Pediatric Triplane Ankle Fractures: Impact of Radiographs and Computed Tomography on Fracture Classification and Treatment Planning.

Background: The purpose of this study was to compare the reliability of triplane fracture classification, displacement measurement, and treatment planning with the use of radiographs with and without computed tomography.

Methods: One pediatric radiologist, one musculoskeletal radiologist, and three fellowship-trained pediatric orthopaedic surgeons rated a spectrum of twenty-five triplane fractures with use of radiographs alone and then with computed tomography scans on two separate occasions (two to four weeks apart). Raters classified the fracture pattern with use of the Rapariz classification system, measured the maximum intra-articular displacement, and drew the fracture on four outlines of the distal part of the tibia: one lateral view, one anteroposterior view, one axial view above the tibial physis, and one axial view below the physis.

Mouse embryonic stem cells undergo charontosis, a novel programmed cell death pathway dependent upon cathepsins, p53, and EndoG, in response to etoposide treatment.

Embryonic stem cells (ESCs) are hypersensitive to many DNA damaging agents and can rapidly undergo cell death or cell differentiation following exposure. Treatment of mouse ESCs (mESCs) with etoposide (ETO), a topoisomerase II poison, followed by a recovery period resulted in massive cell death with characteristics of a programmed cell death pathway (PCD). While cell death was both caspase- and necroptosis-independent, it was partially dependent on the activity of lysosomal proteases.

Epigenetic differences arise during the lifetime of monozygotic twins.

Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences.

Diaminoindanes as microsomal triglyceride transfer protein inhibitors.

The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC(50) values of 0.7 and 70 nM, respectively.

Phenotypic correction of diabetic mice by adenovirus-mediated glucokinase expression.

Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. GK levels are lowered in patients with maturity-onset diabetes of the young and in some diabetic animal models.

Effects of a thyromimetic on apolipoprotein B-100 in rats.

We have studied the effects of a cardiac sparing thyromimetic, CGS 23425, on postprandial levels of triglycerides, abundance of apolipoprotein B (apo B) protein and hepatic apo B mRNA expression in rats. When compared with control rats, triglyceride clearance was significantly accelerated by treatment with CGS 23425. A full return to baseline values was achieved within 8 h after ingesting a large quantity of fat, as compared to >24 h in control animals.

Synthesis and biological activity of phenoxyphenyl oxamic acid derivatives related to L-thyronine.

The synthesis of substituted phenoxyphenyl oxamic acid derivatives related to L-thyronine (L-T3) is described. The in vitro and in vivo cholesterol lowering and cardiovascular effects of these compounds are presented and discussed.

Beneficial effects of a novel thyromimetic on lipoprotein metabolism.

Although L-triiodothyronine (L-T3) lowers cholesterol, this hormone is not used to treat hypercholesterolemia because of its cardiotoxic effects. Thyromimetics, such as the novel compound CGS 23425, that mimic the beneficial but lack the detrimental effects of T3, may be useful in the treatment of hypercholesterolemia. To show that CGS 23425 has no cardiotoxicity, atrial contractility and force were both measured and found to be unchanged in rats treated with up to 10 mg/kg drug.

Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of cardiovascular and thermogenic effects.

A potent lipid-lowering thyromimetic (CGS 26214) devoid of cardiac and thermogenic activity was identified based on its ability to preferentially access and bind the nuclear fraction of hepatocytes over that of myocytes in culture. The difference in access achieved with CGS 26214 was at least 100-fold better for hepatocytes than for myocytes. This in vitro hepatoselectivity resulted in a compound with unprecedented in vivo lipid-lowering potency with a minimal effective dose of 1 microgram/kg in rats and dogs (approximately 25x that of L-T3).

Synthesis and structure-activity relationships of oxamic acid and acetic acid derivatives related to L-thyronine.

Aryloxamic acids 7 and 23, (arylamino)acetic acids 29, arylpropionic acids 33, arylthioacetic acids 37, and (aryloxy)acetic acid 41 related to L-triiodothyronine (L-T3) were prepared and tested in vitro for binding to the rat liver nuclear L-T3 receptor and the rat membrane L-T3 receptor. The structure-activity relationships for these compounds are described, with 7f, 23a, 29c, 33a, 37b, and 41 showing excellent potency (IC50's of 0.19, 0.

The ansamycins: a novel class of hypolipidemic agents with a high affinity for lipoproteins.

The ansamycins are derivatives of 3-piperazino rifamycin with potent hypolipidemic activity in nonprimate and primate species. Since the cholesterol reduction results from increased uptake and catabolism of lipoprotein cholesterol, it was hypothesized that the hydrophobicity of the ansamycins could result in a lipoprotein association which facilitates clearance. When radiolabeled ansamycins CGP 43371 or CGS 24565 were incubated with human plasma, > 95% was lipoprotein-bound up to drug levels of 25 microM.

Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL.

DiI-LDL (3,3'-dioctadecylindocarbocyanine-low density lipoprotein) has been extensively used in morphological and microscopic studies of receptor-mediated metabolism of LDL in many cell lines. To date the use of this fluorescent probe in a quantitative assay of LDL receptor activity has not been widely used in studies with multiple samples due to the lack of a practical method for quantitatively recovering cell-associated DiI. Therefore, detection by 125I-labeled LDL has remained the method of choice for assaying LDL receptor activity rapidly and reliably.

Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid.

This study was designed to determine whether the conjugation product of L-T3 with cholic acid would result in a liver-targeted compound (CGH 509A) with hypocholesterolemic (HC) activity significantly dissociable from cardiovascular (CV) and thyroxine-suppressing (TS) effects normally observed with thyroid hormone. Evaluation of HC activity in lipemic rats showed that CGH 509A was 6 times less potent than L-T3 with ED25 values estimated at 150 and 25 nmol/kg, respectively. CV function measured as changes in atrial rate, atrial tension and heart weight was determined in euthyroid rats.

Species variation in the atherogenic profile of monkeys: relationship between dietary fats, lipoproteins, and platelet aggregation.

Because lipoproteins and platelet aggregation have been implicated in atherogenesis, relative differences in the response of these variables to dietary fat saturation were compared in three species of monkeys differing in their susceptibility to atherosclerosis (cebus, rhesus, and squirrel monkeys). Both long-term (8-12 years) and short-term (8 weeks) responses to diets containing 31% fat calories were examined in the same monkeys. As expected, long-term feeding of coconut oil by comparison to corn oil produced significantly higher plasma concentrations of total cholesterol, LDL cholesterol, apoB, and triglycerides, as well as higher ratios of LDL/HDL cholesterol and apo B/apo A-I.

Lactose protects against estrogen-induced pigment gallstones in hamsters fed nutritionally adequate purified diets.

To evaluate the impact of dietary factors on gallstone induction in hamsters, male Syrian hamsters were fed for 2-8 wk purified diets that varied in type and amount of simple sugar (glucose vs. lactose, 17.5-72%), fat (2-5%), fiber (0-15%) and estrogen (0 or 300 micrograms/kg diet).

Taurine modulates platelet aggregation in cats and humans.

To explore the relationship between whole-body taurine status and function, the taurine concentration in plasma and platelets was measured and evaluated in terms of ex vivo collagen-induced platelet aggregation in taurine-depleted cats and taurine-supplemented humans. Taurine status exerted a significant effect on platelet aggregability. Platelets from taurine-depleted cats were twice as sensitive to aggregation as platelets from cats receiving taurine.

Retinal pigment epithelium possesses both LDL and scavenger receptor activity.

The lipid metabolism of photoreceptors depends in part on the retinal pigment epithelium (RPE). One aspect of cholesterol homeostasis in cultured bovine RPE was evaluated by measuring low-density lipoprotein (LDL) and scavenger receptor activity with [125I]-LDL and [125I]Ac-LDL, respectively. Incubation of RPE cells in the presence of increasing concentrations of LDL or Ac-LDL resulted in down-regulation of the LDL receptor but not the scavenger receptor, patterns consistent with the presence of both receptors on these cells.

Taurine enhances low density lipoprotein binding. Internalization and degradation by cultured Hep G2 cells.

To evaluate the impact of taurine on hepatic cholesterol catabolism low density lipoprotein (LDL) binding, internalization and degradation were measured in cultured Hep G2 cells. Preincubation of cells with 0.1-10 mM taurine for 24 h stimulated LDL receptor activity by as much as 100%.

ApoE distribution among lipoproteins of rhesus monkeys is modulated by dietary fat and cholesterol.

The effect of dietary saturated fat and cholesterol on plasma cholesterol and apolipoprotein E (apoE) distribution among lipoproteins was studied in rhesus monkeys. Two groups of four monkeys had been fed diets containing 31% energy as either corn oil or coconut oil for 5 yr from birth. Each group was then fed short-term their respective diet with a 0.

The apo E/apo CIII molar ratio affects removal of cholesterol ester from modified human lipoproteins injected into cebus monkeys.

The removal of postprandial (PP) and postabsorptive (PA) human LDL and HDL cholesterol was examined in cebus monkeys (Cebus albifrons) following in vitro labelling of these lipoproteins by 3H-cholesterol in the presence or absence of DTNB. The removal of LDL cholesteryl ester was 3.5 and 2 times greater than that of HDL in male and female monkeys, respectively.

Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys.

The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones. To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein free 14C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus).

Effect of Time of Application on the Action of Foliar Sprays of Oxamyl on Meloidogyne hapla in Tomato.

Foliar sprays containing 3,000 or 4,000 ppm oxamyl applied before inoculation with Meloidogyne hapla completely protected tomato plants from intection for up to 36 days but sprays containing 1,000 or 2,000 ppm provided only partial protection. Postinoculation sprays were less effective than preinoculation sprays but they decreased the numbers of females and their rate of development and increased the numbers of males. Similar amounts of oxamyl applied to the soil as a drench or as granules controlled M.

Development of Four Populations of Meloidogyne hapla on Two Cultivars, of Cucumber at Different Temperatures.

The infectivity and development of four populations of Meloidogyne hapla were compared, at three temperatures, on tomato and two varieties of cucumber. A population from Canada produced few root-galls on cucumber and, except at 24 C, no larvae developed into adult females and produced egg masses. In contrast, a population with 45 chromosomes from America produced many galls on cucumber and small proportions of larvae became females and produced egg masses at 20 and 24 C.