Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study

OBJECTIVE: To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII). STUDY DESIGN: 27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH. RESULTS: Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01). CONCLUSIONS: LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.     

Growth and Senescence of the Successive Leaves on a Cocksfoot Tiller. Effect of Nitrogen and Cutting Regime

The effects of nitrogen supply and cutting regime on the morphologicalcharacteristics (leaf appearance and expansion rates, leaf growthduration, leaf lifespan) of a cocksfoot sward were studied overthree growing seasons to gain a better understanding of thechanges in tiller characteristics (length and age of laminae,number of leaves per tiller) over time and in different seasons.We show that, for a given regrowth, the lamina expansion rateat the tiller level depended on herbage nitrogen status, butthe time course of its components differed according to nitrogensupply. When nitrogen was supplied, leaf appearance was fasterbut also decreased faster. In other words, the length of successivelaminae increased faster when nitrogen was supplied. The samewas true for the growth duration of the laminae and their lifespan.These changes resulted from the length of the sheaths from whichthe successive laminae emerged. As nitrogen increased cell number,it changed the ratio of lamina length_n+1/sheath length_nmorethan the ratio lamina length_n/sheath length_nat the same insertionlevel. Therefore sheath length increased faster and leaf appearancedecreased faster when nitrogen was supplied. This finding helpsto explain the effects of different heights and frequenciesof cutting in terms of their effects on sheath length. Copyright2000 Annals of Botany Company Nitrogen, defoliation, cocksfoot, sheath     

Oligocene sivaladapid primate from the Bugti Hills (Balochistan, Pakistan) bridges the gap between Eocene and Miocene adapiform communities in Southern Asia

A new species of Guangxilemur (Sivaladapidae, Adapiformes) is described from the early Oligocene Chitarwata Formation (Bugti Member) of the Bugti Hills, Sulaiman geological Province, Balochistan, Pakistan. Guangxilemur singsilai n. sp. provides further diagnostic morphological characters from its newly described upper and lower dentitions, confirming its intermediate phylogenetic position between Eocene and Miocene Asian sivaladapid adapiforms. G. singsilai possesses moderately developed shearing and puncturing molar features and maintains lingual cusps on upper molars as in Eocene hoanghoniines; in contrast, it possesses a typical molariform P(4) as in Miocene sivaladapines. The important paleogeographic changes that have affected South Asia during the Tertiary (related to the collision between the Indian and Eurasian Plates) have played a critical role in reforming circulation and climatic differentiation. The presence in Pakistan of an unique and well-diversified Oligocene primate fauna, clearly demonstrates that South Asia maintained favourable environmental conditions during the middle Caenozoic global climatic deterioration that coincides with drastic changes in faunal structure on the whole Holarctic Province, including the extinction of adapiform primates.     

Population biology and vulnerability to fishing of deep‐water Eteline snappers

Deep‐water fish in the tropical and sub‐tropical Pacific Ocean have supported important fisheries for many generations. Observations of localised depletions in some fisheries have raised concerns about the sustainability of current fishing rates. However, quantitative assessments of deep‐water stocks in the Pacific region have been limited by the lack of adequate biological and fisheries data. Estimates are provided of age‐based demographic parameters for two important deep‐water snapper species in the Pacific, Etelis carbunculus and E. coruscans. A spawner biomass‐per‐recruit (SPR) model was applied to determine fishing mortality rates for each species that would achieve specified biological targets (40% unexploited levels, SPR₄₀) and limit (30% unexploited levels, SPR₃₀) reference points, and examine the sensitivity of the model to variation in natural mortality and age at first capture. The maximum observed age, based on increment counts from sectioned otoliths, was 21 years for E. carbunculus and 18 years for E. coruscans. Total mortality (Z), estimated from the Hoenig regression, was 0.21 year^?1 for E. carbunculus and 0.25 year^?1 for E. coruscans. The best approximating growth models were the von Bertalanffy model (L_∞ = 896 mm fork length, k = 0.28, t₀ = 0.51) for E. carbunculus and the logistic model (L_∞ = 879 mm fork length, k = 0.32 year^?1, t₀ = 3.42) for E. coruscans. The spawner biomass‐per‐recruit analysis demonstrated that lower rates of fishing mortality were required for E. coruscans than for E. carbunculus to maintain spawning biomass above estimated biological reference points. Estimates of spawner biomass‐per‐recruit were more sensitive to variation in natural mortality than in the age at first capture, suggesting that regulating fishing mortality rather than gear selectivity would be a more effective management measure for both species. Maintaining fishing mortality <0.1 for both species is recommended as a cautious approach to management, given the uncertainty in estimates of natural mortality and mixed fishery considerations.     

Transformations of 2,6-diisopropylphenol by NO-derived nitrogen oxides, particularly peroxynitrite.

To investigate the protective effect of the anesthetic 2, 6-diisopropylphenol, or propofol, in oxidative processes in which (*)NO and peroxynitrite are involved, direct interactions were explored. The reactions of the highly lipophilic propofol with (*)NO in methanolic or aqueous buffered solutions under air were shown to produce the same compounds as those detected with peroxynitrite, but with very low yields and slow rates. In aqueous neutral medium, peroxynitrite (ONOO(-), ONOOCO(-)(2), ONOOH) was able to nitrate and oxidize propofol: In addition to oxidation products, quinone and quinone dimer, the formation of the 4-nitropropofol derivative was detected, increasing with peroxynitrite or CO(2) concentrations. Nitration reached 20% after the addition of 25 mM bicarbonate to an equimolecular mixture of peroxynitrite and propofol in methanol/phosphate-buffered solution (1/4,v/v) at pH 7.4. However, peroxynitrite either in methanol or in alkaline-buffered mixture (optimum pH 10-12) resulted in the rapid and almost complete transformation of propofol to an intermediate compound 1, which further decomposed to 4-nitrosopropofol. The transient compound 1 was obtained from either peroxynitrite or (*)NO in the presence of oxygen. From mass spectrometry determination of compound 1 we propose the involvement of the nitrosodioxyl radical ONOO(*), forming an adduct with the propofoxyl radical, to yield 4-nitrosodioxypropofol and finally 4-nitrosopropofol.     

Formation of glyceryl 2-mononitrate by regioselective bioconversion of glyceryl trinitrate: efficiency of the filamentous fungus Phanerochaete chrysosporium

Various microorganisms have been evaluated for their ability to hydrolyze glyceryl trinitrate (GTN) to glyceryl dinitrates and mononitrates. Provided that the GTN extracellular concentration was under the lethal dose, metabolite formation and regioselectivity depend on the nature of the strain used. In particular, Phanerochaete chrysosporium at a sublethal dose (3 mM) converts GTN into 1,2-glyceryl dinitrate and 2-glyceryl mononitrate (2-GMN) with a 80% regioselectivity in both steps. This bioconversion, when carried out in fermentors at 28 degrees C, allowed formation of 2-GMN at a rate of 12 mumol/h/g of dried mycelium. Successive batches of 3 mM GTN could be converted into 2-GMN as long as consecutive additions of glycerol or glucose were effected to ensure cell survival and the efficiency of the enzymatic system involved.     

Interval mapping methods for detecting QTL affecting survival and time-to-event phenotypes

Quantitative trait loci (QTL) are usually searched for using classical interval mapping methods which assume that the trait of interest follows a normal distribution. However, these methods cannot take into account features of most survival data such as a non-normal distribution and the presence of censored data. We propose two new QTL detection approaches which allow the consideration of censored data. One interval mapping method uses a Weibull model (W), which is popular in parametrical modelling of survival traits, and the other uses a Cox model (C), which avoids making any assumption on the trait distribution. Data were simulated following the structure of a published experiment. Using simulated data, we compare W, C and a classical interval mapping method using a Gaussian model on uncensored data (G) or on all data (G'=censored data analysed as though records were uncensored). An adequate mathematical transformation was used for all parametric methods (G, G' and W). When data were not censored, the four methods gave similar results. However, when some data were censored, the power of QTL detection and accuracy of QTL location and of estimation of QTL effects for G decreased considerably with censoring, particularly when censoring was at a fixed date. This decrease with censoring was observed also with G', but it was less severe. Censoring had a negligible effect on results obtained with the W and C methods.     

What is a Suiforme (Artiodactyla)?: Contribution of Cranioskeletal and Mitochondrial DNA Data

Suiformes (Artiodactyla) traditionally includes three families: Suidae, Tayassuidae, and Hippopotamidae but the monophyly of this suborder has recently been questioned from molecular data. A maximum parsimony analysis of molecular, morphological, and combined data was performed on the same set of taxa including representatives of the three Artiodactyla suborders (Suiformes, Ruminantia, and Tylopoda) and Perissodactyla as outgroup. Mitochondrial (cytochromeband 12S rRNA) sequence comparisons support the monophyly of Suina (Suidae and Tayassuidae) and Ancodonta (Hippopotamidae) but not the monophyly of Suiformes. Inversely, our preliminary morphological analysis supports the monophyly of Suiformes whereas relationships among the three families are not resolved. The combined data set does not resolve the relationships between Suina, Ancodonta, and Ruminantia. These results are discussed in relation to morphological characters and paleontological data. Some improvements are suggested to clarify the morphological definition of Suiformes and relationships among them.     

The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation

The stereochemistry of the hydrogen abstraction in the vitamin K-dependent carboxylation of synthetic peptides has been investigated; the carboxylation rates of various peptidic substrates containing a stereospecifically 4-monodeuterated glutamic acid residue have been compared to that of nondeuterated peptides. A significant isotope effect was found only with the substrates containing (4S)-4-deuterated glutamic acid. These data reveal that the rat liver microsomal vitamin K-dependent carboxylase acts stereospecifically in abstracting the 4-pro-S hydrogen of the glutamyl residue. The low values of the measured isotope effects indicate that the hydrogen abstraction does not constitute a limiting step in the carboxylation mechanism.