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S Hess

Publications and source records attributed to S Hess.

At least 19 recordsLinked to original sources
PubMed2006

Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6 melanoma lung colonies in mice.

BACKGROUND: Treatment with anticoagulant drugs has shown potential inhibitory effect on tumor invasion, although the relationship with clotting inhibition was not clear. AIM: The aim of our study was to evaluate the potential antitumor activity of MCM09, a newly developed, active site-directed, small molecule inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to anticlotting potency. METHODS: MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(-1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo anticoagulant activity was measured by activated partial thromboplastin time (APTT) on mouse plasma. RESULTS AND CONCLUSIONS: MCM09, a selective inhibitor of FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16-BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8 in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P < 0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at 10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10 mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v. injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells, but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as a mechanism underlying antitumor activity.

Animals↗
PubMed2005

Keratoacanthoma centrifugum marginatum accompanied by extensive granulomatous foreign body reaction.

We describe a 58-year-old woman with a 4-year history of papular lesions with a partly verruciform appearance on the eyelids and the adjacent areas of the nose. The lesions progressed slowly but constantly into the surrounding areas with central scarring. Histopathology showed epidermal endophytic proliferations under a pronounced hyperparakeratosis. In the adjacent dermis a lymphohistiocytic infiltrate with giant cells of the foreign-body-reaction type was seen in close contact to extracellular keratin deposits. Although some cytopathological signs typical for viropathic effects were observed, no human papilloma virus-DNA was detected within the lesions by polymerase chain reaction. According to the histological picture and the clinical course we diagnosed a keratoacanthoma centrifugum marginatum. We present this case because of the strong granulomatous foreign body reaction which might complicate the diagnosis and has not been described for this keratoacanthoma variant so far.

Facial Dermatoses↗
PubMed2005

Red-light cameras for the prevention of road traffic crashes.

BACKGROUND: Road crashes are a prime cause of death and disability and red-light running is a common cause of crashes at signalised intersections. Red-light cameras are increasingly used to promote compliance with traffic signals. Manual enforcement methods are resource intensive and high risk, whereas red-light cameras can operate 24 hours a day and do not involve high-speed pursuits. OBJECTIVES: To quantify the impact of red-light cameras on the incidence and severity of road crashes and casualties, and the incidence of red-light violations. SEARCH STRATEGY: We searched the following electronic databases: TRANSPORT (NTIS, TRIS, IRRD,TRANSDOC), Cochrane Injuries Group Specialised Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and the Australian Transport Index. We checked the reference lists of relevant papers and contacted research and advocacy organisations. SELECTION CRITERIA: Randomised or quasi-controlled trials and controlled before-after studies of red-light cameras. For crash impact evaluation, the before and after periods each had to be at least one year in length. For violation studies, the after period had to occur at least one year after camera installation. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data on study type, characteristics of camera and control areas, and data collection period. Before-after data were collected on number of crashes by severity, collision type, deaths and injuries, and red-light violations. Rate ratio was calculated for each study. Where there was more than one, rate ratios were pooled to give an overall estimate, using a generic inverse variance method and a random-effects model. MAIN RESULTS: No randomised controlled trials were identified but 10 controlled before-after studies from Australia, Singapore and the USA met our inclusion criteria. We grouped them according to the extent to which they adjusted for regression to the mean (RTM) and spillover effects. Total casualty crashes: the only study that adjusted for both reported a rate ratio of 0.71 (95% CI to 0.55, 0.93); for three that partially adjusted for RTM but failed to consider spillover, rate ratio was 0.87 (95% CI to 0.77, 0.98); one that made no adjustments had a rate ratio of 0.80 (95% CI 0.58 to 1.12). Right-angle casualty crashes: rate ratio for two studies that partially addressed RTM was 0.76 (95% CI 0.54 to 1.07). Total crashes: the study addressing both RTM and spillover reported a rate ratio of 0.93 (95% CI 0.83 to 1.05); one study that partially addressed RTM had a rate ratio of 0.92 (95% CI 0.73 to 1.15); the pooled rate ratio from the five studies with no adjustments was 0.74 (95% CI 0.53 to 1.03). Red-light violations: one study found a rate ratio of 0.53 (95% CI 0.17 to 1.66). AUTHORS' CONCLUSIONS: Red-light cameras are effective in reducing total casualty crashes. The evidence is less conclusive on total collisions, specific casualty collision types and violations, where reductions achieved could be explained by the play of chance. Most evaluations did not adjust for RTM or spillover, affecting their accuracy. Larger and better controlled studies are needed.

Accident Prevention↗
PubMed2005

Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells.

Rhizomes of butterbur, Petasites hybridus L. (Asteraceae), have been used since ancient times for the treatment of inflammatory diseases. In the present study, the effects of lipophilic extracts from rhizomes of Petasites hybridus on the formation and release of prostaglandin E2 were investigated. The extracts had different contents of petasin and isopetasin: A: 2.1 % and 0.4 %, B: 0.2 % and 0.1 %, C: 12.1 % and 6.1 % and D: 21.9 % and 9.4 %, respectively. Direct inhibition of cyclooxygenase (COX) -1 and -2 isoenzymes and inhibition of the expression of COX-2 and p42/44 MAP kinase in rat primary microglial cells were tested. All extracts were found to be only weak direct inhibitors of COX-1 (IC50> 400 microg/mL). However, most extracts revealed a strong inhibitory activity against the inducible isoform COX-2 ( A: IC50=30.4 microg/mL; B: IC50=60.6 microg/mL; C: IC50=22.6 microg/mL; D: IC50=20.0 microg/mL). This activity was not correlated to the content of petasin and isopetasin. Pure petasin and isopetasin neither inhibited COX-1 nor COX-2 (IC50 > 400 microM for both compounds and enzymes). Petasites extracts dose-dependently inhibited LPS-induced and thus COX-2-mediated PGE2 release in primary rat microglial cells (A: IC50= 2.4 microg/mL; C: IC50=5.8 microg/mL and D: IC50=4.6 microg/mL). Also this effect was independent from the petasin and isopetasin content. COX-2 synthesis in microglia was totally blocked with 5 microg/mL of C whereas COX-1 synthesis was not influenced. C and D did not affect the LPS-induced activation of p38 MAPK and IkappaBalpha, but they prevented the LPS-induced activation of p42/44 MAPK. Therefore, these Petasites hybridus extracts can be regarded as natural selective inhibitors of COX-2 and its expression, an effect which is independent from the petasin content.

Animals↗
PubMed2004

Femtosecond time-resolved guanine oxidation in acridine modified alanyl peptide nucleic acids.

Alanyl peptide nucleic acids have been designed to generate linear and rigid pairing complexes. Femtosecond time resolved electron transfer dynamics studies of alanyl-PNA double strands where both strands contain an intercalated 9-amino-6-chloro-2-methoxy-acridine in its protonated state reveal a strong similarity to nearest neighbor interstrand/intrastrand guanine oxidation in the corresponding B-DNA fragment. This observation implies that the combined influence of electronic couplings and energetic parameters, driving force and reorganization energy, on electron transfer dynamics is similar in both structures. With respect to the alanyl-PNA structure, this result is consistent with the notion of stacking distances in the nucleobase staple similar to the one in B-DNA and thus provides additional structural evidence for nucleobase stacking in alanyl-PNA double strands.

Acridines↗
PubMed2003

[Validation of microMESAM as screening device for sleep disordered breathing].

INTRODUCTION: Polysomnography (PSG) is considered the gold standard in the diagnosis of sleep disordered breathing (SDB). Because of costs and labor-intensity it is, however, performed last in graded diagnostic protocols that often involve respiratory pressure measurements via nasal canula as an alternative sensitive method for SDB detection. MicroMESAM, a newly developed screening device based on this method, allows automated analysis of apnoeas, hypopnoeas and snoring. AIM AND METHODS: To validate the device, we first compared signal quality of MicroMESAM flow-time curves with those generated by a pneumotachograph. Then, in 50 patients suspected of having obstructive sleep apnoea, we compared MicroMESAM-generated automated analysis with manually scored results of simultaneously collected PSG data. RESULTS: MicroMESAM-generated flow-time curves correspond with pneumotachograph-generated curves in 95% of respiratory events, resulting in less 4 +/- 2% difference in respective area under the curves. MicroMESAM and PSG generated numbers of apnoeas (r = 0.99) and hypopnoea (r = 0.81), as well as AHI (r = 0.98) correlated highly, displaying mean differences in AHI of 3.8, and in 1.96 sigma interval of + 11.1 to - 3.5/h. Sensitivities and specificities for SDB were 97.3%, respective 46% at SDB-defining AHI of 5, and 100%, respective 87.5%, at SDB-defining AHI of 10. SUMMARY: MicroMESAM-generated flow-time curves correspond well with pneumotachograph generated curves, producing automated AHIs that are highly sensitive in detecting SDB. MicroMESAM, therefore, is suitable as a screening device for SDB.

Automation↗
PubMed2003

Evaluation of shoulder internal rotator muscle strength in baseball players with physical signs of glenohumeral joint instability.

OBJECTIVES: To identify whether subjects with glenohumeral translational instability present with a strength deficit in their internal rotator musculature, and therefore to determine if general strengthening exercises are warranted for the management of this condition. METHODS: Eighteen male baseball players were allocated to two groups on the basis of expert clinical evaluation of the presence (n=8) or absence (n=10) of shoulder translational instability. A strain gauge was used to calculate the force generated during maximal isometric internal rotation contractions in neutral shoulder rotation and 30 degrees of internal rotation. RESULTS: The Mann-Whitney test identified no significant difference in force production during the maximum contractions in neutral rotation between the two subject groups. In the position of 30 degrees shoulder internal rotation, subjects with glenohumeral translational instability produced significantly greater force than the control group (p<0.05). CONCLUSIONS: High load strength testing cannot be used as a diagnostic tool to identify people with glenohumeral instability. Similarly, heavy resistance strengthening exercises for the internal rotator musculature are not warranted during rehabilitation.

Adolescent↗
PubMed2002

The molecular structure of spider dragline silk: folding and orientation of the protein backbone.

The design principles of spider dragline silk, nature's high-performance fiber, are still largely unknown, in particular for the noncrystalline glycine-rich domains, which form the bulk of the material. Here we apply two-dimensional solid-state NMR to determine the distribution of the backbone torsion angles (phi,psi) as well as the orientation of the polypeptide backbone toward the fiber at both the glycine and alanine residues. Instead of an "amorphous matrix," suggested earlier for the glycine-rich domains, these new data indicate that all domains in dragline silk have a preferred secondary structure and are strongly oriented, with the chains predominantly parallel to the fiber. As proposed previously, the alanine residues are predominantly found in a beta sheet conformation. The glycine residues are partly incorporated into the beta sheets and otherwise form helical structures with an approximate 3-fold symmetry.

Animals↗
PubMed2002

Ultrafast electron transfer in the complex between fluorescein and a cognate engineered lipocalin protein, a so-called anticalin.

Anticalins are a novel class of engineered ligand-binding proteins with tailored specificities derived from the lipocalin scaffold. The anticalin FluA complexes fluorescein as ligand with high affinity, and it effects almost complete quenching of its steady-state fluorescence. To study the underlying mechanism, we have applied femtosecond absorption spectroscopy, which revealed excited-state electron transfer within the FluA*Fl complex to be responsible for the strong fluorescence quenching. On the basis of a comparison of redox potentials, either tryptophan or tyrosine may serve as electron donor to the bound fluorescein group in its excited singlet state, thus forming the fluorescein trianion radical within 400 fs. The almost monoexponential rate points to a single, well-defined binding site, and its temperature independence suggests an (almost) activationless process. Applying conventional electron transfer theory to the ultrafast forward and slower back-rates, the resulting electronic interaction is rather large, with approximately 140 cm(-1) for tyrosine, which would be consistent with a coplanar arrangement of both aromatic moieties within van der Waals distance. The weak residual steady-state fluorescence originates from a small (approximately 10%) component with a time constant in the 40-60 ps range. These results demonstrate the power of time-resolved absorption spectroscopy as a diagnostic tool for the elucidation of a fluorescence quenching mechanism and the temporal profiles of the processes involved. The high structural and dynamic definition of the complexation site suggests the anticalin FluA to be a promising model in order to tailor and probe electronic interactions and energetics in proteins.

Carrier Proteins↗
PubMed2001

Solid-state NMR data support a helix-loop-helix structural model for the N-terminal half of HIV-1 Rev in fibrillar form.

Rev is a 116 residue basic protein encoded by the genome of human immunodeficiency virus type 1 (HIV-1) that binds to multiple sites in the Rev response element (RRE) of viral mRNA transcripts in nuclei of host cells, leading to transport of incompletely spliced and unspliced viral mRNA to the cytoplasm of host cells in the latter phases of the HIV-1 life cycle. Rev is absolutely required for viral replication. Because Rev aggregates and fibrillizes in solution at concentrations required for crystal growth or liquid state NMR measurements, high-resolution structural characterization of full-length Rev has not been possible. Previously, circular dichroism studies have shown that approximately 50 % of the Rev sequence adopts helical secondary structure, predicted to correspond to a helix-loop-helix structural motif in the N-terminal half of the protein. We describe the application of solid-state NMR techniques to Rev fibrils as a means of obtaining site-specific, atomic-level structural constraints without requiring a high degree of solubility or crystallinity. Solid-state NMR measurements, using the double-quantum chemical shift anisotropy and constant-time double-quantum-filtered dipolar recoupling techniques, provide constraints on the phi and psi backbone dihedral angles at sites in which consecutive backbone carbonyl groups are labeled with (13)C. Quantitative analysis of the solid-state NMR data, by comparison with numerical simulations, indicates helical phi and psi angles at residues Leu13 and Val16 in the predicted helix 1 segment, and at residues Arg39, Arg 42, Arg43, and Arg44 in the predicted helix 2 segment. These data represent the first site-specific structural constraints from NMR spectroscopy on full-length Rev, and support the helix-loop-helix structural model for its N-terminal half.

Amino Acid Sequence↗
PubMed2001

On the apparently anomalous distance dependence of charge-transfer rates in 9-amino-6-chloro-2-methoxyacridine-modified DNA.

From previous thermal and photoinduced charge-transfer reactions in duplex DNA there is accumulative evidence for an attenuation parameter beta of the distance dependence in the range 0.6-0.8 A(-1), with the exception of one specific system exhibiting beta = 1.5 A(-1) which is reinvestigated in this paper. Femtosecond to nanosecond time-resolved pump-probe spectroscopy has been used to follow photoinduced charge-shift dynamics in DNA duplexes containing a covalently appended, protonated 9-alkylamino-6-chloro-2-methoxyacridine chromophore. This acridine derivative (X+) resides in the DNA duplex at a specific abasic site, which is highly defined as reflected in the monoexponentiality of the kinetics. In the presence of only neighboring A:T base pairs, no charge transfer occurs within the excited-state lifetime (18 ns) of the chromophore. However, the presence of a guanine nucleobase as either a nearest neighbor or with one interspersed A:T base pair does result in fluorescence quenching. In the case of nearest neighbors, the intermediate radical state X* is formed within 4 ps and decays on the 30 ps time scale. Placing one A:T base pair between the X+ and guanine slows down the forward transfer rate by 3 orders of magnitude, corresponding to an apparent beta value of >2.0 A(-1). This dramatic decrease in the rate is due to a change in charge-transfer mechanism from a (nearly) activationless to a thermally activated regime in which the forward transfer is slower than the back transfer and the X* state is no longer observed. These observations indicate that the distance dependence of charge injection in the X+-labeled DNA duplex is not solely caused by a decrease in electronic couplings but also by a concomitant increase of the activation energy with increasing distance. This increase in activation energy may result from the loss of driving force due to excited-state relaxation competing with charge transfer, or reflect distance-dependent changes in the energetics, predominantly of the low-frequency reorganization energy in this charge-shift reaction, on purely electrostatic grounds. To test the hypothesis of distance-dependent activation energy, guanine has been replaced by 7-deazaguanine, its easier-to-oxidize purine analogue. In these duplexes, a similar change of charge-transfer mechanism is found. However, consistent with an a priori larger driving force this change occurs at a larger donor-acceptor separation than in the X+-guanine systems. Independent of the detailed contributions to the distance-dependent activation energy, this phenomenon illustrates the complex nature of experimental beta values.

Aminoacridines↗
PubMed2001

In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae.

S-adenosylmethionine decarboxylase (AdoMetDC), a key enzyme in the biosynthesis of spermidine and spermine, is first synthesized as a proenzyme, which is cleaved posttranslationally to form alpha and beta subunits. The alpha subunit contains a covalently bound pyruvoyl group derived from serine that is essential for activity. With the use of an Escherichia coli overexpression system, we have purified AdoMetDCs encoded by the E. coli, Saccharomyces cerevisiae, and Salmonella typhimurium genes. Unexpectedly we found by mass spectrometry that these enzymes had been modified posttranslationally in vivo by a mechanism-based "suicide" inactivation. A large percentage of the alpha subunit of each enzyme had been modified in vivo to give peaks with masses m/z = 57 +/- 1 and m/z = 75 +/- 1 daltons higher than the parent peak. AdoMetDC activity decreased markedly during overexpression concurrently with the increase of the additional peaks for the alpha subunit. Sequencing of a tryptic fragment by tandem mass spectrometry showed that Cys-140 was modified with a +75 +/- 1 adduct, which is probably derived from the reaction product. Comparable modification of the alpha subunit was also observed in in vitro experiments after incubation with the substrate or with the reaction product, which is consistent with the in vitro alkylation of E. coli AdoMetDC reported by Diaz and Anton [Diaz, E. & Anton, D. L. (1991) Biochemistry 30, 4078-4081].

Adenosylmethionine Decarboxylase↗
PubMed2001

Computation of the viscosity of a liquid from time averages of stress fluctuations.

The shear viscosity can be calculated from the standard deviation of an equilibrium ensemble of time averages of the shear stress computed along finite duration phase space trajectory segments. The mean square of the segment averages of the shear stress is proportional to the shear viscosity and inversely proportional to the duration of the trajectory segments and the number of particles. We test the fluctuation relation for the shear viscosity and show that it provides a simple but viable means of computing the zero strain rate shear viscosity. We decompose the shear viscosity computed using this fluctuation method, into its "kinetic" and "configurational" components. We also calculate the relevant relaxation times. We compare the computed results with standard nonequilibrium molecular dynamics simulations. Finally we compute the bulk viscosity using an analogous fluctuation method.

Journal Article↗
PubMed2001

Thermophysical properties of gases, liquids, and solids composed of particles interacting with a short-range attractive potential.

A short-range polynomial interaction potential is introduced which has both a repulsive core and an attractive part. It is cut off smoothly such that its first and second derivatives vanish at the cutoff distance. The potential therefore enables efficient simulation studies of a model material that exhibits similarities to a full (but computationally expensive) classical Lennard-Jones system. Thermophysical properties of the model are calculated by (nonequilibrium) molecular dynamics computer simulations and compared with analytical results. Among the quantities studied is the pressure as a function of the density for various temperatures. Equations of state for the fluid and the solid are tested. The coexistence of gaseous, (metastable) liquid, and fcc solid phases is found for a range of temperatures. Bulk and shear moduli are computed. The response of the system to a shear deformation with a constant shear rate is analyzed. The liquid shows viscoelastic behavior that can be described with a Maxwell model. The solid behaves as an elastic medium up to a finite deformation and then undergoes a transition to plastic flow, which is stick-slip-like at small shear rates and continuous at higher ones.

Journal Article↗
PubMed2001

The reprogrammed host: Chlamydia trachomatis-induced up-regulation of glycoprotein 130 cytokines, transcription factors, and antiapoptotic genes.

OBJECTIVE: Infection with Chlamydia trachomatis is a known cause of sexually transmitted diseases, eye infections (including trachoma), and reactive arthritis (ReA). Because the mechanisms of Chlamydia-induced changes leading to ReA are poorly defined, this study sought to identify the target genes involved at the molecular level. METHODS: Chlamydia-induced changes in host cells were investigated by combining a screening technique, which utilized complementary DNA arrays on C trachomatis-infected and mock-infected epithelial HeLa cells, with real-time reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay of gene products. Some responses were additionally demonstrated on human primary chondrocytes and a human synovial fibroblast cell line, both of which served as model cells for ReA. RESULTS: Eighteen genes (of 1,176) were found to be up-regulated after 24 hours of infection with this obligate intracellular bacterium, among them the glycoprotein 130 family members IL-11 and LIF, the chemokine gene MIP2-alpha, the transcription factor genes EGR1, ETR101, FRA1, and c-jun, the apoptosis-related genes IEX-1L and MCL-1, adhesion molecule genes such as ICAM1, and various other functionally important genes. In the context of this rheumatic disease, the cytokines and transcription factors seem to be especially involved, since various connections to chondrocytes, synoviocytes, bone remodeling, joint pathology, and other rheumatic diseases have been demonstrated. CONCLUSION: Infection with C trachomatis seems to reprogram the host cells (independent of activation by lipopolysaccharide or other ultraviolet-resistant bacterial components) at various key positions that act as intra- or intercellular switches, suggesting that these changes and similar Chlamydia-induced functional alterations constitute an important basis of the pathogenic inflammatory potential of these cells in ReA. Our results suggest that this approach is generally useful for the broad analysis of host-pathogen interactions involving obligate intracellular bacteria, and for the identification of target genes for therapeutic intervention in this rheumatic disease.

Apoptosis↗
PubMed2001

Effect of an adenosine A(1) receptor agonist and a novel pyrimidoindole on membrane properties and neurotransmitter release in rat cortical and hippocampal neurons.

Activation of adenosine A(1) receptors by endogenous adenosine plays a neuroprotective role under various pathophysiological conditions including hypoxia. Intracellular recordings were made in rat pyramidal cells of the somatosensory cortex. Hypoxia (5 min) induced a membrane depolarization and a decrease of input resistance. The A(1) receptor agonist N(6)-cyclopentyladenosine (CPA, 100 microM) reversibly inhibited the hypoxic depolarization. The inhibition was also present after blockade of the A(2A), A(2B) and A(3) receptor subtypes by selective antagonists. CPA had no effect on the hypoxic decrease of input resistance. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a selective A(1) receptor antagonist, which did not alter hypoxic depolarization when given alone abolished the inhibitory effect of CPA. Neither CPA nor DPCPX influenced membrane potential or apparent input resistance under normoxic conditions. The novel pyrimidoindole (R)-9-(1-methylbenzyl)-2-(4'-pyridyl)-9H-pyrimido[4,5-b]indole-4-amine (APPPI, 1 and 10 microM) reversibly diminished hypoxic depolarization but had no significant effect on input resistance. The effect of APPPI at a concentration of 1 microM, but not at 10 microM, was blocked by DPCPX (0.1 microM). CPA (100 microM) inhibited [(3)H]-noradrenaline ([(3)H]-NA) release from rat hippocampal brain slices significantly only in the presence of rauwolscine (0.1 microM), an alpha(2)-adrenoceptor antagonist. APPPI (1 and 10 microM) exhibited an inhibitory effect similar to that observed with CPA. The effects of both CPA and APPPI were antagonized by DPCPX (0.1 microM). The present data suggest that mainly presynaptic mechanisms prevent neurons from hypoxic changes by an inhibition of transmitter release. However, in contrast to CPA, APPPI exhibited additional effects, which require further investigation.

Adenosine↗
PubMed2001

Rapid and sensitive LC separation of new impurities in trimethoprim.

Trimethoprim is a chemotherapeutic often used in combination with sulfonamides. Herein, we report on the development and validation of a new HPLC assay of trimethoprim. The test allows the identification of new impurities that have not been detectable with any other known method including European Pharmacopoeia and USP. Trimethoprim and its impurities were eluted on a C18 column with a mobile phase consisting of methanol and a solution of sodium perchlorate at a flow rate of 1.3 ml/min and was quantified by UV detection at 280 nm. Overall, the method is simple, rapid and reliable for the detection of six impurities in trimethoprim batches.

Anti-Infective Agents, Urinary↗