Chromia Scale Thermally Grown on Pure Chromium Under Controlled <Emphasis Type=Italic>p</Emphasis>(O<Subscript>2</Subscript>) Atmosphere: II—Spallation Investigation Using Photoelectrochemical Techniques at a Microscale

Pure chromium oxidized at 900 °C at low oxygen partial pressure (10^?12 atm) gives duplex Cr₂O₃ scale with an internal part made of equiaxed grains and exhibiting an n-type conduction, and an external part made of columnar grains and exhibiting a p-type conduction. Spalled regions occurring during cooling have been studied with photoelectrochemical techniques at a microscale. New information in the form of a specific image (structural quality image) could be obtained and revealed a level of structural defect density in the internal chromia subscale higher than that measured in the non-spalled region. The results complement the spallation scenario proposed in part I of this work.     

Expanding the Spectrum of Antibiotics Capable of Killing Multidrug-Resistant Staphylococcus aureus and Pseudomonas aeruginosa

Infections from antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial-resistant (AMR) pathogens, 600-Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β-lactam antibiotics against Gram-positive bacteria. BPEI binds cell-wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. This study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram-positive pathogens but not Gram-negative bacteria. 600-Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non-β-lactam co-drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL-8 by human epithelial keratinocytes. This enables BPEI to function as a broad-spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care.     

Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase

The four isomers of 4-aminopyrrolidine-2,4-dicarboxylate (APDC) were prepared and evaluated for their effects at glutamate receptors in vitro. (2R,4R)-APDC (2a), an aza analog of the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R)-ACPD, 1), was found to possess relatively high affinity for metabotropic glutamate receptors (mGluRs) (ACPD-sensitive [3H]glutamate binding IC50 = 6.49 +/- 1.21 microM) with no effects on radioligand binding to NMDA, AMPA, or kainate receptors up to 100 microM. None of the other APDC isomers showed significant mGluR binding affinity, indicating that this interaction is highly stereospecific. Both 1 and 2a were effective in decreasing forskolin-stimulated cAMP formation in the adult rat cerebral cortex (EC50 = 8.17 +/- 2.21 microM for 1; EC50 = 14.51 +/- 5.54 microM for 2a); however, while 1 was also effective in stimulating basal tritiated inositol monophosphate production in the neonatal rat cerebral cortex (EC50 = 27.7 +/- 5.2 microM), 2a (up to 100 microM) was ineffective in stimulating phosphoinositide hydrolysis in this tissue preparation, further supporting our previous observations that 2a is a highly selective agonist for mGluRs negatively coupled to adenylate cyclase. Microelectrophoretic application of either 1 or 2a to intact rat spinal neurons produced an augmentation of AMPA-induced excitation (95 +/- 10% increase for 1, 52 +/- 6% increase for 2a). Intracerebral injection of 1 (400 nmol) produced characteristic limbic seizures in mice which are not mimicked by 2a (200-1600 nmol, ic). However, the limbic seizures induced by 1 were blocked by systemically administered 2a in a dose-dependent manner (EC50 = 271 mg/kg, ip). It is concluded that (2R,4R)-APDC (2a) is a highly selective, systemically-active agonist of mGluRs negatively coupled to adenylate cyclase and that selective activation of these receptors in vivo can result in anticonvulsant effects.     

Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.     

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes

Twenty-two cases of ameloblastoma and ten cases of adenomatoid odontogenic tumour (AOT) were analyzed comparatively by the AgNOR technique. Ameloblastomas were distributed into three groups according to their clinical behaviour: primary lesions without recurrences (PLWTR), 5 cases; primary lesions with recurrences (PLWR), 4 cases; and recurrences, 13 cases. The cases were also regrouped according to their histological pattern: follicular (9 cases), plexiform (7 cases), acanthomatous (4 cases) and unicystic (2 cases). Considering histological patterns, there was a significant statistical difference only between follicular and plexiform types. There were no significant differences between the group of ameloblastomas and the group of AOTs or between the three groups of ameloblastomas with different clinical behaviour. Our results strongly suggest that the distinct clinical behaviour of ameloblastomas and AOT is not correlated with their cellular proliferation ratio. Thus, the infiltrative ability of the ameloblastomas is probably not related to the cellular proliferation index of these tumours.     

A study of the diagnostic accuracy and reliability of the Scoliometer and Adam's forward bend test

STUDY DESIGN: Study of the diagnostic accuracy and interexaminer reliability of scoliosis diagnostic tests. OBJECTIVES: To estimate the sensitivity, specificity, and predictive value of the Scoliometer (National Scoliosis Foundation, Watertown, MA) and Adam's forward bend test in diagnosing scoliosis, and to determine the interexaminer reliability of the Scoliometer and Adam's forward bend test. SUMMARY OF BACKGROUND DATA: Exposure to diagnostic radiation in patients with adolescent idiopathic scoliosis may result in a small but significant increase in cancer rates. The full-spine radiographic examination remains the standard procedure for the assessment of scoliosis. There is a need for a valid and reliable noinvasive test to assess scoliosis. METHODS: Two examiners independently assessed 105 patients presenting to a scoliosis clinic for trunk asymmetry with Adam's forward bend test and axial trunk rotation with the Scoliometer. The Cobb method served as the gold standard. RESULTS: The interexaminer agreement for the Scoliometer is excellent in the thoracic spine and substantial in the lumbar spine. The interexaminer measurement error shows poor precision for thoracic and lumbar Scoliometer measurements. The interexaminer agreement for Adam's forward bend test is substantial in the thoracic spine and poor in the lumbar spine. Adam's forward bend test is more sensitive than the Scoliometer in detecting thoracic curves measuring 20 degrees or more by the Cobb method. Receiver operating characteristic curve analysis suggests that the use of the Scoliometer marginally improves the ability of diagnosing a scoliosis in the thoracic spine. CONCLUSIONS: The Scoliometer and Adam's forward bend tests have adequate interexaminer reliability for the assessment of thoracic curves. The Scoliometer has better interexaminer agreement in the lumbar spine. However, the Scoliometer has a high level of interexaminer measurement error that limits its use as an outcome instrument. Because Adam's forward bend test is more sensitive than the Scoliometer, the authors believe that it remains the best noninvasive clinical test to evaluate scoliosis.     

Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant antibodies

Growing evidence suggests that recombinatorial events prior to antigen contact can generate pathogenic autoantibodies in the nonautoimmune individual, thus providing potential disease mediators if conditions arise that permit bypass of tolerance and activation of autoreactive lymphocytes. To examine the disease potential of selected germline antibody genes, Ig were created de novo by in vitro recombination of Ig H and L chains. H chain loss variant (i.e., L-chain only) cell lines were transfected with a DNA construct encoding the variable region and regulatory sequences (LamH) of a nephrotropic murine lupus anti-laminin Ig, and the resultant Ig were examined for in vitro antigen reactivity and in vivo glomerular immune deposition. The results indicate that two light chains, LamL (Vk8, Jk5) and 238L (Vk4, Jk5), expressing unrelated germline V1 genes, combine with LamH to generate Ig that bind basement membrane laminin in vitro, diverge in their capacity to bind ssDNA, and produce two distinct patterns of glomerular immune deposits in vivo: dense mesangial matrix (LamH/LamL) and dramatic linear glomerular basement membrane (LamH/238L) deposits. The Ig genes used by both LamH and 238L are present in nonautoimmune mice as well as in lupus-prone strains. We conclude that certain unmutated Ig genes can contribute to multiple distinct disease associated specificities, including binding to intrinsic kidney antigens, and that mutation is not essential to generate these Ig. Collectively, these observations suggest that pathogenic autoantibodies can be generated in the normal preimmune repertoire by random recombinatorial and somatic events in the absence of mutation.     

Influence of Hydrogen and Water Vapour on the Kinetics of Chromium Oxide Growth at High Temperature

In support of the selection of structural materials for heat exchangers in helium-cooled high temperature reactors, the oxidation behaviour of the Ni-base chromia-former alloy 230 was investigated at 850 °C in diluted helium atmosphere with a low water vapour content. In such a media, the equivalent partial pressure of oxygen (imposed by the $ P_{{{\text{H}}_{2} {\text{O}}}} $ / $ P_{{{\text{H}}_{2}}} $ ratio) is very low ( $ P_{{{\text{O}}_{ 2} }}^{\text{eq}} $ around 10^?16 Pa). The equivalent partial pressure of oxygen has no straight influence on the parabolic rate constant (k _p); on the other hand, $ P_{{{\text{H}}_{2} }} $ and $ P_{{{\text{H}}_{2} {\text{O}}}} $ demonstrate a complex influence on k _p. Photoelectrochemistry analyses revealed that this oxide could simultaneously contain two types of cationic defects. Specific oxidation tests with D₂O showed that the oxide scale also contains hydrogen. A mechanist model is proposed in order to describe the scale growth using both cationic defects. Those theoretical results show, at least qualitatively, how $ P_{{{\text{H}}_{2} }} $ and $ P_{{{\text{H}}_{2} {\text{O}}}} $ may concurrently influence the oxidation rate.     

Bis‐(1,2,3,4‐tetrahydroisoquinolinium): A Chiral Scaffold for Developing High‐Affinity Ligands for SK Channels

N‐Methyl‐bis‐(1,2,3,4‐tetrahydroisoquinolinium) analogues derived from AG525 (1,1′‐(propane‐1,3‐diyl)‐bis‐(6,7‐dimethoxy‐2‐methyl‐1,2,3,4‐tetrahydroisoquinoline)) stereoisomers and tetrandrine, a rigid bis‐(1,2,3,4‐tetrahydroisoquinoline) analogue with an S,S configuration, were synthesized and tested for their affinity for small‐conductance calcium‐activated potassium channel (SK/K_Ca2) subtypes using radioligand binding assays. A significant increase in affinity was observed for the quaternized analogues over the parent 1,2,3,4‐tetrahydroisoquinoline compounds. Interestingly, the impact of stereochemistry was not the same in the two groups of compounds. For quaternized analogues, affinities of S,S and R,R isomers for SK2 and SK3 channels were similar and in both cases higher than that of the meso derivative. Among the bis‐tetrahydroisoquinoline compounds, the S,S isomers exhibited high affinity, while the R,R and meso isomers had similarly lower affinities. Furthermore, the SK2/SK3 selectivity ratio was slightly increased for quaternized analogues. Bis‐(1,2,3,4‐tetrahydroisoquinolinium) represents a new scaffold for the development of high‐affinity ligands for SK channel subtypes.