a well-known H3 receptor antagonist, were conducted. A new series of compounds has been synthesized by modifying the thiourea and cyclohexyl groups of thioperamide, and tested for H3 affinity by receptor binding assay using plasma membrane from rat cerebral cortex. The thiourea group of thioperamide was found to be replaceable with a basic moiety such as formamidine or S-methylisothiourea. Replacement of the cyclohexyl group in thioperamide by a 1-adamantyl or an exo-2-norbornyl group increased the affinity for H3 receptor. Among the compounds synthesized, N-(1-adamantyl)-N',N'-[3-(4(5)-1H-imidazolyl)pentamethylene] formamidine 3f (AQ0145) showed the highest H3 receptor affinity, having a potent antagonistic activity. This compound was at least 1,000-fold more active towards H3 than towards H1 and H2 receptors.

Amidines↗
PubMed1996

Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia.

In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the airway through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-tria zole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally (ip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD50 value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D4 (LTD4) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23c as a novel candidate for the treatment of chronic asthma. Further studies are now underway.

Animals↗
PubMed1996

Synthesis and pharmacological evaluation of N-(6-functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidine s as antihypertensive agents.

A series of amino acid conjugates of N-(6-amino-3-pyridyl)-N'-[exo-bicyclo[2.2.1]hept-2-yl]-N''- cyanoguanidine (4) were prepared and evaluated as antihypertensive agents. The parent compound 4 showed potent potassium channel-opening and antihypertensive activities, but with undesirable changes of the urinary balance of electrolytes. However, alanine and histidine congeners (9,19) reduced this undesirable side effect of 4 through improved pharmacokinetics without loss of antihypertensive activity. They also provided additional information on the structural requirements for pinacidil-type potassium channel openers.

Animals↗
PubMed1994

Synthesis and topical antiinflammatory and antiallergic activities of antioxidant o-aminophenol derivatives.

In order to develop novel compounds for topical use possessing antiallergic as well as antiinflammatory activities, a series of o-aminophenol derivatives bearing H1-antihistaminic structures were synthesized and their effects were investigated on lipid peroxidation in rat brain homogenates, antiinflammatory effection arachidonic acid- and 12-O-tetradecanoylphorbol-13- acetate-induced mouse ear edema and antiallergic effect on 48-h homologous passive cutaneous anaphylaxis in rats. Furthermore, the effects of these compounds on delayed-type hypersensitivity reaction in mice were examined. Several N-monosubstituted amino-4-methylphenols were found to exert potent inhibitory activities in all of these assays. Of these compounds, 4m was chosen for further development as AD0261.

Administration, Topical↗