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1.
J Neurol ; 262(7): 1655-64, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25929656

ABSTRACT

Camptocormia in Parkinson's disease (PD) is an axial postural disorder usually accompanied by histopathological changes in the paravertebral muscles of unknown etiology. The diagnostic potential of magnetic resonance imaging (MRI) of back muscles in camptocormia has not been systematically assessed. Our objective was to characterize pathological muscle changes with MRI and to develop radiological criteria for camptocormia. The criteria edema, swelling and fatty degeneration in 20 idiopathic PD patients with camptocormia were assessed using MRI (T1w and short tau inversion recovery (STIR) sequences) of the lumbar trunk muscles and compared with 20 group-matched PD patients without camptocormia. Edema and fatty degeneration of the paravertebral muscles were significantly more frequent in camptocormia. Edema correlated negatively and fatty degeneration positively with the duration of camptocormia and not PD. Swelling of the paravertebral muscles, edema and swelling of the quadratus lumborum muscle and rare edema of the psoas muscle were only found in camptocormia patients. In this case-control study the defined MRI criteria distinguish the group of PD patients with camptocormia versus those without. Our findings suggest dynamic changes in the MRI signals over time in the paravertebral muscles: edema and swelling are found initially, followed by fatty atrophic degeneration 2-3 years after the beginning of camptocormia. Muscle MRI qualifies as a tool for categorizing phases of camptocormia as acute or chronic, with potential consequences for therapeutic approaches. The involvement of muscles beyond an isolated impairment of the paravertebral muscles implies a more systemic view with a deregulation of lumbar trunk muscles.


Subject(s)
Magnetic Resonance Imaging , Muscle, Skeletal/pathology , Muscular Atrophy, Spinal/pathology , Parkinson Disease/pathology , Spinal Curvatures/pathology , Adipose Tissue/pathology , Aged , Case-Control Studies , Edema/etiology , Female , Humans , Image Processing, Computer-Assisted , Longitudinal Studies , Male , Middle Aged , Muscle, Skeletal/physiopathology , Spinal Cord/pathology , Statistics as Topic
2.
Photodiagnosis Photodyn Ther ; 12(2): 244-51, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25703104

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilms in artificially infected root canals using modified photosensitizers and passive ultrasonic activation. METHODS: Two hundred and seventy extracted human teeth with one root canal were instrumented utilizing ProTaper files, autoclaved, infected with E. faecalis T9 for 72 h and divided into different groups: irrigation with 3% sodium hypochlorite (NaOCl), 20% ethylenediaminetetraacetic acid (EDTA), or 20% citric acid, PDT without irrigation, PDT accompanied by irrigation with NaOCl, EDTA, or citric acid, PDT using an EDTA-based photosensitizer or a citric-acid-based photosensitizer and PDT with ultrasonic activation of the photosensitizer. A 15 mg/ml toluidine blue served as the photosensitizer, activated by a 100 mW LED light source. Sterile paper points were used for sampling the root canals and dentin chips were collected to assess the remaining contamination after treatment. Samples were cultured on blood agar plates and colony forming units were quantified. RESULTS: PDT alone achieved a reduction in E. faecalis counts by 92.7%, NaOCl irrigation alone and combined with PDT by 99.9%. The antibacterial effects increased by the combination of irrigation using EDTA or citric acid and PDT compared to irrigation alone. More than 99% of E. faecalis were killed using PDT with the modified photosensitizers and ultrasonic activation. CONCLUSIONS: NaOCl based disinfection achieved the highest antimicrobial effect. Using PDT with an EDTA-based or citric-acid-based phozosensitizer or activating the photosensitizer with ultrasound resulted in a significantly higher reduction in E. faecalis counts compared to conventional PDT.


Subject(s)
Biofilms/drug effects , Enterococcus faecalis/drug effects , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Therapeutic Irrigation/methods , Ultrasonics/methods , Citric Acid/therapeutic use , Edetic Acid/therapeutic use , Humans , Root Canal Preparation/methods , Sodium Hypochlorite/therapeutic use , Tolonium Chloride/therapeutic use
3.
J Phys Condens Matter ; 26(20): 206001, 2014 May 21.
Article in English | MEDLINE | ID: mdl-24769569

ABSTRACT

The interaction of a current-driven domain wall with an anisotropy boundary in nanowires with perpendicular magnetic anisotropy is investigated. A local reduction of the anisotropy constant is used to create an artificial boundary where the domain wall gets pinned. Micromagnetic simulations and analytical calculations, based on a one-dimensional model, are employed to describe the interaction of the domain wall and the anisotropy boundary and to determine the depinning current densities. Two different pinning regimes-an intrinsic and an extrinsic-can be identified in dependence with the characteristic of the boundary. A very good agreement between simulated and analytically obtained data is achieved.


Subject(s)
Electric Conductivity , Electromagnetic Fields , Models, Chemical , Models, Molecular , Nanowires/chemistry , Nanowires/ultrastructure , Anisotropy , Computer Simulation
4.
Br J Pharmacol ; 171(4): 1019-32, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24251620

ABSTRACT

BACKGROUND AND PURPOSE: Transient receptor potential melastatin 3 (TRPM3) proteins form non-selective but calcium-permeable membrane channels, rapidly activated by extracellular application of the steroid pregnenolone sulphate and the dihydropyridine nifedipine. Our aim was to characterize the steroid binding site by analysing the structural chemical requirements for TRPM3 activation. EXPERIMENTAL APPROACH: Whole-cell patch-clamp recordings and measurements of intracellular calcium concentrations were performed on HEK293 cells transfected with TRPM3 (or untransfected controls) during superfusion with pharmacological substances. KEY RESULTS: Pregnenolone sulphate and nifedipine activated TRPM3 channels supra-additively over a wide concentration range. Other dihydropyridines inhibited TRPM3 channels. The natural enantiomer of pregnenolone sulphate was more efficient in activating TRPM3 channels than its synthetic mirror image. However, both enantiomers exerted very similar inhibitory effects on proton-activated outwardly rectifying anion channels. Epiallopregnanolone sulphate activated TRPM3 almost equally as well as pregnenolone sulphate. Exchanging the sulphate for other chemical moieties showed that a negative charge at this position is required for activating TRPM3 channels. CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that nifedipine and pregnenolone sulphate act at different binding sites when activating TRPM3. The latter activates TRPM3 by binding to a chiral and thus proteinaceous binding site, as inferred from the differential effects of the enantiomers. The double bond between position C5 and C6 of pregnenolone sulphate is not strictly necessary for the activation of TRPM3 channels, but a negative charge at position C3 of the steroid is highly important. These results provide a solid basis for understanding mechanistically the rapid chemical activation of TRPM3 channels.


Subject(s)
Nifedipine/pharmacology , Pregnenolone/pharmacology , TRPM Cation Channels , Animals , Base Sequence , Binding Sites , HEK293 Cells , Humans , Mice , Molecular Sequence Data , TRPM Cation Channels/agonists , TRPM Cation Channels/chemistry , TRPM Cation Channels/metabolism , TRPM Cation Channels/physiology
5.
Allergy ; 64(11): 1597-601, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19392986

ABSTRACT

BACKGROUND: Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). METHODS: Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. RESULTS: Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV(1) were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. CONCLUSIONS: The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids.


Subject(s)
Asthma/immunology , Inflammation/immunology , Neutrophils/immunology , Sputum/immunology , Adolescent , Asthma/physiopathology , Case-Control Studies , Child , Female , Humans , Hypersensitivity, Immediate/immunology , Hypersensitivity, Immediate/physiopathology , Inflammation/physiopathology , Male , Neutrophils/cytology , Sputum/cytology
6.
Water Sci Technol ; 58(10): 1903-9, 2008.
Article in English | MEDLINE | ID: mdl-19039168

ABSTRACT

The occurrence of Transparent Exopolymer Particles (TEP), an acidic fraction of polysaccharides, was monitored for more than six months in the activated sludge of three MBR units, and the relationship between TEP and other fouling indicators was studied. These compounds consist mainly of exopolysaccharides of a sticky nature, a characteristic which makes them a group of interesting substances in processes like sedimentation, flocculation and membrane fouling. The relationship between capillary suction time (CST) and polysaccharides (PS) was linear for the three tested sludges, although the correlation with TEP concentrations was stronger. A slight linear correlation of both TEP and PS was found with the critical flux (CF) measured with a small filtration test cell, which was submerged in the membrane tank to assess the filterability performance of the sludge in situ. However, the correlation CF-PS was clearer. The relationship between TEP, polysaccharides and sludge filterability highlights the potential of this parameter for the monitoring of membrane systems.


Subject(s)
Bioreactors , Membranes, Artificial , Polymers/analysis , Polysaccharides/analysis , Filtration , Polymers/chemistry , Waste Disposal, Fluid
7.
Water Sci Technol ; 57(1): 117-23, 2008.
Article in English | MEDLINE | ID: mdl-18192748

ABSTRACT

Soluble and colloidal materials like soluble microbial products (SMP) or extracellular polymeric substances (EPS) are considered to be major foulants in membrane bioreactors (MBRs). Removing these fouling causing substances is thus thought to reduce the fouling of the membrane in general. In addition to traditional strategies for fouling prevention which mostly try to remedy the effects of fouling by air scour, etc., the new and promising method of adding chemicals is being investigated here. Previous tests with 30 different substances have shown that several of these reduce SMP concentration in the supernatant and enhance filtration. Nevertheless, additive dosing might have unknown side effects in filtration systems. Results presented in this study indicate that these additives may themselves cause severe fouling on different membranes if they remain unbound in the liquid phase. Therefore, the thorough control of the dosing rate of these chemicals will be of paramount importance in full scale applications. Biological toxicity of additives was measured in terms of respiration. OUR tests did not show inhibiting effects for most additives. Chitosan even showed an enhanced OUR due to biodegradability. Oxygen transfer could be enhanced for 25% with the addition of a polymer.


Subject(s)
Bioreactors , Waste Disposal, Fluid/methods , Membranes, Artificial , Reproducibility of Results , Waste Disposal, Fluid/instrumentation
8.
Water Sci Technol ; 56(7): 11-9, 2007.
Article in English | MEDLINE | ID: mdl-17951863

ABSTRACT

For a more effective fouling reduction in membrane bioreactors (MBR) the approach of continuous measurement and control of protein and polysaccharide concentrations is followed. So called extra-cellular polymer substances (EPS) can be partially measured by a newly developed protein sensor based on sequential injection analysis. The sensor is validated by real MBR pilot data, stating the feasibility of the technique for continuous monitoring. Parallel to EPS, other fouling active compounds such as organic bio-polymer were determined in two parallel MBR pilot lines by size exclusion chromatography, proving desired comparable conditions in both lines for later parallel testing. The daily variation of EPS in MBR operation are moderate, where protein changes tend to react more pronounced to operational changes than polysaccharides. This was also the case for the organic bio-polymer fraction, especially in manipulated bench experiments at abruptly changing redox conditions.


Subject(s)
Bioreactors , Biopolymers/metabolism , Chromatography, Liquid , Extracellular Matrix/metabolism , Polysaccharides/metabolism , Proteins/metabolism , Sewage
9.
Water Sci Technol ; 56(6): 115-24, 2007.
Article in English | MEDLINE | ID: mdl-17898450

ABSTRACT

For membrane bioreactors (MBR) with enhanced nutrients removal, rather complex recirculation schemes based on the biological requirements are commonly recommended. The aim of this work was to evaluate other recirculation options. For a laboratory scale MBR, four different recirculation schemes were tested. The MBR was operated with COD degradation, nitrification, post-denitrification without carbon dosing and biological phosphorus removal. For all configurations, efficient COD, nitrogen and phosphorus removal could be achieved. There were no big differences in elimination efficiency between the configurations (COD elimination: 96.6-97.9%, nitrogen removal: 89.7-92.1% and phosphorus removal: 97.4-99.4%). Changes in the degradation, release and uptake rates were levelled out by the changes in contact time and biomass distribution. With relatively constant outflow concentrations, different configurations are still interesting with regard to oxygen consumption, simplicity of plant operation or support of certain degradation pathways such as biological phosphorus removal or denitrification.


Subject(s)
Bioreactors , Nitrogen/isolation & purification , Waste Disposal, Fluid/methods , Nitrogen/metabolism , Reproducibility of Results , Waste Disposal, Fluid/instrumentation
10.
Water Res ; 41(5): 1038-44, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17217981

ABSTRACT

Ten biomass samples from both municipal and industrial pilot and full scale submerged membrane bioreactors (MBRs) with mixed liquor suspended solids concentrations (MLSS) ranging from 7.2 to 30.2g L(-1) were studied at six air-flow rates (0.7, 1.3, 2.3, 3, 4.4 and 6m(3)m(-3)h(-1)). Statistical analyses were applied to identify the relative impacts of the various bulk biomass characteristics on oxygen transfer. Of the biomass characteristics studied, only solids concentration (correlated with viscosity), the carbohydrate fraction of the EPS (EPS(c)) and the chemical oxygen demand (COD) concentration of the SMP (SMP(COD)) were found to affect the oxygen transfer parameters k(L)a(20) (the oxygen transfer coefficient) and alpha-factor. The relative influence on k(L)a(20) was MLSS>aeration>EPS(c)>SMP(COD) and on alpha-factor was MLSS>SMP(COD)>EPS(c)>aeration. Both k(L)a(20) and alpha-factor increased with increasing aeration and EPS(c) and decreased with increasing MLSS and SMP(COD). MLSS was found to be the main parameter controlling the oxygen transfer.


Subject(s)
Bioreactors , Oxygen/metabolism , Sewage/chemistry , Waste Disposal, Fluid , Biomass , Filtration/instrumentation , Sewage/microbiology , Viscosity , Water Purification
11.
Water Sci Technol ; 51(6-7): 391-402, 2005.
Article in English | MEDLINE | ID: mdl-16004001

ABSTRACT

Owing to increasingly stringent effluent quality requirements, intensifications of the conventional activated sludge process (ASP) are required. Due to high biomass concentrations employed, higher metabolic rates and better nutrient removal are possible in membrane bioreactors (MBRs). Decoupling of hydraulic and solids residence times offers additional possibilities for process design and optimisation. Recently, unconventional concepts like post-denitrification and enhanced biological phosphorus removal in MBRs have emerged. The objective of this paper is to present current knowledge on nutrients removal in MBRs and trends in process optimisation in comparison with conventional ASP.


Subject(s)
Bioreactors , Membranes, Artificial , Nitrogen/isolation & purification , Phosphorus/isolation & purification , Waste Disposal, Fluid/methods , Adsorption , Aerobiosis , Anaerobiosis , Biomass , Cities , Filtration , Nitrates/analysis , Nitrites/chemistry , Nitrites/metabolism , Phosphates/analysis , Quaternary Ammonium Compounds/analysis , Sewage/chemistry , Sewage/microbiology
12.
Nucl Med Biol ; 29(4): 375-87, 2002 May.
Article in English | MEDLINE | ID: mdl-12031872

ABSTRACT

This paper reports the synthesis, biological evaluation, in vitro and ex vivo autoradiography of the first Tc-99m ligand with subnanomolar affinity for the 5-HT(1A) receptor and a remarkably high affinity for the alpha1-adrenergic receptor. The neutral "3+1" mixed-ligand complex combines 4-(6-mercaptohexyl)-1-(2-methoxyphenyl)piperazine as monodentate and 3-(N-methyl)azapentane-1,5-dithiol as tridentate unit with oxotechnetium(V). The analogous rhenium complex was synthesized for complete structural characterization and used in receptor binding assays. In competition experiments both complexes display subnanomolar affinity for the 5-HT(1A) receptor (IC(50)0.24 nM for Re, 0.13 nM for Tc) but also very high affinities for the alpha1-adrenergic receptor (IC(50) 0.05 nM for Re, 0.03 nM for Tc). Biodistribution studies show a brain uptake in rat of 0.22% ID five minutes post injection. In vitro autoradiographic studies in rat brain and postmortem human brain indicate accumulation of the Tc-99m complex in brain areas which are rich in 5-HT(1A) receptors or in alpha1-adrenergic receptors. This in vitro enrichment can be blocked respectively by the 5-HT(1A) receptor agonist 8-OH-DPAT or by prazosin hydrochloride, an alpha1-adrenergic receptor antagonist. Ex vivo autoradiographic studies in rats show a slight accumulation of the Tc-99m complex in 5-HT(1A) receptor-rich areas of the brain, which could not be blocked, as well as in regions rich in alpha1-adrenergic receptors, which could be blocked by prazosin hydrochloride.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Organotechnetium Compounds/chemical synthesis , Organotechnetium Compounds/pharmacokinetics , Piperazines/pharmacokinetics , Pyridines/pharmacokinetics , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Serotonin/metabolism , Technetium/pharmacokinetics , Animals , Autoradiography , Cadaver , Humans , In Vitro Techniques , Male , Models, Molecular , Organotechnetium Compounds/metabolism , Piperazines/chemical synthesis , Pyridines/chemical synthesis , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Inbred WF , Receptors, Serotonin, 5-HT1 , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution
13.
Nucl Med Biol ; 29(4): 389-98, 2002 May.
Article in English | MEDLINE | ID: mdl-12031873

ABSTRACT

Tc(III) and Re(III) complexes [M(NS(3))(CNR)] (M = Re, 99mTc, NS(3) = 2,2',2"-nitrilotris(ethanethiol), CNR = functionalized isocyanide bearing a derivative of WAY 100635) have been synthesized and characterized. Re was used as Tc surrogate for chemical characterization and in vitro receptor-binding studies. For two representatives subnanomolar affinities for the 5-HT(1A) as well as for the alpha1-adrenergic receptor were reached. Biodistribution studies in rats of the 99mTc complexes showed brain uptakes between 0.3 and 0.5% ID/organ (5 min p.i.). In vitro autoradiography of one 99mTc representative in sections of post mortem human brain indicate its accumulation in 5-HT(1A) receptor-rich brain regions. However, addition of the specific 5-HT(1A) receptor agonist 8-OH-DPAT as well as the alpha1-adrenoceptor antagonist prazosin could not substantially block this tracer accumulation. A preliminary SPET study in a monkey showed negligible brain uptake.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Piperazines/pharmacokinetics , Pyridines/pharmacokinetics , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Serotonin/metabolism , Technetium/pharmacokinetics , Animals , Autoradiography , Cadaver , Haplorhini , Humans , In Vitro Techniques , Male , Models, Molecular , Piperazines/chemical synthesis , Pyridines/chemical synthesis , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Inbred WF , Receptors, Serotonin, 5-HT1 , Reproducibility of Results , Rhenium/pharmacokinetics , Sensitivity and Specificity , Tissue Distribution , Tomography, Emission-Computed, Single-Photon
14.
J Med Chem ; 44(19): 3132-40, 2001 Sep 13.
Article in English | MEDLINE | ID: mdl-11543682

ABSTRACT

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.


Subject(s)
Chelating Agents/chemical synthesis , Melanoma, Experimental/metabolism , Organotechnetium Compounds/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Animals , Binding, Competitive , Brain/metabolism , Chelating Agents/chemistry , Crystallography, X-Ray , Guinea Pigs , Humans , In Vitro Techniques , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Organotechnetium Compounds/chemistry , Organotechnetium Compounds/pharmacokinetics , Radioligand Assay , Receptors, sigma/metabolism , Stereoisomerism , Structure-Activity Relationship , Sulfhydryl Compounds/chemistry , Tissue Distribution , Tumor Cells, Cultured
15.
Inorg Chem ; 40(1): 59-64, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11195389

ABSTRACT

Five-coordinate oxotechnetium(V) mixed-ligand complexes [TcO(SES)(S-p-C6H4-OMe)], where SES is a tridentate dithiolato fragment of the type -S(CH2)2E(CH2)2S- (E = O, 1; E = S, 2; E = NMe, 3) are converted via reduction-substitution reactions in the presence of PMe2Ph into the corresponding five-coordinate Tc(III) complexes [Tc(SES)(S-p-C6H4-OMe)(PMe2Ph)] (E = O, 4; E = S, 5; E = NMe, 6). Rearrangement of the original square pyramidal "3 + 1" oxo species to the trigonal bipyramidal "3 + 1 + 1" Tc(III) complexes occurs by placing the three thiolate donors on the basal plane, the phosphine phosphorus, and the heteroatom of the tridentate ligand at the apexes of the bipyramid. These Tc(III) complexes are diamagnetic species, thereby allowing multinuclear NMR characterization in solution, which confirm their structures to be identical to those observed in the solid state via X-ray determinations.


Subject(s)
Organotechnetium Compounds/chemical synthesis , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Molecular Structure , Organotechnetium Compounds/chemistry , Structure-Activity Relationship
16.
Appl Radiat Isot ; 53(3): 431-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10972149

ABSTRACT

The preparation and characterisation of 3 + 1 + 1 technetium complexes of the general formula [Tc(SES)(RS)(PMe2Ph)] (SES = tridentate dithiol ligand, E = S, O, NMe; RSH = monothiol ligand) at the n.c.a. level is described. The Tc(III) complexes are prepared in a one-step procedure starting from pertechnetate in yields of 85-95% of radiochemical purity. A comparison of their chromatographic data with the fully characterised 99Tc complexes indicate the identity of the investigated compounds. Stability studies show that the 99mTc complexes undergo some alteration in solution. They are oxidised to the 3 + 1 oxotechnetium (V) complexes and/or decompose in aqueous solution. In challenge experiments performed with glutathione, exchange of the monothiolato ligand occurs in the same manner as known for the 3 + 1 complexes.


Subject(s)
Organophosphorus Compounds/chemistry , Organotechnetium Compounds/chemistry , Sulfhydryl Compounds/chemistry , Technetium , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Drug Stability , Sodium Pertechnetate Tc 99m/chemistry , Structure-Activity Relationship
17.
Bioconjug Chem ; 11(3): 414-24, 2000.
Article in English | MEDLINE | ID: mdl-10821659

ABSTRACT

The organometallic precursor (NEt(4))(2)[ReBr(3)(CO)(3)] was reacted with bidendate dithioethers (L) of the general formula H(3)C-S-CH(2)CH(2)-S-R (R = -CH(2)CH(2)COOH, CH(2)-C&tbd1;CH) and R'-S-CH(2)CH(2)-S-R' (R' = CH(3)CH(2)-, CH(3)CH(2)-OH, and CH(2)COOH) in methanol to form stable rhenium(I) tricarbonyl complexes of the general composition [ReBr(CO)(3)L]. Under these conditions, the functional groups do not participate in the coordination. As a prototypic representative of this type of Re compounds, the propargylic group bearing complex [ReBr(CO(3))(H(3)C-S-CH(2)CH(2)-S-CH(2)C&tbd1;CH)] Re2 was studied by X-ray diffraction analysis. Its molecular structure exhibits a slightly distorted octahedron with facial coordination of the carbonyl ligands. The potentially tetradentate ligand HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH was reacted with the trinitrato precursor [Re(NO(3))(3)(CO)(3)](2-) to yield a cationic complex [Re(CO)(3)(HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH)]NO(3) Re8 which shows the coordination of one hydroxy group. Re8 has been characterized by correct elemental analysis, infrared spectroscopy, capillary electrophoresis, and X-ray diffraction analysis. Ligand exchange reaction of the carboxylic group bearing ligands H(3)C-S-CH(2)CH(2)-S-CH(2)CH(2)-COOH and HOOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH with (NEt(4))(2)[ReBr(3)(CO)(3)] in water and with equimolar amounts of NaOH led to complexes in which the bromide is replaced by the carboxylic group. The X-ray structure analysis of the complex [Re(CO)(3)(OOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH)] Re6 shows the second carboxylic group noncoordinated offering an ideal site for functionalization or coupling a biomolecule. The no-carrier-added preparation of the analogous (99m)Tc(I) carbonyl thioether complexes could be performed using the precursor fac-[(99m)Tc(H(2)O)(3)(CO)(3)](+), with yields up to 90%. The behavior of the chlorine containing (99m)Tc complex [(99m)TcCl(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))] Tc1 in aqueous solution at physiological pH value was investigated. In saline, the chromatographically separated compound was stable for at least 120 min. However, in chloride-free aqueous solution, a water-coordinated cationic species Tc1a of the proposed composition [(99m)Tc(H(2)O)(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))](+) occurred. The cationic charge of the conversion product was confirmed by capillary electrophoresis. By the introduction of a carboxylic group into the thioether ligand as a third donor group, the conversion could be suppressed and thus the neutrality of the complex preserved. Biodistribution studies in the rat demonstrated for the neutral complexes [(99m)TcCl(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))] Tc1 and [(99m)TcCl(CO)(3)(CH(2)-S-CH(2)CH(2)-S-CH(2)-C&tbd1;CH)] Tc2 a significant initial brain uptake (1.03 +/- 0.25% and 0.78 +/- 0.08% ID/organ at 5 min. p.i.). Challenge experiments with glutathione clearly indicated that no transchelation reaction occurs in vivo.


Subject(s)
Ethers/chemistry , Organotechnetium Compounds/chemical synthesis , Rhenium/chemistry , Technetium/chemistry , Animals , Brain/metabolism , Chelating Agents , Crystallography, X-Ray , Hydrogen-Ion Concentration , Ligands , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Molecular Structure , Organ Specificity , Organotechnetium Compounds/pharmacokinetics , Rats , Rats, Wistar , Spectrophotometry, Infrared
18.
J Nutr ; 128(3): 651-60, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9482777

ABSTRACT

The purpose of this work was to develop a method for measurement of the major forms of resistant starch (RS) in foods. The analytical procedure was chosen to mimic physiologic conditions, and included chewing as a prestep before incubation with pepsin, pancreatin and amyloglucosidase. The undigestible polysaccharides, including RS, were recovered by ethanol precipitation and subsequent filtration. RS was analyzed as total starch in the filter residue. The residues were also used for gravimetric determination of dietary fiber after correcting for remaining protein, ash and RS. The potentially available starch fraction was determined from analysis of glucose in the filtrate. The foods included were prepared to resemble products for which RS figures were available from in vivo measurements, and/or from analysis with other current in vitro methods. For six of these foods, and for three additional starchy materials, RS figures were compared with in vivo and/or in vitro data for identical products. The pooled standard deviation for the suggested RS method was 2.9%. A high correlation was obtained with in vivo figures from the literature for 19 realistic foods (r = 0.97; y = 0.77x + 0.45). After correction for RS, dietary fiber figures corresponded well with conventional gravimetric dietary fiber analysis for 14 starchy foods (r = 0.97). It is concluded that the procedure described here provides a convenient way to estimate RS content of realistic foods, allowing parallel determination of the potentially available starch fraction and dietary fiber.


Subject(s)
Dietary Carbohydrates/pharmacokinetics , Dietary Fiber/metabolism , Starch/pharmacokinetics , Biological Availability , Bread/analysis , Dietary Carbohydrates/analysis , Dietary Fiber/analysis , Edible Grain/chemistry , Forecasting , Humans , Mastication/physiology , Methods , Solanum tuberosum/chemistry , Starch/analysis
19.
Clin Infect Dis ; 25(6): 1421-9, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9431390

ABSTRACT

We retrospectively reviewed eight prospective epidemiological studies conducted between 1991 and 1995 for dual respiratory virus infection (DRVI) to determine the frequency, associated comorbid conditions, clinical presentations, and morbidity related to DRVI among immunocompetent persons. Two viruses were identified as the cause of 67 (5.0%) of 1,341 acute respiratory virus infections. DRVI was detected in patients from < 1 year to 79 years of age, in both sexes, and in many races. Forty-two percent of patients with DRVI were < or = 4 years old. Fifty-eight percent of patients with DRVI had underlying chronic lung disease. DRVI was associated with upper respiratory tract illness; lower respiratory tract illness, including pneumonia; systemic influenza-like illnesses; and exacerbations of asthma or chronic obstructive pulmonary disease. All of the common acute respiratory viruses were identified; picornaviruses and influenzavirus A were the most common. The rate of DRVI (11.6%) was highest in the epidemiological studies in which cell culture, serology, and polymerase chain reaction were used together. Patients with DRVI were hospitalized significantly more often than those with respiratory infection due to a single virus (46.3% vs. 21.7%; P < .01). The percentage of DRVIs increased proportionally with the number of diagnostic methods used.


Subject(s)
Respiratory Tract Infections/epidemiology , Virus Diseases/epidemiology , Comorbidity , Female , Humans , Male , Retrospective Studies
20.
J Nutr ; 125(3): 459-65, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7876921

ABSTRACT

The importance of the amylose: amylopectin ratio in the postprandial glycemic and insulinemic responses to corn was studied in food products that might realistically be consumed. Healthy subjects were given test meals in the form of arepas made from ordinary (25% amylose) or high amylose (70% amylose) corn flour. The ordinary corn meal contained 45 g of potentially available starch. To exclude the possible influence of a lowered content of potentially available starch due to formation of resistant starch in the high amylose product, this product was evaluated at two levels and included either on the basis of potentially available starch (45 g) or total starch (including resistant starch) (45 g, i.e., 29 g potentially available starch), respectively. The rate of starch hydrolysis, measured in vitro employing a method based on chewing, was studied. In addition, the content of in vitro resistant starch was analyzed in all products. The meals containing high amylose corn flour produced lower areas under the glucose and insulin response curves (57 and 42% lower, respectively) than did the meals containing ordinary cornmeal. This could not be explained by a lower amount of potentially available starch. No differences were noted when subjects consumed the two high amylose meals of arepas, despite 36% lower potentially available starch in one of the meals. The rate of starch hydrolysis measured in vitro was slower in the high amylose corn products than in the ordinary corn product. Resistant starch in the ordinary product was 3 g/100 g dry matter, vs. approximately 20 g/100 g dry matter in the high amylose products. We concluded that high amylose corn products have a potential to promote favorably low metabolic responses and high resistant starch contents.


Subject(s)
Amylose/administration & dosage , Blood Glucose/metabolism , Food , Insulin/blood , Zea mays , Adult , Amylopectin/administration & dosage , Dietary Carbohydrates/administration & dosage , Female , Humans , Hydrolysis , Male , Starch/administration & dosage , Starch/metabolism
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