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Biomedical subjects

S Nishio

Publications and source records attributed to S Nishio.

At least 235 records · Page 13Linked to original sources

Oculomotor nerve palsy in patients with cerebral aneurysms.

Twenty-six patients with oculomotor nerve palsy due to cerebral aneurysms were examined. There were six males and twenty females with a mean age of 55 years. 25 of the 26 aneurysms were located at the junction of the internal carotid and the posterior communicating artery and one was at the junction of the basilar artery and the superior cerebellar artery. Twelve patients had associated subarachnoid hemorrhage (SAH); the other 14 did not. The initial symptoms in many patients were ptosis and double vision. Twenty-one of the patients had total oculomotor nerve palsy, one had a sparing of medial rectus muscle; three patients had only ptosis and anisocoria, and one had oculomotor nerve palsy with pupillary sparing. All aneurysms, including giant aneurysms, were clipped under a microscope, and six oculomotor nerves were found to be decompressed at surgery. The follow-up periods were from six months to three years. Nine patients had a complete recovery of oculomotor function; thirteen had an incomplete recovery; and four remained unchanged. The mean interval between the onset of palsy and the time of surgery was 24 days in complete recovery cases, 42 days in incomplete recovery cases, and 119 days in unchanged cases. The recovery of oculomotor function started with the levator palpebrae muscle and followed by the medial rectus muscle. The recovery of pupillary function was, however, not consistent. Of the factors influencing recovery from oculomotor nerve palsy, the interval between the onset of palsy and the time of surgery was most important. Therefore, aneurysms with oculomotor nerve palsy should be operated on as early as possible, regardless of the presence or absence of SAH.

Adult↗

Convexity meningioma with galactorrhea and hyperprolactinemia. A case report.

A case is reported of a huge convexity meningioma associated with galactorrhea and an elevated serum prolactin level of 41 ng/mL. Total removal of the tumor resulted in a return of the prolactin level to normal (9.7 ng/mL). Because of a severe mass effect, the distant tumor might have encroached upon the hypothalamic-pituitary axis and interrupted PRL inhibitory factor regulation.

Brain Neoplasms↗

Effects of TRK-100, a stable prostacyclin analogue, on regulation of cyclic AMP metabolism in platelets.

TRK-100 is a chemically stable analogue of prostacyclin and effective in inhibiting platelet aggregation when orally administered in experimental animals. In the present study we compared the potency of TRK-100 with those of PGI2 and PGE1 to cause an activation of adenylate cyclase activity in rat and human platelet membranes. TRK-100 was half as effective as PGI2, and 10 times more effective than PGE1 in both platelet membranes. TRK-100 also induced an activation of phosphodiesterase activity when directly added to intact platelets probably as a feedback mechanism of intracellular cAMP level like PGI2 did. TRK-100 would mimic PGI2 in the regulation of cAMP metabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗

Solubility of uric acid and supersaturation of monosodium urate: why is uric acid so highly soluble in urine?

The solubility of uric acid and the stability of supersaturation of monosodium urate (NaU) were studied in buffer solutions containing 150 mM sodium in the physiological urinary pH range at 37C. The solubility of uric acid increased with the rise in pH, and the total dissolved urate (undissociated uric acid + urate anion) concentration did not change during seven-day incubation in the pH range below 6.6. In this pH range, the calculated concentration of undissociated uric acid was constant (about six mg./dl.). Consequently, the increasing solubility of uric acid with the rise in pH depended solely on the increase of urate anion. As much as 220 mg./dl. of uric acid could be dissolved for 24 hours at pH 7.0. But following seven-day incubation the total dissolved urate concentration decreased to 16 mg./dl. due to NaU crystallization. The stability of NaU supersaturation depended not only on the concentration of sodium and urate anion but also on time and pH. When monopotassium urate crystals were incubated for seven days, the total dissolved urate concentration decreased according to NaU crystallization; the higher the pH, the more marked the decrease. However, at least some 80 mg./dl. of total dissolved urate was stable up to pH 8.2 within 24 hours. These findings can well explain why NaU crystals are seldom formed in the normal urine. Urinary stasis and/or pathological high urinary pH may cause NaU crystallization.

Buffers↗

Radiation-induced osteosarcoma of the sphenoid bone.

The case of a patient who developed osteosarcoma in the sphenoid bone 15 years after radiation therapy for a craniopharyngioma is reported. Radiation-induced osteosarcoma of the sphenoid bone has not been reported previously. Reported cases of radiation-induced osteosarcomas are reviewed.

Bone Neoplasms↗

[Cardiovascular effects of beraprost sodium (TRK-100), a prostacyclin analogue in the dog].

Effect of prostacyclin analogue, beraprost sodium (Sodium (+/-)-(1R*, 2R*, 3aS*, 8bS*)-2, 3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen+ ++-6- ynyl]-1H-cyclopenta-[b]benzofuran-5-butyrate, TRK-100), on the cardiovascular system of the anesthetized dog was investigated. TRK-100 was injected intra-arterially and intravenously to study the vasodilating effect of the drug by a magnetic flow meter. Intra-arterial injection of TRK-100 augmented blood flow of vertebral, coronary, renal, supramesenteric, hepatic and femoral artery at a dose range of 0.0003 to 3,000 micrograms/bed. The threshold doses of TRK-100 and PGI2 in the mesenteric artery were 0.003 micrograms and 0.0003 micrograms, respectively, and the same values were obtained in the splenic artery. Those were slightly lower than those of other arteries. Intravenous injection of TRK-100 augmented mesenteric and renal arterial flow to 193 +/- 30% and 118 +/- 4%, respectively. In this system augmentation of mesenteric and renal arterial flow was 179 +/- 19% and 135 +/- 1%, respectively, while vertebral, carotid, and femoral arterial flow decreased, respectively, to 71.4 +/- 2.1%, 80.0 +/- 9.4% and 61.4 +/- 5.6% by TRK-100 and 70.6 +/- 5.6%, 79.5 +/- 6.9% and 67.1 +/- 4.7% by PGI2. Inhibitory effects on heart functions such as cardiac output, left ventricular pressure, LV dP/dt, oxygen consumption, and cardiac work were seen. The effect was similar to PGI2. Coronary vascular resistance, total peripheral resistance and systemic blood pressure were also decreased by TRK-100 and PGI2.

Anesthesia↗

Effect of TRK-100, a prostacyclin analogue, on endotoxin-induced enhancement of blood coagulation in rats.

TRK-100 (0.03, 0.1 and 0.3 mg/kg, p.o.), a chemically stable analogue of prostacyclin, dose-dependently prevented blood coagulation and glomerular fibrin deposition which were enhanced by 4 hr infusion of endotoxin (100 mg/kg) in rats. In addition, TRK-100 suppressed the generation of endotoxin-induced tissue thromboplastin like activity in cultured human endothelial cells.

Administration, Oral↗

Hypothalamic hamartoma. Report of two cases.

Two cases of hypothalamic hamartoma are presented. The first patient was a 4-year-old boy with precocious puberty, and the second was a 6-year-old boy with epileptic seizures. In both patients, clinical symptoms and signs appeared at the age of 2 years and progressed thereafter. Computerized tomography and magnetic resonance imaging in both cases disclosed a suprasellar mass lesion in continuity with the hypothalamus. Removal of the lesions affected the endocrinological status and/or seizure control. Pathological examination revealed the lesions to be composed of well-differentiated neuronal and glial cells. Immunohistochemical study demonstrated the presence of beta-endorphin, corticotropin-releasing factor, oxytocin, and neurofilament protein (210 kD) in the neuronal cells of the first patient, but no neuropeptides were detected in the second. Electron microscopic examination on the second patient disclosed the presence of many nonmyelinated and some myelinated neuronal processes containing dense-core and clear vesicles. The morphological characteristics and the role of surgery for this lesion are discussed.

Child↗

[A new clinical trial in intravesical chemotherapy with instillation of peplomycin preparation as an emulsion in hydroxypropylcellulosum--preliminary study of patients with bladder tumor].

A new peplomycin (PEP) preparation was employed as an emulsion form in hydroxypropylcellulosum (HPC), which is familiar to have a liniment effect with a strong affinity to mucosa of the organ, in the management of 6 patients with bladder tumors. This emuled PEP in HPC (HPC-PEP) was instillated and thereafter, maintained for at least 2 hours at the frequency of once a week. All 6 patients had histopathologically confirmed T1 or T2 transitional cell carcinoma on biopsied specimen. The histological grading of the tumors were divided to 2 in G1, 3 in G2, and 1 in G3 of transitional cell carcinoma. The instillated agent was prepared from the mixture of 15 ml of 6% HPC and 90 mg PEP in 15 ml saline prior to use. A response to this treatment was evaluated primarily by cystoscopic findings and urine cytology 7 days after the instillation. In the present study, the beneficial effects of this treatment were briefly segregated into 4 categories as follows: excellent, good, fair and no responses were referred respectively to as complete eradication of visible tumor with negative urine cytology, a complete disappearance of the primary tumor with a persistent positive cytology, regression of the tumor size and no change of the primary tumor with sustained positive cytology. According to this estimation, 6 patients were categorized to 1 in excellent, 2 in good, 2 in fair and 1 in no responses to this new therapeutic preparation. Furthermore, urinary and serum levels of PEP were determined daily for 7 days after the instillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.

Acute Disease↗

General pharmacology of beraprost sodium. 1st communication: effect on the central nervous system.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its effect on the central nervous system (CNS) was studied. 1. When orally administered in mice, beraprost sodium at 0.3 mg/kg caused a flush of skin, a suppression of spontaneous motility, and a fall of body temperature. At 1 mg/kg and more, it showed obvious sedation, prolongation of hexobarbital hypnosis, and analgesic action in acetic acid-induced writhing test. However, even at 3 mg/kg beraprost sodium neither induced ataxia nor had anticonvulsant activity. Hypothermia was also observed in rabbits at 1 mg/kg (p.o. and i.v.). 2. When intravenously administered, beraprost sodium exerted long-lasting action on the CNS, while its pharmacological effects resembled those of PGI2. 3. Oral administration of beraprost sodium did not inhibit aggregation toxicity induced by methamphetamine (20 mg/kg i.p.) in mice. Beraprost sodium at doses higher than 1 mg/kg enhanced aggregation toxicity induced by methamphetamine (5 mg/kg i.p.), while intracerebral ventricular administration of beraprost sodium failed to enhance it. 4. In rat spinal reflex, intravenous administration of beraprost sodium (0.1 mg/kg) slightly enhanced monosynaptic reflex and at a high dose (1 mg/kg) suppressed polysynaptic reflex. 5. In the rabbit EEG, intravenous administration of beraprost sodium at a high dose (1 mg/kg) showed some effects such as the continuous pattern of wakefulness and a fall in power of the EEG.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Effect of beraprost sodium on peripheral circulatory disturbances induced by various stimuli.

Effects of beraprost sodium (sodium(+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydr oxy-1- [(E)-(3S*)-3-hydroxy-4-methyl-octen-6-ynyl]-1H-cyclopenta[b] benzofuran- 5-butyrate, TRK-100), a stable prostacyclin analogue, on the peripheral circulatory disturbances induced by various vasoconstrictive stimuli were studied. Orally administered beraprost sodium (10, 30 micrograms/kg) caused increase in skin blood flow in anesthetized rats and rise in skin temperature in conscious rats. Intravenously administered beraprost sodium (0.01-0.3 microgram/kg) reduced the recovery time of decreased pulse pressure by topical cooling of the leg in anesthetized rats. In conscious rabbits, intravenous infusion of beraprost sodium (10 micrograms/kg/min) inhibited the fluctuation of ear artery diameter, and dilated the ear artery and vein, resulting in a rise in the ear temperature. In anesthetized dogs, intravenously administered beraprost sodium (0.313-5 micrograms/kg) caused decrease in femoral blood flow and muscle blood flow in the hindlimb, however, it caused increase in skin blood flow at the hind leg instep. Furthermore, intra-arterially administered beraprost sodium (0.1-0.3 microgram/kg/min) under stimulation of lumbar sympathetic nerve caused increase in femoral artery blood flow and selective increase in the skin blood flow without affecting muscle blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

Studies on the antiplatelet effect of the stable epoprostenol analogue beraprost sodium and its mechanism of action in rats.

Baraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a.8b- tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6- 1H-cyclopenta[b]benzo-furan-5-butyrate, TRK-100) is a novel stable epoprostenol (prostaglandin I2, PGI2) analogue having antiplatelet and vasodilating actions. Its effect on platelet aggregation in whole blood ex vivo and platelet suspension in vitro, formation of cyclic AMP(cAMP), production of malondialdehyde(MDA), and 45Ca++-influx into platelets were studied in rats. Oral administration of TRK-100 (0.3-1 mg/kg) showed a dose-dependent inhibition of platelet aggregation induced by ADP and collagen in whole blood and also inhibited in vitro thrombin-induced aggregation of platelet suspension in the presence or absence of external Ca++. Oral TRK-100 (0.3-3 mg/kg) dose-dependently increased plasma cAMP levels and this action was confirmed in vitro with platelet rich plasma in the presence or absence of theophylline. 45Ca++-influx into platelets stimulated by thrombin was dose-dependently inhibited by TRK-100 (3-100 nmol/l). TRK-100 (3-100 nmol/l) also suppressed MDA production induced by thrombin in platelet suspension but not that induced by arachidonic acid. From these results, TRK-100 which is orally active was suggested to exert its antiplatelet action through the increase of cAMP in platelets by activation of adenylate cyclase, concomitantly followed by the inhibition of Ca++-influx and thromboxane A2 formation.

Animals↗

[Clinical evaluation of osteocalcin in chronic hemodialysis patients].

Serum level of osteocalcin was measured by radioimmunoassay in 52 patients with chronic renal failure and 92 control subjects. The patients were treated by usual hemodialysis over a 3-month period. The osteocalcin level of the patients was significantly higher than that of the control subjects, but the patients with diabetic nephropathy had a lower osteocalcin level than the patients with non-diabetic nephropathy. There was a significant correlation between serum osteocalcin level and alkaline phosphatase or PTH level. On the other hand, there was no relationship between serum osteocalcin level and various parameters such as bone mineral contents, and bone cortex volume measured by the microdensitometry method. Hemodialysis affected the serum osteocalcin level. The clinical value of osteocalcin as a parameter of bone formation in chronic hemodialysis patients was discussed.

Adult↗

Specific binding of the new stable epoprostenol analogue beraprost sodium to prostacyclin receptors on human and rat platelets.

Binding of beraprost sodium (sodium dl-4-[(1R,2R,3aS,8bS)-1,2,3a,8b-tetrahydro-2-hydroxy-1-[(3S, 4RS)- 3-hydroxy-4-methyl-oct-6-yne-(E)-1-enyl] -5- cyclopenta[b]benzofuranyl]butyrate, TRK-100), a new potent antithrombotic agent, to washed platelets of humans and rats was studied. [11-3H]-TRK-100 binding was rapid, reversible, saturable, and highly specific. Scatchard analysis of concentration-dependent binding to human platelets revealed a single class of specific binding sites with an equilibrium dissociation constant (Kd) of 133 nmol/l and a maximal concentration of binding sites (Bmax) of 46 fmol/10(8) platelets (275 sites/cell). Similar binding was observed on rat platelets. The Kd and Bmax were 66 nmol/l and 124 fmol/10(8) platelets (750 sites/cell), respectively. Competitive studies indicated that TRK-100 was 1.5 times less active than prostacyclin (epoprostenol, PGI2), but was 3 times more potent than PGE1 in displacing [3H]-TRK-100 from the binding sites on rat platelets. PGE2, PGD2, PGF2 alpha, and pinane thromboxane A2, a stable thromboxane A2 analogoue, had no affinity for the binding sites. The relative affinity of the four enantiomers of TRK-100--APS-314d, 315d, 3141 and 3151--for the binding sites was 100: 14: less than 1: less than 1, respectively. These results suggest that TRK-100 is a useful tool for studying biological roles of PGI2 as well as for use as an antithrombotic agent since TRK-100 mimics its actions via specific interaction with PGI2 receptors.

Animals↗

Effect of beraprost sodium (TRK-100) on acetic acid-induced skin ulcer.

Effect of beraprost sodium (TRK-100), a stable PGI2 analog, on experimentally induced skin ulcer was studied in rats. An experimental skin ulcer was developed by intradermal injection of acetic acid. Injection of glacial acetic acid to the skin in the left hind leg instep of rats resulted in the necrosis of the skin, and a skin ulcer developed in 3 days. The ulcer area reached its peak on the 5th day, and recovered to its control level within 4 weeks. The effects of TRK-100 and indomethacin on the ulcer were tested. TRK-100 showed suppressive effects on the development of the ulcer. A dose of 30 micrograms/kg (p.o.) accelerated healing of the ulcer when scored macroscopically on the 9th or 15th day. At a dose of 100 micrograms/kg (p.o.), it reduced the development of the ulcer and accelerated healing with statistical significance from the 5th day and thereafter. Indomethacin also reduced the development of the ulcer and accelerated healing with statistical significance from the 7th day and thereafter. These results suggest TRK-100 may be effective on the inhibition of the development and accelerated the healing of the skin ulcer formed in various pathological states.

Acetates↗

[The characteristic changes of immune function with aging].

It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗