Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs

PURPOSE: We report an investigation into the distribution of proteoglycans (PGs) in normal, organ-cultured and dextran-treated human corneas. METHODS: Immunogold labeling was carried out at the electron microscope level to localize keratan sulphate (KS), chondroitin sulphate (CS), and heparan sulphate (HS) PGs. RESULTS: High levels of labeling for CS was found in the epithelium, endothelium, and keratocytes, with light labelling present in the basement membranes and the corneal stroma. Labeling for HS was present in the epithelium, endothelium, and keratocytes, with intense labeling present at the endothelium/Descemet's membrane interface and the epithelium/Bowman's layer interface. Large filaments were also observed in these regions in cuprolinic blue-stained specimens. Keratan sulphate was present at high levels in the stroma and the basement membranes with low levels present within the keratocytes, epithelium, and endothelium. The pattern of KS labeling along the collagen fibrils in the stroma sometimes showed evidence of periodicity. Organ-cultured corneas had extensive collagen-free "lakes," the interior of which immunolabeled positively for KS and showed staining with cuprolinic blue. The lakes were greatly reduced in the dextran-treated samples. CONCLUSION: This investigation determined the ultrastructural distribution of KS, CS, and HS PGs in human cornea and showed that organ culture is associated with a change in distribution of stromal PGs.     

Speech perception performance in experienced cochlear-implant patients receiving the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant

Sixteen experienced cochlear implant patients with a wide range of speech-perception abilities received the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant. Speech perception was assessed in quiet and in noise with SPEAK and with the patients' previous strategies (for most, Multipeak) at the study onset, as well as after using SPEAK for 6 months. Comparisons were made within and across the two test sessions to elucidate possible learning effects. Patients were also asked to rate the strategies on seven speech recognition and sound quality scales. After 6 months' experience with SPEAK, patients showed significantly improved mean performance on a range of speech recognition measures in quiet and noise. When mean subjective ratings were compared over time there were no significant differences noted between strategies. However, many individuals rated the SPEAK strategy better for two or more of the seven subjective measures. Ratings for "appreciation of music" and "quality of my own voice" in particular were generally higher for SPEAK. Improvements were realized by patients with a wide range of speech perception abilities, including those with little or no open-set speech recognition.     

Determination of fat in olestra-containing savory snack products by capillary gas chromatography

A quantitative method to determine fat in olestra-containing savory snack products was validated within the AOAC Peer-Verified Methods Program. The method may be used to demonstrate compliance with the guidelines of the U.S. Nutrition Labeling and Education Act for labeling products as "fat free" or "low fat." The method can measure total and saturated fat in savory snacks when present at levels of 0.2-10 g total fat and 0.1-3 g saturated fat per 30 g serving. The method is standardized to measure C6-C24 fatty acids. Extraction of olestra-containing savory snack samples with chloroform-methanol (modified AOAC Official Method 983.23) yields a lipid extract containing the total fat and olestra. The extracted lipid is hydrolyzed by lipase, yielding fatty acids and unreacted olestra. The fatty acids are precipitated as calcium soaps. Olestra is extracted from insoluble soaps with hexane and then discarded. The isolated soaps are converted back into fatty acids with hydrochloric acid and extracted with hexane. The isolated fatty acids are converted to methyl esters with boron trifluoride-methanol and quantitated by capillary gas chromatography using internal standard. Test samples were prepared by blending olestra-containing and full-fat (triglyceride) snacks to obtain 6 levels of spiking (0-10 g total fat added/30 g serving) in potato chips, potato crisps, cheese puffs, and nacho cheese-flavored corn chips. Results were linear (r2 > 0.997) between 0 and 10 g fat/30 g serving for each product matrix. Mean recovery was 101 +/- 6% standard deviation (SD) for total fat and 104 +/- 6% SD for saturated fat. Mean recovery by peer laboratory was 88 +/- 5% SD for total fat and 95 +/- 4% SD for saturated fat in potato chips (0-3 g total fat added/30 g serving). Two sets of 10 replicates of potato chips (0.5 g total fat/30 g serving and 0.16 g saturated fat/30 g serving) and potato crisps (0.5 g total fat/30 g serving and 0.16 g saturated fat/30 g serving) were analyzed by submitting and peer laboratories. Repeatability relative standard deviations ranged from 3.90 to 7.33% for total fat and from 4.01 to 11.53% for saturated fat. Reproducibility relative standard deviations were 7.33% (total fat, potato chips), 7.15% (total fat, potato crisps), 11.36% (saturated fat, potato chips), and 13.50% (saturated fat, potato crisps).     

Comparison of CT and MR imaging in staging of neck metastases

OBJECTIVE: To determine whether adaptive cytoprotection exists in human intestinal cells under in vitro conditions and what role, if any, endogenous prostaglandins or calcium may play in mediating this protective response. SUMMARY BACKGROUND DATA: Adaptive cytoprotection can be defined as that process whereby the administration of a low concentration of a damaging agent, termed a "mild irritant," which by itself is not injurious, can attenuate gastrointestinal mucosal injury subsequently induced by the application of higher concentrations of the same or other necrotizing agents. Despite substantial investigation, the mediator or mediators of adaptive cytoprotection remain poorly understood. METHODS: Postconfluent Caco-2 cells were used in all experiments. Cellular death was quantitated using a dual-component fluorescent assay. Changes in intracellular calcium concentration were quantitated by measuring fluorescent signal changes of the single wavelength calcium indicator (Fluo-3). Finally, prostaglandin E2 release into the media was quantitated by radioimmunoassay. RESULTS: Pretreatment of Caco-2 cells with low concentrations of ethanol (mild irritant) significantly attenuated injury induced by higher damaging concentrations of ethanol. The protection conferred by the mild irritant was directly dependent on both the concentration of the irritant used and the duration of exposure and was abrogated when cells were pretreated with an endogenous prostaglandin inhibitor (indomethacin) or if the mild irritant was administered in calcium-free media. Cells exposed to ethanol had a significant and concentration-dependent increase in intracellular calcium concentration, an effect that was highly related to cellular injury. Pretreatment with a mild irritant significantly decreased intracellular calcium increases induced by not only ethanol but also by a calcium ionophore (A23187). Cells treated with low concentrations of ethanol demonstrated no significant elevation in prostaglandin E2 release. CONCLUSIONS: Adaptive cytoprotection induced by ethanol exists in human colonocytes under in vitro conditions independent of mucosal blood flow, neural innervation, or circulating humoral factors. The authors' data suggest that this response does not require endogenous prostaglandin synthesis but may involve processes whereby intracellular calcium accumulation is prevented.     

Periodic orbits: a new language for neuronal dynamics

A new nonlinear dynamical analysis is applied to complex behavior from neuronal systems. The conceptual foundation of this analysis is the abstraction of observed neuronal activities into a dynamical landscape characterized by a hierarchy of "unstable periodic orbits" (UPOs). UPOs are rigorously identified in data sets representative of three different levels of organization in mammalian brain. An analysis based on UPOs affords a novel alternative method of decoding, predicting, and controlling these neuronal systems.     

The incidence of drug-related problems as a cause of hospital admissions in children

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.     

Longitudinal assessment of inpatient use and functioning of seriously mentally ill veterans with and without co-occurring substance use disorders

Within a fungal species, a subset of individuals may have more than the minimal complement of chromosomes. If the extra chromosomes are composed primarily of DNA not found in all representatives of the species, they are most appropriately referred to as supernumerary chromosomes. The patterns of repeated DNA sequences on certain supernumerary chromosomes suggest that they have a different evolutionary history from the essential chromosomes in the same genome. Supernumerary chromosomes can carry functional genes and, in at least two fungal species, genes on such chromosomes play important roles in host-pathogen interactions. Supernumerary chromosomes that confer an adaptive advantage in certain habitats, such as the ability to cause disease on a specific host, may be referred to as "conditionally dispensable" chromosomes in order to reflect their importance in some, but not all, growth conditions. In addition to describing the structural and functional characteristics of known supernumerary chromosomes in fungi, this review discusses the relative merits of the terms that have been used to describe them, and establishes experimental criteria for their identification.     

Comparison of the Antiproliferative Activity of Two Antitumour Ruthenium(III) Complexes With Their Apotransferrin and Transferrin-Bound Forms in a Human Colon Cancer Cell Line

Two ruthenium(III) complexes, namely trans-indazolium[tetrachlorobis(indazole)- ruthenate(III)], HInd[RuInd(2)Cl(4)] and trans-imidazolium[tetrachlorobis(imidazole)- ruthenate(III)], HIm[RuIm(2)Cl(4)] exhibit high anticancer activity in an autochthonous colorectal carcinoma model in rats. Recently, it has been shown that both complexes bind specifically to human serum apotransferrin and the resulting adducts have been studied through spectroscopic and chromatographic techniques with the ultimate goal of preparing adducts with good selectivity for cancer cells due to the fact that tumour cells express high amounts of transferrin receptors on their cell surface.In order to investigate whether the cellular uptake of the complexes was mediated by apotransferrin or transferrin, we compared the antiproliferative efficacy of HInd[RuInd(2)Cl(4)] and HIm[RuIm(2)Cl(4)] with its apotransferrin- and transferrin-bound form in the human colon cancer cell line SW707 using the microculture tetrazolium test (MTT).Our results show that especially the transferrin-bound forms exhibit high antiproliferative activity, which exceeds that of the free complex, indicating that this protein can act as a carrier of the ruthenium complexes into the tumor cell.     

Rapid, noninvasive concentration measurements of aqueous biological analytes by near-infrared Raman spectroscopy

Accurate concentration measurements of glucose, lactic acid, and creatinine in saline solution have beena chieved with near-IR Raman spectroscopy and a partial least-squares analysis. The Raman spectra were acquired remotely through optical fibers. A root-mean-squared prediction error of 1.2 mM for glucose concentration was achieved in 100 s. Concentrations of other analytes were predicted with similar accuracy.     

Electronic Raman scattering in CuO2 superconductors

Experimental results for the electronic Raman effect in differently doped cuprate superconductors will be presented. We show that the B_2g-symmetry data are generally closely related to ordinary transport and are therefore most likely originating from the carriers, while the response at B_1g symmetry cannot be assigned to a specific type of excitations. In the superconducting state the B_2g pair breaking peaks scale with the transition temperature over a wide doping range. All results consistently suggest a strong anisotropy of the gap and can be modeled by assuming symmetry for the order parameter.