Brain mass estimation by head circumference and body mass methods in neonatal glycaemic modelling and control

Introduction

Hyperglycaemia is a common complication of stress and prematurity in extremely low-birth-weight infants. Model-based insulin therapy protocols have the ability to safely improve glycaemic control for this group. Estimating non-insulin-mediated brain glucose uptake by the central nervous system in these models is typically done using population-based body weight models, which may not be ideal.

Method

A head circumference-based model that separately treats small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants is compared to a body weight model in a retrospective analysis of 48 patients with a median birth weight of 750 g and median gestational age of 25 weeks. Estimated brain mass, model-based insulin sensitivity (S_I) profiles, and projected glycaemic control outcomes are investigated. SGA infants (5) are also analyzed as a separate cohort.

Results

Across the entire cohort, estimated brain mass deviated by a median 10% between models, with a per-patient median difference in S_I of 3.5%. For the SGA group, brain mass deviation was 42%, and per-patient S_I deviation 13.7%. In virtual trials, 87–93% of recommended insulin rates were equal or slightly reduced (Δ < 0.16 mU/h) under the head circumference method, while glycaemic control outcomes showed little change.

Conclusion

The results suggest that body weight methods are not as accurate as head circumference methods. Head circumference-based estimates may offer improved modelling accuracy and a small reduction in insulin administration, particularly for SGA infants.     

2,2′-oxo-1,1′-azobenzene: microbial transformation of rye (Secale cereale L.) allelochemical in field soils byAcinetobacter calcoaceticus: III

Acinetobacter calcoaceticus, a gram-negative bacterium isolated from field soil, was found to be responsible for the biotransformation of 2(3H)-benzoxazolinone (BOA) to 2,2-oxo-1,1-azobenzene (AZOB). Experiments were conducted to evaluate the transformation of BOA to AZOB by this microbe in sterile and nonsterile soil. Transformation studies with soils inoculated withA. calcoaceticus indicated that the production of AZOB increased linearly with the concentration of BOA in sterile soil and showed a quadratic trend in nonsterile soils. This also indicated that all soil types studied for the transformation experiments might containA. calcoaceticus capable of the conversion of benzoxazolinones.     

Effects of coralline lime on nutrient uptake and yield of field-grown sweet corn and peanuts in Oxidic soils of Western Samoa

Effects of coralline lime on yield and nutrient uptake by sweet corn (Zea mays saccharata Sturt.) and peanut (Arachis hypogea) were studied at three locations in Western Samoa. Coarse (0-10 mm) coralline material containing 31.1% Ca and 1.67% Mg was used as lime. There were two modes of application: band and broadcast, and three rates: 6, 12 and 18 ton ha^–1. In the highest rainfall location, marketable yields were increased by 250% for peanut and 160% for sweet corn by liming at 6 ton ha^–1, relative to the unamended control. Peanut yield increases were associated with reduced Mn toxicity and/or with Ca and Mg deficiency. Sweet corn was less susceptible to Mn toxicity, but more responsive to exchangeable Ca. The critical level of exchangeable Ca was found to be about 2.0 cmol(+)kg^–1. Applying lime to a band of 0.25-m wide did not reduce yield relative to broadcast. Soil cultivation caused the lime to spread over a wider band, diluting the applied calcium with a larger soil volume, suggesting that less than 6 ton ha^–1 broadcast coarse coralline lime could still be adequate for most Samoan soils.     

Classifying algorithms for SIFT-MS technology and medical diagnosis

Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) is an analytical technique for real-time quantification of trace gases in air or breath samples. SIFT-MS system thus offers unique potential for early, rapid detection of disease states. Identification of volatile organic compound (VOC) masses that contribute strongly towards a successful classification clearly highlights potential new biomarkers. A method utilising kernel density estimates is thus presented for classifying unknown samples. It is validated in a simple known case and a clinical setting before-after dialysis. The simple case with nitrogen in Tedlar bags returned a 100% success rate, as expected. The clinical proof-of-concept with seven tests on one patient had an ROC curve area of 0.89. These results validate the method presented and illustrate the emerging clinical potential of this technology.     

Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens

Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity.     

Long latency postural reflexes are under supraspinal dopaminergic control

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.     

Formulaic methods of estimating calorie requirements in mechanically ventilated obese patients: a reappraisal

We reviewed 410 cases, 365 males and 45 females, mean age 64 years, of inguinal and femoral hernia, from 1/1/1991 to 31/12/1994, repaired with Lichtenstein and Trabucco techniques. Recurrent hernias repaired were 36 (8,8%). Local anesthesia was used in 82% and follow-up has ranged from 6 months to 4 years. The meshes used are made with a single layer of polipropylene and the Trabucco plugs T1 were made by hand at the operating table. In our experience these two techniques are simple, but is very important, before application of the mesh, a correct dissection of inguinal region. We made a complete excision of cremasteric fibers preservig, if possible, the genital branch of the genitofemoral nerve. The transversalis fascia is introflected and sutured in direct hernia repair or when there are a loss of tissues. The preliminary results obtained with the "tension free" hernioplasty are satisfying. The most important complications were 9 hematomas and an important and persistent inguinal neuralgia in 1 case. There were no recurrences, but we must considered the short follow-up period.     

Altered properties of the branched chain amino acid-preferring activity contribute to increased cleavages after branched chain residues by the "immunoproteasome"

The multicatalytic proteinase complex (MPC, proteasome) is assembled from 14 nonidentical protein subunits. It expresses five distinct proteolytic activities, including a chymotrypsin-like activity, cleaving after hydrophobic residues, and a branched chain amino acid-preferring component (BrAAP), cleaving preferentially after branched chain residues. Exposure of cells to interferons leads to replacement of the X, Y, and Z subunits by the LMP2, LMP7, and MECL1 subunits. This "immunoproteasome" is critical to processing of certain antigens. The enzymatic basis for enhanced antigen processing has not been determined. To gain insight into this question, we examined sites and relative rates of cleavage of bonds in denatured, reduced, carboxyamidomethylated lysozyme, a 129-amino acid protein, by MPC from bovine spleen, in which the X, Y, and Z subunits are replaced by LMP2, LMP7, and MECL1. We compared cleavages to those catalyzed by MPC from bovine pituitary, which contains only the X, Y, and Z subunits. We found marked increases in the rates and number of cleavages after branched chain residues in reduced, carboxyamidomethylated lysozyme by the spleen MPC. This was largely due to accelerated cleavages of bonds after a Phi-X-Br motif, where Phi is a hydrophobic residue, X is a small neutral or polar residue, and Br is a branched chain residue. Inhibitors with these structural properties were selective and potent inhibitors of the BrAAP activity of the spleen MPC. The above findings indicate that alterations in activity and substrate specificity of the BrAAP activity are important factors underlying the altered cleavages after hydrophobic residues associated with incorporation of interferon-inducible subunits. The potential relevance of the findings to antigen processing functions of MPC is discussed.     

Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3

Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted from the venom of the spider Filistata hibernalis. The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium channels in oocytes showed that DW13.3 had the highest affinity for alpha1A, followed by alpha1B > alpha1C > alpha1E. The affinity of DW13.3 for alpha1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar 1:1 manner for all subtypes, DW13.3 produced a partial block of both alpha1A currents and P-type currents in cerebellar Purkinje cells. Selective occlusion of the P/Q-type channel ligand omega-conotoxin MVIIC (but not omega-agatoxin IVA) from its binding site in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes of calcium channels by DW13.3 reflects a common "macro" binding site present on all calcium channels except T-type.