Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans.

BACKGROUND/OBJECTIVES: Brown adipose tissue (BAT) is a potential therapeutic target against obesity and diabetes through thermogenesis and substrate disposal with cold exposure. The role of BAT in energy metabolism under thermoneutral conditions, however, remains controversial. We assessed the contribution of BAT to energy expenditure (EE), particularly diet-induced thermogenesis (DIT), and substrate utilization in human adults. METHODS: In this cross-sectional study, BAT activity was evaluated in 21 men using 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) after cold exposure (19 °C). The subjects were divided into BAT-positive (n=13) and BAT-negative (n=8) groups according to the 18F-FDG-PET/CT findings. Twenty-four hour EE, DIT and respiratory quotient were measured using a whole-room indirect calorimeter at 27 °C. RESULTS: Body composition, blood metabolites and 24-h EE did not differ between groups. DIT (%), calculated as DIT divided by total energy intake, however, was significantly higher in the BAT-positive group (BAT-positive: 9.7±2.5%, BAT-negative: 6.5±4.0%, P=0.03). The 24-h respiratory quotient was significantly lower (P=0.03) in the BAT-positive group (0.861±0.027) than in the BAT-negative group (0.889±0.024). CONCLUSION: DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.

Age and cardiorespiratory fitness are associated with arterial stiffening and left ventricular remodelling.

Arterial stiffening, hypertension and left ventricular (LV) remodelling are associated with increased risk of cardiovascular disease. Cardiorespiratory fitness is associated with cardiovascular function and reduced risk of cardiovascular disease. This cross-sectional study was carried out to determine the relationships between cardiorespiratory fitness, arterial stiffness, blood pressure (BP) and LV remodelling in women. On the basis of peak oxygen uptake, a total of 159 premenopausal (young) and postmenopausal (older) women were categorized into either low (unfit) or high (fit) cardiorespiratory fitness groups. The arterial stiffness and LV remodelling were measured by brachial-ankle pulse wave velocity (baPWV) and carotid augmentation index (AI) and LV relative wall thickness (RWT). Two-way analysis of variance indicated a significant interaction between age and cardiorespiratory fitness in baPWV, carotid AI, BP and RWT. In the older group, arterial stiffness (baPWV; 1401+/-231 vs 1250+/-125 cm s(-1), P<0.01, AI; 32.9+/-9.9 vs 24.8+/-10.1%, P<0.01), systolic blood pressure (SBP) (130+/-22 vs 117+/-15 mm Hg, P<0.01) and RWT (0.47+/-0.08 vs 0.42+/-0.04, P<0.05) in fit women were lower than in unfit women. In older women, RWT was significantly related to baPWV (r=0.46, P<0.01), carotid AI (r=0.29, P<0.05), SBP (r=0.57, P<0.01) \[V(2peak) (r=-0.32, P<0.05). In young women, they were not significant correlations, except for a weak correlation between RWT and SBP (r=0.21, P<0.05). These results suggest that higher cardiorespiratory fitness is associated with lower arterial stiffness, BP and RWT in older women.

Resting energy expenditure can be assessed by dual-energy X-ray absorptiometry in women regardless of age and fitness.

OBJECTIVE: To evaluate the possibility that measurement of the magnitude and distribution of fundamental somatic heat-producing units using dual-energy X-ray absorptiometry (DXA) can be used to estimate resting energy expenditure (REE) in both young and elderly women with different aerobic fitness levels. SUBJECTS AND METHODS: Peak oxygen uptake (VO(2) peak) and REE(m) were directly measured in 116 young (age: 22.3+/-2.1 years) and 72 elderly (63.3+/-6.4 years) women. The subjects were divided into four groups according to categories of age and VO(2) peak; young: high fitness (YH, n=58); low fitness (YL, n=58); elderly: high fitness (EH, n=37) and low fitness (EL, n=35). Using DXA, systemic and regional body compositions were measured, and REE(e) was estimated from the sum of tissue organ weights multiplied by corresponding metabolic rate. RESULTS: Although there were remarkable differences in systemic and regional body compositions, no significant differences were observed between REE(m) and REE(e) in the four groups. REE(e) significantly correlated with REE(m) in elderly as well as young women; the slopes and intercepts of the two regression lines were statistically not different between the elderly and young groups (elderly: y=0.60x + 472, r=0.667; young: y=0.78x + 250, r=0.798; P<0.001, respectively). A Bland-Altman analysis did not indicate bias in calculation of REE for all the subjects. CONCLUSION: These results suggest that REE can be estimated from tissue organ components in women regardless of age and aerobic fitness.

Muscle mass and bone mineral indices: does the normalized bone mineral content differ with age?

OBJECTIVE: To investigate the relationships between regional skeletal muscle mass (SM mass) and bone mineral indices and to examine whether bone mineral content (BMC) normalized to SM mass shows a similar decrease with age in young through old age. SUBJECTS/METHODS: One hundred and thirty-eight young and postmenopausal women aged 20-76 years participated in this study and were divided into three groups: 61 young women, 49 middle-aged postmenopausal women and 28 older postmenopausal women. Muscle thickness (MTH) was determined by ultrasound, and regional SM mass (arm, trunk and leg) was estimated based on nine sites of MTH. Whole-body and regional lean soft tissue mass (LSTM), bone mineral density (BMD) and BMC (whole body, arms, legs and lumbar spine) were measured using dual-energy X-ray absorptiometry. RESULTS: Ultrasound spectroscopy indicated that SM mass is significantly correlated with site-matched regional bone mineral indices and these relationships correspond to LSTM. The BMC and BMD in older women were significantly lower than those in middle-aged women. When BMC was normalized to site-matched regional SM mass, BMC normalized to SM mass in arm and trunk region were significantly different with age; however, whole-body and leg BMC normalized to SM mass showed no significant difference between middle-aged and older postmenopausal women. CONCLUSIONS: The age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women.

Intermittent exotropia surgery in children: long term outcome regarding changes in binocular alignment. A study of 666 cases.

PURPOSE: To review and determine the long term outcome of surgery for intermittent exotropia in children. CASES: A total of 666 cases were reviewed. They were 15 years old or younger and underwent surgery for intermittent exotropia during the preceding 22 years. Bilateral recession of the lateral rectus muscles was performed in 349 cases. Unilateral recession of the lateral rectus and resection of the medial rectus muscles was performed in 298 cases. One and four muscle procedures were performed in 19 cases. The outcome was evaluated at 1 month and 4 years after surgery. RESULTS: Orthotropia or mini-microtropia was achieved in 401 patients (60.2%) one month after surgery. Bilateral recession of the lateral rectus muscles was more effective than unilateral recession- resection. Out of these 401 patients, half, 199 patients (49.6%) showed orthotropia or mini-microtropia 4 years after surgery while the other half, 202 (50.4%), became exotropic. Bilateral recession of the lateral rectus muscles was also more effective in producing orthotropia or mini-microtropia on a long term basis than unilateral recession-resection. The rate of orthotropia or mini- microtropia was higher when the patients were operated before 3 years and after 11 years of age. CONCLUSIONS: There was a strong tendency for intermittent exotropia to recurr and drift into permanent exotropia during 4 or more years following surgery. It is advocated to aim at orthotropia during the immediate post- surgical period and to avoid overcorrection. Early surgery is not necessary when the patient is over 4 years of age. Bilateral lateral rectus recession is the preferred surgical procedure.

Binocular Function of Intermittent Exotropia Before and After Surgery.

Purpose: We examined the binocular function of intermittent exotropia before and after surgery, and studied the effect of the surgery and the factor that might be involved in its result.Materials and Methods: 402 intermittent exotropic patients, who underwent their first surgical correction for the strabismus at Teikyo University Hospital, were examined for retinal correspondence and stereo acuity before and after surgery.Results: 367 patients (91.3%) had already had good stereo acuity before surgery when their eyes were straight. Regarding retinal correspondence, though 192 patients (47.8%) were abnormal (dual) before surgery, 301 patients (74.9%) were normal after surgery. The eye deviation of 101 patients who could not get normal retinal correspondence after surgery was significantly larger than normal (P <.001), and 77.2% of them had also vertical strabismus which was mainly composed of dissociated vertical deviation.Conclusion: Normal binocular function could be recovered by surgical treatment in most intermittent exotropic patients. When patients could not get normal retinal correspondence after surgery, we supposed that dissociated vertical deviation might exert an important effect upon their binocular function.

[Binocular function of intermittent exotropia before and after surgery].

PURPOSE: We examined the binocular function of intermittent exotropia before and after surgery, and studied the effect of the surgery and the factor that might be involved in its result. MATERIALS AND METHODS: 402 intermittent exotropic patients, who underwent their first surgical correction for the strabismus at Teikyo University Hospital, were examined for retinal correspondence and stereo acuity before and after surgery. RESULTS: 367 patients (91.3%) had already had good stereo acuity before surgery when their eyes were straight. Regarding retinal correspondence, though 192 patients (47.8%) were abnormal (dual) before surgery, 301 patients (74.9%) were normal after surgery. The eye deviation of 101 patients who could not get normal retinal correspondence after surgery was significantly larger than normal (p < 0.001), and 77.2% of them had also vertical strabismus which was mainly composed of dissociated vertical deviation. CONCLUSION: Normal binocular function could be recovered by surgical treatment in most intermittent exotropic patients. When patients could not get normal retinal correspondence after surgery, we supposed that dissociated vertical deviation might exert an important effect upon their binocular function.

Esotropia surgery in children: long term outcome regarding changes in binocular alignment; a study of 956 cases.

PURPOSE: To study the correlation between the outcome at 1 month (when the postoperative eye position is at the earliest stabilized), and 4 years after surgery. METHOD: Retrospective review of medical records. CASES: The authors reviewed 956 patients under 15 years of age who underwent unilateral or bilateral recession of the medial rectus muscle during a 22 year period representing the entire practice period of the senior author since the department was founded in 1977. The series comprised 521 cases of congenital/infantile esotropia (manifest before 6 months of age with no accommodative component) and 435 cases of acquired esotropia (manifest after 6 months of age with no accommodative component or with an accommodative component but excluding those with a high AC/A ratio). A consistent surgical plan was employed throughout this period for each condition. RESULTS: Both types of esotropia showed a slight tendency to become exotropic during the 4 years after surgery. There was no difference in general success with regard to the reconstructive restoration of normal appearance or improvement of appearance between 1 month and 4 years after surgery. Patients with normal retinal correspondence or simultaneous perception achieved better binocular alignments at the 4 year followup than those who did not have such sensory binocular cooperation. CONCLUSIONS: In infantile and acquired esotropia, it is essential that orthotropia or minimal esotropia be present at 1 month of surgery in order to obtain a binocular alignment within +/- 4 PD of orthotropia 4 years after surgery. It is strongly recommended to avoid overcorrection (consecutive exotropia) at 1 month after surgery for both congenital/infantile and acquired esotropia.

Two different types of humoral immune response to Actinobacillus actinomycetemcomitans in high-responder periodontitis patients.

Actinobacillus actinomycetemcomitans is considered to be an aetiological agent in various forms of periodontitis, with serotype b-specific carbohydrate being the immunodominant antigen of A. actinomycetemcomitans Y4 in high-responder patients. Lipopolysaccharide (LPS) of the organism may also be an important antigen. The purpose of the present study was to clarify the importance of LPS as an antigen of A. actinomycetemcomitans. Twenty patients who had high antibody titres to strain Y4 were selected, and the reactivity of their sera with LPS was determined by ELISA and Western blotting. Two groups of patients were observed: group 1 had high IgG titres only to serotype b strain, whereas group 2 had high IgG titres to serotypes a, b and c strains. The results of adsorption tests showed that anti-A. actinomycetemcomitans Y4 antibody in group 1 patients mostly consisted of antibody reactive with the serotype b-specific carbohydrate, whereas the antibody in group 2 patients mostly consisted of antibody reactive with the LPS of all serotypes. These data show that anti-LPS antibody is present and predominant in anti-A. actinomycetemcomitans Y4 antibody from some high-responder patients, and indicate an important role for LPS as an antigen in the humoral immune response to the organism.

Increasing-current electroshock seizure test: a new method for assessment of anti- and pro-convulsant activities of drugs in mice.

We developed the increasing-current electroshock seizure (ICES) test, a new method for assessment of anti- and pro-convulsant activities of drugs in mice. In this method, a single train of pulses (square wave, 5 msec, 20 Hz) of linearly increasing intensity from 5 to 30 mA (increment of 0.1 mA/0.1 sec, i.e., 5-30 mA in 25 sec) was applied via ear electrodes. The current at which tonic hindlimb extension occurred was recorded as the seizure threshold. Thus, this method allows determination of the seizure threshold current for individual animals. Carbamazepine, phenytoin, valproate, phenobarbital, diazepam, and morphine all increased the seizure threshold current in a dose-dependent manner, whereas ethosuximide was not effective. The seizure threshold current decreased after treatment with reserpine, chlorpromazine, aminophylline, strychnine, pentylenetetrazol, bicuculline, picrotoxin, and ethyl-beta-carboline-3-carboxylate (beta-CCE). These results indicate that the ICES test, like the maximal electroshock seizure test, is a model of grand mal-type seizure and is useful for evaluation of both the anti- and pro-convulsant activities of drugs.

Results of surgery for paralytic exotropia due to oculomotor palsy.

In 138 cases of paralytic exotropia due to oculomotor palsy, transposition of the superior oblique muscle and resection of the medial rectus muscle were carried out. Surgery was performed with or without recession of the lateral rectus muscle. The long-term prognosis for 4 years or more was observed in 35 cases. We found that the same results could be obtained by selecting transposition of the superior oblique muscle in cases of complete palsy and resection of the medical rectus muscle in cases of incomplete palsy. There was no benefit in combining resection of the medial rectus muscle when performing the transposition of the superior oblique muscle. Regardless of which method was used, a combination with recession of the lateral rectus muscle greatly improved the effectiveness of the procedure.

Results of surgery for paralytic esotropia due to abducens palsy.

The surgical effects of three methods, transposition of the vertical rectus muscles, Jensen's procedure, and resection (advancement) of the lateral rectus muscle, were compared among 109 cases of paralytic esotropia due to abducens palsy. These procedures were combined with recession of the medial rectus muscle in about half the cases. Of the 109 cases, 22 were followed up for 4 years or longer. Results were similar, provided that the following protocols for surgery were adhered to: in cases of complete paralysis, transposition of the vertical rectus muscles was done, and in cases of incomplete paralysis, resection (advancement) of the lateral rectus muscle was performed. With both procedures, results were improved if recession of the medial rectus muscle was carried out at the same time.

Long-term results of surgery for superior oblique palsy.

The results one month after surgery in 159 cases of superior oblique palsy were compared according to the method of surgery with the results 4 years or longer after surgery. There were 141 cases of congenital palsy and 18 cases of acquired palsy, for a total of 159 cases. Our study showed that surgery on the oblique muscle provided long-lasting effects, while recession of the superior rectus muscle or recession of the contralateral inferior rectus muscle could cause late overcorrection. When performing surgery on the rectus muscle, careful attention must be paid to suturing the muscle.

[Surgical and botulinum toxin treatment in two cases of abnormal retinal correspondence-exotropia with congenital homonymous hemianopsia].

We report 2 unusual cases of congenital occipital hemianopsia associated with abnormal retinal correspondence (ARC)-exotropia. Two Japanese males, 25 and 28 years of age, visited our hospital for surgical correction of manifest exotropia with dissociated vertical deviation and overaction of the superior oblique muscle. Visual field examination demonstrated homonymous hemianopsia with approximately 5 to 10 degrees of macular sparing. Visually evoked potential examination showed small amplitude similar to dissociated vertical deviation patients in all half-field stimulation. Electrooculogram examination demonstrated defective pursuit to the ipsilateral side. Some investigators have speculated that progressive exotropia compensates for homonymous hemianopsia and is a rare contraindication for strabismus surgery. To confirm the deterioration of motor and visual functions before surgery in these patients, we tried injections of botulinum A type toxin into the lateral rectus muscle ipsilateral to the hemianopsia. Contrary to the hypothesis, our patients had no change in their binocular visual fields and visual function. Finally, we performed recession of the lateral rectus muscle, so that both patients were satisfied with their ocular alignment, with no marked change of visual behavior.

General pharmacological profile of the new cognition-enhancing agent nefiracetam.

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)

[The development of occlusion amblyopia following atropine therapy for strabismic amblyopia].

For the treatment of strabismic amblyopia the authors have used atropine in the sound eye under usual optical correction as soon as central fixation of the amblyopic eye is secured by means of proceeding occlusion therapy. Although there may be little effect of occlusion in atropine therapy, six children under five years of age developed amblyopia in their sound eyes. In every case, the first sign of developing amblyopia was the decrease of fixation ability in the sound eye in a binocular fixation test prior to the reduction of visual acuity. On the other hand, fixation ability of the originally amblyopic eye was reinforced more and more not only during atropinization but after its finish until deep amblyopia developed in the sound eye. In three cases, eccentric fixation occurred at 7, 9, and 17 weeks after atropinization. These facts suggest that occlusion amblyopia following atropine therapy is not the result of deprivation but is due to the reversal of the eye used for fixation. Strabismic amblyopia may have the tendency toward an alternation between fixation abilities of the two eyes and such a binocular sensory anomaly may cause strabismic amblyopia itself.

General pharmacological profile of the new anti-ulcer drug 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]-amino-N -methylbenzamide.

Pharmacological properties of the anti-ulcer drug 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl] methyl]-amino-N-methylbenzamide (DQ-2511, CAS 104775-36-2) on the central and autonomic nervous systems, smooth muscle, gastrointestinal system, and other miscellaneous systems were investigated. 1. DQ-2511 showed little or no influence on general behavior, spontaneous motor activity, hexobarbital sleeping time (mouse), conditioned avoidance response (rat), body temperature (rabbit), EEG or spinal reflex (cat) after oral administration (300-1000 mg/kg) or intravenous injection (15, 50 mg/kg). It also had no anticonvulsant or analgesic activities (mouse). 2. DQ-2511 had no influence on pupil size (rabbit). It reduced or tended to reduce contractile responses of the nictitating membrane induced by electrical stimulation of pre- and post-ganglionic sympathetic nerve (cat) at the highest dose. The drug inhibited the pressor response to norepinephrine, but had little or no inhibitory effect on the depressor response to acetylcholine at the highest dose (dog). 3. DQ-2511 reduced contractile responses to nicotine, BaCl2, acetylcholine, histamine and serotonin (isolated guinea pig ileum), to acetylcholine and histamine (trachea), and to norepinephrine (vas deferens) at high concentrations. It also inhibited spontaneous and oxytocin-induced motility (isolated rat uterus). 4. DQ-2511 decreased gastric motility in a dose-related manner at intravenous doses of 5-50 mg/kg (dog). It also reduced gastric emptying rate at oral doses of 100-1000 mg/kg, and gastric secretion at intraperitoneal doses of 100-300 mg/kg (rat). On the other hand, it induced no definite changes in intestinal motility (dog) or gastrointestinal transit (mouse).(ABSTRACT TRUNCATED AT 250 WORDS)

[Central effects of iohexol and iopamidol, non-ionic contrast media].

Central effects of intravenously (i.v.)-administered iohexol were compared with those of iopamidol in a series of tests. Mannitol was used as a reference. As assayed by the primary screening test based on Irwin's method, i.v. administration of mannitol resulted in a score of 0 in ddY mice and a score of 0.6 in ICR mice in the startle response. These results were not different from the data of both iohexol and iopamidol. Iopamidol at a dose of 1750 mgI/kg produced an inhibitory effect on the spontaneous locomotor activity. Iohexol at a dose of 7000 mgI/kg potentiated the duration of thiopental-induced narcosis. Hypothermia was caused by high doses of both iohexol and iopamidol. Electric stimulus increased the mortality of mice pretreated with high doses of iohexol and iopamidol. Both drugs had no notable activities in the anticonvulsant, electroencephalic, muscle relaxant and antinociceptive tests. These results indicate that both iohexol and iopamidol do not necessarily possess a similar pharmacological action. Judging from the LD50 of approximately 15000 mgI/kg for both drugs, they seem unlikely to have a specific pharmacological action on the central nervous system.

General pharmacology of the new quinolone antibacterial agent levofloxacin.

The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin-induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex.