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Biomedical subjects

R Ueno

Publications and source records attributed to R Ueno.

At least 37 records · Page 2Linked to original sources
PubMed1992

[Ocular effects of topical instillation of UF-021 ophthalmic solution in healthy volunteers].

Phase I studies, as divided into two stages, were conducted in healthy volunteers with the ophthalmic solution of UF-021, a novel prostaglandin metabolite-related compound, that was reported to exhibit potent intraocular pressure (IOP)-reducing activity in various species of animals. In the first stage, the vehicle as well as UF-021 ophthalmic solutions at concentration of 0.03%, 0.06% and 0.09% were applied topically to the eyes of 8 healthy volunteers to determine their respective effects through observations on the IOP, and local ocular and systemic side effects. In the second stage, 2 dosages of UF-021 ophthalmic solution, 0.06% and 0.12%, were applied topically to 11 healthy volunteers to investigate the IOP-reducing activities and local ocular side effects. The results revealed that ophthalmic solutions of UF-021 at concentrations ranging from 0.03% to 0.12% reduced IOP in a dose-dependent manner with neither systemic nor local ocular controversial side effects at those dosage levels. In summary, UF-021 ophthalmic solutions, when administered to healthy volunteers through single instillation, reduced IOP significantly without causing any side effects.

Administration, Topical↗
PubMed1992

[Ocular penetration of UF-021, a new prostaglandin related compound, in the rabbit eye].

The ocular penetration and pigment affinity of topically applied UF-021, a newly developed prostaglandin-related compound, were investigated in rabbit eyes using 3H-labeled UF-021. Ten minutes to 24 hours after instillation of 0.12% of 3H-UF-021 solution into New Zealand white or pigmented rabbit eyes, the rabbits were sacrificed and the eyes were immediately enucleated. The extraocular muscles, conjunctiva, aqueous humor, cornea, iris, anterior and posterior sclera, ciliary body, lens, vitreous, retino-choroid complex, optic nerve were separated and blood samples were taken. The concentration of 3H-UF-021 in each sample was determined with a liquid scintillation counter. The peak concentration of UF-021 was obtained at 40 minutes and 1 hour after instillation in the iris-ciliary body and aqueous humor of albino rabbit. According to the pharmacokinetic analysis of the data, UF-021 showed good ocular penetration into the rabbit eye, and the permeability of the epithelial barrier for UF-021 was calculated to be 2.9 x 10(-3) cm/hr. The apparent elimination rate constant and the apparent absorption rate constant were also calculated to be 0.21 hr-1 and 1.28hr-1, respectively. The time course for 3H-UF-021 concentration in the eye of pigmented rabbit was almost the same as that in the eye of non-pigmented rabbit, indicating that UF-021 did not bind to pigmented tissues.

Animals↗
PubMed1992

[The intraocular pressure lowering effects of UF-021, a novel prostaglandin related compound, in animals].

The ophthalmic solution of UF-021, a novel prostaglandin (PG) related compound, was investigated for its intraocular pressure (IOP) reducing activity and local ocular side effects in different species of animals. UF-021 ophthalmic solution (0.03 to 0.24%), when topically applied to the eyes of rabbits, caused dose-dependent IOP reduction (2.8 to 5.2 mmHg), without transient IOP rise. Both in cats and monkeys, UF-021 ophthalmic solution (0.12%) elicited rapid, significant IOP reduction (ca. 9 mmHg and 2 mmHg, respectively), without any controversial, local ocular side effects being revealed. On the other hand, PGE2, PGF2 alpha-isopropyl ester all brought about marked increases in IOP prior to development of their IOP reducing activities. In addition, these primary PGs showed intense local ocular irritation, which presented a striking contrast with UF-021. Enhancement of IOP reducing activity, coupled with freedom from any significant ocular side effects, as described above, suggests that UF-021 ophthalmic solution could be promising as a new anti-glaucoma agent.

Animals↗
PubMed1991

Purification and properties of neutral beta-N-acetylglucosaminidase from carp blood.

A neutral beta-N-acetylglucosaminidase has been purified to homogeneity from carp blood by a seven-step procedure. It was localized in the cytosol of red blood cells. The purified enzyme was specific to beta-N-acetylglucosaminide and inactive to beta-N-acetylgalactosaminide. It was competitively inhibited by free N-acetylglucosamine, but not by free N-acetylgalactosamine. The optimum pH of the enzyme was 6.5, with a stable pH range of 7.0 to 11.0. The enzyme showed greater heat-lability and anodal electrophoretic mobility than acidic beta-N-acetylglucosaminidases. The Mr value, estimated by sucrose density gradient centrifugation, was 122,000, and the enzyme dissociated into two nonidentical subunits with Mr values of 66,000 and 53,000, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With respect to the major characteristics, the neutral enzyme in carp blood was supposed to be a counterpart of hexosaminidase C in human and other mammalian tissues.

Acetylglucosaminidase↗
PubMed1991

Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes.

The mechanism underlying the intraocular pressure (IOP) lowering effect of a prostaglandin-related compound, isopropyl 20-ethyl-9 alpha,11 alpha-dihydroxy-15-keto-cis-delta 5-prostanoate (UF-021), and its possible adverse effects in long-term use were studied in normal human eyes. A single instillation of 0.12% UF-021 significantly lowered IOP without affecting aqueous flow rate, tonographic C value or episcleral venous pressure. Protein concentration in the anterior chamber and corneal endothelial permeability to fluorescein remained unaffected. It was suggested that UF-021 lowers IOP mainly by increasing uveoscleral outflow. Twice daily application of 0.12% UF-021 for 4 weeks caused no significant changes in aqueous protein concentration, aqueous flow rate or corneal endothelial permeability. Neither single nor long-term use of topical UF-021 induced irritative responses in the outer segment of the eye. The present study suggests that UF-021 has potential as a safe and effective ocular hypotensive drug with a mechanism of action different from other drugs currently available for the treatment of glaucoma.

Administration, Topical↗
PubMed1989

Awaking effect of prostaglandin E2 in freely moving rats.

The awaking effect of prostaglandin (PG) E2 was further examined in a long-term bioassay system. PGE2 in saline solution was infused between 11.00 and 17.00 h at 0.1, 1, 10, and 100 pmol/min (infusion volume 10 microliters/h) into the third cerebral ventricle of freely moving rats. These rats were otherwise infused with saline continuously and exhibited a circadian cycle, spending 70% of the daytime and 37% of the night in sleep. In the rats that received PGE2 infusion at 1, 10, and 100 pmol/min, slow wave sleep (SWS) decreased to 84%, 69% and 71% and paradoxical sleep (PS) to 85%, 37% and 40% of the paired controls. Thus, the effect of PGE2 was not specific to either SWS or PS. No effects were observed in the rats that received PGE2 at 0.1 pmol/min. After PGE2 infusion at 10 and 100 pmol/min, marked rebounds of both SWS and PS occurred during the night. SWS reduction by PGE2 was due to the shortened duration of SWS episodes, while SWS increase in the rebound phase was due to the increased number of episodes. PS reduction was due to both the shortened duration and decreased number of PS episodes and PS rebound was due to both the prolonged duration and increased number of episodes. The circadian sleep-wake cycle returned to the baseline on the first or second recovery day after PGE2 infusion. Sleep reduction by PGE2 was accompanied by elevation of the brain temperature and rebound increase of sleep occurred with the fall of the brain temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

STUDY OBJECTIVE: To evaluate the tolerance and safety of oral dextran sulfate (UA001), a potent in-vitro inhibitor of human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. DESIGN: Unblinded, dose-escalation 8-week trial. SETTING: An AIDS outpatient clinic of a university-affiliated municipal hospital. PATIENTS: Thirty-four patients with stage III or IV HIV infection were enrolled. Five patients in six different dosage cohorts completed the study. The population was predominantly homosexual men with persistent generalized lymphadenopathy (stage III). INTERVENTIONS: Oral dextran sulfate was given three times daily in total daily doses of 900 to 5400 mg for 8 weeks. Patients were monitored for tolerance and toxicity. Immunologic and virologic values were also followed. MEASUREMENTS AND MAIN RESULTS: Oral dextran sulfate was given without significant side effects. The commonest minor subjective complications were mental hyperexcitability and gastrointestinal complaints. The most frequent laboratory abnormalities were leukopenia and hepatic transaminase elevations. Eleven patients required dose reductions, and therapy was stopped in 4 because of toxicities. The CD4 lymphocyte numbers did not change appreciably. No decline in beta-2 microglobulin levels occurred. The HIV antigen levels were unchanged from baseline. No assay for dextran sulfate plasma levels has yet proven successful. CONCLUSIONS: Oral dextran sulfate appears to be well tolerated. No evidence of systemic absorption of the parent compound is available. However, in view of the promising in vitro effects and acceptable toxicity, oral dextran sulfate as a potential antiretroviral agent continues to be studied.

AIDS-Related Complex↗
PubMed1989

Late-phase accumulation of inositol phosphates stimulated by prostaglandins D2 and F2 alpha in neuroblastoma x glioma hybrid NG108-15 cells.

The accumulation of inositol phosphates (IPs) in response to prostaglandins (PGs) was studied in NG108-15 cells preincubated with myo-[3H]inositol. As a positive control, bradykinin caused accumulation of IPs transiently at an early phase (within 1 min) and continuously during a late phase (15-60 min) of incubation in the cells. PGD2 and PGF2 alpha did not significantly cause the accumulation of IPs at an early phase but significantly stimulated inositol bisphosphate (IP2) and inositol monophosphate (IP) formation at late phase of incubation. The maximum stimulation was obtained at greater than 10(-7) M concentrations of these PGs, the levels being three-and twofold for IP2 and IP1, respectively. 9 alpha, 11 beta-PGF2 has a slight effect but PGE2 and the metabolites of PGD2 and PGF2 alpha have no effect up to 10(-6)M. The effects of PGD2 and PGF2 alpha were not additive, but the effect of each PG was additive to that of bradykinin at a late phase of incubation. Inositol 1-monophosphate was mainly identified in the stimulation by 10(-5) M PGD2 and 10(-5) M PGF2 alpha, whereas both inositol 1-monophosphate and inositol 4-monophosphate were produced in the stimulation by 10(5) M bradykinin. Depletion of extracellular Ca2+ diminished the stimulatory effect of PGD2 and PGF2 alpha and late-phase effect of bradykinin, but simple Ca2+ influx into the cells by high K+, ionomycin, or A23187 failed to cause such late-phase effects. These results suggest that PGD2 and PGF2 alpha specifically stimulate hydrolysis of inositol phospholipids.

Animals↗
PubMed1989

Salivary prostaglandin concentrations: possible state indicators for major depression.

Salivary prostaglandin concentrations were determined in 42 patients with major depressive disorder, 16 patients with minor depressive disorder, and 39 healthy control subjects. The diagnoses were made according to the Research Diagnostic Criteria. The patients with major depressive disorder had higher salivary prostaglandin concentrations than the control subjects, but the patients with minor depressive disorder did not. Furthermore, the salivary prostaglandin concentrations of the patients with major depressive disorder showed a high correlation with the severity of the depression. These results suggest that high salivary prostaglandin concentrations may be state indicators for major depression.

Adult↗
PubMed1988

Muramyl dipeptide-elicited production of PGD2 from astrocytes in culture.

We used primary cultures of rat brain astroglial cells in order to investigate the interrelationship between PGD2 and other sleep-promoting substances such as muramyl dipeptide (MDP), lipopolysaccharide (LPS), delta-sleep-inducing peptide (DSIP), uridine, and interleukin 1 (IL-1). A large amount of PGD2 was released into the culture medium by stimulation with MDP, LPS, and IL-1 but DSIP and uridine failed to stimulate such release. These results suggest that PGD2 may be part of the series of biochemical steps involved in induction of sleep by MDP, LPS, and IL-1.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Suppression of sleep by prostaglandin synthesis inhibitors in unrestrained rats.

Sleep-suppressive activity of prostaglandin synthesis inhibitors, diclofenac sodium (DF) and indomethacin (IM), was examined in unrestrained male rats. An intraperitoneal injection of 5 mg/kg IM, or an oral administration of 5 mg/kg DF and 10 mg/kg IM at an early phase of the light period transiently decreased slow wave sleep (SWS) and paradoxical sleep (PS) to 30-62% and 0-38%, respectively, of the control level in the first hour. An intravenous infusion of 0.4 mg DF or 0.4 mg IM or an intracerebroventricular infusion of 0.04 mg DF continuously during a 10-h diurnal period resulted in a significant decrease in SWS and PS by 9-17% and 17-21%, respectively, from the baseline value in the 12-h light period. The DF infusion was accompanied by a rebound rise in the nocturnal SWS and PS and the subsequent diurnal PS. The results indicate that the depletion of prostaglandin(s) in the brain is responsible for the DF- and IM-induced suppression of sleep.

Administration, Oral↗
PubMed1988

Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells.

The first step in the infection of human T lymphocytes by human immunodeficiency virus type 1 (HIV-1) is attachment to the target cell receptor, the CD4 antigen. This step may be vulnerable to attack by antibodies, chemicals, or small peptides. Dextran sulfate (molecular weight approximately 8000), which has been given to patients as an anticoagulant or antilipemic agent for more than two decades, was found to block the binding of virions to various target T lymphocytes, inhibit syncytia formation, and exert a potent inhibitory effect against HIV-1 in vitro at concentrations that may be clinically attainable in human beings. This drug also suppressed the replication of HIV-2 in vitro. These observations could have theoretical and clinical implications in the strategy to develop drugs against HIV types 1 and 2.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Awaking effect of PGE2 microinjected into the preoptic area of rats.

We examined the effect of prostaglandin (PG)E2 on the sleep-wake activity and on body temperature by microinjecting PGE2 into the preoptic area of rats that had been chronically implanted with guide cannulae and electrodes for the recordings of electroencephalogram and electromyogram. PGE2 at doses of 2.5 X 10(-13), 2.5 X 10(-11), and 2.5 X 10(-9) mol reduced the time of slow wave sleep (SWS) to 75%, 61%, and 59% and that of paradoxical sleep (PS) to 73%, 50%, and 25% of the controls, respectively. The SWS and PS reductions were mainly due to the shortening of the SWS episode and the less frequent occurrence of PS episodes. The sleep reduction was accompanied by increased behavioral movement. The maximum increases of rectal temperature at doses of 2.5 X 10(-11) and 2.5 X 10(-9) mol of PGE2 were 1.3 degrees C and 2.7 degrees C, respectively. At a dose of 2.5 X 10(-13) mol of PGE2, the time of SWS and that of total sleep (sum of SWS and PS) decreased significantly, but the change in body temperature was negligible. This may imply that the effect of PGE2 on the sleep-wake activity is not caused by the hyperthermia produced by PGE2. Injections of PGE2 at a dose of 2.5 X 10(-15) mol and saline control induced alteration in neither sleep-wake activity nor body temperature. PGD2 at a dose of 2.5 X 10(-9) mol slightly elevated the rectal temperature (0.5 degree C), but did not produce any change in the sleep-wake activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Increased level of salivary prostaglandins in patients with major depression.

We quantified the amounts of salivary prostaglandin (PG) D2, PGE2, and PGF2 alpha by radioimmunoassay in 32 patients with major depressive disorder, 16 patients with minor depressive disorder, 24 patients with neurotic disorders (panic, generalized anxiety, phobic, somatization, and obsessive compulsive), and 28 healthy controls. In the saliva of patients with major depressive disorder, the concentrations of immunoreactive PGs (PGD2, 385 +/- 71 pg/ml; PGE2, 498 +/- 105 pg/ml; PGF2 alpha, 444 +/- 100 pg/ml) were significantly higher than those of the healthy controls (PGD2, 129 +/- 18 pg/ml; PGE2, 207 +/- 25 pg/ml; PGF2 alpha, 164 +/- 17 pg/ml). On the other hand, the salivary concentrations of immunoreactive PGs from patients with minor depressive disorder or neurotic disorders were comparable to those of the controls. These results suggest that the level of salivary PGs may be an indicator of major depressive disorder.

Adult↗
PubMed1988

Prostaglandin D2, a cerebral sleep-inducing substance in monkeys.

The sleep-inducing effect of prostaglandin D2 (PGD2) was studied in five conscious male rhesus monkeys (Macaca mulatta) maintained in a 12-hr light/dark cycle. PGD2 was infused into the lateral or the third ventricle of the cerebrum slowly and continuously for 6 hr in the light period. Infusion of PGD2 into the lateral ventricle at 15-2250 pmol/min induced natural sleep as identified by electroencephalogram, electromyogram, electrooculogram, body temperature, heart rate, and animal behavior. Although sensitivity to PGD2 was slightly different among individual animals, the amount of total sleep time increased maximally up to 3- to 4-fold over the control level. PGD2 infused into the third ventricle induced effects similar to those observed for the lateral ventricular route, but infusion into the third ventricle was about 1000 times more effective than infusion into the lateral ventricle. In three monkeys, PGD2 increased the amount of sleep in a dose-dependent manner. Bell-shaped dose-response curves were observed for the other two monkeys. Infusion of prostaglandin E2 or F2 alpha into the lateral ventricle caused sedation but slightly reduced the amount of slow-wave sleep and produced increases in heart rate and body temperature. These findings suggest that endogenous PGD2 may be involved in the regulation of sleep by acting on the brain structures surrounding the third ventricle in the rhesus monkey.

Animals↗
PubMed1988

Prostaglandin induces Ca2+ influx and cyclic GMP formation in mouse neuroblastoma X rat glioma hybrid NG108-15 cells in culture.

Various prostaglandins (PGs) (10 nM-30 microM) were added to NG108-15 cells in culture, and changes in the levels of intracellular cyclic GMP and Ca2+ were investigated. Exposure of the cells to PGF2 alpha, PGD2, and PGE2 (10 microM) transiently increased the cyclic GMP content 7.5-, 3.9-, and 3.1-fold, respectively. Furthermore, the increased levels of cyclic GMP correlated well with the rise in cytosolic free Ca2+ concentrations induced by the PGs. Other PGs (10 microM), including metabolites and synthetic analogs, which had no effect on intracellular Ca2+, failed to increase the cyclic GMP content in the cells. When extracellular Ca2+ was depleted from the culture medium, the PG-induced increase in cyclic GMP level was almost completely abolished. In addition, treatment of the cells with quin 2 tetraacetoxymethyl ester dose-dependently inhibited the PG-induced cyclic GMP formation. The increase in cyclic GMP content caused by treatment of the cells with a high K+ level (50 mM) was completely blocked by voltage-dependent Ca2+ entry blockers, such as verapamil (10 microM), nifedipine (1 microM), and diltiazem (100 microM); however, the PG (10 microM)-induced increase in cyclic GMP content was not affected by such Ca2+ entry blockers. These findings indicate that PG-induced cyclic GMP formation may require the rise in intracellular Ca2+ level and that the voltage-dependent Ca2+ channels may not be involved in the PG-induced rise in Ca2+ content.

Aminoquinolines↗