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PubMed2005

L-carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferation and differentiation in vitro.

Age-related bone loss is characterized by decreased osteoblast activity, possibly related to the reduction of energy production. Carnitine promotes energy availability and its concentration declines with age; Therefore, two Carnitine derivatives, L-carnitine fumarate (LC) and isovaleryl L-carnitine fumarate (Iso-V-LC), have been tested on several parameters of human osteoblasts in vitro. Both compounds significantly increased osteoblast activity, but the new compound Iso-V-LC was more efficient than LC at lower concentrations. They both significantly enhanced cell proliferation, [3H]-proline incorporation and the expression of collagen type I (COLLI), and the bone sialoproteins (BSPs) and osteopontin (OPN). The percentage of alkaline phosphatase (ALP)-positive cells and the secretion of osteocalcin were not modified by LC and Iso-V-LC. Both molecules increased the formation of mineralized nodules, but Iso-V-LC reached the maximum effect at a concentration 10-fold lower than that of LC. Furthermore, we showed that insulin-like growth factor (IGF)-I and IGF-II mRNA levels were not modified by the treatment. However, the two compounds induced an increase of insulin-like growth factor binding protein (IGFBP)-3 and a decrease of IGFBP-5 in both osteoblast lysates and the extracellular matrix (ECM). In conclusion these data suggest that carnitine and, in particular, its new derivative, Iso-V-LC supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss.

Alkaline Phosphatase↗
PubMed1985

Detection of a tetranuclear iron-sulfur center in fumarate reductase from Escherichia coli by electron paramagnetic resonance spectroscopy.

Soluble fumarate reductase and fumarate reductase complex from Escherichia coli have been investigated by electron paramagnetic resonance spectroscopy. Both succinate- and dithionite-reduced samples show signals associated with a [2Fe-2S]1+ cluster that account maximally for slightly more than one spin/molecule. In addition, at temperatures below 20 K, dithionite-reduced samples exhibit broad and complex features, to high and low field of the [2Fe-2S]1+ signal, that are attributable to a spin coupled [4Fe-4S]1+ cluster. Preliminary attempts to quantify the signals indicate that the [4Fe-4S] cluster is present in an approximate 1:1 stoichiometry with the [2Fe-2S] cluster. The observed enhancement of the spin relaxation of the [2Fe-2S]1+ cluster on dithionite reduction is attributed to spin-spin interaction between the S = 1/2, reduced tetranuclear and binuclear clusters.

Dithionite↗
PubMed1988

ESR studies on iron-sulfur clusters of complex II in Ascaris suum mitochondria which exhibits strong fumarate reductase activity.

Complex II of Ascaris suum mitochondria, which functions as fumarate reductase in physiological conditions, contains three types of iron-sulfur clusters. These correspond to clusters S-1, S-2 and S-3 and are distinguishable by low-temperature ESR studies. Cluster S-1 is reduced by succinate, giving ESR signals with gz, gy and gx values at 2.033, 1.939 and 1.920. The existence of cluster S-2 is suggested by an enhancement of the S-1 spin relaxation induced upon reduction of S-2 by dithionite. Cluster S-3 is ESR detectable under air-oxidized conditions and gives a strong signal at g = 2.025. Cluster S-3 was only partially reduced even with an excess amount of sodium succinate, which is a common characteristic of fumarate reductase but this is not seen in the mitochondrial complex II.

Animals↗
PubMed1991

NADH oxidase and fumarate reductase of Ancylostoma ceylanicum.

Ancylostoma ceylanicum, the hookworm parasite of cat, dog and man, was found to contain NADH and/or NADPH oxidase as well as fumarate reductase activities. Both the enzyme systems were predominantly located in the membranes of mitochondrial-rich preparations. The membranes also exhibited the presence of a reduced pyridine nucleotide transhydrogenase activity which transferred hydrogen from NADPH to NAD. Amongst respiratory inhibitors, rotenone (Site I inhibitor) markedly depressed both NADH oxidase and fumarate reductase while others, namely antimycin-A, KCN and azide, had a lesser effect.

Ancylostoma↗
PubMed1986

Evidence that centre 2 in Escherichia coli fumarate reductase is a [4Fe-4S]cluster.

Redox titrations of the iron-sulphur clusters in fumarate reductase purified from Escherichia coli, monitored by ESR spectroscopy, identified three redox events, similar to those observed in other fumarate reductases and succinate dehydrogenases: Centre 1, a [2Fe-2S] cluster, at g = 2.03, 1.93, appeared on reduction with Em = -20 mV. Centre 3, probably a [3Fe-xS] cluster, at g = 2.02 appeared in the oxidized state with Em = -70 mV. Centre 2 has been observed as an increase in the electron-spin relaxation of Centre 1. It titrates as an n = 1 species with Em = -320 mV, but in our hands did not appear to contribute significant intensity to the g = 2.03, 1.93 signal. It therefore appears to be an additional centre which undergoes spin-spin interaction with Centre 1. The reduction of Centre 2 coincided with the appearance of an extremely broad ESR spectrum, observed at temperatures below 20 K, with features at g = 2.17, 1.9, 1.68. The broad signal was observed in both soluble and membrane-bound preparations. Its midpoint potential was -320 mV. Its integrated intensity was approximately equal to that of Centre 1, if its broad outer wings were taken into account. Consideration of the ESR properties of this signal, together with the amino acid sequence of the frdB subunit of the enzyme, indicates that Centre 2 is a [4Fe-4S] cluster which, in its reduced state, enhances the spin relaxation of the [2Fe-2S] Centre 1.

Electron Spin Resonance Spectroscopy↗
PubMed1986

Evaluation of chronic toxicity and carcinogenesis in rodents with the synthetic analgesic, tilidine fumarate.

The carcinogenic potential of tilidine fumarate, a synthetic analgesic, was studied for 80 and 104 weeks in mice and rats, respectively. Groups of 50 albino CF1 mice and 65 albino Wistar rats of each sex received tilidine fumarate-lactose blend (1:1) at doses of 100, 40 and 16 mg/kg. The control groups consisted of 100 mice and 115 rats of each sex and received the lactose vehicle only. Treatment-related non-neoplastic changes consisted of reversible, increased cytoplasmic eosinophilia of hepatocytes in high and mid dose rats corresponding to areas of proliferating smooth endoplasmic reticulum; and an increased incidence in high dose rats of proliferative or cystic lesions of the biliary epithelium. Adequate survival rates allowed stringent statistical analysis of neoplasia. Tilidine did not evoke increased tumor incidences or changes in the average latency or onset of tumors in either species. The most frequent tumors represented spontaneous neoplasia characteristic of historical background incidence in these strains. In mice, the only statistically significant (P less than 0.01) variation in tumor incidence was an increased rate of lung alveologenic adenocarcinomas in females at 100 mg/kg (24%), compared with the concurrent untreated controls (10%), but without a statistically significant difference from historical control data (27%). Female rats given 100 mg/kg showed statistically significant (P less than 0.01) decreased incidences of mammary fibroadenoma and pituitary adenoma. From these data, it was concluded that the synthetic analgesic tilidine does not possess tumorigenic potential in rodents.

Administration, Oral↗
PubMed1986

Thermodynamics of the conversion of aqueous L-aspartic acid to fumaric acid and ammonia.

The thermodynamics of the conversion of aqueous L-aspartic acid to fumaric acid and ammonia have been investigated using both heat conduction microcalorimetry and high-pressure liquid chromatography. The reaction was carried out in aqueous phosphate buffer over the pH range 7.25-7.43, the temperature range 13-43 degrees C, and at ionic strengths varying from 0.066 to 0.366 mol kg(-1). The following values have been found for the conversion of aqueous L-aspartateH- to fumarate2- and NH4+ at 25 degrees C and at zero ionic strength: K = (1.48 +/- 0.10) x 10(-3), DeltaG degrees = 16.15 +/- 0.16 kJ mol(-1), DeltaH degrees = 24.5 +/- 1.0 kJ mol(-1), and DeltaC(p) degrees = -147 +/- 100 J mol(-1) K(-1). Calculations have also been performed which give values of the apparent equilibrium constant for the conversion of L-aspartic acid to fumaric acid and ammonia as a function of temperature, pH and ionic strength.

Journal Article↗
PubMed2005

Comparison of the effects of ketotifen fumarate 0.025% and olopatadine HCl 0.1% ophthalmic solutions in seasonal allergic conjunctivities: a 30-day, randomized, double-masked, artificial tear substitute-controlled trial.

BACKGROUND: Topical antiallergic agents, such as antihistamines and mast-cell stabilizers, are the main therapeutic options for seasonal allergic conjunctivitis (SAC). Ketotifen fumarate and olopatadine HCl have dual action that offers a combination of these 2 mechanisms. Although clinical studies comparing the efficacy of these 2 drugs have shown that both were effective in the treatment of SAC, the results were contradictory and did not include the effects of these drugs on inflammatory markers. OBJECTIVES: The aims of this study were to compare the clinical efficacy of topical ketotifen and olopatadine eye drops and to determine the effects of these 2 drugs on the expression of cell adhesion molecules (CAMs) and inflammatory markers in conjunctival surface cells in patients with SAC. METHODS: This 30-day, randomized, double-masked, artificial tear substitute (ATS)-controlled clinical trial was conducted at the Department of Ophthalmology, Karadeniz Technical University, School of Medicine, Trabzon, Turkey. Patients with SAC were included in the study and randomly assigned to 1 of 3 groups: topical ketotifen fumarate 0.025% ophthalmic solution, topical olopatadine HCl 0.1% ophthalmic solution, or ATS (control group). All drugs were administered 2 drops per eye BID for 30 days. At the beginning of the study (day 0; baseline), on day 15, and on day 30, clinical scores (itching, tearing, redness, eyelid, swelling, and chemosis) and conjunctival impression cytology specimens were obtained. The percentages of cells expressing intercellular adhesion molecule 1, vascular CAM-1, human leukocyte antigen-DR, and beta1-integrin (CD29) from conjunctival impression cytology specimens were determined using flow cytometry. Patients were questioned about adverse events (AEs) at each visit. Ocular discomfort on installation of the drugs was recorded as an AE. RESULTS: Thirty-nine patients (20 men, 19 women; age range, 18-61 years) with SAC were included. Twelve patients received ketotifen; 13, olopatadine; and 14, ATS. In both active-treatment groups, the improvements of clinical scores (tearing and itching) were more pronounced compared with those in the ATS group, although the day-30 difference in tearing score between the olopatadine and ATS groups was not statistically significant. No significant within-group or between-group differences in mean scores for redness, chemosis, or eyelid swelling were found. The expression rates of CAMs and inflammatory markers in conjunctival surface cells were significantly more reduced with ketotifen and olopatadine compared with ATS. However, clinical and flow cytometric parameters were improved with ATS at 15 and 30 days compared with baseline. No AEs were observed during the study period. CONCLUSIONS: In this short-term study in a selected, small study population with SAC, ketotifen and olopatadine diminished the expression of CAMs and inflammatory markers on the conjunctival surface cells effectively. Both active treatments were more efficacious compared with ATS and were well tolerated.

Adolescent↗
PubMed1999

Platelet adhesion on a bioresorbable poly(propylene fumarate-co-ethylene glycol) copolymer.

Platelet adhesion and aggregation on poly(propylene fumarate-co-ethylene glycol), P(PF-co-EG), hydrogels was examined under both static and flow conditions. Adherent platelets were quantified under static conditions using both 111Indium oxine-labeled platelets as well as a lactate dehydrogenase, LDH, assay. The radiolabeling assay showed a significant decrease in platelet attachment on the copolymer hydrogel films relative to the poly(propylene fumarate), PPF, homopolymer. In addition, there were reductions in adhesion resulting from the increase in poly(ethylene glycol), PEG, weight percent or molecular weight. There was good agreement between both assays under static conditions for the copolymer films. Platelet surface coverage was quantified under flow conditions in a parallel plate flow chamber using the LDH assay. There was a dramatic decrease in the number of adherent platelets on the copolymers relative to glass and silicone rubber controls. All of the copolymer surfaces showed minimal aggregation with no thrombus formation or platelet spreading as assessed qualitatively using scanning electron microscopy. These results suggest that P(PF-co-EG) is a good candidate for development as a cardiovascular implant.

Absorbable Implants↗
PubMed2002

Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection.

BACKGROUND: Tenofovir disoproxil fumarate (DF) is the first nucleotide reverse transcriptase inhibitor approved for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in the United States. Unlike the nucleoside reverse transcriptase inhibitors, which must undergo 3 intracellular phosphorylation steps for activation. nucleotide analogues such as tenofovir require only 2 such steps. This reduction in the phosphorylation requirement has the potential to produce more rapid and complete conversion of the drug to its pharmacologically active metabolite. OBJECTIVE: This article describes the pharmacologic properties and potential clinical usefulness of tenofovir DF. METHODS: Relevant information was identified through searches of MEDLINE (1996-April 2002), Iowa Drug Information Service (1996-April 2002), and International Pharmaceutical Abstracts (1970-April 2002), as well as from meeting abstracts of major HIV/AIDS conferences (1996-2002), using the search terms tenofovir tenofovir disoproxil fumarate, PMPA, bis(POC)PMPA, GS-4331-05, acyclic nucleoside phosphonate, and nucleotide reverse transcriptase inhibitor. Additional information was obtained from material submitted to the US Food and Drug Administration by the manufacturer of tenofovir DF in support of its New Drug Application. RESULTS: In vitro, tenofovir DF has exhibited anti-HIV activity in various HIV-infected cell lines and has produced a synergistic or additive effect against HIV when combined with other antiretroviral agents. In adult humans, tenofovir has a volume of distribution of 0.813 L/kg, is minimally bound to plasma protein (7.2%), has a plasma elimination half-life of 12.0 to 14.4 hours, and is mainly excreted unchanged in urine (70%-80%). Dose adjustment based on sex or body weight does not appear to be necessary, although dose reduction may be necessary in the elderly; there are currently no data on tenofovir DF in renal or hepatic insufficiency. The results of clinical trials suggest the efficacy of tenofovir DF in reducing plasma levels of HIV-1 RNA when used as an add-on to a stable antiretroviral regimen. The most commonly (>3%) reported adverse events in clinical trials have included nausea, diarrhea, asthenia, headache, vomiting, flatulence, abdominal pain, and anorexia. The most commonly (>2%) reported laboratory abnormalities (grade III or IV) included increases in creatine kinase, triglycerides, amylase, aspartate aminotransferase, and alanine aminotransferase, as well as hyperglycemia and glucosuria. Serious adverse events leading to discontinuation of tenofovir DF were infrequent (5%), occurring with an incidence similar to that with placebo (8%). The recommended dosage of tenofovir DF in adults is 300 mg/d PO; pharmacokinetic and efficacy studies in children are ongoing. CONCLUSION: Although additional studies are needed, tenofovir DF appears to be a promising agent for the treatment of HIV infection.

Adenine↗
PubMed2002

A comparison of the relative clinical efficacy of a single dose of ketotifen fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge model.

BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution is an antiallergic treatment currently available in the United States. It is indicated for the temporary prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE: The purpose of this study was to determine the relative efficacy of ketotifen when applied topically to the eye, compared with placebo, in the treatment of nasal signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge (CAC) model. METHODS: This was a randomized, double-blind, parallel-group, single-center clinical study using the CAC model. Patients aged > or = 18 years, able to follow the study instructions, willing to avoid disallowed medications, and having a history of rhinoconjunctivitis and a positive skin test were eligible. At visit 1, the dose of allergen necessary to achieve a qualifying reaction was determined using bilateral ocular instillation of allergen to eligible patients. At visit 2, the allergen dose determined at visit 1 was confirmed, and all patients attaining a qualifying nasal reaction continued in the study. At visit 3, each patient was randomized to receive 1 drop of ketotifen bilaterally in the eyes or 1 drop of placebo bilaterally. Fifteen minutes after instillation of the study medication, bilateral CAC was performed. Patients rated nasal symptoms (sneezing, rhinorrhea and postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) on standardized scales at 10, 20, and 30 minutes after CAC. RESULTS: Thirty-two patients (16 men, 16 women; mean age, 45 years [range, 28-70 years]) were randomized to treatment and completed the study. Nineteen patients received ketotifen and 13 received placebo. Nasal symptom scores in ketotifen-treated patients were statistically and clinically significantly fewer than in those treated with placebo at all time points (mean baseline corrected total nasal score: 10 minutes, P = 0.010; 20 minutes, P = 0.025; 30 minutes, P = 0.006). CONCLUSION: In this study, topical ketotifen fumarate 0.025% ophthalmic solution, when dosed ocularly, offered protecdon against the nasal signs and symptoms of acute allergic rhinoconjunctival reaction as induced by the CAC model.

Adult↗
PubMed2003

A placebo-controlled comparison of ketotifen fumarate and nedocromil sodium ophthalmic solutions for the prevention of ocular itching with the conjunctival allergen challenge model.

BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution and nedocromil sodium 2.0% ophthalmic solution are 2 topical antiallergic medications with different modes of action and efficacy profiles. Both solutions are indicated for ocular itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the efficacy, safety, and comfort of ketotifen fumarate 0.025% ophthalmic solution and nedocromil sodium 2.0% ophthalmic solution for the prevention of ocular itching, using the conjunctival allergen challenge (CAC) model. METHODS: This was a single-center, double-masked, contralateral, randomized, placebo- and active-controlled CAC clinical trial. Subjects aged >10 years with a history of allergic hypersensitivity who responded to the CAC at screening visits 1 and 2 qualified for randomization at visit 3. At visit 3 (day 21) and visit 4 (day 35), subjects received 1 of 3 treatments: ketotifen, nedocromil, or placebo (artificial tears), randomized by eye. Allergen challenges were conducted at 5 minutes posttreatment dose (visit 3) and 12 hours posttreatment dose (visit 4). At each visit, subjects evaluated their ocular itching every 30 seconds for 20 minutes. At visit 4, subjects evaluated the comfort of the medication immediately after instillation, at 30 seconds after instillation, and at l, 2, 5, and 10 minutes after instillation. The subjects were also queried about overall eyedrop comfort by choosing from descriptive terms and about overall eyedrop preference based on comfort and perceived efficacy. RESULTS: Eighty-five subjects were screened for this study. Fifty-nine (28 males, 31 females; mean age, 38.7 years) qualified and were randomized to receive study medications. Ketotifen-treated eyes experienced significantly less ocular itching induced by CAC than nedocromil-treated eyes and those that received placebo at both the 5-minute and 12-hour posttreatment allergen challenges (all P < 0.05). Nedocromil-treated eyes showed no statistical or clinical differences from placebo at any time point. Ketotifen-treated eyes showed no differences in comfort from those that received placebo but were significantly more comfortable than nedocromil-treated eyes at 1, 2, 5, and 10 minutes after instillation (all P < 0.05). On the basis of comfort and subjective efficacy, 60% of subjects preferred ketotifen, 21% preferred nedocromil, and 19% preferred placebo. CONCLUSION: Ketotifen was significantly more effective and comfortable than nedocromil at both 5 minutes and 12 hours after administration in this CAC model.

Adolescent↗
PubMed1997

Cloning and functional characterization of Helicobacter pylori fumarate reductase operon comprising three structural genes coding for subunits C, A and B.

In this study, we cloned and sequenced the Helicobacter pylori genes encoding fumarate reductase (FRD). H. pylori frdA, frdB and frdC specify polypeptides of 715, 245 and 254 aa, respectively. The deduced aa sequences of FrdA and FrdB are highly homologous to those of the corresponding subunits of Wolinella succinogenes FRD and also exhibit a significant sequence identity with other bacterial FRD and succinate dehydrogenase subunits A and B. However, H. pylori FrdC shares a striking degree of sequence identity only with W. succinogenes FrdC, which is a cytochrome b with two haem groups. The products encoded by H. pylori frdA, frdB and frdC were overproduced in maxicells and H. pylori FrdA was characterized using an anti-E. coli FrdA serum. H. pylori FRD activity, which was measured as fumarate-dependent benzyl viologen oxidation, is membrane-associated. Inactivation of frdA led to the loss of such activity and the mutant H. pylori cells were delayed (approx. 10-20 h behind their parent cells) in entering the mid-log phase, suggesting that FRD-driven metabolism plays an active but non-essential role for growth of H. pylori cells in vitro. H. pylori FRD contains three subunits, of which FrdA and FrdB appear to form the catalytic dimer, whereas FrdC serves as a membrane anchor.

Amino Acid Sequence↗
PubMed1990

Determination of a new calcium antagonist, sesamodil fumarate (SD-3211), and its metabolite in plasma by liquid chromatography with electrochemical detection.

A sensitive and selective high-performance liquid chromatographic method is described for the determination of a novel calcium antagonist, (+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4-benzothiazine hydrogen fumarate (sesamodil fumarate; JAN, SD-3211, I), and its N-desmethylated metabolite (II) in plasma. Compounds I and II and an internal standard were isolated from plasma by solid-phase and liquid-liquid extraction. The extract was chromatographed on a reversed-phase C18 column, and the compounds of interest were detected by dual coulometric electrodes operated in an oxidative screen mode. The limit of determination for both I and II was at least 0.4 ng/ml in plasma. The utility of the assay was demonstrated by determining plasma levels of I and II in five dogs administered an oral dose of 60 mg of the drug.

Animals↗
PubMed1985

A comparative study of the succinate dehydrogenase-fumarate reductase complex in the genus Trichinella.

Succinate dehydrogenase and fumarate reductase activities from a particulate fraction of 4 isolates of the supposed 'species' of Trichinella, T. spiralis, T. pseudospiralis, T. nativa and T. nelsoni have been determined using spectrophotometric methods. The 'in vitro' effect of the anthelmintics thiabendazole, mebendazole and ivermectin on succinate dehydrogenase and fumarate reductase activities from the above isolates is also described. The significance of the results is discussed in the context of the controversy that surrounds speciation of the genus Trichinella.

Animals↗
PubMed2002

Role of His505 in the soluble fumarate reductase from Shewanella frigidimarina.

The X-ray structure of the soluble fumarate reductase from Shewanella frigidimarina [Taylor, P., Pealing, S. L., Reid, G. A., Chapman, S. K., and Walkinshaw, M. D. (1999) Nat. Struct. Biol. 6, 1108-1112] clearly shows the presence of an internally bound sodium ion. This sodium ion is coordinated by one solvent water molecule (Wat912) and five backbone carbonyl oxygens from Thr506, Met507, Gly508, Glu534, and Thr536 in what is best described as octahedral geometry (despite the rather long distance from the sodium ion to the backbone oxygen of Met507 (3.1 A)). The water ligand (Wat912) is, in turn, hydrogen bonded to the imidazole ring of His505. This histidine residue is adjacent to His504, a key active-site residue thought to be responsible for the observed pK(a) of the enzyme. Thus, it is possible that His505 may be important in both maintaining the sodium site and in influencing the active site. Here we describe the crystallographic and kinetic characterization of the H505A and H505Y mutant forms of the Shewanella fumarate reductase. The crystal structures of both mutant forms of the enzyme have been solved to 1.8 and 2.0 A resolution, respectively. Both show the presence of the sodium ion in the equivalent position to that found in the wild-type enzyme. The structure of the H505A mutant shows the presence of two water molecules in place of the His505 side-chain which form part of a hydrogen-bonding network with Wat48, a ligand to the sodium ion. The structure of the H505Y mutant shows the hydroxyl group of the tyrosine side-chain hydrogen-bonding to a water molecule which is also a ligand to the sodium ion. Apart from these features, there are no significant structural alterations as a result of either substitution. Both the mutant enzymes are catalytically active but show markedly different pH profiles compared to the wild-type enzyme. At high pH (above 8.5), the wild type and mutant enzymes have very similar activities. However, at low pH (6.0), the H505A mutant enzyme is some 20-fold less active than wild-type. The combined crystallographic and kinetic results suggest that His505 is not essential for sodium binding but does affect catalytic activity perhaps by influencing the pK(a) of the adjacent His504.

Amino Acid Sequence↗
PubMedDate not supplied

Synthesis and characterization of biodegradable cationic poly(propylene fumarate-co-ethylene glycol) copolymer hydrogels modified with agmatine for enhanced cell adhesion.

We synthesized positively charged biodegradable hydrogels by cross-linking of agmatine-modified poly(ethylene glycol)-tethered fumarate (Agm-PEGF) and poly(propylene fumarate-co-ethylene glycol) (P(PF-co-EG)) to investigate the effect of the guanidino groups of the agmatine on hydrogel swelling behavior and smooth muscle cell adhesion to the hydrogels. The weight swelling ratio of these hydrogels at pH 7.0 increased from 279 +/- 4 to 306 +/- 7% as the initial Agm-PEGF content increased from 0 to 200 mg/g of P(PF-co-EG), respectively. The diffusional exponents, n, during the initial phase of water uptake were independent of the initial Agm-PEGF content and were determined to be 0.66 +/- 0.08, 0.71 +/- 0.07, and 0.60 +/- 0.05 for respective initial Agm-PEGF contents of 0, 100, and 200 mg/g. The heat of fusion of water present in the hydrogels increased from 214 +/- 11 to 254 +/- 4 J/g as the initial Agm-PEGF content increased from 0 to 200 mg/g. The number of adherent smooth muscle cells increased dose-dependently from 15 +/- 6 to 75 +/- 7% of the initial seeding density as the initial Agm-PEGF content increased from 0 to 200 mg/g. These results suggest that the incorporation of the guanidino groups of agmatine into P(PF-co-EG) hydrogels increases the hydrogel free water content and the total water content of the hydrogels and also enhances cell adhesion to the hydrogels.

Agmatine↗
PubMed2006

Modeling and experimental investigation of rheological properties of injectable poly(lactide ethylene oxide fumarate)/hydroxyapatite nanocomposites.

Injectable multiphasic polymer/ceramic composites are attractive as bioresorbable scaffolds for bone regeneration because they can be cross-linked in situ and are osteoconductive. The injectability of the composite depends on the nanoparticle content and the energetic interactions at the polymer/particle interface. The objective of this research was to determine experimentally the rheological properties of the PLEOF/apatite composite as an injectable biomaterial and to compare the viscoelastic response with the predictions of a linear elastic dumbbell model. A degradable in situ cross-linkable terpolymer based on low molecular weight poly(L-lactide) and poly(ethylene oxide) linked by unsaturated fumarate groups is synthesized. The poly(L-lactide-co-ethylene oxide-co-fumarate) (PLEOF) terpolymer interacts with the surface of the apatite nanoparticles by polar interactions and hydrogen bonding. A kinetic model is developed that takes into account the adsorption/desorption of polymer chains to/from the nanoparticle surface. Rheological properties of the aqueous dispersion of PLEOF terpolymer reinforced with nanosized hydroxyapatite (HA) particles are investigated using mechanical rheometry. To this end, we performed a series of rheological experiments on un-cross-linked PLEOF reinforced with different volume fractions of HA nanoparticles. The results demonstrate that the observed nonlinear viscoelasticity at higher shear rates is controlled by the energetic interactions between the polymer chains and dispersed particle aggregates and by the rate of the adsorption/desorption of the chains to/from the surface of the nanoparticles.

Animals↗