The effect of multi-porous beads prepared from 80% deacetylated chitin on the activation of mouse peritoneal macrophages was examined. Deacetylated chitin bead (DAC-bead) preparations were shown to activate macrophages for tumoricidal activity depending on the increasing concentration of acetic acid used for the pretreatment of beads. The large DAC-bead was more susceptible to treatment with acetic acid than small DAC-bead, and showed more potent capacity for the activation of macrophages under the same pretreatment conditions with acetic acid. Deacetylated bead preparations, on the other hand, showed less activities. In addition, DAC-bead pretreated with acetic acid stimulated macrophages to produce interleukin 1. The possibilities of multi-porous beads as cancer chemotherapeutic-carrier were examined by the method of column chromatography and of in vitro antitumor experiment. Forty-four percent of adriamycin adsorbed on the surface of and in bead was released within the first 60 min. of elution, and then adriamycin was released more slowly in proportion to the elution time. Antitumor activity of adriamycin-adsorbed bead was less effective than that of free adriamycin if they were compared on the basis of total content of adriamycin.

Animals↗

PubMedDate not supplied

Characterization of the invasive and metastatic phenotype in human renal cell carcinoma.

The purpose of these studies was to identify some characteristics of metastatic cells and deficiencies of non-metastatic cells in the heterogeneous SN12 human renal cell carcinoma. The SN12 parental line and several isolated variants with different metastatic potential were studied both in vivo and in vitro. We compared the ability of metastatic and non-metastatic cells to adhere to components of the extracellular matrix or to endothelial cells, to migrate and invade, to form multicell aggregates, to survive in the circulation, and to produce experimental and spontaneous lung metastases. In general, highly metastatic SN12 cells capable of producing spontaneous lung metastases demonstrated invasion through reconstituted basement membrane-coated filters; the cells also released diffusible collagenolytic activity into the culture medium that could enhance invasion by otherwise non-invasive and non-metastatic SN12 cells. In addition to enhanced invasion, metastatic cells produced more homotypic aggregation then non-metastatic cells and survived to produce experimental metastasis. Collectively, these data confirm that metastatic cells must complete all steps of the process; in this process, failure to produce metastasis is probably due to one or more deficiencies.

Adult↗

PubMedDate not supplied

Activation of rainbow trout (Oncorhynchus mykiss) phagocytes by muramyl dipeptide.

Immunoenhancing activity of synthetic muramyl dipeptide (MDP) was investigated in relation to the activation of rainbow trout (Oncorhynchus mykiss) phagocytes and to nonspecific protection against challenge with the fish pathogen Aeromonas salmonicida. Head kidney phagocytes collected from MDP-injected fish showed significant chemotactic activity against zymosan-activated normal rainbow trout serum, and phagocytic activities against both A. salmonicida and plastic beads. The MDP-activated phagocytes also showed enhanced superoxide generation. When normal phagocytes were exposed to supernatants of phagocyte or peripheral blood lymphocyte cultures of MDP-injected fish, the cells showed significant chemotactic activity, indicating that the MDP-activated cells produced phagocyte-activating factor. Injection of MDP to fish provided protection against challenge with virulent A. salmonicida.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

Effect of the synthetic lipid A-related compound, DT-5461, on resistance to Sendai virus infection in mice.

DT-5461 enhanced host resistance to Sendai virus infection in mice. Intranasal (i.n.) administration of 200 micrograms of DT-5461 per mouse 3 days before infection was the most effective administration route, dose and timing. DT-5461 enhanced the cytotoxicity of murine natural killer (NK) cells. In addition, DT-5461 activated murine peritoneal macrophages, resulted in augmented of cytotoxicity and the induction of tumor necrosis factor-alpha (TNF-alpha). Therefore, these immunomodulating activities presented by DT-5461 caused protection against Sendai virus infection.

Adjuvants, Immunologic↗

PubMedDate not supplied

Effect of topically applied iganidipine dihydrochloride, a novel calcium antagonist, on optic nerve head circulation in rabbits.

PURPOSE: To study the effect of topically applied iganidipine dihydrochloride (iganidipine), a novel water-soluble calcium channel blocker, on blood flow in the optic nerve head (ONH), intraocular pressure, and systemic blood pressure in rabbits. METHODS: After 0.1% iganidipine (20 microL) was instilled into normal eyes, the change in ONH blood flow was measured using a hydrogen gas clearance flowmeter. Iganidipine (0.0001% to 0.1%) was instilled into eyes with impaired ocular circulation before or after the intravitreal injection of endothelin-1, and the change in ONH blood flow was measured. Changes in intraocular pressure and blood pressure after instillation of 0.1% iganidipine were measured. In all experiments, physiological saline was instilled into the contralateral eye as a control. RESULTS: Iganidipine significantly increased the ONH blood flow in normal eyes with the maximum increment of 31.7% at 45 minutes after instillation. Preinstillation of 0.01% and 0.1% iganidipine significantly inhibited the decrease in ONH blood flow in the eyes with impaired circulation. Moreover, ONH blood flow recovered with postinstillation of 0.1% iganidipine. These effects were persistent. Instillation of 0.1% iganidipine did not change either the intraocular pressure or the blood pressure. CONCLUSION: The instillation of iganidipine persistently increased and maintained the ONH blood flow in rabbit eyes with normal and impaired ocular circulation.

Administration, Topical↗

PubMedDate not supplied

Clinical evaluation of a new formula of timolol maleate (WP-934 ophthalmic solution). WP-934 Study Group.

We investigated the ocular hypotensive effect and possible adverse reactions of a new timolol maleate formula, WP-934 ophthalmic solution, which is timolol maleate solution dissolved in a reversible thermo-setting gel. Once-daily instillation of 0.25 or 0.5% WP-934 ophthalmic solution was administered in a prospective, randomized manner at 29 institutions for 8 weeks to patients with primary open-angle glaucoma or ocular hypertension, and for another 16 weeks in a limited number of these patients. Patients were closely monitored throughout the study by ophthalmic and systemic examinations, and by continuous evaluation of symptoms. The new timolol formula demonstrated a significant ocular hypotensive effect throughout the study period. Adverse effects were minor. WP-934 ophthalmic solution, timolol maleate dissolved in a reversible thermo-setting gel, has a significant ocular hypotensive effect in eyes with primary open-angle glaucoma and ocular hypertension.

Administration, Topical↗

PubMedDate not supplied

Effect of continuous intravenous infusion of carteolol chloride on tissue blood flow in rabbit optic nerve head.

PURPOSE: To investigate the effect of an intravenous infusion of carteolol on tissue blood flow in the optic nerve head (ONH) of rabbits. METHODS: Rabbits received either a 3-week topical instillation, or a single intravenous injection (10, 20, 30 microg/kg) or a continuous intravenous injection (2.5, 5, 20, 40, 80 microg/kg per hour) of carteolol. The plasma carteolol level was determined by the gas chromatography negative-ion chemical ionization mass spectrometric method. The ONH blood flow was determined by the hydrogen clearance method. RESULTS: The plasma level of carteolol after a 3-week instillation was 5.55 ng/mL, and a continuous intravenous injection (5 microg/kg per hour) led to approximately the same plasma level. The continuous intravenous infusion of 5 microg/kg per hour of carteolol significantly increased the ONH blood flow compared to the controls from 30 minutes to 2 hours after the beginning of the infusion (n = 10). The mean blood pressure and intraocular pressure (n = 6) were not significantly changed during the continuous intravenous infusion of carteolol. CONCLUSIONS: These results suggest that the plasma carteolol level in rabbits after long-term instillation can increase the ONH blood flow. We conclude that the increase resulted from a reduction in the vascular resistance in the ONH.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Efficacy and safety of latanoprost eye drops for glaucoma treatment: a 1-year study in Japan.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect and safety of latanoprost, a prostaglandin analogue, in patients with primary open-angle glaucoma or ocular hypertension. METHOD: One hundred and twenty-four Japanese patients with primary open-angle glaucoma or ocular hypertension were enrolled in this open-labeled study and were treated with 0.005% latanoprost once daily for 1 year. RESULTS: At all follow-up visits there was a significant (P < .001) reduction in IOP compared with the baseline value. After 1 year, the IOP was reduced by 5.4 +/- 2.9 (mean +/- SD) mm Hg from a baseline value of 23.5 +/- 2.2 mm Hg. No evidence of an upward drift in the IOP was observed during the treatment period. The most frequently reported adverse ocular events were mild conjunctival hyperemia and iris pigmentation. Very few adverse systemic events were observed. CONCLUSIONS: Latanoprost eye drops showed a marked and stable IOP-lowering effect during the 1-year treatment period. Furthermore, latanoprost was well-tolerated and should be a valuable contribution to the management of glaucoma.

Adult↗

PubMedDate not supplied

Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity.

We here demonstrated the prophylactic effect of an extract (KM-110) from Viscum album coloratum, a Korean mistletoe, on tumor metastasis produced by highly metastatic tumor cells, colon 26-M3.1 carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental models in mice. Intravenous (i.v.) administration of KM-110 (100 microg/mouse) 2 days before tumor inoculation significantly inhibited lung metastasis of B16-BL6 and colon 26-M3.1 cells, and liver and spleen metastasis of L5178Y-ML25 cells. The prophylactic effect of KM-110 on tumor metastasis was evident with various administration routes, i.e. subcutaneous, oral, intranasal as well as i.v., and was dependent upon the dose of KM-110 administered. Furthermore, mice given KM-110 (100 microg) 2 days before tumor inoculation showed significantly prolonged survival rates compared with the untreated mice. In a time course analysis of NK activity, i.v. administration of KM-110 (100 microg) significantly augmented NK cytotoxicity to Yac-a tumor cells from 1 to 3 days after KM-110 treatment. Furthermore, depletion NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of KM-110 on lung metastasis of colon 26-M3.1 cells. These results suggest that KM-110 possesses immunopotentiating activity which enhances the host defense system against tumors, and that its prophylactic effect on tumor metastasis is mediated by NK cell activation.

Animals↗

PubMedDate not supplied

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine.

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1 vaccine) to induce immune response against Hantavirus causing hemorrhagic fever with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100 micrograms mouse-1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutralizing antibody titers against HFRS virus than mice immunized with B-1 vaccine alone during 3-9 weeks after the primary immunization. The evaluation of antibody-producing cells by enzyme-linked immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced the number of HFRS virus-specific IgG1 and IgM antibody-producing cells. Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76-118 strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a significantly higher proliferating activity than those treated with B-1 vaccine alone. In addition, when mice were immunized once with B-1 vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B-1/B30-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS virus.

Acetylmuramyl-Alanyl-Isoglutamine↗