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PubMed1992

Subcellular mechanism and site of action of ionic lanthanum at the motor nerve terminal.

The mechanism by which ionic lanthanum (La3+) increases and subsequently decreases spontaneous transmitter release was investigated by recording miniature endplate potentials (MEPPs) at frog neuromuscular junctions. Addition of tetrodotoxin and Co2+ delayed the onset of MEPP frequency increase but did not otherwise prevent the response. Dinitrophenol substantially reduced but did not eliminate the increase, whereas 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8) completely abolished it. Thus, La3+ does not act by depolarizing the terminal or by substituting for Ca2+ at transmitter release sites. Instead, it appears to enter the terminal through Na+ channels and promote Ca2+ release from intracellular organelles. The profound depletion of transmitter with time may be due to the high turnover of transmitter coupled with the inhibition of metabolic processes by La3+.

Animals↗
PubMed2002

Synthesis and biological activity of polygalloyl-dendrimers as stable tannic acid mimics.

Inspired by the structure of tannic acid, first- to third-generation dendrimers containing two, four, and eight galloyl moieties were synthesized. Stability, antioxidant activity and collagen cross-linking activity of the natural product and its dendrimer analogues were compared. The experimental results indicate that polygalloyl dendrimers might be used as new lead compounds to improve the long-term healing characteristics of burn wounds.

Antioxidants↗
PubMed1987

Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells.

Changes in cytoplasmic calcium concentration ([Ca2+]i) activate numerous cellular processes thus mediating the effects of a number of hormones, but whether this mechanism is involved in the activation of osteoblasts by parathyroid hormone (PTH) remains uncertain. To examine this question, [Ca2+]i has been measured in suspensions of UMR 106 cells, a rodent osteosarcoma cell line with an osteoblastic phenotype. Basal [Ca2+]i was 137 +/- 3.7 nM (n = 60) and after the addition of rat PTH-(1-34) [rPTH-(1-34)] there was a rapid, dose-related increase with return to base line within 1 min. Half-maximal stimulation was produced by 5 X 10(-8) M rPTH-(1-34). Complexing of intracellular calcium by EGTA addition immediately before that of rPTH did not affect the calcium transient; neither did MnCl2 (10(-4) M) nor diltiazem (10(-4) M). Verapamil (10(-5) M) reduced the [Ca2+]i peak height after rPTH to 0.48 +/- 0.14 of control (n = 7). 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoic acid and dantrolene both reduced the [Ca2+]i response to rPTH (0.65 +/- 0.08 and 0.29 +/- 0.13 of control, respectively). Forskolin (10(-6) and 10(-5) M) produced a slight [Ca2+]i transient smaller in amplitude than seen with PTH. It is concluded that PTH mobilizes an intracellular calcium pool in these osteoblastlike cells, and the predominant mechanism for this is independent of cAMP.

Animals↗
PubMed2001

Synthesis and conformational property of tannin-like p-tert-butylcalix[4]arene 1,3-diesters stabilized by intramolecular hydrogen bonds.

Tannin-like p-tert-butylcalix[4]arene 1,3-digallate was synthesized, and its conformational property was investigated by dynamic (1)H NMR and X-ray crystallography. It was found that the 3-OH (or 5-OH) group of the galloyl group in p-tert-butylcalix[4]arene 1,3-digallate is placed at the position where an unusual nonbonded close contact is observed between the OH group and the aromatic ring of the galloyl group facing each other. The calixarene 1,3-diesters of various hydroxybenzoic acids were also prepared, and the conformational properties of those calixarenes were compared with that of p-tert-butylcalix[4]arene 1,3-digallate. A significant contribution of the 3- and 5-OH groups in pendant groups toward the close contact was found. It was suggested that the conformation of p-tert-butylcalix[4]arene 1,3-digallate was stabilized by intramolecular hydrogen bonds including OH.O and OH-pi interactions.

Calixarenes↗
PubMed2004

Antioxidant properties of Aller-7, a novel polyherbal formulation for allergic rhinitis.

Allergic rhinitis, a frequently occurring immunological disorder affecting men, women and children worldwide, is a state of hypersensitivity that occurs when the body overreacts to a substance such as pollen, mold, mites or dust. Allergic rhinitis exerts inflammatory response and irritation of the nasal mucosal membranes leading to sneezing; stuffy/runny nose; nasal congestion; and itchy, watery and swollen eyes. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. In this study, the antioxidant efficacy of Aller-7 was investigated by various assays including hydroxyl radical scavenging assay, superoxide anion scavenging assay, 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2-azinobis-ethyl-benzothiozoline-sulphonic acid diammonium salt (ABTS) radical scavenging assays. The protective effect of Aller-7 on free radical-induced lysis of red blood cells and inhibition of nitric oxide release by Aller-7 in lipopolysaccharide-stimulated murine macrophages were determined. Aller-7 exhibited concentration-dependent scavenging activities toward biochemically generated hydroxyl radicals (IC50 741.73 microg/ml); superoxide anion (IC50 24.65 microg/ml by phenazine methosulfate-nicotinamide adenine dinucleotide [PMS-NADH] assay and IC50 4.27 microg/ml by riboflavin/nitroblue tetrazolium [NBT] light assay), nitric oxide (IC50 16.34 microg/ml); 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical (IC50 5.62 microg/ml); and 2,2-azinobis-ethyl-benzothiozoline-sulphonic acid diammonium salt (ABTS) radical (IC50 7.35 microg/ml). Aller-7 inhibited free radical-induced hemolysis in the concentration range of 20-80 microg/ml. Aller-7 also significantly inhibited nitric oxide release from lipopolysaccharide-stimulated murine macrophages. These results demonstrate that Aller-7 is a potent scavenger of free radicals and that it may serve.

Animals↗
PubMed2002

Determination of hydrolyzable tannins (gallotannins and ellagitannins) after reaction with potassium iodate.

A widely used method for analyzing hydrolyzable tannins afer reaction with KIO(3) has been modified to include a methanolysis step followed by oxidation with KIO(3). In the new method, hydrolyzable tannins (gallotannins and ellagitannins) are reacted at 85 degrees C for 20 h in methanol/sulfuric acid to quantitatively release methyl gallate. Dried plant samples can be methanolyzed under the same conditions to convert hydrolyzable tannins to methyl gallate. Oxidation of the methyl gallate by KIO(3) at pH 5.5, 30 degrees C, forms a chromophore with lambda(max) 525 nm, which is determined spectrophotometrically. The detection limit of the method is 1.5 microg of methyl gallate, and with plant samples, relative standard deviations of less than 3% were obtained.

Chromatography, High Pressure Liquid↗
PubMed1985

Mechanism of action of angiotensin II and bradykinin on prostaglandin synthesis and vascular tone in the isolated rat kidney. Effect of Ca++ antagonists and calmodulin inhibitors.

We have studied the effect of angiotensin II and bradykinin on prostaglandin output and vascular tone during extracellular calcium depletion and administration of calcium antagonists and calmodulin inhibitors to elucidate the mechanism of action in the isolated rat kidney perfused with Tyrode's solution. Administration of angiotensin II (0.028-0.28 nmol) or bradykinin (0.28-2.8 nmol) enhanced the output of prostaglandin E2 and 6-keto-prostaglandin F1 alpha in a dose-dependent manner. Angiotensin II, but not bradykinin, produced renal vasoconstriction. Omission of calcium from the medium or infusion of calcium entry blockers, diltiazem (60 microM), or nimodipine (47 microM), failed to alter prostaglandin output elicited by angiotensin II or bradykinin; however, the effect of angiotensin II to produce renal vasoconstriction was inhibited. If calcium was omitted from the medium, the intracellular calcium antagonists, 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (23 microM), dantrolene sodium (31 microM), or ryanodine (2 microM), attenuated prostaglandin output caused by angiotensin II but not bradykinin. Calmodulin inhibitors, trifluoperazine (2 microM), napthalene sulfonamide hydrochloride (2 microM), or calmidazolium (2 microM), diminished prostaglandin output elicited by angiotensin II, but not that caused by bradykinin. Trifluoperazine, but not naphthalene sulfonamide or calmidazolium, attenuated the renal vasoconstrictor effect of angiotensin II. Prostaglandin output induced by angiotensin II and bradykinin were inhibited by mepacrine and indomethacin, whereas, the prostaglandin output caused by exogenous arachidonic acid (33 nmol) was abolished by indomethacin but was unaltered by mepacrine, calcium antagonists, and calmodulin inhibitors. From these data, we conclude that angiotensin II produces renal vasoconstriction by a mechanism dependent on extracellular calcium but not calmodulin, whereas angiotensin II-induced prostaglandin output depends on intracellular calcium and calmodulin. In contrast, bradykinin appears to stimulate prostaglandin synthesis by a calcium/calmodulin-independent mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Role of intracellular Ca2+ on histamine release from rat peritoneal mast cells.

The benzoic acid derivative 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) strongly inhibited histamine release from rat peritoneal mast cells induced by various secretagogues. TMB-8 also inhibited Ca2+ mobilization from intracellar Ca2+ stores. However, histamine release induced by compound 48/80 (condensation product of N-methyl-p-methoxy-phenethylamine and formaldehyde) was not affected by TMB-8. These results indicate that Ca2+ mobilization is necessary to elicit the release of histamine from mast cells.

Animals↗
PubMed1978

Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds.

The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes.

Animals↗
PubMed1995

Induction of oxidative stress by okadaic acid is required for activation of transcription factor NF-kappa B.

The widely used phosphatase 1 and 2A inhibitor okadaic acid is one of the many stimuli activating transcription factor NF-kappa B in cultured cells. Phosphorylation of I kappa B-alpha, one of NF-kappa B's inhibitory subunits, is a prerequisite for I kappa B degradation and the subsequent liberation of transcriptionally active NF-kappa B. This observation suggested that the phosphorylation status of I kappa B is influenced by an okadaic acid-sensitive phosphatase. In this study, we provide evidence that the effect of okadaic acid on NF-kappa B activation is indirect and dependent on the production of reactive oxygen intermediates rather than the inhibition of an I kappa B-alpha phosphatase. Okadaic acid was found to be a strong inducer of cellular H2O2 and superoxide production in two distinct cell lines. The structurally unrelated phosphatase inhibitor calyculin A also induced oxidative stress. The delayed onset of reactive oxygen production in response to okadaic acid correlated with the delayed activation of NF-kappa B. Moreover, NF-kappa B induction was optimal at the same okadaic acid concentration that caused optimal H2O2 production. Both reactive oxygen intermediates production and NF-kappa B activation were inhibited by the antioxidant pyrrolidine dithiocarbamate and 8-(diethylamino)octyl-3,4,5-trimethyoxybenzoate, a Ca2+ chelator. Future experiments using phosphatase inhibitors in intact cells must consider that the compounds can act as strong inducers of oxidative stress, which provides one explanation for their tumor-promoting activity.

Antioxidants↗
PubMed2002

Acute effects of ingestion of black tea on postprandial platelet aggregation in human subjects.

Results of population studies suggest that black tea can reduce cardiovascular risk. Effects of black-tea polyphenols to reduce platelet aggregability may help to explain any benefits. Given that black tea is often consumed with and after meals, and man spends much of his life in the postprandial state, the objective of the present study was to investigate the acute effects of ingestion of black tea on postprandial platelet aggregation ex vivo. Twenty healthy participants had platelet aggregation and blood lipids assessed before and 4 h after the ingestion of 50 g dairy fat on two occasions in random order, corresponding to black tea or hot water. Black tea or hot water (one cup) was consumed immediately following the dairy fat, then after 15 and 30 h. Platelet aggregation ex vivo was assessed in platelet-rich plasma in response to three concentrations of collagen (0.2, 0.6, 20 microg/ml) and ADP (2, 4, 8 microM). Urinary concentrations of 4-O-methylgallic acid were used as an indicator that tea polyphenols were absorbed. Serum total cholesterol and triacylglycerol concentrations increased significantly 4 h after ingesting the dairy fat, but there was no significant difference between black tea and hot-water treatments on the cholesterol or triacylglycerol responses. Urinary 4-O-methylgallic acid concentrations were significantly increased following ingestion of black tea (P=0.0001) but not water. Black tea in comparison to hot water did not inhibit collagen or ADP-induced postprandial platelet aggregation. The results of this study do not support the suggestion that reduced postprandial platelet aggregability contributes to any benefits of black tea on cardiovascular risk.

Adenosine Diphosphate↗
PubMedDate not supplied

Nonisothermal bioreactors in the treatment of vegetation waters from olive oil: laccase versus syringic acid as bioremediation model.

Laccase from Trametes versicolor was immobilized by diazotization on a nylon membrane grafted with glycidil methacrylate, using phenylenediamine as spacer and coupling agent. The behavior of these enzyme derivatives was studied under isothermal and nonisothermal conditions by using syringic acid as substrate, in view of the employment of these membranes in processes of detoxification of vegetation waters from olive oil mills. The pH and temperature dependence of catalytic activity under isothermal conditions has shown that these membranes can be usefully employed under extreme pH and temperatures. When employed under nonisothermal conditions, the membranes exhibited an increase of catalytic activity linearly proportional to the applied transmembrane temperature difference. Percentage activity increases ranging from 62% to 18% were found in the range of syringic acid concentration from 0.02 to 0.8 mM, when a difference of 1 degrees C was applied across the catalytic membrane. Because the percentage activity increase is strictly related to the reduction of the production times, the technology of nonisothermal bioreactors has been demonstrated to be an useful tool also in the treatment of vegetation waters from olive oil mills.

Agriculture↗
PubMed2002

Quercetin dihydrate and gallate supplements lower plasma and hepatic lipids and change activities of hepatic antioxidant enzymes in high cholesterol-fed rats.

This study was designed to test the lipid-lowering and antioxidant activity of two bioflavonoids, quercetin dihydrate and gallate. Four groups of rats were given a semisynthetic diet containing 10 g cholesterol/kg for six weeks. The control group received only a high-cholesterol diet, whereas the other three groups received a diet including 1 g lovastatin, 1 g quercetin dihydrate, or 1 g gallate/kg. The quercetin dihydrate and gallate supplements both significantly lowered the plasma lipid and hepatic cholesterol levels compared to those of the control. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was significantly lowered by the quercetin dihydrate when compared to the other groups, while the hepatic acyl CoA: cholesterol acyltransferase (ACAT) activity was only significantly higher in the control group. The overall potential for antioxidant protection was significantly enhanced by the quercetin dihydrate and gallate supplements through lowering the plasma and hepatic thiobarbituric acid reactive substances (TBARS) levels and increasing the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in high-cholesterol-fed rats. These results suggest that the supplementation of quercetin dihydrate and gallate promotes an increase in fecal sterols, which in turn leads to a decreased absorption of dietary cholesterol as well as lower plasma and hepatic cholesterol.

Animals↗
PubMedDate not supplied

The search for new antiarrhythmics in the group of chirally 1,2-aminoalcohols. I. 3',4',5'-trimethoxybenzoic acid esters of optically active N,N'-dimethyl-N,N'-bis-(1-hydroxybutyl-2) ethylenediamines.

Both enantiomeric (2S, 2'S) and (2'R) N, N'-dimethyl-N, N-bis (1-hydroxybutyl-2)-ethylenediamines (Table 1) were obtained by methylation of the corresponding N,N'-ethylene-bis-2-aminobutanols-1. The esterification of the former aminoalcohols with 3, 4, 5-trimethoxybenzoic acid gave the both enantiomeric in title named esters (Table 2). The isomer with S configuration at both chirally center (C2 and C2), has a particularly strong antiarrhythmic properties (about 10-20 greater than quinidine or procaine amide in different experimental arrhythmia models in animals. The 2R,2'R enantiomere is 10-100 times less active one. It seems that the antiarrhythmic activity of this new group of antiarrhythmically active compounds, derivatives of chirally 1, 2-aminoalcohols is connected with spatial configuration.

Amino Alcohols↗
PubMed1990

Up-regulation of human neutrophil receptors for Neisseria gonorrhoeae expressing PII outer membrane proteins.

In the absence of serum, nonpiliated gonococci expressing PII outer membrane proteins (PIIs) adhere to human neutrophils whereas non-PII-expressing (PII-) gonococci do not. After an observation that neutrophils in monolayers bound more gonococci than neutrophils in suspension, we treated neutrophil suspensions with known stimulants of degranulation and measured subsequent gonococcal adherence to suspended neutrophils. The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fmlp), the potent secretagogue phorbol myristate acetate, and the calcium ionophore A23187 all caused increased adherence of PII+ gonococci, but not PII- gonococci, to neutrophils in a dose-responsive manner. Increased adherence of gonococci to neutrophils was paralleled by increased degranulation of neutrophil myeloperoxidase, lysozyme, and lactoferrin. Inhibition of fmlp-induced neutrophil degranulation by pertussis toxin, the calmodulin inhibitors trifluoperazine and N-5-chloronaphthalene sulfonamide, or the intracellular calcium-binding agent trimethoxybenzoic acid also inhibited fmlp-induced gonococcal adherence to neutrophils. Neither undifferentiated nor myelocytically differentiated HL-60 cells, which possess primary but defective or nonexistent secondary granules, bound PII+ or PII- gonococci. Gonococci did not adhere to human monocytes, monocyte-derived macrophages, lymphocytes, platelets, or erythrocytes, indicating that several receptors, such as the complement receptors CR1, CR3 (CD11b/CD18), and CR4 (CD11c/CD18) or the adherence complex LFA-1 (CD11a/CD18), were probably not involved in gonococcal adherence to human neutrophils.

Antibodies, Monoclonal↗
PubMed2004

DdAlix, an Alix/AIP1 homolog in Dictyostelium discoideum, is required for multicellular development under low Ca2+ conditions.

Apoptosis-linked gene 2 (ALG-2) interacting protein X (Alix), also called AIP1, is a widely conserved protein in eukaryotes. Alix and its homologs are involved in various phenomena such as apoptosis, regulation of cell adhesion, protein sorting, adaptation to stress conditions, and budding of human immunodeficiency virus (HIV). To investigate the role of Alix in development, we identified an Alix homolog in the cellular slime mold Dictyostelium discoideum and disrupted the gene by homologous recombination. The growth of DdAlix deletion mutant (alx-) cells was significantly impaired in the presence of 5 mM Li+. On an agar plate, alx- cells underwent normal development and formed fruiting bodies indistinguishable from those formed by wild-type cells. However, alx- cells could not form fruiting bodies in the presence of 5 mM Li+. Similar results were obtained when cells were developed in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), which is an antagonist of intracellular Ca2+ store. Furthermore, when the extracellular free Ca2+ was reduced to 10 nM, the ability of alx- cells, but not that of wild-type cells, to form fruiting bodies was impaired. The results indicate that DdAlix is essential for development under low Ca2+ conditions and suggest that DdAlix is involved in Ca2+ signaling during development.

Animals↗
PubMedDate not supplied

[Toxicological study of the long-term effects of the antioxidant dodecyl gallate on albino rats].

Toxicity of the antioxidant dodecyl gallate was studied in 150-day experiments on male white rats. The antioxidant was administered intragastrically in doses of 250, 50 and 10 mg/kg bw. The general status and behavior of the animals, the survival rate, weight gain, peripheral blood, the amount of urea, total serum protein, soluble proteins of the liver and kidneys, and activity of enzymes (AST, ALT, LDH, SDH, glucose-6-phosphate dehydrogenase, alkaline and acid phosphatase of the serum, liver and kidneys, the weight of the internal organs) were studied over time, followed by morbid anatomy studies. Quantitative determination of serum lipids (total fats, total cholesterol, esterified cholesterol, free cholesterol, triglycerides, free fatty acids, triglycerides plus free fatty acids, and phospholipids) was made on the 150th day after the onset of experiments. When administered in a dose of 250 mg/kg, dodecyl gallate produced death of the animals and an increase in the content of triglycerides plus free fatty acids, a decrease in the weight of the spleen and morphological alterations in the liver, kidneys and spleen. The dose 50 mg/kg was also toxic. It brought about changes in the activity of serum and liver AST, an increase in the content of TF, TG, FFA, TG plus FFA and phospholipids, a reduction in the weight of the spleen and pathological changes in the liver, kidneys and spleen. The dose 10 mg/kg is regarded as liminal.

Animals↗
PubMed1994

Site-specific DNA cleavage by Cu(II) complexes of podophyllotoxin derivatives.

Site-specific DNA cleavage in the presence of Cu(II) complexes of podophyllotoxin derivatives was investigated with a modified Sanger sequencing method. Cu(II) complexes of 4'-demethylepipodophyllotoxin (DEPD) and syringic acid (SA) cleaved M13mp18 single-strand DNA site-specifically at both cytosine (C) and guanine (G) positions in the GC rich regions and C position, respectively, at pH 7.8. The apparent binding constants of calf thymus DNA-Cu(II) complexes estimated by the differential UV-absorption spectra revealed that both Cu(II)-VP-16 and -DEPD complexes bind to DNA more strongly than does the Cu(II)-SA complex.

Base Sequence↗