gebhart/patrepeval huggingface dataset:
[On the pharmacodynamics of acemetacin (author's transl)]. (1980)

Pharmacodynamic studies were carried out on (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]acetic acid (acemetacin, TV 1322, Rantudil), a new strongly acting non-steroidal anti-inflammatory agent for elucidation of its mechanism of action. Despite its strong anti-inflammatory activity, acemetacin is only a weak inhibitor of prostaglandin release. Release of histamine from mast cells induced by N-methylhomoanisylamine-formaldehyde condensate (compound 48/80) was strongly inhibited by acemetacin in a dose dependent manner. It was also highly effective in in vitro tests, for example, in the protein turbidity test of Mizushima. In accordance to the weak inhibition of prostaglandin release very little damage was done to the mucous membrane of the gastrointestinal tract by this anti-inflammatory agent. From these data and from the strong anti-inflammatory activity a broad therapeutic margin can be derived. Analgetic properties were shown in the benzoquinone test after oral and in the Randall-Selitto test after i.m. application. Hyperthermia caused by Pyrifer and by yeast is inhibited by acemetacin in a dose dependent manner. Corresponding to the weak influence on prostaglandin release the reduction of diuresis by acemetacin was only small. No tocolytic effect could be detected on the gravid uterus in vitro. Function of the heart (isolated heart of guinea-pig) was unaffected, but we registered an increase in sytolic and diastolic blood pressures in the anesthetized dog. Correspondingly, left ventricular pressure also increased, these changes were accompanied by bradycardia. Coronary flow, peripheral flow and dp/dt did not change, only the pressure in the right atrium rose slightly. In cats, acemetacin caused a short-lasting decrease in the arterial blood pressure. Effects on CNS were not found. Smooth muscles (bronchial/intestinal) were not influenced by acemetacin. Like many non-steroidal anti-inflammatory compounds acemetacin inhibits also platelet aggregation. Motility of animals was lowered. In a granuloma pouch test a strong anti-inflammatory action was shown in vivo even without metabolic degradation of acemetacin. For the explanation of the anti-inflammatory action several mechanisms have to be taken into account.
Sialyl Lewis(x) oligosaccharide reduces ischemia-reperfusion injury in the rabbit ear (1995)

Ischemia-reperfusion injury in the rabbit ear is neutrophil (PMN)-mediated, and is significantly reduced by anti-adhesion agents directed against beta 2 integrins, P-selectin, or L-selectin. We further examined selectin-mediated adherence in this setting following the administration of soluble sialyl Lewis(x) (SLe(x)), the principal carbohydrate ligand for P-, L-, and E-selectin, at various times following reperfusion. Under constant ambient temperature conditions, the rabbit ear vascular supply was isolated and occluded with an atraumatic vascular clamp for 6 h, then allowed to reperfuse. Animals receiving i.v. SLe(x) (25 mg/kg bolus + 50 mg/kg infusion over 10 h) 1) at the time of reperfusion, 2) 1 h after reperfusion, 3) 4 h after reperfusion, or 4) 12 h after reperfusion were compared with control animals receiving either saline or sialyl lactosamine, an oligosaccharide structurally similar to SLe(x) but not involved in selectin recognition. Tissue injury was assessed by serial measurement of ear edema and by visual determination of ear necrosis over 7 days. Tissue edema and necrosis were significantly reduced in animals treated with SLe(x) immediately upon reperfusion or after a 1-h delay, but not in animals for whom SLe(x) administration was delayed by 4 or 12 h. Furthermore, SLe(x) administration alone had no effect on circulating leukocyte or PMN counts, or PMN expression of CD18 or L-selectin. We conclude that interruption of selectin-mediated adherence with soluble SLe(x) oligosaccharide attenuates reperfusion in the rabbit ear. The observation that SLe(x) is efficacious only if administered in the first hour after reperfusion suggests that the more immediately available P- and L-selectin participate in this PMN adhesion/injury process, whereas E-selectin, with its delayed endothelial expression, does not.
Gastric Retentive Drug-Delivery Systems (1998)

The development of a long-term oral controlled-release dosage form has been difficult mainly because of the transit of the dosage form through the gastrointestinal (GI) tract. Several approaches to extend gastric residence time have been tried. The most commonly used systems are (1) intragastric floating systems, (2) high-density systems, (3) mucoadhesive systems, (4) magnetic systems, (5) unfoldable, extendible, or swellable systems, and (6) superporous hydrogel systems. The concept of each approach is examined, and improvements that are needed for further development are discussed. Background materials in the GI physiology that are necessary for understanding the concept and usefulness of each approach are also provided.
Classification, epidemiology, risk factors, and natural history of peripheral arterial disease (2002)

Peripheral arterial disease (PAD) is a clinical condition that has often been neglected. The clinical diagnosis of PAD may be made on the basis of an accurate history by using the WHO/Rose Questionnaire or the Edinburgh Questionnaire. From a clinical point of view, PAD may be classified into four stages. The PARTNERS Programme (PAD Awareness, Risk and Treatment: NEw Resources for Survival) is a recent study based on a partnership to improve PAD care. In this population, the prevalence of patients who were PAD+/CVD- was approximately 12% in males and 15% in females; PAD+/CVD+ approximately 18% in males and 14% in females; PAD-/CVD+ 28% in males and 17% in females; and finally, patients without vascular disease (PAD-/CVD-) 42% in males and 54% in females. The lessons derived from the PARTNERS Programme Study were informative; PAD is detectable in routine practice, using a simple, inexpensive, always available, clinical test such as calculation of the ankle-brachial pressure index (ABPI). Fewer than half of individuals with PAD are aware of their condition, while physicians are unaware of the presence of PAD in 70% of their patients with the condition. Diabetics and smokers are at high risk for PAD. Diabetes is present in about 41% of patients with PAD and a history of smoking (> 10 pack for year) is present in over 63% of patients with PAD. Antiplatelet therapy is taken by only about half of patients with PAD. Finally, the lack of diagnosis and treatment means that PAD patients remain at elevated risk of heart attack and stroke. Efforts must be made to diffuse this information to improve the diagnosis and treatment of PAD to reduce the risk of future fatal and nonfatal cardiac and cerebrovascular events.
SalmonellaInteractions with Plants and Their Associated Microbiota (2013)

The increase in the incidence of gastroenteritis outbreaks linked to the consumption of foods of plant origin has ignited public concern and scientific interest in understanding interactions of human enteric pathogens with plants. Enteric disease caused by nontyphoidal Salmonella is a major public health burden, with the number of cases of illness linked to fresh produce, spices, and nuts surpassing those linked to foods of animal origin. Mounting evidence supports the hypothesis that colonization of plants is an important part of the life cycle of this human pathogen. Although plant responses to human pathogens are distinct from the more specific responses to phytopathogens, plants appear to recognize Salmonella, likely by detecting conserved microbial patterns, which subsequently activates basal defenses. Numerous Salmonella genes have been identified as playing a role in its colonization of plant surfaces and tissues, and in its various interactions with other members of the phyto-microbial community. Importantly, Salmonella utilizes diverse and overlapping strategies to interact with plants and their microflora, and to successfully colonize its vertebrate hosts. This review provides insight into the complex behavior of Salmonella on plants and the apparent remarkable adaptation of this human pathogen to a potentially secondary host.
Particle Size Determinants in the Human Immunodeficiency Virus Type 1 Gag Protein (1998)

The retroviral Gag protein plays the central role in the assembly process and can form membrane-enclosed, virus-like particles in the absence of any other viral products. These particles are similar to authentic virions in density and size. Three small domains of the human immunodeficiency virus type 1 (HIV-1) Gag protein have been previously identified as being important for budding. Regions that lie outside these domains can be deleted without any effect on particle release or density. However, the regions of Gag that control the size of HIV-1 particles are less well understood. In the case of Rous sarcoma virus (RSV), the size determinant maps to the CA (capsid) and adjacent spacer sequences within Gag, but systematic mapping of the HIV Gag protein has not been reported. To locate the size determinants of HIV-1, we analyzed a large collection of Gag mutants. To our surprise, all mutants with defects in the MA (matrix), CA, and the N-terminal part of NC (nucleocapsid) sequences produced dense particles of normal size, suggesting that oncoviruses (RSV) and lentiviruses (HIV-1) have different size-controlling elements. The most important region found to be critical for determining HIV-1 particle size is the p6 sequence. Particles lacking all or small parts of p6 were uniform in size distribution but very large as measured by rate zonal gradients. Further evidence for this novel function of p6 was obtained by placing this sequence at the C terminus of RSV CA mutants that produce heterogeneously sized particles. We found that the RSV-p6 chimeras produced normally sized particles. Thus, we present evidence that the entire p6 sequence plays a role in determining the size of a retroviral particle.
Isotachophoretic Determination of Urea-Ammonium in Plasma: A Candidate Reference Method (1990)

Separation and determination of sample constituents by capillary isotachophoresis are entirely based on physical phenomena. The method has therefore been proposed as a universal reference method for ionic constituents. The present paper shows that even neutral species can be adequately determined after suitable preceding reactions. Urea was completely hydrolysed by urease (EC 3.5.1.5) to ammonia and bicarbonate, followed by direct measurement of the ammonium ion concentration by capillary isotachophoresis. Standard Reference Material No. 912a urea (National Bureau of Standards) was used as a primary standard. The analytical linear range of the method extends to 64 mmol urea per litre. The precision of the method was in the range of 1.05-2.64% (CV) and the analytical recovery of added urea was excellent (99.4%, SD 1.13%). Further proof of accuracy was obtained by analysing the NBS human reference serum (standard reference material 909). The mean result by the capillary isotachophoretic method, 9.52 +/- 0.085 mmol/l, agrees well with the reference value, 9.64 mmol/l. The results obtained by capillary isotachophoresis showed good agreement with those obtained by the coupled-enzyme method (r = 0.995).
Reconstruction of ribosomal subunits and rDNA chromatin imaged by scanning force microscopy (1996)

Scanning force microscopy (SFM) reveals surface topography by scanning a sharp tip in close proximity to the sample. Due to tip–sample interaction, artificial broadening of the real surface structure with the tip geometry occurs. One approach for image reconstruction is the use of calibration standards, preferably in the size range of the samples. In the present study, an image reconstruction method based on colloidal gold as a geometric standard was used to reconstruct SFM images of biomolecules. Sample and calibration standard size were in the nanometer range, and the standards were coadsorbed with the specimen. Raw and reconstructed images of the biomolecules were compared, and the reconstruction was characterized by difference images as well as determination of the difference volume. The application of image reconstruction based on colloidal gold as a calibration standard for SFM of biomolecules is discussed.
Late administration of monoclonal antibody to leukocyte function‐antigen 1 abrogates incipient murine cerebral malaria (1991)

We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.
Enantioselective Catalytic Aziridinations and Asymmetric Nitrene Insertions into CH Bonds (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantioselective Catalytic Aziridinations and Asymmetric Nitrene Insertions into CH BondsPaul Müller and Corinne FruitView Author Information Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland Cite this: Chem. Rev. 2003, 103, 8, 2905–2920Publication Date (Web):June 26, 2003Publication History Received21 January 2003Published online26 June 2003Published inissue 1 August 2003https://pubs.acs.org/doi/10.1021/cr020043thttps://doi.org/10.1021/cr020043tresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views13869Altmetric-Citations1030LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aziridines,Catalysts,Hydrocarbons,Ligands,Stereoselectivity Get e-Alerts
Impact of CpG methylation on structure, dynamics and solvation of cAMP DNA responsive element (2001)

Methylation of CpG motifs in DNA is involved in the control of gene expression and in several other epigenic effects. It suppresses also the immuno-stimulation properties of bacterial or viral DNAs that contain CPGS: However, effects of methylation on the DNA structure and dynamics are not clear. Here we carried out a 10 ns MD simulation, confronted to an NMR analysis, of a hexadecanucleotide with the cAMP responsive element (CRE) DNA methylated at its center: d(GAGATGAmCGTCATCTC)(2) (CREmet). Methylation does not introduce significant structure modification but reduces the dynamics. Molecular mechanics and generalized Born solvation energy calculations showed that the stiffness of CREmet arises from both a restriction of the conformational space by the bulky methyl groups and a folding of DNA around the hydrophobic methyls. The latter effect is favored when the GpA steps belonging to the TGA binding half-sites adopt the BII conformation. The inability of the methylated DNAs to interact with their protein partners-either transcription factors for gene regulation or a Toll-like receptor for immunostimulation-could result from both the obstacle created by methyls, preventing crucial interactions, and the loss of DNA flexibility, reducing its adaptability. Results are discussed in the light of NMR and crystallographic data.
Branhamella catarrhalis septic arthritis. (1983)

An adult with spontaneous septic arthritis due to Branhamella catarrhalis is described and the literature reviewed. B. catarrhalis is an organism similar to the Neisseria species and has been implicated in a variety of systemic infections. As it is frequently resistant to penicillin, cephamycins or third generation cephalosporins may be the empiric drugs of choice for infections caused by this organism.
Interaction of A2E with Model Membranes. Implications to the Pathogenesis of Age-related Macular Degeneration (2002)

Deposition of a fluorophoric material, known as lipofuscin, in retinal pigment epithelium cells has been speculated to be one of the biomarkers of age-related macular degeneration. One of the fluorophores of lipofuscin has been characterized as A2E, a pyridinium bisretinoid. Its cationic nature along with two hydrophobic retinal chains suggests that it can disrupt the membrane integrity by its detergent-like activity and can thus cause cellular damage. With this notion, we studied in detail the interaction between A2E and the model membranes of different lipid compositions using fluorescence steady-state and fluorescence anisotropy measurements. A transition from vesicular to micellar structure occurred upon incorporation of A2E into the lipid bilayer. However, the A2E concentration at which this transition occurred depends on the lipid composition. A lipid mixture containing 10% phosphatidylserine (PS) (close to disc membrane PS content) behaved similarly to a lipid mixture having no PS. In contrast, vesicles containing 20% PS showed significantly different behavior. Membrane solubilization by A2E was also confirmed by vesicle leakage experiments. A2E also showed significant activity in liposome-mediated gene transfection. A lipid formulation containing 40% A2E and a helper lipid showed plasmid DNA transfection efficiency comparable to commercially available transfection reagents with no evidence of cytotoxicity. These results contribute to understanding the mechanism underlying the A2E-induced cellular dysfunction.
Ultrasensitive and ultrathin phototransistors and photonic synapses using perovskite quantum dots grown from graphene lattice (2020)

Organic-inorganic halide perovskite quantum dots (PQDs) constitute an attractive class of materials for many optoelectronic applications. However, their charge transport properties are inferior to materials like graphene. On the other hand, the charge generation efficiency of graphene is too low to be used in many optoelectronic applications. Here, we demonstrate the development of ultrathin phototransistors and photonic synapses using a graphene-PQD (G-PQD) superstructure prepared by growing PQDs directly from a graphene lattice. We show that the G-PQDs superstructure synchronizes efficient charge generation and transport on a single platform. G-PQD phototransistors exhibit excellent responsivity of 1.4 × 10<sup>8</sup> AW<sup>-1</sup> and specific detectivity of 4.72 × 10<sup>15</sup> Jones at 430 nm. Moreover, the light-assisted memory effect of these superstructures enables photonic synaptic behavior, where neuromorphic computing is demonstrated by facial recognition with the assistance of machine learning. We anticipate that the G-PQD superstructures will bolster new directions in the development of highly efficient optoelectronic devices.
Precise Dental Implant Placement in Bone Using Surgical Guides in Conjunction With Medical Imaging Techniques (2000)

The use of medical imaging techniques to make a very precise surgical guide for implant placement is described. This template is the combination of a currently used template and a very simple mechanical system designed to transfer a preoperatively defined implant position onto the surgical site. With the planning software, the practitioner determines the implant position according both to the ideal position dictated by the final restorative prosthesis and the available volume of bone. The surgical template then communicates the actual implant position to the surgical site. The template can be used not only in critical anatomical situations but also in placing the implant in an ideal position on bone because it eliminates possible manual placement errors and matches planning to prosthetic requirements.
Holins kill without warning (2001)

Holins comprise the most diverse functional group of proteins known. They are small bacteriophage-encoded proteins that accumulate during the period of late-protein synthesis after infection and cause lysis of the host cell at a precise genetically programmed time. It is unknown how holins achieve temporal precision, but a conserved feature of their function is that energy poisons subvert the normal scheduling mechanism and instantly trigger membrane disruption. On this basis, timing has been proposed to involve a progressive decrease in the energized state of the membrane until a critical triggering level is reached. Here, we report that membrane integrity is not compromised after the induction of holin synthesis until seconds before lysis. The proton motive force was monitored by the rotation of individual cells tethered by a single flagellum. The results suggest an alternative explanation for the lysis "clock," in which holin concentrations build to a critical level that leads to formation of an oligomeric complex that disrupts the membrane.
Compression Forces of Internal and External Ankle Fixation Devices with Simulated Bone Resorption (2010)

Surgeons who perform TTC arthrodesis procedures should be aware of a device's ability to generate and sustain compression with respect to bone resorption.