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At least 37 records · Page 2Linked to original sources
PubMed1986

The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs.

The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquinolinesulfonamide) and HA 1077(1-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 X 10(-6) M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10(-5) M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10(-5) M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a "two-hemorrhage" canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% +/- 2% (mean +/- standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA 1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA 1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Adjuvant properties of aluminum and calcium compounds.

It is likely that aluminum compounds will continue to be used with human vaccines for many years as a result of their excellent track record of safety and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminum adjuvants formulated under optimal conditions are the adjuvants of choice. It is important to select carefully the type of aluminum adjuvant and optimize the conditions of adsorption for every antigen since the degree of adsorption of antigens onto aluminum adjuvants markedly affects immunogenicity. The mechanism of adjuvanticity of aluminum compounds includes formation of a depot at the site of injection from which antigen is released slowly; stimulation of immune-competent cells of the body through activation of complement, induction of eosinophilia, and activation of macrophages; and efficient uptake of aluminum-adsorbed antigen particles by antigen-presenting cells because of their particulate nature and optimal size (< 10 microns). Limitations of aluminum adjuvants include local reactions, production of IgE antibodies, ineffectiveness for some antigens, and inability to elicit cell-mediated immune responses especially cytotoxic T-cell responses. Calcium phosphate, which has adjuvant properties similar to aluminum adjuvants, has the potential advantages of being a natural component of the body and of not increasing IgE production. There is a need for alternative adjuvants, particularly for diseases in which cell-mediated immune responses are important for prevention or cure.

Adjuvants, Immunologic↗
PubMed1989

[Differential staining of calcium compounds in histologic sections].

An experimental protocol is proposed for the differentiation of calcium-hydrogen-phosphate, tri-calcium-phosphate, calcium-oxalate, calcium-urate and fatty acidic calcium. For tissue fixation calcium acetate-formaldehyde is recommended in which fatty acids and earth-metal urates form insoluble calcium-salts which can be demonstrated in paraffin sections.

Animals↗
PubMed2002

Bone formation following implantation of fibrous calcium compounds (beta-Ca(PO3)2, CaCO3(aragonite)) into bone marrow.

Bone formation around three types of fibrous calcium-containing crystals has been examined histologically using rats. The implanted materials are (i) calcium metaphosphate (beta-Ca(PO(3))(2)) fibers having aspect ratios of 15-80 with 2-20 microm in diameter, (ii) beta-Ca(PO(3))(2)) fibers surface-modified using dilute NaOH and (iii) calcium carbonate (CaCO(3); aragonite phase) whiskers having aspect ratios of 15-40 with 0.5-3 microm in diameter. Beta-Ca(PO(3))(2) fibers show a mechanically high strength with a low modulus of elasticity, and the surface-modified fibers have a thin layer consisting of a calcium orthophosphate phase. CaCO(3) whiskers were used for comparison reasons. The materials were implanted for 4, 8, and 12 weeks into bone defects created in the bone marrow of rat tibiae. Cancellous bone formation was observed around beta-Ca(PO3)2 fibers, the surface-modified fibers and CaCO(3) whiskers after implantation for 12, 4 and 4 weeks, respectively. CaCO(3) whiskers were scarcely observed after 12 weeks for resorbing. The calcium phosphate fibrous materials show combined advantages of mechanically high strength for toughening a matrix phase and biological activities; thus, these materials may prove to be useful for novel applications in the biomedical field.

Journal Article↗
PubMed1983

Alizarin red S staining as a screening test to detect calcium compounds in synovial fluid.

A simple, rapid screening method using alizarin red S stain and ordinary light microscopy to detect microcrystalline or noncrystalline calcium phosphate salts was used on wet drop preparations of synovial fluids. This proved to be helpful in detecting apatite crystal clumps and small calcium pyrophosphate dihydrate (CPPD) crystals missed by polarized light. The staining was positive in 100% of synovial fluids from patients later proven to have apatite and/or CPPD deposition diseases. Apatite and CPPD crystals were commonly found together in the same fluids. In addition, some synovial fluids from patients with osteoarthritis, renal failure dialysis, rheumatoid arthritis, and gout also exhibited positive staining. The correlation of positive alizarin red S staining with radiologic evidence of osteoarthritis suggests that apatite crystals might be related to articular cartilage degeneration in different rheumatic diseases.

Anthraquinones↗
PubMed1988

Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate.

It has been shown that calcium acetylhomotaurinate (Ca AOTA; Meram Patent, France) decreased voluntary ethanol intake in rats (1); this was antagonized by bicuculline. Homotaurine did not have this effect. We thought this was due to a different blood-brain barrier crossing ability for the two drugs. The present study was, therefore, planned to confirm blood-barrier crossing by Ca AOTA and to study the drug's physicochemical and pharmacokinetic characteristics. Both in vitro and in vivo (i.p.) administration of Ca AOTA increased the accumulation of [3H] GABA in rat striatal synaptosomal preparations. The chemical study confirmed Ca AOTA's great stability in biological and hydrophilic media, excluding a "homotaurine-dispensing" effect. The molecule was totally dissociated in such media, but the absence of any detectable acid form at any pH indicates that ion pairs are formed to cross barriers, and/or that a carrier system is used. The pharmacokinetic study showed short half-lives (5 and 30 min for the distribution and elimination phases) and small distribution volumes. However, the elimination phase distribution volume was dose-dependent, a further argument for a carrier transport system. From the present study it appears that Ca AOTA is an extremely stable drug, totally dissociated in hydrophilic media, which acts centrally as a GABA agonist after crossing the blood-brain barrier. It is not a precursor of homotaurine and presumably crosses barriers with the help of a transporter.

Acamprosate↗
PubMed1994

Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models: methods and results from the NCI Chemoprevention Drug Development Program.

In the NCI, Chemoprevention Branch drug development program, potential chemopreventive agents are evaluated for efficacy against chemical carcinogen-induced tumors in animal models. This paper summarizes the results of 144 agents in 352 tests using various animal efficacy models. Of these results, 146 were positive, representing 85 different agents. The target organs selected for the animals model are representative of high-incidence human cancers. The assays include inhibition of tumors induced by MNU in hamster trachea, DEN in hamster lung, AOM in rat colon (including inhibition of AOM-induced aberrant crypts), MAM in mouse colon, DMBA and MNU in rat mammary glands, DMBA promoted by TPA in mouse skin, and OH-BBN in mouse bladder. The agents tested may be classified into various pharmacological and chemical structural categories that are relevant to their chemopreventive potential. These categories include antiestrogens, antiinflammatories (e.g., NSAIDs), antioxidants, arachidonic acid metabolism inhibitors, GST and GSH enhancers, ODC inhibitors, protein kinase C inhibitors, retinoids and carotenoids, organosulfur compounds, calcium compounds, vitamin D3 and analogs, and phenolic compounds (e.g., flavonoids). The various categories of compounds have different spectra of efficacy in animal models. In hamster lung, GSH-enhancing agents and antioxidants appear to have high potential for inhibiting carcinogenesis. In the colon, NSAIDs and other antiinflammatory agents appear particularly promising. Likewise, NSAIDs are very active in mouse bladder. In rat mammary glands, retinoids and antiestrogens (as would be expected) are efficacious. Several of the chemicals evaluated also appear to be promising chemopreventive agents based on their activity in several of the animal models. Particularly, the ODC inhibitor DFMO was active in the colon, mammary glands, and bladder models, while the dithiolthione, oltipraz, was efficacious in all the models listed above (i.e., lung, colon, mammary glands, skin, and bladder).

Animals↗
PubMed1992

Modulation of ileal calcium transport by phosphate-exchanging compounds.

Calcium transport in the ileal-ligated loop was studied in the adult rat in the presence of either phosphate alone or phosphate-binding compounds, namely either hydroxylated or aminated substances. Sorbitol or creatine (50 mM) added to a 10-mM CaCl2 solution, which was instilled into ileal loop, markedly enhanced calcium transport, as determined by 45Ca radioactivity appearing in plasma and from 45Ca radioactivity disappearing from the loop. The presence of both compounds maintained Ca soluble in an instilled solution at a constant concentration, whereas with a control solution the Ca concentration progressively decreased towards zero after an incubation period of 60 min. Phosphate, which was either simultaneously added with sorbitol or creatine or which was present as sorbitol or creatine phosphate, led to an equally marked decrease in calcium transport. Calcium transfer was even more reduced when phosphate alone was present with calcium in the ileal loop, in the absence of sorbitol. Similar to the above phosphate-binding compounds, adenosine and its constitutive component, ribose, increased calcium transfer, whereas adenine, the other constitutive component of adenosine, was ineffective. Guanosine was twice more active than adenosine in stimulating ileal calcium transport. Interestingly, the structure of guanosine allows the binding of two phosphates, with one binding site being on the ribose and the other on the guanine base moiety. Thus guanosine is capable of binding a greater amount of phosphate than the two other aminated compounds examined, namely adenosine and alanine, when transphosphorylation from ATP is studied with intestinal microvilli preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗